Beyond Bad Cholesterol
ALTHOUGH LDL frequently sparks the sequence of events I have outlined, scientists have identified several other factors that unequivocally increase a person’s risk for atherosclerosis or its complications. Many of these risk factors, and a few still under study, exhibit intriguing inflammatory properties. Before I describe some of those features, I must first point out that LDL probably plays an even larger role in initiating and perpetuating atherosclerosis than is generally recognized.
A much repeated statistic says that half of all patients who have angina or have had a heart attack do not have above-average LDL levels—a finding frequently interpreted to mean that in such individuals, LDL exerts no influence on the atherosclerosis at the root of those disorders. But typical LDL levels in Western society exceed by far the body’s needs and can actually promote arterial disease.
Indeed, in response to new data correlating heart health with lipoprotein levels, public health experts have progressively refined the definition of “healthy” LDL levels. Guidelines released last year by an expert panel convened in cooperation with the National Institutes of Health now explicitly label LDL-cholesterol levels below 100 milligrams per deciliter of blood (mg/dL) as optimal. They also suggest considering drug treatment earlier than before—at 130 mg/dL instead of 160—for certain people with multiple risk factors. For adults with a relatively low risk of heart disease, the guidelines recommend (as before) initiating “lifestyle changes”—diet and exercise— at 160 mg/dL and considering drug treatment at 190 mg/dL.
Investigators have yet to explore the connections between other risk factors and inflammation with the intensity accorded to LDL, but they have uncovered suggestive links. Diabetes, for instance, elevates glucose levels in the blood; this sugar can enhance the glycation, and thus the inflammatory properties, of LDL. Smoking causes oxidants to form and might hasten the oxidation of LDL’s constituents, thereby fostering arterial inflammation even in individuals with average LDL levels. Obesity contributes to diabetes and vascular inflammation. High blood pressure may not exert direct inflammatory effects, but a hormone partly responsible for much human hypertension—angiotensin II—appears to incite inflammation as well; elevated levels of this hormone, then, might give rise to hypertension and atherosclerosis simultaneously.
Conversely, high-density lipoprotein (HDL) seems beneficial; as levels of this “good cholesterol” decline, the likelihood of suffering a heart attack goes up. Accordingly, to fine-tune estimates of cardiovascular risk, many physicians today measure not only levels of LDL in the blood but also the level of HDL and the ratio of LDL (or LDL plus its various relatives) to HDL. HDL may achieve its beneficial effects in part by reducing inflammation: along with cholesterol, it can transport antioxidant enzymes able to break down oxidized lipids.
Given inflammation’s usual responsibility in the body—blocking and eliminating infectious agents—biologists have naturally looked at whether arterial infections might contribute to inflammation in the arteries. Recent work suggests that atherosclerosis can develop in the absence of infection. Nevertheless, circumstantial evidence suggests that certain microorganisms, such as herpesviruses or the bacterium Chlamydia pneumonia (a frequent cause of respiratory infections), could well induce or aggravate atherosclerosis at times. C. pneumonia, for instance, appears in many atherosclerotic plaques, and its constituents can evoke inflammatory responses by macrophages and by vascular endothelial and smooth muscle cells.