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The influence of heart rate on coronary artery atherosclerosis
J R Kaplan1, S B Manuck, T B Clarkson
1Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
Insights
Elevated resting heart rate (HR) in cynomolgus macaques is linked to more severe coronary artery atherosclerosis (CAA). This association is stable over time and independent of stress response or cholesterol levels, suggesting HR itself may impact coronary health.
Area of Science:
- Cardiovascular Research
- Primate Models
- Atherosclerosis Studies
Background:
- Elevated resting heart rate (HR) is a known predictor of coronary heart disease (CHD) in humans.
- Individual differences in casual HR are stable and consistent in cynomolgus macaques over time.
- Previous research suggests a link between HR and cardiovascular health.
Purpose of the Study:
- To investigate the association between naturally occurring individual differences in casual HR and coronary artery atherosclerosis (CAA) in cynomolgus macaques.
- To determine if the HR-CAA relationship is influenced by stress responsivity or lipid profiles.
- To explore potential mechanisms underlying the HR-CAA association.
Main Methods:
- Measured casual heart rates (HR) in cynomolgus macaques over a 12-month period.
- Quantified coronary artery atherosclerosis (CAA) by measuring plaque area.
- Assessed HR responsivity to stress and serum high-density lipoprotein cholesterol (HDL-C) levels.
- Utilized beta-adrenergic blockade to investigate sympathetic arousal.
Main Results:
- Monkeys with higher casual HR exhibited more than double the plaque area compared to low HR monkeys (p < 0.01).
- The relationship between casual HR and CAA was independent of HR responsivity to stress.
- Higher casual HR was associated with lower HDL-C, but CAA differences were independent of this lipid variation.
- Elevated casual HR in monkeys is linked to sympathetic arousal.
Conclusions:
- Naturally occurring differences in casual HR are significantly associated with coronary artery atherosclerosis in cynomolgus macaques.
- The HR-CAA link may be mediated by HR-induced differences in coronary blood flow, rather than lipid levels or stress response.
- Findings suggest elevated resting HR as a potential risk factor for atherosclerosis, even in non-human primates.
Abstract:
Elevated "casual" heart rate (HR) has been found to be an independent predictor of coronary heart disease (CHD) in human beings. The current study provides data on the association between coronary artery atherosclerosis (CAA) and naturally occurring individual differences in the casual HRs of cynomolgus macaques (Macaca fascicularis). The data demonstrate that naturally occurring differences in casual HR are related to CAA (plaque area in mm) with high HR monkeys having lesions more than twice as extensive as those of low HR monkeys (high HR; n = 7, 159 beats/min: 0.76 mm2 +/- 0.21 SD; low HR; n = 8, 133 beats/min: 0.31 mm2 +/- 0.30; t = 3.01, p less than 0.01). The data show further that the distribution of individual differences in casual HR is consistent and stable over periods of at least 12 months. Importantly, the relationship between elevated casual HR and CAA was independent of the association between an index of HR "responsivity" to stress and CAA, found in the same monkeys. Similar to a recent finding in human beings, high casual HR also was associated with significantly lowered serum concentrations of high-density lipoprotein cholesterol; differences in CAA were, however, independent of the lipid difference. The CAA differences may depend instead on HR-induced differences in coronary blood flow between high and low HR monkeys. Subsequent work with beta-adrenergic blockade suggested that elevated casual HRs in monkeys are associated with sympathetic arousal.