Relation Between Serum Thrombospondin-2 and Cardiovascular Mortality in Older Men Screened for Abdominal Aortic Aneurysm

Thrombospondin-1 and -2 (TSP-1 and -2) have been implicated in the regulation of angiogenesis, thrombosis, and inflammation, which are believed to be critical in the pathogenesis of cardiovascular events. The aim of this study was to assess whether serum TSP-1 and TSP-2 concentrations were associated with cardiovascular mortality in older men. A cohort of 992 elderly men was recruited between 2001 and 2004, and blood was collected for assessment of serum TSP-1 and TSP-2 by immunoassay. The men were followed by means of the Western Australia Data Linkage System until July 31, 2009. The association of TSP-1 and TSP-2 with mortality was assessed using Kaplan-Meier estimates and Cox proportional hazard analysis. Serum TSP-2 quartile was strongly positively associated with all-cause and cardiovascular mortality. Men with serum TSP-2 in the first, second, third, and fourth quartiles had a cumulative incidence of cardiovascular mortality of 3.3%, 8.0%, 9.7%, and 12.5% at 5 years, respectively, p = 0.001. Men with serum TSP-2 in the highest quartile had a 3.37-fold (95% confidence interval: 1.53-7.44, p = 0.003) increased risk of cardiovascular mortality after adjusting for other cardiovascular risk factors. Most deaths were secondary to cardiac causes, and serum TSP-2 was also independently associated with cardiac mortality (relative risk: 3.55, 95% confidence interval: 1.54-8.20 for men in the top compared with the lowest quartile). Serum TSP-1 was not associated with cardiovascular mortality. In conclusion, increased serum TSP-2 concentration is independently and significantly associated with the risk of cardiac mortality in older men.