Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy: part II:the early evidence linking hypercholesterolemia to coronary disease in humans

Abstract

The first in this series of historical reviews dealt with the pioneering animal model work of Anitschkow, implicating blood cholesterol in the pathogenesis of atherosclerosis, and the pivotally important work of Gofman, providing evidence that lipoprotein-bound cholesterol was a major factor in the human disease. This second installment reviews the early lines of evidence linking hypercholesterolemia in humans to the progression of atherosclerosis and the risk of coronary heart disease. The argument is made that by 1970, the evidence was already strong enough to justify intervention to lower blood cholesterol levels if all the available lines of evidence had been taken into account. Yet, it would be almost two decades before lowering blood cholesterol levels became a national public health goal. Some of the reasons the "cholesterol controversy" continued in the face of powerful evidence supporting intervention are discussed. The first in this series of reviews of the history of the "cholesterol controversy" focused on two early developments (1). The first was the groundbreaking studies of Anitschkow and others, showing that inducing hypercholesterolemia in rabbits was sufficient to produce arterial lesions closely resembling those in the human disease. A major, and legitimate, criticism of Anitschkow's work initially was that the rabbit, a strict herbivore, could hardly be considered a suitable model for man, an omnivore. Indeed, dogs and cats, carnivores, did not develop atherosclerosis on cholesterol feeding, as Anitschkow had himself recognized and reported (2). However, this was not because their arteries were somehow immune but simply because, despite the large increase in dietary cholesterol, their blood cholesterol levels did not rise high enough. These species have very effective systems for converting dietary cholesterol to bile acids and excreting it. The demonstration that lesions could also be readily produced in guinea pigs (3, 4), goats (5), hens and parrots (2), and, ultimately, in almost every animal species, including nonhuman primates (6), went a long way toward rebutting this criticism. Nevertheless, the extrapolation from animals to humans, in the absence of supporting evidence, was not and could not be automatically accepted. Evidence in humans was needed.The second focus in the preceding review was on the work of Gofman and coworkers (7), which revealed the complexity of the plasma lipoproteins in humans and also demonstrated, albeit with only relatively small numbers of subjects, good correlations between elevated concentrations of plasma lipoproteins and relative risk of clinical coronary heart disease (CHD). Much larger surveys involving hundreds or thousands of cases would be needed to define the association convincingly.The findings of these two pioneers suggested a causal relationship but fell short of proving the case. In the present review, we describe the several additional lines of evidence that over the ensuing two decades increasingly strengthened the case. By the late ...

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost

“…As early as 1970, many of the country's experts in atherosclerosis and preventive cardiology, and the American Heart Association, were already convinced that there was a causal connection between blood cholesterol and coronary heart disease, as discussed in the earlier installments of this series (1)(2)(3). However, no one could be certain how firm that connection was or how much impact treatment to decrease cholesterol levels would have.…”

Hypocholesterolemic and Growth Promoting Effects of <i>Lactobacillus plantarum</i> AK Isolated from a Nigerian Fermented Cereal Product on Rats Fed High Fat Diet

“…Hypercholesterolemia in humans has been shown to play a major role in atherosclerosis, cardiovascular disease, including coronary heart disease and stroke as well as cerebrovascular diseases [2][3][4]. High cholesterol has also been associated with an increased risk of metabolic syndrome symptoms, including abdominal obesity (large waist circumference), hyperglycemia, hypertriacylglycerolemia and hypertension by as much as 3-fold [5].…”

Setting the Lipid Component of the Diet: A Work in Process

“…The theory that an increased dietary intake of saturated fats and cholesterol results in an increase in serum total cholesterol and LDL cholesterol-and therefore an increase in the risk of heart disease-has been accepted since the Framingham Heart Study (9). The study reported that high serum cholesterol was a major risk factor for coronary artery disease (CAD) (10).…”