In the 1970s, investigators had developed yet another way to quantify the concentration of these circulating lipoproteins, in this case by counting only the number of apo B proteins that provide the structural foundation to the LDL balloon. Because there’s only one protein per LDL particle, and because VLDL is also composed of identical apo B proteins, this technique measured the number of LDL and VLDL particles in a blood sample, rather than the cholesterol or triglycerides they contained. As it turned out, the number of apo B proteins, and so the total number of LDL and VLDL particles combined, is also abnormally elevated in heart-disease patients. This was first reported in 1980 by Peter Kwiterovich, a lipid-metabolism specialist from Johns Hopkins, together with Allan Sniderman, a cardiologist from McGill University. Kwiterovich and Sniderman then collaborated with Krauss on the last of his three papers on the heterogeneity of LDL. In 1983, they reported that the disproportionate elevation in the apo B protein in heart-disease patients was due to a disproportionate elevation in the amount of the smallest and densest of the low-density lipoproteins.

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.