Effect of tirzepatide on the progression of coronary atherosclerosis using MDCT: Rationale and design of the tirzepatide treatment on coronary atherosclerosis progression: The (T-Plaque) randomized-controlled trial design.

INTRODUCTION: Tirzepatide is a novel once-week dual GIP/GLP-1 RA agonist approved for T2DM and its role to reduce cardiovascular events remains to be elucidated. The goal of this trial is to assess how tirzepatide affects the progression of atherosclerotic plaque as determined by multidetector computed tomography angiography (MDCTA). METHODS: This trial is a double blind, randomized, prospective, placebo-controlled multicenter phase IV trial. Participant eligible for the study will be adults with T2DM between 40 and 80 years of age who have HbA1c ≥ 7.0% to ≤ 10.5% and at least 20% stenosis in major epicardial vessel on CCTA. Baseline examination will include the results of their demographics, lab tests, coronary calcium, as well as coronary plaque volume/composition. Following randomization, tirzepatide or placebo will be given at a weekly dose of 2.5 mg, and a fixed dose-escalation strategy will be followed. Patients will undergo quarterly visits for safety assessments and labs, and follow up with repeat CCTA at 1 year. DISCUSSION: This study evaluates the antiatherogenic potential of tirzepatide, providing a mechanism of potential CV benefit. This is crucial to our understanding of T2DM treatment and CVD since plaque progression portends worse outcomes in these populations. MDCTA is a noninvasive method that assesses the volume, composition, and degree of coronary vessel stenosis. CONCLUSION: This study will be the first study to assess the effects of tirzepatide on atherosclerotic plaque progression measured by MDCTA in participants with T2DM.

Effect of colchicine on progression of known coronary atherosclerosis in patients with STable CoROnary artery disease CoMpared to placebo (EKSTROM) trial-rationale and design.

BACKGROUND: Cardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. METHODS: Eighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. RESULTS: As of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1ß, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. CONCLUSION: EKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system. TRIAL REGISTRATION: Registry: clinicaltrials.gov, Registration Number: NCT06342609 url: https://www. CLINICALTRIALS: gov/study/NCT06342609?term=EKSTROM&rank=1.

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. METHODS: A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. RESULTS: In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. CONCLUSIONS: The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Plaque Progression Differences Between Apixaban and Rivaroxaban in Patients With Atrial Fibrillation Measured With Cardiac Computed Tomography and Plaque Quantification.

BACKGROUND: Direct oral anticoagulants (DOACs) have been associated with less calcification and coronary plaque progression than warfarin. Whether different DOACs have different effects on coronary plaque burden and progression is not known. We compared the 12-month effects of apixaban and rivaroxaban on plaque characteristics and vascular morphology in patients with atrial fibrillation through quantitative cardiac computed tomographic angiography. STUDY QUESTION: In patients with nonvalvular atrial fibrillation using apixaban or rivaroxaban, are there differences in plaque quantification and progression measured with cardiac computed tomography? STUDY DESIGN: This is a post hoc analysis of 2 paired prospective, single-centered, randomized, open-label trials with blinded adjudication of results. In total, 74 patients were prospectively randomized in parallel trials: 29 to apixaban (2.5-5 mg BID) and 45 to rivaroxaban (20 mg QD). Serial cardiac computed tomographic angiography was performed at baseline and 52 weeks. MEASURES AND OUTCOMES: Comprehensive whole-heart analysis was performed for differences in the progression of percent atheroma volume (PAV), calcified plaque (CP) PAV, noncalcified plaque (NCP) PAV, positive arterial remodeling (PR) ≥1.10, and high-risk plaque (Cleerly Labs, New York, NY). RESULTS: Both groups had progression of all 3 plaque types (apixaban: CP 8.7 mm 3 , NCP 69.7 mm 3 , and LD-NCP 27.2 mm 3 ; rivaroxaban: CP 22.9 mm 3 , NCP 66.3 mm 3 , and LD-NCP 11.0 mm 3 ) and a total annual plaque PAV change (apixaban: PAV 1.5%, PAV-CP 0.12%, and PAV-NCP 0.92%; rivaroxaban: PAV 2.1%, PAV-CP 0.46%, and PAV-NCP 1.40%). There was significantly lower PAV-CP progression in the apixaban group compared with the rivaroxaban group (0.12% vs. 0.46% P = 0.02). High-risk plaque characteristics showed a significant change in PR of apixaban versus rivaroxaban ( P = 0.01). When the propensity score weighting model is applied, only PR changes are statistically significant ( P = 0.04). CONCLUSIONS: In both groups, there is progression of all types of plaque. There was a significant difference between apixaban and rivaroxaban on coronary calcification, with significantly lower calcific plaque progression in the apixaban group, and change in positive remodeling. With weighted modeling, only PR changes are statistically significant between the 2 DOACs.

Cardiovascular Risk Prediction Models in People Living with HIV in Colombia.

BACKGROUND: People living with HIV are at increased risk of cardiovascular disease. Cardiovascular risk (CVR) prediction scores are powerful tools for individualized assessment that inform decision-making about follow-up frequency, hypolipemiant treatment intensification, and choice antiretroviral therapy. OBJECTIVES: The objectives of the study were to evaluate the performance of multiple cardiovascular assessment scores in predicting major adverse cardiovascular events (MACE) at 5 and 10 years. Framingham (2004, 2008, and Colombia-adjusted), SCORE, PROCAM, ASCVD, and D:A:D scores were included in the analysis. METHODS: Data were obtained from a medical registry of adults living with HIV attended by a teaching hospital in Colombia. All patients with complete information necessary for risk score calculations and determination of MACE at 5 and 10 years were included in the study. Receiver operating characteristic curves (ROC) were generated using calculations with all the aforementioned models for every individual. Differences between curves were compared with De- Long's test. RESULTS: A total of 808 patients were included in the analysis. Mean age was 35 years, and 12% were female. The majority of subjects had low and very low CVR. Eight MACE occurred during follow-up. Area under ROC curves were: Framingham (0.90), Framingham ATP3 (0.92), Framingham calibrated for Colombia (0.90), SCORE (0.92), PROCAM (0.92), ASCVD (0.89), and D:A:D (0.92), with no statistically significant differences. CONCLUSIONS: The evaluated scores had an acceptable performance for HIV-infected patients in the studied cohort, especially for those in low and very low risk categories.

Impact of Nonalcoholic Hepatic Steatosis on the Warranty Period of a Coronary Artery Calcium Score of 0: Results From the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: For individuals with a coronary artery calcium (CAC) score of 0, CAC rescans at appropriate timings are recommended, depending on individual risk profiles. Although nonalcoholic fatty liver disease, recently redefined as metabolic-associated fatty liver disease, is a risk factor for atherosclerotic cardiovascular disease events, its relationship with the warranty period of a CAC score of 0 has not been elucidated. METHODS: A total of 1944 subjects from the MESA (Multi-Ethnic Study of Atherosclerosis) with a baseline CAC score of 0, presence or absence of nonalcoholic hepatic steatosis, and at least 1 follow-up computed tomography scan were included. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. The association between nonalcoholic hepatic steatosis and new CAC incidence (CAC score >0) was evaluated using a Weibull survival model. RESULTS: Nonalcoholic hepatic steatosis was identified in 268 (14%) participants. Participants with nonalcoholic hepatic steatosis had higher CAC incidence than those without nonalcoholic hepatic steatosis. Nonalcoholic hepatic steatosis was independently associated with new CAC incidence after adjustment for atherosclerotic cardiovascular disease risk factors (hazard ratio, 1.28 [95% CI, 1.05-1.57]; P=0.015). Using a 25% testing yield (25% of participants with zero CAC at baseline would be expected to have developed a CAC score >0), the warranty period of a CAC score of 0 in participants with nonalcoholic hepatic steatosis was shorter than in those without nonalcoholic hepatic steatosis (4.7 and 6.3 years). This association was consistent regardless of sex, race/ethnicity, age, and 10-year atherosclerotic cardiovascular disease risk. CONCLUSIONS: Nonalcoholic hepatic steatosis had an impact on the warranty period of a CAC score of 0. The study suggests that the time period until a CAC rescan should be shorter in those with nonalcoholic hepatic steatosis and a CAC score of 0.

Testosterone therapy and the risk of cardiovascular disease in older, hypogonadal men.

The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the context of aging, obesity, and endogenous sex hormones on CV disease (CVD) risk to support informed clinical decision-making. Observational studies have variably linked low endogenous testosterone with increased CVD risk, while randomized controlled trials (RCTs) demonstrate that TT yields cardiometabolic benefits without increasing short-term CV risk. The TRAVERSE trial, as the first RCT powered to assess CVD events, did not show increased major adverse cardiac events (MACE) incidence; however, its limitations - specifically the maintenance of testosterone at low-normal levels, a high participant discontinuation rate, and short follow-up - warrant a careful interpretation of its results. Furthermore, findings from the TTrials cardiovascular sub-study, which showed an increase in non-calcified plaque, indicate the need for ongoing research into the long-term CV impact of TT. The decision to initiate TT should consider the current evidence gaps, particularly for older men with known CVD. The CV effects of maintaining physiological testosterone levels through exogenous means remain to be fully explored. Until more definitive evidence is available, clinical practice should prioritize individualized care and informed discussions on the potential CV implications of TT.

Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design.

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

Regression and stabilization of atherogenic plaques.

Atherosclerotic plaque assessment has become a crucial element in the examination of cardiovascular diseases. Plaque may exhibit progression and could become unstable if not treated, making plaque regression and stabilization among the most important goals of any cardiovascular intervention in cardiovascular medicine. In this review, we explore the current understanding of plaque regression and stabilization, discuss imaging and measurement techniques, and examine the evidence for pharmacological interventions and other interventions aimed at addressing this condition.

Encapsulated Calcified Hematoma Mimicking a Cardiac Tumor, Diagnosed 25 Years Post-Traumatic Injury.

A 45-year-old man presented with nonspecific symptoms caused by a mass compressing the right ventricle. Cardiac computed tomography accurately predicted the operative and pathologic appearance of the mass, and the final diagnosis of an encapsulated cardiac hematoma was confirmed by pathologic examination. This condition is infrequent and mimics a cardiac tumor. (Level of Difficulty: Advanced.).

Artificial intelligence using a deep learning versus expert computed tomography human reading in calcium score and coronary artery calcium data and reporting system classification.

BACKGROUND: Artificial intelligence (AI) applied to cardiac imaging may provide improved processing, reading precision and advantages of automation. Coronary artery calcium (CAC) score testing is a standard stratification tool that is rapid and highly reproducible. We analyzed CAC results of 100 studies in order to determine the accuracy and correlation between the AI software (Coreline AVIEW, Seoul, South Korea) and expert level-3 computed tomography (CT) human CAC interpretation and its performance when coronary artery disease data and reporting system (coronary artery calcium data and reporting system) classification is applied. METHODS: A total of 100 non-contrast calcium score images were selected by blinded randomization and processed with the AI software versus human level-3 CT reading. The results were compared and the Pearson correlation index was calculated. The CAC-DRS classification system was applied, and the cause of category reclassification was determined using an anatomical qualitative description by the readers. RESULTS: The mean age was age 64.5 years, with 48% female. The absolute CAC scores between AI versus human reading demonstrated a highly significant correlation (Pearson coefficient R  = 0.996); however, despite these minimal CAC score differences, 14% of the patients had their CAC-DRS category reclassified. The main source of reclassification was observed in CAC-DRS 0-1, where 13 were recategorized, particularly between studies having a CAC Agatston score of 0 versus 1. Qualitative description of the errors showed that the main cause of misclassification was AI underestimation of right coronary calcium, AI overestimation of right ventricle densities and human underestimation of right coronary artery calcium. CONCLUSION: Correlation between AI and human values is excellent with absolute numbers. When the CAC-DRS classification system was adopted, there was a strong correlation in the respective categories. Misclassified were predominantly in the category of CAC = 0, most often with minimal values of calcium volume. Additional algorithm optimization with enhanced sensitivity and specificity for low values of calcium volume will be required to enhance AI CAC score utilization for minimal disease. Over a broad range of calcium scores, AI software for calcium scoring had an excellent correlation compared to human expert reading and in rare cases determined calcium missed by human interpretation.

Major Global Coronary Artery Calcium Guidelines.

This review summarizes the framework behind global guidelines of coronary artery calcium (CAC) in atherosclerotic cardiovascular disease risk assessment, for applications in both the clinical setting and preventive therapy. By comparing similarities and differences in recommendations, this review identifies most notable common features for the application of CAC presented by different cardiovascular societies across the world. Guidelines included from North America are as follows: 1) the 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease; and 2) the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for Prevention of Adult Cardiovascular Disease. The authors also included European guidelines: 1) the 2019 European Society for Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias; and 2) the 2016 National Institute for Health and Care Excellence Clinical Guidelines. In this comparison, the authors also discuss: 1) the Cardiac Society of Australia and New Zealand Guidelines on CAC; 2) the Chinese Society of Cardiology Guidelines; and 3) the Japanese Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. Last, they include statements made by specialty societies including the National Lipid Association, Society of Cardiovascular Computed Tomography, and U.S. Preventive Services Task Force. Utilizing an in-depth review of clinical evidence, these guidelines emphasize the importance of CAC in the primary and secondary prevention of atherosclerotic cardiovascular disease. International guidelines all empower a dynamic clinician-patient relationship and advocate for individualized discussions regarding disease management and pharmacotherapy treatment. Some differences in precise coronary artery calcium score intervals, risk cut points, treatment thresholds, and stratifiers of specific patient subgroups do exist. However, international guidelines employ more similarities than differences from both a clinical and functional perspective. Understanding the parallels among international coronary artery calcium guidelines is essential for clinicians to correctly adjudicate personalized statin and aspirin therapy and further medical management.

Assessment of left main coronary artery disease: a comparison between invasive and noninvasive.

Left main coronary artery disease has significant therapeutic as well as prognostic implications. The presence of left main coronary artery stenosis is strongly associated with poor short- and long-term prognoses. Accurate identification of left main stenosis is extremely important since it would be the main factor to guide management. There are several modalities used to determine the presence of atherosclerosis and the degree of stenosis in a left main coronary artery. Newer modalities allow for an accurate evaluation of left main stenosis and atherosclerosis. In this review, we go through different invasive and noninvasive modalities to diagnose left main stenosis, shedding more light into coronary computed tomography angiography, and its accuracy in this specific diagnosis.

Serial Changes in Troponin I in COVID-19 Vaccine-Associated Myocarditis.

A 63-year-old woman presented with atypical chest pain after a third dose of the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine. Serial cardiac troponin measurements were performed to evaluate the trajectory of her time-concentration curve which showed a typical myocarditis curve with rapid normalization. The diagnosis of myocarditis was confirmed by cardiac magnetic resonance imaging and follow-up imaging showed resolution. All symptoms resolved with weeks.

LDL receptor and pathogen processes: Functions beyond normal lipids.

Although the role of the LDL receptor concerning lipids is well known, its role in various viral and parasitic infections, and in regulating the inflammatory response is poorly understood. Several infectious agents use the LDL receptor as a port of entry, and others depend on it for their cycle of infection. In this review, we focus on the discovery, structure, and normal function of the LDL receptor, as well as its role in a selection of infections. The LDL receptor plays an important role in certain infections and is a potential target for treatment deserving further research.