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?


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).


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.


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.


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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