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Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology., (© 2024 the European Society of Cardiology.)

Dyslipidaemia is a common chronic kidney disease (CKD) and contributes to excessively elevated cardiovascular mortality. The pathophysiology is complex and modified by comorbidities like the presence/absence of proteinuria, diabetes mellitus or drug treatment. This paper provides an overview of currently available treatment options. We focused on individuals with CKD and excluded those on renal replacement therapy (haemodialysis, peritoneal dialysis, or kidney transplantation). The use of statins is safe and recommended in most patients, but guidelines vary with respect to low-density lipoprotein (LDL) cholesterol goals. While no dedicated primary or secondary prevention studies are available for pro-protein convertase subtilisin/kexin type 9 inhibitors, secondary analyses of large outcome trials reveal no effect modification on endpoints by the presence of CKD. Similar data have been shown for bempedoic acid, but no definite conclusion can be drawn with respect to efficacy and safety. No outcome trials are available for inclisiran while the cholesterol lowering effects seem to be unaffected by CKD. Finally, the value of fibrates and icosapent ethyl in CKD is unclear. Lipid abnormalities contribute to the massive cardiovascular disease burden in CKD. Lowering of LDL cholesterol with statins (and most likely PCSK9 inhibitors) reduces the event rate and thus statin therapy should be initiated in almost all individuals. Other interventions (bempedoic acid, inclisiran, fibrates, or icosapent ethyl) currently need a case-by-case decision before prescription., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood., Objectives: The purpose of this study was to investigate the short-term effects of lower air temperature and cold spells on the risk of hospitalization for MI in Sweden., Methods: This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature (1 km 2 resolution) was estimated using machine learning, and percentiles of daily temperatures experienced by individuals in the same municipality were used as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least 2 consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating conditional logistic regression models with distributed lag nonlinear models using lag 0 to 1 (immediate) and 2 to 6 days (delayed) was used to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI)., Results: A decrease of 1-U in percentile temperature at a lag of 2 to 6 days was significantly associated with increased risks of total MI, NSTEMI, and STEMI, with ORs of 1.099 (95% CI: 1.057-1.142), 1.110 (95% CI: 1.060-1.164), and 1.076 (95% CI: 1.004-1.153), respectively. Additionally, cold spells at a lag of 2 to 6 days were significantly associated with increased risks for total MI, NSTEMI, and STEMI, with ORs of 1.077 (95% CI: 1.037-1.120), 1.069 (95% CI: 1.020-1.119), and 1.095 (95% CI: 1.023-1.172), respectively. Conversely, lower air temperature and cold spells at a lag of 0 to 1 days were associated with decreased risks for MI., Conclusions: This nationwide case-crossover study reveals that short-term exposures to lower air temperature and cold spells are associated with an increased risk of hospitalization for MI at lag 2 to 6 days., Competing Interests: Funding Support and Author Disclosures This study has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 820655 (EXHAUSTION). This work was supported by a scholarship under the State Scholarship Fund by the China Scholarship Council (File No. 201906010316). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analysed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety., Methods: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs vs. VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effects model meta-analysis, and their robustness was investigated using sensitivity and influential analyses., Results: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3587 patients (2489 VKA vs. 1098 DOAC therapy). The pooled estimates for stroke or systemic embolism [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.57, 1.15] and thrombus resolution (OR: 1.12; 95% CI: 0.86, 1.46) were comparable, and there was low heterogeneity overall across the included studies. The use of DOACs was associated with lower odds of all-cause death (OR: 0.65; 95% CI: 0.46, 0.92) and a composite bleeding endpoint (OR: 0.67; 95% CI: 0.47, 0.97). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots., Conclusion: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution, compared with VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention., Methods and Results: Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P =0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups., Conclusions: In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

The working diagnosis Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA) is being increasingly recognized with the common use of high-sensitivity troponins and coronary angiography, accounting for 5% to 10% of all acute myocardial infarction presentations. Cardiac magnetic resonance (CMR) imaging is pivotal in patients presenting with suspected MINOCA, mainly to delineate those with a nonischemic cause, for example, myocarditis and Takotsubo syndrome, from those with true ischemic myocardial infarction, that is, MINOCA. The optimal timing for CMR imaging in patients with suspected MINOCA has been uncertain and, until recently, not been examined prospectively. Previous retrospective studies have indicated that the diagnostic yield decreases with time from the acute event. The SMINC studies (Stockholm Myocardial Infarction with Normal Coronaries) show that CMR should be performed early in all patients with the working diagnosis of MINOCA, with the possible exception of patients who are clearly identified as having Takotsubo syndrome as determined by echocardiography. In addition to CMR imaging, other investigations of importance in selected patients may be pulmonary artery computed tomography to exclude pulmonary embolism, optical coherence tomography to identify plaque disruption, and acetylcholine provocation to identify coronary artery spasm. Imaging of patients with the working diagnosis MINOCA, which is centered on CMR together with supplemental investigations, results in a clear diagnosis in approximately three-quarters of the patients. This is a good example of personalized medicine, because a correct diagnosis will not only increase the satisfaction of the individual patient but also result in optimizing treatment without harming the patient., Competing Interests: Dr Reynolds has received unrestricted donations from Abbott and Siemens. Dr Nickander received speaker fees from Sanofi Genzyme.

Background: A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown., Methods: We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated., Results: We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%., Conclusion: In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker., (© 2023. The Author(s).)

Although cardiovascular diseases (CVDs) are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic CVD and heart failure (HF). The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolaemia, type 2 diabetes, obesity, and HF; the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of CVDs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

As global temperatures rise, extreme heat events are projected to become more frequent and intense. Extreme heat causes a wide range of health effects, including an overall increase in morbidity and mortality. It is important to note that while there is sufficient epidemiological evidence for heat-related increases in all-cause mortality, evidence on the association between heat and cause-specific deaths such as cardiovascular disease (CVD) mortality (and its more specific causes) is limited, with inconsistent findings. Existing systematic reviews and meta-analyses of epidemiological studies on heat and CVD mortality have summarized the available evidence. However, the target audience of such reviews is mainly limited to the specific field of environmental epidemiology. This overarching perspective aims to provide health professionals with a comprehensive overview of recent epidemiological evidence of how extreme heat is associated with CVD mortality. The rationale behind this broad perspective is that a better understanding of the effect of extreme heat on CVD mortality will help CVD health professionals optimize their plans to adapt to the changes brought about by climate change and heat events. To policymakers, this perspective would help formulate targeted mitigation, strengthen early warning systems, and develop better adaptation strategies. Despite the heterogeneity in evidence worldwide, due in part to different climatic conditions and population dynamics, there is a clear link between heat and CVD mortality. The risk has often been found to be higher in vulnerable subgroups, including older people, people with preexisting conditions, and the socioeconomically deprived. This perspective also highlights the lack of evidence from low- and middle-income countries and focuses on cause-specific CVD deaths. In addition, the perspective highlights the temporal changes in heat-related CVD deaths as well as the interactive effect of heat with other environmental factors and the potential biological pathways. Importantly, these various aspects of epidemiological studies have never been fully investigated and, therefore, the true extent of the impact of heat on CVD deaths remains largely unknown. Furthermore, this perspective also highlights the research gaps in epidemiological studies and the potential solutions to generate more robust evidence on the future consequences of heat on CVD deaths., Competing Interests: Disclosures None.

Background: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA)., Objectives: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex., Methods: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and β 2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay., Results: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-β 2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients., Conclusions: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Despite the atherosclerotic cardiovascular disease (ASCVD) risk reduction achieved by low-density lipoprotein cholesterol (LDL-C) lowering therapy, residual ASCVD risk still exists. Previous epidemiological studies have suggested high plasma triglyceride (TG) levels as a risk factor or risk marker for ASCVD independent of LDL-C levels. In this review, we highlighted the underlying pathophysiology of hypertriglyceridaemia, the mechanistic action of therapeutic agents, the interpretation of conflicting results on recent clinical trials, and the present options for primary and secondary prevention. The benefits of fibrates-induced reduction in TG and increase in high-density lipoprotein cholesterol might outweigh the disadvantages of increasing LDL-C levels in primary prevention. In secondary CVD prevention, using eicosapentaenoic acid without docosahexaenoic acid, in addition to statins, will be beneficial. This comprehensive review may prove useful for the development of novel approaches that target hypertriglyceridaemia in future., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values., Methods and Results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [ r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I ² = 30.7%) and 1.20 (1.18-1.23; I ² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I ² = 8.4%) and 1.14 (1.12-1.16; I ²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near ( P < 0.001), +0.0037 for far wall ( P = 0.006)]., Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls., Competing Interests: Conflict of interest: M.J.S. is a full-time employee of AstraZeneca. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA ( n = 99) in Sweden were included, complemented by matched subjects with MI-CAD ( n = 99) and controls ( n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively ( p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Aims: Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) are a heterogenous group and previous studies indicate a decreased Health-related quality-of-life (HRQoL) compared with patients with myocardial infarction with obstructive coronary artery disease and healthy individuals. However, longitudinal data are scarce. Therefore, the aim was to explore HRQoL among patients with MINOCA during a one-year period after the acute event in comparison with a group of healthy individuals and to describe HRQoL in patients with Takotsubo Syndrome (TTS)., Methods and Results: Patients with MINOCA were recruited from five hospitals in the Stockholm region (SMINC-2 study, clinical trials: NCT2318498). Patients responded to the HRQoL questionnaire RAND-36 between days 2-4, after 6 and 12 months respectively. A sample of population-based individuals was used as a comparison group. A total of 142 MINOCA patients, (70% women) mean age of 56 years, responded. A population-based sample of 317 volunteers (66% women) mean age of 57 years. Patients with MINOCA scored lower than the comparison group in the domains role functioning physical, social functioning, and role functioning emotional (P = 0.01-0.02) at 12 months. In these domains of HRQoL there was no improvement in MINOCA patients during 12 months follow-up. In the domains of energy/fatigue vitality and emotional well-being the scores improved and were similar to the comparison group at 12 months. Patients with TTS scored generally lower on RAND-36 than MINOCA patients without TTS., Conclusion: Physical, social, and emotional functioning did not improve during the first year after MINOCA, indicating a need for increased follow-up including psychological support., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To compare a structuralized sick-leave programme with usual care sick-leave management in patients after an acute myocardial infarction. We hypothesize that a structured sick-leave programme will yield a faster return to work without negatively affecting quality of life., Methods: Patients admitted to Oslo University Hospital due to an acute myocardial infarction were included in the study. Patients were randomized into an intervention group or a conventional care group. Patients randomized to the intervention group were provided with a standard programme with full-time sick leave for 2 weeks after discharge and then encouraged to return to work. The sick leave of the conventional group was mainly managed by their general practitioner., Results: A total of 143 patients were included in the study. The conventional care group had a mean of 20.4 days absent from work, while that of the intervention group was significantly lower, with a mean of 17.2 days (p < 0.001) absent. There was no significant change in quality of life between the groups., Conclusion: These findings strengthen the case for structuralized follow-up of patients with acute myocardial infarction, as this will have positive economic consequences for the patient and society as a whole, without making quality of life worse. Further investigation, with a larger study population, is warranted to determine the extent of health benefits conferred by early return to work.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I 2 =63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I 2 =59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I 2 =57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus β-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)