BACKGROUND: Higher, but also lower resting heart rate (HR), has been associated with increased cardiovascular events and mortality. Little is known about the interplay between HR, cardiovascular risk factors, concomitant diseases, vascular (endothelial) function, neurohormonal biomarkers, and all-cause mortality in the general population. Thus, we aimed to investigate these relationships in a population-based cohort.

METHODS: 15,010 individuals (aged 35-74 at enrolment in 2007-2012) from the Gutenberg Health Study were analyzed. Multivariable regression modeling was used to assess the relation between the variables and conditional density plots were generated for cardiovascular risk factors, diseases, and mortality to show their dependence on HR.

RESULTS: There were 714 deaths in the total sample at 7.67 +/- 1.68 years of follow-up. The prevalence of diabetes mellitus, arterial hypertension, coronary and peripheral artery disease, chronic heart failure, and previous myocardial infarction exhibited a J-shaped association with HR. Mortality showed a similar relation with a nadir of 64 beats per minute (bpm) in the total sample. Each 10 bpm HR reduction in HR < 64 subjects was independently associated with increased mortality (Hazard Ratio 1.36; 95% confidence interval 1.06-1.75). This increased risk was also present in HR > 64 subjects (Hazard Ratio 1.29; 95% confidence interval 1.19-1.41 per 10 bpm increase in HR). Results found for vascular and neurohormonal biomarkers exhibited a differential picture in subjects with a HR below and above the nadir.

DISCUSSION: These results indicate that in addition to a higher HR, a lower HR is associated with increased mortality.