Study Confirms Parental History as Heart Attack Risk Factor : Internal Medicine News

Study Confirms Parental History as Heart Attack Risk Factor

By: JEFFREY S. EISENBERG, Internal Medicine News Digital Network
01/24/11

Having a parent with a history of myocardial infarction nearly doubled a person’s own risk of future MI, even after accounting for other risk factors, according to an analysis of a large case-control study.

The findings are consistent in all regions of the world, added the authors of the analysis, who reported their findings in the Feb. 1 issue of the Journal of the American College of Cardiology.

INTERHEART, a multinational case-control study, involved 15,152 patients who presented with a first MI and 14,820 age- and sex-matched control subjects between February 1999 and March 2003. Previous analysis of the study identified nine variables for determining MI risk: abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, physical activity, fruit and vegetable consumption, and alcohol consumption.

The current analysis included 12,149 patients presenting with a first MI and 14,467 control subjects. Dr. Clara K. Chow of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, and her colleagues obtained data on demographic factors, socioeconomic status, and risk factors for all participants, and performed genetic analysis in 8,795 participants using a panel of 1,536 single nucleotide polymorphisms (SNPs) from 103 genes believed to be associated with MI or risk factors for MI (J. Am. Coll. Cardiol. 2011;57:619-27).

In 18.1% of cases and 12% of controls, either parent had a history of MI, while both parents had a history of MI in 2.1% of cases and 0.9% of controls. A maternal history of MI was present in 7.5% of cases and 4.9% of controls, while 12.7% of cases and 8.1% of controls had a paternal history of MI. There were no significant differences in the risks associated with history of MI in either parent.

The relationship between parental history and MI risk remained after adjusting for the nine INTERHEART risk factors.

Genetic risk scores also didn’t alter the relationship. The researchers calculated genotype scores for 3,372 cases and 4,043 controls, and found that the genetic risk scores were not greater in those with a parental history of MI than in those without. The mean genotype score was 11.90 in controls with no parental history of MI, 11.84 in controls with a parental history of MI, 12.26 in cases with no parental history of MI, and 12.14 in cases with a parental history of MI.

Parental history approximately doubled an individual’s risk of MI, and the risk increased if both parents had a history of MI, especially if it occurred at a younger age.

Specifically, the odds ratio of an individual having MI was 1.81 if either parent had a history of MI (1.74 after adjusting for other risk factors). When either parent had an MI at age 50 years or older, the odds ratio fell to 1.67 – but it rose to 2.90 if both parents had an MI at age 50 or older.

The odds ratio was 2.36 for those patients with one parent who had an MI before age 50, but increased to 3.26 if both parents had an MI and one parent was younger than age 50. If both parents had an MI before age 50, the odds ratio reached 6.56.

The study results suggest that parental history of MI is an independent predictor of an individual’s risk of future MI – even after adjusting for age, sex, region, and other risk factors. The association between parental history of MI and MI is consistent across geographic regions, age, sex, and socioeconomic subgroups.

"While other studies have shown the relationship between parental history and risk, they have not established its independence from the extensive list of other potential explanatory factors, as measured by the INTERHEART Study, and not established it in other world regions or ethnic groups," the authors wrote.

The results raise another question: Are there factors other than shared risk factors and genetics that are involved in heart disease, such as early life exposures or home environmental factors? The genotype score obtained in the study analyses represents only a small percentage of possible genotype variants, the researchers noted.

The strengths of the study are its large international coverage; the large number of cases of MI; and the comprehensive measurement of risk factors, including genetic factors, the researchers said. Limitations included a lack of data collected from siblings or other relatives, limited measurement of SNPs in a limited number of individuals, and the possibility of recall biases due to the case-control nature of the study.

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Family History Re-emerges as Heart Disease Risk Factor

Since the 1950s and early 1960s, epidemiology studies have cited familial history as a risk factor for coronary artery disease, explained Dr. Themistocles L. Assimes. The same finding appeared in larger case-control studies in the 1970s and 1980s, yet family history was not included in the Framingham Risk Score, the risk profile established by the Framingham Heart Study. That was primarily because researchers considered the predictive value of family history limited when compared with other major risk factors, and because it was hard to measure reliably, Dr. Assimes noted in an editorial accompanying the analysis (J. Am. Coll. Cardiol. 2011;57:628-29).

Since then, research has been less likely to focus on the role of a carefully documented family history in the prevention of coronary artery disease and more likely to focus on estimating what proportion of unidentified factors responsible for familial aggregation were genetic in nature.

The latest findings from the INTERHEART Study are important because they show how measurement of family (specifically parental) history of cardiovascular disease can help predict an individual’s risk for MI, Dr. Assimes explained. And they can do so independently from other known risk factors.

Although researchers are unlikely to identify the numerous genetic and nongenetic factors responsible for family aggregation of heart disease for years, the latest findings, "combined with recent efforts to develop new risk scores around the world, have undoubtedly reignited interest in understanding the role of this traditional risk factor in the primary prevention of [coronary artery disease]," he said.

Dr. Assimes is an assistant professor at the Stanford (Calif.) University School of Medicine. He had no relationships to disclose.
Study Confirms Parental History as Heart Attack Risk Factor : Internal Medicine News