Sex-specific Associations Research Articles

Association between adipose deposition and mortality among adults without major cardiovascular risk factors

AimTo examine the association between adiposity and mortality in U.S. adults without major cardiovascular risk factors. MethodsWe analyzed 7,948 adults (4,123 women, 3,825 men) aged > 20 years from the National Health and Nutrition Examination Survey (2003-2004, 2011-2016). Participants with cardiovascular disease, estimated glomerular filtration rate < 60 ml/min/1.73m², diabetes, hypertension, or pregnancy were excluded. Adiposity measures, assessed by dual-energy x-ray absorptiometry or anthropometrics, included android and gynoid fat mass index (FMI), android-to-gynoid ratio, subcutaneous, abdominal, and visceral FMI, BMI, and waist circumference. We employed multivariable-adjusted Cox regression and restricted cubic spline models to assess sex-specific associations between adiposity measures and all-cause mortality. ResultsOver a median follow-up of 7.8 years, there were 83 deaths among women and 119 among men. In women, BMI, waist circumference, and gynoid FMI showed non-linear associations with all-cause mortality, while in men, BMI, waist circumference, and android-to-gynoid ratio demonstrated similar non-linear associations. In final adjusted models, a 1-SD increase in visceral, subcutaneous, and abdominal FMI among women was associated with 61% (HR 1.61, 95% CI 1.17-2.21), 87% (HR 1.87, 95% CI 1.13-3.08), and 89% (HR 1.89, 95% CI 1.19-2.99) higher mortality risk, respectively. Women in the lowest tertile of gynoid FMI had an 82% (HR 1.82, 95% CI 1.01-3.29) higher mortality risk compared to those in the middle tertile. In final adjusted models, a 1-SD increase in gynoid, android, visceral, subcutaneous, and abdominal FMI among men was associated with 30% (HR 1.30, 95% CI 1.02-1.65), 41% (HR 1.41, 95% CI 1.09-1.83), 54% (HR 1.54, 95% CI 1.04-2.28), 69% (HR 1.69, 95% CI 1.25-2.29), and 76% (HR 1.76, 95% CI 1.25-2.48) higher mortality risk, respectively. Additionally, men in the middle tertile of android-to-gynoid ratio had a 2.68-fold higher mortality risk compared to the lowest tertile, while men in the highest BMI tertile had an 83% higher mortality risk compared to the lowest tertile. Sex modified the association between gynoid FMI and mortality (P-interaction = 0.008). ConclusionImaging-based adiposity measures have distinct prognostic value for mortality beyond traditional anthropometrics in adults without cardiovascular risk factors.

Sex-specific association of total mineral intake with pulmonary function in middle-aged and older adults with chronic obstructive pulmonary disease

The objective of this study is to assess the impact of dietary intake and supplementation of total magnesium, iron, zinc and selenium on pulmonary function in middle-aged to elderly individuals diagnosed with chronic obstructive pulmonary disease (COPD). This study utilized publicly available data from NHANES, focusing on the 2007–2012 cycles to include participants aged 50 and above with COPD. The definition of COPD followed the 2024 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Dietary mineral intake was assessed through two 24-h dietary recall surveys. Pulmonary function assessments included parameters such as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced mid-expiratory flow (FEF 25–75%), and peak expiratory flow (PEF). Sex-specific associations of total magnesium, iron, zinc, and selenium intakes with pulmonary function parameters were assessed using multivariable regression models adjusted by potential covariates. The study sample had a mean age of 64.56 ± 8.26 years, with 35% being female. The median intakes of total magnesium, iron, zinc, and selenium for males were 312.8 mg, 15.6 mg, 14.4 mg, and 127.9 mcg, respectively, while for females, they were 257.5 mg, 12.8 mg, 11.4 mg, and 96.2 mcg. In males, higher total magnesium and iron intake were significantly associated with increased FEV1, FVC, and PEF (P < 0.05), while in females, only total zinc intake showed a positive association with PEF (P < 0.05). Participants meeting the recommended dietary allowance for total magnesium also exhibited significantly better lung function outcomes in both sexes. This study highlights the importance of adequate dietary mineral intake in managing pulmonary health among COPD patients. Enhancing mineral consumption, particularly magnesium, and iron, may be a viable strategy for improving lung function and overall health in this population, especially in men.

Gestational Exposure to Endocrine-Disrupting Chemicals of Emerging Concern and the Risk of Developing Gestational Diabetes Mellitus: A Comprehensive Investigation of Sex-Specific and Trimester-Specific Associations

Gestational Exposure to Endocrine-Disrupting Chemicals of Emerging Concern and the Risk of Developing Gestational Diabetes Mellitus: A Comprehensive Investigation of Sex-Specific and Trimester-Specific Associations

Air pollution mixture exposure during pregnancy and postpartum psychological functioning: racial/ethnic- and fetal sex-specific associations.

Prenatal air pollution (AP) exposure has been linked to postpartum psychological functioning, impacting health outcomes in both women and children. Extant studies primarily focused on individual pollutants. To assess the association between prenatal exposure to a mixture of seven AP components and postpartum psychological functioning using daily exposure data and data-driven statistical methods. Analyses included 981 women recruited at 24.0 ± 9.9 weeks gestation and followed longitudinally. We estimated prenatal daily exposure levels for constituents of fine particles [elemental carbon (EC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+)], nitrogen dioxide (NO2), and ozone (O3) using validated global 3-D chemical-transport models and satellite-based hybrid models based on residential addresses. Edinburgh Postnatal Depression Scale (EPDS) was administered to participants to derive a total EPDS score and the subconstruct scores for anhedonia and depressive symptoms. A distributed lag model (DLM) was employed within Bayesian Kernel Machine Regression (BKMR) to develop time-weighted exposure profile for each pollutant. These exposures were then input into a Weighted Quantile Sum (WQS) regression to estimate an overall mixture effect, adjusted for maternal age, education, race/ethnicity, season of delivery, and delivery year. Effect modification by race/ethnicity and fetal sex was also examined. Women were primarily Hispanic (51%) and Black (32%) reporting ≤12 years of education (58%). Prenatal exposure to an AP mixture was significantly associated with increased anhedonia subscale z-scores, particularly in Hispanics (β = 0.07, 95%CI = 0.004-0.13, per unit increase in WQS index). It was also borderline associated with increased total EPDS (β = 0.11, 95%CI = 0.00-0.22) and depressive symptom subscale (β = 0.09, 95%CI = -0.02 to 0.19) z-scores, particularly among Hispanic women who gave birth to a male infant. Sulfate (SO42-), O3 and OC were major contributors to these associations. This study utilizes an advanced data-driven approach to examine the temporally- and mixture-weighted effects of prenatal air pollution exposure on postpartum psychological functioning. We found that exposure to a prenatal air pollution mixture predicted poorer postpartum psychological functioning, particularly anhedonia symptoms in Hispanic women. Findings underscore the importance of considering both exposure mixtures as well as potential modifying factors to better help identify particular pollutants that drive effects and susceptible populations, which can inform more effective intervention strategies.

Sex-specific association of per- and polyfluoroalkyl substances (PFAS) exposure with vitamin D concentrations in older adults in the USA: an observational study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are commonly utilized in consumer products. While earlier studies have suggested potential impacts of certain PFAS on serum concentrations of vitamin D, these investigations were constrained to a limited set of conventional PFAS. Moreover, they did not specifically focus on populations with longer duration of PFAS exposure and potentially higher blood PFAS levels, such as older adults, and lacked adequate evidence to examine sex-related disparities.MethodsThis observational investigation utilized cross-sectional data obtained from the U.S. NHANES spanning the years 2003 to 2018. Survey-weighted multiple regression models were employed to evaluate the relationship between PFAS exposure and vitamin D concentrations. Multi-pollutant models were employed to evaluate the association between PFAS mixtures and vitamin D concentrations. Subsequently, environmental risk scores (ERS) were constructed to gauge associations with vitamin D concentrations. ERS was computed through a weighted linear combination of PFAS, utilizing calculations from ridge regression and adaptive elasticity network (adENET) methodologies. All analyses were stratified by sex.ResultsThe study encompassed 3,853 older adults. Our analysis revealed a negative association between PFOA, PFOS, PFNA, and MeFOSAA and serum vitamin D concentrations. In analyses examining mixed exposures, various models consistently indicated an inverse association between PFAS mixed exposure and vitamin D concentrations. Moreover, an increase in ERS of PFAS across the interquartile range was associated with a decrease in vitamin D concentrations (Q4 vs. Q1, adENET: β: -0.083, 95% CI: -0.117, -0.048; ridge regression: β: -0.077, 95% CI: -0.111, -0.042). Notably, these associations were exclusively observed within the female population.ConclusionsOur study indicates that heightened exposure to PFAS correlates with diminished serum vitamin D concentrations in females aged 60 years and older, evident in both single and mixed exposures. These findings find support in in vitro mechanistic studies, suggesting that PFAS may impact the metabolism of 25(OH)D, consequently affecting vitamin D concentrations.

Sex-specific associations of cigarettes and e-cigarettes use with self-reported premature atherosclerotic cardiovascular disease among adults aged 18–54 in the United States

BackgroundPremature atherosclerotic cardiovascular disease (ASCVD) is increasing in young adults (<55 years old). While research suggests females who smoke cigarettes have a higher risk of ASCVD than males, studies on the impact of exclusive e-cigarette and dual use on premature ASCVD are limited. This study investigated the association between tobacco use and self-reported premature ASCVD and explored potential sex differences. MethodsUsing pooled data from 480,317 adults (ages 18–54; ∼50 % female) from the 2020–2022 Behavioral Risk Factor Surveillance System from the United States, logistic regression models assessed associations between cigarette and e-cigarette use patterns and self-reported premature ASCVD. Tobacco use categories were defined as: non-use, former use (cigarettes, e-cigarettes), and current use (cigarettes, e-cigarettes) and dual use. Self-reported premature ASCVD was defined as self-reported angina or coronary heart disease, heart attack, or stroke. Weighted analyses were conducted for the overall sample and stratified by sex. ResultsAfter controlling for potential confounders, former exclusive cigarette (adjusted OR: 1.47 [95 % CI 1.29, 1.67]), current exclusive cigarette (1.68 [1.47–1.94]) and current dual (2.03 [1.69–2.44]) use were associated with higher odds of self-reported premature ASCVD. There was no significant association for e-cigarette use. Sex-specific analyses revealed similar patterns but the magnitude of these associations varied between males and females. ConclusionBoth sexes showed higher odds of self-reported premature ASCVD for dual and exclusive cigarette use. Although the cross-sectional design precludes causal inferences, the findings suggest comprehensive tobacco cessation programs tailored to diverse use patterns are needed to reduce the burden of premature ASCVD.

Abstract 4117640: Thirty-Year Prevalence and Prognosis of the Cardiovascular-Kidney-Metabolic Syndrome in U.S. Females and Males

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US. Methods: We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality. Results: Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) ( Figure 1 ). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P&lt;0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ 2 =19.0, P interaction &lt;0.001); results were similar for cardiovascular mortality (LRT χ 2 =22.3, P interaction &lt;0.001) ( Table 1 ). Conclusions: Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.

Sex-Specific Association of Cardiovascular Risk Factors With Migraine: The Population-Based Rotterdam Study.

Sex-Specific Association of Cardiovascular Risk Factors With Migraine: The Population-Based Rotterdam Study.

Proteo-metabolomic insights for early dual physical and cognitive impairments: A search for biomarkers of healthy aging based on muscle-brain crosstalk.

We employed an untargeted proteo-metabolomic approach to profile circulating biomarkers in plasma samples from the I-Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio-cognitive decline syndrome (PCDS). In 115 propensity score-matched PCDS case-control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex-specific associations were observed, with disruptions in central carbon metabolism (elevated PKM, MDH1, and GAPDH; decreased MINPP1) and tyrosine metabolism (decreased MIF, DBH; increased thyroxine) characterizing in men. In contrast, perturbations in glutathione and phenylalanine metabolism, including increased ANPEP, GSTP1, and decreased pyroglutamic acid, were identified in women. Results suggest that dysregulated energy and redox homeostasis likely contribute to PCDS development. Notably, ANPEP, PKM, and MIF emerged as potential biomarkers, elucidating the muscle-brain crosstalk framework. Our findings provide insights into potential molecular mechanisms underlying PCDS and the muscle-brain crosstalk, marking progress toward elucidating biomarkers in the journey of healthy aging.

Sex-Specific Associations Between Lifestyle Factors and Sick Leave in the Serbian Working Population: Findings from the National Health Survey.

Background/Objectives: Sick leave is influenced by various modifiable lifestyle factors and sex differences. This study investigates the associations between body mass index, fruit and vegetable consumption, physical activity, smoking, and alcohol consumption and sick leave among Serbia's working population, with emphasis on sex differences. Methods: Data from the 2019 National Health Survey of Serbia were analyzed, involving a sample of 4652 individuals. Chi-square tests and logistic regression models assessed the relationships between lifestyle factors and sick leave. Results: Among the participants, 15.8% reported sick leave in the past 12 months, with higher rates among women in both short-term (13.9% vs. 10.6%) and long-term (3.4% vs. 2.2%) sick leave. This study identifies obesity (OR = 2.6), poor dietary habits (fruit OR = 2.1; vegetables OR = 2.8), smoking (OR = 1.9), and risky alcohol consumption (OR = 4.1) as key predictors of sick leave in men, while smoking (OR = 1.8) and risky alcohol consumption (OR = 3.1) are major predictors in women. The inconsistent association between diet, physical activity, and sick leave may be attributed to differences in reporting accuracy, differing definitions of healthy intake, or the influence of unmeasured lifestyle factors. Conclusions: Smoking and risky alcohol consumption increase the odds of sick leave for both sexes. Interventions targeting smoking cessation and mitigating risky alcohol consumption could significantly decrease sick leave rates. While fruit and vegetable consumption, along with physical activity, showed inconsistent effects in both sexes, further studies are warranted to elucidate their roles.

Associations of maternal urinary nitrophenol concentrations with adverse birth outcomes and neurodevelopment delay at 4 years of age: The Japan environment and children's study

Maternal urinary nitrophenol concentrations are reportedly associated with preterm birth and foetal/offspring development delay, but the evidence is still inconclusive. We investigated the association between maternal urinary concentrations of 4-nitrophenol (4NP) and 3-methyl-4-nitrophenol (3M4NP) and adverse birth outcomes, as well as offspring neurodevelopment delay, defined using the Ages and Stages Questionnaires at 4 years of age, stratified by offspring sex. A total of 3650 non-hypertensive mothers with singleton births were enrolled from the Japan Environment and Children's Study. High 4NP (≥0.41 μg/L) and 3M4NP (≥0.29 μg/L) were defined as ≥ lowest concentration minimum reporting level. Four groups were created using these dichotomized 4NP and 3M4NP concentrations: ‘both low’, ‘either high/low’, and ‘both high’. Multivariable logistic regression models were used to estimate the adjusted odds ratios (aOR) and population attributable fraction (PAF). For 4NP and 3M4NP, 68.4% and 19.0% of participants had ’high’ urinary concentrations, respectively. Compared to ‘both low’, the overall analysis showed no significant associations between ‘both high’ and any of the outcomes. However, the stratified analysis showed that the aOR (95% confidence interval [CI]) and PAF (95% CI) for ‘both high’ regarding preterm birth (<37 weeks' gestation) were 2.7 (1.3, 5.7) and 16.3% (2.5%, 28.1%), respectively, in male offspring. Among female offspring, the aOR and PAF for the ‘both high’ regarding small-for-gestational-age (SGA)—defined as weight-for-gestational age <10 percentile based on the Japanese neonatal anthropometric charts—were 1.7 (1.0, 2.8) and 10.6% (−0.2%, 20.2%), respectively. Urinary 4NP and 3M4NP concentrations showed no association with low birth weight (<2500 g) and neurodevelopment delay.In conclusion, offspring sex-specific associations of maternal urinary nitrophenols with preterm birth and SGA were observed. Even slight elevations in their levels may explain a certain proportion of preterm birth and SGA. The exposure source, expressed by urinary nitrophenols, should be identified.

Sex-Specific Associations Between Leucocyte Measures and Obstructive Sleep Apnea in Han Chinese.

White blood cell (WBC) and its subset counts are standard, inexpensive, direct markers of inflammation. Obstructive sleep apnea (OSA) is implicated in changes in inflammation markers, and sex differences are evident in both OSA and inflammation. It is unknown whether sex modulates the relationship between OSA severity and leukocyte measures. 1222 patients (914 males, 308 females) underwent overnight laboratorial polysomnography and measurement of WBC and its subset (lymphocyte, neutrophil, monocyte) counts. Patients were divided into primary snoring and mild, moderate, and severe OSA groups, and differences in leukocyte parameters were analyzed separately by sex in multivariable analyses. In multiple regression models, higher apnea-hypopnea index (AHI) was independently associated with neutrophil counts only in men, and with higher total WBC, lymphocyte and monocyte counts both in women and men. Further ordinal logistic regression analysis revealed a significant association between AHI and total WBC (OR 1.87, 95% CI 1.09-3.23) and neutrophil (OR 1.77, 95% CI 1.02-3.07) counts in men only. Correlation analysis also revealed more robust relationships between leukocyte measures and cardiometabolic risk markers in men than in women. This study provides novel data suggesting a significant association between neutrophil count and OSA severity only in men but not women. Similarly, the relationship between leukocyte parameters and cardiometabolic risk markers were more pronounced in men than women. Our findings suggest a sex-specific impact of OSA on leukocyte measures and on their relationship with indices of cardiometabolic risk.

Sex-specific Associations between Left Ventricular Remodeling at MRI and Long-term Cardiovascular Risk.

Background Left ventricular mass (LVM) is an established marker of cardiovascular risk; however, long-term follow-up studies in individuals with low to intermediate risk are lacking. Purpose To assess the sex-specific association of LVM measured with cardiac MRI with cardiovascular outcomes in those with a less than 20% 10-year risk of cardiovascular disease (CVD). Materials and Methods A total of 1528 volunteers older than 40 years of age with no history of CVD, a 10-year risk of CVD of less than 20%, and a B-type natriuretic peptide level greater than their sex-specific median underwent cardiac MRI between June 2008 and February 2013 as part of the Tayside Screening for Cardiac Events, or TASCFORCE, prospective study. LVM was indexed to body surface area, and the LVM-to-volume ratio was calculated. Follow-up for cardiovascular events was performed using national electronic health records. Cox proportional hazard models and Kaplan-Meier curves were applied to assess the impact of LVM. Results A total of 1495 participants (mean age, 54.5 years ± 8.3 [SD]; 925 female, 570 male) completed cardiac MRI, with a median follow-up of 10 years (IQR, 3 years). In female participants, LVM was associated with age, blood pressure, smoking status, and cholesterol level, while in male participants, LVM was associated with age and blood pressure. In female participants, the LVM-to-volume ratio was associated with cardiovascular events (hazard ratio [HR], 2.3 [95% CI: 1.1, 4.9] for the highest quartile vs the lowest quartile), while the LVM was not. In male participants, the LVM was associated with cardiovascular events (HR, 3.2 [95% CI: 1.5,7.0] for the highest quartile vs the lowest quartile), while the LVM-to-volume ratio was not. Conclusion In those with low to intermediate risk without established CVD, different remodeling patterns predict cardiovascular events, with increased LVM predictive in male participants, while LVM-to-volume ratio is predictive in female participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Garot and Duhamel in this issue.

Sex-specific association between platelet content and bone mineral density in adults: a cross-sectional study

BackgroundOsteoporosis (OP) is a complex skeletal disorder characterized by reduced bone mass, microarchitectural deterioration of bone tissue, and increased susceptibility to fractures. Bone mineral density (BMD), as the best indicator of bone mineral content per unit area of bone, is one of the key diagnostic factors for OP. Platelets (PLT), serving as important immune cells and components of the coagulation system, have been demonstrated to be associated with bone formation, resorption, and remodeling processes. However, no research has established the relationship between BMD and platelet count (PC) in the American population thus far. This study aims to investigate the correlation between BMD and PC among the American population, and to appraise the effects of additional risk factors on this association.MethodsThis investigation examined the relationship between BMD and PC by analyzing data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. A weighted multivariate logistic regression analysis was employed to assess this correlation. Additionally, subgroup and smooth curve analyses were conducted to delve deeper into the BMD-PC relationship and to identify other potential determinants of PC.ResultsThis study reveals a significant negative correlation between BMD and PC in the American adult population (β=-15.05, 95% CI: -22.07 to -8.03, p < 0.0001). Subgroup analysis highlights notable differences in this correlation between genders and various racial groups. Smooth curve fitting and generalized additive models were applied to further explore the relationship between BMD and PC, considering the influence of multiple factors.ConclusionThe present study investigated the correlation between BMD and PC in adults, with a particular focus on the potential risk factors for thrombocytopenia. This negative correlation was found to be markedly pronounced in males, an association not observed in females. Additionally, a potential inverse relationship between BMD and hemoglobin (HGB) levels was identified. Consequently, for individuals with elevated bone mass or osteoporosis (OP), we advocate for routine complete blood count monitoring to identify hematological irregularities. Considering the significant variations by sex, age, and race, special vigilance is advised for changes in PC among non-Hispanic white males under the age of 55.

Sex-specific risk factors and clinical dementia outcomes for white matter hyperintensities in a large South Korean cohort

ObjectiveWhite matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH’s impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes.MethodsParticipants aged 49–89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1–2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific.ResultsThe study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males.DiscussionOlder females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies.Clinical trial registrationThe BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Sex- and metabolic-specific association between cumulative body mass index and incident chronic kidney disease: a prospective community-based cohort study

Background and AimDifference in metabolic status may cause inconsistent association between body mass index (BMI) and chronic kidney disease (CKD) in men and women. This study aimed to quantify sex-specific association between cumulative BMI (cumBMI) and incident CKD by different metabolic status. Methods and ResultsParticipants free of CKD from the Kailuan Study were followed biennially from baseline (June 2006 to October 2007) to December 2019. cumBMI was calculated by use of follow-up BMI and follow-up time and was divided into low weight (<18.5 kg/m2), normal weight (18.5 to 23.9 kg/m2), overweight (24 to 27.9 kg/m2), and obesity (≥28 kg/m2) according to Chinese criteria. Metabolic health was defined as the absence of hypertension, dyslipidemia, and diabetes at baseline. CKD was defined as having estimated glomerular filtration rate <60 mL/min/1.73m2. This study included 76984 participants, with a mean age of 50.0 ± 11.6 years and 80.0% of men. Overweight (HR=1.24, 95% CI: 1.16–1.31) and obesity (HR=1.94, 95% CI: 1.77–2.12) were associated with higher risk of incident CKD in men regardless of metabolic status. Corresponding population attributable risk percentages for overweight and obesity were 10.3% (95%CI: 7.1–12.9) and 12.7% (95%CI: 10.6–14.7), respectively. However, low weight (HR=1.56, 95% CI: 1.05–2.30) and obesity (HR=1.32, 95% CI: 1.01–1.73) were associated with higher risk of incident CKD in metabolically healthy women but not in metabolically unhealthy women. ConclusionsThis study demonstrated sex- and metabolic-specific associations between BMI and CKD occurrence and advocates an individualized weight management strategy.

Serum Levels of Trace Elements (Magnesium, Iron, Zinc, Selenium, and Strontium) are Differentially Associated with Surrogate Markers of Cardiovascular Disease Risk in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD), which is attributed to inflammatory processes that accelerate atherosclerosis. Therefore, the exploration of novel biomarkers association is needed. This study investigated the associations between serum trace elements (Fe, Zn, Mg, Se, and Sr) and surrogate markers of CVD in 219 RA patients and compared them with those with metabolic disorders (MetD, n = 82) and control participants (n = 64). Surrogate markers included carotid intima-media thickness (cIMT), carotid plaque presence (cPP), pulse wave velocity (PWV), distensibility (DIST), and the augmentation index (AIx). RA patients displayed heightened inflammatory markers, increased arterial stiffness and thickness, and elevated CV risk factors. Compared with those in control participants, Se levels in RA patients were lower, regardless of sex. Women and men with RA had lower Sr and Mg levels than those with MetD, respectively. Backward regression models demonstrated inverse associations of Sr and Zn with cIMT in men with RA and those with MetD, respectively. In RA patients, Sr and Zn were predictors of an increased AIx, with sex-specific associations. Increased Fe levels were associated with an increased AIx in women with MetD. Fe and Zn were predictors of increased cIMT in control participants, with sex-specific associations. Serum trace elements are independently associated with surrogate markers of CVD in patients with RA, highlighting their potential role in CV risk assessment. Prospective studies are essential for validating these associations and establishing optimal trace element levels for managing CVD risk in patients with RA.

Sex-Specific Association of Low Muscle Mass with Depression Status in Asymptomatic Adults: A Population-Based Study.

The objective of this study was to examine the correlation between low muscle mass (LMM) and depression, with a specific focus on identifying the sex-specific relationship between LMM and depression in a large sample. This population-based cross-sectional study involved 292,922 community-dwelling adults from 2012 to 2019. Measurements were taken using the Center for Epidemiological Studies Depression (CESD) scale and body composition analyses. Depression was defined as a CESD score ≥ 16, and severe depression as a CESD score ≥ 22. LMM was defined as an appendicular muscle mass/height2 below 7.0 kg/m2 in men and below 5.4 kg/m2 in women. Sex-based multivariable logistic regression analyzed the LMM-depression association, adjusting for confounders, with depression status and severe depression status as dependent variables. Both men and women in the LMM group had an increased odds of depression (men, adjusted odds ratio = 1.13 [95% confidence interval = 1.03-1.12]; women, 1.07 [1.03-1.23]) and severe depression (men, 1.20 [1.05-1.36]; women, 1.10 [1.04-1.15]) compared to those in the control group. Men showed a stronger association between LMM and the presence of depression (p for interaction = 0.025) and the presence of severe depression (p for interaction = 0.025) compared to women. Decreased muscle mass was independently associated with increased chances of depression and severe depression in both sexes, with a significantly stronger association in men compared to women. This highlights the potential significance of LMM as a predictor of depression, particularly in men.

Sex-specific associations between remnant cholesterol and cardiovascular risk in patients undergoing percutaneous coronary intervention: a 5-year large-sample study from the real world

Abstract Background Differences in the pathophysiological characteristics and cardiovascular risk between female and male patients with coronary artery disease (CAD) are well-established. Recent studies on the relationship between remnant cholesterol (RC) and cardiovascular risk in coronary artery disease patients have gained popularity. To date, little is known about the RC-related cardiovascular risk disparities between males and females. Purpose The aim is to investigate sex-specific differences in the association between RC and cardiovascular risk among CAD patients undergoing percutaneous coronary intervention (PCI). Methods A prospective cohort study was conducted among 10,724 CAD patients undergoing PCI from January to December in 2013. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and ischemic stroke) and the secondary outcomes were each component of MACCE. Results Among 9,587 PCI patients included (the average age was 58.43 ± 10.26 years and 2,181 (22.70%) were female), 1,864 (19.4%) MACCEs were recorded during the 5-year follow-up. For primary outcome, a significant interaction was observed between RC levels and sex (P for interaction = 0.007 and 0.011, for continuous and categorical RC variables, respectively). Specifically, in male patients, no significant MACCE risk was observed at any RC level (both P &amp;gt; 0.05) (Figure 1). However, in female patients, both continuous RC levels (hazard ratio [HR] 1.412, 95% confidence interval [CI] 1.103-1.807) and the upper two quartiles of RC relative to the lowest quartile (Q3: HR 1.458, 95% CI 1.062-2.001; Q4: HR 1.496, 95% CI 1.081-2.070) were associated with higher MACCE risk. For secondary outcomes, higher RC levels were linked to an increased risk of cardiac mortality and revascularization in female patients but not in males (Table 1). Conclusions In a large-scale 5-year follow-up study from the real world, we are the first to demonstrate that RC-related cardiovascular risk is specifically observed in female CAD patients undergoing PCI, suggesting that female patients merit closer surveillance and more aggressive RC management to reduce cardiovascular risk.

Sex-specific association of NT-proBNP with clinically inapparent structural heart disease in the general population: results from the STAAB study

Abstract Background Guidelines recommend echocardiography in subjects beyond defined levels of natriuretic peptides. The ACC/AHA guidelines on heart failure (HF) state echocardiographic signs of structural heart disease (SHD) that define the precursor stage B of heart failure. Purpose To study the age- and sex-specific association between echocardiographically assessed structural heart disease (echoSHD) and NT-proBNP levels in the general population. Methods The STAAB study investigates precursor stages of HF in the general population of a medium-sized city in Germany (source population 124,297 inhabitants as of 2011 census). Study participants were recruited between 12/2013 and 10/2017 from the source population without preceding HF diagnosis, stratified for sex and age (30-79 years). For this analysis, we excluded participants with previously diagnosed coronary artery disease. EchoSHD was accepted if one of the following criteria, diagnosed according to current echo guidelines, was detectable at echocardiography: left ventricular (LV) hypertrophy, LV dilation, reduced LV ejection fraction, moderate-to-severe LV valve disease, and LV diastolic dysfunction. Results Of 4,649 subjects analysed (93.6% of STAAB participants, age 30-79 years, 53.5% women), 863 (18.6%) had echoSHD. NT-proBNP depended strongly on age and sex (figure). Frequencies of echoSHD varied between women (23.0%) and men (13.5%; P&amp;lt;0.001). EchoSHD was associated with increased NT-proBNP levels in both women (geometric mean ratio 1.18, 95%CI 1.09–1.27, P&amp;lt;0.001; figure) and men (ratio 1.62, 1.46–1.79, P&amp;lt;0.001); P&amp;lt;0.001 for different ratios in both sexes. Of note, age did not influence these ratios as well as their difference (P=0.34 and P=0.95, resp.). Conclusion Clinically inapparent echoSHD was associated with higher levels of NT-proBNP, of a magnitude that was relevant in men. The sex difference in the strength of this relationship might be due to different pathophysiological processes leading to SHD and ultimately HF in women and men. It might also indicate the need for adopted definitions of echoSHD in women. Our results further point towards the need of age- and sex-specific NT-proBNP thresholds.NTproBNP according to sex, age, and SHD