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What Is the Best Strategy for Reducing Deaths from Heart Disease?

  • Michael E Makover,
  • Shah Ebrahim
  • Published: April 26, 2005
  • DOI: 10.1371/journal.pmed.0020098

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An Improved Explanation of Atherosclerosis

Posted by plosmedicine on 30 Mar 2009 at 23:43 GMT

Author: Lewis Coleman
Position: MD/Anesthesiologist
Institution: Semi-Retired
Submitted Date: June 08, 2005
Published Date: June 8, 2005
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

I have read the informative discussion of Drs. Makeover and Ebrahim about atherosclerosis. A precise explanation of atherosclerosis might facilitate effective treatments.

Present theory attributes atherosclerosis to inadequate "shear stress"[1]but this fails to explain the effects of hypothalamic stimulation[2], chronic illness, smoking, hyperlipidemia, polycythemia, fibrinogen levels, viscosity, hypomagnesemia, and Factor VIII where shear stress is normal.[3,4] It also fails to explain the protective effects of coagulopathy[5], moderate alcohol consumption and anemia[3].

The studies of Hof et al [6] demonstrate that shear stress in pipes causes exponential increases in turbulence and mixing along the inner walls that force slower-moving molecules to the center. This study suggests that inadequate turbulence and mixing may offer a more precise explanation of atherosclerosis than Shear Stress. Turbulence and mixing are inversely proportional to viscosity, but viscosity has minimal effect on Shear Stress. Increased blood viscosity may both accelerate atherosclerosis and increase coagulability.[7]

The turbulence hypothesis appears to explain known facts. Elevated hematocrit, fibrinogen, insoluble fibrin, and hyperlipidemia are known to increase viscosity, and anemia to reduce it. Coagulopathies involve failure to produce functional levels of insoluble fibrin. Magnesium may reduce insoluble fibrin levels by displacing calcium in the coagulation process.[8] Factor VIII may increase insoluble fibrin levels. Moderate alcohol consumption may reduce levels of Factor VIII and fibrinogen, [9] whereas disease states and hypothalamic stimulation may elevate them.[10] Smoking increases both red cell mass and fibrinogen levels.

If this hypothesis is correct, the most effective approach to preventing and treating atherosclerosis may be measures that reduce viscosity and/or increase turbulence and mixing in the blood. Ultrasound, which inhibits coagulation, may offer an effective means of treatment as well as diagnosis.

1. Malek AM, Alper SL, Izumo S: Hemodynamic shear stress and its role in atherosclerosis. JAMA 1999, 282:2035-2042
2. Khomulo PS, Ambrozas IV, Dmitrieva NA, Zharova IP, Nikolaev VI: [Development of atherosclerosis in alternating prolonged electrostimulation of the negative and positive hypothalamic emotiogenic zones]. Kardiologiia 1980, 20:104-108.
3. Tous M, Ferre N, Vilella E, Riu F, Camps J, Joven J: Circulating blood cells modulate the atherosclerotic process in apolipoprotein E-deficient mice. Metabolism 2004, 53:95-100.
4. Kensey KR: The mechanistic relationships between hemorheological characteristics and cardiovascular disease. Curr Med Res Opin 2003, 19:587-596.
5. Roguski J, Durkalec J, Hasik J, Jaroszewski F, Krasnik W, Nowaczyk J, Rachlewicz J, Roguska J, Ruszkowski M: Incidence of Clinical Criteria of Atherosclerosis in Hypo- and Hyperthyroidism, Polycythaemia Vera and Chronic Cor Pulmonale (Para-and Antiatherosclerotic Syndromes). Cor Vasa 1964, 103:219-230.
6. Hof B, van Doorne CW, Westerweel J, Nieuwstadt FT, Faisst H, Eckhardt B, Wedin H, Kerswell RR, Waleffe F: Experimental observation of nonlinear traveling waves in turbulent pipe flow. Science 2004, 305:1594-1598.
7. Coleman LS: Insoluble Fibrin may reduce turbulence and bind blood components into clots (in press). Medical Hypotheses 2005.
8. Kondo H, Kobayashi E, Itani T, Tatsumi N, Tsuda I: Hematology tests of blood anticoagulated with magnesium sulphate. Southeast Asian J Trop Med Public Health 2002, 33 Suppl 2:6-9.
9. Mukamal KJ, Cushman M, Mittleman MA, Tracey RP,Siscovick DS: Alcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study. Atherosclerosis 2004, 173:79-87.
10. Turczynski B, Michalska-Malecka K, Slowinska L, Szczesny S, Romaniuk W: Correlations between the severity of retinopathy in diabetic patients and whole blood and plasma viscosity. Clin Hemorheol Microcirc 2003, 29:129-137

No competing interests declared.