Endogenous opioids such as enkephalins are activated in response to stress, are implicated in pain control, and mediate systemic and organ-specific responses to injury and adaption [1]. In cardiac hypertrophy and failure, the cardiac opioid system is activated. Enkephalins of the opioid system are known to exert several cardiorenal effects. Dr Lisa Emmens (University Medical Center Groningen, the Netherlands) pointed out that proenkephalin is a stable surrogate for enkephalins [2]. It is associated with HF development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. In studies with HF patients, proenkephalin levels were elevated and associated with the severity of HF and adverse clinical outcomes. However, the association between plasma proenkephalin concentrations and new-onset HF in the general population remained unknown. Thus, Dr Emmens and colleagues analysed 6,677 participants from the PREVEND study to evaluate an association of proenkephalin concentrations and new-onset HF, both with reduced and preserved ejection fractions.
Median proenkephalin concentrations were 52.7 pmol/L (IQR 45.1–61.9). Higher proenkephalin concentrations were associated with poorer renal function and higher N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations. “Main determinants of higher concentrations of proenkephalins were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower BMI,” Dr Emmens explained (P<0.001 for all comparisons).
After a median follow-up of 8.3 years, 221 participants developed new-onset heart failure (127 with HFrEF and 94 with HFpEF). Higher proenkephalin concentrations were found in subjects who developed HF compared with those who did not. Patients with higher proenkephalin concentrations had a more than 2-fold elevated relative risk to develop new-onset HF (HR 2.09; P<0.001). An elevated risk was noticed both for HFrEF (HR 2.31; P<0.001) and HFpEF (HR 1.74; P=0.042). These associations were lost after adjustment for GFR. “High proenkephalin concentrations were univariately associated with HF, but this was mainly confounded by a low GFR,” Dr Emmens concluded.
- Bozkurt B. Circ Heart Fail 2019;12:e005851.
- Emmens JE. Proenkephalin and the risk of new-onset heart failure: data from PREVEND. P60182, Heart Failure and World Congress on Acute Heart Failure 2021, 29 June–1 July.
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Table of Contents: HFA 2021
Featured articles
Inconclusive results for dapagliflozin treatment in heart failure
Late-Breaking Trials
Iron substitution improves LVEF in intensively treated CRT patients with iron deficiency
Novel mineralocorticoid receptor antagonist effective irrespective of HF history
Iron substitution in iron-deficient HF patients is highly cost-effective
Omecamtiv mecarbil might be less effective in patients with atrial fibrillation or flutter
Vericiguat effective irrespective of atrial fibrillation status
Baroreflex activation: a novel option to improve heart failure symptoms
Beta-blocker withdrawal to enhance exercise capacity in heart failure?
Inconclusive results for dapagliflozin treatment in heart failure
Computerised cognitive training improves cognitive function in HF patients
COVID-19 and the Heart
COVID-19-related HF: from systemic infection to cardiac inflammation
Myocardial infarction outcomes were significantly affected by the pandemic
TAPSE effective biomarker associated with high-risk of severe COVID-19
COVID-19 in AF patients with HF: no higher mortality but longer hospital stay
Cancer and the Heart
Heart failure patients might be at an increased risk for head and neck cancer
Trastuzumab associated with cardiotoxicity in breast cancer
Heart Failure Prevention and HRQoL in the 21st century
Psychoactive substances put young people at risk of cardiovascular disease
The challenge of improving the quality of life of heart failure patients
SGLT2 Inhibitors in Heart Failure
Empagliflozin linked to lower cardiovascular risk and renal events in real-world study
Efficacy of dapagliflozin and empagliflozin not influenced by diabetes status
Biomarker panel predicts SGLT2 inhibitor response
Best of the Posters
Real-world study suggests sacubitril/valsartan benefits elderly patients with HF
Proenkephalin: A useful biomarker for new-onset heart failure?
Weight loss associated with increased mortality risk in heart failure patients
Echocardiographic parameters linked to dementia diagnosis
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