Hyperhomocysteinemia, B-vitamins, and coronary artery disease risk

Homocysteine (Hcy) is a sulfur-containing amino acid, which is produced during the metabolism of methionine. Impairment in one carbon metabolism (OCM) is believed to be responsible for elevated plasma homocysteine (Hcy) levels or hyperhomocysteinemia (HHcy), which is considered as an independent risk factor of coronary artery disease (CAD). There are multifactorial causes of HHcy including the genetic factors, polymorphisms of key OCM enzymes, particularly in case of nutritional deficiencies of certain B-vitamins (folate, riboflavin, vitamin B6 and B12), disease state, smoking and drugs. The association between plasma homocysteine levels and cardiovascular disease risk has spawned attention to develop strategies to lower plasma homocysteine levels that may improve the vascular disease-associated morbidity and mortality. The data derived largely from observational and cross-sectional studies as well as from some clinical trials indicate that elevated levels of circulating homocysteine (>12 μM/L) are cytotoxic and can cause vascular damage, increase the risk for developing atherothrombotic CAD, peripheral vascular disease, myocardial infarction, and stroke. Understanding the cellular mechanisms by which homocysteine promotes the oxidative stress-induced vascular dysfunction, has provided sufficient evidence to conduct clinical trials to lower homocysteine levels with B-vitamins as a novel therapeutic approach to patients with cardiovascular diseases. This chapter reviews the scientific evidence about the potential causes of hyperhomocysteinemia and its link as a risk factor in the pathobiology of CAD and the role of B-vitamin supplementation in the prevention of hyperhomocysteinemia-associated CAD.