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Residual Inflammatory Risk ASCVD CKD

CE / CME

Expert Insights on Targeting Residual Inflammatory Risk in ASCVD and CKD

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurses: 1.00 Nursing contact hour

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Released: July 22, 2024

Expiration: July 21, 2025

Erin Michos
Erin Michos, MD, MHS, FACC, FAHA, FASE, FASPC
CME/CE Information

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Anti-inflammatory Strategies

It is important to highlight that we should still be ensuring patients are on well-supported, standard-of-care therapy. We should continue to reinforce the use of ASCVD prevention efforts including healthy nutrition, exercise, weight loss, and smoking cessation. These have all been demonstrated to reduce vascular inflammation and lower the risk of CV events.

In addition, we should endeavor to use evidence-based therapies to prevent CVD, including aspirin, which is used in secondary CV prevention and in those who are at high-risk for a first event. Statins are first-line therapy for both primary and secondary prevention, primarily for their LDL-lowering property, but they are also known to lower CRP Finally, we can consider adding colchicine in those with residual inflammatory risk after maximized standard of care therapy has been applied.

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Addressing the Other Side of the Coin: Residual Cholesterol and Inflammatory Risk

When evaluating patients for candidacy for therapy to target residual CV risk, we should consider their individual characteristics. No 2 patients are alike, and each patient’s residual risk may be due to different factors.

Here you can consider a hypothetical example of 2 different patients who have known ASCVD who both started out with a high LDL and a high CRP. Each patient was then treated with intensive lipid-lowering therapy with a statin.

In the case on the left, the LDL is still 110 mg/dL despite being maximized on statin therapy, however, the CRP is now down to 1.8 mg/L. In this case, we have good data from our lipid trials to support further LDL-lowering therapy. Achieving an LDL even lower, <55 mg/dL, can reduce outcomes.

However, what about the patient case on the right? This patient has achieved an LDL of 45 mg/dL, but the CRP remains elevated at 3.8 mg/L. In this case, the patient has a clear residual inflammatory risk and we should consider targeting inflammation reduction. This may be a good example of a patient who is a good candidate for low-dose colchicine, and if the patient is overweight or obese, we could consider adding a GLP-1 RA.

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Treatment for Residual Inflammatory and Cholesterol Risk in Stable Coronary Disease

From a different perspective, consider this proposed clinical decision pathway designed to guide healthcare professionals to evaluate LDL and hsCRP levels after maximizing statin therapy.

In those with an LDL remaining at or above 70 mg/dL while hsCRP is <2 mg/L, consider adding further cholesterol lowering therapies.

Alternately, in those whose LDL is less than 70 mg/dL while hsCRP remains above 2 mg/dL, consider targeting residual inflammation.

Finally, in patients who have LDL and hsCRP above those thresholds, consider targeting both residual risk from cholesterol and systemic inflammation.

When individualizing care, it is important to consider the patient-specific evidence available to you, and target the pathways and risks involved for them specifically. Inflammation is very complex and we should work to target the pathways that we know are engaged for each patient.

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Conclusions

In summary, there is currently good evidence that inflammation is causally related to atherothrombosis, both its genesis and its progression, and is an intriguing new target of therapy. It is increasingly important to diagnose and manage residual CV risk factors to optimize prevention strategies. Remember that not all patients will respond to traditional therapies in the same way, adding to the importance of CRP levels in your patients. As shown with the various secondary prevention statistics and the primary prevention data from the JUPITER trial, residual risk needs to be considered. Consider the 2 hypothetical patients described earlier—one size does not fit all. CV risks can be generated from elevated LDL, elevated lipoprotein(a), triglyceride-ride lipoprotein(a), diabetes, systemic inflammation, or other pathways. Therefore, it is crucial to tailor our prevention strategies, possibly going beyond statin and lifestyle interventions. There are now many more tools in our toolkit along with ongoing studies of new therapies, including the latest IL-6 targeted inhibition offering reduced CV outcomes in patients with ASCVD and CKD.

Listen to this audio clip about personalizing prevention medicine in patients with ASCVD and CKD.

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A 55-year-old man with stable ASCVD, type 2 diabetes (T2D), and CKD (eGFR 53 mL/min/1.73m2) is currently on maximized atorvastatin. His blood pressure and A1C are at goal, low-density lipoprotein cholesterol (LDL-C) is 57 mg/dL, and hsCRP is 3.5 mg/L. Which of the following have demonstrated the potential to reduce residual inflammatory risk in this patient?

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