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AimsGrowth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans.Methods and resultsWe measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart failure hospitalization, stroke, myocardial infarction, death, and their composite endpoint. Left ventricular hypertrophy was evaluated by echocardiography. We used multivariable Cox proportional hazards models to compare rates of cardiovascular events and death across GDF11/8 quartiles and logistic regression models to evaluate the association between GDF11/8 and LVH. Four hundred and fifty participants (48.5%) experienced a cardiovascular event or death during 8.9 years of follow-up. The adjusted risk of the composite endpoint was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3 cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular hypertrophy was present in 368 participants (39.7%) at baseline. Participants in the highest quartile of GDF11/8 were less likely to have LVH than those in the lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels were lower in older individuals (P < 0.001).ConclusionIn patients with stable ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of cardiovascular events and death. Our findings suggest that GDF11/8 has similar cardioprotective properties in humans to those demonstrated in mice.

Background While changes in the left ventricular end-diastolic pressure-volume relationship ( LV- EDPVR) can be estimated using echocardiography, their prognostic utility in stable coronary artery disease ( CAD) is unknown. Methods Using echo-estimated LV end-diastolic volume index and diastolic function category, the relative position of the LV- EDPVR was defined in 901 participants with stable CAD as: (1) left-shifted, (2) right-shifted, or (3) intermediate. We then evaluated the association of LV- EDPVR position relative to the intermediate category with time to hospitalization for heart failure ( HF) or cardiovascular ( CV) death using Cox proportional hazards models. Results During 7.0 ± 3.1 years of follow-up, there were 207 admissions for HF or CV deaths. Both leftward and rightward shifts of LV- EDPVR were associated with a significantly higher risk of HF or CV death ( HR 1.73, 95% CI 1.15-2.62 and HR 6.75, 95% CI 4.02-11.31, respectively). In multivariable-adjusted models, these associations were attenuated but remained significant ( HR 1.66, 95% CI 1.08-2.55 for left-shifted and HR 4.19, 95% CI 2.32-7.55 for right-shifted). The association of LV- EDPVR with HF or CV death was no longer significant after inclusion of N-terminal pro-brain natriuretic peptide level as a covariate. Conclusions In stable CAD, echo-estimated leftward and rightward shifts in the LV- EDPVR are associated with HF and CV death. The loss of these associations after adjustment for N-terminal pro-brain natriuretic peptide level suggests that echo-estimated LV- EDPVR captures changes in LV filling pressure at any given LV end-diastolic volume. [ABSTRACT FROM AUTHOR]

Introduction: C-reactive protein (CRP) level stratifies risk for events in coronary heart disease (CHD) and is independently associated with increased risk of heart failure (HF). It is unknown how CHD-associated risk of stroke, HF, and all-cause mortality is affected by CRP and if it is modifiable. Hypothesis: The risk associated with elevated CRP in patients with CHD can be modified by beta blocker and statin use. Methods: A cohort of outpatients with CHD from the Heart and Soul Study (N = 985) had serum CRP measured. Outcomes after 7.1 years ± 3.2 years including non-fatal MI, HF, stroke, cardiovascular death, and all-cause mortality were analyzed and modifying factors were compared using Kaplan Meier estimates. Results: Elevated CRP level > 3mg/L (CRPH) was associated with an increased risk of stroke (hazard ratio (HR) 2.4, p = 0.01), HF (HR 1.9, p = 0.001), and all-cause mortality (HR 1.4, p = 0.005), compared to low CRP level < 3mg/L (CRPL). CRPH patients not taking a statin had more HF events (HR 2.9, p = 0.001) and increased risk of all-cause mortality (HR 1.5, p = 0.045) compared to CRPL patients not taking a statin. CRPH patients not taking a beta blocker had more HF events (HR 2.5, p = 0.001) and increased risk of all-cause mortality (HR 1.7, p = 0.003) compared to CRPL patients not taking a beta-blocker. CRPH patients on neither beta blocker nor statin had more HF events (HR 2.7, p = 0.002) and increased risk of all-cause mortality (HR 2.0, p = 0.004) compared to CRPH patients on both medications. CRPL patients on both beta blocker and statin had reduced risk of all-cause mortality (HR 0.6, p = 0.04) compared to CRPL patients on neither medication. Conclusions: Among outpatients with CHD, CRPH is associated with an increased risk of adverse CHD outcomes including stroke, HF, and all-cause mortality. The risk of HF and all-cause mortality is considerable but modified by beta blockers and statins. Among those with CRPL, the use of beta blockers and statin reduces risk of all-cause mortality. [ABSTRACT FROM AUTHOR]