Atherosclerosis 147 (1999) 317 – 326 Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction B. Christensen a, *, S. Landaas b , I. Stensvold c , S. Djurovic a,d , L. Retterstøl a,d , J. Ringstad e , K. Berg a,d , D.S. Thelle c a Department of Medical Genetics, Ullea ˚l Uniersity Hospital, N-0407 Oslo, Norway b Department of Clinical Chemistry, Ullea ˚l Uniersity Hospital, N-0407 Oslo, Norway c Department of Epidemiology and Health Sureillance, Ullea ˚l Uniersity Hospital, Oslo, Norway d Institute of Medical Genetics, Uniersity of Oslo, Norway e Østfold Central Hospital, Fredrikstad and Sarpsborg, Norway Received 29 September 1998; received in revised form 6 April 1999; accepted 19 May 1999 Abstract High level of total homocysteine (tHcy) is a risk factor for coronary artery disease (CAD), but the mechanism is not known. The serum concentration of tHcy, total cholesterol, high density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (apo A-I) and the concentration of folate in whole blood were measured in 107 patients with first acute myocardial infarction (MI) and 103 controls. The level of whole blood folate was lower and that of tHcy higher in cases than in controls. An increase of 50 nmol/l whole blood folate was associated with an OR for MI of 0.75, and an increase of 5 mol/l tHcy with an OR for MI of 1.57. Correlations were observed between the levels of whole blood folate and tHcy and between whole blood folate and alcohol intake, and in MI cases, between tHcy, HDL-C, and apo A-I as well as between HDL-C and alcohol intake. The number of cigarette smokers was higher among cases than controls. In smokers, the level of tHcy was higher and that of whole blood folate lower than in non-smokers. After adjustment for smoking, the whole blood folate and tHcy-associated risks of MI became non-significant. We conclude that smoking may affect folate status and tHcy level adversely. The risk of MI in smokers may at least partly be attributed to hyperhomocysteinemia or low folate. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Folate; Homocysteine; Smoking; Myocardial infarction www.elsevier.com/locate/atherosclerosis 1. Introduction High level of total homocysteine (tHcy) (hyperhomo- cysteinemia) is a risk factor for cardiovascular disease (CAD) [1]. The level of extracellular homocysteine is determined by genetic [2] and environmental factors as well as by gene – environment interaction [3]. The intake of the vitamin, folate, is the best known exogenous determinant of the tHcy level [4]. Some recent population studies have demonstrated that cigarette smoking is also significantly associated with hyperhomocysteinemia [5,6]. Because patients with severe hyperhomocysteinemia due to inherited deficiency of several different enzymes in the metabolism of homocysteine and folate all may present with premature cardiovascular disease, homocys- teine itself has long been assumed to be the atherogenic agent. However, recent findings of increased risk of CAD associated with low levels of folate and vitamin B 6 , even after adjustment for tHcy, suggest an independent effect of these vitamins on atherogenesis, tHcy merely function- ing as a marker [7]. The results from some [8,9], but not all [10–12] studies support the idea that there is an association between folate status and risk of CAD. It has been reported that the association between folate status and risk of CAD can be influenced by the intake of alcohol [8]. A number of hypotheses to explain the atherogenic effect associated with hyperhomocysteinemia have been introduced. It has been suggested that tHcy may in- * Corresponding author. Tel.: +47-22-11-9860; fax: +47-22-11- 9868. 0021-9150/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(99)00202-6