Association Between Plasma Homocysteine Levels and Coronary Artery Disease: A Population-Based Study in Northern Greece

Amalia I. Boufidou; Areti D. Makedou; Dimitrios N. Adamidis; Haralampos I. Karvounis; John T. Gourassas; Haralampos T. Kesidis; Kali G. Makedou; Christodoulos E. Papadopoulos; Georgios E. Parharidis; Georgios E. Louridas


Curr Med Res Opin. 2004;20(2) 

In This Article

Summary and Introduction

Objective: Elevated plasma total homocysteine (tHcy) levels constitute a risk factor for coronary artery disease (CAD). We prospectively examined the association of fasting tHcy levels in patients in Northern Greece who had established CAD.
Patients and Methods: Plasma fasting tHcy levels were measured in 42 patients with angiographically documented CAD and compared to 42 age-, sex-, BMI-and smoking habit-matched control subjects. We also determined the plasma vitamin B12, folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated.
Results: In a univariate analysis, tHcy (mmol/l) levels were higher in patients compared to controls almost reaching statistical significance (13 (7-41) vs 11.3 (4-39); p = 0.07). Multivariate analysis of conventional risk factors showed that tHcy levels were not an independent risk factor for CAD. However, tHcy levels were significantly higher in patients with a previous history of myocardial infarction compared to patients without such a history and to controls (15 (8.8-29) vs 11.7 (7-41); p = 0.007 and 15 (8.8-29) vs 11.3 (4-39); p = 0.002, respectively). Hyperhomocysteinaemia (> 15 µmol/l) was detected in 35.7% of patients and 11.9% of controls (p < 0.05).
Conclusions: In Northern Greece, plasma tHcy levels may not be an independent risk factor for CAD in patients with angiographically documented CAD. However, patients with CAD have a trend towards higher tHcy levels. Additionally, plasma tHcy levels may be associated with the development of myocardial infarction.

Homocysteinuria, an autosomal recessive condition, is usually caused by a deficiency of the enzyme cystathionine β-synthase, which is required for the conversion of homocysteine (tHcy), derived from dietary methionine to cystathionine.[1,2] Homozygotes with homocysteinuria have high levels of circulating tHcy (>100 µmol/l), and may have ocular, skeletal and neurological complications.[1,2] Patients with this condition are at high risk for premature arteriosclerotic vascular disease and venous thrombosis.[1,2] If homocysteinuria remains untreated, about 50% of patients may experience thromboembolic events and mortality could reach 20% before the age of 30 years.[2] Observations in patients with homocysteinuria led to the idea that tHcy may be involved in the pathogenesis of arteriosclerosis. This concept prompted a large number of epidemiological studies that assessed the relation between moderately elevated tHcy levels and coronary or peripheral arterial disease. Observations in approximately 80 clinical and epidemiological studies suggested that elevated tHcy is a risk factor for atherosclerotic vascular disease and for arterial and venous thromboembolism.[3]

A meta-analysis showed that tHcy in increments of 5 µmol/l corresponded to a greater risk of coronary artery disease (CAD) in men and women.[4] In contrast, a more recent meta-analysis concluded that tHcy may not be as harmful for the heart as previously thought.[5]

The aim of the present study was to evaluate the relation between plasma tHcy levels and CAD in a population of Northern Greece with angiographically confirmed CAD.


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