Highlights
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Background
Inflammation and hyperlipidemia jointly contribute to atherothrombotic disease. However, when people receive intensive statin treatment, the relative contributions of inflammation and hyperlipidemia to the risk of future cardiovascular events may change, which has implications for the choice of adjuvant cardiovascular therapies.
Our objective was to evaluate the relative importance of high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) as determinants of the risk of major adverse cardiovascular events, cardiovascular death, and all-cause death among patients. who receive statins. .
Methods
We performed a collaborative analysis of patients with, or at high risk for, atherosclerotic disease who were receiving contemporary statins and were participants in the multinational PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials.
Quartiles of increases in baseline high-sensitivity CRP (a biomarker of residual inflammatory risk) and increases in baseline LDLC (a biomarker of residual cholesterol risk) were evaluated as predictors of future major adverse cardiovascular events, cardiovascular death, and death. for all causes.
Hazard ratios (HRs) for cardiovascular events and deaths were calculated in quartiles of CRP and high-sensitivity LDLC in analyzes adjusted for age, sex, BMI, smoking status, blood pressure, history of cardiovascular disease, and random assignment of treatment groups.
Results
31,245 patients were included in the analysis of the PROMINENT (n=9988), REDUCE-IT (n=8179), and STRENGTH (n=13,078) trials. The observed ranges for baseline CRP and high-sensitivity LDLC, and the relationships of each biomarker with subsequent cardiovascular event rates, were nearly identical in all three trials.
Residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (highest high-sensitivity CRP quartile versus lowest high-sensitivity CRP quartile, adjusted HR 1·31, 95% CI 1·20–1·43 ; p<0·0001), cardiovascular mortality (2·68, 2·22–3·23; p<0·0001), and all-cause mortality (2·42, 2·12–2·77; p <0·0001).
In contrast, the residual cholesterol risk relationship was neutral for major adverse cardiovascular events (highest LDLC quartile vs. lowest LDLC quartile, adjusted HR 1.07, 95% CI 0.98–1.17; p= 0.11) and low magnitude for cardiovascular death (1·27, 1·07–1·50; p=0·0086) and death from all causes (1·16, 1·03–1·32; p =0·025).
Interpretation
Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor of risk of future cardiovascular events and death than cholesterol assessed by LDLC.
These data have implications for the selection of adjunctive treatments beyond statin therapy and suggest that the combined use of aggressive lipid-lowering and inflammation-inhibiting therapies may be necessary to further reduce the risk of atherosclerosis.
Perspective:
This study reports that residual inflammatory risk appears to be more strongly associated with future cardiovascular events than patients with residual cholesterol risk taking statin therapy. The current analysis should not be interpreted as diminishing the critical role of lipid lowering beyond statins for patients with persistent or refractory hypercholesterolemia, but suggests that focusing on LDL-C alone may not fully mitigate atherosclerotic risk, and anti-inflammatory pathways may provide incremental CV benefits.
Overall, these data suggest that the combined use of aggressive anti-inflammatory and lipid-lowering therapies may well become the standard of care for atherosclerotic disease in the future.
Reference : Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomized trials. Prof Paul M Ridker, Deepak L Bhatt, Aruna D Pradhan, Prof Robert J Glynn, Jean G MacFadyen, Prof Steven E Nissen, et al. The Lancet . DOI:https://doi.org/10.1016/S0140-6736(23)00215-5
