Family history of coronary heart disease and the incidence and progression of coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA)
Introduction
Coronary artery calcium (CAC), measured using non-contrasted computed tomography gated to the cardiac cycle, is a well-validated metric for determining coronary heart disease (CHD) risk in asymptomatic patients. Across a variety of populations, increasing baseline measurements of CAC are associated with future CHD events, independent of traditional risk factors. Assimilation of CAC scores has been shown to improve established risk prediction models [1], [2], [3], [4], [5]. Clinical guideline statements have recommended that CAC scoring can be used in select groups of patients to further stratify CHD risk [6], [7], [8]. Currently the American Heart Association gives a Class IIa recommendation for measuring CAC in asymptomatic individuals at intermediate CHD risk, having a Framingham risk score (FRS) for 10-year CHD risk between 10% and 20%; there is also a IIa recommendation for testing asymptomatic diabetic patients over the age of 40 [9].
Repeat measurements of CAC enable non-invasive assessment of the development and progression of subclinical atherosclerosis over time. Currently, repeat CAC measurements are being studied for their potential in routine clinical practice in select patients [10]. Although not useful as a marker for near-term responsiveness to statin treatment [11], [12], progression of CAC is predicative of CHD events as well as all-cause mortality [13], [14], [15]. There is increasing evidence indicating that both established as well as novel CHD risk factors are closely associated with CAC incidence and progression [16], [17], [18], [19]. Family history of premature CHD is a recognized risk factor for development of CHD events and overall cardiovascular mortality [20], [21]; however, it is not directly accounted for in traditional risk stratification methods, such as the Framingham risk score. Recent reports have shown that a family history of premature CHD is associated with a higher likelihood of presence of any CAC (>0) as well increased CAC scores among those with any detectable CAC [22], [23]. Moreover, there is evidence that incorporating family history can improve prediction models for identifying individuals with higher burden of subclinical coronary atherosclerosis as measured by CAC scores [24]. However, to date the relationship between family history and the development and progression of CAC has not been described. In this study we sought to examine the association of family history of CHD with the development and progression of CAC in a multiethnic group of asymptomatic patients.
Section snippets
Study participants
Details on the MESA study's prospective design and organization have been previously described [25]. From July 2000 to September 2002, 6814 adults from the general community were enrolled at six field centers in the United States (Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles, California; New York, New York; and St. Paul, Minnesota). Participants were aged 45–84 years at enrollment, free of clinical CVD, and identified themselves as white, black, Hispanic,
Results
The baseline characteristics of the MESA study population are presented in Table 1. Statistical comparisons are made between those without a family history of CHD and those with histories of premature and late CHD. Within the total cohort, 47% of the population was male, with the majority of participants being Caucasian (n = 2166). Overall, 52% (n = 2633) of participants had a positive family history of CHD; 20% (n = 1002) of the individuals had a family history of premature CHD, of whom 456
Discussion
In a population-based multiethnic cohort of asymptomatic, mostly low- and intermediate-risk men and women, a family history of CHD, particularly a combined parental and sibling history of premature CHD, is associated with CAC incidence and progression in MESA. The findings further support and reinforce the addition of family history of CHD in current methods of global risk assessment and practice guidelines.
Previous studies have indicated a relationship between premature family history and
Conflict of interest disclosures
Dr. Budoff is on the speaker's bureau for GE Healthcare.
Acknowledgments
We thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute.
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