Prevention Archives - Cardionerds

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Prevention Archives - Cardionerds episodes

July 23459. The Continuum of Prevention and Heart Failure with Dr. Anu Lala and Dr. Martha Gulati
CardioNerds (Drs. Apoorva Gangavelli, Jenna Skowronski, and Hannah Every) discuss the continuum of prevention and heart failure with Drs. Anu Lala and Martha Gulati. Grounded in a clinical case of a 55-year-old woman with uncontrolled hypertension, type 2 diabetes, and obesity who is on the trajectory toward heart failure, this episode unpacks a paradigm-shifting framework from a joint HFSA/ASPC Scientific Statement. The discussion explores how prevention should not be siloed from heart failure management but rather integrated across a patient’s lifespan—from primary prevention in at-risk individuals, to secondary prevention in those with established heart failure, to tertiary prevention in patients with advanced therapies such as LVADs and heart transplantation. The experts highlight the importance of aggressive risk factor management, biomarker-guided screening, the AHA’s Life’s Essential 8, and the need for multidisciplinary collaboration and systems-level change to shift heart failure care from reactive to proactive. Audio editing for this episode was performed by CardioNerds Intern, Dr. Julia Marques Fernandes.
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Pearls
Systemic inflammatory diseases are associated with an elevated CVD risk that has significant implications for early detection, risk Heart failure prevention is a continuum, not a checkpoint. Prevention applies at every stage—from at-risk (Stage A) through advanced/post-transplant care—and every clinical encounter is an opportunity to intervene. The AHA’s Life’s Essential 8 (diet, physical activity, nicotine exposure, sleep, BMI, blood lipids, blood glucose, blood pressure) forms the foundation at every stage.
Hypertension carries the highest population-attributable risk for heart failure of any modifiable risk factor. In the Framingham Heart Study, 91% of patients with newly diagnosed HF had pre-existing hypertension. The SPRINT trial demonstrated a 38% reduction in HF incidence with intensive blood pressure targets (<120 mm Hg systolic). Agent selection matters: ACE inhibitors, ARBs, and thiazide diuretics should be prioritized for HF prevention.
Overlapping risk factors should prompt parallel, not sequential, intervention. Pharmacotherapies such as SGLT2 inhibitors and GLP-1 receptor agonists target multiple pathways simultaneously (diabetes, obesity, CKD, HF risk), making them ideal for patients with cardiometabolic multimorbidity. The cardio-kidney-metabolic (CKM) syndrome framework reinforces this integrated approach.
Biomarker screening with BNP/NT-proBNP should be used proactively in high-risk populations, not just reactively in the emergency department. Even modestly elevated natriuretic peptide levels (e.g., BNP >30 ng/L or NT-proBNP >125 ng/L) identify individuals at heightened risk for progression to symptomatic HF. The ACC/AHA/HFSA guidelines give a Class IIa recommendation for natriuretic peptide screening in at-risk patients. Urine albumin-to-creatinine ratio (UACR) is an underutilized screening tool that provides additional insight into CKM risk.
The heart failure label does not close the prevention window—it accentuates it. Secondary prevention through GDMT optimization (quadruple therapy in HFrEF) and continued risk factor management remains critical. Tertiary prevention extends to post-LVAD and post-transplant patients, where hypertension, diabetes, obesity, and CKD management remain essential to long-term outcomes.
Show notes
For a comprehensive review, please review the full HFSA/ASPC Joint Scientific Statement: Lala A, Beavers C, Blumer V, et al. The Continuum of Prevention and Heart Failure in Cardiovascular Medicine. J Card Fail. 2026;32:75-105. doi:10.1016/j.cardfail.2025.06.013
1. What is the “continuum of prevention” framework, and how does it differ from traditional approaches to heart failure prevention?
Historically, prevention and heart failure management have been treated as separate disciplines—primary prevention handled by preventive cardiologists and treatment managed by heart failure specialists. This joint HFSA/ASPC Scientific Statement reframes prevention as a dynamic, continuous process that spans a patient’s entire lifespan, regardless of HF stage or ejection fraction.
The framework maps onto the ACC/AHA HF staging system:
Primary prevention targets Stage A (“at risk”) and Stage B (“pre-HF”) patients to reduce the burden of incident HF.
Secondary prevention targets Stage C (symptomatic) and Stage D (advanced) patients to reduce the impact of established HF through GDMT optimization and ongoing risk factor management.
Tertiary prevention encompasses risk factor management in patients with LVADs or heart transplants—populations where hypertension, diabetes, and obesity still drive outcomes.
The Central Figure of the statement illustrates that Life’s Essential 8 (blood pressure and lipid control, diabetes management, exercise, sleep, smoking cessation, weight management, and diet/nutrition counseling) forms the foundation at every stage, with pharmacologic and device-based therapies layered on top as disease progresses (Figure)
2. How do traditional risk factors drive heart failure, and what should clinicians prioritize?
Hypertension carries the greatest population-attributable risk for HF. In the Framingham Heart Study (N=5,143), HTN was associated with a 2- to 3-fold increased risk of HF, with a population-attributable risk of 39% in men and 59% in women. The SPRINT trial showed a 38% reduction in HF incidence and 25% reduction in the primary composite outcome with intensive BP targets (<120 mm Hg). Not all antihypertensives are equal for HF prevention: the ALLHAT trial showed that amlodipine carried a 38% higher risk and lisinopril a 19% higher risk of incident HF compared with chlorthalidone. The statement recommends prioritizing ACE inhibitors, ARBs, or thiazide diuretics as first-line agents when HF prevention is a goal.
Type 2 diabetes confers a 5-fold risk of HF in women and 2-fold in men. Each 5-year increment in diabetes duration is associated with a 17% increased risk of incident HF. SGLT2 inhibitors have a Class 1 recommendation for HF prevention in patients with T2DM and established CVD or high cardiovascular risk. Finerenone (nonsteroidal MRA) reduced new-onset HF by 32% in the FIGARO-DKD trial among patients with T2DM and CKD. GLP-1 receptor agonists reduce CV events in patients with T2DM and ASCVD and are recommended in current guidelines.
Obesity independently leads to myocardial dysfunction through the leptin-aldosterone-neprilysin framework, ectopic fat deposition, and neurohormonal dysregulation. The SELECT trial demonstrated that semaglutide reduced HF composite endpoint events (HR 0.84; 95% CI 0.74–0.97) in patients with obesity and established CVD without T2DM. Women with obesity are at highest risk for HFpEF, while men with obesity are at highest risk for HFrEF.
Chronic kidney disease with albuminuria is deliberately included as a traditional risk factor in this statement. Albuminuria confers a 2- to 3-fold increased risk of incident HF. UACR screening is recommended for patients with T2DM and those at risk for CKD.
3. How can risk stratification tools and biomarkers be used to identify patients on the trajectory toward heart failure?
Natriuretic peptides (BNP/NT-proBNP): The ACC/AHA/HFSA guidelines give a Class IIa recommendation for BNP or NT-proBNP screening in patients at risk for HF. Even modestly elevated levels (BNP >30 ng/L or NT-proBNP >125 ng/L) are associated with heightened risk for progression to symptomatic HF. In the ARIC study, incorporating NT-proBNP reclassified 20% of older adults without HF into Stage B. Factors that affect interpretation include age, sex, obesity (lower values), and CKD (higher values).
High-sensitivity cardiac troponin (hs-cTn): Concentrations above the 99th percentile are now included in the definition of Stage B HF. Troponin testing may complement natriuretic peptides, particularly when BNP/NT-proBNP values are ambiguous.
Risk scores: The PCP-HF equation predicts 10-year HF risk using traditional risk factors plus QRS duration. The AHA PREVENT score incorporates HF risk calculation and includes markers of kidney function (albuminuria, eGFR), though it may underestimate risk in men and Black adults. The CKM syndrome staging framework (Stages 0–4) provides a holistic approach to assessing systemic cardiovascular-kidney-metabolic risk.
4. What are the key nontraditional risk factors and cross-cutting themes in heart failure prevention?
Genetics: Pathogenic cardiomyopathy variants exist in ~1 in 200 individuals in the general population. The HFSA and ACMG recommend cascade testing to identify at-risk family members. Polygenic risk scores for dilated cardiomyopathy show a 3.8-fold risk for DCM in the top 10th percentile compared with the median.
Sex-specific considerations: Women have 2.8 times the odds of developing HFpEF, while men have similarly increased odds of HFrEF. A complete obstetric/gynecologic history is essential—preeclampsia is associated with a 4-fold increased risk of HF. Peripartum cardiomyopathy requires intentional screening in high-risk populations.
Cardiotoxic exposures: Clinicians should be aware of medications that cause direct myocardial toxicity (e.g., anthracyclines, trastuzumab, tyrosine kinase inhibitors). A team-based approach with pharmacists can help optimize medication selection and risk factor modification.
Social determinants of health: Environmental exposures (air pollution, arsenic, lead, cadmium), food insecurity, financial instability, and limited healthcare access contribute to HF risk and progression. Equity-focused, risk-based prevention strategies are needed.
Psychological health: Depression is common in HF and independently associated with worse outcomes. Screening with brief questionnaires (e.g., PHQ-2) is recommended. Meditation, spirituality, and holistic wellness approaches remain underutilized.
5. What systems-level and policy changes are needed to move the needle on heart failure prevention?
Multidisciplinary HF prevention clinics that bring together preventive cardiologists, HF specialists, endocrinologists, nephrologists, dietitians, pharmacists, exercise physiologists, and genetic counselors are advocated by the statement.
EHR-embedded risk stratification could proactively flag patients on a trajectory toward HF—analogous to sepsis alerts or fall risk flags—enabling earlier intervention, particularly for patients who may not reach a cardiologist.
Cardiac rehabilitation remains underutilized, particularly in HFrEF (Class 2b recommendation) and HFpEF (not yet covered by Medicare). The HF-ACTION trial showed quality-of-life benefits, and the REHAB-HF trial showed particular benefit in older patients with HFpEF.
Policy priorities include expanding insurance coverage for preventive screening and novel therapies (SGLT2i, GLP-1 RAs, nsMRAs), reducing clinical inertia through team-based care models with closer follow-up intervals, and ensuring equitable access to evidence-based therapies across diverse populations.
Digital health and AI hold promise for personalized risk prediction, remote monitoring (e.g., wearable devices, implantable PA pressure monitors), and virtual cardiac rehabilitation to overcome access barriers.
Figure
Lala A, Beavers C, Blumer V, et al. The continuum of prevention and heart failure in cardiovascular medicine: a joint scientific statement from the Heart Failure Society of America and the American Society for Preventive Cardiology. J Card Fail. 2026;32(1):75-105. doi:10.1016/j.cardfail.2025.06.013)
References
Key references are bolded.
Lala A, Beavers C, Blumer V, et al. The continuum of prevention and heart failure in cardiovascular medicine: a joint scientific statement from the Heart Failure Society of America and the American Society for Preventive Cardiology. J Card Fail. 2026;32(1):75-105. doi:10.1016/j.cardfail.2025.06.013
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063
Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life’s Essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association. Circulation. 2022;146(5):e18-e43. doi:10.1161/CIR.0000000000001078
SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116. doi:10.1056/NEJMoa1511939
Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. The progression from hypertension to congestive heart failure. JAMA. 1996;275(20):1557-1562. doi:10.1001/jama.1996.03530440037034
Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997. doi:10.1001/jama.288.23.2981
Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153. doi:10.1056/NEJM200001203420301
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098. doi:10.1056/NEJMoa2206286
Filippatos G, Anker SD, Agarwal R, et al. Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial. Circulation. 2022;145(6):437-447. doi:10.1161/CIRCULATIONAHA.121.057983
Solomon SD, McMurray JJV, Vaduganathan M, et al. Finerenone in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2024;391(16):1475-1485. doi:10.1056/NEJMoa2407107
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10454):773-786. doi:10.1016/S0140-6736(24)01498-3
Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963
Ndumele CE, Neeland IJ, Tuttle KR, et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association. Circulation. 2023;148(20):1636-1664. doi:10.1161/CIR.0000000000001175
Khan SS, Matsushita K, Sang Y, et al. Development and validation of the American Heart Association’s PREVENT equations. Circulation. 2024;149(6):430-449. doi:10.1161/CIRCULATIONAHA.123.067626
Khan SS, Ning H, Shah SJ, et al. 10-year risk equations for incident heart failure in the general population. J Am Coll Cardiol. 2019;73(19):2388-2397. doi:10.1016/j.jacc.2019.02.057
Bozkurt B, Fonarow GC, Goldberg LR, et al. Cardiac rehabilitation for patients with heart failure: JACC expert panel. J Am Coll Cardiol. 2021;77(11):1454-1469. doi:10.1016/j.jacc.2021.01.030
Packer M. Leptin-aldosterone-neprilysin axis: identification of its distinctive role in the pathogenesis of the three phenotypes of heart failure in people with obesity. Circulation. 2018;137(15):1614-1631. doi:10.1161/CIRCULATIONAHA.117.032474
Lala A, Tayal U, Hamo CE, et al. Sex differences in heart failure. J Card Fail. 2022;28(3):477-498. doi:10.1016/j.cardfail.2021.10.006
Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and classification of heart failure. Eur J Heart Fail. 2021;23(3):352-380. doi:10.1002/ejhf.2115
Hershberger RE, Givertz MM, Ho CY, et al. Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline. J Card Fail. 2018;24(5):281-302. doi:10.1016/j.cardfail.2018.03.004
Levine GN, Cohen BE, Commodore-Mensah Y, et al. Psychological health, well-being, and the mind-heart-body connection: a scientific statement from the American Heart Association. Circulation. 2021;143(10):e763-e783. doi:10.1161/CIR.0000000000000947
Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022;399(10333):1391-1400. doi:10.1016/S0140-6736(22)00369-5
27 min
June 20, 2025420. Cardio-Rheumatology: Cardiovascular Multimodality Imaging & Systemic Inflammation with Dr. Monica Mukherjee
In this episode, CardioNerds Dr. Gurleen Kaur, Dr. Richard Ferraro, and Dr. Jake Roberts are joined by Cardio-Rheumatology expert, Dr. Monica Mukherjee, to discuss the role of utilizing multimodal imaging for cardiovascular disease risk stratification, monitoring, and management in patients with chronic systemic inflammation. The team delves into the contexts for utilizing advanced imaging to assess systemic inflammation with cardiac involvement, as well as the role of imaging in monitoring various specific cardiovascular complications that may develop due to inflammatory diseases. Audio editing by CardioNerds academy intern, Christiana Dangas.
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Pearls – Cardiovascular Multimodality Imaging & Systemic Inflammation
Systemic inflammatory diseases are associated with an elevated CVD risk that has significant implications for early detection, risk stratification, and implementation of therapeutic strategies to address these risks and disease-specific complications. As an example, patients with SLE have a 48-fold increased risk for developing ASCVD compared to the general population. They may also develop disease-specific complications, such as pericarditis, that require focused imaging approaches to detect.
In addition to increasing the risk for CAD, systemic inflammatory diseases can also result in cardiac complications, including myocardial, pericardial, and valvular involvement. Assessment of these complications requires the use of different imaging techniques, with the modality and serial studies selected based on the suspected disease process involved.
In most contexts, echocardiography remains the starting point for evaluating cardiac involvement in systemic inflammatory diseases and can inform the next steps in terms of diagnostic study selection for the assessment of specific cardiac processes. For example, if echocardiography is completed in an SLE patient and demonstrates potential myocardial or pericardial inflammation, the next steps in evaluation may include completing a cardiac MRI for better characterization.
While no current guidelines or standards of care directly guide our selection of advanced imaging studies for screening and management of CVD in patients with systemic inflammatory diseases, our understanding of cardiac involvement in these patients continues to improve and will likely lead to future guideline development.
Due to the vast heterogeneity of cardiac involvement both across and within different systemic inflammatory diseases, a personalized approach to caring for each individual patient remains central to CVD evaluation and management in these patients. For example, patients with systemic sclerosis and symptoms of shortness of breath may experience these symptoms due to a range of causes. Echocardiography can be a central guiding tool in assessing these patients for potential concerns related to pulmonary hypertension or diastolic dysfunction. Based on the initial echocardiogram, the next steps in evaluation may involve further ischemic evaluation or right heart catheterization, depending on the pathology of concern.
Show notes – Cardiovascular Multimodality Imaging & Systemic Inflammation
Episode notes drafted by Dr. Jake Roberts.
What are the contexts in which we should consider pursuing multimodal cardiac imaging, and are there certain inflammatory disorders associated with systemic inflammation and higher associated CVD risk for which advanced imaging can help guide early intervention?
Systemic inflammatory diseases are associated with elevated CVD risk, which has significant implications for early detection, risk stratification, prognostication, and implementation of therapeutic strategies to address CVD risk and complications in these patient populations.
The most well-characterized autoimmune diseases with an association between systemic inflammation and CVD risk are inflammatory arthritic conditions such as rheumatoid arthritis. Additional inflammatory diseases with elevated CVD risk include spondyloarthropathies and psoriatic arthritis.
Patients with rheumatoid arthritis have a 1.5- 2x risk of developing coronary artery disease compared to the general population.
The mechanism of elevated CVD risk in inflammatory disease patients is likely related to a combination of abnormalities in lipid metabolism, endothelial dysfunction, and vascular inflammation.
Conditions including systemic lupus erythematosus (SLE), myositis, vasculitis disorders, and systemic sclerosis may have additional cardiovascular complications beyond CAD, including pericarditis, myocarditis, electrical, and valvular complications.
Are there any established or emerging technologies to help with improving early detection or characterization of cardiac involvement in systemic inflammatory diseases?
Echocardiography remains the most common and useful starting point for screening and early detection of cardiac involvement in systemic inflammatory diseases due to its widespread availability, real-time interpretation, low cost, and noninvasive nature. Furthermore, echocardiography remains a crucial tool in serial monitoring for disease progression and the detection of therapeutic effects. This modality additionally provides significant utility for early detection and screening of pericardial and valvular involvement.
Given that patients with inflammatory disorders have an elevated risk for developing CAD, utilizing CAC scores and CCTA are often additionally helpful for CAD detection in these patient populations.
Are there different imaging techniques that should be used to assess complications specific to different systemic inflammatory diseases?
Based on the specific disease involved, the choice of imaging technique may vary depending on the clinical context and the cardiovascular complication requiring further investigation.
As an example, in systemic sclerosis, there can be a wide range of variable cardiac manifestations that emerge depending on the subtype of the disease, with the cardiac complications developing either because of the fibrotic disease process or from other secondary effects of the disease. Specifically, if the patient’s phenotype involves interstitial lung disease, the right ventricle of the heart will encounter chronic increased afterload, which can lead to adverse adaptive responses and remodeling over time. As a result, screening tools such as echocardiography can be very useful in this patient population, with these patients often requiring regular annual screening echocardiograms coupled with pulmonary function testing to screen for coupled changes in individual patients’ physiology. When these patients develop complications of their disease, including pulmonary hypertension, echocardiography can help evaluate the underlying cause of this complication and inform subsequent diagnostic steps.
In terms of assessing myocardial disease and inflammation in myocardial tissue, cardiac MRI remains a valuable tool in detecting subclinical myocardial disease and can identify areas of low-grade myocardial inflammation. One of the advantages of cardiac MRI over other imaging techniques involves its ability to allow for noninvasive tissue characterization.
For disease complications such as pericarditis, which can commonly develop in SLE, 2D echocardiography remains the first-line imaging modality of choice to detect pericardial disease involvement. In SLE patients who have long-standing pericardial disease with progression, they can also develop constrictive symptoms resulting from this process. In those cases, either CT or cardiac MRI can assist in defining the pericardial or myocardial anatomy.
As an example, what would be the approach to utilizing advanced imaging to assess for CVD detection and monitoring in a patient with SLE with relatively well-controlled symptoms on chronic immunosuppressive agents and no prior history of heart failure or CVD?
As a starting point, all patients with systemic inflammatory diseases should undergo comprehensive ASCVD risk assessment. Initial stratification involves completing a laboratory assessment with a standard lipid panel and diabetes screening studies. Further evaluation of any symptoms that a patient may describe, which could indicate potential early cardiovascular disease processes, should also be thoroughly assessed and may influence the next steps in screening.
In the context of SLE, pericardial disease is common, and therefore, obtaining a baseline echocardiogram to assess for any early pericardial involvement should be the initial step in evaluation. If the patient also has an elevated ASCVD risk, they should also undergo assessment for coronary artery disease.
What should be the approach to the sequence of imaging technique selection, serial imaging, monitoring, and follow-up in patients with systemic inflammatory disorders undergoing evaluation of CVD screening and monitoring?
The initial selection of imaging modality should be based on what is suspected to be the primary driver of the patient’s symptoms or as the primary underlying process of concern that requires further evaluation.
As an important consideration in the context of systemic inflammatory diseases such as SLE, ischemic disease may involve atypical presentations due to underlying myocardial dysfunction and microvascular disease. Therefore, imaging and other diagnostic studies may be warranted to assess for reversible ischemia. There is emerging evidence that cardiac PET perfusion and cardiac MRI may be particularly useful in this patient population to assess coronary flow reserve to evaluate for coronary microvascular disease.
What evidence currently exists to demonstrate the impact on cardiovascular outcomes resulting from the utilization of advanced multimodality imaging for CVD detection and monitoring in patients with systemic inflammatory disorders?
While there is limited evidence that has directly measured the impact of advanced imaging utilization on CVD outcomes in this patient population, there is growing recognition of the increased risk of cardiac complications in patients with systemic inflammatory diseases. With increasing recognition of the commonality of cardiac involvement in these diseases, we are now more often utilizing appropriate testing in these patients.
Directly measuring outcomes in these patient populations is somewhat challenging in large part due to the wide heterogeneity of phenotypes both across and within specific inflammatory diseases. Much of the approach in cardio-rheumatology should emphasize personalized medicine specific to each patient, given the wide range of cardiovascular complications and unique presentations of cardiac involvement in individual patients. Providing care for patients with systemic inflammatory diseases further requires a collaborative approach across disciplines and subspecialties within medicine to provide appropriate comprehensive care.
Is there a need for more standardized approaches for utilizing imaging in patients with systemic inflammatory diseases?
Currently, there are no formal guidelines or standards of care to direct the use of multimodality imaging to assess CVD risk and direct management in patients with systemic inflammatory diseases.
Many of the current standardized approaches are institution-dependent and often informed by clinical observations at individual medical centers.
As we work to better understand the role of cardiac involvement in systemic inflammatory diseases and gain more experience in the evaluation of CVD and specific cardiovascular complications in these disorders, we will likely have ongoing development of standards of care and guidelines for management of CVD in these patients.
References – Cardiovascular Multimodality Imaging & Systemic Inflammation
Weber BN, Paik JJ, Ayaz Aghayev, et al. Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases. Journal of the American College of Cardiology. 2023;82(22):2128-2151. doi:https://doi.org/10.1016/j.jacc.2023.09.819
Mortensen MB, Jensen JM, Sand NP, et al. Association of Autoimmune Diseases with Coronary Atherosclerosis Severity and Ischemic Events. Journal of the American College of Cardiology. 2024;83(25):2643-2654. doi:https://doi.org/10.1016/j.jacc.2024.04.030
Thackeray JT, Lavine KJ, Liu Y. Imaging Inflammation Past, Present, and Future: Focus on Cardioimmunology. The Journal of Nuclear Medicine. 2023;64(Supplement 2):39S48S. doi:https://doi.org/10.2967/jnumed.122.264865
West HW, Katerina Dangas, Antoniades C. Advances in Clinical Imaging of Vascular Inflammation. JACC Basic to Translational Science. 2023;9(5):710-732. doi:https://doi.org/10.1016/j.jacbts.2023.10.007
Milner JJ, Kim AHJ. Cardiac Manifestations of Systemic Lupus Erythematosus. Rheumatic Disease Clinics of North America. 2024;40(1):51-60. https://doi.org/10.1016/j.rdc.2013.10.003
Lu J, Jani V, Mercurio V, et al. Stress Echocardiographic Prediction of Emerging Pulmonary Vascular Disease in Systemic Sclerosis. Journal of the American Society of Echocardiography. 2023;36(2):259-261. https://doi.org/10.1016/j.echo.2022.10.006
Gilotra NA, Griffin JM, Pavlovic N, et al. Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review. Journal of Cardiac Failure. 2022;28(1):113-132. https://doi.org/10.1016/j.cardfail.2021.06.016
Trivieri MG, Spagnolo P, Birnie P, et al. Challenges in Cardiac and Pulmonary Sarcoidosis: JACC State-of-the-Art Review. 2020;76(16):1878-1901. https://doi.org/10.1016/j.jacc.2020.08.042
18 min
November 14, 2024403. Cardio-Rheumatology: Treating Inflammation and Real-World Implementation of Therapies with Dr. Brittany Weber and Dr. Michael Garshick
In this episode, CardioNerds Dr. Gurleen Kaur and Dr. Akiva Rosenzveig are joined by Cardio-Rheumatology experts, Dr. Brittany Weber and Dr. Michael Garshick to discuss treating inflammation, delving into the pathophysiology behind the inflammatory hypothesis of atherosclerotic cardiovascular disease and the evolving data on anti-inflammatory therapies for reducing ASCVD risk, with insights on real-world implementation.
Show notes were drafted by. Dr. Akiva Rosenzveig.
This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Agepha Pharma.
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
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.
CardioNerds Prevention Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll
CardioNerds Journal Club
Subscribe to The Heartbeat Newsletter!
Check out CardioNerds SWAG!
Become a CardioNerds Patron!
Pearls – Treating Inflammation
Our understanding of the pathophysiology of atherosclerosis has undergone a few iterations from the incrustation hypothesis to the lipid hypothesis to the response-to-injury hypothesis and culminating with our current understanding of the inflammation hypothesis.
Both the adaptive and innate immune systems play instrumental roles in the pathogenesis of atherosclerosis.
After adequately controlling classic modifiable risk factors such as blood pressure, dyslipidemia, glucose intolerance, and obesity, systemic inflammation as assessed by CRP can be ascertained as CRP is associated with ~1.8-fold increased risk of cardiovascular events
Although the most common side effect of colchicine is gastrointestinal intolerance, colchicine can induce lactose intolerance, so a lactose free diet may help ameliorate colchicine-induced GI symptoms.
Anti-inflammatory therapeutics have shown promise in reducing cardiovascular risk but much more is to be learned with ongoing and future basic, translational, and clinical research.
Show notes – Treating Inflammation
What are the origins of the inflammatory hypothesis?
The first hypothesis as to the pathogenesis of atherosclerosis was the incrustation hypothesis by Carl Von Rokitansky in 1852. He suggested that atherosclerosis begins in the intima with thrombus deposition.In 1856, Rudolf Virchow suggested the lipid hypothesis whereby high levels of cholesterol in the blood lead to atherosclerosis. He observed inflammatory changes in the arterial walls associated with atherosclerotic plaque growth, called endo-arteritis chronica deformans.In 1977, Russell Ross suggested the response-to-injury hypothesis, that atherosclerosis develops from injury to the arterial wall.In the 1990’s the role of inflammation in ASCVD became more recognized. Both the adaptive and innate immune system are critical in atherosclerosis. Lipids and inflammation are synergistic in that lipid exposure is required but they translocate through damaged endothelium which occurs by way of inflammatory cytokines, namely within the NLRP3 inflammasome (IL-1, IL-6 etc.).Smooth muscle cells are also involved. They migrate to the endothelial region and secrete collagen to create the fibrous cap. They can also transform into macrophage-like cells to take up lipids and become foam cells.
T, B, and K cells are also part of this milieu. In fact, neutrophils, macrophages and monocytes make up only a small portion of the cells involved in the atherosclerotic process.
What are ways to individually optimize one’s ASCVD risk?
Ensure the patient is on appropriate antiplatelet therapy, lipid lowering therapy, blood pressure is well controlled, and the Hemoglobin A1c is well controlled. Smoking cessation is pivotal.
If the patient has an elevated Lipoprotein (a), pursue more aggressive lipid lowering therapy. Targeted therapies may become available in the future.
Assess the patient’s systemic inflammatory risk as measured by C-Reactive Protein (CRP)
What is the evidence for utilizing CRP in risk stratification?
CRP, initially termed Fraction C (discovered as a c polysaccharide component of the pneumococcal cell wall), was first discovered at Rockefeller University in the 1930’s. It was discovered to be an acute phase reactant in the 1940’s and noted to be synthesized in the liver in the 1960’s.
Although it is not causal in atherosclerosis, elevated CRP is associated with elevated rates of cardiovascular disease. This was first noted in the landmark New England Journal of Medicine study by Ridker et al that showed elevated CRP was associated with elevated cardiovascular risk and treating with anti-inflammatory medication (aspirin) lowered CRP and CV risk.
The statin trials also showed reduction in CRP levels was associated with better outcomes.
High-sensitivity CRP (hsCRP) >3 mg/L has odds ratio of ~1.8 for risk of CV disease.
Recent analyses of the PROMINENT, REDUCE-IT, and STRENGTH trials demonstrated that hsCRP was a more powerful determinant of recurrent CV events, CV death, and all-cause mortality than LDL-C.
After effectively controlling the previously stated modifiable risk factors, what therapeutic options remain in a patient with an elevated CRP?
CANTOS trial was the first proof of concept trial investigating Canakinumab (an IL-1 inhibitor) which showed a ~15% relative risk reduction in cardiovascular events
CIRT trial investigated methotrexate in patients without autoimmune disease. It was stopped early due to it being a negative trial. This emphasized the complex role inflammation plays in ASCVD, and that both patient selection and chosen anti-inflammatory therapy are important to consider for ASCVD risk reduction.
Colchicine has seen a lot of focus in this space with trials such as COLCOT, COPS, LODOCO, LODOCO 2, LODOCO MI. Overall, it appears that colchicine may be more effective in chronic stable ischemic heart disease. The CLEAR SYNERGY trial investigated colchicine in the peri-MI period and was a negative trial. However, we do not yet have the published data to further analyze it.
A review article by Potere et al (referenced below) provides a useful summary of novel therapies and upcoming trials in the inflammation in ASCVD space.
How do we approach inflammation in women?
We know that immune response differs between men and women. Women have more robust immune response to vaccines and viruses and greater innate and adaptive immune responses.
Women have slightly higher CRP than men. Studies have shown that average high sensitivity hsCRP is 1.7 for women and 1.2 for men. In the JUPITER trial, the subgroup of patients with hsCRP>7 mg/L had the highest proportion of women relative to men.
Regardless, hsCRP remains a reliable predictor of CV events in both men and women.
What are some practical considerations when starting colchicine?
It may help with adherence, if you walk patients through what to expect with the medication.
Obtain renal and liver function tests as both organs contribute to colchicine metabolism and clearance.
Obtain a thorough medication reconciliation as colchicine has some notable drug-drug interactions.
The most common side effects is GI intolerance; cytopenias are rare occurrences.
Note that colchicine can induce lactose intolerance, a potential mechanism for causing GI intolerance, so a lactose free diet may help with adherence.
What do we have to look forward to in the anti-inflammation space in CV disease?
There is still a lot to be learned and discovered in this space. Some clinical trials to look out for are the ZEUS, ARTEMIS, and HERMES trials which look at Ziltivekimab, an IL-6 inhibitor, in chronic kidney disease, acute myocardial infarction, and heart failure, respectively.
References – Treating Inflammation
Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61(4):404-410. doi:10.1016/j.jacc.2012.10.027
Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383(19):1838-1847. doi:10.1056/NEJMoa2021372
Tardif JC, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497-2505. doi:10.1056/NEJMoa1912388
Hennessy T, Soh L, Bowman M, et al. The Low Dose Colchicine after Myocardial Infarction (LoDoCo-MI) study: A pilot randomized placebo controlled trial of colchicine following acute myocardial infarction. Am Heart J. 2019;215:62-69. doi:10.1016/j.ahj.2019.06.003
Tong DC, Quinn S, Nasis A, et al. Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial. Circulation. 2020;142(20):1890-1900. doi:10.1161/CIRCULATIONAHA.120.050771
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-1131. doi:10.1056/NEJMoa1707914
Ridker PM, Everett BM, Pradhan A, et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019;380(8):752-762. doi:10.1056/NEJMoa1809798
Potere N, Bonaventura A, Abbate A. Novel Therapeutics and Upcoming Clinical Trials Targeting Inflammation in Cardiovascular Diseases. Arterioscler Thromb Vasc Biol. Published online October 10, 2024. doi:10.1161/ATVBAHA.124.319980
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men [published correction appears in N Engl J Med 1997 Jul 31;337(5):356]. N Engl J Med. 1997;336(14):973-979. doi:10.1056/NEJM199704033361401
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. doi:10.1056/NEJMoa0807646
Ridker PM, Bhatt DL, Pradhan AD, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023;401(10384):1293-1301. doi:10.1016/S0140-6736(23)00215-5
Fernandez DM, Rahman AH, Fernandez NF, et al. Single-cell immune landscape of human atherosclerotic plaques. Nat Med. 2019;25(10):1576-1588. doi:10.1038/s41591-019-0590-4
Moran CA, Collins LF, Beydoun N, et al. Cardiovascular Implications of Immune Disorders in Women. Circ Res. 2022;130(4):593-610. doi:10.1161/CIRCRESAHA.121.319877
Kushner I. C-reactive protein – My perspective on its first half century, 1930-1982. Front Immunol. 2023;14:1150103. Published 2023 Mar 2. doi:10.3389/fimmu.2023.1150103
37 min
November 06, 2024400. Cardio-Rheumatology: Targeting Inflammation for Cardiovascular Risk Reduction with Dr. Paul Ridker
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.
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
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
“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.
Recognize the dual benefits of statins in lowering both LDL and inflammation, particularly in patients with elevated hs-CRP.
Encourage patients to adopt heart-healthy habits, as lifestyle changes remain foundational in reducing both cholesterol and inflammatory risk.
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
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 with stable CAD, patients who received colchicine in addition to standard of care had a significantly lower composite rate of ACS compared to those who only received standard of care at a median follow-up of 3 years.
LoDoCo-213– randomized control, multicentric trial in patients with stable CAD showing group randomized to colchicine + standard of compare had reduced MACE compared to those with placebo + standard of care at a median follow-up of 2.8 years.
COLCOT14– Addition of colchicine within 30 days of ACS resulted in a reduction of the primary composite outcome of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina
What are examples of ongoing trials that will shape the future of our anti-inflammatory toolbox?
ZEUS Trial15– ongoing trial that randomizes patients with ASCVD, hs-CRP ≥ 2 and CKD (eGFR between 15-60 OR EGFR ≥ 60 and urinary albumin-to-creatinine ratio ≥200) to Ziltivekimab or placebo, and assesses time to first occurrence of MACE.
Hermes HFpEF16– ongoing trial that randomizes patients with HFpEF and HFmrEF to Ziltivekimab or placebo, and assesses time to first occurrence of cardiovascular death, heart failure hospitalization, or urgent heart failure visit
Artemis Acute Ischemia17– ongoing trial that randomizes patients hospitalized with MI to Ziltivekimab or placebo, and assess time to MACE.
Clazakizumab in patients receiving maintenance dialysis18– this study randomized adults with known cardiovascular disease and/or DM2 receiving dialysis with hs-CRP ≥ 2 to receive Clazakizumab or placebo. The primary endpoint is a reduction in hs-CRP over 12 weeks.
References – Targeting Inflammation for Cardiovascular Risk
Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-Reactive Protein Levels in Overweight and Obese Adults. JAMA. 1999;282:2131-2135. doi: 10.1001/jama.282.22.2131
Tonstad S, Cowan JL. C-reactive protein as a predictor of disease in smokers and former smokers: a review. Int J Clin Pract. 2009;63:1634-1641. doi: 10.1111/j.1742-1241.2009.02179.x
Esteghamati A, Morteza A, Khalilzadeh O, Anvari M, Noshad S, Zandieh A, Nakhjavani M. Physical inactivity is correlated with levels of quantitative C-reactive protein in serum, independent of obesity: results of the national surveillance of risk factors of non-communicable diseases in Iran. J Health Popul Nutr. 2012;30:66-72. doi: 10.3329/jhpn.v30i1.11278
Anand SS, Razak F, Yi Q, Davis B, Jacobs R, Vuksan V, Lonn E, Teo K, McQueen M, Yusuf S. C-reactive protein as a screening test for cardiovascular risk in a multiethnic population. Arterioscler Thromb Vasc Biol. 2004;24:1509-1515. doi: 10.1161/01.ATV.0000135845.95890.4e
La Grotta R, de Candia P, Olivieri F, Matacchione G, Giuliani A, Rippo MR, Tagliabue E, Mancino M, Rispoli F, Ferroni S, et al. Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin. Cell Mol Life Sci. 2022;79:273. doi: 10.1007/s00018-022-04289-z
Mazidi M, Karimi E, Rezaie P, Ferns GA. Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. J Diabetes Complications. 2017;31:1237-1242. doi: 10.1016/j.jdiacomp.2016.05.022
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843. doi: 10.1056/nejm200003233421202
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Jr., Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207. doi: 10.1056/NEJMoa0807646
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine. 2017;377:1119-1131. doi: 10.1056/NEJMoa1707914
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. New England Journal of Medicine. 2015;372:2387-2397. doi: 10.1056/NEJMoa1410489
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine. 2017;376:1713-1722. doi: 10.1056/NEJMoa1615664
Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404-410. doi: 10.1016/j.jacc.2012.10.027
Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383:1838-1847. doi: 10.1056/NEJMoa2021372
Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381:2497-2505. doi: 10.1056/NEJMoa1912388
ZEUS – Effects of Ziltivekimab Versus Placebo on Cardiovascular Outcomes in Participants With Established Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease and Systemic Inflammation. In; 2021.
Effects of Ziltivekimab Versus Placebo on Morbidity and Mortality in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Systemic Inflammation. In; 2022.
ARTEMIS – Effects of Ziltivekimab Versus Placebo on Cardiovascular Outcomes in Patients With Acute Myocardial Infarction. In: Duke Clinical Research I, ed.; 2023.
Chertow GM, Chang AM, Felker GM, Heise M, Velkoska E, Fellström B, Charytan DM, Clementi R, Gibson CM, Goodman SG, et al. IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial. Nature Medicine. 2024. doi: 10.1038/s41591-024-03043-1
52 min
October 01, 2024393. SGLT Inhibitors: Clinical Implementation of SGLT Inhibitors with Dr. Alison Bailey
CardioNerds Drs. Jason Feinman, Gurleen Kaur, and Rick Ferraro discuss the implementation of SGLT inhibitors in clinical practice with Dr. Alison Bailey. Notes were drafted by Dr. Jason Feinman.
In this episode, we discuss the implementation of SGLTi in clinical practice scenarios, including for individuals with heart failure regardless of ejection fraction, those with chronic kidney disease, and those with diabetes mellitus. The group also discusses important side effects to monitor for, as well as how to counsel patients when prescribing these medications.
This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals.
We Were Thrilled to Join the American Heart Association’s Scientific Sessions 2025!
AHA Scientific Sessions 2025 took place November 7–10 in New Orleans, LA — one of the premier annual gatherings in cardiovascular science and education.
It was an incredible opportunity to connect with colleagues, hear cutting-edge research, and contribute to the ongoing conversations shaping the future of cardiovascular care.
We’re grateful to everyone who joined us in New Orleans and made this year’s meeting so impactful.
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.
CardioNerds Prevention Page
CardioNerds Episode Page
CardioNerds Academy
Cardionerds Healy Honor Roll
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Pearls – Clinical Implementation of SGLT Inhibitors
For patients with heart failure with reduced ejection fraction, SGLT inhibitors reduce the composite outcome of cardiovascular death or heart failure hospitalization by 25%.
SGLT inhibitors can be safely started in patients with an eGFR as low as 20. There are ongoing trials investigating the safety of these medications in individuals with eGFR lower than 20 or those who are receiving dialysis.
An eGFR decrease of 3-5 ml/min on average is expected after starting an SGLTi, but this will stabilize over time and provides protective effects of renal dysfunction in the long run.
Early data that suggested an association between SGLTi and bacterial UTI development hasn’t panned out in the long run, but there is an association between SGLTi and the development of either genital mycotic infections or yeast infections. Perineal hygiene is important to prevent the development of either.
A patient-centered, shared decision-making approach should guide the choice of agents for individuals with type 2 diabetes mellitus. In certain patients, it may be reasonable to choose an SGLTi as the first-line agent.
Show notes – Clinical Implementation of SGLT Inhibitors
What is the data supporting the use of SGLTi in HFpEF?
The EMPEROR-Preserved and DELIVER trials investigated the impact of empagliflozin and dapagliflozin, respectively, on cardiovascular outcomes in patients with mildly reduced or preserved ejection fraction.
The SOLOIST-WHF trial investigated a combined SGLT1/2 inhibitor, sotagliflozin, in patients with recently worsening heart failure, irrespective of ejection.SGLTi have been demonstrated to reduce the risk of cardiovascular death or worsening heart failure, including heart failure hospitalization, in these individuals.
A meta-analysis of the EMPEROR-Preserved and DELIVER trials demonstrated a hazard ratio of 0.80 for cardiovascular death or first hospitalization for heart failure for empagliflozin or dapagliflozin over placebo in the setting of HFpEF.
What is the data supporting the use of SGLTi in HFrEF?
In addition to the SOLOIST-WHF trial that was previously discussed, the EMPEROR-HF and DAPA-HF investigated the impact of SGLTi medications in patients with HFrEF.
In patients with HFrEF, SGLTi medications have been demonstrated to reduce the risk of either cardiovascular death or heart failure hospitalization.
Dapagliflozin and empagliflozin had a pooled risk reduction of all-cause death of 13%, a pooled risk reduction of cardiovascular death of 14%, and a 26% reduction in the combination of CV death or first hospitalization for heart failure.
What is the expected impact of SGLTi on renal function?
Dapagliflozin, empagliflozin, sotagliflozin, ertugliflozin, and canagliflozin have all been studied for their impact on renal dysfunction in individuals both with and without diabetes.
In the CANVAS trial, canagliflozin was associated with an initial decrease in eGFR of 3.2ml/min compared to placebo but overall decreased change from baseline in eGFR compared to placebo at trial end.In a large meta-analysis, SGLTi medications reduced the progression of kidney disease by 37%.
The risk of acute kidney injury was reduced by 23%.
What are the recommendations for SGLTi in patients with type 2 diabetes mellitus?
ADA guidelines emphasize a patient-centered shared decision-making approach when choosing which pharmacologic agent to prescribe for an individual with diabetes mellitus.
Factors in choosing which agent include the risk of cardiovascular disease, the risk of renal disease, and whether there is an emphasis on weight reduction.
What side effects should be monitored for when starting an individual on an SGLTi medication?
Side effects with SGLTi medications are overall rare but include DKA, genital mycotic infections, necrotizing fasciitis, and volume status derangements.
In the CANVAS trial, SGLTi was associated with an increased risk of amputation, but this has not been shown to be consistent in other trials. Nevertheless, in a meta-analysis including CANVAS, SGLTi medications were associated with a 15% relative risk of amputation over placebo medications.The relative risk of DKA in the same meta-analysis was 2.12.
Careful assessment of an individual’s volume status and whether they are on any other diuretic medications when initiating an SGLTi medication may allow for upfront adjustment of these medications to reduce the risk of dehydration.
References – Clinical Implementation of SGLT Inhibitors
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-1098.
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461.
Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021;384(2):117-128.
Vaduganathan M, Docherty KF, Claggett BL, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022;400(10354):757-767.
Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424.
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.
Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819-829.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657.
Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400(10365):1788-1801.
American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S158-S178.
20 min
September 18, 2024390. Cardio-Rheumatology: Deciphering Cardiovascular Risk in Patients with Rheumatologic Conditions with Dr. Brittany Weber and Dr. Michael Garshick
CardioNerds Cardio-Rheumatology Series Co-Chairs Dr. Rick Ferraro, Dr. Gurleen Kaur, and and Dr. Bree Hansen discuss how to decipher cardiovascular risk in patients with rheumatological conditions with cardio-rheumatology experts Dr. Brittany Weber and Dr. Michael Garshick.
In this episode, Drs. Weber and Garshick take us through the role of inflammation in patients with rheumatologic conditions and cardiovascular disease. They discuss the increased prevalence of traditional cardiac risk factors in this population and how these standard cardiac risk factors do not account for the full extent of cardiovascular risk. Dr. Bree Hansen drafted show notes. Audio editing by CardioNerds intern Christiana Dangas.
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.
This episode is supported by the 5th Annual Going Back to the Heart of Cardiology (A MedscapeLIVE Conference). Join co-chairs Dr. Robert Harrington and Dr. Fatima Rodriguez January 24-26, 2025 at the Fontainebleau Hotel in Miami Beach, Florida.
The agenda will explore the latest advancements in cardiology including cardiovascular prevention, atherosclerosis and thrombosis, cardiovascular dysfunction, arrhythmias, and valvular heart disease. Network, attend engaging presentations by renowned cardiologists, visit the exhibit and poster hall, participate in an exclusive immersive experience, and earn up to 13 CME/CE credits.
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Pearls – Cardio-Rheumatology – Deciphering Cardiovascular Risk in Patients with Rheumatological Conditions
Cardiovascular disease prevalence: cardiovascular disease is common in patients with autoimmune rheumatologic disease; therefore, we must take every opportunity to screen patients early.
Limitations of Traditional Scores: conventional risk calculators often underestimate cardiovascular risk for autoimmune disease patients, necessitating additional methods to assess risk accurately.
Integration of Disease-Specific Biomarkers: using biomarkers specific to autoimmune diseases, such as lupus, enhances risk assessment and helps in tailoring treatment strategies.
Value of Imaging and Risk Enhancers: incorporating imaging (like CAC scoring and carotid ultrasound) and evaluating additional risk factors (such as lipoprotein(a) and high-sensitivity CRP) provides a more comprehensive view of cardiovascular risk and guides more effective management.
Show notes – Cardio-Rheumatology – Deciphering Cardiovascular Risk in Patients with Rheumatological Conditions
Show notes (Drafted by Dr. Bree Hansen):
How does inflammation contribute to atherosclerosis, specifically in autoimmune rheumatologic diseases like psoriasis?
Lipids need to enter the intimal space of blood vessels, which can be facilitated by endothelial damage caused by chronic cytokine stimulation, such as TNF or IL-6. Once in the intima, lipids are recognized as foreign, leading to the recruitment of monocytes that transform into macrophages to clear these lipids. However, this process often exacerbates the problem, leading to persistent inflammation and atherosclerotic plaque formation.
Specifically, in psoriasis, the endothelial damage is particularly pronounced due to cytokines like TNF, IL-17, and interferons. The inflammasome pathway, which is highly active in psoriasis, also contributes to endothelial damage. Additionally, hyperactivated platelets in psoriasis can further damage the endothelium and contribute to atherosclerosis.
Overall, atherosclerosis results from a combination of traditional risk factors and systemic inflammation, leading to the development of cardiovascular disease.
Which traditional cardiovascular risk factors are increased in patients with rheumatologic conditions?
Patients with autoimmune diseases may be up to > three times more likely to develop cardiovascular disease, similar to the risk of type 2 diabetes; therefore, it is important to screen patients with autoimmune rheumatologic disorders for cardiovascular disease
Most common cardiovascular risk factors, such as smoking, diabetes, hypertension, and dyslipidemia, are also increased in patients with autoimmune rheumatologic disorders. Smoking, specifically, is highly prevalent in psoriasis and exhibits a dose-response relationship with psoriasis severity.
Hyperlipidemia is another common risk factor present in patients with autoimmune rheumatologic disease; however, a “lipid paradox” also exists. The “lipid paradox,” where lower LDL (low-density lipoprotein) levels are associated with higher inflammation, seems counterintuitive since lower LDL is often thought to indicate lower cardiovascular risk. This paradox is particularly well-documented in rheumatoid arthritis (RA) but may apply to various other conditions as well. In clinical practice, it’s important to assess lipid levels not only during periods of high inflammation but also when the patient is in a state of disease remission or stability. This is because lipid levels can fluctuate based on the level of inflammation and the medications a patient takes, such as biologics.
How can cardiovascular disease risk be estimated in patients with rheumatologic conditions beyond that of traditional risk factor calculators?
Traditional cardiovascular risk scores like the Framingham Risk Score and ACC/AHA Pool Cohort Equation often underestimate risk, particularly for patients with autoimmune diseases. Risk calculators in women with RA underestimated cardiovascular risk at least 2‐fold.
The Run-On Risk Score includes inflammatory markers like CRP but can still fall short in risk assessment. While some specialized calculators like The British SCORE2 system, which initially included rheumatoid arthritis (RA), and later QRISK3, which added lupus and steroid use, include these autoimmune conditions, no standard tool is universally applied for these diseases. Therefore, clinicians need to integrate multiple data sources to assess risk effectively
Recent research, such as a study from Dr. Weber’s group, has highlighted that incorporating lupus-specific biomarkers such as persistently positive double-stranded DNA, low complement levels, and lupus anticoagulant into risk calculators improves risk prediction for lupus patients.
Thus, beyond traditional risk factors, clinicians should assess disease duration, activity biomarkers, and the impact of treatments (including medications like hydroxychloroquine that have potential cardiotoxicity). Clinicians should also use other risk enhancers, like lipoprotein(a) and high-sensitivity CRP, and consider imaging techniques like coronary artery calcium (CAC) scoring to evaluate atherosclerotic burden. Elevated lipoprotein(a) levels and high CAC scores indicate higher risk, even if traditional risk scores suggest otherwise.
References – Deciphering Cardiovascular Risk in Patients with Rheumatological Conditions
Conrad N, Verbeke G, Molenberghs G, et al. Autoimmune diseases and cardiovascular risk: a population‐based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet. 2022;400:733–743.
Crowson CS, Liao KP, Davis JM 3rd, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622-628.e1. doi:10.1016/j.ahj.2013.07.010
Garshick MS, Ward NL, Krueger JG, Berger JS. Cardiovascular Risk in Patients With Psoriasis: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(13):1670-1680. doi:10.1016/j.jacc.2021.02.009
Weber, B, Paik, J, Aghayev, A. et al. Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases: JACC Scientific Statement. JACC. 2023 Nov, 82 (22) 2128–2151. https://doi.org/10.1016/j.jacc.2023.09.819
Mortensen M, Jensen J, Sand N, et al. Association of Autoimmune Diseases with Coronary Atherosclerosis Severity and Ischemic Events. JACC. 2024. Jun, 83 (25) 2643-2654. Doi: 10.1016/j.jacc.2024.04.030
Choi M, Guan H, Yoshida K, et al. Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus. Seminars in Arthritis and Rheumatism. 2024. Aug:67:152468. Doi: 10.1016/j.semarthrit.2024.152468.
49 min
August 18, 2024387. Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease with Dr. Antonio Abbate
CardioNerds Cardio-Rheumatology Series Co-Chairs Dr. Rick Ferraro, Dr. Gurleen Kaur, and Episode Lead Dr. Ronaldo Correa discuss “The Role of Inflammation in Cardiovascular Disease” with Dr. Antonio Abbate.
Join the CardioNerds as they kick off the Cardio-Rheumatology series with Dr. Antonio Abbate. In this episode, Dr. Abbate, a leading expert in cardio-immunology, discusses the role of inflammation in cardiovascular disease. We explore the molecular mechanisms linking inflammation to atherosclerosis, the impact of chronic low-grade systemic inflammation on heart disease, and potential therapeutic targets. Dr. Abbate shares insights on how genes and lifestyle factors contribute to inflammation, the use of inflammatory markers in clinical practice, and emerging anti-inflammatory therapies in atherosclerotic cardiovascular disease. Tune in for an enlightening conversation on the intersection of inflammation and cardiovascular health.
Dr. Ronaldo Correa drafted the notes. Episode audio was engineered by Dr. Amit Goyal.
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Pearls – Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease
Inflammation is key in the pathogenesis and progression of atherosclerosis. Estimating systemic inflammation is part of a comprehensive preventive assessment (primary/secondary).
Patients with autoimmune inflammatory diseases are at a higher risk for cardiovascular events.
C-reactive protein (CRP) can estimate systemic inflammation and help assess residual inflammatory risk in patients with traditional intermediate/low cardiovascular disease, guiding management consideration with lipid-lowering therapy, aspirin, and colchicine.
The pharmacological management of atherosclerosis is evolving beyond primarily lipid-lowering therapies to focus on targeting the underlying residual inflammatory process. Colchicine (inflammasome blocker as an anti-mitotic drug) is approved for use in chronic stable CVD in selected cases, and interleukin pathway blockers, especially IL-1 and IL-6, are under clinical trial investigation.
First things first! Prioritize treating and optimizing traditional risk factors and comorbidities and emphasize lifestyle modifications to reduce cardiovascular disease (control diabetes and hypertension, reduce or cease smoking/alcohol, lose weight, and engage in regular physical activity). They all impact inflammation directly or indirectly
Show notes – Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease
Notes: Notes drafted by Dr. Ronaldo Correa.
What is the link between inflammation and cardiovascular atherosclerosis?
Inflammation is involved both in the pathogenesis and progression of atherosclerosis.
Histopathological coronary atherosclerosis studies have demonstrated the presence of inflammatory mediators as well as a central role of factors of innate immunity such as macrophages and T cells which can interact with vascular smooth muscle cells in the progression of atherosclerotic plaque.
Patients with autoimmune inflammatory conditions have earlier and higher cardiovascular event rates (accelerated atherosclerosis due to residual inflammatory risk).
Elevated inflammatory markers (for example, high CRP) predict cardiovascular events.
How should inflammation be considered in the context of residual cardiovascular risk?
Inflammation may be the inciting factor in atherosclerosis, or it may amplify the process driven primarily by other risk factors. Therefore, treating the comorbidities and traditional CVD contributors is key to reducing the vicious inflammatory cycle.
Assessing residual risk using inflammatory markers can assist in management. C-reactive protein (CRP) can estimate systemic inflammation and help assess residual inflammatory risk in patients with traditional intermediate/low cardiovascular disease, guiding management consideration with lipid-targeting therapies, aspirin, and colchicine.
Optimizing traditional risk factors, emphasizing appropriate treatment for hypertension, diabetes, dyslipidemia, weight loss, obstructive sleep apnea (OSA), depression, underlying inflammatory conditions, and lifestyle modifications such as consuming a Mediterranean diet, alcohol/smoking reduction/cessation, and getting regular physical activity can help directly and indirectly reduce inflammatory contributors.
How does inflammation contribute to thrombosis, and what are the implications for cardiovascular disease?
Inflammation increases the expression of procoagulant factors through the inflammasome pathway, including mediators like IL-6.
Proinflammatory changes in endothelial cells, leukocytes, and platelets promote thrombosis.
The concept of immunothrombosis has emerged, especially highlighted by conditions like COVID-19.
Inflammation-induced thrombosis has significant implications for cardiovascular disease.
What are the key inflammatory pathways involved in atherosclerosis, and what therapeutic targets have emerged?
The inflammatory process is complex, and we still have much to learn about it. Three inflammatory therapeutic targets are highlighted: NLRP3 inflammasome, IL-1, and IL-6.
Colchicine is an NLRP3 inflammasome blocker that is FDA-approved as an add-on medication for secondary ischemic prevention in patients with stable CAD who remain at higher risk despite optimal medical therapy with aspirin and statin.
The CANTOS trial showed a significant reduction in MACE and hsCRP in post-MI patients who received canakinumab (IL-1 inhibitor) as an add-on therapy.
The ZEUS trial is investigating Ziltivekimab (an IL-6 inhibitor) for secondary ASCVD prevention. Rilonacept (an IL-1 inhibitor) is FDA-approved for recurrent pericarditis based on the RHAPSODY trial. Ongoing trials are further exploring inflammation-targeting therapies for the treatment of cardiovascular disease.
References – Cardio-Rheumatology: The Role of Inflammation in Cardiovascular Disease
Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?. Nat Rev Cardiol. 2022;19(8):522-542. doi:10.1038/s41569-021-00668-4
Kong P, Cui ZY, Huang XF, Zhang DD, Guo RJ, Han M. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduct Target Ther. 2022;7(1):131. Published 2022 Apr 22. doi:10.1038/s41392-022-00955-7
Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 2020;17(7):387-401. doi:10.1038/s41569-020-0352-5
Sage AP, Tsiantoulas D, Binder CJ, Mallat Z. The role of B cells in atherosclerosis. Nat Rev Cardiol. 2019;16(3):180-196. doi:10.1038/s41569-018-0106-9
Suero-Abreu GA, Zanni MV, Neilan TG. Atherosclerosis With Immune Checkpoint Inhibitor Therapy: Evidence, Diagnosis, and Management: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2022;4(5):598-615. Published 2022 Dec 20. doi:10.1016/j.jaccao.2022.11.011
Zhao TX, Mallat Z. Targeting the Immune System in Atherosclerosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(13):1691-1706. doi:10.1016/j.jacc.2018.12.083
Geovanini GR, Libby P. Atherosclerosis and inflammation: overview and updates. Clin Sci (Lond). 2018;132(12):1243-1252. Published 2018 Jun 21. doi:10.1042/CS20180306
Fragoulis GE, Soulaidopoulos S, Sfikakis PP, Dimitroulas T, D Kitas G. Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reduction. J Inflamm Res. 2021;14:1915-1931. Published 2021 May 14. doi:10.2147/JIR.S282691
Giles JT, Sattar N, Gabriel S, et al. Cardiovascular Safety of Tocilizumab Versus Etanercept in Rheumatoid Arthritis: A Randomized Controlled Trial. Arthritis Rheumatol. 2020;72(1):31-40. doi:10.1002/art.41095
Del Buono MG, Bonaventura A, Vecchié A, et al. Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1. Eur J Clin Invest. 2024;54(2):e14110. doi:10.1111/eci.14110
Abbate A, Toldo S, Marchetti C, Kron J, Van Tassell BW, Dinarello CA. Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease. Circ Res. 2020;126(9):1260-1280. doi:10.1161/CIRCRESAHA.120.315937
Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases. Nat Rev Cardiol. 2024;21(4):219-237. doi:10.1038/s41569-023-00946-3
45 min
July 28, 2024382. SGLT Inhibitors: The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan
CardioNerds Dr. Rick Ferraro, Dr. Gurleen Kaur, and Dr. Maryam Barkhordarian discuss the evidence and data supporting SGLT inhibition for cardiovascular and kidney health outcomes with expert faculty Dr. Muthu Vaduganathan. They discuss the role of SGLT inhibitors in different populations, including those with diabetes mellitus, heart failure, CKD, and myocardial infarction. Show notes and audio editing by CardioNerds Academy Fellow Dr. Maryam Barkhordarian.
This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals.
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Pearls – The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan
The benefit of SGLT inhibition extends beyond diabetes, and improves cardiovascular and kidney health outcomes independent of diabetes in appropriate patient populations.
SGLT inhibition decreases cardiovascular mortality and heart failure hospitalization independent of left ventricular ejection fraction.
SGLT inhibitors reduce clinically relevant events such as dialysis and transplantation in CKD patients irrespective of etiology and are now a cornerstone for the prevention of CKD progression.
The introduction of polypills in heart failure can simplify GDMT implementation.
Show notes – The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan
How did SGLT inhibitors transition from “diabetes medication” to guideline-directed cardiovascular medicine?
Most therapies in cardiology were developed for a particular purpose and ended up being indicated for a vastly different reason. The SGLT-2 inhibitors are no different.
Cardiovascular safety concerns about diabetes medications led to a mandate to conduct cardiovascular outcomes trials for all novel diabetes medications. This federal requirement shed light on the cardiovascular benefits of SGLT inhibitors in patients with diabetes.
These initial trials showed that not only are these medications safe but also, surprisingly, proved their role in preventing heart failure and delaying progression of chronic kidney disease.
What are the mechanisms of action of SGLT-2 and SGLT-1/2 inhibitors?
The central mechanism(s) of how these medications confer health outcomes benefits patients is/are not well understood.
The main organ involved in the action of SGLT-2 inhibitors is the kidney at the level of the proximal tubule, impacting the cardiovascular system by handling salt and water and improving kidney efficiency. Conversely, SGLT-1/2 inhibitors also act at the level of the gut, the predominant location of the SGLT-1 cotransporter.
Their effects on the cardiovascular system are secondary, given there is no SGLT-1 or -2 cotransporters in the myocardium. These secondary effects can be impacted through blood pressure reduction, volume regulation, improved glycemic control, etc. to overall improve cardiovascular status.
Whatever the underlying mechanisms, the empirical data for their use is strong and growing.
What is the role of SGLT inhibitors in preventing CKD progression?
RAAS inhibitors (ACE inhibitors and ARBs) have been the cornerstone of CKD management for the past two to three decades.
SGLT inhibitors have been the first add-on to this background therapy.
Four trials, DAPA-CKD, EMPA-CKD, CREDENCE, and the SCORED, investigated the effects of SGLT-2 and SGLT-1/2 inhibitors in patients with CKD with or without diabetes.
The outcomes of these trials include modifying the course of CKD and reducing events such as dialysis initiation and transplantation. These effects were regardless of participants’ diabetic status, CKD etiology, or individual patient profile.
The addition of SGLT-2 inhibitors to ACEI or ARB can be considered as GDMT of CKD.
What is the role of SGLT-2 inhibitors in combination with other medications as polypill?
Polypills have been beneficial in many areas such as cardiometabolic medicine, hypertension, and diabetes mellitus. In addition, a multi-drug regimen is strongly recommended in heart failure with reduced ejection fraction.
Developing polypills in HFrEF has been challenging because adjacent compounds are not available in the armamentarium of sponsored pharmaceutical companies.
Investigations of various polypills are underway for the management of heart failure.
References – The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816
The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. doi:10.1056/NEJMoa2204233
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. doi:10.1056/NEJMoa1811744
Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021;384(2):129-139. doi:10.1056/NEJMoa2030186
25 min
July 09, 2024379. SGLT Inhibitors: The Biology of SGLT Inhibition with Dr. Katherine Tuttle
CardioNerds (Drs. Gurleen Kaur and Richard Ferraro) and episode FIT Lead Dr. Saahil Jumkhawala (Cardiology Fellow at the University of Miami) discuss SGLT inhibitors, focusing on the biology of SGLT and its inhibition, with Dr. Katherine Tuttle (Executive Director for Research at Providence Healthcare, Co-Principal Investigator of the Institute of Translational Health Sciences, and Professor of Medicine at the University of Washington). Show notes were drafted by Dr. Saahil Jumkhawala. The episode audio was engineered by CardioNerds intern Christiana Dangas.
This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals.
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Pearls – The Biology of SGLT Inhibition with Dr. Katherine Tuttle
SGLT inhibitors, while initially developed as antidiabetic medications, have been shown to be beneficial for cardiovascular and renal outcomes. These benefits result from their on-target glucosuric effects and additional off-target effects.
The side effect profiles of SGLTis are primarily mediated by glucose reabsorption in their target tissues. The side effect profile of SGLTis must be considered when prescribing these medications and is generally favorable for SGLT2is versus SGLT1is.
Once SGLTis are prescribed, patients should be given specific attention to their eGFR, serum potassium, and clinical evaluations of volume status and blood pressure.
Strategies to increase implementation of and reduce clinical inertia for these important class of medication remain an area of active investigation
Show notes – The Biology of SGLT Inhibition with Dr. Katherine Tuttle
What should prompt consideration of starting an SGLT inhibitor?
Considerations for SGLT inhibitor initiation are based on a history of heart failure, kidney disease, and diabetes status.
In the EMPA-KIDNEY trial, empagliflozin improved cardiovascular and kidney outcomes in those with low GFR (regardless of level of albuminuria).
What is the mechanism of action of SGLT2 inhibitors?
SGLT2 inhibitors improve glycemic control by blocking SGLT2 receptor-mediated reabsorption of glucose in the proximal convoluted tubule, where 80-90% of this reuptake occurs, and increased downstream excretion of glucose and sodium chloride. SGLT2 inhibitors provide only a modest glucose-lowering effect, particularly for patients with GFR <45.
How do SGLT2 inhibitors improve cardiac function?
Through corrected glomerular hyperfiltration, there is a reduction in blood pressure, a reduction in sympathetic neural activity, and increased glucosuria, improving diuresis. Systemically, there is an increase in erythropoietin, which raises red blood cell mass and oxygen-carrying capacity.
Beyond inhibition of the SGLT2 receptor, which is isolated to the proximal convoluted tubule, there are additional off-target effects. Through non-receptor-mediated mechanisms, glucose transport is blocked into cells by blocking GLUT1 and GLUT4 receptors. They also reduce the mTORC signal transduction pathway, thereby reducing inflammation and glycolysis, leading to a cardioprotective effect in myocytes.
In the DAPA-CKD and CREDENCE trials, GFR decreases of up to 30% were correlated with improved renal and cardiovascular outcomes.
The cardiovascular benefit of SGLT2 inhibitors is not dose-dependent.
Where are SGLT1 receptors located?
SGLT1 receptors are found primarily in small and large bowel enterocytes, as well as the kidney proximal tubule, beyond the convoluted segment.
Around 10% of glucose re-uptake is mediated by SGLT1 receptors in the proximal tubule.
What are some common side effects of SGLT inhibitors?
Given SGLT1 receptors’ presence in the gastrointestinal tract, the side effects of SGLT1 inhibition are primarily gastrointestinal upset through decreased glucose reabsorption in the gut.
SGLT2 inhibitors’ side effects are primarily sequelae of glucosuria, particularly those of genitourinary infections, volume depletion, and euglycemic ketoacidosis (most commonly in patients with diabetes who are longstanding insulin users).
Additionally, a GFR decline of >30% should be suggestive of other issues for patients taking these medications, most commonly volume depletion or hypotension.
References – The Biology of SGLT Inhibition with Dr. Katherine Tuttle
Cowie M.R., Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020 Dec; 17(12):761-722.
Kuboto Y, Shimizu W. Clinical Benefits of Sodium-Glucose Cotransporter 2 Inhibitors and the Mechanisms Underlying their Cardiovascular Effects. JACC: Asia. 2022 Jun; 2:287-293.
Lopaschuk G.D., Verma S. Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors. JACC Basic Trans Sci. 2020 Jun; 5(6):632-644.
Harrington J., Udell J.A., Jones W.S., Anker S.D., Bhatt D.L., Petrie M.C., & Butler J. Empagliflozin in patients post myocardial infarction: rationale and design of the EMPACT-MI trial. American Heart Journal. 2022; 253:86-98.
Talha K.M., Anker S.D., & Butler J. SGLT-2 inhibitors in heart failure: a review of current evidence. International Journal of Heart Failure. 2023; 5(2):82.
Tuttle K.R. Digging deep into cells to find mechanisms of kidney protection by SGLT2 inhibitors. J Clin Invest. 2023; 133(5).
34 min
May 05, 2024368. Obesity: Procedural Management of Obesity with Dr. Steve Nissen
CardioNerds (Drs. Richard Ferraro, Gurleen Kaur, and Rupan Bose) discuss the growing epidemic of obesity and dive into the role of its procedural management with Dr. Steve Nissen, Chief Academic Officer at the Cleveland Clinic HVTI and past president of the American College of Cardiology. This is an exciting topic that reflects a major inflection point in cardiovascular care. In this episode, we discuss the importance of addressing obesity in cardiovascular care, as it is a major driver of cardiovascular disease and the progression of associated cardiovascular comorbidities. We look at the role of bariatric surgery and its ability to produce sustained weight loss. Finally, we look into the emerging role of new medical therapies such as GLP1 and GIP agonist medications. Notes were drafted by Dr. Rupan Bose and episode audio was edited by CardioNerds Intern Dr. Atefeh Ghorbanzadeh.
This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Novo Nordisk. See below for continuing medical education credit.
Claim CME for this episode HERE.
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Pearls and Quotes – Procedural Management of Obesity with Dr. Steve Nissen
Obesity is associated with adverse cardiovascular outcomes. Returning to a healthy weight can largely prevent the downstream consequences of obesity.
Regarding lifestyle modifications, diet alone is insufficient in sustaining prolonged weight loss. It is associated with short-term weight loss, but it is generally necessary to supplement with exercise and activity to ensure sustained weight loss.
Bariatric surgery should be considered for patients with BMI ≥40 kg/m2 or BMI ≥35 kg/m2 with obesity-related comorbid conditions who are motivated to lose weight and who have not responded to behavioral treatment with or without pharmacotherapy.
New emerging medications, including GLP1 receptor agonists, GIP receptor agonists, and glucagon receptor agonists, are beginning to approach weight loss levels that were previously only seen with bariatric surgery. Further research in this dynamic area is ongoing.
Show notes – Procedural Management of Obesity with Dr. Steve Nissen
Notes drafted by Dr. Rupan Bose.
What is the role of obesity in the burden of cardiovascular disease, and why is it so important for CardioNerds to address it?
According to the AHA, approximately 2.8 to 3.5 billion people worldwide are either overweight or obese. It is estimated that by 2030, 30% of people in the US will have a BMI greater than 30.
Adipose tissue is associated with cytokine release. Cytokines, in turn, can activate and increase levels of IL-1 beta, IL-6, and CRP, leading to an increased inflammatory state. This pro-inflammatory state then accelerates the rate of cardiovascular disease.
Obesity is also associated with significant joint and orthopedic diseases, which further impact patients’ quality of life and morbidity.
Additionally, obesity is associated with NASH cirrhosis. These adverse liver outcomes hold additional significant systemic implications and morbidity.
How do you determine one’s goal weight and goal BMI? Is BMI a good standard for measuring obesity?
BMI is a variable of both weight and height. However, it cannot differentiate those whose weight is from adipose tissue versus from muscle mass. Therefore, BMI measurements can sometimes be misleading. Waist circumference may be a better measurement standard for obesity and risk assessment.
The “apple shape” body type, with more abdominal fat, is associated with higher inflammation and cardiovascular risk than the “pear-shaped” body type, which is where there is more fat deposition in the buttocks and thighs. A fat distribution that is more centralized corresponds with greater cardiovascular risk.
“Normal” BMI and “normal” waist circumference can differ based on ethnicity. For example, a BMI of 22.6 in South Asians carries a similar risk to a BMI of 30 in White European patients. Therefore, providers must remain cognizant of these differences when making individual patient recommendations.
Does childhood obesity correlate with obesity at later ages? At what age should we start screening for and addressing obesity?
Childhood obesity, or obesity at a young age, often correlates with continued obesity later in life. But it is interesting that if one can return to a healthy body weight at some point in their life, one can largely prevent the downstream consequences of obesity
The USPSTF recommends clinicians screen for obesity in children and adolescents age 6 and older and offer behavioral interventions to promote improvements in weight status (grade B recommendation)
What procedures or surgeries are available to patients with obesity?
Bariatric surgery is an excellent option with great outcomes if done for the right patient.
The 2013 AHA/ACC/TOS guidelines for the management of overweight and obesity in adults recommend bariatric surgery for patients with BMI ≥40 kg/m2 or BMI ≥35 kg/m2 with obesity-related comorbid conditions who are motivated to lose weight and who have not responded to behavioral treatment with or without pharmacotherapy.
Several studies have shown that patients with bariatric surgery had a huge reduction in myocardial infarction, stroke, kidney disease, and death.
Bariatric surgery can help address other cardiovascular comorbidities. For example, the STAMPEDE trial (Schauer, R et al.) demonstrated that bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing or, in some cases, resolving hyperglycemia.
Additionally, the magnitude of weight loss from bariatric surgery is often greater than the absolute magnitude of weight loss through medical therapy alone. Therefore, for patients with a very high BMI, bariatric surgery may be better suited to achieve the necessary weight loss.
What emerging medications are available to patients with obesity? And what medications are just around the corner?
GLP1 agonists, or dual GIP-GLP1 receptor agonists, drugs are associated with approximately 20% reduction in body weight.
In the SELECT trial, semaglutide was associated with a 9.3% reduction in body weight (Please see GLP1 series for additional details!).
In the SURMOUNT-1 trial, tirzepatide was associated with a 22% reduction in body weight.
Future trials will look at triple agonists that combine GLP1, GIP, and glucagon agonist properties. One such drug is retatrutide, which previously demonstrated a 24% (and approximately 28.5% in females) reduction in body weight. These medications are approaching similar weight loss magnitudes to bariatric surgery (a Roux en Y procedure achieves approximately 25% weight loss on average), though additional studies are ongoing.
What other strategies can one use to lower body weight and maintain that weight loss?
Diet alone is not sustainable in reducing weight and keeping weight off. Unfortunately, the body subconsciously activates adaptive responses that down-regulate metabolism, which in turn burns fewer calories.
Therefore, exercise and activity play a key role in continuing to burn calories, allowing for sustained weight loss.
All patients should, therefore, be counseled on both diet and exercise strategies to address obesity and weight loss.
Discussing weight and body image is often a sensitive subject and can carry a stigma for some patients. What are some recommendations on how we can address these topics in a safe and supportive manner?
It is important to create a safe, supportive, and non-judgmental space when discussing weight with patients.
We should also make an effort to understand the specific drivers of each individual patient’s weight gain. Some drivers include emotional stress, socio-economic factors, lifestyle barriers, etc. By understanding each specific driver, we can be more targeted in our approach and build more individualized plans with our patients.
We can also recruit other clinical team members to assist the patient in their weight loss journey. Some such teammembers include dieticians, psychiatrists, social workers, etc.
References – Procedural Management of Obesity with Dr. Steve Nissen
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., … & Stefanski, A. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205-216.
https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
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