Abstract
Whether autonomic dysfunction predates the development of symptomatic heart failure (HF) or is simply a consequence of severe HF is unknown. We hypothesized that reduced heart rate variability (a marker of abnormal autonomic function) at baseline is associated with incident HF in subjects free of clinically recognized cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical cardiovascular disease in adults aged 45 to 84 years, we measured the heart rate variability using a standard 30-second, 12-lead electrocardiogram to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). During a median follow-up of 7.6 years, 95 participants developed HF (incidence rate 2.7/1,000 person-years). After adjusting for age, gender, and ethnicity, the hazard ratio for incident HF stratified by the RMSSD tertile was 2.4 (95% confidence interval 1.4 to 4.2) for the lowest tertile and 1.7 (95% confidence interval 1.0 to 3.2) for the middle tertile (highest tertile was the referent group; p for trend <0.001). The inverse association between the RMSSD and incident HF persisted after adjustment for additional covariates, including diabetes, systolic blood pressure, heart rate, subclinical atherosclerosis, left ventricular end-systolic volume, interim myocardial infarction, and high-sensitivity C-reactive protein (p for trend = 0.009). A similarly significant inverse association was also observed for SDNN. In conclusion, baseline autonomic dysfunction was a risk factor for the development of HF in a multiethnic cohort. These population-based findings implicate autonomic dysfunction in the pathogenesis of HF, and decreased short-term heart rate variability might be a novel form of stage B (asymptomatic) HF.