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C-REACTIVE PROTEIN AS A PREDICTOR OF HEART ATTACK
Risk factors such as family history, elevated blood pressure, smoking, and high levels of cholesterol are some of the conditions known to increase the risk of heart attacks. However, between a third and a half of all heart attacks strike people, who have no idea they are at risk, have normal cholesterol levels, don't smoke, and are apparently low-risk individuals without classical risk conditions. Recent evidence suggests that heart disease is the endpoint of a decades-long inflammatory process, that it is not simply the accumulation of cholesterol and fat in the arteries. Inflammation is the process in which the body, including the blood vessels, responds to injury. Various injurious agents include bacterial or viral infections, free radicals resulting from oxidized lipoproteins, even the chemicals the white blood cells release when fighting infection. Injury to the blood vessel wall kicks off the process of inflammation and plaque formation. Dr. Paul M. Ridker, a cardiologist at Brigham and Women's Hospital in Boston and Harvard Medical School, knew that people who have just suffered a heart attack have a high level of C-Reactive Protein (CRP). Since CRP is a naturally produced substance that sends white blood cells to an injured or infected site, it is a sensitive measure of inflammation. He wondered if CRP could indicate risk in healthy people. Dr. Ridker and his coworkers turned to the Physician's Health Study of more than 22,000 male physicians. The team selected 1,086 of the participants, half of whom had developed a heart condition during the 14-year study. Ridker's group decided to measure the level of CRP, with a high-sensitive test procedure, in the samples initially collected and stored. Because all the middle-aged men were healthy when initial samples were collected, the CRP levels were within normal range. However, those with high-normal CRP values ended up over the next 10 years having three times as many heart attacks and twice as many strokes as those who had lower levels of CRP. This suggested that inflammation is present years in advance of the heart attack. The correlation between CRP and future heart attacks was independent of known risk factors such as smoking, hypertension, obesity or high cholesterol. The study showed the risk of future heart attack among those with high levels of both CRP and cholesterol was greater than the risk of each one. High cholesterol alone could predict a twofold increased risk of heart attack, while high cholesterol and high CRP was associated with a fivefold increased risk. In another study, Dr. Ridker and associates measured the CRP level in blood samples from participants in the Women's Health Study, an ongoing evaluation of 39,876 healthy, post-menopausal American women. Women with the highest levels of CRP had a five-fold increase in the risk of developing cardiovascular disease and a seven-fold increase in risk of having a heart attack or stroke. Levels of CRP also predicted similar events among low-risk women. The researchers suspect the higher levels of CRP in women versus men was because the women studied were more likely to smoke, weigh more and have high blood pressure and high cholesterol. There is also a possible relationship between the inflammatory process and menopause. These data confirm that increased levels of CRP are a strong marker of risk not only in middle-aged men, but also in healthy women, especially since the correlation between CRP and future heart attacks was independent of other risk factors. The two studies indicate that CRP may help identify beforehand those at high risk for future heart disease, as well as those who do not have classical risk factors. If patients knew they were at risk for heart disease, they may change their perception and be more compliant with lifestyle changes to reduce their chance of heart attack. The researchers state the standard laboratory test for CRP is not sufficient to determine cardiac risk. Only high-sensitive or ultrasensitive tests will pick up the small differences noted in the research. The Physicians' Health Study also suggests that certain people may benefit from anti-inflammatory drugs. At the beginning of the study, participants were randomly placed in one to two groups: one group took an aspirin every other day, while the rest took a placebo on the same schedule. Among the men with the initial highest CRP levels, taking the aspirin correlated with a significant reduction in heart attack rate. For men with the lowest CRP, there was not a significant correlation. Those men who had the most inflammation were getting the greatest benefit from the aspirin. Aspirin is a blood-thinning agent, which discourages the formation of blood clots, and this helps prevent heart attacks. The new findings suggest that aspirin may also help prevent heart attacks because of its ability to subdue inflammation. The aspirin data hint at a futuristic approach to the prevention of heart disease by halting the inflammation of blood vessels, perhaps with other drugs more effective than aspirin. References: 1. Paul M. Ridker, MD; Julie E. Buring, ScD; Jessie Shih, PhD; Mathew Matias, BS; Charles H. Hennekens,MD. Prospective study of C-Reactive Protein and the risk of future cardiovascular events among apparently healthy women. Circulation.1998; 98:731-733. 2. Paul M. Ridker,MD; Robert J. Glynn, ScD; Charles H. Hennekens,MD. C-Reactive Protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation.1998; 97:2007-2011. 3. Ridker, P., et al. 1997. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New England Journal of Medicine. 1997; 336:973-979.
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