HDL-Associated Specific Paraoxonase-1 Activity Is Linked to Atherogenic Lipoprotein Measures in a High Cardiovascular Risk Population: A Cross-Sectional Study

Despite increasing efforts to improve cardiovascular disease (CVD) risk evaluation and management, it remains a leading cause of mortality and morbidity worldwide. This has driven interest in high-density lipoprotein (HDL)-related biomarkers as indicators of oxidative stress and atherogenic processes not fully captured by traditional lipid measurements. In this study, we examined specific paraoxonase 1 (PON1) activity and its relationship with anthropometric, blood pressure, and lipid metabolism measures in 100 middle-aged Lithuanian individuals at high cardiovascular risk. HDL fractions were isolated using iodixanol-based density gradient centrifugation. PON1 concentration and arylesterase activity were measured, and specific activity was defined as arylesterase activity normalized to PON1 concentration. No significant associations were observed between specific PON1 activity and age, body mass index, waist circumference, blood pressure, smoking status, or statin use. Specific PON1 activity was independently associated with lower risk-weighted apolipoprotein B and lower low-density lipoprotein cholesterol levels. These exploratory findings suggest that higher specific PON1 activity may reflect a less atherogenic lipid profile in individuals at high cardiovascular risk, as indicated by its association with LDL-C and with risk-weighted apolipoprotein B. Because direct oxidative stress and inflammatory markers were not measured, interpretations regarding oxidative burden should be considered indirect and hypothesis-generating. Given the cross-sectional nature of the study and the relatively small sample size, these results should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies in larger populations are needed to confirm these observations.