Good Calories, Bad Calories

This explained what Krauss had set out to understand: why two people can have identical LDL-cholesterol levels and yet one develops atherosclerosis and coronary heart disease and the other doesn’t—why LDL cholesterol is only a marginal risk factor for heart disease. If we have low LDL cholesterol, but it’s packaged almost exclusively in small, dense LDL particles—the smaller balloons—that translates to a higher risk of heart disease. If we have high LDL cholesterol, but it’s packaged in a smaller number of large, fluffy LDL particles—the larger balloons—then our heart-disease risk is significantly lower. Small, dense LDL, simply because it is small and dense, appears to be more atherogenic, more likely to cause atherosclerosis. Small, dense LDL can squeeze more easily through damaged areas of the artery wall to form incipient atherosclerotic plaques. Sniderman describes small, dense LDL as the equivalent of “little bits of sand” that get in everywhere and stick more avidly. The relative dearth of cholesterol in these particles may also cause structural changes in the protein that make it easier for it to adhere to the artery wall to begin with. And because small, dense LDL apparently remains in the bloodstream longer than larger and fluffier LDL, it has more time and greater opportunities to do its damage. Finally, it’s possible that LDL has to be oxidized—the biological equivalent, literally, of rusting—before it can play a role in atherosclerosis, and the existing evidence suggests that small, dense LDL oxidizes more easily than the larger, fluffier variety.

Through the 1980s, Krauss continued to refine this understanding of how LDL subspecies affect heart disease. He discovered that the appearance of LDL in the population falls into two distinct patterns or traits, which he called pattern A and pattern B. Pattern A is dominated by large, fluffy LDL and implies a low risk of heart disease; pattern B is the dangerous one, with predominantly small, dense LDL. Pattern B is invariably accompanied by high triglycerides and low HDL. Pattern A is not. In 1988, Krauss and his collaborators reported in JAMA that heart-disease patients were three times more likely to have pattern B than pattern A. Krauss called pattern B the atherogenic profile. Diabetics have the identical pattern.

The effect of diet on this atherogenic profile now became the pivotal issue. In the 1960s and most of the 1970s, the dietary goal was to lower total cholesterol. After the 1977 revelations about HDL, the best diet became the one that lowered LDL cholesterol and maybe raised HDL in the process. But if Krauss and his collaborators were right, a diet that lowers total cholesterol or LDL cholesterol can conceivably do so in a way that actually increases the proportion of small, dense LDL in the blood turning the healthy pattern A trait into the atherogenic pattern B. If we focus on LDL cholesterol alone, such a diet might appear to prevent heart disease. But if the size, density, and number of the LDL subspecies are indeed the important variables, the diet could in fact increase heart-disease risk.

Though pattern A and B traits appear to be strongly influenced by genetics, diet and other lifestyle factors play a critical role. In the late 1980s, Krauss began a series of clinical trials to explore the association between diet and the dangerous small, dense LDL. The results of his seven trials have been consistent: the lower the fat in the diet and the higher the carbohydrates, the smaller and denser the LDL and the more likely the atherogenic pattern B appears; that is, the more carbohydrates and the less fat, the greater the risk of heart disease.

On a diet that Krauss calls the “average American diet,” with 35 percent of the calories from fat, one in three men will have the atherogenic pattern B profile. On a diet of 46 percent fat, this proportion drops: only one man in every five manifests the atherogenic profile. On a diet of only 10 percent fat, of the kind advocated by diet doctors Nathan Pritikin and Dean Ornish, two out of every three men will have small, dense LDL and, as a result, a predicted threefold higher risk of heart disease. The same pattern holds true in women and in children, but the percentages with small, dense LDL are lower. Krauss and his colleagues even tested the effect of types of fat on these lipoproteins, and reported that, the more saturated fat in the diet, the larger and fluffier the LDL—a beneficial effect.^*50