State-of-the-Art Paper
Vascular Pathophysiology in Response to Increased Heart Rate

https://doi.org/10.1016/j.jacc.2010.09.014Get rights and content
Under an Elsevier user license
open archive

This review summarizes the current literature and the open questions regarding the physiology and pathophysiology of the mechanical effects of heart rate on the vessel wall and the associated molecular signaling that may have implications for patient care. Epidemiological evidence shows that resting heart rate is associated with cardiovascular morbidity and mortality in the general population and in patients with cardiovascular disease. As a consequence, increased resting heart rate has emerged as an independent risk factor both in primary prevention and in patients with hypertension, coronary artery disease, and myocardial infarction. Experimental and clinical data suggest that sustained elevation of heart rate—independent of the underlying trigger—contributes to the pathogenesis of vascular disease. In animal studies, accelerated heart rate is associated with cellular signaling events leading to vascular oxidative stress, endothelial dysfunction, and acceleration of atherogenesis. The underlying mechanisms are only partially understood and appear to involve alterations of mechanic properties such as reduction of vascular compliance. Clinical studies reported a positive correlation between increased resting heart rate and circulating markers of inflammation. In patients with coronary heart disease, increased resting heart rate may influence the clinical course of atherosclerotic disease by facilitation of plaque disruption and progression of coronary atherosclerosis. While a benefit of pharmacological or interventional heart rate reduction on different vascular outcomes was observed in experimental studies, prospective clinical data are limited, and prospective evidence determining whether modulation of heart rate can reduce cardiovascular events in different patient populations is needed.

Key Words

atherosclerosis
endothelium
heart rate
vascular response

Abbreviations and Acronyms

Apo
apolipoprotein
eNOS
endothelial nitric oxide synthase
FMD
flow-mediated dilation
I(f)
hyperpolarization-activated pacemaker current
NADPH
nicotinamide adenine dinucleotide phosphate
VSMC
vascular smooth muscle cell

Cited by (0)

This work was supported by the Universität des Saarlandes(Homburger Forschungsförderungsprogramm). Drs. Heusch, Laufs, and Böhm are supported by the Deutsche Forschungsgemeinschaft(DFG, KFO 196, and He 1320). The Universität des Saarlandes has received financial support from Servier(France) for basic research. Drs. Heusch and Böhm have received honoraria from Servier (France). Dr. Laufs has received grants (to institution) from Servier. All other authors have reported that they have no relationships to disclose.