Journal of the American Heart Association
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Background Neprilysin is a transmembrane endopeptidase involved in the breakdown of a variety of vasoactive peptides and serves as a therapeutic target in heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the relationship of circulating neprilysin with neurohumoral activation and the impact of plasma neprilysin activity on prognosis in HFrEF. Methods and Results A total of 369 chronic HFrEF patients were enrolled prospectively. ⋯ Neither circulating neprilysin concentrations nor activity were associated with outcome. Conclusions Plasma neprilysin concentrations and activity are not directly related to neurohumoral activation, indicating that neprilysin regulation is either more complex or not correctly mirrored by circulating neprilysin as a biomarker. Circulating neprilysin concentrations and activity were not associated with overall survival, implicating limited prognostic value of plasma neprilysin measurements in HFrEF patients.
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Background Ankle-brachial indexes (ABI) are a noninvasive diagnostic tool for peripheral arterial disease and a marker of increased cardiovascular risk. ABI is calculated using the highest systolic blood pressure of the 4 ankle arteries (bilateral dorsalis pedis and posterior tibial). Accordingly, patients may be assigned a normal ABI when the result would be abnormal if calculated using one of the other blood pressure readings. ⋯ Patients with discordant ABIs had a greater risk of myocardial infarction (hazard ratio [HR], 1.31; 95% CI, 1.10-1.56), ischemic stroke (HR, 1.53; 95% CI, 1.37-1.72), and all-cause mortality (HR, 1.27; 95% CI, 1.16-1.39), including after adjustment for baseline comorbidities. Conclusions Discordant ABI results were associated with an increased risk of myocardial infarction, stroke, and all-cause mortality in the studied population. Clinicians should examine ABI calculations using all 4 ankle arteries to better characterize a patient's cardiovascular risk.