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(Circulation. 1999;99:2251-2254.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Heritability of Heart Rate Variability

The Framingham Heart Study

Jagmeet P. Singh, MD, DPhil; Martin G. Larson, ScD; Christopher J. O'Donnell, MD, MPH; Hisako Tsuji, MD; Jane C. Evans, MPH; Daniel Levy, MD

From the National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Mass (J.P.S., M.G.L., C.J.O., H.T., J.C.E., D.L.); the National Heart, Lung, and Blood Institute, Bethesda, Md (C.J.O., D.L.); the Division of Epidemiology and Preventive Medicine, Boston University School of Medicine, Boston, Mass (J.P.S., M.G.L., J.C.E., D.L.); the Divisions of Cardiology and Clinical Epidemiology, Beth Israel Hospital (D.L.) and the Cardiac Unit (C.J.O) and Department of Medicine (J.P.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; and Kansai Medical University, Osaka, Japan (H.T.).

Correspondence to Daniel Levy, MD, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702. E-mail dan{at}fram.nhlbi.nih.gov

Background—There is evolving evidence that heart rate (HR) is genetically determined. Heart rate variability (HRV) measured by power spectral analysis provides quantitative phenotypic markers of autonomic nervous system activity. Reported determinants of HR and HRV only partially explain their variability in the population. The purpose of this study was to assess the heritability of HR and HRV and estimate the contribution of genetic factors to their variance.

Methods and Results—Subjects who underwent ambulatory recordings at a routine examination were eligible; subjects with congestive heart failure, coronary artery disease, diabetes mellitus, and those taking cardioactive medications were excluded. We analyzed high-frequency power, low-frequency power, very low-frequency power, total power, low-frequency/high-frequency ratio, and the standard deviation of normal R-R intervals from 2-hour continuous ECG recordings. Heritability analysis was done by studying correlations between siblings (n=682, in 291 sibships, 517 pairs) and between spouse pairs (n=206 pairs) after adjusting for important covariates. Results from separate models were combined to estimate the components of variance attributable to measured covariates, additive genetic effects (heritability), and household effects. After adjusting for covariates, the correlations were consistently higher among siblings (0.21 to 0.26) compared with spouses (0.01 to 0.19). The measured covariates in general accounted for 13% to 40% of the total phenotypic variance, whereas genetic factors accounted for 13% to 23% of the variation among HR and HRV measures.

Conclusions—Heritable factors may explain a substantial proportion of the variance in HR and HRV. These results highlight the contribution of genetic versus environmental factors to autonomic nervous system activity.

Key Words: heart rate • genetics • epidemiology

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