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Plasma homocyst(e)ine as a risk factor for early familial coronary artery disease
1Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City 84132.
Insights
Elevated plasma homocysteine (H(e)) is linked to early familial coronary artery disease. Genetic factors likely contribute to high H(e) levels, increasing heart disease risk in affected families.
Area of Science:
- Cardiovascular Genetics
- Metabolic Disorders
- Biochemistry
Background:
- Early-onset coronary artery disease (CAD) often has a familial component.
- Elevated plasma homocysteine (H(e)) is a known risk factor for cardiovascular disease.
- The genetic basis for familial hyperhomocysteinemia in early CAD requires further elucidation.
Purpose of the Study:
- To investigate the association between plasma homocysteine (H(e)) levels and early-onset familial coronary artery disease.
- To determine if genetic factors contribute to elevated H(e) in families with multiple affected siblings.
- To identify H(e) as a potential biomarker for genetic predisposition to early CAD.
Main Methods:
- Cross-sectional study comparing plasma H(e) in patients with early CAD and controls.
- Analysis of H(e) concentrations adjusted for covariates like serum creatinine, uric acid, and LDL cholesterol.
- Examination of H(e) distribution and familial aggregation in affected families.
Main Results:
- Proband cases with early CAD exhibited significantly higher adjusted mean H(e) (12.0 mumol/L) compared to controls (10.1 mumol/L).
- 17.6% of proband cases had H(e) levels above the 95th percentile of controls, indicating a substantial risk.
- Bimodal distribution of H(e) in cases and concordant high H(e) in 12% of families suggest a major gene effect.
Conclusions:
- Elevated plasma H(e) is strongly associated with early-onset familial coronary artery disease.
- A significant proportion of early familial CAD is likely attributable to genetic factors influencing H(e) production.
- Targeting hyperhomocysteinemia may be a strategy for managing genetic risk in early CAD.
Abstract:
We measured plasma homocyst(e)ine [H(e)] and other coronary risk factors in 266 patients with early coronary artery disease from 170 families in which two or more siblings were affected and in 168 unmatched controls. The mean H(e) concentration adjusted for significant correlates (serum creatinine, uric acid, and low-density lipoprotein cholesterol) was 12.0 mumol/L in proband cases compared with 10.1 mumol/L in controls (P = 0.0001). Many (17.6%) of the proband cases had H(e) concentrations exceeding the 95th percentile for the controls (relative odds = 4.9, P < 0.001). H(e) among cases was bimodally distributed even after adjustment for concentrations of plasma vitamins. Concordant high H(e) was seen in at least 10 (12%) of 85 families with two or more affected siblings. We conclude that a substantial proportion of early familial coronary artery disease is probably related to production of high concentrations of H(e) by one or more major genes.