Diagnostic value of mirna 208a and pregnancy associated plasma protein A (papp a) in relation to n terminal pro b type natriuretic peptide (nt probnp) for early detection of heart failure with preserved ejection fraction

Abstract

Objective: Heart failure with preserved ejection fraction (HFpEF) remains diagnostically challenging owing to non‑specific symptoms and limitations of conventional biomarkers. This study evaluated the diagnostic value of pregnancy‑associated plasma protein‑A (PAPP‑A) and microRNA‑208a (miRNA‑208a), alone and in combination with N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP), for early detection of HFpEF.

Methods: A case‑control study enrolled 119 patients with confirmed HFpEF (left ventricular ejection fraction ≥50%) and 120 age‑ and sex‑matched healthy controls. Serum PAPP‑A (ELISA), plasma miRNA‑208a (real‑time PCR), and NT‑proBNP (chemiluminescence immunoassay)were measured. Clinical and metabolic parameters were also recorded. Group comparisons, correlation analyses, receiver operating characteristic (ROC) curves, and multiple linear regression were performed.

Results: All three biomarkers were significantly elevated in HFpEF patients compared with controls (p<0.001). miRNA‑208a showed an 11‑fold increase (61.26±11.06 vs 5.53±2.62), PAPP‑A a 7‑fold increase (48.63±12.32 vs 7.12±5.71 ng/mL), and NT‑proBNP a 12‑fold increase (618.70±247.93 vs 50.85±21.19 pg/mL). Strong positive correlations with NT‑proBNP were observed for miRNA‑208a (ρ=0.775 overall; ρ=0.708 within HFpEF) and PAPP‑A (ρ=0.809 overall; ρ=0.445 within HFpEF). ROC analysis demonstrated excellent diagnostic accuracy (area under the curve >0.95 for all), with optimal cut‑off values: PAPP‑A ≥31.0 ng/mL, miRNA‑208a ≥40.0 (relative expression), and NT‑proBNP ≥239.0 pg/mL. In regression analysis, miRNA‑208a and body mass index were the strongest independent predictors of NT‑proBNP.

Conclusions: Circulating miRNA‑208a and PAPP‑A are significantly elevated in HFpEF and correlate strongly with NT‑proBNP.A multi‑biomarker panel including these markers may improve early identification of HFpEF, particularly in resource‑limited settings where advanced imaging is unavailable.