Atherosclerosis 150 (2000) 441 – 442
Letter to the Editor
www.elsevier.com/locate/atherosclerosis
Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction
I read with interest the study reported by Christensen et al. in the December 1999 issue ofAtherosclerosis[1]. The authors concluded that smoking lowers whole blood folate status and in this way increases homocys-teine concentrations which could be risk factors for first acute myocardial infarction. Interestingly, correlations were observed between the risk of myocardial infarc-tion, total homocysteine levels and alcohol intake. However, alcohol consumption has been reported to have both beneficial and harmful effects on the inci-dence of artery diseases, including myocardial infarc-tion and stroke, and it has been found that heavy alcohol intake is an independent risk factor for all major subtypes of cardiovascular diseases [2,3]. Fur-thermore, elevated homocysteine levels has been found in patients suffering from myocardial infarction [4]. Thus, Dr Christensen’s observations are in agreement with other studies. However, the underlying mecha-nisms leading to the increased risk are still unclear.
Arterial hypertension, cardiac disease and heavy al-cohol use are important risk factors in the development of cardiovascular diseases [3,5], but the significance of alcohol in the pathogenesis of these diseases is less well defined. It has been suggested that an increased homo-cysteine concentration causes abnormal metabolism of Mg2+ in cerebral vascular smooth muscle cells priming
these cells for homocysteine-induced atherogenesis, cerebral vasospasm and stroke [6]. Recently, it has been shown that chronic alcoholism is associated with hyper-homocysteinemia, possibly through its effect on vitamin status [7]. In addition, hyperhomocysteinemia was ob-served in chronic alcoholics who underwent withdrawal from alcohol, whereby the plasma homocysteine con-centration was positively correlated with the blood alcohol concentration [8]. In contrast, a moderate alco-hol consumption seems to be associated with a lower total homocysteine level [3]. Dr Christensen and col-leagues have demonstrated increased plasma homocys-teine concentrations in patients with myocardial infarction and it is well known that chronic alcoholism leads to an elevation of blood pressure. Thus, the association between alcohol and myocardial infarction
or coronary artery disease might be both a blood pressure effect of alcohol and an ethanol-induced hyperhomocysteinemia.
In summary, there is growing evidence that chronic alcoholism is associated with a derangement in this sulfur amino acid metabolism. The balance of evidence from observational studies suggests that elevated levels of homocysteine are associated with an increased risk of carotid artery decease and stroke. I believe that ethanol-induced hyperhomocysteinemia could be a sig-nificant risk factor in coronary artery disease and/or myocardial infarction induction. This would explain the increased incidence of coronary artery disease related to high alcohol consumption, as well as the increased risk of myocardial infarction during alcohol withdrawal. Hyperhomocysteinemia is a treatable condition taking into account that folate therapy will reliably reduce plasma homocysteine levels [3]. Furthermore, the ad-ministration of NMDA receptor antagonists such as flupirtine might be beneficial in these risk patients [9]. Nevertheless, further investigations and controlled stud-ies are wanted to clarify a possible risk assessment between alcohol and homocysteine and the role of therapeutic agents in patients with the risk of the development of different cardiovascular diseases.
References
[1] Christensen B, Landaas S, Stensvold I, Djurovic S, Retterstøl L, Ringstad J, Berg K, Thelle DS. Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction. Atheroscle-rosis 1999;147(2):317 – 26.
[2] Leppala JM, Paunio M, Virtamo J, Fogelholm R, Albanes D, Taylor PR, Heinonen OP. Alcohol consumption and stroke inci-dence in male smokers. Circulation 1999;100:1209 – 14.
[3] Refsum H, Ueland PM, Nyga˚rd O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31 – 62.
[4] Israelsson B, Brattstro¨m LE, Hultberg BL. Homocysteine and myocardial infarction. Atherosclerosis 1988;71:227 – 33.
[5] Sacco RL, Wolf PA, Gorelick PB. Risk factors and their manage-ment for stroke prevention: outlook for and beyond. Neurology 1999;53:S15 – 24.
[6] Li W, Zheng T, Wang J, Altura BT, Altura BM. Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magne-sium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+]
i, atherogenesis and stroke. Neurosci Lett
1999;274:8386.
Letter to the Editor 442
[7] Cravo ML, Glo´ria LM, Selhub J, Nadeau MR, Camilo ME, Resende MP, Cardoso JN, Leitao CN, Mira FC. Hyperhomocys-teinemia in chronic alcoholism: coffelation with folate, vitamin 13-12, and vitamin B-6 status. Am J Clin Nutr 1996;63:220 – 4. [8] Bleich S, Degner D, Porzig J, Poser W, Ru¨ther E, Kornhuber J.
Homocysteine in alcohol withdrawal. Pharmacopsychiatry 1999;32(5):172A.
[9] Kornhuber J, Bleich S, Wiltfang J, Maler M, Parsons CG. Flupirtine shows functional NMDA receptor antagonism by en-hancing Mg2+block via activation of voltage independent
potas-sium channels. J Neural Transm 1999;106(9/10):857 – 67.
Stefan Bleich, Detlef Degner
Department of Psychiatry,
Georg-August-Uni6ersity of Go¨ttingen,
Von-Siebold-Str. 5,
537075 Go¨ttingen,
Germany
E-mail: stefan.bleich@t-online.de
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