Sex Hormones and Incident Heart Failure in Men and Postmenopausal Women: The Atherosclerosis Risk in Communities Study.
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ABSTRACT: Context
Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes.Objective
To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).Design
Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years.Setting
General community.Participants
4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation [SD] 5.7) and 62.8 (5.5) years, respectively.Exposure
Plasma sex hormone levels were measured at visit 4 (1996-1998).Main outcome measures
Incident HF events were identified through hospital discharge codes and death certificates.Results
The Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant.Conclusion
In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex.
SUBMITTER: Zhao D
PROVIDER: S-EPMC7455306 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: The relationship of endogenous sex hormones (SH) with vascular endothelial function and with cardiovascular disease (CVD) is incompletely understood. We examined the associations between SH and endothelial function measured by brachial artery flow-mediated dilation (FMD). Materials and Methods: We included 1368 postmenopausal women and 1707 men, free of clinical CVD, participating in MESA Visit 1 (2000-2002). Serum SH [total testosterone, SH binding globulin (SHBG), dehydroepiandrosterone (DHEA), estradiol] were measured; free testosterone was calculated. The percent FMD difference (%FMD) was measured by high-resolution ultrasound. Using multivariable-adjusted linear regression, we tested the cross-sectional associations of SH (log transformed, compared per one SD increment) with %FMD. Results: The mean age of women and men were 64.2 and 61.4 years, respectively. Among women, after adjusting for demographics, CVD risk factors, and hormone therapy, higher SHBG was associated with greater %FMD [β = 0.215% (95% CI 0.026-0.405)], whereas higher free testosterone was associated with a smaller %FMD [-0.209% (-0.402, -0.017)]. Estradiol and DHEA were not associated with %FMD in women after multivariable adjustment. There was an age interaction, with higher free testosterone and lower SHBG associated with worse FMD in women <65 years of age, but not in those ≥65 years (p = 0.04). We did not see similar associations in men. Conclusions: A more androgenic SH profile of higher free testosterone and lower SHBG was associated with worse %FMD in postmenopausal women. Changes in SH with aging and menopause may result in vascular changes in women. Further studies are needed to assess longitudinal changes in SH levels and their association with vascular function.
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Project description:The decline in carotid distensibility with age is steeper in women than in men, however, the correlates of this sex difference are not known. We examined the association of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone-binding globulin, in 2783 postmenopausal women and 2987 men aged 45 to 84 years at the Multi-Ethnic Study of Atherosclerosis baseline examination. Carotid artery lumen diameters by ultrasound and brachial artery blood pressures were measured at systole and diastole. Regression models to determine the association of carotid distensibility coefficient and lumen diameter with sex-specific quartiles of sex hormones were adjusted for age, race, height, weight, diabetes mellitus, current smoking, antihypertensive medication use, total and high-density lipoprotein cholesterol levels, and hormone replacement therapy in women. A higher DC indicates a more distensible vessel. In women, higher dehydroepiandrosterone (P=0.008) and lower sex hormone-binding globulin (P=0.039) were associated with lower distensibility; higher dehydroepiandrosterone and lower estradiol were associated with smaller carotid diameters. In men, higher Bio-T (P=0.009) and lower estradiol (P=0.007) were associated with greater distensibility and also with smaller diameters (P=0.012 and 0.002, respectively). An androgenic internal milieu is associated with lesser carotid distensibility and diameter remodeling in women, but the opposite is true for men. Higher levels of estradiol are associated with smaller carotid diameters in both the sexes. Future longitudinal and experimental studies are needed to reveal the mechanism and clinical consequences of these associations.
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Project description:This study was designed to assess the relationship between insulin resistance and incident heart failure (HF) in a community-based cohort.Diabetes mellitus increases the risk for HF, but the association between insulin resistance and HF in individuals without diabetes is unclear.We prospectively analyzed 12,606 participants without diabetes mellitus, prevalent HF, or history of myocardial infarction at baseline (1987 to 1989) from the ARIC (Atherosclerosis Risk in Communities) study. We assessed the relationship between insulin resistance and incident HF using the homeostatic model assessment of insulin resistance (HOMA-IR) equation, adjusting for age, sex, race, body mass index, smoking, hypertension, center, and interim myocardial infarction. We tested for interactions by age, sex, obesity, and race.Participants with insulin resistance, defined as HOMA-IR ≥2.5 (n = 4,810, 39%), were older, more likely female, African American, hypertensive, and had a higher body mass index as compared with those without insulin resistance. There were 1,455 incident HF cases during a median of 20.6 years of follow-up. Insulin resistance defined by this threshold was not significantly associated with an increased risk for incident HF after adjustment (hazard ratio: 1.08, 95% confidence interval: 0.95 to 1.23). However, when analyzed continuously, this relationship was nonlinear, which indicated that risk increased, and was significantly associated with incident HF between HOMA-IR of 1.0 to 2.0, adjusting for baseline covariates; however, values over 2.5 were not associated with additional increased risk in adjusted models.In a community cohort, insulin resistance, defined by lower levels of HOMA-IR than previously considered, was associated with an increased risk for HF.
| S-EPMC3893700 | biostudies-other
Project description:BackgroundThe 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB's role in heart failure (HF) is unclear.MethodsWe studied 80 982 women in the Women's Health Initiative Observational Study, aged 50 to 79 years, who were without known HF and reported ability to walk ≥1 block unassisted at baseline. Mean follow-up was 9 years for physician-adjudicated incident HF hospitalization (1402 cases). SB was assessed repeatedly by questionnaire. Time-varying total SB was categorized according to awake time spent sitting or lying down (≤6.5, 6.6-9.5, >9.5 h/d); sitting time (≤4.5, 4.6-8.5, >8.5 h/d) was also evaluated. Hazard ratios and 95% CI were estimated using Cox regression.ResultsControlling for age, race/ethnicity, education, income, smoking, alcohol, menopausal hormone therapy, and hysterectomy status, higher HF risk was observed across incremental tertiles of time-varying total SB (hazard ratios [95% CI], 1.00 [referent], 1.15 [1.01-1.31], 1.42 [1.25-1.61], trend P<0.001) and sitting time (1.00 [referent], 1.14 [1.01-1.28], 1.54 [1.34-1.78], trend P<0.001). The inverse trends remained significant after further controlling for comorbidities including time-varying myocardial infarction and coronary revascularization (hazard ratios: SB, 1.00, 1.11, 1.27; sitting, 1.00, 1.09, 1.37, trend P<0.001 each) and for baseline physical activity (hazard ratios: SB 1.00, 1.10, 1.24; sitting 1.00, 1.08, 1.33, trend P<0.001 each). Associations with SB exposures were not different according to categories of baseline age, race/ethnicity, body mass index, physical activity, physical functioning, diabetes, hypertension, or coronary heart disease.ConclusionsSB was associated with increased risk of incident HF hospitalization in postmenopausal women. Targeted efforts to reduce SB could enhance HF prevention in later life.
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Project description:ContextIn postmenopausal women, endogenous bioavailable testosterone (T) and estradiol (E2) have been positively associated, and SHBG has been negatively associated, with incident type 2 diabetes (T2DM). Previous studies have not explored possible factors explaining these relationships.ObjectiveOur objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors.Design, setting, and participantsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective study that included 1612 postmenopausal women aged 45-84 yr, followed between the years 2000-2006, who were not taking hormone replacement therapy, had no prevalent cardiovascular disease or diabetes, and had complete ascertainment of sex hormones.Main outcome measuresT2DM was defined based on fasting glucose and/or treatment for diabetes.ResultsThere were 116 incident cases of diabetes during follow-up. Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG, we found significantly greater hazards of developing incident T2DM (all P for trend <or=0.001). After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance, bioavailable T was no longer associated with incident T2DM. The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models (both P for trend <0.02). Dehydroepiandrosterone had no relationship with incident T2DM.ConclusionsAdiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.
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Project description:ObjectivesThis study assessed the association of diabetes duration with incident heart failure (HF).BackgroundDiabetes increases HF risk. However, the independent effect of diabetes duration on incident HF is unknown.MethodsWe included 9,734 participants (mean age 63 years, 58% women, 22% Black) at ARIC (Atherosclerosis Risk In Communities) Visit 4 (1996-1998) without HF or coronary heart disease. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first 4 ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident HF, accounting for intercurrent coronary heart disease and other risk factors. We performed analyses stratified by age (<65 years or ≥65 years), race, sex, and glycemic control (hemoglobin A1C [HbA1C] consistently <7%, vs HbA1C ≥7%), with tests for interaction.ResultsOver 22.5 years of follow-up, there were 1,968 HF events. Compared to those without diabetes, HF risk rose with longer diabetes duration, with the highest risk among those with ≥15 y diabetes duration (HR: 2.82; 95% CI: 2.25-3.63). Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk. Similar results were observed across HF subtypes. The HF and diabetes duration associations were stronger among those aged <65 years, those with HbA1C ≥7%, those with a body mass index ≥30 kg/m2, women, and Blacks (all P interactions <0.05).ConclusionsDelaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration.
| S-EPMC8629143 | biostudies-literature
Project description:BackgroundA simple and effective heart failure (HF) risk score would facilitate the primary prevention and early diagnosis of HF in general practice. We examined the external validity of existing HF risk scores, optimized a 10-year HF risk function, and examined the incremental value of several biomarkers, including N-terminal pro-brain natriuretic peptide.Methods and resultsDuring 15.5 years (210 102 person-years of follow-up), 1487 HF events were recorded among 13 555 members of the biethnic Atherosclerosis Risk in Communities (ARIC) Study cohort. The area under curve from the Framingham-published, Framingham-recalibrated, Health ABC HF recalibrated, and ARIC risk scores were 0.610, 0.762, 0.783, and 0.797, respectively. On addition of N-terminal pro-brain natriuretic peptide, the optimism-corrected area under curve of the ARIC HF risk score increased from 0.773 (95% CI, 0.753-0.787) to 0.805 (95% CI, 0.792-0.820). Inclusion of N-terminal pro-brain natriuretic peptide improved the overall classification of recalibrated Framingham, recalibrated Health ABC, and ARIC risk scores by 18%, 12%, and 13%, respectively. In contrast, cystatin C or high-sensitivity C-reactive protein did not add toward incremental risk prediction.ConclusionsThe ARIC HF risk score is more parsimonious yet performs slightly better than the extant risk scores in predicting 10-year risk of incident HF. The inclusion of N-terminal pro-brain natriuretic peptide markedly improves HF risk prediction. A simplified risk score restricted to a patient's age, race, sex, and N-terminal pro-brain natriuretic peptide performs comparably to the full score (area under curve, 0.745) and is suitable for automated reporting from laboratory panels and electronic medical records.
| S-EPMC3412686 | biostudies-literature
Project description:Background and aimsLipoprotein(a) [Lp(a)] is a proatherogenic lipoprotein associated with coronary heart disease, ischemic stroke, and more recently aortic stenosis and heart failure (HF). We examined the association of Lp(a) levels with incident HF hospitalization in the Atherosclerosis Risk in Communities (ARIC) study. We also assessed the relationship between Lp(a) levels and arterial stiffness as a potential mechanism for development of HF.MethodsLp(a) was measured in 14,154 ARIC participants without prevalent HF at ARIC visit 1 (1987-1989). The association of Lp(a) quintiles with incident HF hospitalization was assessed using Cox proportional-hazards models. Arterial stiffness parameters were stratified based on Lp(a) quintiles, and p-trend was calculated across ordered groups.ResultsAt a median follow-up of 23.4 years, there were 2605 incident HF hospitalizations. Lp(a) levels were directly associated with incident HF hospitalization in models adjusted for age, race, gender, systolic blood pressure, history of hypertension, diabetes, smoking status, body mass index, heart rate, and high-density lipoprotein cholesterol (quintile 5 vs. quintile 1: hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.09-1.41; p-trend across increasing quintiles <0.01), but not after excluding prevalent and incident myocardial infarction cases (HR 1.07, 95% CI 0.91-1.27; p-trend = 0.70). When adjusted for age, gender, and race, Lp(a) quintiles were not significantly associated with arterial stiffness parameters.ConclusionsIncreased Lp(a) levels were associated with increased risk of incident HF hospitalization. After excluding prevalent and incident myocardial infarction, the association was no longer significant. Lp(a) levels were not associated with arterial stiffness parameters.
| S-EPMC5523851 | biostudies-literature
Project description:BackgroundAssociations between sex hormones and vascular remodeling have been extensively studied, but the results vary widely among different races and sex. We aimed to investigate whether total testosterone (TT), estrogen (E2), and dehydroepiandrosterone (DHEA) associate with macrovascular complications and diabetic kidney disease (DKD) among community-dwelling patients with diabetes.MethodsA total of 4720 participants with type 2 diabetes were recruited from Shanghai, China. Common carotid artery (CCA) plaques and diameter were assessed by ultrasound. Cardiovascular disease (CVD) was defined by prior diagnosis of coronary heart disease, myocardial infarction or stroke. DKD was defined according to the ADA Guidelines.Results(1) In men, TT was negatively associated with CCA diameter (regression coefficient (β) - 0.044, 95% CI - 0.087, 0). E2 levels were positively associated with CVD and CCA plaque prevalence (OR 1.151, 95% CI 1.038, 1.277 and OR 1.13, 95% CI 1.017, 1.255, respectively). DHEA was negatively associated with CVD (OR 0.809, 95% CI 0.734, 0.893). In postmenopausal women, TT levels were negatively associated with CCA diameter (β - 0.046, 95% CI - 0.083, - 0.010) and positively associated with CVD (OR 1.154, 95% CI 1.038, 1.284). (2) In both men and postmenopausal women, TT levels were negatively associated with the albumin/creatinine ratio and DKD (β - 0.098, 95% CI - 0.154, - 0.043 and OR 0.887, 95% CI 0.790, 0.997 vs. β - 0.084, 95% CI - 0.137, - 0.031 and OR 0.822, 95% CI 0.731, 0.924, respectively) and DHEA levels were positively associated with DKD (OR 1.167, 95% CI 1.038, 1.313 vs. OR 1.251, 95% CI 1.104, 1.418, respectively).ConclusionsOur study indicates that macrovascular complications were associated with low TT, DHEA and high E2 in men and with high TT in postmenopausal women. DKD was associated with low TT and high DHEA levels in both genders. Sex hormone replacement therapy requires careful and comprehensive consideration. Trial registration ChiCTR1800017573, http://www.chictr.org.cn . Registered 04 August 2018.
| S-EPMC6668151 | biostudies-literature