Abstract 9935: Association of Hypertension and Growth Differentiation Factor 15 With Incident Coronary Heart Disease: The Kuakini Honolulu Heart Program

Abstract

Introduction: Hypertension is a pathophysiological stress. Growth differentiation factor 15 (GDF15) is a stress-response protein, and a predictor for heart disease. The effects of the longevity genotype of FOXO3, a stress-response and prominent longevity-associated gene, on mortality vary in normotensive and hypertensive men. Hypothesis: The effect of GDF15 concentration on the risk of incident coronary heart disease (CHD) is different in men with different hypertension status. Methods: The Kuakini Honolulu Heart Program (KHHP) is a longitudinal study of cardiovascular diseases that started in 1965 involving 8,006 Japanese-American men in Hawaii. Proteomic analyses were performed using serum from KHHP exam 4 (1991-1993, ages 71-93) in a random sample (n=1,000) of men who in mid-life had been free of chronic diseases such as CHD, stroke, cancer, and diabetes. Participants were followed for incident CHD event (first event of MI, coronary insufficiency, angina, CABG, angioplasty, silent MI and CHD death) through December 1999. The Cox proportional hazards model was used to assess potential association of GDF15 concentration and hypertension (SBP/DBP≥160/95 mmHg or on anti-hypertensives) with incident CHD. Results: We excluded 5 men missing GDF15 data and 221 men with diseases including CHD, CHF, atrial fibrillation, LVH and stroke at baseline (KHHP exam 4). During 9 years of follow-up (median 7.92 years), 60 men developed CHD. To eliminate the possible recursive-effect of preclinical CHD on GDF15 at baseline, 6 CHD cases diagnosed within the first year of follow-up were excluded. So, there were 768 men available for analysis. Participants were divided, using tertiles of GDF15 concentration, into two groups: low-medium GDF15 (in low or middle tertile) and high GDF15 (in upper tertile). Multivariate Cox model adjusting for age, BMI, smoking (pack-years), cholesterol, HDL, diabetes and serum glucose showed a significant interaction effect of hypertension and high GDF15 on incident CHD (p=0.019); HR (95%CI) of high GDF15 vs low-medium GDF15 on CHD was 4.56 (1.51-13.76; p=0.007) in normotensive men, and 0.97 (0.49-1.92; p=0.93) in hypertensive men. Conclusions: High GDF15 concentration increases CHD risk in normotensive men, but not in hypertensive men.