These findings led directly to the notion that low-density lipoproteins carry “bad” cholesterol and high-density lipoproteins carry “good” cholesterol. And then the precise terminology was jettisoned in favor of the common shorthand. The lipoproteins LDL and HDL became “good cholesterol” and “bad cholesterol,” and the lipoprotein transport vehicle was now conflated with its cholesterol cargo. Lost in translation was the evidence that the causal agent in heart disease might be abnormalities in the lipoproteins themselves.

Image Credit... Noah Woods

The truth is, we’ve always had reason to question the idea that cholesterol is an agent of disease. Indeed, what the Framingham researchers meant in 1977 when they described LDL cholesterol as a “marginal risk factor” is that a large proportion of people who suffer heart attacks have relatively low LDL cholesterol.

So how did we come to believe strongly that LDL cholesterol is so bad for us? It was partly due to the observation that eating saturated fat raises LDL cholesterol, and we’ve assumed that saturated fat is bad for us. This logic is circular, though: saturated fat is bad because it raises LDL cholesterol, and LDL cholesterol is bad because it is the thing that saturated fat raises. In clinical trials, researchers have been unable to generate compelling evidence that saturated fat in the diet causes heart disease.

The other important piece of evidence for the cholesterol hypothesis is that statin drugs like Zocor and Lipitor lower LDL cholesterol and also prevent heart attacks. The higher the potency of statins, the greater the cholesterol lowering and the fewer the heart attacks. This is perceived as implying cause and effect: statins reduce LDL cholesterol and prevent heart disease, so reducing LDL cholesterol prevents heart disease. This belief is held with such conviction that the Food and Drug Administration now approves drugs to prevent heart disease, as it did with Zetia, solely on the evidence that they lower LDL cholesterol.

But the logic is specious because most drugs have multiple actions. It’s like insisting that aspirin prevents heart disease by getting rid of headaches.

One obvious way to test the LDL cholesterol hypothesis is to find therapies that lower it by different means and see if they, too, prevent heart attacks. This is essentially what the Vytorin trial did and why its results argue against the hypothesis.

Other such tests have likewise failed to confirm it. A recent trial of torcetrapib, a drug that both raises HDL and lowers LDL cholesterol, was halted midstream because the drug seemed to cause heart attacks and strokes rather than prevent them. Estrogen replacement therapy also lowers LDL cholesterol, but it too has failed to prevent heart disease in clinical trials. The same goes for eating less saturated fat.