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Inflammation and Cholesterol as Predictors of CV Events With Statin Therapy
Quick Takes
- Residual inflammatory risk appears to be more strongly associated with future CV events than residual cholesterol-risk patients taking statin therapy.
- Targeting LDL-C alone may not completely mitigate atherosclerotic risk, and anti-inflammatory pathways may provide incremental CV benefits.
- The combined use of aggressive lipid-lowering and anti-inflammatory therapies may well become standard of care for atherosclerotic disease in the future.
Study Questions:
What is the relative importance of high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDL-C) as determinants of risk for major adverse cardiovascular events (MACE), cardiovascular (CV) death, and all-cause death among patients receiving statins?
Methods:
The investigators did a collaborative analysis of patients with or at high risk of atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (clinicaltrials.gov NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Quartiles of increasing baseline hsCRP (a biomarker of residual inflammatory risk) and of increasing baseline LDL-C (a biomarker of residual cholesterol risk) were assessed as predictors of future MACE, CV death, and all-cause death. Hazard ratios (HRs) for CV events and deaths were calculated across quartiles of hsCRP and LDL-C in analyses adjusted for age, gender, body mass index, smoking status, blood pressure, previous history of CV disease, and randomized treatment group assignment.
Results:
A total of 31,245 patients were included in the analysis from the PROMINENT (n = 9,988), REDUCE-IT (n = 8,179), and STRENGTH (n = 13,078) trials. The observed ranges for baseline hsCRP and LDL-C, and the relationships of each biomarker to subsequent CV event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident MACE (highest hsCRP quartile vs. lowest hsCRP quartile, adjusted HR, 1.31; 95% confidence interval [CI], 1.20–1.43; p < 0.0001), CV mortality (2.68, 2.22–3.23; p < 0.0001), and all-cause mortality (2.42, 2.12–2.77; p < 0.0001). By contrast, the relationship of residual cholesterol risk was neutral for MACE (highest LDL-C quartile vs. lowest LDL-C quartile, adjusted HR, 1.07; 95% CI, 0.98–1.17; p = 0.11), and of low magnitude for CV death (1.27, 1.07–1.50; p = 0.0086) and all-cause death (1.16, 1.03–1.32; p = 0.025).
Conclusions:
The authors report that inflammation assessed by hsCRP was a stronger predictor for risk of future CV events and death than cholesterol assessed by LDL-C among patients receiving statins.
Perspective:
This study reports that residual inflammatory risk appears to be more strongly associated with future CV events than residual cholesterol-risk patients taking statin therapy. The current analysis must not be interpreted as diminishing the critical role of lipid lowering beyond statins for patients with persistent or refractory hypercholesterolemia, but suggests that targeting LDL-C alone may not completely mitigate atherosclerotic risk, and anti-inflammatory pathways may provide incremental CV benefits. Overall, these data suggest that combined use of aggressive lipid-lowering and anti-inflammatory therapies may well become standard of care for atherosclerotic disease in the future.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins
Keywords: ACC23, ACC Annual Scientific Session, Atherosclerosis, Biomarkers, Blood Pressure, Body Mass Index, Cardiovascular Diseases, Cholesterol, LDL, C-Reactive Protein, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Inflammation, Lipids, Primary Prevention, Risk
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