1. Blood Viscosity May be the Most Sensitive Biomarker for Risk of Atherosclerosis 

Improved prediction of cardiovascular risk is necessary because 50% of myocardial infarctions occur in individuals without overt hyperlipidemia. If we hope to prospectively identify the 20% of myocardial infarctions which occur in the absence of any classic risk factors, [1] we should evaluate new risk factors. All of the major risk factors for atherosclerosis, including hypercholesterolemia, hypertension, cigarette smoking, diabetes mellitus, obesity, male gender, and advanced age, are associated with increased blood viscosity. Measuring blood viscosity can give the accumulated risk for atherosclerosis associated with your patient’s entire risk profile, not simply the increased risk imparted by one factor like hypercholesterolemia. 

2. Increased Blood Viscosity May be More Than Just a Biomarker But Rather the Effector by Which These Risk Factors Cause Atherosclerosis 

Two theories have been advanced to explain how blood viscosity accelerates atherosclerosis. According to the protective adaptation theory, increased blood viscosity chronically injures the endothelium in areas of high shear stress. An atherosclerotic plaque is viewed as an adaptive thickening, much like a callus on your foot in an area of chronic rubbing. According to the hemorheologic-hemodynamic theory, increased blood viscosity creates larger areas of lower shear, which favors the development of intravascular thrombi. Atherosclerotic plaques are the result of organization of these thrombi. These two mechanisms are not mutually exclusive. Friction may be responsible for damage in areas of high shear stress, and thrombosis may the cause of pathology in areas of low shear stress. 

3. Increased Blood Viscosity is Very Treatable 

Cholesterol-lowering medication will decrease blood viscosity by virtue of lowering serum cholesterol levels. Drinking 8 to 12 glasses of water per day will also decrease blood viscosity. [2] Another option is to donate blood. A growing body of evidence shows that blood donation prevents cardiovascular disease. Unfortunately, only about half of the U.S. population is eligible to donate blood. For those who are ineligible, therapeutic

phlebotomy is an option. Currently, therapeutic phlebotomy is most widely utilized in managing polycythemia vera and iron overload. The procedure is very similar to collecting blood for transfusion, and protocols for performing the procedure are readily available on the internet. The CPT code for therapeutic phlebotomy is 99195. 

“The philosophies of one age have become the absurdities of the next, and the foolishness of yesterday has become the wisdom of tomorrow.” Sir William Osler (1849-1919), eminent physician. 

Mention of therapeutic phlebotomy usually elicits snarky remarks about bloodletting and leeches. On the contrary, I found reading about bloodletting to be enlightening. Despite the limitations of their therapeutic armamentarium, there is no reason to believe that 19th century physicians had lesser powers of observation than their 21st century counterparts. Physicians of that time felt that patients with “plethora” responded best to bloodletting. 

… physicians usually recognized plethora by the context in which it appeared: it ”is ascribed to indulgence in diet, with little exercise and excess of sleep”. Plethora “is produced by taking into the body an excessive quantity of new materials, by indulgence in the pleasures of the table, by eating and drinking too much”; it “occurs most commonly in persons who have retired from active life; who eat, drink, and gorge themselves; who take little exercise, and have torpid bowels”…. Who was most likely to become plethoric (and so to require bloodletting)? This is the same as asking: for people of what class would it have been possible to retire from active life, to regularly eat and drink to the point of gorging themselves, and to spend their time in warm baths and soft beds? Of course, on a short term basis, almost anyone could overeat or be indolent, but only the wealthy could regularly engage in these unhealthy excesses and so become dangerously plethoric. [3] 

There are similarities between the patients who reportedly responded best to bloodletting and the stereotypical consumer of the 21st century western lifestyle. Of course with no well-defined therapeutic goal or endpoint, these clinical observations are of limited value. However, it is not unreasonable to speculate that these plethoric patients had elevated blood viscosity and enjoyed increased exercise tolerance and sense of well-being following bloodletting. It is tempting to think that an anecdotal observation of successful therapy using bloodletting in a patient with polycythemia vera (typically described as “plethoric”) led to utilization of bloodletting in other patients with a similar phenotype. Given the few therapies available at the time, it is not surprising that bloodletting was used in many other situations, as well. However, the limitations of bloodletting were recognized in the 19th century: “there is no form of disease which at all times and under all circumstances admits of [bloodletting, and,] …few which may not occasionally justify its use.” [2] Personally, I am impressed by the sophistication of the observations of the 19th century physicians quoted above. 

4. Avoid Adverse Effects of Therapy 

I suspect that when the efficacy of therapeutic phlebotomy is widely recognized, statin therapy may begin to fall by the wayside. Only then will the side-effects of statins be fully recognized by patients who took the medicines and accepted their side effects in order to combat the number one killer on the planet. Certainly, a trial of therapeutic phlebotomy should be undertaken before bariatric surgery. In metabolic syndrome, Houschyar et al. showed a significant decrease in blood pressure, blood glucose, HbA1c, and heart rate in a randomized, controlled, single-blind clinical trial of 64 patients, 33 of whom underwent therapeutic phlebotomy [4]. The interested reader may wish to review my commentary “The Role of Blood Flow in the Metabolic Syndrome” in the commentary archive of this website. 

5. Potential Benefits 

“Longevity is a vascular question.” -Osler 

The benefits of long-term therapy for subclinical elevated blood viscosity are unknown. It is possible that poorly-understood vascular diseases, such as hypertensive arteriosclerosis and nephrosclerosis, are due to

increased friction and shear stress on the endothelium and could be prevented by control of blood viscosity. Like Dr. Osler, I feel that perfusion is a critical variable in aging, and control of blood viscosity could forestall fatigue and failure of the elastic elements in the vasculature. Perhaps, increased blood viscosity and decreased perfusion play a role in other degenerative diseases, such as macular degeneration. Only long-term monitoring and control of blood viscosity will elucidate the role of elevated blood viscosity in aging. However, I am optimistic. I feel the gaps in our understanding of aging will be filled with increased knowledge of blood viscosity, and longevity will be increased. 

References: 

1. Risk Markers for Atherothrombotic Disease. Ridker, PM, and Libby P. In: Bonow: Braunwald’s Heart Disease- A Textbook of Cardiovascular Medicine. 9th Edition. P. 922. 

2. The Blood Thinner Cure. A Revolutionary Seven-Step Lifestyle Plan for Stopping Heart Disease and Stroke. Kensey, KR, and Turkington, CA. McGraw-Hill, 2001. 

3. Change of type as an explanation for the decline of therapeutic bloodletting. Carter KC. Studies in History and Philosophy of Biological and Biomedical Sciences. 2010; 41: 1-11. 

4. KS Houschyar, R Ludtke, GJ Dobos, U Kalus, M Brocker-Preuss, T Rampp, B Brinkhaus, and A Michalsen. Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: Results from a randomized clinical trial. BMC Medicine 2012;10:54 doi: 10.1186/1741-7015-10-54. 

For Further Reading: 

Bloodletting is back! Here’s everything you need to know about this ancient practice. http://www.medtech.edu/blog/the-history-progression-and-modern-stance-on-bloodletting