There’s “a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point.”
Evidence continues to build that cholesterol levels—including LDL—are not accurate indicators of cardiovascular disease risk and that the medical community as a whole may have gotten “the cholesterol story” quite wrong. For example findings that high LDL-C is inversely associated with mortality in most people over sixty years of age have given researchers “reason to question the validity of the cholesterol hypothesis.” And researchers have noted a “reverse epidemiology” involving traditional markers (such as blood pressure BMI and serum cholesterol) among the elderly wherein elevated cholesterol seems to be protective for health possibly necessitating a reevaluation of traditional treatment guidelines for older patients.
As the quote at the beginning of this piece says cholesterol is a surrogate. Neither high total cholesterol nor high LDL-C in particular is a disease in and of itself. They have long been considered markers for cardiovascular disease or risk of heart attack but this ignores the crucial fact that neither the number of HDL or LDL particles nor the amount of cholesterol carried in them indicates anything about the degree of atherosclerotic plaque accumulated in someone’s major arteries. Measuring the amount of cholesterol in the blood provides no information whatsoever about the accumulation of unstable calcified plaques in coronary arteries. With this in mind the somewhat obsessive focus on lowering cholesterol by any means necessary may have actually worsened the epidemic of heart disease these treatments were intended to stop. (One paper’s authors made a powerful case that “the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs” and proposed “that current statin treatment guidelines be critically reevaluated.”)
Using serum cholesterol measurements as cut-and-dried proof of whether someone is or is not at risk for a cardiovascular event is as misguided as gauging metabolic health and carbohydrate tolerance solely through measurements of blood glucose as opposed to insulin which might be a much stronger predictor of long-term health consequences.
With all this in mind more physicians are taking advantage of the coronary artery calcium scan (CAC). Unlike serum cholesterol measurements which again are surrogates the CAC provides direct observation of arterial calcification that has already occurred. Not atherosclerosis an individual might or might not be at risk for but the actual disease already in progress. Why rely solely on surrogates when a picture of the existent disease can be had?
Data is accumulating that confirms what is already known: serum cholesterol levels often do not correlate with atherosclerosis. Data show that “significant ASCVD [atherosclerotic cardiovascular disease] risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy.” In plain English: half the people who would have been put on statins based on cholesterol measurements were not candidates for these potentially dangerous drugs when their actual coronary artery calcification was measured.
Other studies bear similar findings. According to a study in Korean adults over 50% of individuals for whom statin therapy was recommended had a CAC score of zero. (60% of those for whom statins were “considered” also had a zero CAC score.) Based on actual arterial calcification these individuals were at low risk for cardiovascular events but they might have been treated with statins based on surrogate measurements of LDL.
Of course it should be noted that this works both ways: people at high risk based on traditional markers might have low CAC scores and therefore be at lower risk for a CV event and people at low risk based on traditional markers could have high CAC scores and thus be at greater risk for an event than would have been indicated by their cholesterol levels. Indeed the latter situation was found in a study of coronary artery calcification in low-risk women: “Among women at low ASCVD risk CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors.” Plain English translation of this one: one third of women assessed to be at low risk for atherosclerosis already had measurable arterial calcification.
Bottom line: cholesterol measurements have their place in clinical practice and need not be abandoned entirely but it’s appropriate to call into question their utility as indicators of atherosclerosis or any other cardiovascular disease for that matter. Not all patients will be willing to undergo the CAC scan but it should be presented as an option particularly when the primary pharmaceutical option brings so many potential risks of its own—including worsened cardiovascular health.