Per Magne Ueland

Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease

BACKGROUND Elevated plasma homocysteine levels are a risk factor for coronary heart disease, but the prognostic value of homocysteine levels in patients with established coronary artery disease has not been defined. METHODS We prospectively investigated the relation between plasma total homocysteine levels and mortality among 587 patients with angiographically confirmed coronary artery disease. At the time of angiography in 1991 or 1992, risk factors for coronary disease, including homocysteine levels, were evaluated. The majority of the patients subsequently underwent coronary-artery bypass grafting (318 patients) or percutaneous transluminal coronary angioplasty (120 patients); the remaining 149 were treated medically. RESULTS After a median follow-up of 4.6 years, 64 patients (10.9 percent) had died. We found a strong, graded relation between plasma homocysteine levels and overall mortality. After four years, 3.8 percent of patients with homocysteine levels below 9 micromol per liter had died, as compared with 24.7 percent of those with homocysteine levels of 15 micromol per liter or higher. Homocysteine levels were only weakly related to the extent of coronary artery disease but were strongly related to the history with respect to myocardial infarction, the left ventricular ejection fraction, and the serum creatinine level. The relation of homocysteine levels to mortality remained strong after adjustment for these and other potential confounders. In an analysis in which the patients with homocysteine levels below 9 micromol per liter were used as the reference group, the mortality ratios were 1.9 for patients with homocysteine levels of 9.0 to 14.9 micromol per liter, 2.8 for those with levels of 15.0 to 19.9 micromol per liter, and 4.5 for those with levels of 20.0 micromol per liter or higher (P for trend=0.02). When death due to cardiovascular disease (which occurred in 50 patients) was used as the end point in the analysis, the relation between homocysteine levels and mortality was slightly strengthened. CONCLUSIONS Plasma total homocysteine levels are a strong predictor of mortality in patients with angiographically confirmed coronary artery disease.

Homocysteine metabolism : from basic science to clinical medicine

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The Hordaland Homocysteine Study: Lifestyle and Total Plasma Homocysteine in Western Norway

The Hordaland Homocysteine Study is a cohort of approximately 18,000 men and women, ages 40–67, who had their total plasma homocysteine (tHcy) determined in 1992 or 1993. The long-term aim of the study is to relate plasma tHcy to future cardiovascular disease incidence, cause-specific, and all-cause mortality. In Norway, complete mortality follow-up is assured for all individuals who do not leave the country permanently, and the study will have access to mortality data kept at the Central Bureau of Statistics. Furthermore, we plan to register all hospitalizations for cardiovascular disease, including coronary angiographies, coronary surgery, and balloon angioplasties in the six hospitals that serve Hordaland. Complete cancer incidence data for the cohort members will also be available through the Cancer Registry of Norway, which keeps records of all cancer cases diagnosed in the country. No follow-up data are available yet, and so far we have focused on the study of cross-sectional associations between plasma tHcy and established cardiovascular risk factors and lifestyle.

On the Formation and Fate of Total Plasma Homocysteine

The total concentration of homocysteine (tHcy)* in plasma is a useful marker of impaired function of cobalamin and folate. Moreover, it is an independent risk factor for atherosclerotic disease [1]. These findings have encouraged the search for determinants of plasma tHcy level [1, 2].

Homocysteine and Drug Therapy

Several agents other than vitamins involved in homocysteine (Hcy) metabolism affect plasma homocysteine (tHcy) total concentration. The mechanisms behind the hyperhomocysteinemia vary from altered homocysteine production, impaired homocysteine metabolism, and possibly by direct reaction (through thiol-disulphide exchange) with extracellular Hcy. Some drugs change plasma Hcy by mechanisms not known. This review summarizes effects of drug therapy on plasma tHcy, with emphasis on data obtained during the last five years.

Homocysteine and Vascular Disease: The European Concerted Action Project

Aterosclerotic cardiovascular disease, notably coronary heart disease, remains the major cause of death in developed countries [1]. A high-fat diet, hypertension, and smoking are regarded as causal factors [2], and changes in these factors appear to contribute to coronary heart disease mortality trends [3]. Nevertheless, these factors remain incomplete predictors of both the occurrence of and changes in cardiovascular mortality.