ELEVATED GROWTH AND DIFFERENTIATION FACTOR 15 (GDF-15) LEVELS AMPLIFIES THE ASSOCIATION BETWEEN HOME BLOOD PRESSURE VARIABILITY AND CARDIOVASCULAR OUTCOME

Abstract

Objective: Growth and differentiation factor 15 (GDF-15) is a marker of cell senescence. Although age is strongly determinant of GDF-15 level, several studies suggest that GDF-15 reflects biological age rather than chronological age. Since age is also associated with increased blood pressure variability, we hypothesized that the association between day-by-day home blood pressure variability (HBPV) and cardiovascular outcome may be steeper in patients with elevated GDF-15. Design and method: We analyzed 4030 patients from a practitioner-based population (mean±SD age 64.9±10.9 years: 79.0% taking antihypertensive medication) with at least one cardiovascular risk factor who underwent home blood pressure monitoring in the Japan Morning Surge-Home Blood Pressure Study. The standard deviation was assessed as indexes of day-by-day home systolic blood pressure variability. We divided patients into elevated (1200 ng/L or more) and non-elevated GDF-15 (less than 1200 ng/L) groups. Results: During a mean follow-up of 6.2 years, 247 cardiovascular events occurred. Participants with the highest HBPV tertile without elevated GDF-15 (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.03-2.23) or those with elevated GDF-15 without the highest BPV tertile (HR, 1.52; 95%CI, 1.03-2.16) had approximately 1.5-fold higher risk of cardiovascular events compared with those with low HBPV without elevated GDF-15. Adjusted risk of cardiovascular events was approximately 2.3-fold higher among participants with elevated GDF-15 and the highest HBPV tertile, compared with those with low HBPV without elevated GDF-15 (HR, 2.34; 95%CI, 1.58-3.45). Conclusions: We conclude that elevated GDF-15 contributes to the association between home BP variability and cardiovascular events.