The primary finding in this study was that, in repeat exercise treadmill testing between ages 18 and 50, the decline of MHR with age was less at younger ages than at older ones. The fitted rates of loss of MHR according to a quadratic age function, 179+0.29*age-0.011*age2, are similar to the observed rates of loss between years 0 and 7 (0.37 beats/minute/year) and between years 7 and 20 (0.63 beats/minute/year), respectively. Another important observation is that the rate of decline of MHR with age was slower in people who were thinner at baseline than in those who had higher BMI.
Our findings are consistent with those of two other longitudinal studies. Plowman et al. (15
) reported on 36 healthy women retested after an interval of 6.1 years. MHR in symptom-limited testing remained relatively steady during ages in the 20’s and 30’s, then declined at a faster rate in the 50- and 60-year-old age groups. Gellish et al. (8
) studied 908 symptom-limited maximal exercise treadmill tests in 132 men and women attending a university fitness center over several years. Although they concluded that eMHR = 207 – 0.7 x age fit their data well, eMHR = 191.5-.007*Age2
fit the data better. There is a negligible difference between the curvature of our formula and that of Gellish among ages 27-50 that occur in both studies. In their study, the rate of decline in MHR was close to zero through about age 40, and was about 0.5 beats/minute/year between ages 40 and 50. We showed a reduced rate of decline in CARDIA participants who were thinner or fitter at baseline, at ages 18 to 30 years. Consistent with this finding, it is likely that the participants in the Gellish study were thinner and more fit than were members of the general population studied in CARDIA, which may account for the slower rate of loss of MHR in the Gellish study than in CARDIA.
On the other hand, our findings conflict with those of Tanaka et al., who found that eMHR = 208- 0.7 × age in a summary of 492 groups that included true maximal exercise tests in 18,712 persons, confirmed in their own specific study of true maximal tests in 514 individuals. There was no sign of curvature in the MHR and age relationship in this monumental study. Tanaka's (22
) finding differs from ours in important ways. Tanaka's results were based on cross-sectional study designs, so could not capture individual changes over time, whereas the longitudinal study designs used by Plowman (15
), Gellish (8
), and CARDIA were able to assess individual changes. In individual changes, the slope of MHR over age was consistently lower in persons initially younger than at older ages. Thus, in this respect, the CARDIA study that included tests in 97% of the general population sample recruited into the study, suggests curvature in the MHR and age relationship that is missed in cross-sectional study designs.
The true maximal exercise test is a superior measure of cardiorespiratory capacity compared to the symptom-limited test that CARDIA, Plowman (15
), and Gellish (8
) used, but it may restrict the sample to those who are willing and able to do the test, and in this way skew the estimate of the relation of MHR to age in the general population. A characteristic of the symptom-limited maximal exercise protocol is that it does not in most cases achieve true maximum, as reflected in by the higher age-specific eMHR using the Tanaka or Fox formula than using any of the CARDIA findings. Furthermore, in a symptom limited test, the extent of full effort is a differential proportion of true maximum that varies by person. A common strategy is to eliminate from statistical analysis all tests deemed to be “less than full effort” (eg using 85% of the Tanaka prediction). As shown in the Supplement, all restriction methods considered, whether based on RPE, stage achieved, excluding tests with MHR less than 85% of the Tanaka eMHR, or any other rule for excluding less than full effort tests, yielded a quadratic relationship between MHR and age. However, viewed from a population perspective, we think that the volunteers in Tanaka's paper (22
) almost certainly were highly selected, excluding those for whom a true maximal test would be uncomfortable. Since CARDIA was able to test 97% of its participants at baseline, we were able to assess selection bias in future testing. Among important baseline characteristics of those least likely to complete 1 or 2 more tests over 20 years were reduced fitness and lung capacity, adiposity, smoking, and sedentary lifestyle. Consequently, participants who completed 3 tests, who tended to be the healthiest at baseline, had relatively higher eMHR than the overall CARDIA cohort. Therefore, the formula derived from these participants was less generalizable than the formula derived from the whole CARDIA cohort. Moreover, the CARDIA formula may also be more realistic for the general population than the Gellish (8
) formula. CARDIA showed a slightly steeper rate of decline in MHR with age at each age than did Gellish et al., but the Gellish et al. sample was considerably selected compared to the population-based CARDIA sample as is visually apparent in .
The decrease of MHR with advancing age is a reasonable expectation for physiologic change. Rodeheffer et al. (16
) performed serial gated blood pool scans at rest and during exercise treadmill tests for 61 participants aged 25 to 79 years. They found an age-related increase in end-diastolic volume and stroke volume, and an age-related decrease in heart rate during treadmill tests, such that cardiac output both at rest and during exercise was maintained across ages. The changes in the cardiovascular system associated with aging (5
) and adiposity, (13
) tend to decrease heart rate and heart rate response to exercise. These changes include apoptosis of sinoatrial node pacemaker cells, decreased responsiveness to β-adrenergic receptor stimulation and decreased reactivity to baroreceptors and chemoreceptors (5
Furthermore, the quadratic component to the age-related MHR decrease, implying more rapid MHR decrease in older than in younger ages, might be partly explained by physiologic change. Cheitlin pointed out that apoptosis of sinoatrial node pacemaker cells leads to a loss of 50% - 75% of cells by age 50, resulting in slower intrinsic heart rate. Since the exact rate of the loss of cells is not available and has not been proven to be linear, it is possible that this rate of loss is quadratic, leading to greater loss of intrinsic heart rate at older than at younger ages and thus contributing to greater loss of MHR at older than at younger ages. In addition, Cheitlin et al. (5
) pointed to decreased responsiveness to β-adrenergic receptor stimuli with aging, partly compensated by an increase in circulating catecholamines. However, whether this compensation is at a constant rate with aging or not was not assessed. Therefore, further cardiovascular physiological studies would be helpful, related to the change, especially the change rate of atrial pacemaker cells, responsiveness to β-adrenergic receptor stimuli and compensation by circulating catecholamines with aging.
We previously reported a finding that is consistent with slower loss of cardiorespiratory capacity in thinner than in heavier people, namely that the people in the lowest quartile of baseline BMI maintained their lung function through their mid-30s (24
). Thus structure and function of cardiovascular and pulmonary tissue was maintained in the smaller leaner participants. The steeper rate of decline in the participants with higher BMI was not due to reduced physical activity, since physical activity itself was not a strong correlate of MHR. Another possible explanation of the more rapid rate of decline in people with higher BMI is that they did not work as hard on the treadmill as thinner people, especially as they aged, as would be evidenced by stopping the test at lower RPE. However, adjustment for RPE did not much alter the pattern of the decline of MHR with age across baseline BMI quartiles. Furthermore, the rate of decline of the MHR at older ages was likely underestimated because the people with higher BMI had tendency not to return for retesting ().
Apart from age and BMI, several variables were related to MHR. The underlying mechanisms are not well studied. For example, smoking was related to a reduced MHR, but smokers did not have a greater rate of decline of MHR than nonsmokers. It is known that nicotine increases heart rate, myocardial contractility, and blood pressure by stimulation of sympathetic neurotransmission. However, the norepinephrine-releasing effect of nicotine cannot explain the smoking-MHR association in this study (10
). We hypothesize that during exercise nicotine acts as a beta blocker, which lowers MHR acutely (21
), but is not associated with MHR decreases over time.
The large, population-based sample of adults and the 20 year follow-up of participants with 3 tests in many cases are the strengths of this study. Our results may be more generalizable than previous studies due to the population-based sampling of participants, the substantial proportion of women and black participants, and the inclusion of smokers and obese persons. While the repeat testing is a strength, a limitation for determining repeatability is that testing was completed only 3 times by each participant spread out over 20 years. Due to the symptom-limited maximal test protocol that was used, it is difficult in these data to distinguish differences among participants in true maximal heart from differences in proportion of true maximum achieved. However, use of the symptom-limited test allowed us to perform testing in nearly everyone in the study.
In conclusion, for those using exercise testing for providing a target heart rate during exercise, one implication from this study is that people with lower BMI lose MHR very slowly through their 20s and 30s, then start to lose more quickly in the 40s, yet at a slower rate than was observed in Tanaka's equation. People with higher BMI lose MHR throughout age 18-50 at about the rate of 0.7 beats/minute per year of age as specified by Tanaka et al. (22
). While no precise alteration to the formula 208-0.7*age is possible from these CARDIA data, partly because such an alteration would only apply to ages 18-50. Clinicians making exercise prescriptions should be aware that the loss of MHR is quadratic in most people, and is very slow in the smallest younger individuals. For those with higher BMI, the clinician should be aware that the rate of loss of MHR is steep, even at younger ages. Future study involving participants at older ages (>50 years) is needed. Further characterization of the distribution of the percent of true MHR achieved in submaximal testing would be helpful.