Association Between Life’s Crucial 9 and Testosterone Deficiency in U.S. Men: The Mediating Role of Central Obesity

Association Between Life’s Crucial 9 and Testosterone Deficiency in U.S. Men: The Mediating Role of Central Obesity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association Between Life’s Crucial 9 and Testosterone Deficiency in U.S. Men: The Mediating Role of Central Obesity Dongmei Tang, Beibei Yuan, Chunqiang Gu, Hui Zhou, Jian Jiang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6893841/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Objective Testosterone deficiency (TD) is a prevalent and clinically significant condition with implications for both reproductive and cardiometabolic health. Life’s Crucial 9 (LC9) serves as an integrative indicator for evaluating overall cardiovascular health status, and the weight-adjusted waist index (WWI) is an emerging anthropometric measure that reflects central obesity. This study aimed to investigate the association between LC9 and TD, and to assess whether WWI mediates this relationship. Methods We analyzed data from 5,276 male participants aged 20–79 years from the NHANES 2013–2018 cycles. LC9 scores were calculated based on nine health domains, while WWI was derived from waist circumference and weight. Testosterone deficiency (TD) was defined as a total testosterone level below 300 ng/dL. The associations among LC9, WWI, and TD were assessed using weighted logistic regression models. Restricted cubic spline (RCS) models were applied to assess the dose–response associations. Additionally, subgroup and mediation analyses were performed to assess effect modification and to investigate whether WWI acted as a mediator. Results A 10-point rise in LC9 corresponded to a 27% lower likelihood of testosterone deficiency (OR = 0.73, 95% CI: 0.67–0.79), in contrast, every one-unit increase in WWI was associated with a 121% elevation in the likelihood of developing testosterone deficiency (OR = 2.21, 95% CI: 1.87–2.62). The observed associations remained stable across all examined subgroups and followed an approximately linear dose–response pattern. Mediation analysis revealed that WWI accounted for 52.54% of the total effect of LC9 on TD. Conclusion LC9 was inversely associated with testosterone deficiency, with central obesity (WWI) partially mediating this relationship. These findings underscore the importance of integrated strategies targeting cardiovascular health and central adiposity in efforts to prevent or mitigate testosterone deficiency. Testosterone deficiency NHANES weight-adjusted waist index Life’s Crucial 9 cardiovascular health mediation analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Testosterone deficiency (TD) is a prevalent and clinically significant condition that affects a substantial proportion of adult men, especially with advancing age [ 1 , 2 ]. Estimates suggest that up to 20–30% of men over the age of 40 experience TD, with prevalence increasing markedly in older populations [ 3 , 4 ]. TD is associated not only with reproductive symptoms, such as decreased libido and erectile dysfunction, but also with broader health consequences including osteoporosis, anemia, mood disorders, and impaired quality of life [ 5 – 11 ]. Furthermore, growing evidence links TD to metabolic syndrome, type 2 diabetes, and cardiovascular disease, suggesting its relevance beyond the scope of endocrinology alone [ 12 – 14 ]. Despite its growing burden, modifiable risk factors for TD remain inadequately explored. Identifying and targeting such factors may provide opportunities for early intervention and improved long-term outcomes. Recent studies have highlighted the intricate association between cardiovascular health and testosterone levels [ 15 ]. TD has been linked to increased cardiovascular risk, and conversely, poor cardiovascular profiles may contribute to the development of TD via inflammatory, metabolic, and neuroendocrine mechanisms [ 16 , 17 ]. To enhance the assessment of cardiovascular health, the American Heart Association initially proposed the “Life’s Essential 8” framework, which was subsequently updated with an additional component, giving rise to the “Life’s Crucial 9” (LC9). which incorporates nine domains: diet, smoking status, physical activity, blood pressure, sleep health, body mass index, blood lipids, blood glucose, and psychological health [ 18 , 19 ]. LC9 offers a comprehensive evaluation of modifiable health behaviors and metabolic risk factors. However, despite its broad applications in cardiovascular and all-cause mortality research, the relationship between LC9 and testosterone deficiency remains unexplored. Investigating this connection could shed light on shared mechanisms and inform integrative prevention strategies for TD. Obesity, particularly central adiposity, is a shared contributor to both cardiovascular dysfunction and TD [ 20 , 21 ]. Previous research has shown that excess visceral fat is associated with reduced testosterone levels through increased aromatase activity, insulin resistance, and chronic low-grade inflammation [ 22 – 24 ]. Conventional anthropometric measures such as body mass index (BMI) are limited in capturing body fat distribution and visceral adiposity. The weight-adjusted waist index (WWI), calculated as waist circumference divided by the square root of weight, has emerged as a promising metric that more accurately reflects central obesity and cardiometabolic risk than BMI alone [ 25 , 26 ]. While WWI has been independently associated with cardiovascular diseases and TD [ 26 ], its potential role as a mediator in the relationship between overall cardiovascular health (as captured by LC9) and testosterone deficiency has not yet been investigated. Accordingly, this study investigates whether WWI serves as a mediator in the relationship between LC9 and testosterone deficiency, utilizing data from the 2013–2018 cycles of the National Health and Nutrition Examination Survey (NHANES), a nationally representative dataset of the U.S. population. Uncovering this potential mediation pathway may shed light on how central obesity connects cardiovascular health with male reproductive function. Methods Study Population This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative program administered by the National Center for Health Statistics (NCHS) aimed at evaluating the health and nutritional profiles of the U.S. non-institutionalized population. NHANES employs a multistage, stratified sampling strategy and gathers information through structured interviews, clinical examinations, and laboratory testing. All procedures were reviewed and approved by the NCHS Research Ethics Review Board, with informed written consent obtained from all participants. The present analysis combined data from three NHANES waves: 2013–2014, 2015–2016, and 2017–2018. A total of 29,400 participants were initially identified. We excluded individuals who were female or aged < 20 years, as well as those ≥ 80 years due to top-coded age variables. We also excluded participants with missing or incomplete data on LC9 components, WWI, testosterone levels, or key covariates. Following the application of all exclusion criteria, a total of 5,276 adult men aged between 20 and 79 years were retained for the final weighted analysis. The dataset utilized in this research is publicly accessible and fully de-identified (available at https://www.cdc.gov/nchs/nhanes/index.htm ). A detailed participant selection process is illustrated in Fig. 1 . Measurement Definition of Life’s Crucial 9 LC9 is a composite cardiovascular health index that integrates nine modifiable domains: diet quality, physical activity, smoking status, sleep health, BMI, blood pressure, blood glucose, blood lipids, and psychological well-being. Scoring criteria for each component were adapted from the American Heart Association’s Life’s Essential 8 framework and prior published methods, with the addition of mental health as the ninth domain. Each component was scored from 0 to 100 based on standardized thresholds, and the total LC9 score was calculated as the average of the nine component scores. Comprehensive information on the scoring method can be found in Supplementary Table S1 . Definition of weight-adjusted-waist index WWI was used as a surrogate marker for central adiposity. WWI was obtained using the equation below: $$\:\mathbf{W}\mathbf{W}\mathbf{I}=\:\frac{\mathbf{W}\mathbf{a}\mathbf{i}\mathbf{s}\mathbf{t}\:\mathbf{c}\mathbf{i}\mathbf{r}\mathbf{c}\mathbf{u}\mathbf{m}\mathbf{f}\mathbf{e}\mathbf{r}\mathbf{e}\mathbf{n}\mathbf{c}\mathbf{e}\:\left(\mathbf{c}\mathbf{m}\right)}{\sqrt{\mathbf{W}\mathbf{e}\mathbf{i}\mathbf{g}\mathbf{h}\mathbf{t}\:\left(\mathbf{k}\mathbf{g}\right)}}$$ This index accounts for waist circumference relative to body weight and has been validated as a better predictor of visceral obesity and cardiometabolic risk than BMI alone. Diagnosis of Testosterone deficiency TD was defined based on total serum testosterone levels. Morning fasting blood samples were collected and analyzed using isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS), the gold standard method for testosterone quantification in NHANES. Consistent with Endocrine Society guidelines, TD was defined as a total testosterone concentration < 300 ng/dL. Covariates Several demographic and clinical covariates were included in the analysis based on prior literature and biological plausibility. Age was categorized into three groups: 20–40 years, 41–60 years, and > 60 years. Race/ethnicity was categorized into Non-Hispanic White, Non-Hispanic Black, Mexican American, and Other groups. Educational attainment was divided into two levels: less than high school and high school or higher. Marital status was classified as either married/living with a partner or not married. Poverty-to-income ratio (PIR), an indicator of socioeconomic status, was categorized as poor (< 1.3) or not poor (≥ 1.3). Clinical comorbidities were also included. Hypertension was defined by any of the following: a self-reported history of hypertension, current use of antihypertensive medication, systolic blood pressure (SBP) ≥ 140 mmHg, or diastolic blood pressure (DBP) ≥ 90 mmHg. Diabetes was defined as a self-reported history of diabetes, a fasting plasma glucose level ≥ 126 mg/dL, or a hemoglobin A1c level ≥ 6.5%. Hyperlipidemia was defined as meeting any of the following criteria: triglycerides ≥ 150 mg/dL, total cholesterol ≥ 200 mg/dL, LDL-C ≥ 130 mg/dL, HDL-C < 40 mg/dL for men, or current use of lipid-lowering medication. All covariate definitions and coding criteria are detailed in Supplementary Table S2. Statistical Analysis All statistical analyses were conducted using R software (version 4.3.1). To account for NHANES’s complex multistage sampling design and ensure nationally representative results, sample weights, strata, and primary sampling units were incorporated into the analyses. The combined sample weights for the 2013–2018 cycles were calculated by dividing the 2-year MEC examination weights (WTMEC2YR) by three, following NHANES analytic guidelines. To explore the relationships among LC9, WWI, and testosterone deficiency, a series of logistic regression models were built. Model 1 was unadjusted. Model 2 included adjustments for age, race/ethnicity, marital status, educational attainment, and PIR. Model 3 further incorporated clinical covariates, including hypertension, diabetes, and hyperlipidemia. Both LC9 and WWI were evaluated as continuous variables and categorized into tertiles. Trend analyses were performed by treating tertile groups as ordinal variables. To explore possible nonlinear associations with TD risk, restricted cubic spline (RCS) models were applied, incorporating full adjustments as specified in Model 3. Stratified analyses were also carried out to determine whether the relationships between LC9, WWI, and TD differed by demographic or clinical subgroups. Interaction terms were introduced to test for the significance of effect modification. To investigate whether WWI mediates the association between LC9 and TD, causal mediation analysis was performed utilizing the “mediation” package in R. The total, direct, and indirect effects were estimated using the product-of-coefficients method, and the proportion mediated was calculated as: indirect effect / (indirect effect + direct effect)) × 100%. All statistical tests were two-sided, and a p-value < 0.05 was considered statistically significant. Results Participant Characteristics A total of 5,276 male individuals drawn from the 2013–2018 NHANES cycles were analyzed, representing an estimated 58.3 million adult men in the U.S. population. Among them, 27% were identified as having TD. The participant selection process is illustrated in Fig. 1 . As presented in Table 1 , participants with testosterone deficiency tended to be older, with a greater percentage falling into the 41–60 and 60 + age groups compared to those without TD (40% and 30% vs. 35% and 25%, respectively; P < 0.001). The TD group also exhibited markedly higher rates of hypertension (49% vs. 36%), diabetes (21% vs. 11%), and hyperlipidemia (80% vs. 65%) compared to the non-TD group, with all differences reaching statistical significance (P < 0.001). Participants with TD had lower LC9 scores (66.37 vs. 72.47, P < 0.001), with a greater proportion falling into the lowest LC9 tertile (46% vs. 29%). In contrast, WWI was significantly higher in TD individuals (11.16 vs. 10.72, P < 0.001), with 49% of TD participants in the highest WWI tertile compared to 27% in the non-TD group. No significant differences were observed for race, educational level, or poverty-to-income ratio (PIR). Supplementary characteristics of LC9 component scores are shown in Supplementary Table S1 , and covariate definitions are outlined in Supplementary Table S2 . Table 1 Weighted demographic and clinical profiles of participants stratified by testosterone deficiency status. Characteristic Overall, N = 58,309,199 (100%) Non-TD, N = 42,478,994 (73%) TD, N = 15,830,206 (27%) P Value Sample size 5,276 3,818 1,458 - Age (%) 60 15,268,421 (26%) 10,468,402 (25%) 4,800,019 (30%) Race (%) 0.165 Non-Hispanic White 40,697,777 (70%) 29,411,946 (69%) 11,285,830 (71%) Other 7,329,763 (13%) 5,421,801 (13%) 1,907,961 (12%) Non-Hispanic Black 5,581,679 (9.6%) 4,272,127 (10%) 1,309,553 (8.3%) Mexican American 4,699,981 (8.1%) 3,373,120 (7.9%) 1,326,861 (8.4%) Married/live with partner (%) < 0.001 no 19,076,930 (33%) 15,098,382 (36%) 3,978,548 (25%) yes 39,228,783 (67%) 27,380,612 (64%) 11,848,171 (75%) Level of Education (%) 0.677 < high school 7,837,031 (13%) 5,655,027 (13%) 2,182,005 (14%) ≥ high school 50,467,685 (87%) 36,821,538 (87%) 13,646,146 (86%) PIR (%) 0.360 Poor 10,687,846 (19%) 7,966,362 (20%) 2,721,483 (18%) Not Poor 44,216,025 (81%) 32,091,625 (80%) 12,124,400 (82%) Hypertension (%) < 0.001 no 35,188,363 (60%) 27,126,794 (64%) 8,061,569 (51%) yes 23,120,837 (40%) 15,352,200 (36%) 7,768,636 (49%) Diabetes (%) < 0.001 no 50,218,908 (86%) 37,791,306 (89%) 12,427,602 (79%) yes 8,090,292 (14%) 4,687,688 (11%) 3,402,603 (21%) Hyperlipidemia (%) < 0.001 no 17,947,117 (31%) 14,785,771 (35%) 3,161,346 (20%) yes 40,362,083 (69%) 27,693,223 (65%) 12,668,859 (80%) Mean LC9 score (mean (SE)) 70.81 (12.96) 72.47 (12.60) 66.37 (12.88) < 0.001 LC9, Tertile (%) < 0.001 T1 19,476,637 (33%) 12,190,820 (29%) 7,285,817 (46%) T2 18,943,883 (32%) 13,763,844 (32%) 5,180,040 (33%) T3 19,888,680 (34%) 16,524,331 (39%) 3,364,349 (21%) Mean psychological health score (mean (SE)) 91.44 (21.37) 91.53 (21.57) 91.18 (20.81) 0.195 Mean HEI-2015 diet score (mean (SE)) 38.21 (31.10) 38.69 (31.44) 36.95 (30.14) 0.282 Mean physical activity score (mean (SE)) 78.92 (37.67) 81.32 (36.20) 72.48 (40.66) < 0.001 Mean tobacco exposure score (mean (SE)) 68.72 (39.04) 67.77 (39.95) 71.25 (36.39) 0.549 Mean sleep health score (mean (SE)) 84.25 (23.23) 84.10 (23.33) 84.67 (22.95) 0.659 Mean body mass index score (mean (SE)) 60.88 (31.35) 66.45 (29.40) 45.92 (31.54) < 0.001 Mean blood lipid score (mean (SE)) 63.22 (29.91) 65.53 (29.75) 57.01 (29.45) < 0.001 Mean blood glucose score (mean (SE)) 84.60 (25.17) 87.43 (23.12) 77.03 (28.64) < 0.001 Mean blood pressure score (mean (SE)) 67.09 (30.06) 69.43 (29.45) 60.82 (30.76) < 0.001 WWI (mean (SE)) 10.84 (0.77) 10.72 (0.77) 11.16 (0.70) < 0.001 WWI, Tertile (%) < 0.001 T1 19,437,324 (33%) 16,658,357 (39%) 2,778,967 (18%) T2 19,430,423 (33%) 14,158,293 (33%) 5,272,130 (33%) T3 19,441,453 (33%) 11,662,344 (27%) 7,779,109 (49%) Continuous variables are reported as mean values with standard errors, and the associated P values were derived using a weighted Student’s t-test. Categorical variables are reported as weighted frequencies and percentages, with P values determined by applying weighted chi-square tests. Association Between LC9, WWI, and Testosterone Deficiency LC9 and WWI demonstrated significant associations with the prevalence of testosterone deficiency across all analytical models (Table 2 ). In the fully adjusted model (Model 3), which accounted for age, educational attainment, marital status, PIR, race/ethnicity, as well as comorbidities such as hypertension, diabetes, and hyperlipidemia, each 10-point increase in LC9 was associated with a 27% reduction in the odds of TD (odds ratio [OR] = 0.73, 95% confidence interval [CI]: 0.67–0.79, P < 0.001). Participants in the highest LC9 tertile (T3) had a 59% lower risk of TD compared to those in the lowest tertile (T1) (OR = 0.41, 95% CI: 0.30–0.57, P < 0.001). In contrast, WWI was positively associated with TD; each one-unit increase in WWI was linked to a 121% increase in TD risk (OR = 2.21, 95% CI: 1.87–2.62, P < 0.001). Those in the highest WWI tertile had a 3.79-fold higher risk of TD than those in the lowest tertile (OR = 3.79, 95% CI: 2.75–5.22, P < 0.001). All trend tests were statistically significant (P for trend < 0.001), indicating consistent dose-response relationships across tertiles. Table 2 Association between LC9, WWI, and TD, NHANES 2013–2018. Characteristics Model 1 [OR (95% CI)] p-value Model 2 [OR (95% CI)] p-value Model 3 [OR (95% CI)] p-value LC9 - TD Continuous (per 10 scores) 0.69(0.66,0.73) < 0.001 0.68(0.64,0.72) < 0.001 0.73(0.67,0.79) < 0.001 Tertile T1 1 (ref.) 1 (ref.) 1 (ref.) T2 0.63(0.51,0.78) < 0.001 0.61(0.49,0.76) < 0.001 0.68(0.54,0.87) 0.003 T3 0.34(0.27,0.43) < 0.001 0.33(0.26,0.43) < 0.001 0.41(0.30,0.57) < 0.001 P for trend < 0.001 < 0.001 < 0.001 WWI - TD Continuous 2.19(1.94,2.47) < 0.001 2.43(2.08,2.85) < 0.001 2.21(1.87,2.62) < 0.001 Tertile T1 1 (ref.) 1 (ref.) 1 (ref.) T2 2.23(1.74,2.86) < 0.001 2.32(1.79,3.02) < 0.001 2.10(1.59,2.77) < 0.001 T3 4.00(3.09,5.17) < 0.001 4.53(3.39,6.06) < 0.001 3.79(2.75,5.22) < 0.001 P for trend < 0.001 < 0.001 < 0.001 Linear Relationship Between LC9 and WWI To explore whether LC9 is associated with WWI, a multivariable linear regression analysis was conducted (Table 3 ). After adjusting for all covariates, LC9 was negatively associated with WWI (β = − 0.21, 95% CI: − 0.23 to − 0.19, P < 0.001), suggesting that better cardiometabolic health is strongly related to lower central adiposity. Table 3 Results of multivariable linear regression analysis examining the association between LC9 and WWI. β 95%CI P-value LC9 - WWI -0.21 (-0.23, -0.19) < 0.001 Dose–response associations of LC9 and WWI with testosterone deficiency Restricted cubic spline analysis demonstrated clear linear relationships between LC9, WWI, and TD (Fig. 2 ). After full adjustment, LC9 showed a significant inverse association with TD risk (overall P < 0.001; nonlinearity P = 0.476), while WWI showed a significant positive association (overall P < 0.001; nonlinearity P = 0.527). These results suggest that the protective effect of higher LC9 scores and the risk-enhancing effect of higher WWI values increase in a near-linear fashion, with no evidence of non-linear thresholds. Subgroup Analyses As shown in Fig. 3 , detailed subgroup analyses were performed across major demographic and clinical factors. including age group, race/ethnicity, marital status, educational attainment, PIR, as well as the presence of hypertension, diabetes, and hyperlipidemia. The results demonstrated a consistent inverse relationship between LC9 and the likelihood of testosterone deficiency, alongside a robust positive association between WWI and TD risk, across all examined strata. Furthermore, no statistically significant interaction terms were observed (all P for interaction > 0.05), suggesting that these associations remain stable and generalizable across diverse population subgroups, irrespective of individual sociodemographic or health-related characteristics. Mediation Effect of WWI on the Association Between LC9 and Testosterone Deficiency To explore the potential mediating role of WWI in the association between LC9 and testosterone deficiency, a mediation analysis was performed (Fig. 4 ). LC9 was significantly associated with WWI as noted above, and both the direct and indirect effects of LC9 on TD were statistically significant. The mediation analysis revealed that WWI contributed 52.54% to the overall effect, suggesting that central obesity serves as a partial mediator in the association between compromised cardiometabolic status and elevated risk of testosterone deficiency. Supplementary Table S3 provides a comprehensive summary of the mediation analysis. Discussion In this nationally representative cross-sectional study based on NHANES 2013–2018 data, we found that higher LC9 scores were significantly associated with lower odds of TD in adult males, while higher WWI values were positively associated with TD. Notably, the mediation analysis revealed that WWI served as a partial mediator in the link between LC9 and testosterone deficiency, contributing to roughly 52.54% of the overall effect, thereby highlighting the role of central adiposity in this pathway. These findings suggest that better overall cardiovascular health, as reflected by a higher LC9 score, may confer protective effects against TD, and that central adiposity, indexed by WWI, may serve as a modifiable intermediate factor in this relationship. To the best of our knowledge, this study is the first to systematically investigate the interrelationship among LC9, WWI, and male reproductive health through the application of a mediation analysis framework. These insights provide new perspectives on the shared metabolic and hormonal pathways linking lifestyle and body composition with androgen status, and they highlight the potential utility of LC9 and WWI as early screening tools in men at risk for TD. Emerging evidence suggests that testosterone deficiency is not only a hormonal disorder but also a reflection of underlying cardiometabolic dysregulation [ 27 , 28 ]. The inverse association between LC9 and TD observed in our study is biologically plausible and consistent with prior literature linking healthier lifestyles to better gonadal function. LC9 captures a broad spectrum of modifiable cardiovascular health behaviors and risk factors—including diet, physical activity, sleep, smoking, BMI, blood pressure, blood glucose, blood lipids, and mental health—all of which have been individually implicated in testosterone regulation [ 29 ]. For example, regular physical activity has been associated with higher total testosterone and improved luteinizing hormone signaling through hypothalamic–pituitary–gonadal axis stimulation [ 30 ]. Diets rich in fiber and healthy fats, along with limited ultra-processed food intake, have been shown to support testosterone production and reduce systemic inflammation [ 31 , 32 ]. Sleep health, another component of LC9, plays a critical role in testosterone secretion, which occurs primarily during deep sleep cycles [ 33 ]. Moreover, mental health status—recently included in the updated cardiovascular health metrics—is increasingly recognized as a factor influencing testosterone [ 34 ], with depression and chronic stress being associated with suppressed androgen levels. Therefore, the LC9 score may serve as a comprehensive proxy for the constellation of behaviors and physiological states that maintain healthy testosterone levels in adult men. WWI’s intermediary function in linking LC9 with testosterone deficiency highlights the pivotal role of visceral fat distribution in regulating male hormonal balance. Unlike traditional indices such as BMI or waist circumference alone, WWI adjusts waist circumference by weight, providing a more accurate reflection of fat distribution, particularly visceral fat accumulation [ 35 ]. Visceral adipose tissue is metabolically active and has been shown to exert deleterious endocrine and inflammatory effects [ 36 ]. Furthermore, aromatase activity in adipose tissue can convert testosterone to estradiol, creating a negative feedback loop that further suppresses gonadotropin release [ 37 , 38 ]. Findings from the mediation analysis indicated that WWI accounted for approximately 52.54% of the overall effect linking LC9 to testosterone deficiency, suggesting a substantial mediating influence of central adiposity in this association. This finding is in line with prior research demonstrating that interventions targeting visceral fat—through caloric restriction, exercise, or pharmacological means—can improve serum testosterone concentrations in obese men [ 39 , 40 ]. From a public health perspective, WWI offers a practical and easily obtainable metric for identifying individuals at elevated risk of TD due to underlying central adiposity, and it may serve as a useful intermediate marker in lifestyle-based prevention strategies. The associations between LC9, WWI, and testosterone deficiency remained robust across multiple subgroups, including strata of age, ethnicity, educational attainment, marital status, income level, and presence of comorbid conditions. No significant interactions were observed, suggesting that the observed relationships are consistent and broadly applicable across different populations. Moreover, restricted cubic spline analyses confirmed linear dose–response trends for both LC9 and WWI in relation to TD, with no evidence of nonlinearity. These findings, combined with rigorous multivariable adjustments and nationally representative sampling, reinforce the reliability and generalizability of our results. This study has several notable strengths. First, it is the first to investigate the relationship between LC9 and testosterone deficiency, incorporating WWI as a mediator, thus offering novel insights into the metabolic and behavioral pathways influencing male reproductive health. Second, leveraging the nationally representative NHANES dataset enhances the applicability of our findings to the broader U.S. adult male population. Third, LC9 and WWI are both modifiable and readily available in clinical settings, underscoring their value as practical indicators for early risk assessment and prevention. However, some limitations warrant consideration. The cross-sectional design precludes causal inference, and the single-time measurement of serum testosterone may not fully capture diurnal variation or long-term status. In addition, potential confounding from unmeasured factors, such as medication use, physical illness, or androgen therapy history, cannot be entirely excluded. Finally, while WWI is a useful proxy for central adiposity, direct imaging-based assessments (e.g., visceral fat area by CT or MRI) were not available. Further longitudinal research is warranted to confirm these results and to investigate the complex interactions among lifestyle factors, central adiposity, and hormonal homeostasis over time. Incorporating inflammatory and metabolic biomarkers may also help clarify mechanistic pathways underlying the LC9–WWI–TD axis. Conclusion In conclusion, our study demonstrates a significant inverse association between LC9 scores and testosterone deficiency in adult males, with central adiposity—measured by WWWI—acting as a partial mediator. These findings highlight the interconnected nature of cardiovascular health, body composition, and endocrine function. By identifying WWI as a modifiable factor that partially explains the link between lifestyle quality and testosterone levels, our results underscore the importance of integrated, lifestyle-based strategies for maintaining hormonal health. There is a need for future longitudinal and experimental research to confirm these observations and to further investigate the underlying biological pathways involved. Declarations Acknowledgements We sincerely acknowledge the NHANES program for providing open access to its valuable datasets, which served as the foundation for this research. Funding Not applicable. Author information Authors and Affiliations Department of Laboratory Medicine, The First Hospital of Jiaxing, Jiaxing, Zhejiang Province, 314000, China Dongmei Tang, Beibei Yuan, Chunqiang Gu, jian Jiang and jiayuan Peng Department of Laboratory Medicine, Jiaxing Maternal and Child Health Hospital, Jiaxing, Zhejiang Province, 314000, China Xiaoxuan Cao Contributions Dongmei Tang conceived the study, performed data analysis, and wrote the main manuscript text. Beibei Yuan and Chunqiang Gu assisted with data interpretation and literature review. Hui Zhou, Jian Jiang and Jiayuan Peng prepared Figuresand Tables. Xiaoxuan Cao supervised the project, provided critical revisions. All authors reviewed and approved the final manuscript. Corresponding author Correspondence to Xiaoxuan Cao. Ethics declarations Ethics Approval and Consent to Participate The NHANES data collection protocol was approved by the Research Ethics Review Board of the National Center for Health Statistics (NCHS). Given that the dataset is anonymized and publicly accessible, additional institutional ethics approval was not required for this secondary analysis. Clinical Trial Number Not applicable. Consent for Publication Not applicable. Competing Interests The authors report no conflicts of interest related to this study. References Araujo AB, Esche GR, Kupelian V, O'Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92(11):4241–7. 10.1210. /jc.2007 – 1245. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–35. 10.1056/NEJMoa0911101 . Gryzinski GM, Bernie HL. Testosterone deficiency and the aging male. Int J Impot Res. 2022;34(7):630–4. 10.1038/s41443 . -022-00555-7. Saad F, Röhrig G, von Haehling S, Traish A. Testosterone Deficiency and Testosterone Treatment in Older Men. Gerontology. 2017;63(2):144–56. 10.1159/000452499 . Zitzmann M. Testosterone, mood, behaviour and quality of life. Andrology. 2020;8(6):1598–605. 10.1111/andr.12867 . Halpern JA, Brannigan RE. Testosterone Deficiency. JAMA. 2019;322(11):1116. 10.1001. /jama.2019.9290. Travison TG, Morley JE, Araujo AB, O'Donnell AB, McKinlay JB. The relationship between libido and testosterone levels in aging men. J Clin Endocrinol Metab. 2006;91(7):2509–13. 10.1210/jc.2005–2508 . Agrawal P, Singh SM, Able C, Kohn TP, Herati AS. Sleep disorders are associated with testosterone deficiency and erectile dysfunction-a U.S. claims database analysis. Int J Impot Res. 2024;36(1):78–82. 10.1038/s41443-022-00649-2: https://doi.org/10.1038/s41443-022-00649-2 . Shigehara K, Izumi K, Kadono Y, Mizokami A. Testosterone and Bone Health in Men: A Narrative Review. J Clin Med. 2021;10(3). 10.3390/jcm10030530 . Lee JH, Choi JD, Kang JY, Yoo TK, Park YW. Testosterone deficiency and the risk of anemia: A propensity score-matched analysis. Am J Hum Biol. 2022;34(8):e23751. 10.1002/ajhb.23751: https://doi.org/10.1002/ajhb.23751 . Zito S, Nosari G, Pigoni A, Moltrasio C, Delvecchio G. Association between testosterone levels and mood disorders: A minireview. J Affect Disord. 2023;330:48–56. 10.1016/j.jad.2023.02.108 . Zhao N, Han X, Kim Y, Lu Y. The association between testosterone deficiency and metabolic syndrome in middle-aged and elderly men in Korea: a comparative analytical cross-sectional study. Rev Int Androl. 2025;23(1):57–66. 10.22514/j.androl.2025.008 . Kumari N, Khan A, Shaikh U, Lobes K, Kumar D, Suman F, Bhutto NS, Anees F, Shahid S, Rizwan A. Comparison of Testosterone Levels in Patients With and Without Type 2 Diabetes. Cureus. 2021;13(7):e16288. 10.7759/cureus.16288: https://doi.org/10.7759/cureus.16288 . Cittadini A, Isidori AM, Salzano A. Testosterone therapy and cardiovascular diseases. Cardiovasc Res. 2022;118(9):2039–57. https://doi.org/10.1093/cvr/cvab241 . 10.1093/cvr/cvab241. Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90(2):224–51. 10.1016/j.mayocp.2014.10.011 . Goodale T, Sadhu A, Petak S, Robbins R. Testosterone and the Heart. Methodist Debakey Cardiovasc J. 2017;13(2):68–72. 10.14797. /mdcj-13-2-68. Kaur H, Werstuck GH. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data. CJC Open. 2021;3(10):1238–48. 10.1016/j.cjco.2021.05.007 . Ge J, Peng W, Lu J. Predictive Value of Life's Crucial 9 for Cardiovascular and All-Cause Mortality: A Prospective Cohort Study From the NHANES 2007 to 2018. J Am Heart Assoc. 2024;13(20):e036669. 10.1161/jaha.124.036669 . Lloyd-Jones DM, Allen NB, Anderson CAM, Black T, Brewer LC, Foraker RE, Grandner MA, Lavretsky H, Perak AM, Sharma G, et al. Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association. Circulation. 2022;146(5):e18–43. 10.1161/cir.0000000000001078 . Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16(7):581–606. 10.1111/obr.12282 . Okop KJ, Agabi YA, Joseph V. Weight underestimation and high cardiovascular disease risk among South African adults with obesity: implications for integrated obesity prevention. BMC Public Health 2025, 25(1):2087. 10.1186/s12889-025-23378-9: https://doi.org/10.1186/s12889-025-23378-9 Wang Y, Dai B, Ye DW. Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients. Asian J Androl. 2017;19(2):178–83. 10.4103/1008-682x.174856: https://doi.org/10.4103/1008-682x.174856 . Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, et al. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015;314(6):595–603. https://doi.org/10.1001/jama.2015.8841 . Tsai EC, Boyko EJ, Leonetti DL, Fujimoto WY. Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men. Int J Obes Relat Metab Disord. 2000;24(4):485–91. 10.1038/sj.ijo.0801183 . Tao Z, Zuo P, Ma G. Association of weight-adjusted waist index with cardiovascular disease and mortality among metabolic syndrome population. Sci Rep. 2024;14(1):18684. 10.1038/s41598-024-69486-1: https://doi.org/10.1038/s41598-024-69486-1 . Han Y, Shi J, Gao P, Zhang L, Niu X, Fu N. The weight-adjusted-waist index predicts all-cause and cardiovascular mortality in general US adults. Clin (Sao Paulo). 2023;78:100248. 10.1016/j.clinsp.2023.100248 . Cattabiani C, Basaria S, Ceda GP, Luci M, Vignali A, Lauretani F, Valenti G, Volpi R, Maggio M. Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men. J Endocrinol Invest. 2012;35(1):104–20. 10.3275/8061 . Jones TH. Testosterone deficiency: a risk factor for cardiovascular disease? Trends Endocrinol Metab. 2010;21(8):496–503. 10.1016/j. tem.2010.03.002 . Wang B, Jiang C, Yu P, Nie Z, Wang N, Zhang X. Curvilinear relationship between life's crucial 9 and metabolic syndrome in U.S. adults: a cross-sectional study. Front Endocrinol (Lausanne). 2025;16:1559413. 10.3389/fendo.2025.1559413 . Alghadir AH, Gabr SA, Aly FA. The effects of four weeks aerobic training on saliva cortisol and testosterone in young healthy persons. J Phys Ther Sci. 2015;27(7):2029–33. 10.1589/jpts.27.2029 . Whittaker J, Wu K. Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies. J Steroid Biochem Mol Biol. 2021;210:105878. 10.1016/j.jsbmb.2021.105878 . Kityo A, Choi B, Lee JE, Kim C, Lee SA. Association of ultra-processed food-related metabolites with selected biochemical markers in the UK Biobank. Nutr J. 2025;24(1):21. 10.1186/s12937-025-01077-w: https://doi.org/10.1186/s12937-025-01077-w . Wittert G. The relationship between sleep disorders and testosterone in men. Asian J Androl. 2014;16(2):262–5. 10.4103/1008-682x.122586 . Indirli R, Lanzi V, Arosio M, Mantovani G, Ferrante E. The association of hypogonadism with depression and its treatments. Front Endocrinol (Lausanne). 2023;14:1198437. 10.3389/fendo.2023.1198437 . Li X, Huang P, Wang H, Hu Z, Zheng S, Yang J, Wu X, Huang G. Relationship between weight-adjusted waist index (WWI) and osteoarthritis: a cross-sectional study using NHANES data. Sci Rep. 2024;14(1):28554. 10.1038/s41598-024-80151-5: https://doi.org/10.1038/s41598-024-80151-5 . Cesaro A, De Michele G, Fimiani F, Acerbo V, Scherillo G, Signore G, Rotolo FP, Scialla F, Raucci G, Panico D et al. Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options. Front Cardiovasc Med 2023, 10:1187735. 10.3389/fcvm.2023.1187735 : https://doi.org/10.3389/fcvm.2023.1187735. Ahmed F, Hetty S, Laterveer R, Surucu EB, Mathioudaki A, Hornbrinck E, Patsoukaki V, Olausson J, Sundbom M, Svensson MK, et al. Altered expression of aromatase and estrogen receptors in adipose tissue from men with obesity or type 2 diabetes. J Clin Endocrinol Metab. 2025. 10.1210/clinem/dgaf038 . Colleluori G, Chen R, Turin CG, Vigevano F, Qualls C, Johnson B, Mediwala S, Villareal DT, Armamento-Villareal R. Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects. Front Endocrinol (Lausanne). 2020;11:277. 10.3389/fendo.2020.00277 . Ng Tang Fui M, Prendergast LA, Dupuis P, Raval M, Strauss BJ, Zajac JD, Grossmann M. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Med. 2016;14(1):153. 10.1186/s12916-016-0700-9: https://doi.org/10.1186/s12916-016-0700-9 . Brzozowska MM, Bliuc D, Mazur A, Baldock PA, Eisman JA, Greenfield JR, Center JR. Sex-differential testosterone response to long-term weight loss. Int J Obes (Lond). 2024;48(10):1481–8. 10.1038/s41366-024-01591-7: https://doi.org/10.1038/s41366-024-01591-7 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6893841","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":492930154,"identity":"8bce09fa-f91a-4fba-8ba8-e26800e75256","order_by":0,"name":"Dongmei Tang","email":"","orcid":"","institution":"The First Hospital of Jiaxing","correspondingAuthor":false,"prefix":"","firstName":"Dongmei","middleName":"","lastName":"Tang","suffix":""},{"id":492930155,"identity":"c4a8549e-7865-47b6-8abd-cd18c2ee0ebb","order_by":1,"name":"Beibei Yuan","email":"","orcid":"","institution":"The First Hospital of Jiaxing","correspondingAuthor":false,"prefix":"","firstName":"Beibei","middleName":"","lastName":"Yuan","suffix":""},{"id":492930156,"identity":"8ac645bf-ff5e-42c2-b808-f24aa8156f69","order_by":2,"name":"Chunqiang Gu","email":"","orcid":"","institution":"The First Hospital of Jiaxing","correspondingAuthor":false,"prefix":"","firstName":"Chunqiang","middleName":"","lastName":"Gu","suffix":""},{"id":492930157,"identity":"73d45e77-0431-437a-8b82-0be5397e324b","order_by":3,"name":"Hui Zhou","email":"","orcid":"","institution":"The First Hospital of Jiaxing","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Zhou","suffix":""},{"id":492930158,"identity":"f03682c0-e721-43f5-bcb7-057c72e0baa9","order_by":4,"name":"Jian Jiang","email":"","orcid":"","institution":"The First Hospital of Jiaxing","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Jiang","suffix":""},{"id":492930159,"identity":"8bd18a40-b39b-45dc-82fd-3f777876042e","order_by":5,"name":"jiayuan Peng","email":"","orcid":"","institution":"The First Hospital of Jiaxing","correspondingAuthor":false,"prefix":"","firstName":"jiayuan","middleName":"","lastName":"Peng","suffix":""},{"id":492930160,"identity":"870725c0-4427-4ad9-9917-8ee393b64d7c","order_by":6,"name":"Xiaoxuan Cao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYBAC+/kHGx8k8Pyr52dvIFKLgQRzs8EDmQMJkj0HiNbC3ib5wOZAgsGNBCK1mEs3Nhsk5NzJk5z5eOMNhhqbaIJaLOeA/HLmWTG/dFqxBcOxtNwGgnoOJDYbJPYwM86cnWMmwdhwmCgtbRKJ/5gZN9w8Q6QWgxtALQk8hxM33OAhUotkz0Gg93nSjCV7gH5JIMYv/OztDx/+4LGR42c/vPHGhxobIvyC7EiJBFKUQ7SQqmMUjIJRMApGBgAAPgBGoz6ywvcAAAAASUVORK5CYII=","orcid":"","institution":"Jiaxing Maternal and Child Health Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xiaoxuan","middleName":"","lastName":"Cao","suffix":""}],"badges":[],"createdAt":"2025-06-14 12:08:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6893841/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6893841/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88094081,"identity":"662547d3-d437-4be3-a6f9-87780f20a7ea","added_by":"auto","created_at":"2025-08-01 10:45:58","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":140865,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDiagram outlining the participant selection procedure from the NHANES.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation Between LC9, WWI, and Testosterone Deficiency\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6893841/v1/cfce083d1a77fae17de02360.jpeg"},{"id":88094087,"identity":"9eb83487-2226-46b3-8256-136e24f4c370","added_by":"auto","created_at":"2025-08-01 10:45:58","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":359595,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDose-dependent association between LC9, TD and WWI. \u003c/strong\u003eA, LC9 - TD; B, WWI - TD.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6893841/v1/6597b8f3e592fbd81cc75118.jpeg"},{"id":88094089,"identity":"0d0d575a-c3e2-4845-a7ba-f935a73b7f0a","added_by":"auto","created_at":"2025-08-01 10:45:58","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":699624,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analysis of the association between LC9, TD, and WWI.\u003c/strong\u003e A, LC9 - TD; B, WWI - TD. ORs were calculated to quantify the association, with estimates corresponding to each 10-point increase in LC9 and to every one standard deviation increase in WWI, allowing for standardized interpretation of effect sizes across both indicators.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6893841/v1/1bc630de4dc6b11fad091398.jpeg"},{"id":88096811,"identity":"788ccf99-59b6-4559-86c8-ffa34cf4af02","added_by":"auto","created_at":"2025-08-01 11:01:58","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":221026,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIllustration of the mediation analysis framework.\u003c/strong\u003e Path C represents the overall effect, while path C′ denotes the direct effect.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6893841/v1/7bd1763aae768c22eabb3f92.jpeg"},{"id":88098623,"identity":"4ef7e79c-e953-4480-8ccd-59f44b726961","added_by":"auto","created_at":"2025-08-01 11:10:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2916065,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6893841/v1/bb1f5c6c-be3a-46b5-b50a-f5e0f2ace6f5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Life’s Crucial 9 and Testosterone Deficiency in U.S. Men: The Mediating Role of Central Obesity","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTestosterone deficiency (TD) is a prevalent and clinically significant condition that affects a substantial proportion of adult men, especially with advancing age [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Estimates suggest that up to 20–30% of men over the age of 40 experience TD, with prevalence increasing markedly in older populations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. TD is associated not only with reproductive symptoms, such as decreased libido and erectile dysfunction, but also with broader health consequences including osteoporosis, anemia, mood disorders, and impaired quality of life [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, growing evidence links TD to metabolic syndrome, type 2 diabetes, and cardiovascular disease, suggesting its relevance beyond the scope of endocrinology alone [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Despite its growing burden, modifiable risk factors for TD remain inadequately explored. Identifying and targeting such factors may provide opportunities for early intervention and improved long-term outcomes.\u003c/p\u003e\u003cp\u003eRecent studies have highlighted the intricate association between cardiovascular health and testosterone levels [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. TD has been linked to increased cardiovascular risk, and conversely, poor cardiovascular profiles may contribute to the development of TD via inflammatory, metabolic, and neuroendocrine mechanisms [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. To enhance the assessment of cardiovascular health, the American Heart Association initially proposed the “Life’s Essential 8” framework, which was subsequently updated with an additional component, giving rise to the “Life’s Crucial 9” (LC9). which incorporates nine domains: diet, smoking status, physical activity, blood pressure, sleep health, body mass index, blood lipids, blood glucose, and psychological health [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. LC9 offers a comprehensive evaluation of modifiable health behaviors and metabolic risk factors. However, despite its broad applications in cardiovascular and all-cause mortality research, the relationship between LC9 and testosterone deficiency remains unexplored. Investigating this connection could shed light on shared mechanisms and inform integrative prevention strategies for TD.\u003c/p\u003e\u003cp\u003eObesity, particularly central adiposity, is a shared contributor to both cardiovascular dysfunction and TD [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Previous research has shown that excess visceral fat is associated with reduced testosterone levels through increased aromatase activity, insulin resistance, and chronic low-grade inflammation [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e–\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Conventional anthropometric measures such as body mass index (BMI) are limited in capturing body fat distribution and visceral adiposity. The weight-adjusted waist index (WWI), calculated as waist circumference divided by the square root of weight, has emerged as a promising metric that more accurately reflects central obesity and cardiometabolic risk than BMI alone [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. While WWI has been independently associated with cardiovascular diseases and TD [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], its potential role as a mediator in the relationship between overall cardiovascular health (as captured by LC9) and testosterone deficiency has not yet been investigated. Accordingly, this study investigates whether WWI serves as a mediator in the relationship between LC9 and testosterone deficiency, utilizing data from the 2013–2018 cycles of the National Health and Nutrition Examination Survey (NHANES), a nationally representative dataset of the U.S. population. Uncovering this potential mediation pathway may shed light on how central obesity connects cardiovascular health with male reproductive function.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative program administered by the National Center for Health Statistics (NCHS) aimed at evaluating the health and nutritional profiles of the U.S. non-institutionalized population. NHANES employs a multistage, stratified sampling strategy and gathers information through structured interviews, clinical examinations, and laboratory testing. All procedures were reviewed and approved by the NCHS Research Ethics Review Board, with informed written consent obtained from all participants. The present analysis combined data from three NHANES waves: 2013–2014, 2015–2016, and 2017–2018. A total of 29,400 participants were initially identified. We excluded individuals who were female or aged \u0026lt; 20 years, as well as those ≥ 80 years due to top-coded age variables. We also excluded participants with missing or incomplete data on LC9 components, WWI, testosterone levels, or key covariates. Following the application of all exclusion criteria, a total of 5,276 adult men aged between 20 and 79 years were retained for the final weighted analysis. The dataset utilized in this research is publicly accessible and fully de-identified (available at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/nchs/nhanes/index.htm\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/nchs/nhanes/index.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). A detailed participant selection process is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMeasurement\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDefinition of Life’s Crucial 9\u003c/b\u003e\u003c/p\u003e\u003cp\u003eLC9 is a composite cardiovascular health index that integrates nine modifiable domains: diet quality, physical activity, smoking status, sleep health, BMI, blood pressure, blood glucose, blood lipids, and psychological well-being. Scoring criteria for each component were adapted from the American Heart Association’s Life’s Essential 8 framework and prior published methods, with the addition of mental health as the ninth domain. Each component was scored from 0 to 100 based on standardized thresholds, and the total LC9 score was calculated as the average of the nine component scores. Comprehensive information on the scoring method can be found in \u003cb\u003eSupplementary Table S1\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDefinition of weight-adjusted-waist index\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWWI was used as a surrogate marker for central adiposity. WWI was obtained using the equation below:\u003c/p\u003e\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\mathbf{W}\\mathbf{W}\\mathbf{I}=\\:\\frac{\\mathbf{W}\\mathbf{a}\\mathbf{i}\\mathbf{s}\\mathbf{t}\\:\\mathbf{c}\\mathbf{i}\\mathbf{r}\\mathbf{c}\\mathbf{u}\\mathbf{m}\\mathbf{f}\\mathbf{e}\\mathbf{r}\\mathbf{e}\\mathbf{n}\\mathbf{c}\\mathbf{e}\\:\\left(\\mathbf{c}\\mathbf{m}\\right)}{\\sqrt{\\mathbf{W}\\mathbf{e}\\mathbf{i}\\mathbf{g}\\mathbf{h}\\mathbf{t}\\:\\left(\\mathbf{k}\\mathbf{g}\\right)}}$$\u003c/div\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThis index accounts for waist circumference relative to body weight and has been validated as a better predictor of visceral obesity and cardiometabolic risk than BMI alone.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDiagnosis of Testosterone deficiency\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTD was defined based on total serum testosterone levels. Morning fasting blood samples were collected and analyzed using isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS), the gold standard method for testosterone quantification in NHANES. Consistent with Endocrine Society guidelines, TD was defined as a total testosterone concentration \u0026lt; 300 ng/dL.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCovariates\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSeveral demographic and clinical covariates were included in the analysis based on prior literature and biological plausibility. Age was categorized into three groups: 20–40 years, 41–60 years, and \u0026gt; 60 years. Race/ethnicity was categorized into Non-Hispanic White, Non-Hispanic Black, Mexican American, and Other groups. Educational attainment was divided into two levels: less than high school and high school or higher. Marital status was classified as either married/living with a partner or not married. Poverty-to-income ratio (PIR), an indicator of socioeconomic status, was categorized as poor (\u0026lt; 1.3) or not poor (≥ 1.3). Clinical comorbidities were also included. Hypertension was defined by any of the following: a self-reported history of hypertension, current use of antihypertensive medication, systolic blood pressure (SBP) ≥ 140 mmHg, or diastolic blood pressure (DBP) ≥ 90 mmHg. Diabetes was defined as a self-reported history of diabetes, a fasting plasma glucose level ≥ 126 mg/dL, or a hemoglobin A1c level ≥ 6.5%. Hyperlipidemia was defined as meeting any of the following criteria: triglycerides ≥ 150 mg/dL, total cholesterol ≥ 200 mg/dL, LDL-C ≥ 130 mg/dL, HDL-C \u0026lt; 40 mg/dL for men, or current use of lipid-lowering medication. All covariate definitions and coding criteria are detailed in \u003cb\u003eSupplementary Table S2.\u003c/b\u003e\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were conducted using R software (version 4.3.1). To account for NHANES’s complex multistage sampling design and ensure nationally representative results, sample weights, strata, and primary sampling units were incorporated into the analyses. The combined sample weights for the 2013–2018 cycles were calculated by dividing the 2-year MEC examination weights (WTMEC2YR) by three, following NHANES analytic guidelines.\u003c/p\u003e\u003cp\u003eTo explore the relationships among LC9, WWI, and testosterone deficiency, a series of logistic regression models were built. Model 1 was unadjusted. Model 2 included adjustments for age, race/ethnicity, marital status, educational attainment, and PIR. Model 3 further incorporated clinical covariates, including hypertension, diabetes, and hyperlipidemia.\u003c/p\u003e\u003cp\u003eBoth LC9 and WWI were evaluated as continuous variables and categorized into tertiles. Trend analyses were performed by treating tertile groups as ordinal variables. To explore possible nonlinear associations with TD risk, restricted cubic spline (RCS) models were applied, incorporating full adjustments as specified in Model 3. Stratified analyses were also carried out to determine whether the relationships between LC9, WWI, and TD differed by demographic or clinical subgroups. Interaction terms were introduced to test for the significance of effect modification.\u003c/p\u003e\u003cp\u003eTo investigate whether WWI mediates the association between LC9 and TD, causal mediation analysis was performed utilizing the “mediation” package in R. The total, direct, and indirect effects were estimated using the product-of-coefficients method, and the proportion mediated was calculated as: indirect effect / (indirect effect + direct effect)) × 100%. All statistical tests were two-sided, and a p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eParticipant Characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 5,276 male individuals drawn from the 2013\u0026ndash;2018 NHANES cycles were analyzed, representing an estimated 58.3\u0026nbsp;million adult men in the U.S. population. Among them, 27% were identified as having TD. The participant selection process is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. As presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, participants with testosterone deficiency tended to be older, with a greater percentage falling into the 41\u0026ndash;60 and 60\u0026thinsp;+\u0026thinsp;age groups compared to those without TD (40% and 30% vs. 35% and 25%, respectively; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The TD group also exhibited markedly higher rates of hypertension (49% vs. 36%), diabetes (21% vs. 11%), and hyperlipidemia (80% vs. 65%) compared to the non-TD group, with all differences reaching statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Participants with TD had lower LC9 scores (66.37 vs. 72.47, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with a greater proportion falling into the lowest LC9 tertile (46% vs. 29%). In contrast, WWI was significantly higher in TD individuals (11.16 vs. 10.72, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with 49% of TD participants in the highest WWI tertile compared to 27% in the non-TD group. No significant differences were observed for race, educational level, or poverty-to-income ratio (PIR). Supplementary characteristics of LC9 component scores are shown in \u003cb\u003eSupplementary Table S1\u003c/b\u003e, and covariate definitions are outlined in \u003cb\u003eSupplementary Table S2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eWeighted demographic and clinical profiles of participants stratified by testosterone deficiency status.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall, N\u0026thinsp;=\u0026thinsp;58,309,199 (100%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-TD, N\u0026thinsp;=\u0026thinsp;42,478,994 (73%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTD, N\u0026thinsp;=\u0026thinsp;15,830,206 (27%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP Value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSample size\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,276\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3,818\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,458\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e20\u0026ndash;40\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21,909,066 (38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17,238,895 (41%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4,670,171 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e41\u0026ndash;60\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21,131,714 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14,771,697 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6,360,016 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e\u0026gt;\u0026thinsp;60\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15,268,421 (26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10,468,402 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4,800,019 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRace (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.165\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eNon-Hispanic White\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40,697,777 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29,411,946 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11,285,830 (71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eOther\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7,329,763 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5,421,801 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,907,961 (12%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eNon-Hispanic Black\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,581,679 (9.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4,272,127 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,309,553 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMexican American\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,699,981 (8.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3,373,120 (7.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,326,861 (8.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMarried/live with partner (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eno\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,076,930 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15,098,382 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3,978,548 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39,228,783 (67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27,380,612 (64%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11,848,171 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLevel of Education (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.677\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003e\u0026lt; high school\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7,837,031 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5,655,027 (13%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2,182,005 (14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge; high school\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50,467,685 (87%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36,821,538 (87%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13,646,146 (86%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePIR (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.360\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ePoor\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10,687,846 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7,966,362 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2,721,483 (18%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eNot Poor\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44,216,025 (81%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32,091,625 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12,124,400 (82%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHypertension (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eno\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35,188,363 (60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27,126,794 (64%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8,061,569 (51%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23,120,837 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15,352,200 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7,768,636 (49%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiabetes (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eno\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50,218,908 (86%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37,791,306 (89%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12,427,602 (79%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8,090,292 (14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4,687,688 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3,402,603 (21%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHyperlipidemia (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eno\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17,947,117 (31%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14,785,771 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3,161,346 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eyes\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40,362,083 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27,693,223 (65%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12,668,859 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean LC9 score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70.81 (12.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72.47 (12.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66.37 (12.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLC9, Tertile (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eT1\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,476,637 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12,190,820 (29%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7,285,817 (46%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eT2\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18,943,883 (32%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13,763,844 (32%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5,180,040 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eT3\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,888,680 (34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16,524,331 (39%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3,364,349 (21%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean psychological health score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e91.44 (21.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91.53 (21.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e91.18 (20.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.195\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean HEI-2015 diet score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.21 (31.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.69 (31.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36.95 (30.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.282\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean physical activity score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.92 (37.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.32 (36.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72.48 (40.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean tobacco exposure score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68.72 (39.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67.77 (39.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e71.25 (36.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.549\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean sleep health score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84.25 (23.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84.10 (23.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e84.67 (22.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.659\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean body mass index score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.88 (31.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.45 (29.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e45.92 (31.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean blood lipid score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63.22 (29.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65.53 (29.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e57.01 (29.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean blood glucose score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84.60 (25.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e87.43 (23.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77.03 (28.64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean blood pressure score (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67.09 (30.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69.43 (29.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60.82 (30.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWWI (mean (SE))\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.84 (0.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.72 (0.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.16 (0.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWWI, Tertile (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eT1\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,437,324 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16,658,357 (39%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2,778,967 (18%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eT2\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,430,423 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14,158,293 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5,272,130 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eT3\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,441,453 (33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11,662,344 (27%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7,779,109 (49%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eContinuous variables are reported as mean values with standard errors, and the associated P values were derived using a weighted Student\u0026rsquo;s t-test.\u003c/p\u003e\u003cp\u003eCategorical variables are reported as weighted frequencies and percentages, with P values determined by applying weighted chi-square tests.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAssociation Between LC9, WWI, and Testosterone Deficiency\u003c/b\u003e\u003c/p\u003e\u003cp\u003eLC9 and WWI demonstrated significant associations with the prevalence of testosterone deficiency across all analytical models (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In the fully adjusted model (Model 3), which accounted for age, educational attainment, marital status, PIR, race/ethnicity, as well as comorbidities such as hypertension, diabetes, and hyperlipidemia, each 10-point increase in LC9 was associated with a 27% reduction in the odds of TD (odds ratio [OR]\u0026thinsp;=\u0026thinsp;0.73, 95% confidence interval [CI]: 0.67\u0026ndash;0.79, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Participants in the highest LC9 tertile (T3) had a 59% lower risk of TD compared to those in the lowest tertile (T1) (OR\u0026thinsp;=\u0026thinsp;0.41, 95% CI: 0.30\u0026ndash;0.57, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, WWI was positively associated with TD; each one-unit increase in WWI was linked to a 121% increase in TD risk (OR\u0026thinsp;=\u0026thinsp;2.21, 95% CI: 1.87\u0026ndash;2.62, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Those in the highest WWI tertile had a 3.79-fold higher risk of TD than those in the lowest tertile (OR\u0026thinsp;=\u0026thinsp;3.79, 95% CI: 2.75\u0026ndash;5.22, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). All trend tests were statistically significant (P for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating consistent dose-response relationships across tertiles.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation between LC9, WWI, and TD, NHANES 2013\u0026ndash;2018.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eModel 1\u003c/p\u003e\u003cp\u003e[OR (95% CI)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eModel 2\u003c/p\u003e\u003cp\u003e[OR (95% CI)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eModel 3\u003c/p\u003e\u003cp\u003e[OR (95% CI)]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLC9 - TD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eContinuous (per 10 scores)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.69(0.66,0.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.68(0.64,0.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.73(0.67,0.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTertile\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (ref.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (ref.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (ref.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63(0.51,0.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.61(0.49,0.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.68(0.54,0.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.34(0.27,0.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.33(0.26,0.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.41(0.30,0.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP for trend\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWWI - TD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eContinuous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.19(1.94,2.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.43(2.08,2.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.21(1.87,2.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTertile\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (ref.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (ref.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (ref.)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.23(1.74,2.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.32(1.79,3.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.10(1.59,2.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.00(3.09,5.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.53(3.39,6.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.79(2.75,5.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP for trend\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eLinear Relationship Between LC9 and WWI\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003cp\u003eTo explore whether LC9 is associated with WWI, a multivariable linear regression analysis was conducted (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). After adjusting for all covariates, LC9 was negatively associated with WWI (β = \u0026minus;\u0026thinsp;0.21, 95% CI: \u0026minus;\u0026thinsp;0.23 to \u0026minus;\u0026thinsp;0.19, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suggesting that better cardiometabolic health is strongly related to lower central adiposity.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eResults of multivariable linear regression analysis examining the association between LC9 and WWI.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLC9 - WWI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.21\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(-0.23, -0.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eDose\u0026ndash;response associations of LC9 and WWI with testosterone deficiency\u003c/b\u003e\u003c/p\u003e\u003cp\u003eRestricted cubic spline analysis demonstrated clear linear relationships between LC9, WWI, and TD (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After full adjustment, LC9 showed a significant inverse association with TD risk (overall P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; nonlinearity P\u0026thinsp;=\u0026thinsp;0.476), while WWI showed a significant positive association (overall P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; nonlinearity P\u0026thinsp;=\u0026thinsp;0.527). These results suggest that the protective effect of higher LC9 scores and the risk-enhancing effect of higher WWI values increase in a near-linear fashion, with no evidence of non-linear thresholds.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSubgroup Analyses\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, detailed subgroup analyses were performed across major demographic and clinical factors. including age group, race/ethnicity, marital status, educational attainment, PIR, as well as the presence of hypertension, diabetes, and hyperlipidemia. The results demonstrated a consistent inverse relationship between LC9 and the likelihood of testosterone deficiency, alongside a robust positive association between WWI and TD risk, across all examined strata. Furthermore, no statistically significant interaction terms were observed (all P for interaction\u0026thinsp;\u0026gt;\u0026thinsp;0.05), suggesting that these associations remain stable and generalizable across diverse population subgroups, irrespective of individual sociodemographic or health-related characteristics.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMediation Effect of WWI on the Association Between LC9 and Testosterone Deficiency\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo explore the potential mediating role of WWI in the association between LC9 and testosterone deficiency, a mediation analysis was performed (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). LC9 was significantly associated with WWI as noted above, and both the direct and indirect effects of LC9 on TD were statistically significant. The mediation analysis revealed that WWI contributed 52.54% to the overall effect, suggesting that central obesity serves as a partial mediator in the association between compromised cardiometabolic status and elevated risk of testosterone deficiency. \u003cb\u003eSupplementary Table S3\u003c/b\u003e provides a comprehensive summary of the mediation analysis.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this nationally representative cross-sectional study based on NHANES 2013\u0026ndash;2018 data, we found that higher LC9 scores were significantly associated with lower odds of TD in adult males, while higher WWI values were positively associated with TD. Notably, the mediation analysis revealed that WWI served as a partial mediator in the link between LC9 and testosterone deficiency, contributing to roughly 52.54% of the overall effect, thereby highlighting the role of central adiposity in this pathway. These findings suggest that better overall cardiovascular health, as reflected by a higher LC9 score, may confer protective effects against TD, and that central adiposity, indexed by WWI, may serve as a modifiable intermediate factor in this relationship. To the best of our knowledge, this study is the first to systematically investigate the interrelationship among LC9, WWI, and male reproductive health through the application of a mediation analysis framework. These insights provide new perspectives on the shared metabolic and hormonal pathways linking lifestyle and body composition with androgen status, and they highlight the potential utility of LC9 and WWI as early screening tools in men at risk for TD.\u003c/p\u003e\u003cp\u003eEmerging evidence suggests that testosterone deficiency is not only a hormonal disorder but also a reflection of underlying cardiometabolic dysregulation [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The inverse association between LC9 and TD observed in our study is biologically plausible and consistent with prior literature linking healthier lifestyles to better gonadal function. LC9 captures a broad spectrum of modifiable cardiovascular health behaviors and risk factors\u0026mdash;including diet, physical activity, sleep, smoking, BMI, blood pressure, blood glucose, blood lipids, and mental health\u0026mdash;all of which have been individually implicated in testosterone regulation [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. For example, regular physical activity has been associated with higher total testosterone and improved luteinizing hormone signaling through hypothalamic\u0026ndash;pituitary\u0026ndash;gonadal axis stimulation [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Diets rich in fiber and healthy fats, along with limited ultra-processed food intake, have been shown to support testosterone production and reduce systemic inflammation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Sleep health, another component of LC9, plays a critical role in testosterone secretion, which occurs primarily during deep sleep cycles [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Moreover, mental health status\u0026mdash;recently included in the updated cardiovascular health metrics\u0026mdash;is increasingly recognized as a factor influencing testosterone [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], with depression and chronic stress being associated with suppressed androgen levels. Therefore, the LC9 score may serve as a comprehensive proxy for the constellation of behaviors and physiological states that maintain healthy testosterone levels in adult men.\u003c/p\u003e\u003cp\u003eWWI\u0026rsquo;s intermediary function in linking LC9 with testosterone deficiency highlights the pivotal role of visceral fat distribution in regulating male hormonal balance. Unlike traditional indices such as BMI or waist circumference alone, WWI adjusts waist circumference by weight, providing a more accurate reflection of fat distribution, particularly visceral fat accumulation [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Visceral adipose tissue is metabolically active and has been shown to exert deleterious endocrine and inflammatory effects [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Furthermore, aromatase activity in adipose tissue can convert testosterone to estradiol, creating a negative feedback loop that further suppresses gonadotropin release [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Findings from the mediation analysis indicated that WWI accounted for approximately 52.54% of the overall effect linking LC9 to testosterone deficiency, suggesting a substantial mediating influence of central adiposity in this association. This finding is in line with prior research demonstrating that interventions targeting visceral fat\u0026mdash;through caloric restriction, exercise, or pharmacological means\u0026mdash;can improve serum testosterone concentrations in obese men [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. From a public health perspective, WWI offers a practical and easily obtainable metric for identifying individuals at elevated risk of TD due to underlying central adiposity, and it may serve as a useful intermediate marker in lifestyle-based prevention strategies.\u003c/p\u003e\u003cp\u003eThe associations between LC9, WWI, and testosterone deficiency remained robust across multiple subgroups, including strata of age, ethnicity, educational attainment, marital status, income level, and presence of comorbid conditions. No significant interactions were observed, suggesting that the observed relationships are consistent and broadly applicable across different populations. Moreover, restricted cubic spline analyses confirmed linear dose\u0026ndash;response trends for both LC9 and WWI in relation to TD, with no evidence of nonlinearity. These findings, combined with rigorous multivariable adjustments and nationally representative sampling, reinforce the reliability and generalizability of our results.\u003c/p\u003e\u003cp\u003eThis study has several notable strengths. First, it is the first to investigate the relationship between LC9 and testosterone deficiency, incorporating WWI as a mediator, thus offering novel insights into the metabolic and behavioral pathways influencing male reproductive health. Second, leveraging the nationally representative NHANES dataset enhances the applicability of our findings to the broader U.S. adult male population. Third, LC9 and WWI are both modifiable and readily available in clinical settings, underscoring their value as practical indicators for early risk assessment and prevention.\u003c/p\u003e\u003cp\u003eHowever, some limitations warrant consideration. The cross-sectional design precludes causal inference, and the single-time measurement of serum testosterone may not fully capture diurnal variation or long-term status. In addition, potential confounding from unmeasured factors, such as medication use, physical illness, or androgen therapy history, cannot be entirely excluded. Finally, while WWI is a useful proxy for central adiposity, direct imaging-based assessments (e.g., visceral fat area by CT or MRI) were not available. Further longitudinal research is warranted to confirm these results and to investigate the complex interactions among lifestyle factors, central adiposity, and hormonal homeostasis over time. Incorporating inflammatory and metabolic biomarkers may also help clarify mechanistic pathways underlying the LC9\u0026ndash;WWI\u0026ndash;TD axis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study demonstrates a significant inverse association between LC9 scores and testosterone deficiency in adult males, with central adiposity\u0026mdash;measured by WWWI\u0026mdash;acting as a partial mediator. These findings highlight the interconnected nature of cardiovascular health, body composition, and endocrine function. By identifying WWI as a modifiable factor that partially explains the link between lifestyle quality and testosterone levels, our results underscore the importance of integrated, lifestyle-based strategies for maintaining hormonal health. There is a need for future longitudinal and experimental research to confirm these observations and to further investigate the underlying biological pathways involved.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely acknowledge the NHANES program for providing open access to its valuable datasets, which served as the foundation for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Laboratory Medicine, The First Hospital of Jiaxing, Jiaxing, Zhejiang Province, 314000, China\u003c/p\u003e\n\u003cp\u003eDongmei Tang, Beibei Yuan, Chunqiang Gu, jian Jiang and jiayuan Peng\u003c/p\u003e\n\u003cp\u003eDepartment of Laboratory Medicine, Jiaxing Maternal and Child Health Hospital, Jiaxing, Zhejiang Province, 314000, China\u003c/p\u003e\n\u003cp\u003eXiaoxuan Cao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDongmei Tang conceived the study, performed data analysis, and wrote the main manuscript text. Beibei Yuan and Chunqiang Gu assisted with data interpretation and literature review. Hui Zhou, Jian Jiang and Jiayuan Peng prepared Figuresand Tables. Xiaoxuan Cao supervised the project, provided critical revisions. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Xiaoxuan Cao.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe NHANES data collection protocol was approved by the Research Ethics Review Board of the National Center for Health Statistics (NCHS). Given that the dataset is anonymized and publicly accessible, additional institutional ethics approval was not required for this secondary analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest related to this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAraujo AB, Esche GR, Kupelian V, O'Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92(11):4241\u0026ndash;7. 10.1210. /jc.2007\u0026thinsp;\u0026ndash;\u0026thinsp;1245.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123\u0026ndash;35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa0911101\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa0911101\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGryzinski GM, Bernie HL. Testosterone deficiency and the aging male. Int J Impot Res. 2022;34(7):630\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41443\u003c/span\u003e\u003cspan address=\"10.1038/s41443\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. -022-00555-7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaad F, R\u0026ouml;hrig G, von Haehling S, Traish A. Testosterone Deficiency and Testosterone Treatment in Older Men. Gerontology. 2017;63(2):144\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000452499\u003c/span\u003e\u003cspan address=\"10.1159/000452499\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZitzmann M. Testosterone, mood, behaviour and quality of life. Andrology. 2020;8(6):1598\u0026ndash;605. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/andr.12867\u003c/span\u003e\u003cspan address=\"10.1111/andr.12867\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHalpern JA, Brannigan RE. Testosterone Deficiency. JAMA. 2019;322(11):1116. 10.1001. /jama.2019.9290.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTravison TG, Morley JE, Araujo AB, O'Donnell AB, McKinlay JB. The relationship between libido and testosterone levels in aging men. J Clin Endocrinol Metab. 2006;91(7):2509\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/jc.2005\u0026ndash;2508\u003c/span\u003e\u003cspan address=\"10.1210/jc.2005\u0026ndash;2508\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAgrawal P, Singh SM, Able C, Kohn TP, Herati AS. Sleep disorders are associated with testosterone deficiency and erectile dysfunction-a U.S. claims database analysis. Int J Impot Res. 2024;36(1):78\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41443-022-00649-2: https://doi.org/10.1038/s41443-022-00649-2\u003c/span\u003e\u003cspan address=\"10.1038/s41443-022-00649-2: 10.1038/s41443-022-00649-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShigehara K, Izumi K, Kadono Y, Mizokami A. Testosterone and Bone Health in Men: A Narrative Review. J Clin Med. 2021;10(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm10030530\u003c/span\u003e\u003cspan address=\"10.3390/jcm10030530\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee JH, Choi JD, Kang JY, Yoo TK, Park YW. Testosterone deficiency and the risk of anemia: A propensity score-matched analysis. Am J Hum Biol. 2022;34(8):e23751. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ajhb.23751: https://doi.org/10.1002/ajhb.23751\u003c/span\u003e\u003cspan address=\"10.1002/ajhb.23751: 10.1002/ajhb.23751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZito S, Nosari G, Pigoni A, Moltrasio C, Delvecchio G. Association between testosterone levels and mood disorders: A minireview. J Affect Disord. 2023;330:48\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jad.2023.02.108\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2023.02.108\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao N, Han X, Kim Y, Lu Y. The association between testosterone deficiency and metabolic syndrome in middle-aged and elderly men in Korea: a comparative analytical cross-sectional study. Rev Int Androl. 2025;23(1):57\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.22514/j.androl.2025.008\u003c/span\u003e\u003cspan address=\"10.22514/j.androl.2025.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKumari N, Khan A, Shaikh U, Lobes K, Kumar D, Suman F, Bhutto NS, Anees F, Shahid S, Rizwan A. Comparison of Testosterone Levels in Patients With and Without Type 2 Diabetes. Cureus. 2021;13(7):e16288. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.16288: https://doi.org/10.7759/cureus.16288\u003c/span\u003e\u003cspan address=\"10.7759/cureus.16288: 10.7759/cureus.16288\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCittadini A, Isidori AM, Salzano A. Testosterone therapy and cardiovascular diseases. Cardiovasc Res. 2022;118(9):2039\u0026ndash;57. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/cvr/cvab241\u003c/span\u003e\u003cspan address=\"10.1093/cvr/cvab241\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 10.1093/cvr/cvab241.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90(2):224\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.mayocp.2014.10.011\u003c/span\u003e\u003cspan address=\"10.1016/j.mayocp.2014.10.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoodale T, Sadhu A, Petak S, Robbins R. Testosterone and the Heart. Methodist Debakey Cardiovasc J. 2017;13(2):68\u0026ndash;72. 10.14797. /mdcj-13-2-68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaur H, Werstuck GH. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data. CJC Open. 2021;3(10):1238\u0026ndash;48. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cjco.2021.05.007\u003c/span\u003e\u003cspan address=\"10.1016/j.cjco.2021.05.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGe J, Peng W, Lu J. Predictive Value of Life's Crucial 9 for Cardiovascular and All-Cause Mortality: A Prospective Cohort Study From the NHANES 2007 to 2018. J Am Heart Assoc. 2024;13(20):e036669. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/jaha.124.036669\u003c/span\u003e\u003cspan address=\"10.1161/jaha.124.036669\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLloyd-Jones DM, Allen NB, Anderson CAM, Black T, Brewer LC, Foraker RE, Grandner MA, Lavretsky H, Perak AM, Sharma G, et al. Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association. Circulation. 2022;146(5):e18\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/cir.0000000000001078\u003c/span\u003e\u003cspan address=\"10.1161/cir.0000000000001078\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16(7):581\u0026ndash;606. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/obr.12282\u003c/span\u003e\u003cspan address=\"10.1111/obr.12282\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOkop KJ, Agabi YA, Joseph V. Weight underestimation and high cardiovascular disease risk among South African adults with obesity: implications for integrated obesity prevention. BMC Public Health 2025, 25(1):2087. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12889-025-23378-9: https://doi.org/10.1186/s12889-025-23378-9\u003c/span\u003e\u003cspan address=\"10.1186/s12889-025-23378-9: 10.1186/s12889-025-23378-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Dai B, Ye DW. Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients. Asian J Androl. 2017;19(2):178\u0026ndash;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/1008-682x.174856: https://doi.org/10.4103/1008-682x.174856\u003c/span\u003e\u003cspan address=\"10.4103/1008-682x.174856: 10.4103/1008-682x.174856\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePoets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, et al. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015;314(6):595\u0026ndash;603. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jama.2015.8841\u003c/span\u003e\u003cspan address=\"10.1001/jama.2015.8841\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTsai EC, Boyko EJ, Leonetti DL, Fujimoto WY. Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men. Int J Obes Relat Metab Disord. 2000;24(4):485\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/sj.ijo.0801183\u003c/span\u003e\u003cspan address=\"10.1038/sj.ijo.0801183\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTao Z, Zuo P, Ma G. Association of weight-adjusted waist index with cardiovascular disease and mortality among metabolic syndrome population. Sci Rep. 2024;14(1):18684. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-024-69486-1: https://doi.org/10.1038/s41598-024-69486-1\u003c/span\u003e\u003cspan address=\"10.1038/s41598-024-69486-1: 10.1038/s41598-024-69486-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHan Y, Shi J, Gao P, Zhang L, Niu X, Fu N. The weight-adjusted-waist index predicts all-cause and cardiovascular mortality in general US adults. Clin (Sao Paulo). 2023;78:100248. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clinsp.2023.100248\u003c/span\u003e\u003cspan address=\"10.1016/j.clinsp.2023.100248\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCattabiani C, Basaria S, Ceda GP, Luci M, Vignali A, Lauretani F, Valenti G, Volpi R, Maggio M. Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men. J Endocrinol Invest. 2012;35(1):104\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3275/8061\u003c/span\u003e\u003cspan address=\"10.3275/8061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJones TH. Testosterone deficiency: a risk factor for cardiovascular disease? Trends Endocrinol Metab. 2010;21(8):496\u0026ndash;503. 10.1016/j. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003etem.2010.03.002\u003c/span\u003e\u003cspan address=\"http://tem.2010.03.002\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang B, Jiang C, Yu P, Nie Z, Wang N, Zhang X. Curvilinear relationship between life's crucial 9 and metabolic syndrome in U.S. adults: a cross-sectional study. Front Endocrinol (Lausanne). 2025;16:1559413. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2025.1559413\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2025.1559413\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlghadir AH, Gabr SA, Aly FA. The effects of four weeks aerobic training on saliva cortisol and testosterone in young healthy persons. J Phys Ther Sci. 2015;27(7):2029\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1589/jpts.27.2029\u003c/span\u003e\u003cspan address=\"10.1589/jpts.27.2029\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWhittaker J, Wu K. Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies. J Steroid Biochem Mol Biol. 2021;210:105878. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jsbmb.2021.105878\u003c/span\u003e\u003cspan address=\"10.1016/j.jsbmb.2021.105878\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKityo A, Choi B, Lee JE, Kim C, Lee SA. Association of ultra-processed food-related metabolites with selected biochemical markers in the UK Biobank. Nutr J. 2025;24(1):21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12937-025-01077-w: https://doi.org/10.1186/s12937-025-01077-w\u003c/span\u003e\u003cspan address=\"10.1186/s12937-025-01077-w: 10.1186/s12937-025-01077-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWittert G. The relationship between sleep disorders and testosterone in men. Asian J Androl. 2014;16(2):262\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/1008-682x.122586\u003c/span\u003e\u003cspan address=\"10.4103/1008-682x.122586\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIndirli R, Lanzi V, Arosio M, Mantovani G, Ferrante E. The association of hypogonadism with depression and its treatments. Front Endocrinol (Lausanne). 2023;14:1198437. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2023.1198437\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2023.1198437\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi X, Huang P, Wang H, Hu Z, Zheng S, Yang J, Wu X, Huang G. Relationship between weight-adjusted waist index (WWI) and osteoarthritis: a cross-sectional study using NHANES data. Sci Rep. 2024;14(1):28554. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-024-80151-5: https://doi.org/10.1038/s41598-024-80151-5\u003c/span\u003e\u003cspan address=\"10.1038/s41598-024-80151-5: 10.1038/s41598-024-80151-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCesaro A, De Michele G, Fimiani F, Acerbo V, Scherillo G, Signore G, Rotolo FP, Scialla F, Raucci G, Panico D et al. Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options. Front Cardiovasc Med 2023, 10:1187735. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fcvm.2023.1187735\u003c/span\u003e\u003cspan address=\"10.3389/fcvm.2023.1187735\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e: https://doi.org/10.3389/fcvm.2023.1187735.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhmed F, Hetty S, Laterveer R, Surucu EB, Mathioudaki A, Hornbrinck E, Patsoukaki V, Olausson J, Sundbom M, Svensson MK, et al. Altered expression of aromatase and estrogen receptors in adipose tissue from men with obesity or type 2 diabetes. J Clin Endocrinol Metab. 2025. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/clinem/dgaf038\u003c/span\u003e\u003cspan address=\"10.1210/clinem/dgaf038\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eColleluori G, Chen R, Turin CG, Vigevano F, Qualls C, Johnson B, Mediwala S, Villareal DT, Armamento-Villareal R. Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects. Front Endocrinol (Lausanne). 2020;11:277. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fendo.2020.00277\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2020.00277\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNg Tang Fui M, Prendergast LA, Dupuis P, Raval M, Strauss BJ, Zajac JD, Grossmann M. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Med. 2016;14(1):153. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12916-016-0700-9: https://doi.org/10.1186/s12916-016-0700-9\u003c/span\u003e\u003cspan address=\"10.1186/s12916-016-0700-9: 10.1186/s12916-016-0700-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrzozowska MM, Bliuc D, Mazur A, Baldock PA, Eisman JA, Greenfield JR, Center JR. Sex-differential testosterone response to long-term weight loss. Int J Obes (Lond). 2024;48(10):1481\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41366-024-01591-7: https://doi.org/10.1038/s41366-024-01591-7\u003c/span\u003e\u003cspan address=\"10.1038/s41366-024-01591-7: 10.1038/s41366-024-01591-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Testosterone deficiency, NHANES, weight-adjusted waist index, Life’s Crucial 9, cardiovascular health, mediation analysis","lastPublishedDoi":"10.21203/rs.3.rs-6893841/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6893841/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTestosterone deficiency (TD) is a prevalent and clinically significant condition with implications for both reproductive and cardiometabolic health. Life\u0026rsquo;s Crucial 9 (LC9) serves as an integrative indicator for evaluating overall cardiovascular health status, and the weight-adjusted waist index (WWI) is an emerging anthropometric measure that reflects central obesity. This study aimed to investigate the association between LC9 and TD, and to assess whether WWI mediates this relationship.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe analyzed data from 5,276 male participants aged 20\u0026ndash;79 years from the NHANES 2013\u0026ndash;2018 cycles. LC9 scores were calculated based on nine health domains, while WWI was derived from waist circumference and weight. Testosterone deficiency (TD) was defined as a total testosterone level below 300 ng/dL. The associations among LC9, WWI, and TD were assessed using weighted logistic regression models. Restricted cubic spline (RCS) models were applied to assess the dose\u0026ndash;response associations. Additionally, subgroup and mediation analyses were performed to assess effect modification and to investigate whether WWI acted as a mediator.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA 10-point rise in LC9 corresponded to a 27% lower likelihood of testosterone deficiency (OR\u0026thinsp;=\u0026thinsp;0.73, 95% CI: 0.67\u0026ndash;0.79), in contrast, every one-unit increase in WWI was associated with a 121% elevation in the likelihood of developing testosterone deficiency (OR\u0026thinsp;=\u0026thinsp;2.21, 95% CI: 1.87\u0026ndash;2.62). The observed associations remained stable across all examined subgroups and followed an approximately linear dose\u0026ndash;response pattern. Mediation analysis revealed that WWI accounted for 52.54% of the total effect of LC9 on TD.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eLC9 was inversely associated with testosterone deficiency, with central obesity (WWI) partially mediating this relationship. These findings underscore the importance of integrated strategies targeting cardiovascular health and central adiposity in efforts to prevent or mitigate testosterone deficiency.\u003c/p\u003e","manuscriptTitle":"Association Between Life’s Crucial 9 and Testosterone Deficiency in U.S. Men: The Mediating Role of Central Obesity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-01 10:45:53","doi":"10.21203/rs.3.rs-6893841/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-08-08T17:23:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-06T12:25:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"292840287210024461471272196148763458331","date":"2025-08-06T12:23:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-04T08:18:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246893072943887088492151649392010876557","date":"2025-08-03T16:36:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40768195876497897894466719144321367201","date":"2025-07-29T01:29:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-28T12:47:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-03T11:36:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-02T03:37:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-02T03:37:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-06-14T11:59:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"69bac10f-7665-4f1f-9ca0-1bee1c0b8036","owner":[],"postedDate":"August 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-08-01T10:45:53+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-01 10:45:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6893841","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6893841","identity":"rs-6893841","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}