Shared and non-shared familial susceptibility of coronary heart disease, ischemic stroke, peripheral artery disease and aortic disease.

BACKGROUND: Little is known about whether the four main manifestations of arterial vascular disease (coronary heart disease=CHD, ischemic stroke, peripheral artery disease=PAD, and aortic (i.e. atherosclerosis/aneurysm) disease=AD) share familial susceptibility. The aim of this nationwide study was to determine the familial risks of concordant (same disease in proband and exposed relative) and discordant (different disease in proband and exposed relative) cardiovascular disease (CVD). METHODS: Data from the Swedish Multigeneration Register on individuals aged 0-76years were linked to Swedish Hospital Discharge Register data for the period 1964-2008. Standardized incidence ratios (SIRs) for CHD (n=140,708 cases), ischemic stroke (n=73,771), PAD (n=18,982) and AD (n=7879) were calculated for siblings of individuals hospitalized due to CHD, stroke, PAD or AD compared to those of unaffected siblings. The procedure was repeated for parent-offspring and spouses. RESULTS: All concordant and discordant sibling risks were increased for both males and females. Concordant risks were generally higher than discordant risks. The highest sibling risks were observed for premature concordant disease (<55years for males and <65years for females): SIR for CHD=1.93 (95% CI: 1.90-1.96), SIR for ischemic stroke=1.45 (1.39-1.50), SIR for PAD=2.76 (2.54-3.00), and SIR for AD=6.36 (5.28-7.59). Premature parent-offspring transmission followed the same pattern. The disease risk was modestly increased in spouses, highest for AD (SIR=1.48 (1.28-1.69)) and PAD (SIR=1.27 (1.21-1.32)). CONCLUSIONS: The four main manifestations of CVD share familial susceptibility, but unique site-specific familial factors may exist.