By Michelle S. Cotroneo, Ph.D., Scientific Advisor

Coronary artery disease (CAD) is a narrowing or blockage of the arteries leading to the heart. It is the leading cause of mortality in the United States. This condition can reduce blood flow to the heart, which can lead to angina (pain). Complete blockage of the vessels can lead to death of heart muscle (heart attack).

CAD results from the formation of plaques in the lining of the arterial walls, a condition referred to as atherosclerosis. Plaques are composed of fat, cholesterol, cellular waste products, calcium, platelet clumps, and fibrin. Their accumulation over time leads to narrowing of the blood vessels and potential clot formation.

Factors known to increase risk of CAD include hypertension, diabetes, hypercholesterolemia, hyperlipidemia, smoking, sedentary lifestyle, high blood levels of the amino acid, homocysteine, and obesity. Other lifestyle factors, such as excess alcohol consumption, sleep apnea, and stress can also contribute to the development of CAD. Most of these factors can be managed or changed.

Non-modifiable risk factors are family history and age. The incidence of cardiovascular diseases, including CAD, increases with age. Men develop coronary artery disease at a younger age than women. However, the incidence for CAD in women increases following menopause, eventually becoming equal to that in men. This is thought to be due to the loss of the protective effects of estrogen on the arteries.

Why is age is a risk factor for cardiovascular disease?

Age-related changes in the arteries may play a role in the development of CAD. Arterial walls stiffen and thicken with age, losing their elasticity and ability for expansion to accommodate blood flow, resulting in hypertension. Understanding the cellular mechanisms behind vascular aging is the subject of a vast number of research studies.

Oxidative stress and inflammatory processes occurring in the endothelial cells have been hypothesized to contribute to CAD by promoting atherosclerosis. The formation of reactive oxygen species (ROS), such as peroxide, in aging endothelial cells activates the production of inflammatory cytokines and depletes nitric oxide (NO) levels. Nitric oxide has protective functions, including the prevention of platelet aggregation and control of inflammatory signaling pathways. The increase in inflammatory cytokines, coupled with a reduction in vasculoprotective NO can result in dysfunction or death of the endothelial cells.

Interestingly, comparative biologists have provided insight into the underlying cellular mechanisms of aging by comparing species with a short lifespan with those having longer ones. Existing comparisons support the theory that oxidative stress and production of ROS contribute to aging, and that vasculoprotection are predicted to occur with a reduced and/or delayed onset of production of ROS and increased defense mechanisms (Ungvari Z, et. al, Front Biosci. 2008, 13:5056-70). Ongoing and future biomedical research will continue to shed light on the relationship between vascular aging and coronary artery disease. Clinical research, such as the VALIDATE Study (ClinicalTrials.gov identifier: NCT00246493) will aid in understanding why age is such an important risk factor for the development of coronary artery disease.