Time course of remnant cholesterol and the risk of heart failure.

Background and aim: Previous studies have shown that remnant cholesterol (RC) was associated with heart failure (HF). However, lack of evidence regarding the long-term trend of RC with HF risk. We aimed to investigate the association between cumulative RC exposure with incident HF and to further explore the modulating effects of the time course of RC accumulation.

Methods and results: We enrolled 41,168 participants free of CVD from the Kailuan Study who completed the first three health examinations from 2006 to 2010. Cumulative RC exposure included cumulative RC and time-weighted cumulative RC. The combination of cumulative RC and RC slope over time was characterized as the time course of RC accumulation. Multivariable adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HF risk. We also considered non-HF-related death as a competing event by performing competing risk models as a sensitivity analysis. During 8.84 years, 839 participants developed HF events. Cumulative RC exposure increased the HF risk, with HRs for cumulative RC of 1.72 (1.41-2.10) and for time-averaged cumulative RC of 1.54 (1.25-1.89). There was a nonlinear relationship between cumulative RC exposure and HF risk. Participants with higher cumulative RC and negative slope had the highest HF risk (HR, 1.46; 95% CI, 1.16-1.83).

Conclusions: Both cumulative long-term exposure and the time course of RC accumulation were associated with HF risk. Early RC accumulation resulted in a greater increase in risk compared to later accumulation. This finding suggests that long-term exposure to RC may be useful in identifying individuals at high risk of developing HF and highlights the need for early initiation of appropriate RC control to prevent or reduce incident HF.