Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study

Coronary artery disease (CAD) still represents the major cause of mortality in developed countries. Large research programs have been focused on the identification of new risk factors to prevent CAD, with special attention to homocysteine (Hcy), due to the known associated increased thrombogenicity, oxidative stress status and endothelial dysfunction. However, controversy still exists on the association between Hcy and CAD. Therefore, aim of the current study was to investigate the association of Hcy with the prevalence and extent of CAD in a large consecutive cohort of patients undergoing coronary angiography.

Our population is represented by a total of 3056 consecutive patients undergoing coronary angiography between at the Azienda Ospedaliera "Maggiore della Carità", Novara, Italy. Fasting samples were collected for homocysteine levels assessment. Coronary disease was defined for at least 1 vessel stenosis>50% as evaluated by QCA.

Study population was divided according to Hcy tertiles (<13,3, 13,3-18.2, >18.2nmol/ml). High plasmatic level of homocysteine was related with age (p<0.001), male gender (p<0.001), hypertension (p<0.001) renal failure (p<0.001), family history of CAD (p<0.001), previous cerebrovascular accident (p<0.001), previous MI (p=0.002), previous CABG (p=0.003), ejection fraction (p<0.001), higher baseline creatinine (p<0.001), in treatment with nitrates (p<0.001), calcium antagonists (p<0.001), diuretics (p<0.001), Ace inhibitors (ACE-I) (p=0.006), Clopidogrel (p=0.05), haemoglobin (p=0.001), white blood cells (WBC) count (p=0.008), total cholesterol (p=0.04), Low-Density Lipoproteins (LDL) (p=0.01). A significant relationship was found between Hcy levels and the extent of coronary artery disease (71.8% vs 77.8% vs 77.4%, OR[95%CI]=1.18[1.11-1.252.], p<0.001 and severe CAD (23.6% vs 29.5% vs 32.1%, OR [95%CI]=1.275 [1.209-1.344], p<0.001). Elevated Hcy was significantly associated with increased risk of CAD (adjusted OR[95%CI]=1.087[1.009-1.171], p=0.02 and severe CAD (adjusted OR [95%CI]=1.07 [1.01-1.16, P=0.04]). The results were confirmed in the majority of high risk subsets of patients.

This study showed that high levels of plasmatic Hcy are independently associated with CAD. Further large studies are certainly needed to explore the adjunctive benefits from vitamin administration in patients with elevated Hcy to prevent the occurrence and progression of CAD.