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 vi tamin B-12 status with coronary artery disease (CAD) and left ventricu lar ejection fraction in 367 elderly patients undergoing coronary angi ography. The extent of CAD was scored, left ventricular ejection fract ion was assessed and vitamins B-12 and folate and the metabolites homo cyst(e)ine, methylmalonic acid and 2-methylcitric acid were measured. There was no significant trend in change in homocyst(e)ine as the exte nt of CAD increased. There was an association between vitamin B-12 def iciency, 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 sam ples, selected for vitamin B-12 < 221 pmol/ 1 or high normal vitamin B -12 and folate levels, metabolites including methylmalonic acid reveal ed a specific diagnosis of vitamin B-12 deficiency in 18 patients. The trend among these vitamin B-12-deficient patients and low left ventri cular 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 ejec tion fractions than nonvitamin B-12-deficient patients. Whether low le ft ventricular ejection fraction results in malabsorption of vitamin B -12 and vitamin B-12 deficiency, or conversely, whether vitamin B-12 a nd its marker, elevated homocyst(e)ine, depress left ventricular funct ion warrants further evaluation.