Dataset Information

Proenkephalin and the risk of new-onset heart failure: data from prevention of renal and vascular end-stage disease.

ABSTRACT:

Background

Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new-onset HF in the general population remains to be established.

Hypothesis

We hypothesized that plasma PENK concentrations are associated with new-onset HF in the general population.

Methods

We included 6677 participants from the prevention of renal and vascular end-stage disease study and investigated determinants of PENK concentrations and their association with new-onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]).

Results

Median PENK concentrations were 52.7 (45.1-61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT-proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8-8.8) years follow-up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2-67.6) versus 52.7 (45.1-61.6) pmol/L, respectively (p = .003). In competing-risk analyses, higher PENK concentrations were associated with higher risk of new-onset HF (hazard ratio [HR] = 2.09[1.47-2.97], p < .001), including both HFrEF (HR = 2.31[1.48-3.61], p < .001) and HFpEF (HR = 1.74[1.02-2.96], p = .042). These associations were, however, lost after adjustment for eGFR.

Conclusions

In the general population, higher PENK concentrations were associated with lower eGFR and higher NT-proBNP concentrations. Higher PENK concentrations were not independently associated with new-onset HFrEF and HFpEF and mainly confounded by eGFR.

SUBMITTER: Emmens JE

PROVIDER: S-EPMC8715404 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Proenkephalin and the risk of new-onset heart failure: data from prevention of renal and vascular end-stage disease.

Emmens Johanna E JE Ter Maaten Jozine M JM Brouwers Frank P FP Kieneker Lyanne M LM Damman Kevin K Hartmann Oliver O Schulte Janin J Bakker Stephan J L SJL de Boer Rudolf A RA Voors Adriaan A AA

Clinical cardiology 20211030 12

<h4>Background</h4>Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new-onset HF in the general population remains to be established.<h4>Hypothesis</h4>We hypothesized that plasma PENK concentrations are associated with new-onset HF in the ...[more]

PMID: 34716603

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Project description:AimsSacubitril/valsartan (SV) reduced heart failure hospitalization and cardiovascular mortality compared with enalapril in the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure trial. However, this trial excluded patients with end stage of renal disease (ESRD); thus, the efficacy and safety of SV in heart failure with reduced ejection fraction (HFrEF) with ESRD remains uncertain.Methods and resultsWe retrospectively analysed the clinical and laboratory data of 501 HFrEF patients who administered with SV from March 2017 to April 2019 in a single tertiary university hospital. A total of 23 HFrEF patients with ESRD on dialysis [58.3% non-ischaemic heart failure; left ventricular ejection fraction (LVEF): 29.7 ± 4.4%] were included in this study. At baseline and follow-up visit, we evaluated cardiovascular biomarkers such as high-sensitive troponin T (hsTnT), soluble ST2 (sST2), echocardiographic parameters, and clinical and adverse events. The mean dose of SV was 90 ± 43 mg/day at baseline and 123 ± 62 mg/day at last follow-up (follow-up duration: median 132 days). The level of hsTnT was significantly reduced from 236.2 ± 355.3 to 97.0 ± 14.0 pg/mL (P = 0.002), and the sST2 level was significantly reduced from 40.4 ± 44.0 to 19.6 ± 14.1 ng/mL (P = 0.005). LVEF was significantly improved from 29.7 ± 4.4% to 40.8 ± 10.4% (P = 0.002). During the follow-up, up-titration, down-titration, and maintenance of SV dosing were observed in 7 (30%), 5 (21.7%), and 11 patients (47.8%), respectively. SV down-titration group had adverse events including symptomatic hypotension (systolic blood pressure <100 mmHg) (n = 4) and dizziness (n = 1), but they did not discontinue SV therapy.ConclusionsWe found that SV could safely reduce the hsTnT and sST2 levels and improve LVEF in HFrEF patients with ESRD. As far as we know, this is the first study to show the efficacy and safety of SV in HFrEF with ESRD on dialysis. Larger prospective, long-term follow-up study should be warranted.

Dataset Information

Proenkephalin and the risk of new-onset heart failure: data from prevention of renal and vascular end-stage disease.

Background

Hypothesis

Methods

Results

Conclusions

Publications

Proenkephalin and the risk of new-onset heart failure: data from prevention of renal and vascular end-stage disease.

Similar Datasets

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