METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM AND PREMATURE CORONARY ARTERY DISEASE

Abstract

SESSION TITLE: Cardiovascular Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Its deficiency leads to increased homocysteine levels. Elevated serum levels of homocysteine have been associated with premature coronary artery disease (CAD). we present a case of recurrent acute coronary syndrome in patient with heterozygote mutation for methylenetetrahydrofolate reductase (MTHFR) with normal homocysteine level. CASE PRESENTATION: A 23 year-old man with history of MTHFR polymorphism and anterior wall ST segment elevation myocardial infarction requiring drug eluting stent (DES) in the left anterior descending artery (LAD) presented to the emergency department with substernal chest pain, T wave inversions in inferior leads on his ECG and elevated troponin levels. Coronary angiography demonstrated an acute occlusion of the proximal right coronary artery (RCA) and a chronic total occlusion of the proximal LAD with collaterals from the circumflex territory. Aspiration thrombectomy of the RCA lesion was partially successful and required continuous infusion of unfractionated heparin and tirofiban for 48 hours in addition to aspirin and ticagrelor. He underwent a successful deployment of 3 DES to his RCA. His left ventriculogram showed a mildly reduced left ventricular ejection fraction of 45 % with hypokinesis of the basal inferior wall segment. DISCUSSION: Hypercoagulability workup was unrevealing. Homocysteine levels were normal at the time of his first myocardial infarction two years prior. Repeat homocysteine level was 11.7 mg/dl (n <11.2mg/dl). His total cholesterol was 153mg/dl, LDL 80mg/dl, Apo lipoprotein B was 67 (n 52-109mg/dl), Lp(a) <10(n <75nmol/L). He was then discharge on folic acid. He was brought back to the cardiac catheterization laboratory a month later to reassess the LAD lesion but the angiogram showed complete re-occlusion of RCA. The patient was referred for coronary artery bypass surgery. CONCLUSIONS: This case demonstrates the association of MTHFR polymorphism with premature CAD and myocardial infarction despite normal homocysteine levels. Screening for MTHFR polymorphisms in addition to homocysteine levels should be considered for patients presenting with premature CAD and a normal lipid profile. Aggressive risk reduction with lifestyle modification, guideline-driven medical therapy and folic acid might be necessary for secondary cardiovascular disease prevention until more specific therapeutic options are available for this subgroup of patients. Reference #1: Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vasculardisease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet.1995; 10: 111–113 Reference #3: DISCLOSURES: No relevant relationships by Corina Iorgoveanu, source=Web Response No relevant relationships by Ahmed Zaghloul, source=Web Response