Relationship among homocyst(e)ine, vitamin B-12 and cardiac disease in the elderly: Association between vitamin B-12 deficiency and decreased left ventricular ejection fraction

We evaluated the association of moderate hyperhomocyst(e)inemia and vitamin B-12 status with coronary artery disease (CAD) and left ventricular ejection fraction in 367 elderly patients undergoing coronary angiography. The extent of CAD was scored, left ventricular ejection fraction was assessed and vitamins B-12 and folate and the metabolites homocyst(e)ine, methylmalonic acid and 2-methylcitric acid were measured. There was no significant trend in change in homocyst(e)ine as the extent of CAD increased. There was an association between vitamin B-12 deficiency, i.e., vitamin B-12 < 221 pmol/l and homocyst(e)ine > 16 nmol/ mi and low left ventricular ejection fraction (P = 0.014). Of 105 samples, selected for vitamin B-12 < 221 pmol/ 1 or high normal vitamin B-12 and folate levels, metabolites including methylmalonic acid revealed a specific diagnosis of vitamin B-12 deficiency in 18 patients. The trend among these vitamin B-12-deficient patients and low left ventricular ejection fraction was significant (P = 0.028). In vitro studies on rat heart revealed that nitrous oxide in the presence of 200 mu M/1 methionine reduced contractility of the heart. In conclusion, vitamin B-12-deficient patients had significantly lower left ventricular ejection fractions than nonvitamin B-12-deficient patients. Whether low left ventricular ejection fraction results in malabsorption of vitamin B-12 and vitamin B-12 deficiency, or conversely, whether vitamin B-12 and its marker, elevated homocyst(e)ine, depress left ventricular function warrants further evaluation.