Clinical Study Summary | Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials

Key Take Aways

1. Residual inflammatory risk, measured by high-sensitivity CRP, strongly predicts adverse cardiovascular events and mortality in patients on modern statin therapy.
2. Residual cholesterol risk, indicated by LDLC levels, has a minor impact on cardiovascular events but influences cardiovascular and all-cause mortality in statin-treated patients.
3. Consistency in findings across diverse trials underscores the robustness of associations between CRP and LDLC levels and cardiovascular outcomes.
4. Clinical attention should focus on assessing and managing residual inflammatory risk to enhance cardiovascular outcomes in statin-treated patients
5. Integrating CRP and LDLC levels in risk assessment facilitates personalized strategies to mitigate cardiovascular risk and improve patient outcomes during statin therapy.
 

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This summarises an original research article which first appeared in the Lancet on the 6th March 2024.  It does not replace the original work, which has been linked below.

Overview

Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, in patients undergoing intensive statin therapy, the balance of influences of the two on future cardiovascular events may shift, which could have implications for the selection of additional cardiovascular treatments.

Objectives

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Study Design & Methods

Participants
 

The sample group included 31245 individuals who had either been diagnosed with atherosclerotic disease or were at high risk of developing the condition and who were currently undergoing modern statin therapy.  The data was obtained from three randomised trials namley:

• PROMINENT (n=9988), 
• REDUCE-IT (n=8179), 
• STRENGTH (n=13 078) trials

 

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Study Design


The study was set up as follows:

 

• Quartiles of baseline high-sensitivity CRP (a marker of residual inflammatory risk) and LDLC (a marker of residual cholesterol risk) were evaluated for their predictive value.

• Hazard ratios (HRs) for major adverse cardiovascular events, cardiovascular death, and all-cause death were calculated across quartiles of CRP and LDLC.

• Analyses were adjusted for various factors, including age, gender, BMI, smoking status, blood pressure, prior cardiovascular disease history, and randomized treatment group assignment.

 

Learn more| Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk

Das Pradhan, A., Glynn, R. J., Fruchart,J. C., & MacFadyen, J. G., et al,. PROMINENT Investigators (2022). Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. The New England journal of medicine, 387(21), 1923–1934. https://doi.org/10.1056/NEJMoa2210645

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Findings 

• Residual inflammatory risk showed significant associations with incident major adverse cardiovascular events (adjusted HR 1·31, 95% CI 1·20–1·43; p<0·0001), cardiovascular mortality (adjusted HR 2·68, 95% CI 2·22–3·23; p<0·0001), and all-cause mortality (adjusted HR 2·42, 95% CI 2·12–2·77; p<0·0001) when comparing the highest high-sensitivity CRP quartile to the lowest.
• In contrast, the relationship of residual cholesterol risk had a neutral impact on major adverse cardiovascular events (adjusted HR 1·07, 95% CI 0·98–1·17; p=0·11) and a low-magnitude effect on cardiovascular death (adjusted HR 1·27, 95% CI 1·07–1·50; p=0·0086) and all-cause death (adjusted HR 1·16, 95% CI 1·03–1·32; p=0·025) when comparing the highest LDLC quartile to the lowest.

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Conclusion

In patients who were currently on statin therapy, assessing inflammation using high-sensitivity CRP proved more reliable in predicting cardiovascular events and mortality than cholesterol assessment via LDLC. 

These results underscore the importance of considering additional treatments alongside statins, suggesting that combining aggressive lipid-lowering with inflammation-inhibiting therapies may be essential for further reducing atherosclerotic risk.

Clinical trial registration no. PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials.
 

Learn more| Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

Bhatt, D. L., Steg, P. G., Miller, & M., Brinton et al., REDUCE-IT Investigators (2019). Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. The New England journal of medicine, 380(1), 11–22. https://doi.org/10.1056/NEJMoa1812792
 

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