Abstract P268: Plasma Levels of sIL-2Ra Relate to Cardiovascular Disease and All-cause Mortality in the Elderly: Results from the Cardiovascular Heart Study
Activated lymphocytes are known to play an important role in atherosclerosis. Interleukin-2 (IL-2) is produced by activated T lymphocytes and induces further lymphocyte activation through its interaction with the IL-2 receptor (IL-2R). The IL-2R consists of three subunits (IL-2Rα, IL-2Rβ, and IL-2Rγc). We measured the soluble form of IL-2Rα (sIL-2Rα), generated by IL-2 binding and therefore a biomarker of T lymphocyte activation, in order to explore the hypothesis that a measure of lymphocyte activation is associated with cardiovascular disease (CVD). We measured baseline levels of sIL-2Rα in 3680 European-American (EA) and 683 African-American (AA) adults 65 years and older from the Cardiovascular Health Study. Participants have been followed for clinical CVD and mortality outcomes up to 20 years. At baseline, mean sIL-2Rα levels were 1146.4 pg/mL (standard deviation (SD)=507.5 pg/mL) and 1101.6 pg/mL (SD=556.4 pg/mL) in European-American men and women, respectively; and 873.1 pg/mL (SD=505.5 pg/mL) and 910.9 pg/mL (SD=581.2 pg/mL) in African-American men and women, respectively. sIL-2Rα levels correlated with several CVC risk factors: age, smoking status, hypertension, C-reactive protein, interleukin-6, fibrinogen, and carotid wall thickness (all p<0.0001) at baseline. In a multivariable survival model adjusted for age, sex, and race, a one standard deviation increase in sIL-2Rα (SD=544.5 pg/mL)was associated with all cause mortality (hazard ratio (HR)=1.26; 95% confidence interval (CI)=1.22-1.30), coronary heart disease(CHD) (HR=1.15; CI=1.09-1.21), and congestive heart failure (CHF) (HR=1.30; CI=1.22-1.36). When models were additionally adjusted for CVD risk factors and baseline CVD status, carotid IMT, and ankle-brachial index, sIL-2Rα remained statistically significantly associated with all cause mortality(HR 1.11; CI=1.07-1.16), CHD (HR 1.11; CI=1.05-1.18) and CHF (HR 1.15; CI=1.08-1.21). Using data from the Candidate Gene Association Resource (CARe) Study generated by the ITMAT-Broad-CARe (IBC) chip ( ~49,000 SNPs in 2,100 genes), we investigated genetic loci associated with sIL-2Rα. In European Americans, there was significant IBC-wide association (p<2.2E-6) for SNPs in the IL2Rα gene (rs12722515; p=3.3E-53) and the HLA-B associated transcript 1 gene (BAT1), located in the HLA region on chromosome 6 (rs2734583; p=1.3E-7). No associations were identified in African Americans. In conclusion, we have shown that sIL-2Rα levels, a surrogate marker of T lymphocyte activation, are associated with risk of all cause mortality, incident CVD and CHF in older adults. In addition, we identified IL2Rα and BAT1 as genes associated with sIL-2Rα levels in European Americans.
- © 2013 by American Heart Association, Inc.