Multiplex sibling history of coronary heart disease is a strong risk factor for coronary heart disease.

AIMS Familial risks for coronary heart disease (CHD) in families with multiple affected siblings have not been thoroughly studied. This nationwide cohort study aimed to determine familial risks for hospitalization or death due to CHD in families with multiple affected siblings. METHODS AND RESULTS The study is a nationwide follow-up study. The Swedish Multigeneration Register data on 0-76-year-old subjects were linked to Hospital Discharge Register and Cause of Death Register data for 1964-2008. Standardized incidence ratios (SIRs) were calculated for individuals whose siblings were hospitalized or died (without previous hospitalization, i.e., primary fatal cases) due to CHD compared with those whose siblings were not affected. The procedure was repeated for spouses. Among a total of 185 810 cases of hospitalization or death due to CHD, the SIRs for hospitalization and death in the siblings of affected probands were 1.82 (95% CI: 1.27-2.60) and 1.60 (95% CI: 1.10-2.36), respectively. The SIRs for hospitalization in siblings of two and three affected probands were 6.92 (95% CI: 4.77-10.03) and 7.88 (95% CI: 5.31-11.70), respectively. The SIRs for death in siblings of two and three affected probands were 7.31 (95% CI: 4.76-11.19) and 6.61 (95% CI: 3.91-11.10), respectively. Spouses had low overall familial risks (SIR = 1.05, 95% CI: 1.05-1.06). CONCLUSION Family history of multiple affected siblings increases the CHD risk. Family history is not a binary trait. There are degrees of risk associated with family history with more than one affected sibling.