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.

Background: The risk of cardiovascular disease (CVD) varies among patients with diabetes. Evidence is insufficient for comparing coronary artery calcium (CAC) and measures of renal dysfunction in reclassifying CVD risk among these patients. Hypothesis: This study assesses whether CAC enhances discrimination and net reclassification improvement (NRI) compared to measures of renal dysfunction in persons with diabetes. Methods: We used Cox proportional hazard models to compare the performance of CAC and measures of renal dysfunction in predicting CVD in the Multi-Ethnic Study of Atherosclerosis (MESA). Models adjusted for age, sex, race, ever smoking, body mass index, systolic blood pressure, total cholesterol, high-density cholesterol, triglycerides, A1c, fasting blood sugar, hypertension medication use, and insulin use. Measures of renal dysfunction included estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR), assessed individually or as composite variables (eGFR <60 mL/min/1.73 m 2 or UACR >30 mg/g). Improvements in c-statistics and the 10-year area under the curve (AUC) were calculated. Results: A total of 839 participants, with a mean age of 64.5 ± 9 years, 396 female (47.2%), 155 White (18.4%), 321 Black (38%), 260 Hispanic (31%), and 103 Chinese (12%), were included. Of the total, 528 (63%) had CAC >0, 139 (17%) had eGFR <60 mL/min/1.73 m 2 , and 232 (28%) had UACR >30 mg/g. Patients were followed up for a mean of 13.4 years. CAC, eGFR, and UACR were associated with an increased risk of CVD in all predefined models. CVD risk increased incrementally with the increase in CAC category (Table). The addition of CAC significantly increased AUC in Model 1 with baseline variables (0.680 vs. 0.726, p=0.002), Model 2 with individual measures of renal dysfunction (0.702 vs. 0.745 p=0.003), and Model 3 with composite measures of renal dysfunction (0.706 vs. 0.746, p=0.004). Conclusion: CAC reclassifies CVD risk beyond measures of renal dysfunction and may be used to identify higher-risk patients among those with diabetes.

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.

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.

As the prevalence of coronary artery disease continues to increase worldwide, understanding the nuances of complex calcific coronary lesions becomes paramount. Coronary artery calcium (CAC) is a well-established, widely available, and highly specific marker of subclinical and advanced atherosclerosis. It remains a vital adjudicator of atherosclerotic cardiovascular disease (ASCVD) and facilitates the up- or down-stratifying of asymptomatic, intermediate risk patients. Notably, the high prevalence of CAC in coronary heart disease (CHD) patients makes the percutaneous treatment of heavily calcified coronary lesions particularly challenging. These cases have a higher risk of immediate complications, late failures due to stent underexpansion or malapposition, and poor clinical outcomes. In this setting, understanding lesion pathophysiology and characterizing calcium deposition with multimodal imaging are crucial steps to improve the successful treatment of these lesions. Therefore, this review explores CAC in the context of complicated and severely calcified lesions. We seek to ameliorate clinical uncertainties and synthesize growing amounts of research to help encourage a homogenous approach to complex calcific coronary lesions. To that end, this comprehensive review paper will first cover epidemiology, pathophysiology, and the types of calcific lesions. Next, we will review acute and long-term complications, as well as lesion preparation and intervention. Last, this review will explore the role of imaging and the contemporary management of severely calcified lesions.

Background: Coronary computed tomography angiography -derived plaque burden is associated with the risk of cardiovascular events and is expected to be utilized in clinical practice. Understanding of CT quantitative plaque volume compares to normative values in the general population is clinically important for determining management. This study aimed to investigate the distribution of coronary artery plaque volume in general population and to develop nomographic quantitative plaque volume using the Miami Heart Study, a large community-based cohort study. Methods: A total of 2,301 asymptomatic subjects without coronary artery disease (CAD) enrolled in the Miami Heart Study were included. Quantitative assessments of atherosclerotic plaque volume (total, calcified, and non-calcified plaque) were performed using artificial intelligence-guided quantitative coronary computed tomography angiography analysis (AI-QCT). The percentiles of the plaque distribution by gender and age were estimated with nonparametric techniques. Results: The mean age was 53.5 years and 50.4% were male. The majority of study participants were Hispanic/Latino (47.2%) and White (85.5%). In terms of traditional risk factors, approximately one-third of the cohort were current or former smokers, 4.3% had diabetes, 24.9% had hypertension, and 34.9% had high cholesterol or lipid abnormalities. Overall, 93.1% of men and 84.6% of women had any plaque using AI-QCT. The median total plaque volume was 54 mm 3 (IQR 16-126 mm 3 ) and increased with age. Male subjects had more median total plaque volume, calcified plaque volume, and noncalcified plaque volume than female subjects (80 mm 3 vs 34mm 3 , 4 mm 3 vs 2 mm 3 , and 66 mm 3 vs 27 mm 3 , respectively). Younger individuals tend to have a higher percentage of noncalcified plaque. Conclusions: In this asymptomatic population without known CAD, 93.1% of men and 84.6% of women had CAD detected using AI-QCT. Additionally, we developed age- and sex-specific nomograms for atherosclerotic plaque volume. Our data enhance the understanding of plaque volume distribution in general population and should be an important indicator in clinical practice.

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-1β, 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.

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 multi-center 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 anti-atherogenic 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.