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Santa Ana, CA 92705-3606
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Jeremy E. Kaslow, MD, FACP, FACAAI Physician and Surgeon
Board Certified Internal Medicine

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Fibrinogen is a protein that plays a key role in blood clotting.  Fibrinogen is a sticky, fibrous coagulant in the blood that appears to significantly increase the risk of experiencing one of the leading causes of death and disability - stroke.

Analysis of the large-scale EUROSTROKE project (J Epidemiol Community Health 2002;56(Suppl I):i14-i18) showed that "fibrinogen is a powerful predictor of stroke" - including fatal and nonfatal strokes, first time strokes, and hemorrhagic and ischemic strokes. Dividing the population into four groups (quartiles) based on their fibrinogen levels, researchers estimated that the risk of stroke increased by nearly 50% for each ascending quartile. Individuals whose fibrinogen levels were in the highest quartile were almost seven times more likely to suffer a hemorrhagic stroke, and more than twice as likely to die from a stroke.

 

Importantly, higher levels of fibrinogen raised the risk of stroke independently of cardiovascular risk factors such as smoking and hypertension. Still, high blood pressure and high fibrinogen levels appeared to be the most dangerous combination, elevating a person's risk of stroke even more.  Each year, strokes account for about 1 of every 15 deaths in the United States. More than one-fourth of the people who suffer a stroke are under age 65.

 

A recent study measured baseline fibrinogen levels in over 2000 men and women being treated at a preventive cardiology unit of a large city hospital.  About half of the patients had coronary artery disease (CAD).  Acevedo M et al (Am Heart J 2002;143:277-82) found that patients with CAD tended to have higher fibrinogen levels than those without the disease. Of the patients whose fibrinogen levels fell within the two highest quartiles (>331 mg/dL), about 75% of men and 50% of women were diagnosed with clinical CAD. A previous history of heart attack in the group with CAD was also associated with significantly higher average levels of fibrinogen.

 

These results show that patients with CAD, particularly those who have experienced a heart attack, often have higher fibrinogen levels.  But are elevations of this marker merely an after-effect of the disease?  To find out, investigators further tracked the health of the patients for an average of 24 months after their treatment at the cardiac care unit. They discovered fibrinogen was a strong and significant independent predictor of death from all causes in both men and women.  The percent mortality rate jumped by over seven-fold in those with the highest fibrinogen levels, compared to those with the lowest levels.

 

Fibrinogen's association with increased mortality is probably directly related to its ability to promote thromboses, or clots, by causing platelets to clump inside blood vessels.  This is one of the main mechanisms underlying ischemia and heart attack. Exercise, quitting smoking, and certain medications have been shown to lower fibrinogen in the short term.

A number of studies show elevated fibrinogen to be a major risk factor for coronary heart disease (heart attacks) and cerebrovascular disease (strokes), which together account for about 60% of deaths in the elderly. In fact, fibrinogen may possibly be the major risk factor, exceeding the “contributions” of homocysteine, cholesterol and other lipids in the pathogenesis of these diseases.  Elevated fibrinogen levels have also been associated with a number of other diseases, including cancer, diabetes and hypertension (N Engl J Med, 1987, 317: 521; The Framingham Study. JAMA, 1987, 258: 1183).

SG Thomson, et al prospectively studied over 3,000 patients with angina pectoris (chest pain due to coronary artery insufficiency) in his 1995 New England Journal of Medicine article (332: 635-641) and found if fibrinogen levels were low, even highly elevated levels of cholesterol and/or C-reactive protein presented little risk of heart attacks. However, high levels of fibrinogen in combination with low-moderate levels of cholesterol presented a significant risk.

Fibrinogen levels have been shown by a number of research teams to rise about 25 mg/dl per decade of age (Yarnell in Circulation, 1991, 83: 836-844; Fu and Nair in Am J Physiology 275 (Endocrinol Metab 38), 1998 E1203-E1030) even if they are described as being in good health.  A team of scientists in China also recently compared fibrinogen levels in two families, one family with a history of long life in many of its members, compared to another family with traditionally shorter life expectancies. The scientists concluded that low plasma fibrinogen levels are correlated with longer life (Wang, et al, Weisheng Yanjiu, 1998, 27: 5, 315-316).

No drug (with the possible exception of estrogen) or lifestyle change is known to significantly alter fibrinogen levels, although quitting smoking does result in slight reductions in fibrinogen levels. However, for those of us who don’t smoke, there has been little, if any, advice which could be given to lower fibrinogen from the conventional medical approach.

Nutritional supplements can reduce fibrinogen levels and the presumably the inherent risk of hyper-fibrinogenemia-related diseases.  Ramirez-Bosca’s studies in Spain have demonstrated that certain antioxidants are capable of dramatically reducing blood levels of lipid peroxides and oxidized lipoproteins (Age 1995, 167-9 and in 1997, 20: 165-8) after only 15 days with no adverse effects noted by any of the subjects or adverse changes in any other blood chemistries (Mech Aging Dev, 2000, 114: 207-20).

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