Faster resting heart rates (RHRs) are associated with shorter life expectancies.[1] Epidemiologic studies[2–19] have demonstrated that elevated RHRs increase the risk of mortality, from cardiovascular disease (CVD) in particular. The relationship has been demonstrated in diverse subgroups, including the general population,[2–11,19] hypertensives,[3,18,20] and those with established coronary artery disease (CAD).[12–17] Resting heart rate has previously been shown to fulfill several of the criteria for causality.[21, 22] In men, the relationship has been shown to be strong and graded.[4,8,9] Animal studies have demonstrated reduced rates of atherogenesis post experimental heart rate reduction.[23, 24] In addition, several biologically plausible mechanisms for the effect of elevated RHR have been proposed including the antiischemic and antiarrhythmic benefits of a low heart rate and the atherogenic hemodynamic effects of an elevated heart rate; a faster heart rate will necessarily impose more shear stresses than a slow one. …
… In men, on univariable analysis CVD, CHD, and total mortality rates increased with each successive increase in RHR quintile. Rate ratio comparing extreme quintiles was 3.87 (2.24–6.68) for CVD mortality …
… In women, on univariable analysis, the associations with mortality end points were also strong with a hazard ratio of 3.29 (2.32–4.65) comparing extreme quintiles for CVD mortality. However, in general, the relationships were less strongly graded than in men …
… In multivariable analyses (Table III), RHR as a continuous variable remained a significant predictor of CVD mortality after full adjustment. … To investigate whether elevated RHR was an independent risk factor or merely a marker of subclinical disease, we reanalyzed the effect excluding all fatal events that occurred within the first 2 years of follow-up. This resulted in virtually no difference in the hazard ratios … This analysis has clearly demonstrated the association between resting heart rate and CVD, CHD, and total mortality. We have confirmed the strength of the relationship. For example, in men, RHR >90 beats/min compared to RHR <60 beats/min was associated with an almost 2-fold increased risk of CVD mortality in men and 3-fold increased risk in women. This effect was independent and similar in magnitude to the risk associated with current smoking (data not shown). These estimates are similar to those of previous studies, which ranged from 1.5- to 3.3-fold increased risk in the higher RHR category.[3,4,6,8,10,11,25]
We have confirmed the graded nature of the relationship, particularly in men. The risk seems to increase more steeply in the highest quintile of RHR, in line with the findings of previous studies.[28] …
… Previously, there was doubt concerning the independence of the effect, particularly regarding possible confounders such as blood pressure, physical activity, and comorbidities.[19] This analysis has demonstrated that RHR is strongly related to other risk factors including smoking, SBP, BMI, total cholesterol, HDL cholesterol (inversely), and physical activity levels. Because of these associations, the effect of RHR on CVD end points attenuated on addition of the other CV risk factors to the model. However, despite this, the effect of RHR on CVD end points remained statistically significant even after inclusion of all of the risk factors, including physical activity as a categorical variable and persisted within strata of physical activity. In addition, the relationship remained after exclusion of those with comorbidities, which could potentially have been confounding the relationship. The effect of RHR was not substantially altered by the addition of waist circumference and triglycerides …