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Dr Thomas Nero discusses inflammation and the role of rheumatologic disorders on coronary artery disease with Dr Nehal Mehta, exploring how chronic inflammation serves as a cornerstone for various health issues, particularly in patients with conditions like psoriasis and serves as a model for investigating cardiovascular therapies. The discussion highlights the role of immune responses, the impact of lifestyle factors, and the importance of early diagnosis and risk assessment in managing cardiovascular health.

Early Research

• Dr Mehta's research began by observing obese patients with heart attacks despite few cardiovascular risk factors.
• He found adipose inflammation was driving obesity and insulin resistance.
• Psoriasis became a model for studying chronic inflammation's effects on cardiovascular health.

Inflammation and Cardiovascular Disease

• Atherosclerosis requires both injury and lipids.
• Endothelial damage initiates inflammation in atherosclerosis.
• Neutrophils and myeloid cells play a critical role in the inflammatory process.
• Different inflammatory diseases have distinct cytokine profiles (e.g., psoriasis vs. lupus).

Adipose Tissue and Inflammation

• Visceral fat is metabolically active and a key site of inflammation.
• Psoriatic flares increase visceral fat volume and adipose tissue macrophages.
• Obese psoriasis patients have higher risks of cardiovascular events.

Coronary Artery Disease in Inflammatory Conditions

• Coronary inflammation can be detected by perivascular fat attenuation index (pFAI).
• Untreated psoriasis patients show progression from inflammation to plaque formation.
• Coronary artery calcium (CAC) scoring may underestimate disease in younger patients.

Diagnostic Approaches

• Dr. Mehta recommends assessing blood pressure, body mass index, lipids, and glucose.
• Neutrophil-lymphocyte ratio (NLR) and GlycA are useful inflammatory markers.
• Imaging like carotid intima-media thickness and pFAI can help identify early vascular disease.

Treatment Strategies

• Early statin initiation is recommended for psoriasis patients.
• Ongoing trials are exploring various anti-inflammatory agents (e.g., colchicine, IL-6 inhibitors).
• Future therapies may include oral IL-23 inhibitors and weight loss medications.

Future Research Directions

• Retinal arteries as a model for studying vascular disease and lipid deposition.
• Exploring lipid accumulation in various tissues, including the central nervous system.
• Developing therapies to address lipid-driven processes in diseases of aging.

The discussion emphasizes the complex interplay between inflammation, lipid metabolism, and cardiovascular disease, highlighting the need for personalized approaches and continued research in this field.

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Prof. Stefan Neubauer and Dr. Thomas Nero discuss two recent papers on the utility of coronary inflammation imaging on CT coronary angiography with Fat Attenuation Index (FAI)FAI score. The ORFAN study demonstrated a 20 fold increased risk in CV event rates with low vs high FAI score and a 10 fold increased event rate in patients with elevated FAI score who have no coronary plaque. FAI score re-categorized 40% of patients in their follow-up studies.

Prof. Neubauer is the head of the Division of Cardiovascular Medicine and Director of the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) at the University of Oxford and Past President of the Society for Cardiovascular Magnetic Resonance (SCMR). We discussed two recently published landmark papers from his division:

Kenneth Chan, Elizabeth Wahome , et al. Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study. Lancet. 2024;403(10392):1823-1835. doi:10.1016/S0140-6736(24)00596-8

Christopher J. Farina, Michael H. Davidson, Prediman K. Shah, Charles Stark, Wenqi Lu, Cheerag Shirodaria, Timothy Wright, Charalambos A. Antoniades, Jan Nilsson and Nehal N. Mehta (2024). Inhibition of oxidized low-density lipoprotein with orticumab inhibits coronary inflammation and reduces residual inflammatory risk in psoriasis: a pilot randomized, double-blind placebo-controlled trial. Cardiovascular Research, European Society of Cardiology, March 25, 2024.

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Dr Gibson and Dr Nero discuss the oft maligned issue of medical statistics. Their discussion covers the pros and cons of traditional Cox proportional hazards regression models and Kaplan-Meier curves and newer techniques including win ratios. They then dip their toes into AI. A great overview by one of our leading clinical trialists.

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This episode is a deep dive into Lipoprotein a with Dr Steven Nissen from the Cleveland Clinic. He and Dr Nero discuss the genetics of Lp(a), its pathophysiology, current treatment strategies and research into lowering Lp(a) levels. This is a fascinating conversation that also discusses the role of coronary inflammation in the work of Dr. Paul Ridker as well as the role of CT angiography in future clinical trials.

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Dr Steven Nissen from the Cleveland Clinic discuses with Dr. Thomas Nero the basic clinical approach to Lp(a) with need for routine testing and a few simple case studies. In the second (longer podcast) they take a deep deep dive into Lp(a) genetic, pathophysiology and the current research trials.

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Dr Thomas Nero speaks with Dr Aaron Baggish about coronary artery disease in the endurance athlete (and non-athlete as well!) They discuss cardiovascular testing in Masters athletes including ETT, coronary calcium scoring and CT angiography as well as risk factor identification, inflammation, physical & emotional stress and ongoing research. Dr Baggish is a Professor of Sports Cardiology at Université de Lausanne and founder of the Cardiovascular Performance Program, Massachusetts General Hospital, Harvard Medical School. He has been team cardiologist for USA rowing, US Soccer, and the New England Patriots. He was the medical director for the Boston Marathon and is a consultant to the IADA, IOC and FIFA.

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Dr Mandrola discusses recent trail data with Dr. Thomas Nero including the results from Artesia, NOAH Afnet 6, Frail AF, Azalea and Oceanic-AF. They also discuss Left Atrial Appendage Occlusion and utility of wearable devices. Finally, a shout out to Dr. Andre Foy and his work on multi-morbidity and its role in clinical trial interpretation.

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Dr. Thomas Nero speaks with Dr. Mathew Budoff about Coronary Calcium Scoring, CT Coronary Angiography and cardiovascular outcomes. The discussion goes beyond basic risk factor enhancement, highlighting its role to help evaluate disease progression, power future clinical trials and determine efficacy of therapy. Along the way, they discuss coronary inflammation, perivascular adipose tissue imaging and fat attenuation index (FAI) as well as diving into the plaque stabilizing effects of EPA.