Effect of dual residual risk of cholesterol and inflammation on all-cause mortality in patients with cardiovascular disease

Background: Randomized controlled trials confirm that risks of residual cholesterol and residual inflammation remains in patients with cardiovascular disease (CVD) even after lipid-lowering therapy. This study aims to investigate the association between dual residual risk of cholesterol and inflammation and all-cause mortality in a real-world population with CVD.

Methods: Patients with a CVD history who first took statins between 1 January 2010 and 31 December 2017 in the Kailuan Study were selected as study participants. According to low-density lipoprotein cholesterol (LDL-C) and hypersensitive C-reactive protein levels, patients were divided into those with no residual risk, residual inflammatory risk (RIR), residual cholesterol risk (RCR), and residual cholesterol and inflammatory risk (RCIR). Cox proportional hazard model was conducted to determine hazard ratio (HR) of all-cause mortality for RIR, RCR, and RCIR. Stratified analysis was conducted according to good medication adherence and 75% of the percentage LDL-C decline, high SMART 2 risk score, and blood pressure and blood glucose at standard levels.

Results: After 6.10 years of follow-up, 377 all-cause deaths occurred in 3509 participants (mean age 63.69 ± 8.41 years, 86.78% men). After adjusting for related risk factors, the HR and (95% confidence interval [CI]) of all-cause mortality in the RIR, RCR, and RCIR was 1.63 (1.05, 2.52), 1.37 (0.98, 1.90), and 1.75 (1.25, 2.46), compared with no residual risk. Similar associations were observed in participants with moderate or low statin compliance, a lower percentage of LDL-C decline, high SMART 2 risk score, uncontrolled blood pressure, and uncontrolled blood glucose, in the RCIR had a 1.66-fold, 2.08-fold, 1.69-fold, 2.04-fold, and 2.05-fold higher risk of all-cause mortality, respectively, than the reference.

Conclusion: Risks of residual cholesterol and residual inflammation remain in patients with CVD after receiving statins, and their combined effect significantly increases the risk of all-cause mortality. Here, this increased risk was dependent on statin compliance, LDL-C reduction, SMART 2 risk score, and blood pressure and blood glucose control.