Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: meta-analysis and dose–response meta-regression

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.