Smoking is inversely linked to Lp(a) in a Korean cohort of 146,129 (J Lipid Atheroscler 2026)

Objective: Lipoprotein(a) (LP(a)) is a genetically regulated lipoprotein associated with cardiovascular disease. Although primarily heritable, the impact of modifiable factors such as smoking on LP(a) remains unclear, particularly when assessed using objective biomarkers like urinary cotinine. This study examined the association between smoking status-based on both self-reported and cotinine-verified measures-and LP(a) concentrations in Korean adults.

Methods: We analyzed 146,129 participants (mean age, 37.1 years; 59.2% men) from the Kangbuk Samsung Health Study from 2011 to 2013. Smoking was defined by self-report (never, former, current) and urinary cotinine ≥50 ng/mL. Serum LP(a) was measured using an immunoturbidimetric assay, with high LP(a) defined as ≥50 mg/dL. Multivariable regression analyses adjusted for relevant covariates.

Results: The median LP(a) level was 23.3 mg/dL (interquartile range, 13.4-39.2), and 16.0% of participants had high LP(a). Both cotinine-verified and self-reported current smokers had significantly lower LP(a) levels compared with non-smokers (p<0.001). Urinary cotinine levels were inversely associated with continuous LP(a) concentrations (β=-0.147, p<0.001), demonstrating an inverse dose-dependent trend. Among categorical smoking variables, only total smoking duration showed a significant inverse association (p=0.029), while daily amount (p=0.089) and pack-years (p=0.068) demonstrated non-significant trends. No sex interaction was observed.

Conclusion: Both self-reported and cotinine-verified smoking status were inversely associated with serum LP(a) levels. Although causality cannot be established due to the cross-sectional design, these findings suggest a possible interaction between tobacco exposure and genetically determined LP(a) concentrations, highlighting the need for future longitudinal investigations.