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The Hemorheologic-Hemodynamic Theory of Atherosclerosis -- Insights Provided by the Hemorheologic-Hemodynamic Theory (Part 7)

Insights Provided by the Hemorheologic-Hemodynamic Theory

The hemorheologic-hemodynamic theory explains the significant remaining risk of adverse cardiovascular events in patients with established coronary artery disease despite aggressive lowering of LDL-cholesterol using high dose statin therapy. Such therapy does not address the adverse consequences of arterial stiffening or increased blood viscosity caused by other factors. The hemorheologic-hemodynamic theory provides a more plausible explanation for the protective effect of HDL than “reverse transport of cholesterol.”

The hemorheologic-hemodynamic theory explains the existence of atherosclerotic plaques in synthetic arteriovenous grafts [1]. These provide an extreme hemodynamic environment, where extremely high velocity blood flows through a curved vessel. These vessels are prone to thrombosis and development of atherosclerotic plaques despite anticoagulation. These vessels lack a tunica media, which received wisdom maintains is the origin of smooth muscle cells in atherosclerotic plaques via migration. The identification of the fibrocyte provides an alternative explanation for the origin of smooth muscle cells in atherosclerotic plaques [2, 3, 4]. Being largely inanimate, the capacity of these vessels to respond to an injury with an inflammatory response, would be very limited to put it mildly. Further, this theory explains the benefit of blood donation [5] and drinking large quantities of water[6]. Both of these very low risk interventions reduce blood viscosity.

The hemorheologic-hemodynamic eliminates reliance on the fatty streak in atherogenesis. Fatty streaks routinely resolve without sequelae [7]. This is acknowledged by mainstream atherogenesis theory, which is unable to predict why a particular fatty streak progresses into an atherosclerotic plaque while the majority regress [8]. Increased HDL particle size and increased low-shear blood viscosity caused by torcetrapib therapy could account for the increased cardiovascular mortality seen in clinical trials.

Last Section: The Future (Part 8)


1. Sloop GD, Fallon KB, Zieske AW. Atherosclerotic plaque-like lesions in synthetic arteriovenous grafts: implications for atherogenesis. Atherosclerosis 2002;1260: 133-9.

2. Bellini A, Mattoli S. The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibrosis. Laboratory Investigation 2007;87: 858-70.

3. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Molecular Medicine 1994;1: 71-81.

4. Caplice NM, Bunch TJ, Stalboerger PG, Wang S, Simper D, Miller DV, Russell SJ, Litzow MR, Edwards WD. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proceedings of the National Academy of Science 2003;100: 4754-9.

5. Sloop GD. Possible association of a reduction in cardiovascular events with blood donation. Heart 1998;79:422. 

6. Chan J, Knutsen SF, Blixx GG, Lee JW, Fraser GE. Water, other fluids, and fatal coronary heart disease: the Adventist Health Study. American Journal of Epidemiology 2002;155: 827-33. 

7. Sloop GD, Perret RS, Brahney JS, Oalmann M. A description of two morphologic patterns of aortic fatty streaks and a hypothesis of their pathogenesis. Atherosclerosis 1998;141: 153-60. 

8. Sloop GD. A critical analysis of the role of cholesterol in atherogenesis. Atherosclerosis 1999;142: 265-8.

ⓒ 2011 Gregory Sloop. All Rights Reserved.


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