Abstract 12358: Abnormal Left Ventricular Midwall Fractional Shortening and Elevated Circulating Biomarkers Predict High Mortality in Elderly Individuals in the General Population

Abstract

Background: Individuals in the general population with a minimal elevation of cardiac biomarkers and left ventricular hypertrophy are at high cardiovascular risk and may be candidate for early strategies of prevention and treatment. We investigated the combination of several circulating biomarkers with abnormal midwall fractional shortening (MFS), an early echocardiographic indicator of preclinical systolic dysfunction, with adverse outcomes. Methods: Circulating levels of N-terminal probrain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT), and intercellular adhesion molecule-1 (ICAM-1) were measured in 550 elderly community-dwelling individuals (65-84 years) from the PREDICTOR study. Participants were referred to cardiology centers for clinical examination and Doppler echocardiography with centrally-measured MFS. Causes of death or hospitalization were available after a median follow-up of 46 [39-54] months from record-linkage of administrative data. Results: Individuals with LV midwall dysfunction (MFS<15%, n= 204 (38%)) had higher levels of NT-proBNP (148 [57-311] ng/L), hs-cTnT (7.3 [3.9-11.6] ng/L)and ICAM-1 (211 [177-261] ng/mL) than those with normal function (82 [42-171] and 5.0 [3.0-8.3] ng/L, 193 [165-230], respectively, p<0.001). The cumulative incidence of total mortality (n=36) among individuals with abnormal MFS and elevated NT-proBNP (>75th age- and sex-specific percentile) was 14% vs. 2% (abnormal MFS, low NT-proBNP), 6% (normal MFS, high NT-proBNP) and 1% (normal MFS, low NT-proBNP). Corresponding values for hs-cTnT (> 3ng/L) were 14, 0, 5 and 3% (p<0.0001) and 15, 5, 7 and 2% for ICAM-1 above median concentration (all p<0.0001). After adjustment for sex, age, eGFR and hypertension, subjects with abnormal MFS and an elevated biomarker had a higher risk of total mortality compared to those with normal MFS and low biomarker: HR = 11.4 [1.5-87.7] (p=0.02) for NT-proBNP and 7.4 [2.1-25.6] (p=0.002) for ICAM-1, but not for hs-cTnT. Similar trends were seen for GDF-15. Conclusions: Elevation of circulating biomarkers combined with early alterations in LV systolic function with MFS identifies a subgroup of individuals in the general population aged 65 or more at higher risk for mortality.