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Combined NT-proBNP, DLK-1, PSP-D, and PCSK-9 detection shows moderate diagnostic performance for HFpEF.

Combined NT-proBNP, DLK-1, PSP-D, and PCSK-9 detection shows moderate diagnostic performance for HFp…
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Key Takeaway
Consider combined NT-proBNP, DLK-1, PSP-D, and PCSK-9 detection as a potential diagnostic aid for HFpEF with moderate accuracy.

This prospective biomarker study enrolled 58 patients with heart failure with preserved ejection fraction (HFpEF) and 30 healthy controls. The primary objective was to evaluate the diagnostic performance of combined biomarker detection compared to individual markers. Serum levels of DLK-1, PSP-D, and PCSK-9 were observed to be higher in the HFpEF group than in healthy controls. Regression analysis identified NT-proBNP, uric acid (UA), and PCSK-9 as risk factors, with regression coefficients of 0.009, 0.006, and 1.061, respectively.

The study assessed the area under the curve (AUC) for various diagnostic combinations. The combination of NT-proBNP, DLK-1, PSP-D, and PCSK-9 achieved an AUC of 0.794. The combination of PCSK-9 and NT-proBNP alone resulted in an AUC of 0.788. In contrast, the combination of DLK-1, PSP-D, and PCSK-9 yielded an AUC of 0.622. Individual marker performance varied, with NT-proBNP alone showing an AUC of 0.778, while DLK-1, PSP-D, and PCSK-9 alone showed AUCs of 0.578, 0.523, and 0.628, respectively.

No adverse events, serious adverse events, discontinuations, or tolerability issues were reported. The study authors note that combined detection of these markers may enhance diagnostic specificity and sensitivity for HFpEF. However, the findings are derived from a small cohort without a control group for clinical outcomes or long-term follow-up. Consequently, these results should be interpreted as preliminary evidence regarding diagnostic utility rather than established clinical practice.

Study Details

Study typeCohort
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
BackgroundHeart failure with preserved ejection fraction (HFpEF) remains a formidable clinical challenge due to its intricate pathophysiology and the difficulty in early diagnosis. Traditional biomarkers for HFpEF are often insufficient in clinical practice, driving the need for more novel, sensitive diagnostic markers.MethodsSerum samples from 58 HFpEF patients and 30 healthy controls were analyzed using Olink proteomics technology. Advanced machine-learning algorithms were employed to comprehensively compare the diagnostic performance of individual biomarkers and their combinations.ResultsThe serum levels of DLK-1, PSP-D, and PCSK-9 in HFpEF patients were higher than those in the control group. NT-proBNP, UA and PCSK-9 were identified as risk factors for HFpEF, with regression coefficients of 0.009 for NT-proBNP, 0.006 for UA, and 1.061 for PCSK-9 respectively. The area under the receiver operating characteristic curve (AUC) of the combination of NT-proBNP, DLK-1, PSP-D and PCSK-9 for the diagnosis of HFpEF reached 0.794. This value outperformed the AUC of the combination of PCSK-9 and NT-proBNP, 0.788, the combination of three markers (DLK-1, PSP-D, and PCSK-9, 0.622), as well as the AUCs of each of the four markers alone (NT-proBNP: 0.778, DLK-1: 0.578, PSP-D: 0.523, PCSK-9: 0.628).ConclusionThe combined detection of NT-proBNP, DLK-1, PSP-D and PCSK-9 can significantly enhance the specificity and sensitivity of the clinical diagnosis of HFpEF patients, holding great potential for improving the diagnostic accuracy of HFpEF in clinical settings.
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