Background —Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. Methods and Results —We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. Conclusions —Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

Heart rate variability (HRV) is associated with cardiovascular disease (CVD) in individuals with known CVD. It is less clear whether HRV is associated with a first cardiovascular event. Therefore, we performed a meta-analysis to study the association between HRV and incident cardiovascular events in populations without known CVD. We performed a meta-analysis and dose–response meta-regression of studies assessing the association between HRV and CVD. We searched Pubmed, Embase, Web of Science, Cochrane library, ScienceDirect, and CINAHL up to December 2011 for eligible studies. We selected studies that used the standard deviation of the normalized N–N interval (SDNN), low-frequency (LF) or high-frequency (HF) spectral component as a measure of HRV. Primary outcomes were (non)fatal cardiovascular events. Eight studies with a total number of 21 988 participants were included. The pooled relative risk (RR) comparing the lowest level to the highest level of SDNN was 1.35 (95% CI 1.10, 1.67). The pooled RRs for LF and HF were 1.45 (95% CI 1.12, 1.87) and 1.32 (95% CI 0.96, 1.81), respectively. In a meta-regression, the predicted RR of incident CVD of the 10th and 90th HRV (SDNN) percentiles compared with the 50th percentile were 1.50 (95% CI 1.22, 1.83) and 0.67 (95% CI 0.41, 1.09). In conclusion, low HRV is associated with a 32–45% increased risk of a first cardiovascular event in populations without known CVD. An increase in SDNN of 1% results in an ∼1% lower risk of fatal or non-fatal CVD.

Low heart rate variability is associated with high risk of sudden death in myocardial infarction patients. This has been attributed to unfavorable autonomic cardiac control. In the present study, the predictive value of heart rate variability for sudden death, mortality from coronary heart disease, and from all causes was investigated in the general population, using brief electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men, aged 40–60 years, were followed and repeatedly examined as part of the Zutphen Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65–85 years, and followed until 1990. Heart rate variability (standard deviation of duration of normal RR intervals) was determined from the resting 12-lead electrocardiogram. The 5-year age-adjusted relative rate of total mortality of men with heart rate variability of <20 milliseconds (msec) compared with men with heart rate variability of 20–39 msec was 2.1 (95 percent confidence interval 1.4–3.0) in middle-aged men and 1.4 (95% confidence interval 0.9–2.2) in elderly men. Death from noncoronary causes, especially cancer, contributed significantly to this elevated risk. The association of low heart rate variability with sudden death or coronary heart disease mortality was less consistent. In conclusion, in middle-aged men and probably in elderly men, low heart rate variability is predictive of mortality from all causes. This suggests that low heart rate variability is an indicator of compromised health in the general population. Am J Epidemiol 1997; 145: 899–908.

Background— In patients with primary prevention implantable cardioverter-defibrillators (ICDs), the incidence of life-threatening ventricular arrhythmias resulting in ICD therapy is relatively low,...