Genetic Risk Factors for Cardiovascular Disease
Family History of Cardiovascular Disease
The term cardiovascular disease (CVD) is frequently used interchangeably with 'heart disease', but for some medical professionals, the term CVD is used to describe only those medical conditions that lead to the narrowing or blocking of blood vessels (Mayo Clinic Staff, 2012). For others, the term CVD encompasses a number of medical conditions affecting the health of all aspects of the cardiovascular system, including blood vessels, the heart, and the autonomic circuits regulating heart rhythm (Kathiresan and Srivastava, 2012). Other terms used interchangeably with CVD include coronary artery disease (CAD) and coronary heart disease (Superko, Roberts, Garret, Pendyla, and King III, 2010; National Heart, Lung and Blood Institute, 2011). For the purposes of this review, CVD will be used in the same umbrella-like manner that Kathiresan and Srivastava (2010) have used the term, except when discussing a study that has used a different definition.
Close to 25% of all deaths in the United States are caused by CVD, which translated into 616,000 deaths in 2008 (Centers for Disease Control and Prevention [CDC], 2012). This makes CVD the number one killer of both men and women in the U.S. The resultant financial burden of this disease was estimated to be $109 billion in 2010. For these reasons, CVD prevention strategies have become a major healthcare policy issue for several U.S. agencies and organizations, including the CDC, National Institutes of Health, American Heart Association, American Stroke Association, and the Association of State and Territorial Health Officials (CDC, 2010).
Prevention strategies are at the forefront of CVD health policy, because medical interventions that treat CVD risk have cut the number of deaths due to this disease in half over the past 30 years (Viera and Sheridan, 2010). However, there is still plenty of room for improvement because two thirds of people currently at risk for developing CVD are not being treated to lower their risk. Treating risk is effective because the dominant risks are environmental and thus modifiable, such as obesity, high serum cholesterol, smoking, hypertension, sedentary lifestyle, and diabetes. The other major risk factors that are not modifiable are age and being male.
Environmental risk factors are believed to be sufficient for explaining close to 80% of CVD prevalence, which suggests heritable factors explain the remaining 20% (Thanassoulis and Vasan, 2010). This conclusion is an oversimplification of what is actually occurring, because many of associated risk factors also have a genetic component. For this reason, a family history of CVD is likely to be due to a number of environmental and genetic factors interacting in complex ways. This review will delve into what is currently understood regarding the risk that a family history confers to CVD prevalence.
The Epidemiology of Heritable CVD Risk Factors
When CVD is defined as including CAD, cardiac insufficiency, myocardial infarction, angina pectoris, and ischemic attacks, the overall prevalence of CVD events is 6.54 per 1000 person years for a Boston area community (Murabito et al., 2005). For siblings with a family history of CVD disease, the prevalence was found to be 15.27 per 1000 person years for the same community. If the analysis is adjusted for age and sex, then the odds that a sibling with a family history of CVD will develop this disease is 1.55 (95% CI, 1.19-2.03). If the analysis is further corrected for contributions from hypertension, high cholesterol, obesity, diabetes, and current smoker, the odds ratio is reduced insignificantly (OR = 1.45; 95% CI, 1.10-1.91). These results suggest that genetic factors, independent of other associated medical conditions, increase the risk of CVD by about 50%.
Early onset CVD disease was found to be a significant factor contributing to disease risk (Murabito et al., 2005). When siblings were grouped by age of onset, either before or after 48 years of age, risk was found to be significantly stratified after correcting for all confounding risk factors (OR = 2.22; 95% CI, 1.22-4.02 vs. 1.33; 95% CI, 0.98-1.08). If the analysis was limited to only those families for which parental CVD histories were known for both parents, the CVD risk for siblings increased to 1.99 (95% CI, 1.32-3.00). This suggests a family history of CVD doubles the risk for developing this disease.
One of the main unexpected results from this study was that sibling CVD represented a greater risk for disease than premature parental and sibling CVD combined (1.53; 95% CI, 0.93-2.51) (Murabito et al., 2005). The authors suggested that this difference can be explained by the higher prevalence of associated risk factors, such as hypertension (31.5%) and diabetes (12.2%), among the latter group, which would tend to suppress the odds ratio compared to that calculated...
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