C-reactive protein may have superior prognostic value compared to low-density lipoprotein cholesterol for patients on statin therapy

1. High-sensitivity C-reactive protein increased the risk of all-cause mortality by two- to three-fold among all three randomized trials.

2. The effect of residual cholesterol on major cardiovascular events, cardiovascular mortality, and all-cause mortality was insignificant.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Statins are first-line therapy in patients with clinical atherosclerosis. While inflammation and hyperlipidemia may contribute to atherothrombotic disease, their effects on cardiovascular events and mortality following statin initiation are unclear. This meta-analysis of three randomized trials aimed to assess the importance of two key biomarkers: high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) for the assessment of cardiovascular events, cardiovascular death, and all-cause mortality. The primary outcome was the mean baseline change in said biomarkers across the different quartiles. According to study results, high-sensitivity CRP was more strongly associated with an increased risk for all-cause and cardiovascular-related mortality compared to LDLC. Additionally, adverse mortality outcomes were further increased in patients with higher CRP levels compared to lower measured values. Thus, a combination of lipid-lowering and inflammation-inhibiting drugs may better help reduce cardiovascular mortality in patients on statin therapy. Although this study was well done, it did not compare the effect of different statin therapies on CRP and LDLC levels.

Click to read the study in The Lancet

Relevant Reading: Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients

In-depth [meta-analysis]: This collaborative study included 31 245 patients from 3 randomized trials: STRENGTH (n=13078), PROMINENT (n=9988), and REDUCE-IT (n=8179). High-sensitivity CRP was a significant predictor of all-cause mortality with an adjusted hazard ratio [HR] between the highest and lowest high-sensitivity CRP quartiles of 2.69 (95% confidence interval [CI] 2.13-3.40) in STRENGTH, 2.29 (95% CI 1.85-2.84) in PROMINENT, and 2.32 (95% CI 1.81-2.96) in REDUCE-IT. A similar trend was noted for inflammatory risk associated with major adverse cardiovascular events (highest vs. lowest high-sensitivity CRP quartile, HR 1.31, 95% CI 1.20-1.43, p<0.0001) and cardiovascular mortality (HR 2.68, 95% CI 2.22-3.23, p<0.0001). In contrast, residual cholesterol was not as strong of a predictor of major cardiovascular events (highest vs. lowest LDLC quartile, HR1.07, p=0.11), cardiovascular mortality (HR 1.27, p=0.0086), and all-cause mortality (HR 1.16, p=0.025). Overall, findings from this study suggest that high-sensitivity CRP may be a stronger predictor than cholesterol assessed by LDLC for risk of future cardiovascular events and death.

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