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In this episode, Dr. Paul Ridker, a pioneer in the field of cardiovascular inflammation, joins the CardioNerds (Dr. Gurleen Kaur, Dr. Richard Ferraro, and Dr. Nidhi Patel) to discuss the evolving landscape of inflammation as a key factor in cardiovascular risk reduction. The discussion dives into the importance of biomarkers like high-sensitivity C-reactive protein (hs-CRP) in guiding treatment strategies, the insights gleaned from landmark trials like the JUPITER and CANTOS studies, and the future of targeted anti-inflammatory therapies in cardiology.

Show notes were drafted by Dr. Nidhi Patel. Audio editing by CardioNerds academy intern, Grace Qiu. 

This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here.

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Pearls – Targeting Inflammation for Cardiovascular Risk

1. “If you don’t measure it, you can’t treat it”: Incorporate hs-CRP into routine practice for patients at risk of cardiovascular events, as it provides crucial information for risk stratification and management.


2. Recognize the dual benefits of statins in lowering both LDL and inflammation, particularly in patients with elevated hs-CRP.


3. Encourage patients to adopt heart-healthy habits, as lifestyle changes remain foundational in reducing both cholesterol and inflammatory risk.


4. Reminder that most autoimmune or inflammatory diseases, from psoriasis to Addison’s disease to lupus to scleroderma to inflammatory bowel disease, have been shown to have elevated cardiovascular risk


5. Ongoing randomized trials including ZEUS, HERMES, and ARTEMIS will inform whether novel targeting of IL-6 can safely lower cardiovascular event rates or slow renal progression

Show notes – Targeting Inflammation for Cardiovascular Risk

Why is it important to measure both LDL and hs-CRP, and what factors increase hs-CRP?

• Inflammation and hyperlipidemia are synergistic in promoting atherosclerosis. They interact to exacerbate plaque formation and instability, increasing the risk of cardiovascular events.


• Just like we measure blood pressure and LDL to know what to treat, we should measure hs-CRP to guide targeted therapy.


• Clinical Example: in Ms. Flame’s case, despite achieving target LDL levels with statins, her elevated hs-CRP indicates ongoing inflammation and residual cardiovascular risk that should be assessed.


• Residual inflammatory risk should be assessed in both primary and secondary prevention.


• Increased BMI¹, smoking², a sedentary lifestyle³, and genetics⁴ (such as a higher risk of metabolic disease in South Asians) all raise hs-CRP levels.


• SGLTi⁵ and GLP-1 agonists⁶ have also been shown to decrease hs-CRP levels.

What data do we have to support measuring hs-CRP? 

• Women’s Health Study⁷: an early study showing that hs-CRP predicted risk at least as well as LDL cholesterol and that models incorporating hs-CRP in addition to lipids were significantly better at predicting risk than models based on lipids alone.


• JUPITER Trial⁸ (Primary Prevention): Among patients with normal LDL but elevated hs-CRP there was a 44% reduction in major cardiovascular events (>50% in MI and stroke) and a 20% reduction in all-cause mortality in patients treated with statins. These results led to changes in guidelines in recognizing the need to measure and treat inflammation.


• CANTOS Trial⁹ (Secondary Prevention): Randomized >10K patients with previous MI and hs-CRP ≥ 2mg/L and found that canakinumab reduced hs-CRP level from baseline in a dose-dependent manner, without reduction in the LDL, ApoB, TG, or blood pressure.

What are the guidelines and supportive data on using Colchicine? 

• Colchicine 0.5 mg is the first FDA-approved anti-inflammatory therapy indicated for reducing cardiovascular events among adults who have established ASCVD or are at risk of developing it.


• The use of Colchicine is supported by the LoDoCo, LoDoCo-2, and COLCOT trials, which showed a ~25-30% risk reduction in cardiovascular risk. In comparison, studies using ezetimibe¹⁰ have shown a 6-7% relative risk reduction and PCSK9 inhibitors¹¹ ~15% risk reduction for LDL reduction.
  
  
  
  • LoDoCo¹²– in those wit