In people not treated for cardiovascular (CV) risks, inflammation and hyperlipidemia jointly contribute to future atherosclerotic event risks. However, with advent of intensive lipid-lowering therapy, the causal role of inflammation and hyperlipidemia in future CV risk changes. Nonetheless, this has implications for patients receiving statin therapy, if an adjunctive CV therapeutic or anti-inflammatory agent is warranted. In a collaborative analysis, PROMINENT, REDUCE-IT, and STRENGTH investigators examined whether residual inflammation or hyperlipidemia most impacted risk of future CV events.
Which biomarker is a stronger predictive residual-risk factor for future CV events?
In this study, patients with—or at high risk of—atherosclerotic disease taking contemporary statins were examined. Whereby, over 31,000 patients receiving contemporary statins were part of the analysis. Researchers assessed residual high-sensitivity C-reactive protein [CRP] versus residual low-density lipoprotein cholesterol [LDL-C]), to predict future CV events. Both are biomarkers considered indicators of residual CV risk. Primary outcomes included major adverse CV events (MACE), CV death, and all-cause death. Hazard ratios (HRs) were calculated across high-sensitivity CRP and LDL-C quartiles, and adjusted for patient characteristics (including age, gender, smoking status, history of CV disease, etc.).
Results show targeting LDL-C alone will not predict residual atherosclerotic risk
Interestingly, results showed vascular inflammation was a stronger driver of residual future CV events risk than cholesterol. Also, residual inflammatory risk was significantly associated with incident MACE, CV death, and all-cause mortality (HRs: 1.31, 2.68, 2.42 respectively; all p<0.0001). The relationship of residual cholesterol risk remained neutral for MACE (HR 1.07; p=0.11), CV death (HR 1.27; p=0.0086), and all-cause mortality (HR 1.16; p=0.025).
Investigators concluded inflammation assessed by high-sensitivity CRP was a stronger predictor of future CV events risk (and death) than cholesterol (LDL-C). Therefore, physicians managing patients with high-risk atherosclerotic disease should focus on more than LDL-C to reduce fatal and non-fatal CV events. Inflammatory pathways in atherosclerotic disease must also be targeted. Finally, patients at high risk of CV events, combination adjunctive anti-inflammatory therapy and aggressive lipid-lowering therapy should become ‘standard-of-care’.
Author: Saskia van Tetering
Original article: Ridker PM et al. Lancet. 2023 Mar 3;S0140-6736(23)00215-5.