Author + information
- Yiannis S. Chatzizisis, MD, PhD⁎ ( and )
- George D. Giannoglou, MD, PhD
- ↵⁎Cardiovascular Engineering and Atherosclerosis Laboratory, 1st Cardiology Department, AHEPA University Hospital, Aristotle University Medical School, 1 Stilp. Kyriakidi Street, 54636 Thessaloniki, Greece
We congratulate Custodis et al. (1) on their review regarding the role of increased heart rate (HR) in vascular pathophysiology. We would like to underscore the importance of local hemodynamic conditions on the atherosclerotic effect of increased HR and to expand on the pathophysiologic mechanisms involved in this effect.
Elevated HR appears to promote atherosclerosis by modulating the local hemodynamic environment (2). Low and oscillatory endothelial shear stress (ESS), which plays a critical role in the pathogenesis of atherosclerosis (3), occurs in geometrically irregular regions of the coronary arteries during systole, whereas in the same regions, ESS increases to more physiologic levels during diastole (2). As HR increases, the fraction of the cardiac cycle corresponding to diastole decreases, thereby increasing the exposure of endothelium to the atherogenic effect of systolic low ESS and attenuating the atheroprotective effect of diastolic ESS (2). Moreover, moderately elevated HR increases the frequency of ESS oscillations between systole and diastole in atherosclerosis-prone regions, further enhancing the local atherogenic environment (2).
Also, high HR may increase the cardiac output, increasing the blood pressure and subsequently the local tensile stress, which also plays a critical role in atherosclerosis (2,4). In addition to the magnitude of tensile stress, elevated HR may also increase the frequency of the periodic tensile stress fluctuations between systole and diastole, resulting in a cumulative “fatigue effect” on the coronary endothelium (2,4).
By increasing tensile stress, increased HR may alter the structure and organization of the extracellular matrix within the coronary wall, thereby promoting stiffening of the wall. Within stiff coronary arteries, the proatherogenic local hemodynamic environment may be enhanced (2,5).
The pulsatile motion of the heart during the cardiac cycle induces periodic changes in the geometry of the coronary arteries, which in turn influence the local hemodynamic environment. By increasing the frequency of the pulsatile heart motion, high HR enhances the periodic geometric changes of the coronary arteries, accelerating the atherosclerotic process (2).
Further experimental and clinical studies are warranted to elucidate the underlying molecular mechanisms implicating increased HR in coronary atherosclerosis. Slowing HR could potentially decrease the progression of atherosclerosis by reducing the local atherogenic vascular environment. This effect may be involved in any beneficial role of HR-lowering agents in preventing coronary artery disease.
- American College of Cardiology Foundation
- Custodis F.,
- Schirmer S.H.,
- Baumhäkel M.,
- et al.
- Chatzizisis Y.S.,
- Coskun A.U.,
- Jonas M.,
- et al.