Key result
Serum soluble neprilysin levels >76.0 pg/ml were not significantly associated with long-term all-cause mortality compared to levels ≤76.0 pg/ml in patients with coronary artery disease undergoing PCI (HR 1.558).
Why the study?
Neprilysin regulates fluid balance and vascular resistance, but the predictive value of neprilysin levels as a biomarker for cardiovascular risk remains unclear.
Does a higher soluble neprilysin level predict all-cause mortality or cardiovascular events in patients with coronary artery disease undergoing percutaneous coronary intervention?
Cohort (n=694)
Does a higher soluble neprilysin level predict all-cause mortality or cardiovascular events in patients with coronary artery disease undergoing percutaneous coronary intervention?
Hazard Ratio: 1.558 (95% CI 0.848–2.863)
Absolute Event Rate: 8.1% vs 5.7%
p-value: p=0.153
Serum soluble neprilysin levels do not predict long-term mortality in the general CAD population undergoing PCI, but may serve as a prognostic biomarker for increased mortality in the subgroup with reduced LVEF (<40%).
sNEP levels lack prognostic value post-PCI in CAD overall; leaves open hypothesis-generating mortality link in LVEF <40% subgroup.
BACKGROUND: Neprilysin has an essential role in regulating fluid balance and vascular resistance, and neprilysin inhibitors have shown beneficial effects in patients with heart failure. However, the potential predictive value of neprilysin levels as a biomarker for cardiovascular risk remains unclear. The aim of this study was to assess the prognostic value of soluble neprilysin (sNEP) levels in patients with ischemic heart disease. METHODS: Neprilysin levels were measured in 694 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). These patients were classified into two groups according to their serum levels of neprilysin and categorized into the lower neprilysin group (n = 348) and the higher neprilysin group (n = 346). The primary clinical endpoint was all-cause mortality, and the secondary endpoint was a composite of major adverse cardiac events (MACE). RESULTS: The median sNEP level was 76.0 pg/ml. The median sNEP levels were higher in patients with left ventricular ejection fraction (LVEF) ≥40% (77.6 pg/ml, interquartile range 46.6-141.3) than in those with LVEF < 40% (70.0 pg/ml, interquartile range 47.1-100.6; P = 0.032). Among all patients, each clinical outcome and MACE did not differ significantly according to the groups divided into median, tertile, or quartile of sNEP levels during a median follow-up of 28.4 months. We did not find a significant relationship between sNEP levels and clinical outcomes in multivariate Cox regression analysis. Among patients with LVEF < 40%, an increased sNEP level was associated with a higher rate of all-cause death (adjusted hazard ratio 2.630, 95% confidence interval 1.049-6.595, P = 0.039). CONCLUSION: Serum sNEP levels are not associated with long-term mortality or cardiovascular outcomes after PCI in patients with CAD. In the LVEF < 40% group, increased sNEP levels may be associated with a higher risk of all-cause death.
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Choi et al. (2020) conducted a cohort in Coronary artery disease (n=694). Higher soluble neprilysin (sNEP) levels (> 76.0 pg/ml) vs. Lower soluble neprilysin (sNEP) levels (≤ 76.0 pg/ml) was evaluated on All-cause mortality (HR 1.558, 95% CI 0.848-2.863, p=0.153). Serum soluble neprilysin levels >76.0 pg/ml were not significantly associated with long-term all-cause mortality compared to levels ≤76.0 pg/ml in patients with coronary artery disease undergoing PCI (HR 1.558).
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