Homocysteine and Cardiovascular Disease

Abstract

An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003–2004)

“…39,40 Several studies also showed a significant association between Hcy and BP, [4][5][6][41][42][43][44][45] or HTN; 1,46 however, no association was found in other studies 47,48 (Table 6). Recently, a randomized, placebo-controlled, Hcy-lowering trial reported a decrease in BP in response to treatment.…”

Iron-dependent formation of homocysteine from methionine and other thioethers

“…On the basis of our findings, it may be reasonable to postulate that plasma tHcy concentration is affected by the amount of iron available to react with thioethers, and reflects, in part, body iron stores that are generally positively associated with the amount of free iron. The association between hyperhomocysteinemia and cardiovascular disease stems largely from epidemiological studies (Clarke et al, 1991;Refsum et al, 1998), and it is disappointing to see that the mechanism of the association remains unsolved even after about 15 years of extensive research. In the last several years, skepticism concerning the causal association to hyperhomocysteinemia for cardiovascular disease has surfaced (Brattström and Wilcken, 2000), and there is even dampened enthusiasm that lowering Hcy will decrease the disease risk (Davey Smith and Ebrahim, 2005).…”

“…In humans, homocysteine (Hcy) is derived solely from methionine through the transmethylation pathway and is remethylated to methionine by methionine synthase or is metabolized to cysteine via the transsulfuration pathway (Refsum et al, 1998). A blockage in these pathways leads to elevated plasma total homocysteine (tHcy) concentration (hyperhomocysteinemia).…”

Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study

“…A number of cross-sectional studies have noted higher concentrations of plasma total homocysteine (tHcy) in patients with cardiovascular disease (CVD) as compared with controls, suggesting that elevated plasma tHcy concentration is a risk factor for cardiovascular disease CVD (Boushey et al, 1995;Refsum et al, 1998). This association has been con®rmed in some, but not in all prospective studies (Stampfer et al, 1992;Verhoef et al, 1994;Perry et al, 1995;Arnesen et al, 1995;Folsom et al, 1998;Wald et al, 1998;Alfthan et al, 1994;Evans et al, 1997).…”