Hyperhomocyst(e)inemia, hypertension, coronary artery disease and history of cardiovascular events in the “GENICA” (genetic and environmental factors in coronary atherosclerosis) study

Abstract

Hyperhomocyst(e)inemia (HpHcy) might be an important correctable cardiovascular risk factor; however, its prevalence in patients (pts) with hypertension (HT) and coronary artery disease (CAD) is unknown. In the GENICA study we assessed the plasma levels of homocyst(e)ine (pHcy) and folate in a cross sectional study of 1130 (276 women, 854 men, age 61±13 yrs) pts who underwent coronary angiography for suspected CAD. We defined hypertension according to the WHO-ISH guidelines, CAD as stenosis ≥50% in at least one major epicardial vessel and HpHcy as the pHcy ≥15.46 mmol/L, eg levels exceeding the 90th percentile of values observed in a parallel group of 101 healthy volunteers. We investigated the determinants of HpHcy and folate and the association with history of cardiovascular events (TIA, stroke, angina, MI, PTCA, peripheral vascular disease, vascular surgery and chronic renal failure) by multiple regression and logistic regression analysis, respectively. CAD was diagnosed in 715 (63%) and ruled out in 415 (37%); HT was present in 617 (54.6%) and absent in 508 (45.4%) (NT). The prevalence of HpHcy was similar in HT and NT pts (21.7% vs 19.3%, respectively); no difference was seen in either group when pts were divided according to the extent of CAD. No differences between HT and NT became evident when pHcy values were adjusted for significant covariates (ageing, serum creatinine, serum folate levels and LV ejection fraction). The logistic regression analysis, which took into consideration cardiovascular risk factors, showed that HpHcy was: a) associated with the history of peripheral vascular disease in HT (p=0.011) but not in NT pts; b) strongly associated with history of chronic renal failure in both HT and NT pts (p< 0.0001); c) was not associated with histoy of TIA, stroke, angina and MI either in HT or in NT pts. In consecutive pts referred for coronary angiography the prevalence of HpHcy: 1) did not differ between HT and NT pts; 2) did not show any association with the extent of CAD; 2) was associated with the history of peripheral vascular disease in HT but not in NT pts; 3) it was similarly strongly associated with history of chronic renal failure in both HT and NT pts.