Associations between atherogenic index of plasma and endometriosis: The National Health and Nutrition Examination Survey 1999 to 2006

1. Introduction Endometriosis is a corporate benign gynecological disorder featured by chronic inflammation, featured by the evolution of endometrioid tissue external the uterine cavity. In people of childbearing age, the prevalence is about 10%.[] female with EMS often experience health problems such as menstrual pain, pelvic pain, infertility, or hardy getting pregnant, which can not only influence their physical health, but can also lead to serious financial burdens such as medical expenses and loss of ability to work.[] The standard method for diagnosing endometriosis is laparoscopically guided biopsy,[,] which often leads to meaningful delays in diagnosis, typically ranging from 6 to 11 years.[] The evolution of innovative diagnostic methods and predictive biomarkers is essential for improving diagnostic accuracy and sensitivity, ultimately enhancing sicks’ quality of life. Lately, endometriosis has been clearly connection with an added danger of Many bad health conditions, covering cardiovascular illness, bad reproductive consequences, autoimmune, endocrine maladjustment, and certain cancers.[] Epidemiological researches clearly point to an added danger of cardiovascular illness in female with endometriosis. However, the exact principle behind this is not yet clear.[,] AIP, a new lipid marke.[] The calculation method of AIP is to logarithm the proportion of TG to HDL-C, which is a new calculation method by logarithmic transformation.[] The works show a meaningful connection between AIP and cardiovascular danger, and therefore AIP can be employed as a reliable forecast of cardiovascular affairs and connection mortality.[] Recent researches have demonstrated that sicks with endometriosis have higher grades of oxidative stress and atherosclerotic lipid profiles, the principle of which is similar to changes in endothelial dysFeature and atherosclerosis.[,] Therefore, it is particularly important to survey the potential link between AIP and the danger of developing endometriosis. This research to probe the connection between AIP and endometriosis through in-depth analysis of NHANES data from 1999 to 2006, to offer a strong scientific basis for the up connection. 2. Materials and methods 2.1. Study population NHANES is a global research whose procedures were permitted by the RERB of the NCHS and administered by the CDCP. All joins had to sign an valid consent form before entering the research. The research covered 4 consecutive 2-year NHANES cycles (1999–2000, 2001–2002, 2003–2004, and 2005–2006) with a aggregate of 6508 individuals. We covered 2405 female aged 18years and older excluded joins with missing data on endometriosis, AIP and other covariates. Ultimately, joins who satisfied these criteria were assigned to the endometriosis or control group according to their diagnosis. 2.2. Endometriosis A questionnaire-based inquiry inquired “Has a doctor or other health professional ever told you that you had endometriosis (age at interview 18–54 years)?” were collected to diagnose endometriosis. joins who responded affirmatively were classified as endometriosis group, otherwise they were in the control group. 2.3. Measurement of the AIP AIP is confirmed by analysis of blood samples and is calculated using the proportion between triglycerides and HDL-C as the logarithm of base 10. Next, the data is classified using the quartile method. During the physical examination, moreover to analyzing blood samples, fasting blood glucose, aggregate cholesterol, triglycerides, and HDL-C grades need to be measured. Moreover, we collect information on demographic peculiarities, lifestyle elements, medical history, and drug employ through questionnaires. 2.4. Covariables The covariates covered age, income poverty proportion [PIR], BMI, number of smokers, race/ethnicity, marital conditions, education level, hypertension, diabetes, alcohol expend, fasting triglycerides (mg/dL), aggregate cholesterol (mg/dL), HDL-C, (mg/dL), and AIP. Related laboratory assays with units and measurement techniques were shown in STable 1, Supplemental Digital Content 1. Among them, the classification of smoking conditions is on account of whether the respondents have smoked at least 100 cigarettes in their life, and the number of cigarettes is. Marital conditions is divided into 3 categories: partner (married/cohabiting), unmarried, widowed/divorced/separated; Education grades divided joins into those under collegiate and those up collegiate. Alcohol expend was affirmed as people who expended at least 12 drinks; The diagnosis of hypertension and diabetes was on account of self-reported responses. 2.5. Statistical analysis In the assessment of persistent variables, the student’s T-experiment was employed to contrast the imparitys between the 2 groups considered. With the help of this experiment, we can determine whether there is a meaningful imparity in the average between the 2 groups. For categorical variables, the Chi-square experiment was employed, which assess whether there was a meaningful connection between the categorical consequences across the groups. By selecting these appropriate statistical methods, the analysis ensured robust evaluation of the data. We formed a multiple linear regression pattern to assess the connection between AIP and endometriosis. The nonlinear connection between AIP and aggregate endometriosis was featured by smooth curve fitting. To further assess the connection between AIP and endometriosis, we formed a logistic regression pattern. An aggregate of 3 patterns are formed: pattern 1, which is unjustified; pattern 2, in which we regulatory for age and race indices; pattern 3, in which we further regulatory for variables that might influence background, e.g., education level, smoking, alcohol expend, marital conditions, PIR, BMI, hypertension and diabetes. Further, stratified analysis was performed for educational attainment (under collegiate, up collegiate), marital conditions (married/cohabiting, unmarried, widowed/divorced/separated), smoking, alcohol expend, and hypertension. Prevalence was calculated on account of the ORs and its 95% ci. To assess the robustness and adequacy of the models, we performed sensitivity analyses using AIP scaled per 1-SD increase, winsorized AIP scaled per 1-SD increase, and rank-based inverse-normal transformed AIP, and evaluated model diagnostics using variance inflation factors, the Hosmer-Lemeshow goodness-of-fit test, and receiver operating characteristic curve analysis with the area under the curve. Using analytical tools for the R statistical software version 4.2 and empowerments statistical software version 5.0 (http://www.empowerstats.net). Any P-value <.05 was deemed statistically meaningful all analyses. 3. Results 3.1. Baseline peculiarities Between 1999 and 2006, the NHANES research covered 6508 joins. Among them, 951 joins were excluded due to endometriosis, 3044 due to AIP, and 108 due to incomplete covariate information. After screening, 2405 joins were covered in the final analysis. According to the diagnosis of endometriosis, 182 sicks were covered in the endometriosis group and 2223 in the control group (Fig. 1). Table 1 lists the detailed descriptive peculiarities of the joins. A aggregate of 2405 volunteers aged 18 years and older were enlisted for the research, with a population average age of 37.53 years and a average AIP of 0.27. joins with endometriosis were older and higher Education level, and were more often non-Hispanic White female, contrast to those without the condition. Moreover, endometriosis sufferers have higher rates of smoking and marriage, and are more likely to be higher grades of hypertension. It is worth noting that their fasting triglyceride, aggregate cholesterol, and AIP grades are also exceed those in sicks without endometriosis. Fasting triglyceride, total cholesterol, and AIP levels were higher in participants with endometriosis than in those without endometriosis. (Table 1). Table 1 Characteristics of NHANES participants included in the analysis. | Characteristics | Overall (N = 2405) | Non-endometriosis (N = 2223) | Endometriosis(N = 182) | P-value | |---|---|---|---|---| | Age (years) | 37.53 (9.89) | 37.20 (10.02) | 40.41 (8.16) | <.001 | | PIR (%) | 3.01 (1.59) | 2.99 (1.59) | 3.19 (1.66) | .233 | | BMI (kg/m2) | 28.10 (7.16) | 28.04 (7.21) | 28.61 (6.66) | .271 | | Smoked ≥ 100cigarettes | |||| | Yes | 925 (42.7%) | 831 (41.0%) | 94 (58.0%) | .001 | | No | 1480 (57.3%) | 1392 (59.0%) | 88 (42.0%) | | | Race(%) | |||| | Mexican American | 550 (7.8%) | 540 (8.5%) | 10 (1.4%) | <.001 | | Other Hispanic | 110 (5.1%) | 105 (5.5%) | 5 (1.9%) | | | Non-Hispanic White | 1141 (69.6%) | 1015 (68.0%) | 126 (83.8%) | | | Non-Hispanic Black | 501 (12.2%) | 466 (12.5%) | 35 (9.2%) | | | Other | 103 (5.2%) | 97 (5.4%) | 6 (3.7%) | | | Marital status(%) | |||| | Married/Living with partner | 1592 (67.2%) | 1468 (66.3%) | 124 (74.6%) | .034 | | Never married | 357 (15.4%) | 323 (18.5%) | 34 (8.8%) | | | Widowed/Divorced/Separated | 456 (17.5%) | 432 (15.2%) | 24 (16.6%) | | | Education level(%) | |||| | Less than high school | 571 (16.0%) | 550 (16.6%) | 21 (10.5%) | .037 | | Above high school | 1834 (84.0%) | 1673 (83.4%) | 161 (89.5%) | | | Hypertension(%) | |||| | Yes | 433 (18.7%) | 383 (18.4%) | 50 (21.4%) | .287 | | No | 1972 (81.3%) | 1840 (81.6%) | 132 (78.6%) | | | Diabetes (%) | |||| | Yes | 105 (3.7%) | 97 (3.7%) | 8 (3.2%) | .732 | | No | 2300 (96.3%) | 2126 (96.3%) | 174 (96.8%) | | | Drinking (%) | |||| | Yes | 1468 (68.2%) | 1344 (67.9%) | 124 (70.7%) | .559 | | No | 937 (31.8%) | 879 (32.1%) | 58 (29.3%) | | | Fasting triglyceride (mg/dL) | 122.44 (105.96) | 117.42 (82.01) | 166.58 (221.16) | .015 | | Total cholesterol (mg/dL) | 195.75 (40.95) | 194.64 (40.58) | 205.55 (42.99) | .002 | | HDL-C(mg/dL) | 57.15 (15.79) | 57.29 (15.71) | 55.88 (16.49) | .402 | | AIP | 0.27 (0.30) | 0.26 (0.29) | 0.37 (0.35) | <.001 | 3.2. Associations between the AIP and endometriosis Table 2 illustrates the connection between the AIP and endometriosis, analyzed through 3 different patterns. In all the patterns, a persistent increase in the AIP was visibly connection with an elevated prevalence rate of endometriosis. concretely, in the unjustified pattern (pattern 1), OR for persistent AIP was 3.139 (95% CI: 1.858–5.304, P < .001), whereas in the pattern regulated for age and ethnicity (pattern 2), OR for persistent AIP was 3.053 (95% CI: 1.781–5.235, P < .001). After further adjustment for various elements covering educational level, smoking, alcohol expend, marriage, PIR, BMI, hypertension and diabetes(pattern 3), the OR retained meaningful at 2.624 (95% CI: 1.479–4.657, P =.002), indicating a consistent connection between higher AIP and the prevalence of endometriosis. When stratified by quartiles, the highest quartile of AIP (Q4) was connection with visibly added odds of endometriosis across all the patterns, with ORs of 1.932 (95% CI: 1.225–3.049, P = .005) in pattern 1, 1.937 (95% CI: 1.198–3.132 P = .008) in pattern 2, and 1.709 (95% CI: 1.017–2.871, P = .043) in pattern 3. These results suggest that elevated AIP was associated with higher odds of endometriosis after controlling for multiple demographic and clinical factors; however, the trend across quartiles did not reach statistical significance in the fully adjusted model. In Figure 2, the relationship of the predicted values was visualized by plotting the restricted cubic spline. The restricted cubic spline analysis did not show statistically significant nonlinearity between AIP and the prevalence of endometriosis (nonlinearity P = .257). Table 2 Association between AIP and endometriosis. | Exposures | OR (95% CI) P | || |---|---|---|---| | Model 1 | Model 2 | Model 3 | | | AIP (continuous) | 3.139 (1.858–5.304) < .001 | 3.053 (1.781–5.235) < .001 | 2.624 (1.479–4.657) .002 | | Q1 | Reference | Reference | Reference | | Q2 | 1.064 (0.669–1.693) .790 | 1.073 (0.670–1.717) .765 | 0.990 (0.616–1.591) .965 | | Q3 | 1.170 (0.715–1.914) .527 | 1.183 (0.719–1.945) .501 | 1.107 (0.674–1.816) .682 | | Q4 | 1.932 (1.225–3.049) .005 | 1.937 (1.198–3.132) .008 | 1.709 (1.017–2.871) .043 | | P for trend | .014 | .022 | .119 | 3.3. Subgroup analyses We conducted subgroup analyses with education, marital conditions, alcohol expend, smoking, and hypertension as categorical variables to probe the connections between AIP and endometriosis and their interactions (Fig. 3). The results showed no significant interactions between AIP and education level, marital status, alcohol use, smoking, or hypertension (all P for interaction >.05). 3.4. Sensitivity analysis Sensitivity analyses showed that the positive association between AIP and endometriosis was generally consistent across different AIP specifications, including per 1-SD scaling, winsorization, and rank-based inverse-normal transformation. The direction and magnitude of the associations were largely unchanged after covariate adjustment, suggesting that the main findings were not driven by extreme values or a single exposure scale (STable 2, Supplemental Digital Content 2). The trend across quartiles was attenuated after full adjustment. Model diagnostics showed no serious multicollinearity, and the fully adjusted models demonstrated acceptable calibration and moderate discrimination. Overall, these results supported the robustness of the positive association between AIP and endometriosis (STable 3, Supplemental Digital Content 3). 4. Discussion The research, which covered a representative sample of 2405 joins, discovered a active connection between AIP and endometriosis, regardless of education, marital conditions, drinking habits, smoking conditions, or high blood pressure. The consequences demonstrated that, after controlling for various demographic and clinical elements, higher AIP grades were strongly connection with an added danger of endometriosis. The research is the first to look in depth at the connection between AIP and endometriosis. At present, AIP, as a reliable biomarker, has been widely employed in the assessment of comprehensive lipid grades and the quantification of dyslipidemia.[] Researches have also discovered that AIP is connected with various biological affairs, covering mortality in sicks with coronary artery illness, bone trabecular mark in postmenopausal female, and even obstructive sleep apnea.[] On this basis, Zhang et al further probed the genetic susceptibility of HDL-C, LDL-C, TG and TC to EM danger phenotypes through Mendelian randomization analysis. Consequences show that there is a significant causal connection between triglyceride grades and the added danger of EMS in populations of European descent.[] Pischon and colleagues first raised a link between dietary polyunsaturated fatty acid intake and reduced circulating inflammatory cytokines in 2003.[] researches have discovered that inflammation is deemed to be a pivotal element in the pathogenesis of endometriosis.[] In 2012, Li et al conducted a retrospective cohort research that covered sicks diagnosed with endometriosis between 2000 and 2012 and enrolled in the TLHI database.[] The consequences demonstrated that Asian female with endometriosis had a remarkable higher danger of coronary artery illness than another female. A previous large prospective cohort research discovered that sicks with laparoscopically confirmed endometriosis had a higher danger of coronary heart illness. This connection was even more pronounced in young female.[] Our works are similar to previously reported connections between endometriosis and coronary artery illness. Early observational researchers have discovered that dyslipidemia is an important element in endometriosis.[] Lipids are not only a component of biological constructions, but also act an important impact in various signaling ways, with rediscovered effects on metabolism, appetite regulation, insulin sensitivity, immune response, and vascular illness in other tissues. Abnormal lipid metabolism may influence hormone balance and may mediately influence endometrial evolution and Feature by regulating inflammatory response and immune Feature.[] Many case-control researches have discovered that sicks with endometriosis have higher serum grades of LDL or oxidized LDL, with significant imparitys contrast to controls.[] Inflammation acts a central impact in the pathogenesis of endometriosis. Dyslipidemia is connected with chronic inflammation,[] which may influence estrogen regulation and endometrial receptivity in female, thus promoting the appear and evolution of endometriosis.[,] Moreover, in conditions e.g., obesity and metabolic syndrome, high TG grades are together by an inflammatory response in adipose tissue. The accumulation and stimulate of inflammatory cells in adipose tissue releases a series of pro-inflammatory elements, such as prostaglandins and leukotrienes.[] Inflammatory lipid mediators exacerbate systemic inflammation and may cause more violent pain and other correlative symptoms in EMS sicks. Recent works have highlighted the potential impact of oxidative stress (an stagger between free radicals and antioxidants) in endometriosis.[] Dyslipidemia and abdominal obesity often lead to oxidative stress and insulin resistance, which together act on endometrial stromal cells, thus promoting the progression of endometriosis.[] Therefore, abnormal metabolic peculiarities may influence the appear and progression of endometriosis. Our works are consistent with earlier research showing a significant link between dyslipidemia and endometriosis.[] Given the close connection between AIP and endometriosis, it is critical that clinical practice mediate this connection among female with high AIP grades for timely evaluation and implementation of effective interventions. This approach to probe innovative ways to prevent and manage the illness. This is the first research to inspect the connection between AIP index and endometriosis in a nationwide sample of adults in the United States. In all analyses, we took into account the appropriate NHANES sampling rights to make the research sample more representative. To ensure the reliability of the consequences, the researchers regulatory for condiscovereding covariates and performed subgroup analyses. The results showed no significant interactions by education level, marital status, drinking, smoking, or hypertension (all P for interaction > 0.05), suggesting no clear evidence of effect modification across these subgroups. This means that dyslipidemia and the presence of endometriosis may be intricately intertwined. However, the research has some limitations. First, it is hard to set a causal relation between AIP and endometriosis due to the cross-sectional design. Second, because joins under the age of 18 were not covered, the relevance of the works to younger sicks is unclear. Third, because much of the data was derived from self-reported questionnaires or interviews, the control group may have covered undiagnosed sicks with endometriosis, leading to recall and reporting bias. Finally, due to the small sample size, potential condiscovereding elements e.g., family history of EM, history of pelvic surgery, and pelvic pain were not fully considered, which may influence the consequences of the research. Therefore, future researches should expand the population sample and consider other potential covariates to further clarify the causal connection between AIP and endometriosis. 5. Conclusion This research revealed a strong active connection of the AIP with endometriosis. This finding is showed that doctors, by regularly monitoring AIP grades, can identify female at danger of endometriosis early, allowing for early intervention to slow the progression of the illness. However, additional discover research is necessary to survey the possible connections among them. Acknowledgments We would like to express our sincere gratitude to the National Health and Nutrition Examination Survey (NHANES) for providing the data used in this study. Author contributions Conceptualization: Shaoqing Wang. Data curation: Ren Xu. Methodology: Yanan Ren. Supervision: Jing Zhao. Writing – original draft: Yanan Ren, Ying Jin, Xinjun Li, Ren Xu, Luyang Su. Writing – review & editing: Shaoqing Wang. atherogenic index of plasma body mass index coronary heart disease endometriosis high-density lipoprotein cholesterol low-density lipoprotein cholesterol National Center for Health Statistics National Health and Nutrition Examination Survey family income-to-poverty ratio total cholesterol triglyceridesAbbreviations: References [1] Huang Y, Yan S, Dong X, et al. Deficiency of MST1 in endometriosis related peritoneal macrophages promoted the autophagy of ectopic endometrial stromal cells by IL-10. Front Immunol. 2022;13:993788.[2] Bulun SE, Yilmaz BD, Sison C, et al. 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