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Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial
R W Evans1, B J Shaten, J D Hempel
1Department of Epidemiology, University of Pittsburgh, Penn., USA. RWE2@vms.cis.pitt.edu
Insights
This study found no link between homocyst(e)ine levels and heart disease risk in men. Homocysteine is not a significant independent risk factor for myocardial infarction or coronary heart disease deaths.
Area of Science:
- Cardiovascular Research
- Biomarkers
- Epidemiology
Background:
- Homocysteine is a proposed independent risk factor for heart disease.
- Previous studies suggest a potential association between homocysteine and cardiovascular events.
- The Multiple Risk Factor Intervention Trial (MRFIT) provided a unique cohort for investigation.
Purpose of the Study:
- To investigate the association between serum homocysteine levels and the risk of nonfatal myocardial infarction (MI) and coronary heart disease (CHD) death.
- To determine if homocysteine is an independent risk factor for cardiovascular disease.
- To explore potential correlations between homocysteine and acute-phase proteins.
Main Methods:
- A nested case-control study design within the MRFIT cohort.
- Analysis of serum samples from 712 men, stored for up to 20 years.
- Measurement of serum homocysteine concentrations and comparison between cases (MI, CHD death) and controls.
Main Results:
- Mean homocysteine concentrations did not significantly differ between cases and controls for MI or CHD death.
- Odds ratios for combined CHD deaths and MIs showed no significant association across homocysteine quartiles.
- A weak association was observed between homocysteine levels and C-reactive protein.
Conclusions:
- Serum homocysteine concentration is not associated with an increased risk of nonfatal MI or CHD death in this prospective study.
- The findings do not support homocysteine as an independent risk factor for heart disease.
- Further research may be needed to clarify the role of homocysteine in cardiovascular pathology.
Abstract:
A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for up to 20 years, were analyzed for homocyst(e)ine. Cases involved nonfatal myocardial infarctions (MIs), identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease (CHD), monitored through 1990. The nonfatal MIs occurred within 7 years of sample collection, whereas the majority of CHD deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: MI cases, 12.6 mumol/L; MI controls, 13.1 mumol/L; CHD death cases, 12.8 mumol/L; and CHD controls, 12.7 mumol/L. Odds ratios versus quartile 1 for CHD deaths and MIs combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase protein (C-reactive protein). These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease.