Aging, Resting Pulse Rate, and Longevity

Discussion

This study describes the changes in RPR in a representative sample of community-dwelling older people followed from age 70 to 85 and examines its association with mortality. Although RPR remained stable at age 70 and 78, there was a significant decline of comparable magnitude from age 78 to 84 in men and women. The study also demonstrated that the association between rising RPR and greater mortality observed in younger populations is found with advancing age. Therefore although a falling pulse rate is part of physiological aging in the oldest old, it also appears to be a harbinger of longevity, being observed in subjects surviving onto advanced age.

The finding that RPR declines in the oldest old is consistent with longitudinal data from the Framingham Study^[7,8] and is important because it confirms the longitudinal observation in a cohort that differs in time, place, and culture. Although numerous physiological changes have been described as part of the cardiovascular aging process, falling RPR has not consistently been recognized as a hallmark of aging. Evidence exists in support of lower maximum heart rate, beat-to-beat variability, blunting of autonomic responses with age, and the intrinsic decline in response to adrenergic stimulation.^[1–4] Studies have often focused on small samples, with underrepresentation of the oldest old.^[28] The greater frequency of cardiac arrhythmias in older people is well known, with fibrous changes and ischemic damage often being cited as causes.^[29] Nonetheless the finding that a falling RPR is a predictor of greater longevity demands a clinical differentiation between pathology and what most likely is normal, and possibly successful, aging. The finding of the current study suggests that the decreased adrenergic response seen with aging is an important mechanism related to lower RPR and its protective effect, and this is an important subject for future research.

Previous studies have examined the association between high heart rate and mortality in elderly adults. One found high heart rate to be a significant risk factor for mortality in men aged 65 and older, and a nonsignificant trend was noted in women.^[15] A second report from the same group confirmed the finding of an association between RPR and mortality in elderly men but not women.^[18] The subjects were examined in an office setting, and no information was provided about the use of beta-blockers. The mean age of the population in this study was 73; the current findings extend these observations to a very elderly cohort examined in the home. The Chicago Heart Association Detection Project demonstrated a non-significant trend toward greater mortality in a subgroup of subjects aged 60 to 74 with high heart rate. This study recruited subjects from the workplace, did not include subjects aged 75 and older, and did not provide information related to beta-blocker therapy.^[17]

Several mechanisms may explain the relationship between high RPR and mortality. Animal studies have demonstrated that higher heart rate may directly cause coronary atherosclerosis.^[30] High heart rate may also cause coronary vasoconstriction in subjects with existing atherosclerosis^[31] and may be associated with greater vascular stiffening, a mechanism potentially particularly important in elderly adults given the poorer arterial compliance seen in this population.^[32,33] Lower heart rate has been shown to lead to angiogenesis through increases in vascular growth factor expression.^[34] Imbalances of the autonomic nervous system leading to greater sympathetic as opposed to parasympathetic tone may be associated with mortality secondary to cardiac arrhythmias. Less adrenergic responsiveness in elderly adults may partially mediate this imbalance.^[4] In elderly adults, high heart rate may also be a reflection of impaired cardiac functional reserve due to comorbidities such as IHD and congestive heart failure.^[35] An association was not found between RPR and mortality in the subgroup of men aged 70 to 77. The reasons for this finding are unclear. It has previously been demonstrated that cohort subjects aged 70 were relatively "healthy" and comparable with younger populations, and it is possible that effects of aging on RPR and mortality are not yet apparent in this age group, at least in men.^[21] It is also possible that this is a chance finding related to small sample size.

Regular physical activity has been associated with lower mortality in elderly adults.^[27] In the current study, RPR was not significantly associated with physical activity, suggesting that reductions in heart rate do not mediate the survival benefit of physical activity in elderly adults. The effects of physical activity on heart rate seen in younger populations may be muted in elderly adults because of changes in autonomic function or other mechanisms. It has previously been demonstrated that physical activity in the oldest old is not associated with changes in cardiac function on echocardiography.^[36] These results suggest that the benefits of physical activity in this population may at least in part be related to other, noncardiovascular mechanisms such as direct effects on cellular aging.^[37]

Another novel finding in the current study was related to use of beta-blockers. Although beta-blockers significantly reduced pulse rate, as expected, there were no differences in RPR between survivors and nonsurvivors in the subgroup of subjects receiving beta-blocker therapy. The use of beta-blockers has been shown to reduce mortality in cardiovascular disease, but it remains unclear whether this is due to pulse rate–lowering effects of beta-blockers or other pleiotropic effects. The current study suggests a role for non-pulse-rate-lowering effects in mortality reduction at least in this elderly population. Studies using the direct sinus node inhibitor ivabradine for the treatment of chronic IHD did not conclusively demonstrate lower mortality despite lower heart rate in the treated group, findings consistent with this hypothesis.^[38] Because use of beta-blocker therapy was not randomized, definitive conclusions from this study concerning this are limited.

The major limitation of this study, as well as of previous studies on this topic, is the difficulty in accounting for all potential confounding variables that may affect heart rate, such as mental stress, sleep disorders, and genetic factors. This is particularly relevant in the subgroup of individuals receiving beta-blockers, in whom the potential for confounding may be more significant. In addition, RPR is a potentially variable physiological measurement. This was corrected for by using a standardized protocol with multiple measurements of heart rate after prolonged resting.

In conclusion, RPR declines in the oldest old and is associated with greater longevity independent of associated comorbidities, physical activity, or beta-blocker therapy. RPR may serve as a simple prognostic sign in the oldest old.

J Am Geriatr Soc. 2013;61(1):40-45. © 2013  Blackwell Publishing