Homocysteine Metabolism and Risk of Myocardial Infarction: Relation with Vitamins B6, B12, and Folate

Abstract

Elevated plasma homocyst(e)ine levels are an independent risk factor for vascular disease. In a case-control study, the authors studied the associations of fasting plasma homocyst(e)ine and vitamins, which are important cofactors in homocysteine metabolism, with the risk of myocardial infarction. The cases were 130 Boston area patients hospitalized with a first myocardial infarction and 118 population controls, less than 76 years of age, enrolled in 1982 and 1983. Dietary intakes of vitamins B6, B12, and folate were estimated from a food frequency questionnaire. After adjusting for sex and age, the authors found that the geometric mean plasma homocyst(e)ine level was 11% higher in cases compared with controls (p = 0.006). There was no clear excess of cases with extremely elevated levels. The age- and sex-adjusted odds ratio for each 3-mumol/liter (approximately 1 standard deviation) increase in plasma homocyst(e)ine was 1.35 (95% confidence interval 1.05-1.75; p trend = 0/007). After further control for several risk factors, the odds ratio was not affected, but the confidence interval was wider and the p value for trend was less significant. Dietary and plasma levels of vitamin B6 and folate were lower in cases than in controls, and these vitamins were inversely associated with the risk of myocardial infarction, independently of other potential risk factors. Vitamin B12 showed no clear association with myocardial infarction, although methylmalonic acid levels were significantly higher in cases. Comparing the mean levels of several homocysteine metabolites among cases and controls, the authors found that impairment of remethylation of homocyst(e)ine (dependent of folate and vitamin B12 rather than on vitamin B6-dependent transsulfuration) was the predominant cause of high homocyst(e)ine levels in cases. Accordingly, plasma folate and, to a lesser extent, plasma vitamin B12, but not vitamin B6, correlated inversely with plasma homocyst(e)ine, even for concentrations at the high end of normal values. These data provide further evidence that plasma homocyst(e)ine is an independent risk factor for myocardial infarction. In this population, folate was the most important determinant of plasma homocyst(e)ine, even in subjects with apparently adequate nutritional status of this vitamin.

Holotranscobalamin and methylmalonic acid as prognostic markers following an acute myocardial infarction

“…This event rate is not different from the event rates observed for quartiles of holoTC or MMA analysed separately. The present results are in accordance with previous studies evaluating the association between total vitamin B 12 in plasma and risk CVD (Verhoef et al, 1996;Folsom et al, 1998;Robinson et al, 1998;Moleerergpoom et al, 2004).…”

“…For MMA, significantly higher concentrations in MI patients as compared with healthy controls have been demonstrated in a case-control study (Verhoef et al, 1996). Higher concentrations have also been found in renal transplant patients, especially those with a history of cardiovascular complications in the post-transplantation period (Franke et al, 2003).…”

“…So far, most studies performed have mainly focused on folate and vitamin B 6 (Graham and O'Challaghan, 2002), and even though not completely consistent (Folsom et al, 1998;Moleerergpoom et al, 2004), an inverse Hcy-independent relation between these vitamins and atherosclerotic vascular disease has been demonstrated (Verhoef et al, 1996;Folsom et al, 1998;Robinson et al, 1998;Verhaar et al, 2002).…”

“…Most other clinical studies have not been able to demonstrate an inverse relation between vitamin B 12 deficiency and cardiovascular disease (CVD) (Verhoef et al, 1996;Folsom et al, 1998;Robinson et al, 1998;Moleerergpoom et al, 2004). This might be related to the fact that cobalamin deficiency often is under-diagnosed when measuring total amount of plasma vitamin.…”

Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage

“…The risk increases progressively with increased homocysteine levels (Boushey et al, 1995;Boston et al, 1997). Hyperhomocysteinaemia can result from genetic and dietary factors which influence the transsulphuration or remethylation pathways of homocysteine metabolism (Mudd et al, 1995;Verhoef et al, 1996). Of these, the most important to the general population are homozygosity for a relatively common mutation of 5,10-methylene tetrahydrofolate reductase (C677T MTHFR; Todesco et al, 1999), and inadequate intake of folate.…”