The associations of baseline lipid levels with incident sick sinus syndrome: a nationwide cohort study
S Sohn, S Y Roh, K Y Lee, D I Lee, K Han, G E NamAbstract
Background
Lower lipid levels are a cornerstone of atherosclerotic cardiovascular disease prevention. However, in certain chronic conditions such as heart failure or atrial fibrillation, lower lipid levels have been associated with poor prognosis. The relationship between lipid profiles and sick sinus syndrome (SSS) remains unclear.
Methods
Using Korean National Health Insurance Service health screening data (2012), we assembled a nationwide population-based cohort after applying a 3-year lag period to reduce reverse causality. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) were categorized into quartiles (reference: Q1 for TC/LDL-C/TG; Q4 for HDL-C). Incident SSS was identified from claims and analyzed using multivariable Cox proportional hazards models.
Results
Among 3,346,579 adults (mean age 44.8 years; 55% men) followed for a mean of 7.2 years, 1,409 incident SSS events occurred (0.067 per 1,000 person-years). In adjusted models, the highest versus lowest quartile was associated with lower SSS risk for TC (HR 0.674, 95% CI 0.577–0.788), LDL-C (HR 0.732, 95% CI 0.626–0.855) and TG (HR 0.589, 95% CI 0.499–0.696). HDL-C showed a nonmonotonic pattern. The lowest quartile was associated with lower risk compared with the highest quartile (HR 0.838, 95% CI 0.721–0.974), with the second quartile tending to have the lowest risk.
Conclusion
Lower baseline TC, LDL-C, and TG were paradoxically associated with long-term SSS risk, while HDL-C showed a nonmonotonic (potentially J-shaped) association. These findings challenge the universal applicability of the "lower-is-better" lipid paradigm to SSS pathophysiology. Further studies incorporating longitudinal lipid trajectories are warranted to clarify causality and mechanisms.Figure_1Figure_2