Setting the Agenda for Preventive Cardiology.

What Is Preventive Cardiology? To some, it is a general concept encompassing a range of interests so wide to include basic research, population studies, community medicine, and public policy work. To others, it is a philosophy that informs and defines an aspect of a more general clinical practice stance, be it general cardiology, endocrinology, or internal medicine. To us, practitioners of this clinical art, it is a discipline in its own right and worthy of attaining subspecialty status. Atherosclerotic cardiovascular disease (ASCVD) remains the leading killer in the world, and yet we all know it is largely preventable. The notion of dedicating significant resources to ASCVD prevention in the clinical setting, although of intuitive value, poses challenges of political and logistical nature. Yet, these challenges must be overcome as the threat we face is colossal. All of us after a certain age are at measurable risk of heart attack or stroke. This brief perspective will examine the origins of what is currently known as preventive cardiology, review the current status of this discipline in its myriad forms, and provide a call to action for its future if it is to evolve as a defined subspecialty. Scientists from diverse backgrounds have been interested in the link between cholesterol and ASCVD for over a century. In 1913, Nikolai Anitschkow fed pure cholesterol to rabbits and demonstrated the development of hypercholesterolemia and extensive aortic atherosclerosis. The Framingham Heart Study, launched in 1948, established the principle of ASCVD risk factors, contributory agents with no single sufficient cause. It was not until the 1950s that a physicist, John Gofman, described the major classes of plasma lipoproteins using the analytic ultracentrifuge and showed the association of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, direct and inverse respectively, with rates of myocardial infarction. A decade later, Konrad Bloch and Feodor Lynen received the Nobel Prize for unraveling the metabolic pathway of cholesterol synthesis. Ten more years and Akira Endo discovered compactin, the forbearer to the first statin, from a blue-green mold. Shortly thereafter, in 1973, Michael Brown and Joe Goldstein made their seminal discovery of the low-density lipoprotein receptor and its feedback regulation, their work largely inspired by a young child with homozygous familial hypercholesterolemia who had a heart attack. Around this time, sufficient interest mounted to test the impact of cholesterol lowering on rates of cardiovascular disease (CVD). The Lipid Research Clinics—Coronary Primary Prevention Trial with cholestyramine and the Coronary Drug Project with niacin ushered in the era of lipid modulation for prevention of heart disease. Beyond those already mentioned, there are many other important forefathers of preventive cardiology. Remarkably, they emerged from strikingly disparate backgrounds, encompassing basic science, nuclear physics, internal medicine, public health, cardiovascular medicine, clinical research, surgery, endocrinology and metabolism, pediatrics, and medical genetics. So, to which medical specialty does preventive cardiology belong? And why is there an unspoken assumption that a preventive cardiology service is mostly an embellished lipid clinic and therefore an endocrine enterprise at its root? Although the fragmented history of the discipline does not reveal a rightful owner, the first real home for such activities can be traced to the Lipid Clinic. These specialized centers spawned mostly within the realm of endocrine enterprises within academic medical centers and maintained a 2-fold focus, executing research and catering to rare medical curiosities. Though important, their impact on the health of local populations was minimal. The introduction of the statins into the market changed the mom-and-pop poise of most lipid clinics and triggered an adjustment of scale if not of approach. Starting with the landmark publication of the 4S trial in 1994, a seemingly unending litany of prospective randomized controlled trials tested and proved the effectiveness of these drugs in virtually all clinically relevant patient groups. Because of the success of early studies, trial design progressed from placebo-controlled to statin-controlled (high-intensity versus low or moderate-intensity) randomizations. The clinical outcomes from these studies suggested that there was no low-density lipoprotein cholesterol below which patients did not receive further benefit, thus setting the stage for the current standard of statin allocation for all above a certain risk threshold. The results of these trials were stunningly consistent and revolutionized the way clinicians approach dyslipidemia, both in terms of risk assessment and treatment. As the understanding that low-density lipoprotein cholesterol lowering is safe, simple, and effective at Setting the Agenda for Preventive Cardiology