Subclinical Atherosclerosis to Guide Treatment in Dyslipidemia and Diabetes Mellitus.

PURPOSE OF REVIEW: Dyslipidemia and type 2 diabetes mellitus are two common conditions that are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we aimed to provide an in-depth and contemporary review of non-invasive approaches to assess subclinical atherosclerotic burden, predict cardiovascular risk, and guide appropriate treatment strategies. We focused this paper on two main imaging modalities: coronary artery calcium (CAC) score and computed tomography coronary angiography. RECENT FINDINGS: Recent longitudinal studies have provided stronger evidence on the relationship between increased CAC, thoracic aorta calcification, and risk of cardiovascular events among those with primary hypercholesterolemia, highlighting the beneficial role of statin therapy. Interestingly, resilient profiles of individuals not exhibiting atherosclerosis despite dyslipidemia have been described. Non-conventional markers of dyslipidemia have also been associated with increased subclinical atherosclerosis presence and burden, highlighting the contribution of apolipoprotein B-100 (apoB)-rich lipoprotein particles, such as remnant cholesterol and lipoprotein(a), to the residual risk of individuals on-target for low-density lipoprotein cholesterol (LDL-C) goals. Regarding type 2 diabetes mellitus, variability in atherosclerotic burden has also been found, and CAC testing has shown significant predictive value in stratifying cardiovascular risk. Non-invasive assessment of subclinical atherosclerosis can help reveal the continuum of ASCVD risk in those with dyslipidemia and diabetes mellitus and can inform personalized strategies for cardiovascular disease prevention in the primary prevention setting.

Recent advances in cardiovascular risk assessment: The added value of non-invasive anatomic imaging.

In 2022, multiple original research studies were conducted highlighting the utility of coronary artery calcium (CAC) imaging in young individuals and provided further evidence for the role of CAC to improve atherosclerotic cardiovascular disease (ASCVD) risk assessment. Mean calcium density was shown to be a more reliable predictor than peak density in risk assessment. Additionally, in light of the ACC/AHA/Multispecialty Chest Pain Guideline's recent elevation of coronary computed tomography angiography (CCTA) to a Class I (level of evidence A) recommendation as an index diagnostic test for acute or stable chest pain, several studies support the utility of CCTA and guided future directions. This review summarizes recent studies that highlight the role of non-invasive imaging in enhancing ASCVD risk assessment across different populations.

Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta-analysis.

OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of tirzepatide compared to glucagon-like peptide-1 receptor agonists (GLP-1 RA) and other weight loss drugs in the treatment of overweight and obesity. METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. RESULTS: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects. CONCLUSIONS: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study.

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1-100, 101-400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1-100, 160 (16%) had CAC 101-400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1-100 (8% [n = 15] vs 18% [n = 26]), CAC 101-400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50-59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]). Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.