Expanding the definition of a positive family history for early-onset coronary heart disease

Abstract

Purpose: Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD. Methods: By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity. Results: Of 4035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years;4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD. Coronary heart disease (CHD) is the leading cause of premature death and disability in the United States and other developed countries. 1 Several risk factors are known to contribute to CHD. Global risk assessment is an approach to CHD prevention that estimates the absolute risk based on the summation of risks contributed by each risk factor. 2 Although not all risk factors are modifiable, all can contribute to the risk assessment, and the intensity of risk factor management can be adjusted according to the severity of the overall risk.Family history is an important and independent CHD risk factor, especially for early-onset disease. Many studies have found a two-to threefold increase in CHD given a first-degree relative with CHD, 3-6 and the strength of this association increases as the number of affected first-degree relatives increases 7,8 and with younger ages of CHD onset in relatives. [7][8][9][10] Less is known about the effects of later-onset CHD in relatives, second-degree relatives with CHD, or the presence of stroke and diabetes among relatives. Furthermore, few studies have assessed the impact of the type of relative affected with CHD (e.g., parent or sibling) or the lineage of affected relatives (i.e., maternal or paternal) on CHD risk.The Framingham Risk Score is a common global risk assessment method for CHD that is used to guide preventive interventions. Age is a prominent determinant of the Framingham risk estimate, and family history is not included as a risk factor. 11 Therefore, the Framingham score may underestimate CHD risk for individuals with family history, particularly at young ages when prevention could have substantial benefits given the risk for early-onset disease.The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) guidelines provide recommendations for CHD prevention, fo...

Is Family History a Useful Tool for Detecting Children at Risk for Diabetes and Cardiovascular Diseases? A Public Health Perspective

“…Algorithms for stratifying risk that incorporate these features of family history to rank individual people are being evaluated in adult populations. [91][92][93] Algorithms to predict the risk of chronic conditions in susceptible children may have to be modified to account for the potentially prolonged period between exposure and outcomes. Ideally, the algorithm should identify children at increased risk who would benefit the most from early preventive measures and children at very high risk, who may be referred to a specialist.…”

The family history: the first genetic test, and still useful after all those years?

“…43 Once thought to be relevant only if parental disease was "early" (the definition of which has varied in numerous studies, typically being age 55 or younger in men and age 60 in women), risk is now associated with coronary heart disease of any age of onset in any first-or second-degree relative. 44 In addition, family history is relevant for subclinical disease, such as coronary artery calcification 45,46 and the risk of sudden death during an acute coronary event. 47 As with type 2 diabetes, GWAS has uncovered dozens of loci that are associated with increased risk of coronary artery disease.…”

Familial risk assessment for early-onset coronary heart disease

“…1,[5][6][7]9,[11][12][13] Studies that have investigated family histories of late-onset CHD have also found significant positive associations with CHD, although the relative risks are comparatively smaller. 5,6,9,[11][12][13] Recent studies have demonstrated an increased CHD risk associated with CHD in second-degree relatives, 14,15 and in maternal relatives, 13 although other studies have not found an association between CHD and lineage. 4,7,10,16 Despite the importance of family history as a CHD risk factor, it is underused in CHD prevention efforts.…”