Jewish World Review Nov. 15, 2002 / 10 Kislev, 5763

C-Reactive Protein & Cardiovascular Disease Risk

By Robert A. Wascher, M.D., F.A.C.S. | At the present time, the most commonly used "biomarker" for increased cardiovascular disease risk is the blood cholesterol profile. Levels of high-density lipoprotein (HDL, the "good cholesterol") and low-density lipoprotein (LDL, the "bad cholesterol") in the blood have been shown to correlate with overall risk of cardiovascular disease.

High levels of LDL have been linked with an increase in the rate and severity of arterial atherosclerosis (narrowing of the arteries due to build-up of fatty plaques). As I have discussed in previous columns, however, the modern view of heart attack and stroke physiology now encompasses more than just the mere development of arterial plaques. Indeed, there is a great deal of evidence that inflammation of these atherosclerotic plaques, and the subsequent formation of blood clots on the surface of these plaques, are critical events that lead to most strokes and heart attacks secondary to atherosclerosis. A crucial link in this inflammatory process appears to be a substance known as C-reactive protein (CRP). High levels of CRP have been conclusively shown to be associated with a significantly increased risk of cardiovascular disease events, including stroke and heart attack.

A new study in the current issue of the New England Journal of Medicine further advances our understanding of the implications of elevated CRP levels in the blood with respect to the risk of cardiovascular disease events. This is the first study to simultaneously measure both LDL and CRP levels in the blood of a large number of healthy adults, and to follow these study volunteers for a long period of time to look at the incidence of subsequent cardiovascular events.

A total of 27,949 healthy American women without known cardiovascular disease entered the study, at which time LDL and CRP blood levels were measured. The study participants were then followed for an average of eight years. The incidences of heart attack, severe heart ischemia requiring invasive treatment, and stroke secondary to atherosclerosis were then observed. The value of the LDL and CRP tests as predictors of these cardiovascular events was then analyzed.

Following adjustments for the contributing effects of blood pressure, age, smoking status, presence or absence of diabetes, and other cardiovascular disease risk factors, the authors found that elevated levels of both LDL and CRP correlated significantly with the risk of cardiovascular disease events. Moreover, screening for both biomarkers appeared to provide more accurate prognostic information than either test alone.

When used alone, the CRP test also appeared to correlate more closely with already established cardiovascular disease risk factors than did the LDL test by itself. Among the study volunteers, the women with the highest blood levels of CRP had more than twice the risk of experiencing a cardiovascular disease event than did the women with the lowest CRP levels.

The results of this study suggest that cardiovascular disease prevention strategies should target not only LDL and total cholesterol levels in the blood, but also CRP levels. The study's authors concluded that CRP may be a more accurate prognostic factor for the development and progression of cardiovascular disease than the currently used LDL assay.

The combined use of both CRP and LDL tests may also enhance our ability to predict which patients are at greatest risk of experiencing a heart attack or stroke due to atherosclerotic arterial disease. The ability of anti-inflammatory medications such as aspirin, and the statin class of drugs, to reduce CRP levels may explain, at least in part, their well known cardiovascular disease prevention effects. At the present time, however, the evidence that reducing high CRP levels in the blood directly translates into a reduced risk of cardiovascular events is lacking. Such a study would, of course, be a logical next step.


There have been several studies published recently that have touted the "rejuvenating effects" of growth hormone supplements in older adults. Growth hormone (GH) levels rapidly decline following adolescence, and again in middle age. This progressive decline in GH levels is thought to play an important role in the loss of lean muscle mass that begins to develop in middle age.

In men, testosterone levels also play a key role in maintaining lean body muscle mass and, like GH, levels of testosterone in the blood fall significantly during mid-life.

In this week's Journal of the American Medical Association is an interesting study that looks at the effects of human GH on strength and endurance in older men and women.

The study looked at the effects of the sex hormones (SH) progesterone, estradiol and testosterone as well.

A total of 57 healthy men and 74 women, aged 65 to 88 years, participated in the study for a duration of six years. The women received GH and the female SH progesterone and estradiol. The men received GH and testosterone supplements. Some of the patients received GH alone, SH alone, or placebo (sugar pills) only. Lean body mass, fat mass, muscle strength, oxygen consumption during exercise and adverse health effects were evaluated.

Among the women, lean body mass increased significantly while fat mass significantly decreased with GH and SH and, to a slightly lesser extent, with GH alone. Muscle strength did not increase significantly with GH plus SH, or with GH alone, among the women. Oxygen consumption with exercise was also not significantly improved in the women taking GH and SH, or with GH alone. The women also tended to experience an increase in edema (swelling of the arms and legs) with GH, and with GH plus SH.

Among the men, lean body mass increased with GH, and even more dramatically with GH plus SH, while fat mass decreased among the men taking GH, with or without SH. The men's strength, unlike the women's, appeared to be marginally increased by the combination of GH and SH. Carpal tunnel syndrome was more common in the men taking GH. Diabetes and glucose intolerance was also more common among the men receiving GH.

This study suggests that the benefits of growth hormone in elderly patients are moderate in terms of improving lean body mass (i.e., muscle), while the adverse effects of such treatment may be quite significant in this age group. Only marginal improvements in muscle strength and improved oxygen uptake occurred with GH plus SH, and then only in the men.

This study, though encompassing a rather small number of participants, would appear to suggest that the benefits of GH supplementation, with or without SH supplementation, are modest, while the side effects are significant. Thus, based upon this study anyway, it may be premature to recommend such supplements to overcome the loss of lean body mass and endurance that comes with aging. On the brighter side, however, weight training in older adults has been conclusively shown to increase lean body muscle mass while reducing body fat levels. As a side benefit of strength training among the elderly, the risk of diabetes is reduced, along with the incidence of high blood pressure, heart disease and other life-threatening age-related maladies!


While we're on the topic of the manifold benefits of exercise, a new study in the current issue of the journal Circulation takes a look at some of the effects of even short-term dieting and exercise on blood pressure and overall health. The study looked at the relatively short-term health effects of a rigorous diet and exercise program on 11 adult men. The study volunteers were placed on a low-fat high-fiber diet combined with 45-60 minutes per day of aerobic exercise for three weeks. Blood was drawn at the beginning and the end of the study, and tested for cholesterol (HDL and LDL), insulin, and glucose levels. Blood pressure readings were regularly recorded throughout the study as well.

At the end of only three weeks, the study confirmed that the diet and exercise program resulted in a significant decrease in blood pressure, LDL and insulin levels in the men. The level of oxidative metabolic stress (due to the production of cell-damaging free radicals), which has been linked to the development of atherosclerosis, also declined after only three weeks on the program. These beneficial changes were present even among those study volunteers who did not lose any significant weight or fat mass during this brief period of diet modification and exercise. These findings should encourage even those of us who are allergic to exercise and good dietary habits to exercise and watch what we eat. This study confirms that even very short-term modifications in diet and exercise levels can reap very significant health rewards in return!

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.


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© 2002, Dr. Robert A. Wascher