~ Fibrinogen Adds to Value of CRP Levels For Predicting Cardiovascular Events

A report published in the August 1, 2006 issue of the journal Circulation revealed that fibrinogen levels add to the value of high-sensitivity C-reactive protein (hs-CRP, a marker of inflammation) levels to predict cardiovascular events. Fibrinogen is a protein that is involved in blood clot formation, which, when elevated, is associated with an increase in vascular and nonvascular mortality.

For the current study, Harvard researchers evaluated data from women enrolled in the Women’s Health Study, a placebo-controlled trial of the effect of low dose aspirin and vitamin E on the prevention of cardiovascular disease and cancer in women aged 45 and older. Participants completed questionnaires from 1992 to 1995 to provide information on demographics, medical history, and other factors. Blood samples from 27,742 women were analyzed upon enrollment for CRP and fibrinogen. The participants were followed through February, 2005, during which time cardiovascular events were recorded.

Over the approximate ten year follow-up there were 898 cardiovascular events. Not surprisingly, both fibrinogen and CRP were associated with the risk of cardiovascular incidents. When women whose fibrinogen levels were in the top one-fifth of participants were compared to those in the lowest fifth they were found to have a 35 percent greater risk (adjusted for established risk factors) of experiencing a cardiovascular event. Similar analysis of CRP levels found a 68 percent greater risk among women whose levels were highest. Having an elevated level of both fibrinogen and CRP was associated with the greatest cardiovascular risk. Women whose fibrinogen levels were greater than 393 milligrams per deciliter and whose CRP levels were higher than 3 milligrams per liter had 3.45 times the risk of experiencing a cardiovascular event than those whose fibrinogen was lower than 329 milligrams per deciliter and whose CRP was under 1 milligrams per liter.

“Although both fibrinogen and hs-CRP were positively correlated, their combined effect provided cardiovascular disease risk information that was greater than that provided by either biomarker separately, potentially reflecting different pathophysiological processes in the development of atherothrombotic events,” the authors conclude. They remark that increased adipose tissue is associated both with a prothrombotic and proinflammatory state, which may be reflected in both higher fibrinogen and CRP levels.

Related Health Concern: Blood Clot Prevention: Battling a Dangerous Condition

The best way to avoid damage from a blood clot is to take preventive action. A person with multiple risk factors for blood clots may consider taking active steps to reduce his or her risk. Risk factors for a blood clot include:
  • Elevated homocysteine levels—Homocysteine is an intermediary amino acid that is formed from the conversion of methionine into glutathione. High levels in the body indicate impaired homocysteine metabolism (via depressed methylation) or oxidative stress. Elevated homocysteine levels have been linked to increased risk of arterial blood clots (Ebbesen LS 2004). The Life Extension Foundation recommends keeping homocysteine levels between 7 and 8 millimoles per liter.

  • History of heart attack or CAD—Atherosclerosis rarely occurs in isolation. Rather, it tends to be widespread throughout the body, so a history of atherosclerosis or heart attack translates into increased risk of blood clots.

  • History of stroke or TIA—One of the strongest predictors of stroke risk is a history of previous stroke or TIA. All patients who have had an ischemic brain event should take steps to lower their risk of future (and possibly more serious) events.

  • Inflammation—Chronic inflammation is associated with a variety of chronic diseases, including cardiovascular disease. C-reactive protein (CRP) is a sensitive indicator of inflammation throughout the body. A feature article in the May 2002 issue of Scientific American emphasized the link between chronic inflammation and the evolution of CAD (Libby P 2002). The Life Extension Foundation highly recommends measuring CRP levels using a high-sensitivity CRP blood test.

  • Elevated fibrinogen—Fibrinogen has a number of effects in the blood coagulation process. It reacts with thrombin to produce fibrin, it promotes platelet aggregation (which can lead to diminished blood flow), and it can cause platelets to bind together. An article in the journal Neurology found that prior stroke and elevated fibrinogen levels predicted new brain events in patients who have had a stroke (Beamer NB et al 1998).

  • Abnormal blood lipids—Cholesterol’s role in atherosclerosis and blood clotting is well documented. LDL cholesterol molecules, which are large and unstable, contribute to plaque formation on arterial walls. When plaque ruptures, the resulting blood clot may cause a heart attack or stroke. Elevated levels of triglycerides, another kind of blood lipid, are also associated with heart disease, while depressed high-density lipoprotein (HDL) cholesterol levels are associated with elevated risk of heart attacks and strokes.

  • Hypothyroidism—A deficiency in thyroid hormone is associated with elevated levels of several clotting factors (Chadarevian R et al 2001; Muller B et al 2001) and with elevated homocysteine and depressed folate levels (Lien EA et al 2000; Nedrebo BG et al 2003). Supplemental thyroid hormone returns homocysteine levels to normal (Diekman MJ et al 2001; Hussein WI et al 1999). Furthermore, thyroid hormone inhibits LDL oxidation (Diekman MJ et al 2000). Hypothyroidism, even at levels detected only by an elevation of thyroid-stimulating hormone (TSH) level in the blood, is also a known risk factor for the development of atherosclerosis (Carantoni M et al 1997; Hak AE et al 2000).


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