Parental History and Myocardial Infarction Risk Across the World: The INTERHEART Study

Study Questions:

Is parental history of myocardial infarction (MI) independently associated with risk for MI among offspring after adjustment for cardiovascular (CV) risk factors and genetic variants?

Methods:

Data from the INTERHEART study between February 1999 and March 2003 were used for the present analysis. After excluding those with missing data, a total of 12,149 MI cases and 14,467 controls, who were matched on age, ethnicity, and sex, were included. A total of 3,372 cases and 4,032 controls had complete clinical and genetic data including participants from five ethnic groups (Arab, European, Iranian, Nepalese, and South Asian). Participants were genotyped using a panel of 1,536 single nucleotide polymorphisms (SNPs) from 103 genes that were chosen based on previous knowledge suggesting a relationship with MI or MI risk factors. A genotype score was then calculated from eight genes (APOE, AGT, LPA, LDLR, PPARG, PON2, APOC3, and INSIG2).

Results:

The odds ratio for MI associated with a positive family history was 1.66 (95% confidence interval [CI], 1.49-1.84) if one parent (≥50 years of age) had experienced an MI. The risk increased if the parent experienced an MI before the age of 50 (odds ratio [OR], 2.21; 95% CI, 1.63-3.00). If both parents had experienced an MI after the age of 49, the odds were 2.48 (95% CI, 1.80-3.42). The risk increased if both parents had experienced an MI with one parent experiencing the MI prior to the age of 50 (OR, 3.26; 95% CI, 1.25-8.50). These associations were minimally attenuated after adjusting for multiple cardiovascular risk factors including hypertension, diabetes, lipids, waist-to-hip ratio, tobacco use, alcohol use, physical activity, fruit and vegetable intake, and psychosocial factors in addition to genetic data, and genotype score. The strength of association of a parental history of MI and MI risk was similar across all geographic and socioeconomic strata studied.

Conclusions:

The authors concluded that parental history of MI is an important, consistent, and global determinant of MI risk. A graded relationship existed with the degree of prematurity of the parental history that was independent of other risk factors.

Perspective:

The study confirms the value of a good family history. As the authors note, candidate gene polymorphisms were limited to those associated with cholesterol metabolism; thus, further examination of additional polymorphisms may add information to the present study. For now, family histories are a low-cost way of assisting a clinician to identify patients at higher risk for heart disease.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Hypertension

Keywords: Cholesterol, Odds Ratio, Myocardial Infarction, Waist-Hip Ratio, Polymorphism, Single Nucleotide, Lipids, European Continental Ancestry Group, Motor Activity, Tobacco Use, Genotype, Hypertension, Diabetes Mellitus


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