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Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individuals complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

AimsLipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.Methods and resultsCardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 [-13.6, 0] mg/dL) and corrected LDL-C (median -51.3 [-67.1, -34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.ConclusionBaseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.

AimsDespite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients.Methods and resultsA total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P

AimsBiomarkers of kidney tubule injury, inflammation and fibrosis have been studied extensively and established as risk markers of adverse kidney and cardiovascular disease (CVD) outcomes. However, associations of markers of kidney tubular function with adverse clinical events have not been well studied, especially in persons with chronic kidney disease (CKD).Methods and resultsUsing a sample of 2377 persons with CKD at the baseline Systolic Blood Pressure Intervention Trial (SPRINT) visit, we evaluated the association of three urine tubular function markers, alpha-1 microglobulin (α1m), beta-2 microglobulin (β2m), and uromodulin, with a composite CVD endpoint (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes) and mortality using Cox proportional hazards regression, adjusted for baseline estimated glomerular filtration rate (eGFR), albuminuria, and CVD risk factors. In unadjusted analysis, over a median follow-up of 3.8 years, α1m and β2m had positive associations with composite CVD events and mortality, whereas uromodulin had an inverse association with risk for both outcomes. In multivariable analysis including eGFR and albuminuria, a two-fold higher baseline concentration of α1m was associated with higher risk of CVD [hazard ratio (HR) 1.25; 95% confidence interval (CI): 1.10-1.45] and mortality (HR 1.25; 95% CI: 1.10-1.46), whereas β2m had no association with either outcome. A two-fold higher uromodulin concentration was associated with lower CVD risk (HR 0.79; 95% CI: 0.68-0.90) but not mortality (HR 0.86; 95% CI: 0.73-1.01) after adjusting for similar confounders.ConclusionAmong non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology—e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction. [ABSTRACT FROM AUTHOR]

Aims:There is a paucity of data on the influence of diabetes on long-term outcomes after ischaemic stroke (IS). We assessed whether outcomes after IS differ between patients with and without diabetes. Methods and results:Patients aged ≥65 years (n = 409 060) in Get With The Guidelines-Stroke (nationwide registry of stroke patients from 1690 sites in the USA) were followed for 3 years post-discharge. The outcomes of interest were mortality, cardiovascular and non-cardiovascular hospitalizations, heart failure (HF), and recurrence of IS/transient ischaemic attack (TIA). Patients with diabetes (29.6%) were younger and had more comorbidities. At 3 years post-discharge after IS, diabetes was associated with higher risks of adverse outcomes: all-cause mortality [cumulative incidence 46.0% vs. 44.2%, absolute difference (AD) 1.8%; adjusted hazard ratio (aHR) 1.24, 95% confidence interval 1.23-1.25], all-cause readmission (71.3% vs. 63.7%, AD 7.6%; aHR 1.22, 1.21-1.23), composite of mortality and all-cause readmission (84.1% vs. 79.3%, AD 4.8%; aHR 1.21, 1.20-1.22), composite of mortality and cardiovascular readmission (69.5% vs. 64.3%, AD 5.2%; aHR 1.19, 1.18-1.20), IS/TIA readmission (15.9% vs. 13.3%, AD 2.6%; aHR 1.18, 1.16-1.20), HF readmission (10.3% vs. 6.4%, AD 3.9%; aHR 1.60, 1.56-1.64), non-cardiovascular readmission (58.3% vs. 50.3%, AD 8.0%; aHR 1.28, 1.26-1.29), and non-IS/TIA readmission (67.6% vs. 59.7%, AD 7.9%; aHR 1.23, 1.22-1.25). Accounting for the initial severity of stroke using the National Institute of Health Stroke Scale as well as using propensity score matching method as a sensitivity analysis, did not modify the results. Conclusion:Among older IS patients diabetes was associated with increased risks of death, cardiovascular and non-cardiovascular hospitalizations, HF, and IS/TIA recurrence.

AimsPost-stroke hypertension is associated with poor short-term outcome, although the results have been conflicting. Our objective was to evaluate the association of blood pressure (BP) and in-hospital outcomes in patients with acute ischaemic stroke.Methods and resultsPatients in the Get With The Guidelines-Stroke registry with acute ischaemic stroke were included. Admission systolic and diastolic BP was used to compute mean arterial pressure (MAP) and pulse pressure (PP). The outcomes of interest were: in-hospital mortality, not discharged home, inability to ambulate independently at discharge and haemorrhagic complications due to thrombolytic therapy. A total of 309 611 patients with an ischaemic stroke were included. There was a J-shaped/U-shaped relationship between systolic BP and outcomes. Both lower and higher systolic BP values, compared with a central reference value, had higher risk of in-hospital death [e.g. adjusted odds ratio (95% confidence interval) (OR[CI]) = 1.16[1.13-1.20] for 120 vs. 150 mmHg and 1.24[1.19-1.30] for 200 vs. 150 mmHg], not discharged home (OR[CI] = 1.11[1.09-1.13] for 120 vs. 150 mmHg and 1.15[1.12-1.18] for 200 vs. 150 mmHg), inability to ambulate independently at discharge (OR[CI] = 1.16[1.13-1.18] for 120 vs. 150 mmHg and 1.09[1.06-1.11] for 200 vs. 150 mmHg). However, risk of haemorrhagic complications of thrombolytic therapy was lower with lower systolic BP (OR[CI] = 0.89[0.83-0.97] for 120 vs. 150 mmHg), while higher with higher systolic BP (OR[CI] = 1.21[1.11-1.32] for 200 vs. 150 mmHg). The results were largely similar for admission diastolic BP, MAP, and PP.ConclusionIn patients hospitalized with ischaemic stroke, J-shaped, or U-shaped relationships were observed between BP variables and short-term outcomes. However, haemorrhagic complications with thrombolytic therapy were lower with lower BP.

Background and Aims Guideline-directed medical therapy (GDMT) is recommended before mitral valve transcatheter edge-to-edge repair (MTEER) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR). Whether MTEER is being performed on the background of optimal GDMT in clinical practice is unknown. Methods Patients with left ventricular ejection fraction (LVEF) < 50% who underwent MTEER for FMR from 23 July 2019 to 31 March 2022 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were identified. Pre-procedure GDMT utilization was assessed. Cox proportional hazards models were constructed to evaluate associations between pre-MTEER therapy (no/single, double, or triple therapy) and risk of 1-year mortality or HF hospitalization (HFH). Results Among 4199 patients across 449 sites, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor–neprilysin inhibitors were used in 85.1%, 44.4%, 28.6%, and 19.9% before MTEER, respectively. Triple therapy was prescribed for 19.2%, double therapy for 38.2%, single therapy for 36.0%, and 6.5% were on no GDMT. Significant centre-level variation in the proportion of patients on pre-intervention triple therapy was observed (0%–61%; adjusted median odds ratio 1.48 [95% confidence interval (CI) 1.25–3.88]; P <.001). In patients eligible for 1-year follow-up (n = 2014; 341 sites), the composite rate of 1-year mortality or HFH was lowest in patients prescribed triple therapy (23.0%) compared with double (24.8%), single (35.7%), and no (41.1%) therapy (P <.01 comparing across groups). Associations persisted after accounting for relevant clinical characteristics, with lower risk in patients prescribed triple therapy [adjusted hazard ratio (aHR) 0.73, 95% CI.55–.97] and double therapy (aHR 0.69, 95% CI.56–.86) before MTEER compared with no/single therapy. Conclusions Under one-fifth of patients with LVEF <50% who underwent MTEER for FMR in this US nationwide registry were prescribed comprehensive GDMT, with substantial variation across sites. Compared with no/single therapy, triple and double therapy before MTEER were independently associated with reduced risk of mortality or HFH 1 year after intervention. [ABSTRACT FROM AUTHOR]

This article presents a post hoc analysis of two clinical trials, SUSTAIN 6 and PIONEER 6, which examined the effects of semaglutide on major adverse cardiovascular events (MACE) in individuals with type 2 diabetes. The analysis aimed to determine the impact of semaglutide compared to a placebo based on baseline glycated hemoglobin (HbA1c) levels. The findings indicate that semaglutide reduced the risk of MACE, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, across various baseline HbA1c values. The study was conducted ethically and with participant consent. The article also mentions that semaglutide effectively reduces HbA1c and body weight compared to a placebo, regardless of baseline HbA1c levels. The analysis suggests that semaglutide can be used to reduce MACE in individuals with type 2 diabetes, regardless of their HbA1c values, aligning with current guidelines. The study was funded by Novo Nordisk. [Extracted from the article]

The Canadian Cardiovascular Society (CCS) has proposed a new classification system for acute atherothrombotic myocardial infarction (AMI) based on tissue injury severity. The classification consists of four stages: Stage 1 is characterized by reversible injury and myocardial edema, Stage 2 involves irreversible cardiomyocyte necrosis, Stage 3 includes microvascular dysfunction, and Stage 4 is marked by microvascular destruction and hemorrhage. This new classification provides a more nuanced understanding of AMI and could be used for risk assessment and personalized care. It also offers potential targets for therapeutic interventions to improve patient outcomes. [Extracted from the article]

The article discusses the use of icosapent ethyl (IPE) for the treatment of hypertriglyceridemia and atherosclerosis. Hypertriglyceridemia is a significant risk factor for cardiovascular disease, and various medications have been developed to target elevated triglyceride levels. IPE, a highly purified omega-3 fatty acid, has shown promise in reducing adverse cardiovascular events. Three major clinical trials have demonstrated the clinical benefits of IPE, including a reduction in major coronary events and cardiovascular mortality. Despite some concerns about side effects and cost, the evidence supports the use of IPE in appropriate patients. [Extracted from the article]

This article, titled "Smoking habit change after cancer diagnosis: effect on cardiovascular risk," explores the patterns and cardiovascular consequences of post-diagnosis smoking habit change among cancer survivors. The study, conducted in Korea, analyzed data from a nationwide database of adults newly diagnosed with cancer. The findings highlight the need for strategies to address cardiovascular disease, the leading cause of death among cancer survivors, particularly in relation to smoking cessation. The study cohort consisted of 309,095 participants, and the research complied with ethical guidelines. [Extracted from the article]

For decades, heart failure with preserved ejection fraction (HFpEF) proved an elusive entity to treat. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to reduce the composite of heart failure hospitalization or cardiovascular death in patients with HFpEF in the landmark DELIVER and EMPEROR-Preserved trials. While improvements in blood sugar, blood pressure, and attenuation of kidney disease progression all may play some role, preclinical and translational research have identified additional mechanisms of these agents. The SGLT2 inhibitors have intriguingly been shown to induce a nutrient-deprivation and hypoxic-like transcriptional paradigm, with increased ketosis, erythropoietin, and autophagic flux in addition to altering iron homeostasis, which may contribute to improved cardiac energetics and function. These agents also reduce epicardial adipose tissue and alter adipokine signalling, which may play a role in the reductions in inflammation and oxidative stress observed with SGLT2 inhibition. Emerging evidence also indicates that these drugs impact cardiomyocyte ionic homeostasis although whether this is through indirect mechanisms or via direct, off-target effects on other ion channels has yet to be clearly characterized. Finally, SGLT2 inhibitors have been shown to reduce myofilament stiffness as well as extracellular matrix remodelling/fibrosis in the heart, improving diastolic function. The SGLT2 inhibitors have established themselves as robust, disease-modifying therapies and as recent trial results are incorporated into clinical guidelines, will likely become foundational in the therapy of HFpEF. [ABSTRACT FROM AUTHOR]