Proenkephalin: A useful biomarker for new-onset heart failure?

An analysis of the PREVEND cohort found an association between high concentrations of proenkephalin and a higher likelihood of new-onset heart failure (HF). However, this association was mainly driven by glomerular filtration rate.

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.

1. 
   
   1. Bozkurt B. Circ Heart Fail 2019;12:e005851.
   2. 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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Posted on 19 August, 202120 August, 2021