Introduction

Atherosclerosis kills more people in the United States than any other disease. In fact, one third of all people die from atherosclerosis and/or its complications, a rather startling statistic.

Atherosclerosis is the narrowing of the arteries as a result of the formation of plaques on the inner walls of arteries. The plaques are made of lipoproteins (a kind of fat), decaying muscle tissue, fibrous tissue, clumps of blood cells and, of course, cholesterol. More and more of these plaques accumulate as we age, eventually causing partial blockage of the blood circulation. Unfortunately, the plaques tend to form in areas that require a good blood flow, such as the arteries feeding the heart muscle. By blocking or slowing down blood flow, atherosclerosis causes heart attacks. And sometimes the plaques break off and block smaller arteries such as those in the brain, causing a stroke and other problems. Between the ages of 35 and 44, men are six times more likely to get atherosclerosis than women.

Since atherosclerosis is painless until something serious happens, it is difficult for physicians to detect. Magnetic resonance imaging (MRI) and electron beam computed tomography (a special x-ray technique using CT that shows slices of organs) are used to help diagnose atherosclerosis, but these methods are too expensive for routine diagnostic screening. Physicians are constantly looking for ways to screen people for atherosclerosis that are effective and cheap. Measuring the blood cholesterol level (including the "good' and "bad" cholesterols) has served fairly well, but other, newer, tests are tried out from time to time. Medical scientists carried out this study to find a way to improve detection of the risk of one form of atherosclerosis - peripheral arterial disease (PAD), that chiefly affects the leg arteries - early-on before it is too late.

Method

The investigators collected blood samples almost 15,000 healthy American male doctors aged forty to eighty-four. They monitored this group carefully for nine years and found that 140 of them had developed PAD. The saved blood samples of these 140 doctors were thawed and analyzed, as were samples from 140 randomly selected healthy doctors who formed a control or comparison group. This way they hoped to find which tests were indicative of a risk for developing PAD. They measured:

• Total cholesterol (TC)
• High density lipoprotein cholesterol (HDL-C, the 'good' cholesterol)
• Low density lipoprotein cholesterol (LDL-C, the 'bad' cholesterol)
• Triglyceride
• Homocysteine
• C-reactive protein (CRP)
• Fibrinogen
• Lipoprotein (a)
• Apolipoprotein A-1
• Apolipoprotein B-100

The first 4 tests were classical blood lipid tests, the next 3 were newer tests meant to show the presence of inflammatory activity in the body, and the last 3 were more sophisticated lipid tests. To improve the accuracy of their results, they adjusted their analysis for such other factors as age, smoking, high blood pressure, obesity, family history of disease, diabetes, and exercise frequency.

Results

The scientists found that those people who developed PAD had significantly high levels of TC, CRP and fibrinogen, with increased ratios of TC to HDL-C. Both high levels of CRP and the total cholesterol/HDL-C ratio proved to be the strongest predictors of future PAD. Fibrinogen levels also had a significant predictive value, but were not better than CRPs. Since their study used doctors as their subjects, they felt that the chances of unreported PAD were very slight, thus reinforcing the accuracy of their results.

Combining the total cholesterol result with the CRP result provided the highest level of prediction of subsequent PAD.

The abnormally elevated numbers for these risk factors in the physicians who developed PAD 9 years later were as follows:

• Total cholesterol: 202-254 mg/dL (5.2-6.6 mmol/L), average 221 mg/dL (5.7 mmol/L).
• Fibrinogen: 0.30-0.40 g/dL (8.8-11.8 micromol/L), average 0.34 g/dL (10 micromol/L).
• CRP: 0.07-0.33 mg/dl, average 0.14
• TC/HDL-C ratio: 4.27-6.53, average 5.39

Conclusion

With this study the medical scientists found a relatively inexpensive but efficient way to determine who might be at risk for PAD, which is a clear indicator of atherosclerosis elsewhere in the body. The tests can be used in routine medical examinations and, possibly, to screen the general population. Combining one of the newer tests for inflammatory changes in the body with the more classical lipid (cholesterol) tests gives the best prediction.

In those people who have a positive reading from such tests (i.e. those who are at risk of developing progression of atherosclerosis), changes in lifestyle - improved diet, more exercise, no smoking, etc - can arrest, or even in some cases reverse the harmful changes in the arteries. There is more information on this in other articles on this site.