Nonlinear associations of dietary selenium intake with all-cause and cardiovascular mortality after stroke in US adults: findings from NHANES 1999-2018

Nonlinear associations of dietary selenium intake with all-cause and cardiovascular mortality after stroke in US adults: findings from NHANES 1999-2018 | 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 Nonlinear associations of dietary selenium intake with all-cause and cardiovascular mortality after stroke in US adults: findings from NHANES 1999-2018 Yi Deng, Senlin Du, Jiarong Tao, Ruiyun Jin, Feng Tong, Jiaxing Peng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4264317/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The association between dietary selenium intake and mortality in stroke patients remains unclear. We aimed to explore these associations through NHANES 1999-2018. Methods: Stroke participants ≥20 years of age were enrolled and were followed until December 31, 2019. Dietary selenium intake and stroke diagnosis were obtained by self-report on the questionnaire. Mortality information was obtained through prospective matching with the National Death Index database. Results: 1334 stroke survivors were included. Dietary selenium intake was significantly and inversely associated with all-cause mortality in stroke patients after adjusting for all confounders (hazard ratio [HR]=0.997, p=0.024). Compared to the reference population, stroke patients with dietary selenium intake in quartiles Q2, Q3, and Q4 were associated with reduced all-cause mortality (p for trend=0.02). Dietary selenium intake at Q2 was associated with reduced CVD mortality after stroke and not significantly associated with cancer mortality. Restricted cubic spline analysis indicated that dietary selenium intake was nonlinearly associated with all-cause (p for nonlinear=0.0361) and CVD mortality (p for nonlinear=0.0189) in stroke patients. Segmented regression showed that dietary selenium intake was inversely associated with all-cause and CVD mortality at <81 mcg/d and 87 mcg/d, respectively, with no additional protective effects thereafter. Stratified analyses suggested that these effects were only present in specific ages and genders. Conclusions: In a national longitudinal cohort, dietary selenium intake was nonlinearly associated with all-cause and CVD mortality but not cancer mortality after stroke in U.S. adults. Dietary selenium intake at 81 mcg/d and 87 mcg/d had the optimal protective effect on post-stroke all-cause and CVD mortality, respectively. selenium stroke mortality dietary intake NHANES Figures Figure 1 Figure 2 Figure 3 1. INTRODUCTION Stroke is an acute cerebrovascular disease caused by cerebrovascular accidents and is the leading cause of disability and death worldwide[ 1 ]. Stroke primarily consists of ischemic and hemorrhagic strokes, with most cases being ischemic strokes[ 2 ]. The recent Global Burden of Disease Study 2019 suggests that in 2019, stroke is the second leading cause of death and the third leading cause of death and disability[ 3 ]. The burden of disease for stroke has risen significantly over the past 30 years, especially among younger populations[ 4 ]. The World Stroke Organization predicts that stroke mortality will continue to increase by 50% over the next 30 years, as will its disability-adjusted life years[ 5 ]. Despite significant advances in stroke treatment over the past decade, primordial, primary, and secondary prevention of stroke remains the cornerstone of reducing the risk and consequences of stroke[ 6 ]. Identifying risk factors for stroke onset and/or progression and implementing solid stroke prevention strategies have important public health implications for reducing the disease burden associated with stroke[ 7 ]. Selenium is an essential trace mineral that plays an important role in human health. Proper dietary selenium intake has positive implications for maintaining physical health and preventing the onset of certain diseases. Selenium is well recognized as having an essential role in the body's antioxidant, anti-inflammatory, and maintenance of normal immune system function[ 8 – 10 ]. Dietary selenium intake or blood selenium levels have been shown to be strongly associated with the occurrence or progression of stroke. A recent meta-analysis showed an inverse correlation between circulating selenium levels and the risk of stroke, suggesting the preventive value of adequate blood selenium levels for stroke[ 11 ]. A recent study using the National Health and Nutrition Examination Survey (NHANES) database indicated that dietary selenium intake was inversely associated with the prevalence of stroke in the U.S. population[ 12 ]. Similar findings from other countries have demonstrated a negative correlation between dietary selenium intake and the occurrence of stroke[ 13 , 14 ]. However, there is still a lack of exploration regarding the effect of dietary selenium intake on mortality in stroke survivors. Given that stroke populations are associated with high mortality rates, understanding the association between dietary selenium intake and mortality after stroke is of public health importance. In this longitudinal cohort study, we aimed to explore the association of dietary selenium intake with all-cause and cause-specific mortality after stroke through a nationally representative population-based survey, NHANES 1999–2018. These findings support the importance of appropriate dietary selenium intake for improving clinical outcomes in stroke populations, and excessive deaths may be able to be reduced by intervening in dietary selenium intake, a modifiable risk factor, in stroke patients. 2. METHODS Study design and population NHANES is a serial ongoing nationwide cross-sectional survey aimed at assessing the health and nutritional status of non-institutionalized citizens in the U.S. Beginning in 1999, NHANES is conducted in biennial cycles and uses a staged probability sampling design to draw nationally representative participants. NHANES is run by the National Center for Health Statistics (NCHS) and contains standardized interview and physical examination data. More information can be found on the official NHANES website ( https://www.cdc.gov/nchs/nhanes/index.htm ). The study population selection flowchart was presented in Fig. 1 . In this study, we included stroke participants in a total of 10 consecutive cycles of NHANES 1999–2018 and followed them until December 31, 2019, thus it was a longitudinal cohort study. We first included 2,264 stroke participants from NHANES 1999–2018 and sequentially excluded pregnancy (n = 1), those with missing survival (n = 3) and dietary intake information (n = 533), and those missing other covariates (n = 393). Ultimately, 1334 stroke patients were enrolled in further analyses. Assessment of dietary selenium intake Dietary selenium intake was calculated using the USDA's Food and Nutrient Database for Dietary Studies (FNDDS). In NHANES 1999–2002, information on dietary selenium intake was obtained through 24-h face-to-face dietary recall interviews, whereas in 2003–2018, dietary selenium intake was obtained by averaging data obtained from a single face-to-face interview and a telephone follow-up 3–10 days later. Selenium intake from non-dietary sources such as supplements and medications were not considered. Stroke evaluation Participants' stroke status was determined by self-report on the Medical Conditions Questionnaire. A history of stroke was obtained by a participant's positive response to the question "Has a doctor or other health professional ever told you that you had a stroke?". Mortality data collection Mortality data were obtained by prospectively matching to the National Death Index database. We followed baseline stroke patients through December 31, 2019. Our study outcomes were all-cause, CVD, and cancer-related mortality among stroke patients. CVD mortality information was derived from codes associated with cardiac and cerebrovascular disease deaths, including I00-I09, I11, I13, I20-I51, and I60-I69. Information on cancer-related mortality was obtained through codes C00-C97. Covariates Participants' age, gender, race/ethnicity, education level, marital status, family income-poverty ratio (PIR), body mass index (BMI), smoking, alcohol consumption, physical activity, diabetes, hypertension, and coronary heart disease (CHD) information was collected. BMI = body weight (kg) divided by height (m) squared. Smoking status was divided into never smokers (< 100 lifetime cigarettes), former smokers (≥ 100 lifetime cigarettes but now quit), and current smokers based on self-report[ 15 ]. Drinking patterns were categorized into never drinkers, former drinkers, and current light, moderate, and heavy drinkers based on previous studies[ 16 , 17 ]. Physical activity intensity was categorized as never, moderate, and vigorous based on self-reports in the Global Physical Activity Questionnaire. Diabetes was ascertained by a self-reported history of diabetes (as reported by a physician or other professional), glycated hemoglobin ≥ 6.5%, fasting blood glucose ≥ 7.0 mmol/L, blood glucose ≥ 11.1 mmol/L on a glucose tolerance test, or taking diabetes-related medications[ 18 ]. Hypertension was determined based on one of the following: a self-reported history of hypertension, a blood pressure value of ≥ 140/90 mmHg, or the use of anti-hypertensive medications[ 19 ]. CHD history was determined by participants' affirmative responses to specific questions in the questionnaire. Statistical analysis All statistical analyses were performed using R software version 4.2.3 and EmpowerStats software with appropriate weighting to make the sample nationally representative. A two-sided P value of less than 0.05 was considered statistically significant. In the baseline analysis, we grouped the stroke population according to quartiles of dietary selenium intake. Between-group differences for continuous variables were analyzed by analysis of variance (ANOVA) and reported as mean ± standard error, whereas categorical variables were tested by chi-square analysis and reported as number (percentage). We employed Kaplan-Meier (KM) survival analyses and log-rank tests to explore the differences in all-cause, CVD, and cancer-related survival probabilities over time after stroke between different levels of selenium intake. To explore whether the association between selenium intake and mortality in stroke patients was independent of other confounders, we performed multivariate Cox proportional hazards regression analyses. Model 1 was a crude model that did not adjust for any covariates; Model 2 adjusted for sociodemographic variables including age, gender, race, education level, PIR, and marital status; and Model 3 additionally adjusted for BMI, smoking, alcohol consumption, physical activity, diabetes, hypertension, and CHD. We applied restricted cubic spline (RCS) to explore potential nonlinear associations between dietary selenium intake and post-stroke mortality (p for nonlinear). In addition, to explore whether the effect of dietary selenium intake on post-stroke mortality was consistent across subgroups of two important sociodemographic variables (age and sex), we performed stratified analyses. Finally, we excluded populations within 2 years of follow-up in sensitivity analyses to rule out the effect of short-term follow-up. Ethics statement All NHANES survey cycles have been reviewed and approved by the NCHS Ethics Review Board. All participants provided written informed consent. Therefore, since this study analyzed pre-existing data and all participants were de-identified and anonymized, local institutional ethical review approval was waived. 3. RESULTS Baseline stroke population analysis based on dietary selenium intake Quartiles of dietary selenium intake were Q1 ( 115.815 mcg/d). The mean age of stroke survivors was 63.935 years, of which 43.785% were male. Age, BMI, gender, race, marital status, education, and drinking status of stroke patients differed significantly between dietary selenium intakes (all p < 0.05). As dietary selenium intake increased, stroke patients were younger, had a higher BMI, were more likely to be male, of other races, non-single, greater than a high school education, and current drinkers (Table 1 ). Table 1 Baseline analysis of stroke populations according to dietary selenium intake, NHANES 1999–2018. Total Q1 Q2 Q3 Q4 P value Age 63.935(0.544) 64.660 (0.970) 65.399 (1.086) 65.088 (0.874) 60.847 (1.087) 0.011 PIR 2.433(0.059) 2.263 (0.102) 2.351 (0.116) 2.441 (0.113) 2.661 (0.130) 0.134 BMI , kg/m2 30.127(0.254) 29.843 (0.412) 29.120 (0.495) 30.879 (0.535) 30.705 (0.489) 0.049 Selenium intake mcg/day 95.732(1.915) 45.771 (0.983) 74.497 (0.497) 99.906 (0.626) 158.675 (3.237) < 0.0001 Sex < 0.0001 Male 669(43.785) 116(26.650) 140(33.125) 173(42.851) 240(70.696) Female 665(56.215) 218(73.350) 194(66.875) 160(57.149) 93(29.304) Race 0.027 Mexican American 143(3.834) 31(2.689) 34(3.874) 43(4.877) 35(3.942) Non-Hispanic Black 330(13.161) 94(15.143) 76(12.168) 77(13.393) 83(12.090) Non-Hispanic White 727(74.494) 177(75.145) 195(77.593) 183(74.340) 172(71.035) Other Hispanic 68(3.006) 19(3.454) 15(2.578) 15(3.004) 19(3.007) Other Race 66(5.506) 13(3.570) 14(3.788) 15(4.386) 24(9.925) Marital Status 0.007 Non-single 727(59.748) 165(54.913) 176(54.641) 182(58.686) 204(70.066) Single 607(40.252) 169(45.087) 158(45.359) 151(41.314) 129(29.934) Education 0.036 high school 517(44.054) 114(38.358) 132(42.983) 126(43.657) 145(50.689) Smoking 0.749 Never 536(41.015) 134(38.388) 139(44.974) 137(41.692) 126(39.028) Former 508(35.769) 121(35.672) 128(32.495) 132(36.536) 127(38.352) Now 290(23.215) 79(25.940) 67(22.531) 64(21.773) 80(22.621) Drinking 0.041 Never 211(15.544) 64(16.962) 54(17.365) 59(18.614) 34(9.802) Former 478(30.949) 132(36.208) 114(28.718) 123(31.030) 109(28.179) Mild 397(32.814) 82(28.902) 95(28.608) 104(36.945) 116(36.882) Moderate 116(9.528) 28(8.862) 33(12.133) 24(5.657) 31(11.004) Heavy 132(11.165) 28(9.066) 38(13.175) 23(7.754) 43(14.132) Physical activity 0.49 No 868(61.225) 235(65.961) 227(63.784) 208(57.632) 198(57.518) Moderate 306(26.152) 66(23.050) 73(24.729) 92(29.995) 75(27.037) Vigorous 160(12.623) 33(10.988) 34(11.486) 33(12.373) 60(15.446) Diabetes 0.902 No 816(65.326) 207(66.067) 200(66.632) 205(65.250) 204(63.449) Yes 518(34.674) 127(33.933) 134(33.368) 128(34.750) 129(36.551) Hypertension 0.637 No 244(21.696) 62(22.110) 59(20.132) 55(19.604) 68(24.649) Yes 1090(78.304) 272(77.890) 275(79.868) 278(80.396) 265(75.351) CHD 0.659 No 1095(81.355) 270(80.178) 276(80.811) 284(84.480) 265(80.241) Yes 239(18.645) 64(19.822) 58(19.189) 49(15.520) 68(19.759) Continuous variables were expressed using means (standard errors) and categorical variables were expressed using numbers (percentages). PIR, income-poverty ratio; BMI, body mass index; CHD, coronary heart disease. Association between dietary selenium intake and mortality after stroke After a median follow-up duration of 84 months (interquartile range: 44.5–130 months), 599 (40.101%) stroke patients died, with 241 and 95 CVD- and cancer-related deaths, respectively. KM survival curves and log-rank tests revealed a significantly higher probability of all-cause survival in stroke patients with increasing quartiles of dietary selenium intake (p = 0.023), whereas there was no significant difference in the probability of CVD (p = 0.159) and cancer-related survival (p = 0.442) ( Supplementary Figs. 1–3 ). Consistently, multivariate Cox proportional hazards regression analyses demonstrated that dietary selenium intake was significantly and inversely associated with all-cause mortality in stroke patients after adjusting for all covariates (hazard ratio [HR] and 95% confidence interval [CI] = 0.997 (0.995,1.000), p = 0.024). Compared to Q1, stroke patients with dietary selenium intake at Q2, Q3, and Q4 had 32.5%, 32.2%, and 27% lower all-cause mortality, respectively (p for trend = 0.02) (Table 2 ). Compared to the reference population, dietary selenium intake at Q2 was associated with significantly lower CVD mortality among stroke patients (HR = 0.647, p = 0.035) ( Supplementary Table 1 ). However, dietary selenium intake was not significantly associated with cancer mortality in the stroke population ( Supplementary Table 2 ). Table 2 Association of dietary selenium intake with all-cause mortality in the stroke population, NHANES 1999–2018. Model 1 HR (95%CI) p Model 2 HR (95%CI) p Model 3 HR (95%CI) p Dietary selenium intake 0.995(0.993,0.998) < 0.0001 0.997(0.994,1.000) 0.049 0.997(0.995,1.000) 0.024 Dietary selenium intake quartiles Q1 ref ref ref ref ref ref Q2 0.788(0.593,1.048) 0.101 0.704(0.516,0.960) 0.027 0.675(0.512,0.891) 0.005 Q3 0.815(0.625,1.063) 0.132 0.712(0.546,0.928) 0.012 0.678(0.530,0.868) 0.002 Q4 0.609(0.446,0.832) 0.002 0.764(0.551,1.060) 0.108 0.730(0.548,0.973) 0.032 P for trend 0.002 0.061 0.02 Model 1 was a crude model that did not adjust for any covariates; Model 2 adjusted for sociodemographic variables including age, gender, race, education level, PIR, and marital status; and Model 3 additionally adjusted for BMI, smoking, alcohol consumption, physical activity, diabetes, hypertension, and CHD. Nonlinear correlations exploration RCS analysis showed that dietary selenium intake was significantly nonlinearly associated with all-cause (p for nonlinearity = 0.0189) and CVD mortality (p for nonlinearity = 0.0361) in patients with stroke, whereas there was no significant association with cancer mortality (Fig. 2 ). Further segmented regression analyses suggested that dietary selenium intake was inversely associated with all-cause mortality in stroke patients only at < 81 mcg/d (HR = 0.988, p < 0.001) and lost significant association above this value (Table 3 ). Similarly, dietary selenium intake was marginally associated with CVD mortality at < 87 mcg/d ( Supplementary Table 3 ). Table 3 Segmented regression analysis of dietary selenium intake and all-cause mortality in stroke patients, NHANES 1999–2018. HR (95% CI) p p for interaction All-cause 0.025 Dietary selenium intake ≥ 81 mcg/d 0.999(0.995,1.004) 0.792 Dietary selenium intake < 81 mcg/d 0.988(0.981,0.995) 0.05). Subgroup analyses indicated that the association of dietary selenium intake with CVD mortality in stroke patients was only present in those < 45 years of age and in men, whereas the association with all-cause mortality was only present in those ≥ 60 years of age and in women. Dietary selenium intake was not significantly associated with cancer mortality in stroke patients in any of the subgroups (Fig. 3 ). Sensitivity analysis Similar results were obtained by removing stroke patients with follow-up duration within two years. Dietary selenium intake remained inversely associated with all-cause mortality in stroke patients (HR = 0.997, p = 0.018). Dietary selenium intake remained associated with post-stroke CVD mortality only in Q2 (compared to Q1) and was not significantly associated with cancer mortality ( Supplementary Table 4–6 ). 4. DISCUSSIONS This is the first time the association of dietary selenium intake with all-cause, CVD, and cancer-related long-term mortality in stroke patients has been explored in a nationally representative longitudinal cohort study. After a median follow-up of 7 years among stroke participants in NHANES 1999–2018, dietary selenium intake was independently and inversely associated with all-cause mortality after stroke, nonlinearly associated with CVD mortality, and not associated with cancer mortality. Dietary selenium intake was significantly associated with all-cause and CVD mortality in stroke patients only at < 81 mcg/d and 87 mcg/d, respectively. In addition, these associations were only present in specific age groups and gender. Our findings suggest that dietary selenium intake is an independent prognostic factor for all-cause mortality in stroke patients and that maintaining adequate dietary selenium intake may be associated with improved prognosis in stroke patients. In contrast, excessive dietary selenium intake did not provide additional protective effects. Selenium is an essential trace mineral that is primarily consumed through the diet and plays an important role in human health. Selenium acts as a component of antioxidant enzymes in the body, helping to protect against cellular damage caused by free radicals, which in turn fights a variety of diseases, including stroke[ 20 , 21 ]. There is still a paucity of exploration of the association of dietary selenium intake with all-cause and cause-specific mortality in stroke patients. A previous longitudinal study using NHANES 2005–2014 revealed that the composite dietary antioxidant index encompassing vitamins A, C, E, selenium, zinc, and carotenoids was independently and jointly significantly associated with poststroke depression and all-cause mortality[ 22 ]. Although studies on the effect of dietary selenium intake on mortality after stroke are still lacking, dietary selenium intake has been shown to be associated with stroke occurrence. A previous study similarly using NHANES 2003–2018 suggested that dietary selenium intake was inversely and nonlinearly associated with the prevalence of stroke in the general U.S. population[ 12 ]. Dietary selenium intake was associated with stroke prevalence only within a certain threshold (105 µg/day), and there was no significant protective effect above this cutoff. Our study similarly demonstrated that dietary selenium intake was nonlinearly associated with both all-cause and CVD mortality after stroke, and significant associations existed only before 81 mcg/d and 87 mcg/d, respectively. Hu et al.[ 13 ] similarly showed that both dietary selenium and blood selenium were inversely associated with stroke prevalence in a cross-sectional study that included 2077 Canadian Inuit participants. The association between dietary selenium and stroke prevalence was L-shaped, with dietary selenium associated with reduced stroke odds until 350 µg/d and a plateau thereafter. Zhang et al.[ 14 ] included 11,532 participants from the China Health and Nutrition Survey 2004–2015 in a retrospective cohort study and suggested that the protective effect of dietary selenium intake on stroke risk was only present at ≤ 60 µg/d, with no significant associations thereafter. These studies consistently indicated an inverse association of dietary selenium intake with stroke occurrence, whereas excessive selenium intake had no additional protective effect. Indeed, excessive selenium intake/exposure may lead to selenium toxicity and is associated with adverse health outcomes, such as positive associations with the prevalence of non-alcoholic fatty liver disease and type 2 diabetes[ 23 , 24 ]. Our study obtained similar findings, providing new evidence for the prognostic value of dietary selenium intake in stroke patients. It is worth noting that the average dietary selenium intake of populations in different countries/regions varies significantly, for example, the average selenium intake of the Chinese population was 47.36 µg/d[ 14 ], which is significantly lower than that of the general population in the U.S.[ 12 ], and even lower than that of the stroke population included in our study (95.732 µg/d). The current recommendation for adequate dietary selenium intake in the adult population is 70 µg/d[ 25 ], and our study suggested that the recommended adequate intake for the prevention of all-cause and CVD mortality in the US stroke population is higher, suggesting the need for population- and target-specific adequate intake values. Several clinical investigations and experimental studies have explored the effect of selenium supplementation on clinical outcomes in stroke patients. A clinical trial enrolling 44 patients with acute ischemic stroke demonstrated that Selenase supplementation for 5 days improved neurological deficits, antioxidant activity, and levels of inflammatory markers in stroke patients compared to the placebo group[ 26 ]. Another randomized clinical trial that included 40 patients with acute ischemic stroke demonstrated that selenium selenite supplementation for 5 days was associated with short-term neurological improvement in stroke patients, but not with long-term clinical outcomes[ 27 ]. Zhuo et al.[ 28 ] demonstrated that selenium supplementation (selenomethionine) in a mouse model of overt middle cerebral artery occlusion ameliorated cerebral infarct volume, oxidative stress, and ferroptosis, and was associated with improvements in stroke-induced gut dysbiosis, suggesting multifaceted potential neuroprotective effects of long-term selenium supplementation. In a comprehensive experimental exploration, Alim et al.[ 29 ] demonstrated that brain-permeable selenopeptide supplementation improves neurological function in stroke by coordinating the activation of the transcription factors TFAP2c and Sp1 to protect neurons, thereby enhancing glutathione peroxidase 4 (GPX4) and other genes, and thereby inhibiting GPX4-dependent ferroptosis and other GPX4-independent cell death. Additional experimental studies have similarly shown that selenium supplementation ameliorates oxidative stress, iron death, metabolic, and inflammatory signaling pathways in mouse ischemic stroke models[ 30 – 33 ]. Several clinical studies have also suggested an inverse association between circulating/blood selenium levels and stroke occurrence. A meta-analysis that included 11 observational studies indicated a significant inverse correlation between circulating selenium levels and stroke occurrence (relative risk = 0.48, 95% CI = 0.24–0.94; p = 0.033)[ 11 ]. A recent cross-sectional study utilizing NHANES 2011–2018 similarly suggested that blood selenium was negatively associated with stroke prevalence (odds ratio = 0.57, p = 0.014) and that there was a dose-response association[ 34 ]. However, Mendelian randomization studies suggested that single-nucleotide polymorphisms associated with circulating selenium levels were not associated with ischemic stroke, which seems to indicate that circulating selenium levels are not causally associated with ischemic stroke as genetically predicted[ 35 , 36 ]. Although age and sex did not significantly influence the association of dietary selenium intake with mortality after stroke, we observed that these associations were only present in specific age groups and genders. Previous studies have similarly suggested that the association between dietary selenium intake and stroke prevalence is age- and sex-specific[ 12 , 37 ]. Age and gender are recognized as important sociodemographic risk factors for stroke. Stroke prevalence and dietary selenium intake may differ significantly by age. In addition, dietary selenium intake and selenium metabolism may be gender-specific due to differences in the effects of estrogen on selenoprotein metabolism and other sociodemographic factors[ 38 ]. Our findings emphasize that the association of dietary selenium intake with all-cause and CVD mortality in stroke patients requires consideration in specific age groups and genders. There are several notable strengths of this study. This is the first time that the association between dietary selenium intake and post-stroke mortality has been explored in a nationwide longitudinal cohort study, and the prognostic value of dietary selenium intake in the U.S. stroke population has been revealed through a comprehensive exploration. Our study has a relatively large sample, a nationally representative multiethnic cohort, and included stroke participants over a 20-year period with long-term follow-up to ensure reliability and generalizability of the results. In addition, we have fully considered the effects of potential confounders to ensure the robustness of our results. However, our study has some shortcomings. It was a longitudinal cohort study, and therefore temporal causality could not be derived, and residual confounders may exist. The diagnosis of stroke was based on self-report rather than imaging, which may lack accuracy. However, previous studies have shown good agreement with the questionnaire in NHANES[ 39 ]. In addition, we were unable to obtain stroke subtypes (ischemic and hemorrhagic), stroke severity, and other clinical characteristics, and thus may have lacked deeper levels of exploration. Future high-quality studies with large samples are needed to validate our findings. 5. CONCLUSIONS In a national longitudinal cohort study, dietary selenium intake was nonlinearly associated with all-cause and CVD mortality after stroke, but not with cancer mortality. Inverse associations of dietary selenium intake with all-cause and CVD mortality in stroke patients were only present at < 81 mcg/d and 87 mcg/d, respectively, and only in specific age groups and genders. These findings support the prevention of excess mortality in stroke patients by adequate dietary selenium intake, and more well-designed studies are warranted to confirm our conclusions in the future. Declarations Data availability : This study analyzed publicly available datasets and can be found at https://www.cdc.gov/nchs/nhanes/. Ethics statement : The studies involving human participants were reviewed and approved by the NCHS Ethics Review Board and no additional ethical review consent is required. All participants have provided written informed consent. Funding : The National Natural Science Foundation of China (grant number 82060214) and the Natural Science Foundation of Jiangxi Province (grant number 20212BAB206047). Conflict of interest : The authors declare no conflict of interest in this study. Acknowledgments : We thank all the participants in the NHANES for providing data for this study. Author contributions :These authors contributed equally:Yi Deng, Senlin Du and Jiarong Tao: [email protected] ; [email protected] ; [email protected] ; References Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A et al (2013) An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44(7):2064–2089. 10.1161/STR.0b013e318296aeca Campbell BCV, Khatri P, Stroke (2020) Lancet 396(10244):129–142. 10.1016/s0140-6736(20)31179-x Global regional, national burden of stroke and its risk factors (2021) 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. 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Hepatol Commun 6(2):399–410. 10.1002/hep4.1803 Wang L, Li X, Wang Z, Bancks MP, Carnethon MR, Greenland P et al (2021) Trends in Prevalence of Diabetes and Control of Risk Factors in Diabetes Among US Adults, 1999–2018. JAMA 326(8):1–13. 10.1001/jama.2021.9883 Muntner P, Hardy ST, Fine LJ, Jaeger BC, Wozniak G, Levitan EB et al (2020) Trends in Blood Pressure Control Among US Adults With Hypertension, 1999–2000 to 2017–2018. JAMA 324(12):1190–1200. 10.1001/jama.2020.14545 Naderi M, Puar P, Zonouzi-Marand M, Chivers DP, Niyogi S, Kwong RWM (2021) A comprehensive review on the neuropathophysiology of selenium. Sci Total Environ 767:144329. 10.1016/j.scitotenv.2020.144329 Dominiak A, Wilkaniec A, Wroczyński P, Adamczyk A (2016) Selenium in the Therapy of Neurological Diseases. Where is it Going? Curr Neuropharmacol 14(3):282–299. 10.2174/1570159x14666151223100011 Xu Q, Qian X, Sun F, Liu H, Dou Z, Zhang J (2023) Independent and joint associations of dietary antioxidant intake with risk of post-stroke depression and all-cause mortality. J Affect Disord 322:84–90. 10.1016/j.jad.2022.11.013 Liu X, Shen H, Chen M, Shao J (2022) Clinical Relevance of Selenium with Liver Stiffness and Steatosis Detected by Transient Elastography in Adults. Biol Trace Elem Res 200(7):3041–3049. 10.1007/s12011-021-02912-x Steinbrenner H, Duntas LH, Rayman MP (2022) The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities. Redox Biol 50:102236. 10.1016/j.redox.2022.102236 Gać P, Czerwińska K, Macek P, Jaremków A, Mazur G, Pawlas K et al (2021) The importance of selenium and zinc deficiency in cardiovascular disorders. Environ Toxicol Pharmacol 82:103553. 10.1016/j.etap.2020.103553 Ramezani M, Simani L, Abedi S, Pakdaman H (2021) Is Selenium Supplementation Beneficial in Acute Ischemic. Stroke? Neurologist 27(2):51–55. 10.1097/nrl.0000000000000365 Sharifi-Razavi A, Karimi N, Jafarpour H (2022) Evaluation of Selenium Supplementation in Acute Ischemic Stroke Outcome: An Outcome Assessor Blind, Randomized, Placebo-Controlled, Feasibility Study. Neurol India 70(1):87–93. 10.4103/0028-3886.336328 Zhuo Z, Wang H, Zhang S, Bartlett PF, Walker TL, Hou ST (2023) Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice. J Cereb Blood Flow Metab 43(7):1060–1076. 10.1177/0271678x231156981 Alim I, Caulfield JT, Chen Y, Swarup V, Geschwind DH, Ivanova E et al (2019) Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke. Cell 177(5):1262–79e25. 10.1016/j.cell.2019.03.032 Shi Y, Han L, Zhang X, Xie L, Pan P, Chen F (2022) Selenium Alleviates Cerebral Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Fusion and Ferroptosis. Neurochem Res 47(10):2992–3002. 10.1007/s11064-022-03643-8 Amani H, Habibey R, Shokri F, Hajmiresmail SJ, Akhavan O, Mashaghi A et al (2019) Selenium nanoparticles for targeted stroke therapy through modulation of inflammatory and metabolic signaling. Sci Rep 9(1):6044. 10.1038/s41598-019-42633-9 Turovsky EA, Baryshev AS, Plotnikov EY (2024) Selenium Nanoparticles in Protecting the Brain from Stroke: Possible Signaling and Metabolic Mechanisms. Nanomaterials (Basel) 14(2). 10.3390/nano14020160 Tuo QZ, Masaldan S, Southon A, Mawal C, Ayton S, Bush AI et al (2021) Characterization of Selenium Compounds for Anti-ferroptotic Activity in Neuronal Cells and After Cerebral Ischemia-Reperfusion Injury. Neurotherapeutics 18(4):2682–2691. 10.1007/s13311-021-01111-9 Zhao K, Zhang Y, Sui W (2024) Association Between Blood Selenium Levels and Stroke: A Study Based on the NHANES (2011–2018). Biol Trace Elem Res 202(1):25–33. 10.1007/s12011-023-03649-5 Fang H, Liu W, Zhang L, Pei L, Gao Y, Zhao L et al (2022) A Bidirectional Mendelian Randomization Study of Selenium Levels and Ischemic Stroke. Front Genet 13:782691. 10.3389/fgene.2022.782691 Chen R, Liu H, Zhang G, Zhang Q, Hua W, Zhang L et al (2024) Antioxidants and the risk of stroke: results from NHANES and two-sample Mendelian randomization study. Eur J Med Res 29(1):50. 10.1186/s40001-024-01646-5 Hu H, Bi C, Lin T, Liu L, Song Y, Wang B et al (2021) Sex difference in the association between plasma selenium and first stroke: a community-based nested case-control study. Biol Sex Differ 12(1):39. 10.1186/s13293-021-00383-2 Liampas A, Zis P, Hadjigeorgiou G, Vavougios GD (2023) Selenium, Stroke, and Infection: A Threefold Relationship; Where Do We Stand and Where Do We. Go? Nutrients 15(6). 10.3390/nu15061405 McManus M, Ovbiagele B, Markovic D, Towfighi A (2015) Association of Insurance Status with Stroke-Related Mortality and Long-term Survival after Stroke. J Stroke Cerebrovasc Dis 24(8):1924–1930. 10.1016/j.jstrokecerebrovasdis.2015.05.007 Additional Declarations No competing interests reported. Supplementary Files Suplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-4264317","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":291366279,"identity":"988fb7a1-f03c-4122-bcf3-53c25a40831b","order_by":0,"name":"Yi Deng","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Deng","suffix":""},{"id":291366280,"identity":"ed706019-30a8-42ed-9142-a0e3fb49951f","order_by":1,"name":"Senlin Du","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Senlin","middleName":"","lastName":"Du","suffix":""},{"id":291366281,"identity":"f4d7859a-1a9b-4aa4-a620-2e3a89d8f425","order_by":2,"name":"Jiarong Tao","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Jiarong","middleName":"","lastName":"Tao","suffix":""},{"id":291366282,"identity":"7a8ec660-a1dd-4c13-9a14-065691aad5e6","order_by":3,"name":"Ruiyun Jin","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Ruiyun","middleName":"","lastName":"Jin","suffix":""},{"id":291366283,"identity":"9382a272-8fac-4edd-b490-250b5b6f197d","order_by":4,"name":"Feng Tong","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Tong","suffix":""},{"id":291366284,"identity":"711af7ba-73db-448e-986b-5ee03122cdc1","order_by":5,"name":"Jiaxing Peng","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Jiaxing","middleName":"","lastName":"Peng","suffix":""},{"id":291366285,"identity":"ff8781fa-8a00-49dc-a68a-f6848473e3cb","order_by":6,"name":"Hua Fang","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Hua","middleName":"","lastName":"Fang","suffix":""},{"id":291366286,"identity":"5ac4c1b8-1381-46ec-a2bd-d1a0e379b63a","order_by":7,"name":"Miaojing Wu","email":"","orcid":"","institution":"Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Miaojing","middleName":"","lastName":"Wu","suffix":""},{"id":291366287,"identity":"9d35ba54-b30e-454d-a058-ccdec6973258","order_by":8,"name":"Zhenyu Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYPACNgZ+ZubDD4hSywPTItnOlmZAihYGBoPzPAoSRGmxZz97+OXPNr5848M8DAYMNTbRhG3hyUuzkGxjs9x2mPfAA4ZjabkNhB2WY2Zg2MZmYHaYL8GAseEwEVr435gZJAK1GDfzGEgQp0Uix/jBQaAWA2aitdx4Y8bYcI7NQOIwMJATiPELe3+O8ccfZccM+PsPH37wocaGsBYgYJNgZDsGYSYQoRwEmD8w/KkhUu0oGAWjYBSMSAAAVpo5IQzU7UwAAAAASUVORK5CYII=","orcid":"","institution":"Nanchang University","correspondingAuthor":true,"prefix":"","firstName":"Zhenyu","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2024-04-14 09:14:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4264317/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4264317/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55063211,"identity":"cee0c141-a271-48ca-bd55-e9b16e7e60a0","added_by":"auto","created_at":"2024-04-22 03:04:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25471,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of study population selection, NHANES 1999-2018.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4264317/v1/a9959d20dedec1af6f3ab071.png"},{"id":55063212,"identity":"53e5a53f-af59-4e8d-a42c-6c60c0b5d831","added_by":"auto","created_at":"2024-04-22 03:04:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47248,"visible":true,"origin":"","legend":"\u003cp\u003eRCS analysis of the association between dietary selenium intake and mortality after stroke, NHANES 1999-2018. A, all-cause mortality; B, CVD mortality; C, cancer mortality.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4264317/v1/97cd3d23bb296891a7982795.png"},{"id":55063213,"identity":"68cffc46-91a7-4d1c-80eb-df657c11f4ca","added_by":"auto","created_at":"2024-04-22 03:04:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":12314,"visible":true,"origin":"","legend":"\u003cp\u003eStratified analysis by age and sex of the association between dietary selenium intake and mortality after stroke, NHANES 1999-2018.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4264317/v1/c2418c45e79d5477b34e02cc.png"},{"id":55064001,"identity":"6099a589-c7af-4771-b599-fef54d631a41","added_by":"auto","created_at":"2024-04-22 03:20:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":618236,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4264317/v1/9015dd99-8174-476f-9614-8d9c7e878e01.pdf"},{"id":55063214,"identity":"78ff84c8-5c13-40c5-83ab-540698cce41e","added_by":"auto","created_at":"2024-04-22 03:04:27","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":964252,"visible":true,"origin":"","legend":"","description":"","filename":"Suplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4264317/v1/d8ce8631172a91b3a7a07e13.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Nonlinear associations of dietary selenium intake with all-cause and cardiovascular mortality after stroke in US adults: findings from NHANES 1999-2018","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eStroke is an acute cerebrovascular disease caused by cerebrovascular accidents and is the leading cause of disability and death worldwide[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Stroke primarily consists of ischemic and hemorrhagic strokes, with most cases being ischemic strokes[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The recent Global Burden of Disease Study 2019 suggests that in 2019, stroke is the second leading cause of death and the third leading cause of death and disability[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The burden of disease for stroke has risen significantly over the past 30 years, especially among younger populations[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The World Stroke Organization predicts that stroke mortality will continue to increase by 50% over the next 30 years, as will its disability-adjusted life years[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite significant advances in stroke treatment over the past decade, primordial, primary, and secondary prevention of stroke remains the cornerstone of reducing the risk and consequences of stroke[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Identifying risk factors for stroke onset and/or progression and implementing solid stroke prevention strategies have important public health implications for reducing the disease burden associated with stroke[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSelenium is an essential trace mineral that plays an important role in human health. Proper dietary selenium intake has positive implications for maintaining physical health and preventing the onset of certain diseases. Selenium is well recognized as having an essential role in the body's antioxidant, anti-inflammatory, and maintenance of normal immune system function[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Dietary selenium intake or blood selenium levels have been shown to be strongly associated with the occurrence or progression of stroke. A recent meta-analysis showed an inverse correlation between circulating selenium levels and the risk of stroke, suggesting the preventive value of adequate blood selenium levels for stroke[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A recent study using the National Health and Nutrition Examination Survey (NHANES) database indicated that dietary selenium intake was inversely associated with the prevalence of stroke in the U.S. population[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Similar findings from other countries have demonstrated a negative correlation between dietary selenium intake and the occurrence of stroke[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, there is still a lack of exploration regarding the effect of dietary selenium intake on mortality in stroke survivors. Given that stroke populations are associated with high mortality rates, understanding the association between dietary selenium intake and mortality after stroke is of public health importance.\u003c/p\u003e \u003cp\u003eIn this longitudinal cohort study, we aimed to explore the association of dietary selenium intake with all-cause and cause-specific mortality after stroke through a nationally representative population-based survey, NHANES 1999\u0026ndash;2018. These findings support the importance of appropriate dietary selenium intake for improving clinical outcomes in stroke populations, and excessive deaths may be able to be reduced by intervening in dietary selenium intake, a modifiable risk factor, in stroke patients.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cp\u003e \u003cb\u003eStudy design and population\u003c/b\u003e \u003c/p\u003e \u003cp\u003eNHANES is a serial ongoing nationwide cross-sectional survey aimed at assessing the health and nutritional status of non-institutionalized citizens in the U.S. Beginning in 1999, NHANES is conducted in biennial cycles and uses a staged probability sampling design to draw nationally representative participants. NHANES is run by the National Center for Health Statistics (NCHS) and contains standardized interview and physical examination data. More information can be found on the official NHANES website (\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).\u003c/p\u003e \u003cp\u003eThe study population selection flowchart was presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In this study, we included stroke participants in a total of 10 consecutive cycles of NHANES 1999\u0026ndash;2018 and followed them until December 31, 2019, thus it was a longitudinal cohort study. We first included 2,264 stroke participants from NHANES 1999\u0026ndash;2018 and sequentially excluded pregnancy (n\u0026thinsp;=\u0026thinsp;1), those with missing survival (n\u0026thinsp;=\u0026thinsp;3) and dietary intake information (n\u0026thinsp;=\u0026thinsp;533), and those missing other covariates (n\u0026thinsp;=\u0026thinsp;393). Ultimately, 1334 stroke patients were enrolled in further analyses.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAssessment of dietary selenium intake\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDietary selenium intake was calculated using the USDA's Food and Nutrient Database for Dietary Studies (FNDDS). In NHANES 1999\u0026ndash;2002, information on dietary selenium intake was obtained through 24-h face-to-face dietary recall interviews, whereas in 2003\u0026ndash;2018, dietary selenium intake was obtained by averaging data obtained from a single face-to-face interview and a telephone follow-up 3\u0026ndash;10 days later. Selenium intake from non-dietary sources such as supplements and medications were not considered.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStroke evaluation\u003c/b\u003e \u003c/p\u003e \u003cp\u003eParticipants' stroke status was determined by self-report on the Medical Conditions Questionnaire. A history of stroke was obtained by a participant's positive response to the question \"Has a doctor or other health professional ever told you that you had a stroke?\".\u003c/p\u003e \u003cp\u003e \u003cb\u003eMortality data collection\u003c/b\u003e \u003c/p\u003e \u003cp\u003eMortality data were obtained by prospectively matching to the National Death Index database. We followed baseline stroke patients through December 31, 2019. Our study outcomes were all-cause, CVD, and cancer-related mortality among stroke patients. CVD mortality information was derived from codes associated with cardiac and cerebrovascular disease deaths, including I00-I09, I11, I13, I20-I51, and I60-I69. Information on cancer-related mortality was obtained through codes C00-C97.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCovariates\u003c/b\u003e \u003c/p\u003e \u003cp\u003eParticipants' age, gender, race/ethnicity, education level, marital status, family income-poverty ratio (PIR), body mass index (BMI), smoking, alcohol consumption, physical activity, diabetes, hypertension, and coronary heart disease (CHD) information was collected. BMI\u0026thinsp;=\u0026thinsp;body weight (kg) divided by height (m) squared. Smoking status was divided into never smokers (\u0026lt;\u0026thinsp;100 lifetime cigarettes), former smokers (\u0026ge;\u0026thinsp;100 lifetime cigarettes but now quit), and current smokers based on self-report[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Drinking patterns were categorized into never drinkers, former drinkers, and current light, moderate, and heavy drinkers based on previous studies[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Physical activity intensity was categorized as never, moderate, and vigorous based on self-reports in the Global Physical Activity Questionnaire. Diabetes was ascertained by a self-reported history of diabetes (as reported by a physician or other professional), glycated hemoglobin\u0026thinsp;\u0026ge;\u0026thinsp;6.5%, fasting blood glucose\u0026thinsp;\u0026ge;\u0026thinsp;7.0 mmol/L, blood glucose\u0026thinsp;\u0026ge;\u0026thinsp;11.1 mmol/L on a glucose tolerance test, or taking diabetes-related medications[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Hypertension was determined based on one of the following: a self-reported history of hypertension, a blood pressure value of \u0026ge;\u0026thinsp;140/90 mmHg, or the use of anti-hypertensive medications[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. CHD history was determined by participants' affirmative responses to specific questions in the questionnaire.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAll statistical analyses were performed using R software version 4.2.3 and EmpowerStats software with appropriate weighting to make the sample nationally representative. A two-sided P value of less than 0.05 was considered statistically significant. In the baseline analysis, we grouped the stroke population according to quartiles of dietary selenium intake. Between-group differences for continuous variables were analyzed by analysis of variance (ANOVA) and reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error, whereas categorical variables were tested by chi-square analysis and reported as number (percentage). We employed Kaplan-Meier (KM) survival analyses and log-rank tests to explore the differences in all-cause, CVD, and cancer-related survival probabilities over time after stroke between different levels of selenium intake. To explore whether the association between selenium intake and mortality in stroke patients was independent of other confounders, we performed multivariate Cox proportional hazards regression analyses. Model 1 was a crude model that did not adjust for any covariates; Model 2 adjusted for sociodemographic variables including age, gender, race, education level, PIR, and marital status; and Model 3 additionally adjusted for BMI, smoking, alcohol consumption, physical activity, diabetes, hypertension, and CHD. We applied restricted cubic spline (RCS) to explore potential nonlinear associations between dietary selenium intake and post-stroke mortality (p for nonlinear). In addition, to explore whether the effect of dietary selenium intake on post-stroke mortality was consistent across subgroups of two important sociodemographic variables (age and sex), we performed stratified analyses. Finally, we excluded populations within 2 years of follow-up in sensitivity analyses to rule out the effect of short-term follow-up.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEthics statement\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAll NHANES survey cycles have been reviewed and approved by the NCHS Ethics Review Board. All participants provided written informed consent. Therefore, since this study analyzed pre-existing data and all participants were de-identified and anonymized, local institutional ethical review approval was waived.\u003c/p\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003e \u003cb\u003eBaseline stroke population analysis based on dietary selenium intake\u003c/b\u003e \u003c/p\u003e \u003cp\u003eQuartiles of dietary selenium intake were Q1 (\u0026lt;\u0026thinsp;61.650 mcg/d), Q2 (61.650\u0026ndash;85.800 mcg/d), Q3 (85.800-115.815 mcg/d), and Q4 (\u0026gt;\u0026thinsp;115.815 mcg/d). The mean age of stroke survivors was 63.935 years, of which 43.785% were male. Age, BMI, gender, race, marital status, education, and drinking status of stroke patients differed significantly between dietary selenium intakes (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). As dietary selenium intake increased, stroke patients were younger, had a higher BMI, were more likely to be male, of other races, non-single, greater than a high school education, and current drinkers (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\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\u003eBaseline analysis of stroke populations according to dietary selenium intake, NHANES 1999\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=\"char\" char=\".\" 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 \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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQ1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQ3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQ4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\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\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.935(0.544)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.660\u003c/p\u003e \u003cp\u003e(0.970)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.399\u003c/p\u003e \u003cp\u003e(1.086)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.088\u003c/p\u003e \u003cp\u003e(0.874)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60.847\u003c/p\u003e \u003cp\u003e(1.087)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.011\u003c/p\u003e \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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.433(0.059)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.263\u003c/p\u003e \u003cp\u003e(0.102)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.351\u003c/p\u003e \u003cp\u003e(0.116)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.441\u003c/p\u003e \u003cp\u003e(0.113)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.661\u003c/p\u003e \u003cp\u003e(0.130)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e, kg/m2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30.127(0.254)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.843\u003c/p\u003e \u003cp\u003e(0.412)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.120\u003c/p\u003e \u003cp\u003e(0.495)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.879\u003c/p\u003e \u003cp\u003e(0.535)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.705\u003c/p\u003e \u003cp\u003e(0.489)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelenium intake\u003c/b\u003e mcg/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95.732(1.915)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.771\u003c/p\u003e \u003cp\u003e(0.983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.497\u003c/p\u003e \u003cp\u003e(0.497)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e99.906\u003c/p\u003e \u003cp\u003e(0.626)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e158.675\u003c/p\u003e \u003cp\u003e(3.237)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e669(43.785)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116(26.650)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e140(33.125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e173(42.851)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e240(70.696)\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\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e665(56.215)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e218(73.350)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e194(66.875)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e160(57.149)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93(29.304)\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\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMexican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e143(3.834)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31(2.689)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34(3.874)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43(4.877)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35(3.942)\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\u003eNon-Hispanic Black\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e330(13.161)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94(15.143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76(12.168)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77(13.393)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e83(12.090)\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\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e727(74.494)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177(75.145)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e195(77.593)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e183(74.340)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e172(71.035)\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\u003eOther Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68(3.006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(3.454)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15(2.578)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15(3.004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19(3.007)\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\u003eOther Race\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66(5.506)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(3.570)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(3.788)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15(4.386)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24(9.925)\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\u003eMarital Status\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-single\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e727(59.748)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e165(54.913)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e176(54.641)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e182(58.686)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e204(70.066)\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\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e607(40.252)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169(45.087)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e158(45.359)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e151(41.314)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e129(29.934)\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\u003eEducation\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e216(9.654)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65(12.322)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51(8.925)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65(12.476)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35(5.436)\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\u003ehigh school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e601(46.292)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155(49.320)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e151(48.092)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e142(43.867)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e153(43.875)\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\u0026gt; high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e517(44.054)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114(38.358)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132(42.983)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e126(43.657)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e145(50.689)\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\u003eSmoking\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e536(41.015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e134(38.388)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139(44.974)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e137(41.692)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e126(39.028)\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\u003eFormer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e508(35.769)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121(35.672)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e128(32.495)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e132(36.536)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e127(38.352)\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\u003eNow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e290(23.215)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79(25.940)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67(22.531)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64(21.773)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e80(22.621)\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\u003eDrinking\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e211(15.544)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64(16.962)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54(17.365)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59(18.614)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34(9.802)\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\u003eFormer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e478(30.949)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132(36.208)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114(28.718)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e123(31.030)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e109(28.179)\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\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e397(32.814)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82(28.902)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95(28.608)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e104(36.945)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e116(36.882)\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\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e116(9.528)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(8.862)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33(12.133)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24(5.657)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31(11.004)\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\u003eHeavy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e132(11.165)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(9.066)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38(13.175)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23(7.754)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43(14.132)\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\u003ePhysical activity\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e868(61.225)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e235(65.961)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e227(63.784)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e208(57.632)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e198(57.518)\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\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e306(26.152)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66(23.050)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73(24.729)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92(29.995)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75(27.037)\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\u003eVigorous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e160(12.623)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(10.988)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34(11.486)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33(12.373)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60(15.446)\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\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e816(65.326)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e207(66.067)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e200(66.632)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e205(65.250)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e204(63.449)\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\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e518(34.674)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127(33.933)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e134(33.368)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128(34.750)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e129(36.551)\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\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.637\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e244(21.696)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62(22.110)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59(20.132)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55(19.604)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68(24.649)\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\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1090(78.304)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e272(77.890)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e275(79.868)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e278(80.396)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e265(75.351)\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\u003eCHD\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=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.659\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1095(81.355)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270(80.178)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e276(80.811)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e284(84.480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e265(80.241)\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\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e239(18.645)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64(19.822)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58(19.189)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49(15.520)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68(19.759)\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 \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eContinuous variables were expressed using means (standard errors) and categorical variables were expressed using numbers (percentages). PIR, income-poverty ratio; BMI, body mass index; CHD, coronary heart disease.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAssociation between dietary selenium intake and mortality after stroke\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAfter a median follow-up duration of 84 months (interquartile range: 44.5\u0026ndash;130 months), 599 (40.101%) stroke patients died, with 241 and 95 CVD- and cancer-related deaths, respectively. KM survival curves and log-rank tests revealed a significantly higher probability of all-cause survival in stroke patients with increasing quartiles of dietary selenium intake (p\u0026thinsp;=\u0026thinsp;0.023), whereas there was no significant difference in the probability of CVD (p\u0026thinsp;=\u0026thinsp;0.159) and cancer-related survival (p\u0026thinsp;=\u0026thinsp;0.442) (\u003cb\u003eSupplementary Figs.\u0026nbsp;1\u0026ndash;3\u003c/b\u003e). Consistently, multivariate Cox proportional hazards regression analyses demonstrated that dietary selenium intake was significantly and inversely associated with all-cause mortality in stroke patients after adjusting for all covariates (hazard ratio [HR] and 95% confidence interval [CI]\u0026thinsp;=\u0026thinsp;0.997 (0.995,1.000), p\u0026thinsp;=\u0026thinsp;0.024). Compared to Q1, stroke patients with dietary selenium intake at Q2, Q3, and Q4 had 32.5%, 32.2%, and 27% lower all-cause mortality, respectively (p for trend\u0026thinsp;=\u0026thinsp;0.02) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Compared to the reference population, dietary selenium intake at Q2 was associated with significantly lower CVD mortality among stroke patients (HR\u0026thinsp;=\u0026thinsp;0.647, p\u0026thinsp;=\u0026thinsp;0.035) (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). However, dietary selenium intake was not significantly associated with cancer mortality in the stroke population (\u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e).\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 of dietary selenium intake with all-cause mortality in the stroke population, NHANES 1999\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=\"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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\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\u003eModel 1\u003c/p\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep\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\u003eDietary selenium intake\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.995(0.993,0.998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.997(0.994,1.000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.997(0.995,1.000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDietary selenium intake quartiles\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\u003eQ1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eref\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eref\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eref\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eref\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eref\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eref\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQ2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.788(0.593,1.048)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.704(0.516,0.960)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.675(0.512,0.891)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQ3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.815(0.625,1.063)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.712(0.546,0.928)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.678(0.530,0.868)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQ4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.609(0.446,0.832)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.764(0.551,1.060)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.730(0.548,0.973)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP for trend\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eModel 1 was a crude model that did not adjust for any covariates; Model 2 adjusted for sociodemographic variables including age, gender, race, education level, PIR, and marital status; and Model 3 additionally adjusted for BMI, smoking, alcohol consumption, physical activity, diabetes, hypertension, and CHD.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eNonlinear correlations exploration\u003c/b\u003e \u003c/p\u003e \u003cp\u003eRCS analysis showed that dietary selenium intake was significantly nonlinearly associated with all-cause (p for nonlinearity\u0026thinsp;=\u0026thinsp;0.0189) and CVD mortality (p for nonlinearity\u0026thinsp;=\u0026thinsp;0.0361) in patients with stroke, whereas there was no significant association with cancer mortality (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Further segmented regression analyses suggested that dietary selenium intake was inversely associated with all-cause mortality in stroke patients only at \u0026lt;\u0026thinsp;81 mcg/d (HR\u0026thinsp;=\u0026thinsp;0.988, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and lost significant association above this value (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Similarly, dietary selenium intake was marginally associated with CVD mortality at \u0026lt;\u0026thinsp;87 mcg/d (\u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \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\u003eSegmented regression analysis of dietary selenium intake and all-cause mortality in stroke patients, NHANES 1999\u0026ndash;2018.\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\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep for interaction\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll-cause\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 \u003cp\u003e0.025\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\u003eDietary selenium intake\u0026thinsp;\u0026ge;\u0026thinsp;81 mcg/d\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.999(0.995,1.004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.792\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDietary selenium intake\u0026thinsp;\u0026lt;\u0026thinsp;81 mcg/d\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.988(0.981,0.995)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eStratified analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eStratified analyses showed that age and sex did not significantly affect the association of dietary selenium intake with mortality after stroke (all p for interaction\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Subgroup analyses indicated that the association of dietary selenium intake with CVD mortality in stroke patients was only present in those\u0026thinsp;\u0026lt;\u0026thinsp;45 years of age and in men, whereas the association with all-cause mortality was only present in those\u0026thinsp;\u0026ge;\u0026thinsp;60 years of age and in women. Dietary selenium intake was not significantly associated with cancer mortality in stroke patients in any of the subgroups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSensitivity analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eSimilar results were obtained by removing stroke patients with follow-up duration within two years. Dietary selenium intake remained inversely associated with all-cause mortality in stroke patients (HR\u0026thinsp;=\u0026thinsp;0.997, p\u0026thinsp;=\u0026thinsp;0.018). Dietary selenium intake remained associated with post-stroke CVD mortality only in Q2 (compared to Q1) and was not significantly associated with cancer mortality (\u003cb\u003eSupplementary Table\u0026nbsp;4\u0026ndash;6\u003c/b\u003e).\u003c/p\u003e"},{"header":"4. DISCUSSIONS","content":"\u003cp\u003eThis is the first time the association of dietary selenium intake with all-cause, CVD, and cancer-related long-term mortality in stroke patients has been explored in a nationally representative longitudinal cohort study. After a median follow-up of 7 years among stroke participants in NHANES 1999\u0026ndash;2018, dietary selenium intake was independently and inversely associated with all-cause mortality after stroke, nonlinearly associated with CVD mortality, and not associated with cancer mortality. Dietary selenium intake was significantly associated with all-cause and CVD mortality in stroke patients only at \u0026lt;\u0026thinsp;81 mcg/d and 87 mcg/d, respectively. In addition, these associations were only present in specific age groups and gender. Our findings suggest that dietary selenium intake is an independent prognostic factor for all-cause mortality in stroke patients and that maintaining adequate dietary selenium intake may be associated with improved prognosis in stroke patients. In contrast, excessive dietary selenium intake did not provide additional protective effects.\u003c/p\u003e \u003cp\u003eSelenium is an essential trace mineral that is primarily consumed through the diet and plays an important role in human health. Selenium acts as a component of antioxidant enzymes in the body, helping to protect against cellular damage caused by free radicals, which in turn fights a variety of diseases, including stroke[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. There is still a paucity of exploration of the association of dietary selenium intake with all-cause and cause-specific mortality in stroke patients. A previous longitudinal study using NHANES 2005\u0026ndash;2014 revealed that the composite dietary antioxidant index encompassing vitamins A, C, E, selenium, zinc, and carotenoids was independently and jointly significantly associated with poststroke depression and all-cause mortality[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although studies on the effect of dietary selenium intake on mortality after stroke are still lacking, dietary selenium intake has been shown to be associated with stroke occurrence. A previous study similarly using NHANES 2003\u0026ndash;2018 suggested that dietary selenium intake was inversely and nonlinearly associated with the prevalence of stroke in the general U.S. population[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Dietary selenium intake was associated with stroke prevalence only within a certain threshold (105 \u0026micro;g/day), and there was no significant protective effect above this cutoff. Our study similarly demonstrated that dietary selenium intake was nonlinearly associated with both all-cause and CVD mortality after stroke, and significant associations existed only before 81 mcg/d and 87 mcg/d, respectively. Hu et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] similarly showed that both dietary selenium and blood selenium were inversely associated with stroke prevalence in a cross-sectional study that included 2077 Canadian Inuit participants. The association between dietary selenium and stroke prevalence was L-shaped, with dietary selenium associated with reduced stroke odds until 350 \u0026micro;g/d and a plateau thereafter. Zhang et al.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] included 11,532 participants from the China Health and Nutrition Survey 2004\u0026ndash;2015 in a retrospective cohort study and suggested that the protective effect of dietary selenium intake on stroke risk was only present at \u0026le;\u0026thinsp;60 \u0026micro;g/d, with no significant associations thereafter. These studies consistently indicated an inverse association of dietary selenium intake with stroke occurrence, whereas excessive selenium intake had no additional protective effect. Indeed, excessive selenium intake/exposure may lead to selenium toxicity and is associated with adverse health outcomes, such as positive associations with the prevalence of non-alcoholic fatty liver disease and type 2 diabetes[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Our study obtained similar findings, providing new evidence for the prognostic value of dietary selenium intake in stroke patients.\u003c/p\u003e \u003cp\u003eIt is worth noting that the average dietary selenium intake of populations in different countries/regions varies significantly, for example, the average selenium intake of the Chinese population was 47.36 \u0026micro;g/d[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], which is significantly lower than that of the general population in the U.S.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and even lower than that of the stroke population included in our study (95.732 \u0026micro;g/d). The current recommendation for adequate dietary selenium intake in the adult population is 70 \u0026micro;g/d[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and our study suggested that the recommended adequate intake for the prevention of all-cause and CVD mortality in the US stroke population is higher, suggesting the need for population- and target-specific adequate intake values.\u003c/p\u003e \u003cp\u003eSeveral clinical investigations and experimental studies have explored the effect of selenium supplementation on clinical outcomes in stroke patients. A clinical trial enrolling 44 patients with acute ischemic stroke demonstrated that Selenase supplementation for 5 days improved neurological deficits, antioxidant activity, and levels of inflammatory markers in stroke patients compared to the placebo group[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Another randomized clinical trial that included 40 patients with acute ischemic stroke demonstrated that selenium selenite supplementation for 5 days was associated with short-term neurological improvement in stroke patients, but not with long-term clinical outcomes[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Zhuo et al.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] demonstrated that selenium supplementation (selenomethionine) in a mouse model of overt middle cerebral artery occlusion ameliorated cerebral infarct volume, oxidative stress, and ferroptosis, and was associated with improvements in stroke-induced gut dysbiosis, suggesting multifaceted potential neuroprotective effects of long-term selenium supplementation. In a comprehensive experimental exploration, Alim et al.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] demonstrated that brain-permeable selenopeptide supplementation improves neurological function in stroke by coordinating the activation of the transcription factors TFAP2c and Sp1 to protect neurons, thereby enhancing glutathione peroxidase 4 (GPX4) and other genes, and thereby inhibiting GPX4-dependent ferroptosis and other GPX4-independent cell death. Additional experimental studies have similarly shown that selenium supplementation ameliorates oxidative stress, iron death, metabolic, and inflammatory signaling pathways in mouse ischemic stroke models[\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral clinical studies have also suggested an inverse association between circulating/blood selenium levels and stroke occurrence. A meta-analysis that included 11 observational studies indicated a significant inverse correlation between circulating selenium levels and stroke occurrence (relative risk\u0026thinsp;=\u0026thinsp;0.48, 95% CI\u0026thinsp;=\u0026thinsp;0.24\u0026ndash;0.94; p\u0026thinsp;=\u0026thinsp;0.033)[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A recent cross-sectional study utilizing NHANES 2011\u0026ndash;2018 similarly suggested that blood selenium was negatively associated with stroke prevalence (odds ratio\u0026thinsp;=\u0026thinsp;0.57, p\u0026thinsp;=\u0026thinsp;0.014) and that there was a dose-response association[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, Mendelian randomization studies suggested that single-nucleotide polymorphisms associated with circulating selenium levels were not associated with ischemic stroke, which seems to indicate that circulating selenium levels are not causally associated with ischemic stroke as genetically predicted[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough age and sex did not significantly influence the association of dietary selenium intake with mortality after stroke, we observed that these associations were only present in specific age groups and genders. Previous studies have similarly suggested that the association between dietary selenium intake and stroke prevalence is age- and sex-specific[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Age and gender are recognized as important sociodemographic risk factors for stroke. Stroke prevalence and dietary selenium intake may differ significantly by age. In addition, dietary selenium intake and selenium metabolism may be gender-specific due to differences in the effects of estrogen on selenoprotein metabolism and other sociodemographic factors[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Our findings emphasize that the association of dietary selenium intake with all-cause and CVD mortality in stroke patients requires consideration in specific age groups and genders.\u003c/p\u003e \u003cp\u003eThere are several notable strengths of this study. This is the first time that the association between dietary selenium intake and post-stroke mortality has been explored in a nationwide longitudinal cohort study, and the prognostic value of dietary selenium intake in the U.S. stroke population has been revealed through a comprehensive exploration. Our study has a relatively large sample, a nationally representative multiethnic cohort, and included stroke participants over a 20-year period with long-term follow-up to ensure reliability and generalizability of the results. In addition, we have fully considered the effects of potential confounders to ensure the robustness of our results. However, our study has some shortcomings. It was a longitudinal cohort study, and therefore temporal causality could not be derived, and residual confounders may exist. The diagnosis of stroke was based on self-report rather than imaging, which may lack accuracy. However, previous studies have shown good agreement with the questionnaire in NHANES[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. In addition, we were unable to obtain stroke subtypes (ischemic and hemorrhagic), stroke severity, and other clinical characteristics, and thus may have lacked deeper levels of exploration. Future high-quality studies with large samples are needed to validate our findings.\u003c/p\u003e"},{"header":"5. CONCLUSIONS","content":"\u003cp\u003eIn a national longitudinal cohort study, dietary selenium intake was nonlinearly associated with all-cause and CVD mortality after stroke, but not with cancer mortality. Inverse associations of dietary selenium intake with all-cause and CVD mortality in stroke patients were only present at \u0026lt;\u0026thinsp;81 mcg/d and 87 mcg/d, respectively, and only in specific age groups and genders. These findings support the prevention of excess mortality in stroke patients by adequate dietary selenium intake, and more well-designed studies are warranted to confirm our conclusions in the future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e: This study analyzed publicly available datasets and can be found at https://www.cdc.gov/nchs/nhanes/.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e: The studies involving human participants were reviewed and approved by the NCHS Ethics Review Board and no additional ethical review consent is required. All participants have provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: The National Natural Science Foundation of China (grant number 82060214) and the Natural Science Foundation of Jiangxi Province (grant number 20212BAB206047).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: The authors declare no conflict of interest in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: We thank all the participants in the NHANES for providing data for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e:These authors contributed equally:Yi Deng, Senlin Du and Jiarong Tao: \u003ca href=\"mailto:[email protected];\"\[email protected];\u003c/a\u003e \u003ca href=\"mailto:[email protected];\"\[email protected];\u003c/a\u003e \u003ca href=\"mailto:[email protected];\"\[email protected];\u003c/a\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A et al (2013) An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. 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J Stroke Cerebrovasc Dis 24(8):1924\u0026ndash;1930. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jstrokecerebrovasdis.2015.05.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jstrokecerebrovasdis.2015.05.007\" 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":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"selenium, stroke, mortality, dietary intake, NHANES","lastPublishedDoi":"10.21203/rs.3.rs-4264317/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4264317/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The association between dietary selenium intake and mortality in stroke patients remains unclear. We aimed to explore these associations through NHANES 1999-2018.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Stroke participants ≥20 years of age were enrolled and were followed until December 31, 2019. Dietary selenium intake and stroke diagnosis were obtained by self-report on the questionnaire. Mortality information was obtained through prospective matching with the National Death Index database.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 1334 stroke survivors were included. Dietary selenium intake was significantly and inversely associated with all-cause mortality in stroke patients after adjusting for all confounders (hazard ratio [HR]=0.997, p=0.024). Compared to the reference population, stroke patients with dietary selenium intake in quartiles Q2, Q3, and Q4 were associated with reduced all-cause mortality (p for trend=0.02). Dietary selenium intake at Q2 was associated with reduced CVD mortality after stroke and not significantly associated with cancer mortality. Restricted cubic spline analysis indicated that dietary selenium intake was nonlinearly associated with all-cause (p for nonlinear=0.0361) and CVD mortality (p for nonlinear=0.0189) in stroke patients. Segmented regression showed that dietary selenium intake was inversely associated with all-cause and CVD mortality at \u0026lt;81 mcg/d and 87 mcg/d, respectively, with no additional protective effects thereafter. Stratified analyses suggested that these effects were only present in specific ages and genders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e In a national longitudinal cohort, dietary selenium intake was nonlinearly associated with all-cause and CVD mortality but not cancer mortality after stroke in U.S. adults. Dietary selenium intake at 81 mcg/d and 87 mcg/d had the optimal protective effect on post-stroke all-cause and CVD mortality, respectively.\u003c/p\u003e","manuscriptTitle":"Nonlinear associations of dietary selenium intake with all-cause and cardiovascular mortality after stroke in US adults: findings from NHANES 1999-2018","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-22 03:04:22","doi":"10.21203/rs.3.rs-4264317/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"10d23a19-918c-44f3-a28b-5d2305b8eb35","owner":[],"postedDate":"April 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-09T14:17:46+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-22 03:04:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4264317","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4264317","identity":"rs-4264317","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}