Association of Coronary Artery Calcium in Adults Aged 32 to 46 Years With Incident Coronary Heart Disease and Death

Abstract

Importance: Coronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults.

Objective: To determine if CAC in adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up.

Design, setting, and participants: The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.

Main outcomes and measures: Incident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years.

Results: At year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1.0-5.7), 5.8 (95% CI, 2.6-12.1), and 9.8 (95% CI, 4.5-20.5), respectively. A CAC score of 100 or more had an incidence of 22.4 deaths per 100 participants (HR, 3.7; 95% CI, 1.5-10.0); of the 13 deaths in participants with a CAC score of 100 or more, 10 were adjudicated as CHD events. Risk factors for CVD in early adult life identified those above the median risk for developing CAC and, if applied, in a selective CAC screening strategy could reduce the number of people screened for CAC by 50% and the number imaged needed to find 1 person with CAC from 3.5 to 2.2.

Conclusions and relevance: The presence of CAC among individuals aged between 32 and 46 years was associated with increased risk of fatal and nonfatal CHD during 12.5 years of follow-up. A CAC score of 100 or more was associated with early death. Adults younger than 50 years with any CAC, even with very low scores, identified on a computed tomographic scan are at elevated risk of clinical CHD, CVD, and death. Selective use of screening for CAC might be considered in individuals with risk factors in early adulthood to inform discussions about primary prevention.

Figure 1.. Individuals Aged 32 to 46 Years With Prevalent Coronary Artery Calcium (CAC) and Progression During the Following 10 Years

The geometric means and 95% CIs by CAC score category at the year 15 examination (2000-2001), estimated in repeated measures regression with banded covariance structure, are presented. The geometric mean was used to address the skewness of the distribution and can be interpreted as comparable to the median of the distribution. Although CAC was initially minimal in the group with the lowest score (1-19), during the following 10 years the geometric mean CAC score increased from 5.7 at year 15 to 27.4 at year 20 to 89.8 at year 25. In the group with a score of 20-99, the geometric mean CAC score increased from 43.6 at year 15 to 117.8 at year 20 to 255.7 at year 25. In the group with a score of ≥100, the geometric mean CAC score increased from 217.2 at year 15 to 440.4 at year 20 to 680.0 at year 25. The linear increase observed, when plotted on the log scale y-axis, indicates exponential increase over time in the amount of CAC.

Figure 2.. Incidence Density of Coronary Heart Disease (CHD) Events per 100 Persons

Incidence density of CHD events per 100 persons in a fully adjusted Poisson regression model, for coronary artery calcium (CAC) score category within Framingham Heart Study 10-year predicted CHD risk as determined at the year 15 examination (2000-2001) and then followed up for 12.5 years.