Resting heart rate and all-cause and cardiovascular mortality in the general population: a meta-analysis

Background: Data on resting heart rate and risk of all-cause and cardiovascular mortality are inconsistent; the magnitude of associations between resting heart rate and risk of all-cause and cardiovascular mortality varies across studies. We performed a meta-analysis of prospective cohort studies to quantitatively evaluate the associations in the general population. Methods: We searched PubMed, Embase and MEDLINE from inception to Jan. 1, 2015. We used a random-effects model to combine study-specific relative risks and 95% confidence intervals (CIs). We used restricted cubic spline functions to assess the dose–response relation. Results: A total of 46 studies were included in the meta-analysis, involving 1 246 203 patients and 78 349 deaths for all-cause mortality, and 848 320 patients and 25 800 deaths for cardiovascular mortality. The relative risk with 10 beats/min increment of resting heart rate was 1.09 (95% CI 1.07–1.12) for all-cause mortality and 1.08 (95% CI 1.06–1.10) for cardiovascular mortality. Compared with the lowest category, patients with a resting heart rate of 60–80 beats/min had a relative risk of 1.12 (95% CI 1.07–1.17) for all-cause mortality and 1.08 (95% CI 0.99–1.17) for cardiovascular mortality, and those with a resting heart rate of greater than 80 beats/min had a relative risk of 1.45 (95% CI 1.34–1.57) for all-cause mortality and 1.33 (95% CI 1.19–1.47) for cardiovascular mortality. Overall, the results did not differ after adjustment for traditional risk factors for cardiovascular disease. Compared with 45 beats/min, the risk of all-cause mortality increased significantly with increasing resting heart rate in a linear relation, but a significantly increased risk of cardiovascular mortality was observed at 90 beats/min. Substantial heterogeneity and publication bias were detected. Interpretation: Higher resting heart rate was independently associated with increased risks of all-cause and cardiovascular mortality. This indicates that resting heart rate is a predictor of all-cause and cardiovascular mortality in the general population.

[1]  E Casiglia,et al.  High heart rate: a risk factor for cardiovascular death in elderly men. , 1999, Archives of internal medicine.

[2]  J. Tardif,et al.  Ivabradine in stable coronary artery disease without clinical heart failure. , 2014, The New England journal of medicine.

[3]  Michael J Blaha,et al.  Relation of resting heart rate to risk for all-cause mortality by gender after considering exercise capacity (the Henry Ford exercise testing project). , 2014, The American journal of cardiology.

[4]  F. Harrell,et al.  Regression models in clinical studies: determining relationships between predictors and response. , 1988, Journal of the National Cancer Institute.

[5]  Yutaka Imai,et al.  Prognostic value of home heart rate for cardiovascular mortality in the general population: the Ohasama study. , 2004, American journal of hypertension.

[6]  Jennifer G. Robinson,et al.  2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014, Circulation.

[7]  Jennifer G. Robinson,et al.  2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014, Circulation.

[8]  Susan Cheng,et al.  Long‐term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study , 2014, Journal of the American Heart Association.

[9]  P. Palatini Heart rate as a cardiovascular risk factor: do women differ from men? , 2001, Annals of medicine.

[10]  L. Køber,et al.  Resting, night-time, and 24 h heart rate as markers of cardiovascular risk in middle-aged and elderly men and women with no apparent heart disease. , 2013, European heart journal.

[11]  Rebecca Hardy,et al.  Association between resting heart rate across the life course and all-cause mortality: longitudinal findings from the Medical Research Council (MRC) National Survey of Health and Development (NSHD) , 2014, Journal of Epidemiology & Community Health.

[12]  J. Myers,et al.  Heart rate at rest, exercise capacity, and mortality risk in veterans. , 2013, The American journal of cardiology.

[13]  K Rodahl,et al.  Physical fitness as a predictor of mortality among healthy, middle-aged Norwegian men. , 1993, The New England journal of medicine.

[14]  A. Dyer,et al.  Resting heart rate is a risk factor for cardiovascular and noncardiovascular mortality: the Chicago Heart Association Detection Project in Industry. , 1999, American journal of epidemiology.

[15]  P W Macfarlane,et al.  Heart rate, physical activity, and mortality from cancer and other noncardiovascular diseases. , 1994, American journal of epidemiology.

[16]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[17]  P. Elliott,et al.  Resting heart rate and cause-specific death in a 16.5-year cohort study of the Japanese general population. , 2004, American heart journal.

[18]  M. Marmot,et al.  Combined effects of depressive symptoms and resting heart rate on mortality: the Whitehall II prospective cohort study. , 2011, The Journal of clinical psychiatry.

[19]  A. Folsom,et al.  Associations of Psychosocial Factors With Heart Rate and Its Short-Term Variability: Multi-Ethnic Study of Atherosclerosis , 2008, Psychosomatic medicine.

[20]  L Guize,et al.  Associations between heart rate and other risk factors in a large French population. , 1999, Journal of hypertension.

[21]  Jean-Claude Tardif,et al.  Resting heart rate in cardiovascular disease. , 2007, Journal of the American College of Cardiology.

[22]  M. Gold,et al.  Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial , 2011 .

[23]  G. Berglund,et al.  Sleep disturbance in association with elevated pulse rate for prediction of mortality – consequences of mental strain? , 2001, Journal of internal medicine.

[24]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[25]  B. Psaty,et al.  Variation in resting heart rate over 4 years and the risks of myocardial infarction and death among older adults , 2014, Heart.

[26]  T. Ohkubo,et al.  High long-chain n-3 fatty acid intake attenuates the effect of high resting heart rate on cardiovascular mortality risk: a 24-year follow-up of Japanese general population. , 2014, Journal of cardiology.

[27]  J. Feldman,et al.  Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study. , 1991, American heart journal.

[28]  R. Weiskopf,et al.  High Oxygen Partial Pressure Decreases Anemia-induced Heart Rate Increase Equivalent to Transfusion , 2011, Anesthesiology.

[29]  Vidar Hjellvik,et al.  Heart rate and mortality from cardiovascular causes: a 12 year follow-up study of 379,843 men and women aged 40-45 years. , 2008, European heart journal.

[30]  P. Tugwell,et al.  The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses , 2014 .

[31]  P Ducimetière,et al.  Resting heart rate, mortality and future coronary heart disease in the elderly: the 3C study , 2011, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[32]  Dan Jackson,et al.  Extending DerSimonian and Laird's methodology to perform multivariate random effects meta‐analyses , 2009, Statistics in medicine.

[33]  Nicola Orsini,et al.  Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. , 2012, American journal of epidemiology.

[34]  L Guize,et al.  Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure. , 1999, Hypertension.

[35]  B. Nordestgaard,et al.  Resting heart rate is associated with cardiovascular and all-cause mortality after adjusting for inflammatory markers: The Copenhagen City Heart Study , 2012, European journal of preventive cardiology.

[36]  H. Hein,et al.  Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. , 2004, European heart journal.

[37]  S. Blair,et al.  Heart rate reserve as a predictor of cardiovascular and all-cause mortality in men. , 2002, Medicine and science in sports and exercise.

[38]  K. Asayama,et al.  Predictive value for mortality of the double product at rest obtained by home blood pressure measurement: the Ohasama study. , 2012, American journal of hypertension.

[39]  A. Dyer,et al.  Relation of heart rate with cardiovascular disease in normal-weight individuals: the Chicago Heart Association Detection Project in Industry. , 2008, Preventive cardiology.

[40]  Gert B. M. Mensink,et al.  The relationship between resting heart rate and all-cause, cardiovascular and cancer mortality. , 1997, European heart journal.

[41]  L. Vatten,et al.  Combined effect of resting heart rate and physical activity on ischaemic heart disease: mortality follow-up in a population study (the HUNT study, Norway) , 2010, Journal of Epidemiology & Community Health.

[42]  I. Piña,et al.  Heart rate: a prognostic factor and therapeutic target in chronic heart failure. The distinct roles of drugs with heart rate‐lowering properties , 2014, European journal of heart failure.

[43]  W. Srikusalanukul,et al.  Does heart rate predict mortality in older, low-level care residents? , 2006, The American journal of geriatric cardiology.

[44]  Martin Wehling,et al.  How to measure heart rate? , 2004, European Journal of Clinical Pharmacology.

[45]  G. Jensen,et al.  Elevated resting heart rate is associated with greater risk of cardiovascular and all-cause mortality in current and former smokers. , 2011, International journal of cardiology.

[46]  M. Böhm,et al.  BEAUTIFUL results—the slower, the better? , 2008, The Lancet.

[47]  E. O’Brien,et al.  Prognostic Value of Ambulatory Heart Rate Revisited in 6928 Subjects From 6 Populations , 2008, Hypertension.

[48]  D. Mozaffarian,et al.  Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. , 2006, Journal of the American College of Cardiology.

[49]  Yiannis Koutedakis,et al.  Effects of active and passive tobacco cigarette smoking on heart rate variability. , 2013, International journal of cardiology.

[50]  S. Giampaoli,et al.  Heart rate as a predictor of mortality: the MATISS project. , 2001, American journal of public health.

[51]  Michael Böhm,et al.  Resting heart rate: risk indicator and emerging risk factor in cardiovascular disease. , 2015, The American journal of medicine.

[52]  Shah Ebrahim,et al.  European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (Version 2012) , 2012, International Journal of Behavioral Medicine.

[53]  Sander Greenland,et al.  Generalized Least Squares for Trend Estimation of Summarized Dose–response Data , 2006 .

[54]  A. Reunanen,et al.  Heart rate and mortality , 2000, Journal of internal medicine.

[55]  Rainer Rauramaa,et al.  Heart rate response during exercise test and cardiovascular mortality in middle-aged men. , 2006, European heart journal.

[56]  Erkki Vartiainen,et al.  Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. , 2010, American heart journal.

[57]  É. Marijon,et al.  Heart Rate and Risk of Cancer Death in Healthy Men , 2011, PloS one.

[58]  X. Jouven,et al.  Gender-specific trends in heart rate in the general population from 1992–2007: a study of 226,288 French adults , 2013, European journal of preventive cardiology.

[59]  H. Theobald,et al.  Effect of heart rate on long-term mortality among men and women , 2007, Acta cardiologica.

[60]  C. Nam,et al.  Modifying Effects of Resting Heart Rate on the Association of Binge Drinking With All-cause and Cardiovascular Mortality in Older Korean Men: the Kangwha Cohort Study , 2014, Journal of epidemiology.

[61]  K. Swedberg,et al.  Effect of ivabradine in patients with left-ventricular systolic dysfunction: a pooled analysis of individual patient data from the BEAUTIFUL and SHIFT trials. , 2013, European heart journal.

[62]  S. Cummings,et al.  Rapid Resting Heart Rate: A Simple and Powerful Predictor of Osteoporotic Fractures and Mortality in Older Women , 2002, Journal of the American Geriatrics Society.

[63]  Shuohua Chen,et al.  Resting Heart Rate and Risk of Cardiovascular Diseases and All-Cause Death: The Kailuan Study , 2014, PloS one.

[64]  S. Blair,et al.  Protective role of resting heart rate on all-cause and cardiovascular disease mortality. , 2013, Mayo Clinic proceedings.

[65]  E Kristal-Boneh,et al.  The association of resting heart rate with cardiovascular, cancer and all-cause mortality. Eight year follow-up of 3527 male Israeli employees (the CORDIS Study) , 2000, European heart journal.

[66]  Mark Woodward,et al.  The association between resting heart rate, cardiovascular disease and mortality: evidence from 112,680 men and women in 12 cohorts , 2014, European journal of preventive cardiology.

[67]  Javaid Nauman,et al.  Temporal changes in resting heart rate and deaths from ischemic heart disease. , 2011, JAMA.

[68]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[69]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[70]  L. Fried,et al.  Relation of heart rate at rest and mortality in the Women's Health and Aging Study. , 2003, The American journal of cardiology.

[71]  Julian P T Higgins,et al.  Controlling the risk of spurious findings from meta‐regression , 2004, Statistics in medicine.

[72]  Finn Gyntelberg,et al.  Elevated resting heart rate, physical fitness and all-cause mortality: a 16-year follow-up in the Copenhagen Male Study , 2013, Heart.

[73]  Martin J Shipley,et al.  Walking pace, leisure time physical activity, and resting heart rate in relation to disease-specific mortality in London: 40 years follow-up of the original Whitehall study. An update of our work with professor Jerry N. Morris (1910-2009). , 2010, Annals of epidemiology.

[74]  Hanna E Bloomfield,et al.  Relation of heart rate parameters during exercise test to sudden death and all-cause mortality in asymptomatic men. , 2008, The American journal of cardiology.