Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques “unstable” and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10–12% at one year and 18–20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial. The challenge is now to find the best strategies to achieve this in real-world practice. This review outlines the role that inflammation plays in atherosclerosis and provides an update on anti-inflammatory therapies currently being investigated to target atherosclerosis.

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management.

Background: Peak troponin level has been shown to predict benefit from early invasive management in type 1 MI (T1MI), but this relationship has not been established for type 2 MI (T2MI). The aim of this study was to investigate whether peak cardiac troponin T (cTnT) level in the first 24 hours of presentation is associated with rate of revascularisation in patients with T2MI. Methods: A statewide, multicentre, prospective cohort study with enrolment between 1 February 2020 and February 2021 was performed, with follow-up extending for 12 months. Those presenting to emergency departments with any form of myocardial injury (defined as troponin T above the upper limit of normal, >14 ng/l) in the first 24 hours of presentation were considered. Those under 18 years of age, those who had a previous emergency department assessment with troponin T and/or who had undergone coronary angiography in the 6 months prior to identification, were excluded. Results: T2MI or acute myocardial injury was associated with higher 12-month mortality (HR 1.87; 95% CI [1.43–2.43]; p<0.001) but a lower rate of subsequent T1MI (HR 0.46; 95% CI [0.31–0.68]; p<0.001) compared with patients presenting with T1MI. Peak cTnT was significantly associated with higher overall mortality on multivariable analysis (HR 1.01 per 100 ng/l cTnT; 95% CI [1.01–1.02]; p<0.001). Troponin level was not associated with a higher rate of revascularisation in patients with T2MI/acute myocardial injury who underwent a coronary angiogram. Conclusion: Patients with T2MI or acute myocardial injury have increased cardiovascular risk. Peak cTnT level appears to be a poor predictor for revascularisation requirement in patients with T2MI/acute myocardial injury who undergo coronary angiography.

Background: Autophagy is a homeostatic pathway supporting stress adaptation and is dysregulated in atherosclerosis. Its potential as a biomarker or therapeutic target in atherosclerotic vascular disease (ASVD) remains incompletely defined. We measured autophagic flux in peripheral blood mononuclear cells (PBMCs) from patients with peripheral arterial disease (PAD) or carotid stenosis (CS), compared with healthy controls, and explored clinical outcome associations. Methods: Ninety-four patients with PAD or CS and 19 healthy controls were studied. Autophagic flux was quantified from fresh blood using a validated ex vivo chloroquine-inhibition ELISA measuring LC3B-II accumulation. Major adverse cardiovascular events (MACE) and major adverse limb events (MALE) were ascertained over a median follow-up of 828 days. Results: The ASVD cohort comprised claudication (n = 16), chronic limb-threatening ischemia (CLTI; n = 49), and CS (n = 29). Autophagic flux was higher in ASVD than controls (mean 281.4 vs. 182.3 ng LC3B-II/mg protein/h; p < 0.0001) and remained independently associated after multivariable adjustment. Within CLTI, concurrent infection was associated with lower flux (p = 0.001), approaching control levels (p = 0.327). In CLTI, higher flux quartiles were associated with lower MACE risk, most strongly for quartile 3 (hazard ratio 0.07 vs. quartile 1, 95% CI 0.01–0.50; p = 0.009). Conclusion: Autophagic flux is elevated in PBMCs from ASVD patients, independent of age and sex. Attenuated flux in CLTI with concurrent infection may indicate autophagic exhaustion in advanced disease. The association between higher flux and lower MACE in CLTI suggests prognostic utility, warranting evaluation in larger prospective studies.