SUN-121 ASSOCIATION BETWEEN A NOVEL BIOMARKER, SERUM MIDKINE, AND ASYMPTOMATIC AND CLINICAL CARDIOVASCULAR DISEASE IN ELDERLY WOMEN

Abstract

Elevated Midkine (MK) levels have been associated with acute cardiac events in patients with chronic heart failure. However its prognostic value in predicting subclinical and clinical outcomes of CVD in the elderly general population remains unknown. This study aims to determine the relationship between serum MK and asymptomatic measures and clinical outcomes of CVD in a large cohort of elderly women with long-term clinical follow-up. This was a prospective study of ageing women. Serum MK was measured in 1998 (baseline). The univariate association between baseline serum MK with baseline abdominal aortic calcification (AAC) 24 scores was analysed using Spearman’s correlation. Differences in baseline AAC24 scores, change in AAC24 scores at 5 years, and common carotid artery intimal medial thickness (CCA-IMT) at 3 years between medians of serum MK were assessed using analysis of covariance, adjusting for age, body mass index (BMI), baseline estimated glomerular filtration rate (eGFR), smoking history, diabetes, use of blood pressure lowering medications, use of statins, calcium treatment code and prevalent atherosclerotic vascular disease (ASVD). Associations between baseline serum MK and the occurrence of atherosclerotic plaques at 3 years, and atherosclerotic vascular disease (ASVD)-related hospitalisations and deaths at 14.5 years as a composite outcome were examined using logistic and Cox regression analyses respectively, adjusting for similar risk factors. The baseline cohort consisted of women aged over 70 years, with a median age of 75. Throughout the follow-up period of 15 years, there were a total of 206 deaths, and 225 ASVD-related hospitalisations and deaths. Baseline serum MK was correlated with baseline AAC24 scores in the univariate analysis (r = 0.111, p = 0.035). Baseline AAC24 scores were not significantly different between below and above-median baseline serum MK (below-median: 3.15 ± 0.26 vs above-median: 3.30 ± 0.27, p = 0.684), however the increase in AAC24 scores at 5 years was significantly higher in participants with above-median baseline serum MK as compared to those with below-median baseline serum MK (below median: 0.90 ± 0.18 vs above-median 1.64 ± 0.20, p = 0.007) after multivariable-adjustment. At 3 years, mean and maximum CCA-IMT were significantly greater in participants with above-median baseline serum MK as compared to those with below-median baseline serum MK after multivariable adjustment (below median: 0.769 ± 0.011 mm vs above-median: 0.802 ± 0.011 mm, p = 0.035; below-median: 0.910 ± 0.012 mm vs above-median: 0.951 ± 0.013 mm, p = 0.024, respectively), however above-median baseline serum MK was not associated with an increased risk of occurrence of atherosclerotic plaques (odds ratio = 0.99, 95% CI = 0.63-1.55, p = 0.964). Compared to below-median, above-median baseline serum MK was associated with a 1.3-fold increased risk of ASVD-related hospitalisations and deaths at 14.5 years (hazard ratio = 1.37, 95% CI = 1.05, 1.80, p = 0.022) after adjusting for known risk factors. In older women, elevated serum MK is associated with AAC outcomes and asymptomatic measures and clinical outcomes of ASVD. These results suggest that MK could be potential risk factor for CVDs, and further prospective studies are needed to determine the prognostic importance of elevated MK with CVD clinical outcomes.