Prognostic Value of Asymmetric Dimethylarginine in Patients with Heart Failure: A Systematic Review and Meta‐analysis

Objective . Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, is reported to be a risk factor for cardiovascular disease. The purpose of the present study is to investigate whether ADMA is an independent predictor for future mortality and adverse clinical events among patients with heart failure (HF). Methods . Electronic literature databases (Central, MEDLINE, and Embase) were searched for relevant observational studies on the prognostic value of ADMA in HF patients published before January 2019. Pooled hazard ratios (HRs) or odds ratio and the corresponding 95% confidence interval (CI) were calculated for risk evaluation. Results . 10 studies with 2195 participants were identified and analyzed. The pooled HR of composite clinical events for the highest vs. lowest quartiles from categorical variable results was 1.34 (95% CI: 1.15‐1.57, P < 0.001, I 2 = 0%), which is 1.31 (95% CI: 1.10‐1.55, P < 0.005, I 2 = 0%) in the subgroup of acute decompensated HF. The pooled HR of composite clinical events from continuous variable results was 1.41 (95% CI: 1.21‐1.63, P < 0.001, I 2 = 21.9%), with 0.1 μ M increment accounting for the increasing 25% risk for composite adverse clinical events. The pooled HR for all‐cause mortality was 2.38 (95% CI: 1.48‐3.82, P < 0.001, I 2 = 0%) after sensitivity analysis. Two studies reporting the HR of inhospital mortality in HF patients regarded it as a prognostic indicator, with categorical variable HR as 1.26 (95% CI: 1.07‐1.84, P < 0.05) and continuous variable OR as 2.15 (95% CI: 1.17–4.29, P < 0.05). Conclusions . ADMA is an independent predictor for composite clinical outcomes among HF patients with both short‐term and long‐term prognostic value.