However, the tide began to slowly turn some years ago, as epidemiologic studies bore out what many of us in practice had already observed: a strikingly high number of our patients succumbed to heart disease and other vascular complications. In the earlier days of rheumatology, the debility caused by our illnesses, the necrotic skin, the infected nodules, the scarred lungs, coupled with the frequent use of corticosteroids and the limited repertoire of antibiotics available to combat microorganisms, enabled many infections to become fatal. With better overall medical care, thankfully, deadly infections have become rare and, like the rest of the population, morbidity and mortality related to cardiovascular causes have assumed top billing in the rheumatology clinic.
Cholesterol: A Brief History
From a practical standpoint, it can be challenging for many of us to assume the management of the conditions that contribute to the metabolic syndrome. Yes, we all routinely measure and record blood pressures, but most rheumatology practices are not focused on treating hypertension. For similar reasons, though some of us may keep tabs on a patient’s hemoglobin A1C level, diabetes is a complex disease and its proper management belongs with their endocrinologist or primary care doctor. But getting involved in managing our patients’ hyperlipidemia may be more feasible. First, it is easy to measure and follow a patient’s lipid levels. Second, generic statin drugs are cheap and readily available without the need for prior authorization. Third, we are well versed in managing two of the most common statin-drug-induced side effects, myalgia and elevated liver enzymes.
The association between cholesterol and vascular disease was first established at the turn of the 20th century by the Russian pathologist, Nikolay Anitschkow, MD, who described this link after feeding rabbits a purified cholesterol diet.3 However, his observations were dismissed by critics who were skeptical of the relevance of this model, which relied on an herbivorous creature to serve as a surrogate for carnivorous humans.
When it comes to inflicting havoc on our health, what seems to matter most is whether fat cells are taking up residence in visceral organs, such as the liver, or merely depositing themselves under the skin.
The field lay dormant until the post-World War II era, when the singular efforts of the late John Gofman, MD, professor emeritus of molecular and cell biology at the University of California at Berkeley, transformed our understanding of cholesterol’s critical role.4 A gifted polymath, Dr. Gofman was enlisted in the Manhattan Project, where he isolated 1.2 mg of plutonium, creating the world’s largest existing quantity of this radioactive substance at that time. After the war, he changed careers and focused his attention on cholesterol and its role in cardiovascular disease. Using one of the first analytic ultracentrifuges designed for detailed characterization of proteins and other large biomolecules, he elegantly demonstrated that the key to ultracentrifugal isolation and analysis of cholesterol-bearing lipoproteins was to adjust the density of serum by adding salt and, thereby, float them away from the other, denser sedimenting proteins. This led to the discovery of the three major classes of lipoproteins in human serum: the very low-density (VLDL-C), low-density (LDL-C) and high-density lipoproteins (HDL-C).4
