Homocysteine

1: Thromb Res 2001 Sep 30;103 Suppl 1:S35-9

Homocysteine plasma levels in young patients with coronary artery disease. relation to history of acute myocardial infarction and anatomical extent of disease.

Nikfardjam M, Graf S, Hornykewycz S, Zorn G, Huber-Beckmann R, Wojta J, Huber K.

Department of Cardiology, University of Vienna, Wahringer Gurtel 18-20 1090, Vienna, Austria

Although there is considerable epidemiologic evidence for a relationship between plasma homocysteine (Hcy) levels and cardiovascular disease, not all prospective studies have shown such a relationship. Furthermore, data concerning the role of hyperhomocysteinemia in patients with premature coronary artery disease (CAD) are rare. It was the aim of the study to investigate a possible association between Hcy plasma levels in young patients with the extent of CAD and the history of myocardial infarction (MI). A cohort of 94 patients was examined for conventional risk factors and the history of previous transmural MI. Furthermore, coronary angiography was performed to assess the anatomical extent of vessel disease. Plasma Hcy levels were measured by use of a commercial enzyme-linked immunosorbent assay. Only a history of previous MI was significantly associated with hyperhomocysteinemia. There was no relationship between elevated Hcy levels and the anatomical extent of vessel disease in patients with premature CAD. Our data may indicate that hyperhomocysteinemia represents an independent risk factor for acute coronary thrombosis rather than for the development of coronary sclerosis. Thereby, hyperhomocysteinemia may influence the clinical situation after plaque rupture not only by prothrombotic action but also by favouring endothelial dysfunction and vasospasm.

PMID: 11567667 [PubMed - in process]

1: Angiology 2001 Oct;52(10):681-7

Biochemical risk factors for cardiovascular disease in an aged male population: emerging vascular pathogens.

Lippi G, Arosio E, Prior M, Guidi G.

Istituto di Chimica e Microscopia Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Universita degli Studi di Verona, Italy.

The progressive increase of deaths and morbidity from cardiovascular disease (CVD) in most developed societies has led to the formulation of preventive strategies and application of several diagnostic guidelines. However, there is emerging evidence that most panels and algorithms are inadequate and require urgent revision and updating. Therefore, the aim of this study was the evaluation of a wide cardiovascular risk profile in elderly male patients with acute myocardial infarction (AMI) or peripheral occlusive disease (POD). The risk profile was assessed by measuring conventional serum lipid and lipoprotein levels and emerging parameters: lipoprotein(a) (Lp[a]), homocysteine (Hcy), and C-reactive protein (CRP). The concentration of triglycerides, Lp(a), Hcy and the total cholesterol/high-density lipoprotein (TC/HDL) ratio were significantly higher in both classes of patients than in a population of matched healthy controls and, similarly, patients with CVD displayed lower plasma values of HDL. No significant differences were observed for TC, low-density lipoprotein (LDL), and CRP. Patients with POD exhibited a marked atherogenic profile, as attested by substantially increased values of Hcy, Lp(a), triglycerides, and TC/HDL ratio. The frequency distributions of Lp(a) and Hcy concentrations were markedly shifted toward upper values in both classes of patients than in controls. In multivariate regression analysis, Lp(a) and Hcy were the best predictors for AMI, whereas Lp(a), Hcy, and the TC/HDL ratio were the best predictors for POD. Taken together, these data suggest that Lp(a) and Hcy excesses might exert a central role in the development of atherosclerotic disease in elderly male patients. Thereby, the inclusion of those tests, along with the TC/HDL ratio and other more conventional analyses in panels for the evaluation of the cardiovascular risk might be profitable in terms of effectual prevention.

PMID: 11666132 [PubMed - in process]

1: Chin Med J (Engl) 1999 Jul;112(7):586-9

Hyperhomocysteinemia and hyperlipidemia in coronary heart disease.

Gao W, Jiang N, Meng Z, Tang J.

Department of Cardiology, First Teaching Hospital of Beijing Medical University, Beijing 100034, China.

OBJECTIVE: To examine the relationship between coronary heart disease (CHD) and serum lipid, plasma homocysteine (HCY) as well as the factors related to HCY metabolisms. METHODS: The mutation of the 677C-->T transition of 5, 10-methylenetetrahydrofolate reductase (MTHFR) was determined by PCR-based assay. Whole-blood and plasma folate and plasma vitamin B12, as cofactors of MTHFR, were determined by radio-immunologic assay. Plasma HCY was determined by HPLC. RESULTS: Patients with CHD had elevated plasma HCY concentrations (17.38 +/- 1.94 mumol/L vs 10.25 +/- 1.57 mumol/L, P < 0.01). In patients with myocardial infarction (MI) and family history (FH) of CHD, plasma HCY were elevated even higher (P < 0.05). Plasma HCY concentrations had significant non-linear inverse correlation with plasma folate and B12 concentrations, i.e. the lower the serum folate or B12 concentrations, the higher the plasma HCY concentrations (P < 0.01). Patients with homozygous mutants had higher plasma HCY concentrations. Patients with CHD had increased serum Chol and LDL-C and Apo-B levels (P < 0.01, P < 0.05 and P < 0.05 respectively). But plasma HCY concentrations had no correlation with serum lipid levels. 24.1% of the patients had high lipid and high HCY level, 25.9% had high lipid level and normal HCY level, 20.4% had normal lipid and high HCY level, and 29.6% had normal lipid and HCY level. CONCLUSIONS: HCY may have strong association with the genesis of CHD. Low plasma folate and B12 concentrations may induce Hyperhomocysteinemia [HH(e)]. Plasma HCY concentrations have no correlation with serum lipid levels, so HCY may be an independent risk factor. CHD may be induced by different mechanisms and can be classified into hyperlipidemia, HH (e) and normolipidemia, and normohomocysteinemia.

PMID: 11601248 [PubMed - in process]

1: Harv Rev Psychiatry 2001 Nov;9(6):280-293

Omega-3 Fatty Acids, Homocysteine, and the Increased Risk of Cardiovascular Mortality in Major Depressive Disorder.

Severus WE, Littman AB, Stoll AL.

Psychopharmacology Research Laboratory, McLean Hospital, Belmont, Mass. (Drs. Severus and Stoll), the Department of Psychiatry and the Behavioral Medicine Division of Preventive Cardiology, Massachusetts General Hospital, Boston, Mass. (Dr. Littman), the Consolidated Department of Psychiatry, Harvard Medical School, Boston, Mass. (Drs. Severus, Littman, and Stoll), and the Department of Psychiatry, University Hospital Benjamin Franklin, Berlin, Germany (Dr. Severus).

Depression is associated with elevated rates of cardiovascular morbidity and mortality. This elevation seems to be due to a significantly increased risk of coronary artery disease and myocardial infarction and, once the ischemic heart disease is established, sudden cardiac death. Recent data suggest that the increased rates of cardiovascular disease in patients with depression may be the result of one or more still-unrecognized underlying physiological factors that predispose a patient to both depression and cardiovascular disease. Two possibly related factors that may have a causal relation with both depressive disorders and cardiovascular disease are an omega-3 fatty acid deficiency and elevated homocysteine levels. We present the available data connecting cardiovascular disease, depression, omega-3 fatty acids, and homocysteine. In addition, we suggest research strategies and some preliminary treatment recommendations that may reduce the increased risk of cardiovascular mortality in patients with major depressive disorder.

PMID: 11600487 [PubMed - as supplied by publisher]

1: JAMA 2001 Aug 22-29;286(8):936-43

Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond.

Tice JA, Ross E, Coxson PG, Rosenberg I, Weinstein MC, Hunink MG, Goldman PA, Williams L, Goldman L.

Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0320, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

CONTEXT: A high homocysteine level has been identified as an independent modifiable risk factor for coronary heart disease (CHD) events and death. Since January 1998, the US Food and Drug Administration has required that all enriched grain products contain 140 microg of folic acid per 100 g, a level considered to decrease homocysteine levels. OBJECTIVES: To examine the potential effect of grain fortification with folic acid on CHD events and to estimate the cost-effectiveness of additional vitamin supplementation (folic acid and cyanocobalamin) for CHD prevention. DESIGN AND SETTING: Cost-effectiveness analysis using the Coronary Heart Disease Policy Model, a validated, state-transition model of CHD events in adults aged 35 through 84 years. Data from the third National Health and Nutrition Examination Survey (NHANES III) were used to estimate age- and sex-specific differences in homocysteine levels. INTERVENTION: Hypothetical comparison between a diet that includes enriched grain products projected to increase folic acid intake by 100 microg/d with the same diet without folic acid fortification; and a comparison between vitamin therapy that consists of 1 mg of folic acid and 0.5 mg of cyanocobalamin and the diet that includes grains fortified with folic acid. MAIN OUTCOME MEASURES: Incidence of myocardial infarction and death from CHD, quality-adjusted life-years (QALYs) saved, and medical costs. RESULTS: Grain fortification with folic acid was predicted to decrease CHD events by 8% in women and 13% in men, with comparable reductions in CHD mortality. The model projected that, compared with grain fortification alone, treating all patients with known CHD with folic acid and cyanocobalamin over a 10-year period would result in 310 000 fewer deaths and lower costs. Over the same 10-year period, providing vitamin supplementation in addition to grain fortification to all men aged 45 years or older without known CHD was projected to save more than 300 000 QALYs, to save more than US $2 billion, and to be the preferred strategy. For women without CHD, the preferred vitamin supplementation strategy would be to treat all women older than 55 years, a strategy projected to save more than 140 000 QALYs over 10 years. CONCLUSIONS: Folic acid and cyanocobalamin supplementation may be cost-effective among many population subgroups and could have a major epidemiologic benefit for primary and secondary prevention of CHD if ongoing clinical trials confirm that homocysteine-lowering therapy decreases CHD event rates.

PMID: 11509058 [PubMed - indexed for MEDLINE]