Mild hyperhomocysteinemia: risk factor or just risk predictor for cardiovascular diseases?
Elevated plasma levels of homocysteine (hyperhomocysteinemia) are increasingly recognized as a potential risk for atherothrombotic vascular diseases by numerous epidemiological and clinical studies. There are increasing experimental data that indicate mechanisms by which homocysteine may alter the vasculature in a way that predisposes to atherosclerotic vascular disease. A key event in the vascular pathobiology of hyperhomocysteinemia seems to involve the induction of endothelial dysfunction due to a reduction of the endogenous antiatherothrombotic molecular nitric oxide. Elevated homocysteine levels can be efficiently and safely reduced in most of hyperhomocysteinemic patients by supplementation of folic acid and cobalamin. This reduction is associated with an improvement in endothelial function and other surrogate markers of atherothrombosis, like carotid plaque area and the rate of abnormal stress electrocardiograms. Whether or not this translates into clinical benefits, is still under investigation. The first clinical study on homocysteine-lowering vitamin supplementation in patients that had undergone coronary intervention showed a benefitial effect on the rate on restenosis and the need for revascularization which translated into a reduction of major coronary events. In contrast, in three larger scaled secondary intervention trials in patients with stable coronary disease or post non-disabling stroke, vitamin supplementation had no effect on future vascular events although baseline homocysteine levels were significantly associated with a worse prognosis. Until the results of more clinical trials are available, the clinical relevant question whether or not homocysteine is just a risk predictor or a modifiable risk factor can not definitely be answered.
Weiss
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Gefässzentrum, Angiologie, Medizinische Poliklinik Innenstadt, Klinikum der Universität München, Germany. Norbert.Weiss@med.uni-muenchen.de
Hilge
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Hoffmann
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U
D001161:Arteriosclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D015984:Causality; D002986:Clinical Trials as Topic; D015897:Comorbidity; D004198:Disease Susceptibility; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index