Sex-Specific Association of Sleep Apnea Severity With Subclinical Myocardial Injury, Ventricular Hypertrophy, and Heart Failure Risk in a Community-Dwelling Cohort: The Atherosclerosis Risk in Communities-Sleep Heart Health Study

Abstract

Background: Risk factors for obstructive sleep apnea (OSA) and the development of subsequent cardiovascular (CV) complications differ by sex. We hypothesize that the relationship between OSA and high-sensitivity troponin T (hs-TnT), cardiac structure, and CV outcomes differs by sex.

Methods and results: Seven hundred fifty-two men and 893 women free of CV disease participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies were included. All participants (mean age, 62.5 ± 5.5 years) underwent polysomnography and measurement of hs-TnT. OSA severity was defined by using established clinical categories. Subjects were followed for 13.6 ± 3.2 years for incident coronary disease, heart failure, and CV and all-cause mortality. Surviving subjects underwent echocardiography after 15.2 ± 0.8 years. OSA was independently associated with hs-TnT among women (P=0.03) but not in men (P=0.94). Similarly, OSA was associated with incident heart failure or death in women (P=0.01) but not men (P=0.10). This association was no longer significant after adjusting for hs-TnT (P=0.09). Among surviving participants without an incident CV event, OSA assessed in midlife was independently associated with higher left ventricle mass index only among women (P=0.001).

Conclusions: Sex-specific differences exist in the relationship between OSA and CV disease. OSA, assessed in midlife, is independently associated with higher levels of concomitantly measured hs-TnT among women but not men, in whom other comorbidities associated with OSA may play a more important role. During 13-year follow-up, OSA was associated with incident heart failure or death only among women, and, among those without an incident event, it was independently associated with left ventricular hypertrophy only in women.

Keywords: echocardiography; heart failure; sex; sleep disorders; troponin T.

Figure 1

Box-and-whisker plot of hs-TnT levels among OSA categories stratified by sex. Hs-TnT is shown using a logarithmic scale from row hs-TnT values. Values under the limit of measurement (3 ng/L) are assigned to a value of 2 ng/L. Values below the limit of quantification (5 ng/L) –marked as a dotted line in the figure- are included in the first of the five hs-TnT categories. †Multivariable ordinal logistic regression adjusted by age, BMI, smoking status, alcohol intake, hypertension, diabetes, chronic lung disease, pulmonary function tests, eGFR, systolic and diastolic blood pressure and blood levels of total cholesterol, LDL, HDL, triglycerides and insulin (model 3).

Figure 2

Kaplan-Meier survival curves for the risk of HF or death of moderate/severe OSA vs none/mild OSA stratify by sex. Shown hazard ratios are showing the linear unadjusted association among all OSA categories.

Figure 3

Left ventricular mass index (LVMI) among OSA categories stratified by sex. P values are based in multivariable linear regression adjusted by age, BMI, hypertension, diabetes, smoking status, systolic blood pressure, and self-reported use of statins, beta-blockers, angiotensin-blockers, or mineralocorticoid blockers assessed at both time points (the polysomnography and the echocardiography times) and by self-reported use of CPAP at the time of the echocardiography.