Temporal Reduction in Chronotropic Index Predicts Risk of Cardiovascular Death Among Healthy Middle‐Aged Men: a 28‐Year Follow‐Up Study

Abstract

BackgroundChronotropic index is a standardized measure of heart rate (HR) increment during exercise that reflects the combined effects of age, resting HR, and physical fitness. Low chronotropic index has been reported to predict disease and death. We tested whether temporal change in chronotropic index over 7 years influenced risk of cardiovascular death through up to 28 years.Methods and ResultsChronotropic index was calculated ([achieved maximal HR−resting HR]/[age‐predicted maximal HR−resting HR]) after a symptom‐limited bicycle ECG exercise test in 1420 healthy men at 2 examinations 7 years apart, in 1972 and 1979. Events of cardiovascular death were registered by manual scrutiny of all participants’ hospital charts and the Norwegian Cause of Death Registry. The participants were divided into quartiles of temporal change in chronotropic index, with quartile one having the most negative value. Cox proportional hazard regression models were used to estimate risks and adjusted for classical cardiovascular risk factors. Incidence of cardiovascular death was 310 (22%) during median of 21 years of follow‐up. After multivariable adjustment, and comparison with quartile four (mean +0.11), quartiles one (−0.16), two (−0.04), and three (+0.02) were associated with hazard ratios 1.50 (95% CI 1.10–2.05), 1.10 (0.79–1.53), and 1.04 (0.74–1.45) for cardiovascular death. Results remained robust also after exclusion of 31 participants with exercise ECG‐induced signs of coronary ischemia.ConclusionsTemporal reduction in chronotropic index was associated with increased long‐term risk of cardiovascular death and might be a clinically important predictor when assessing risk in healthy individuals over a longer time.

Physical fitness is a modifiable predictor of early cardiovascular death: A 35-year follow-up study of 2014 healthy middle-aged men

“…Our findings add to the growing amount of evidence that physical fitness and other parameters derived from exercise testing are important cardiovascular risk predictors. [3][4][5][6]10,[19][20][21][22] Our findings also indicate that a single measurement of maximal physical fitness is a time-limited powerful cardiovascular risk predictor, and we substantiated that repeated physical fitness measurements may be valuable for assessing a patient's risk profile over time. Physical fitness is easily measured by ergometer or treadmill exercise testing, and allows self-assessment of the intensity of endurance training using commonly available exercise monitoring equipment such as watches, smart phone applications, treadmills and other gym facility training machines.…”

“…In order to minimize bias generated by differences in body weight during a non-weight bearing activity, total work was divided by body weight. Hence, in the present study, and in a number of previous studies, 4,5,8,13 physical fitness is defined as total work divided by body weight, which we consider to be the best possible measure given the data available in our study.…”

“…Risk predictors derived from exercise testing have gained interest, and are now important complements to classical risk factors such as family history, smoking, blood pressure and cholesterol. [2][3][4][5][6][7] Physical fitness and physical activity level, measured during exercise testing and self-reported, have previously been shown to predict cardiovascular death and disease; hence measurement of physical fitness and activity level could improve cardiovascular risk stratification. [8][9][10][11][12][13] However, an individual's level of physical fitness may vary from year to year due to changes in health, lifestyle and physical activity level.…”

Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers

“…The presence of chronotropic incompetence is associated with poor prognosis in both symptomatic and asymptomatic patients. [1][2][3][4][5][6] The frequency of chronotropic incompetence depends on the definition used as well as the population examined and ranges from 9% to 89%. 7 The Euro-EX prevention trial reported that, among healthy individuals, chronotropic incompetence assessed as an inability to achieve 80% of the age-predicted HR reserve, was present in 70% of patients.…”

Application of exercise ECG stress test in the current high cost modern-era healthcare system

“…Anginal chest pain during exercise is strongly predictive of underlying CAD 10 and cardiac mortality 23 . Reduction in chronotropic indices in serial exercise stress testing was proposed as a marker of cardiovascular death in a 28 year follow up study 46 . In a study of 1959, predominantly male patients, Leeper et al 47 demonstrated that a rapid initial rise in heart rate was associated with reduced mortality, though there have been conflicting reports of the same finding 48 .…”