Other Major Risk Factors for Atherosclerosis
In some people with perfectly normal levels of cholesterol and lipoproteins, atherosclerosis still develops. Some of the factors that are known to predispose to ath-erosclerosis are (1) physical inactivity and obesity, (2) diabetes mellitus, (3) hypertension, (4)hyperlipidemia, and (5) cigarette smoking.
Hypertension, for example, increases the risk for atherosclerotic coronary artery disease by at least twofold. Likewise, a person with diabetes mellitus has, on average, more than a twofold increased risk of devel-oping coronary artery disease. When hypertension and diabetes mellitus occur together, the risk for coronary artery disease is increased by more than eightfold. And when hypertension, diabetes mellitus, and hyperlipemia are all present, the risk for atherosclerotic coronary artery disease is increased almost 20-fold, suggesting that these factors interact in a synergistic manner to increase the risk of developing atherosclerosis. In many overweight and obese patients, these three risk factors do occur together, greatly increasing their risk for atherosclerosis, which in turn may lead to heart attack, stroke, and kidney disease.
In early and middle adulthood, men are more likely to develop atherosclerosis than are women of compa-rable age, suggesting that male sex hormones might be atherogenic or, conversely, that female sex hormones might be protective.
Some of these factors cause atherosclerosis by increasing the concentration of low-density lipoproteins in the plasma. Others, such as hypertension, lead to atherosclerosis by causing damage to the vascular en-dothelium and other changes in the vascular tissues that predispose to cholesterol deposition.
To add to the complexity of atherosclerosis, experi-mental studies suggest that excess blood levels of iron can lead to atherosclerosis, perhaps by forming free rad-icals in the blood that damage the vessel walls. About one quarter of all people have a special type of low-density lipoprotein called lipoprotein(a), containing an additional protein, apoprotein(a), that almost doubles the incidence of atherosclerosis. The precise mecha-nisms of these atherogenic effects have yet to be discovered.