Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden

Abstract

Background: This nationwide study sought to determine age- and gender-specific familial risks in siblings hospitalized for venous thromboembolism (VTE).

Methods and results: The Swedish Multigeneration Register on 0- to 75-year-old subjects was linked to the Hospital Discharge Register for the years 1987-2007. Standardized incidence ratios were calculated for individuals whose siblings were hospitalized for VTE compared with those whose siblings were not affected. Among a total of 45 362 hospitalized cases with VTE, 2393 affected siblings were identified, with a familial standardized incidence ratio of 2.45 (95% confidence interval [CI], 1.66 to 3.61). Gender-specific differences in incidence rates were observed. The familial risks were significantly increased from the age of 10 to 69 years, with a familial standardized incidence ratio of 4.77 (95% CI, 1.96 to 10.83) at ages 10 to 19 years, which decreased to 2.08 (95% CI, 1.35 to 3.20) at ages 60 to 69 years, although the absolute risk increased with age. The familial standardized incidence ratios for siblings with 2 and ≥3 affected probands were 51.87 (95% CI, 31.47 to 85.00) and 53.69 (95% CI, 25.59 to 108.50), respectively. Spouses had low familial risks (standardized incidence ratio=1.07; 95% CI, 1.04 to 1.10; observed spouse cases=3900).

Conclusions: Familial factors, although influenced by age and gender, are important risk factors for VTE. The present study shows that VTE is aggregated in families and suggests that uncovering the sources of familial aggregation (genetic and nongenetic) may be worthwhile. Moreover, in a small fraction of siblings, the familial risk was very high, suggesting segregation of rare but strong genetic risk factors.