Background-Aim The ability of high-density lipoprotein (HDL) to remove cholesterol (known as cholesterol efflux efficiency) is crucial in the reverse cholesterol transport pathway and depends on the HDL cholesterol uptake capacity (CUC). CUC represents a novel, faster and simpler assessing HDL functionality that has been suggested as a potential predictor of cardiovascular disease (CVD) risk. Our goal was to explore the correlation between serum CUC and CVD in participants from the Birjand longitudinal aging study (BLAS). Patients-Methods This cohort study involved 128 CVD patients (mean age 68.3 ± 6.8 years, 43.0% females) and 214 non-CVD individuals (mean age 69.5 ± 6.8 years, 52.3% females) from the BLAS. A refined CUC methodology was employed to assess serum HDL CUC. The connections between CUC and CVD, coronary artery disease (CAD), acute myocardial infarction (AMI), and stroke risk was explored. Results Serum HDL CUC was non-significantly higher in the non-CVD group compared with CVD patients (1.19 ± 0.58 vs. 1.08 ± 0.42; p = 0.2), non-significantly lower in the non-AMI vs. AMI group (1.11 ± 0.45 vs. 1.16 ± 0.55; p = 0.6) and non-significantly higher in the non-CAD vs. CAD group (1.18 ± 0.58 vs. 1.09 ± 0.42; p = 0.3). Conversely, HDL CUC showed a significant decrease in the stroke vs. non-stroke group (0.09 ± 0.30 vs. 1.17 ± 0.54; p = 0.05; odds ratio 0.31, 95% confidence interval 0.11–0.90; p = 0.03). We determined 1.6 a.u as the optimum cut-off value for CUC using a decision tree (DT). The DT produced five layers of different risk factors contributing to CVD risk, with “history of HTN” being the strongest predictor of CVD risk, followed by CUC, total cholesterol, LDL-C levels, and blood pressure. Conclusions In this investigation, serum HDL CUC was significantly decreased in stroke patients in comparison to the non-stroke group in a sample from the BLAS. Further studies are necessary to assess the relationships between CUC and CVD risk in several clinical settings.

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