Incidence of coronary artery disease in siblings of patients with premature coronary artery disease: 10 years of follow-up

Abstract

Although family history of premature coronary artery disease (CAD) confers increased risk of CAD, the magnitude of this increase beyond that expected from the risk factors incorporated in the Framingham Risk Equation (FRE) remains unknown. We prospectively determined the accuracy of the FRE 10-year incident CAD events prediction in initially healthy siblings of patients with documented premature CAD. We recruited 784 siblings (30 to 59 years) of 449 patients hospitalized with CAD <60 years of age (1983 to 1995). We compared the estimated 10-year incidence of total CAD events by the gender-specific FREs at baseline, to the observed incidence at 10 years of follow-up. In men, the 10-year actual CAD event rate was 20%, only half of which was predicted by the FRE (12% vs 20%, p <0.001). In women, the observed CAD event rate was 7.1% (p <0.001 vs men), modestly but not significantly greater than the 6.3% predicted by the FRE (p = 0.34). Thus, there was a significant 66.6% excess risk in men, and a nonsignificant 12.7% excess risk in women beyond the risk predicted by the FRE for total CAD events. The FRE and its known classic risk factor profile failed to accurately predict total incident 10-year CAD events in individuals with a sibling history of premature CAD, most particularly in men. In conclusion, in families with a history of premature CAD, the excess risk observed cannot be attributed to traditional risk factors, suggesting a major role for as yet undetermined genetic and other susceptibility factors.

Figure 1

Percentage of coronary artery disease events comprising the total 10-year coronary disease events, N=108 events

Figure 2

Kaplan-Meier survival curves over 10-year follow-up, by sex, n=404 men, 380 women

Figure 3

The predicted 10-year event rate using the Framingham Risk Equation and observed the 10-year coronary artery disease event rate in the sibling cohort by sex.

Figure 4

Comparison of predicted and observed coronary artery disease event rate by deciles of baseline Framingham 10-year risk, by sex. FRE Baseline Deciles in men: 1st: ≤4.0%, 2nd: 4.1–5.803%, 3rd: 5.804–6.81%, 4th: 6.85–8.41%, 5th: 8.42–10.00% 6th: 10.01–11.70%, 7th: 11.72–14.00%, 8th: 14.08–16.41%, 9th: 16.43–21.86%, 10th: ≥22.16%. FRE Baseline Deciles in women: 1st: ≤1.0%, 2nd: 1.31–1.63%, 3rd: 1.66–2.50%, 4th: 2.53–3.56%, 5th: 3.58–4.58% 6th: 4.62–5.67%, 7th: 5.70–7.31%, 8th: 7.32–9.74%, 9th: 9.97–13.76%, 10th: ≥14.16%. The predicted event rate for each baseline FRE decile was the mean FRE within that decile. The observed rate was the actual cumulative event rate at 10-years within each decile. Using the higher cohort-specific average event rate and the cohort-specific offset for mean cohort risk characteristics (G-statistic), a recalibrated Framingham score was calculated. The nodes on the solid line represent the mean recalibrated Framingham risk score for each decile.