Atherosclerosis: Making a U Turn

Abstract

The development of potent cholesterol-reducing medications in the last decade of the twentieth century has altered the approach to prevention and treatment of cardiovascular disease (CVD). Initial experience with statins, and more recently with the addition of PCSK9 inhibitors, has proven that human CVD, like that in animal models, can be halted and regressed. Available clinical data show that the lower the achieved level of low-density lipoprotein cholesterol, the greater the regression of disease. Investigative studies are now aimed to understand those factors that both accelerate and impede this healing process. Some of these are likely to be modifiable, and the future of atherosclerotic CVD treatment is likely to be early screening, use of measures to repair atherosclerotic arteries, and prevention of most CVD events.

Keywords: cholesterol; coronary artery disease; myocardial infarction; statin.

Figure 1

Cholesterol effects on atherosclerotic lesion biology. Hypercholesterolemia, found in the circulation of most adults in the western world, leads to lipid collection within the arterial wall (yellow arrow). This promotes or is accompanied by the influx of inflammatory macrophages (indicated in red). But atherosclerosis is reversible (gray arrow). Marked reductions in cholesterol reduce the lipid content of the atherosclerotic plaque. Repair also requires the influx of alternatively activated or reparative macrophages (shown in blue) and an increase in arterial collagen. A more stable lesion results, which in humans translates to a reduction in acute clinical events.