Elsevier

Atherosclerosis

Volume 232, Issue 2, February 2014, Pages 369-376
Atherosclerosis

Family history of coronary heart disease and the incidence and progression of coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA)

https://doi.org/10.1016/j.atherosclerosis.2013.11.042Get rights and content

Highlights

  • We evaluate how family history influences changes in coronary artery calcium (CAC).

  • Family history of premature CHD increases CAC incidence and progression.

  • Individuals with parental and sibling histories of premature CHD have the greatest CAC evolution.

Abstract

Objective

We evaluated family history as a predictor of incident and progressive coronary artery calcium (CAC) using data from the Multi-Ethnic Study of Atherosclerosis (MESA).

Background

MESA is a multi-center prospective study of 6814 asymptomatic individuals. The relationship between family history of coronary heart disease (CHD) and CAC incidence or progression has not been described previously.

Methods

A total of 5099 participants had detailed information about family history of CHD (late versus premature and parental versus sibling history). The mean time between CAC scans was 3.1 ± 1.3 years. The association of late versus premature family history was assessed against CAC change using multivariate regression model adjusted for demographics and cardiac risk factors.

Results

A family history of premature CHD was associated with an odds ratio (OR) of 1.55 (p < 0.01) for incident development of CAC after adjusting for risk factors and demographics. A premature family history was associated with 14.4 units (p < 0.01) greater volume scores compared to those with no family history in similarly adjusted models by median regression analysis. A combined parental and sibling family history was associated with the greatest incidence and progression in demographic-adjusted models. Caucasians demonstrated the most consistent predictive relationship between family history of premature CHD and incidence (p < 0.01) and progression (p < 0.05) of CAC, though no significant interaction with ethnicity was noted.

Conclusions

Family history of premature CHD is associated with enhanced development and progression of subclinical disease, independent of other risk factors, in a multiethnic, population-based study.

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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