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Familial aggregation of coronary heart disease: partial mediation by high density lipoproteins?
L A Simons1, Y Friedlander, J Simons
1School of Medicine, University of NSW, Sydney, Australia.
Insights
Family history of heart attack modifies the impact of high-density lipoprotein-cholesterol (HDL-C) on coronary heart disease (CHD). Lower HDL-C levels are linked to CHD only in those with a family history, suggesting a genetic interaction.
Area of Science:
- Cardiovascular Medicine
- Genetics and Epidemiology
- Lipid Metabolism
Background:
- Coronary heart disease (CHD) has a significant heritable component.
- Major coronary risk factors are well-established, but their interaction with genetic predisposition requires further investigation.
- Understanding these interactions is crucial for personalized risk assessment and prevention strategies.
Purpose of the Study:
- To explore how major coronary risk factors explain the inheritance of coronary heart disease.
- To investigate the interplay between family history of heart attack and lipid profiles, specifically high-density lipoprotein-cholesterol (HDL-C), in relation to CHD.
- To identify significant predictors of CHD, considering both genetic predisposition and traditional risk factors.
Main Methods:
- Analysis of a random sample of 1044 males aged 40-70 years from the Jerusalem Lipid Research Clinic Prevalence Study.
- Collection of standardized data on personal and family history, coronary risk factors, and electrocardiography (resting and exercise).
- Application of multiple logistic regression models to assess the predictive value of risk factors and family history on CHD presence, including interaction terms.
Main Results:
- Twelve percent of subjects had CHD; 20% reported a family history of heart attack before age 60.
- In subjects with a family history of heart attack, lower mean HDL-C levels were observed in CHD cases compared to controls.
- HDL-C was a significant negative predictor of CHD, but only in the presence of a positive family history. A 10 mg/dl increase in HDL-C was associated with a two-thirds reduction in heart disease risk in this subgroup. Age, total plasma cholesterol, hypertension, family history, and HDL-C were significant predictors in the overall model, with a significant interaction between family history and HDL-C.
Conclusions:
- Family history of heart attack significantly modifies the relationship between HDL-C and CHD risk.
- Low HDL-C levels are particularly detrimental for individuals with a genetic predisposition to heart disease.
- Combined assessment of family history and HDL-C offers a more refined approach to CHD risk stratification.
Abstract:
The potential explanation of coronary heart disease inheritance by the major coronary risk factors was explored in a random sample of 1044 males, aged 40-70 years, who formed part of the Jerusalem Lipid Research Clinic Prevalence Study. Standardised data were available on personal and family history, coronary risk factors, resting and exercise electrocardiography. Twelve percent of subjects had coronary heart disease (previous myocardial infarction or electrocardiographic changes) and 20% had a family history of heart attack before 60 years in first degree relatives. In the presence of a family history of heart attack, the mean level of high density lipoprotein-cholesterol (HDL-C) was 5 mg/dl lower in cases of coronary heart disease than in controls. No such difference existed in the absence of a family history of heart attack. In multiple logistic regression, HDL-C was a significant negative predictor of coronary heart disease presence, but only in subjects having a positive family history. A 1 standard deviation (10 mg/dl) increment in HDL-C was associated with a two-thirds reduction in heart disease risk. Other risk factors did not predict the occurrence of coronary heart disease to any significant extent in subjects with a positive family history of heart attack. In an overall logistic model combining family history with other risk factors, the significant predictors of heart disease were: age, total plasma cholesterol, hypertension, family history and HDL-C. The interaction term, family history X HDL-C, was also a significant negative predictor of heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)