Assessment of serum caveolin-3 levels in patients with heart failure

Ahmet Süsenbük¹Hakan Kaya²Sabri Abuş^2*Abdulmecit Afşin³

• ¹Abdülkadir Yüksel State Hospital, Gaziantep, Türkiye
• ²Adiyaman University, Adıyaman, Türkiye
• ³Malatya Turgut Özal University, Malatya, Türkiye

Background: Heart failure (HF) is a complex syndrome caused by structural and functional abnormalities that impair ventricular filling and ejection. Caveolin-3 (Cav-3), a muscle-specific membrane protein, is essential for T-tubule formation and maintenance in cardiomyocytes. Although caveolin deficiency leads to severe cardiac phenotypes, Cav-3's specific mechanistic role in chronic HF remains insufficiently defined. Objective: The principal objective of this investigation was to assess serum Cav-3 concentrations in patients diagnosed with chronic HF. Methods: This case-control study encompassed 90 participants, comprising 45 individuals with chronic HF (HF group) and 45 age-and sex-matched healthy controls (non-HF group). Blood specimens were obtained from both groups, and Cav-3 concentrations were quantified utilizing the enzyme-linked immunosorbent assay (ELISA) methodology. In addition, all participants underwent comprehensive transthoracic echocardiography (TTE). Both echocardiographic and laboratory parameters, including Cav-3 levels, were systematically compared between the two cohorts. Results: Among 90 participants (45 HF; 45 matched controls), HF patients showed typical adverse remodeling (LVEF 35% [20–50] vs 60% [55–65], p<0.001) and higher inflammatory/coagulation activity. Median serum Cav-3 was higher in HF than controls (4.83 [4.34–5.60] vs 3.97 [3.30–4.96] ng/L; p<0.001). On ROC analysis, NT-proBNP provided the strongest single-marker discrimination (AUC 0.850; cutoff 254.50 pg/mL; sensitivity 79.5%; specificity 80.0%), Cav-3 alone showed moderate accuracy (AUC 0.705; cutoff 4.36 ng/L; sensitivity 75.0%; specificity 73.3%), and the Cav-3 + NT-proBNP combination achieved the highest AUC (0.878; sensitivity 81.8%; specificity 84.4%; p<0.001). In multivariable models predicting EF, WBC, NT-proBNP, and ESR were independent negative predictors, whereas Cav-3 was not significant after adjustment. Cav-3 concentrations were higher in HFrEF and HFmrEF versus controls, with no difference between HF subgroups. Conclusions: Serum Cav-3 is elevated in chronic HF and enhances diagnostic discrimination when added to NT-proBNP, but does not independently predict EF after adjustment. These findings support Cav-3 as an adjunctive—rather than stand-alone—biomarker within a multimarker strategy. Prospective multicenter studies should validate reproducibility, define clinically actionable thresholds, and quantify incremental value over natriuretic peptide–based and multimarker baselines.