High Levels of Growth Differentiation Factor 11 Are Associated With Lower Prevalence of Left Ventricular Hypertrophy, Heart Failure and Mortality

Blood levels of growth differentiation factor 11 (GDF11) decline in mice with age, accompanied by development of cardiac hypertrophy. Treatment of old mice to restore GDF11 to youthful levels regresses cardiac hypertrophy (Cell 2013: 153, 828–839). Thus, GDF-11 is a potential therapeutic target for preventing or reversing left ventricular hypertrophy (LVH), but no data are available on GDF-11 in humans.

To determine whether circulating GDF-11 levels are associated with LVH, heart failure, or death in humans, we conducted a prospective cohort study (Heart and Soul cohort) in 885 outpatients with stable coronary heart disease (CHD) recruited from 12 clinics in the San Francisco Bay Area between 9/00 and 12/02. We measured plasma GDF-11 level in baseline blood samples using an aptamer-based proteomic platform (SOMAscanÔ, SomaLogic, Inc.) and assessed LVH by echocardiography. We followed subjects for heart failure (HF) hospitalization and all-cause mortality for an average of 8.9 years.

LVH was present in 40% of our cohort. Both in unadjusted models and after multivariate adjustment, high GDF-11 levels were associated with lower prevalence of LVH. A total of 161 heart failure hospitalizations and 353 deaths occurred during follow-up. High levels of GDF-11 were associated with lower rates of both HF hospitalizations and deaths.

In the Heart and Soul cohort of patients with stable CHD, higher levels of GDF-11 are associated with lower prevalence of LVH and lower rates of heart failure hospitalization and death. These findings are consistent with GDF-11 as a circulating factor that protects against LVH and reduces cardiac risk in humans.