Rethinking Primary Prevention of Atherosclerosis-Related Diseases

Abstract

Crucial advances in our understanding of basic pathogenic mechanisms involved in atherogenesis have been achieved during the past 2 decades. The historical hypothesis of pathogenesis (“lipid accumulation”) has evolved to integrate several causal events contributing to the initiation and evolution of atherosclerosis. Vascular inflammation and apoptosis may play a joint pivotal role in its progression and onset. Hypercholesterolemia and hypertension have synergistic deleterious effects on coronary endothelial function.1 Impaired fasting glucose, triglycerides and triglyceride-rich lipoprotein remnants, lipoprotein(a), homocysteine, and high-sensitivity C-reactive protein (hsCRP) might contribute to an increased risk of atherosclerosis.2 The disease also has been related to infiltration of immune cells, which are involved in both systemic and local, innate as well as adaptive, immune responses.3 Distinct pathways of atherothrombosis seem to develop at different sites of the vascular system (brain, heart, and peripheral circulation). Endothelial dysfunction induced by cardiovascular risk factors is considered to be 1 of the earliest stages in vascular damage and is associated independently with cardiovascular events.4 There is a synergic action between genetic, ambient, local, and systemic factors, and ultimately the progression of atherosclerosis is responsible for coronary heart disease (CHD) and its complications (such as unstable “in crescendo” angina, myocardial infarction, and sudden death), peripheral arterial disease, and ischemic stroke. The evolution of atherosclerosis, however, is characterized by a long lag time between onset and clinical manifestation, thereby providing an opportunity for implementation of early detection, prevention, and intervention strategies. Because the development of atherosclerosis commences early in humans, we need to rethink the timing of what is currently considered to be “primary” prevention of atherosclerosis-related diseases. It is likely that we need to start administering effective treatments much earlier than previously assumed. Indeed, much attention would be important when subjects are in a state of wellness before the …