Baris Gencer

Background and Aims: Lipoprotein(a) (Lp(a)) is considered a causal risk factor for atherogenesis. A higher prevalence of certain adverse events, including diabetes mellitus (DM), has been reported for patients with low Lp(a) concentrations. Therapeutics that lower Lp(a) are now in clinical testing. Thus, the association between lower Lp(a) concentration and safety outcomes is of clinical importance. Methods: The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized 27 564 patients with stable atherosclerotic cardiovascular disease (ASCVD) to evolocumab versus placebo on a background of statin therapy. The relationship between Lp(a) and the risk of prevalent and incident adverse outcomes of interest was examined, adjusting for relevant predictors. Results: Lp(a) was assessed in 25 090 participants at baseline (median 37 nmol/L, interquartile range 13–165). There was no association between Lp(a) concentration and incident risk of haemorrhagic stroke, serious bleeding, neurocognitive events, malignancy, or atrial fibrillation, including those with Lp(a) levels ≤13 nmol/L. There was an inverse association between lower baseline Lp(a) levels and prevalent DM at baseline (adjusted odds ratio 1.03, 95% confidence interval [CI] 1.02–1.04, P < .001; for every 50 nmol/L lower Lp(a)), as well as the incident risk of developing DM during follow-up (adjusted hazard ratio [HR] 1.05, 95% CI 1.02–1.08, P = .002; for every 50 nmol/L lower Lp(a)), with consistent results by treatment arm. Evolocumab did not increase the risk of DM irrespective of baseline Lp(a), even in participants in the top decile of baseline Lp(a) (adjusted HR .72, 95% CI .38–1.35) in whom evolocumab reduced Lp(a) by a median of 71 nmol/L. Conclusions: In patients with ASCVD, low Lp(a) concentration was not associated with an increased risk of most adverse safety outcomes, but lower Lp(a) was associated with an increased risk of prevalent and incident DM.

Aims: Overweight and obesity are common among patients with acute coronary syndromes (ACS), yet the long-term cardiovascular consequences of post-ACS weight change remain uncertain. We investigated the association between 1-year weight change after ACS and 5-year clinical outcomes in overweight and obese patients. Methods and results: We analysed 1473 overweight and obese ACS participants from the Swiss ELIPS cohort with available weight measurements. Hazard ratios (HRs) were estimated per 1% and 5% weight change for the 5-year risk of major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, stroke, or transient ischaemic attack. Models were adjusted for age, sex, body mass index (BMI), smoking, total cholesterol, hypertension, diabetes, and estimated glomerular filtration rate. Predefined subgroups included BMI ≥ 27 kg/m2 vs. 25–27 kg/m2. Among the participants (15.1% women, mean age 61.5 years), the median BMI was 28.1 kg/m2 (67% BMI ≥ 27 kg/m2). Median 1-year weight change was 0%; 47.5% lost weight and 18.7% achieved >5% weight loss. Patient characteristics associated with weight loss were older age, higher BMI, non-smoking status, and participation in cardiac rehabilitation. During follow-up, 278 MACE events occurred. Weight loss was associated with a lower risk of MACE [multivariate-adjusted HR per 5%: 0.90, 95% confidence interval (CI): 0.82–1.00, P = 0.04]. The association was stronger in patients with BMI ≥ 27 kg/m2 (adj HR per 5% 0.87, 95% CI: 0.77–0.97) compared to those with BMI 25–27 kg/m2 (adj HR per 5% 1.01, 95% CI: 0.85–1.20, interaction P = 0.16). Conclusion: Overweight and obese ACS patients who lose weight may have a lower risk of cardiovascular events.

Background: The lifetime risk of stroke among non‐anticoagulated patients with atrial fibrillation (AF) approximates 1 in 3. Oral anticoagulation (OAC) reduces stroke and systemic embolism by at least two thirds and mortality by one fourth. Methods: The present narrative review summarizes current evidence and practical recommendations on OAC in AF and highlights recent advances and remaining gaps in knowledge. Results: The threshold for net clinical benefit of OAC is met when stroke risk exceeds 1%–2% per year, typically corresponding to ≥ 1 traditional stroke risk factor (CHA ₂ DS ₂ ‐VA ≥ 1), with increasing risk per additional risk factor. OAC also appears beneficial in device‐detected (subclinical) AF, possibly at higher CHA ₂ DS ₂ ‐VA scores. Direct oral anticoagulants (DOACs) reduce intracranial haemorrhage compared to vitamin K antagonists (VKAs), and meta‐analyses of randomized trials showed further reduction in stroke and mortality with DOACs, including in the elderly and chronic kidney disease. VKAs are preferred in patients with mechanical heart valves, mitral stenosis, antiphospholipid syndrome and Child‐Turcotte‐Pugh C cirrhosis. Modifiable bleeding risk factors should be assessed periodically and mitigated. These include anti‐inflammatory drugs, antiplatelet therapy, drug interactions, excessive alcohol consumption, uncontrolled hypertension, diabetes, risk factors for gastrointestinal bleeding, major organ dysfunction and frailty. There are very few contraindications to OAC and most are relative or temporary conditions. Follow‐up involves reassessing adherence, thrombotic and bleeding risk, co‐medication and dosing. Integrated patient‐centred AF management additionally involves risk factor management, symptom control and dynamic reassessment. Lifelong OAC is currently recommended, but recent data suggested that discontinuing OAC after successful catheter ablation of AF and/or left atrial appendage closure could be safe. OAC in specific settings is discussed, including cardioversion, catheter ablation, surgery, post‐operative AF, elderly patients, pregnancy and bleeding. Conclusion: OAC is the cornerstone of thromboembolism prevention in AF, but knowledge gaps remain, including on risk stratification, device‐detected AF, trigger‐induced AF, cardioversion, OAC resumption after major bleeding, and potential safety of OAC discontinuation after successful catheter ablation or left atrial appendage occlusion.

Thyroid hormones play an important role in regulating the cardiovascular system. Thyroid dysfunction, which encompasses hypothyroidism and hyperthyroidism, is relatively common and has been linked to a range of cardiovascular manifestations, including dyslipidaemia, abnormal blood pressure regulation, endothelial dysfunction, impaired cardiac function, and arrhythmias. The effects of levothyroxine replacement therapy on cardiovascular endpoints in subclinical hypothyroidism remain uncertain. The largest randomized controlled trial (TRUST) to date was underpowered to assess cardiovascular outcomes, although the results demonstrated a pattern towards a beneficial effect of levothyroxine. The aim of this review was to provide a summary of current knowledge on the relationship between thyroid dysfunction and cardiovascular health, with a focus on molecular and pathophysiological mechanisms underlying thyroid dysfunction and cardiovascular disease. Evidence from recent omics and Mendelian randomization studies is discussed, alongside an overview of the epidemiology of thyroid diseases and the impact of levothyroxine treatment on cardiovascular outcomes in subclinical hypothyroidism.

Background: The prognostic significance of cardiovascular‐kidney‐metabolic (CKM) multimorbidity in acute heart failure (AHF) remains unclear. We evaluated its association with clinical outcomes in a real‐world, multinational cohort of patients with AHF. Methods: We included patients with AHF hospitalized from 2005 to 2020 at 2 tertiary care centers in Switzerland and Kyrgyzstan. Patients were categorized based on the number of CKM conditions in addition to HF (0–3). CKM conditions included prior myocardial infarction, impaired kidney function (estimated glomerular filtration rate 2 ), and diabetes. The association between the number of CKM conditions and the primary outcome of HF hospitalization or all‐cause death was assessed with Cox models. Results: Among 1745 patients (69% Swiss, 44% female, age 74±13 years, left ventricular ejection fraction 43±16%), at baseline, 18.9% had HF alone, 39.0% had 1 CKM condition, 30.7% had 2, 11.4% had 3. Impaired kidney function was the most prevalent CKM condition (n=1011), followed by prior myocardial infarction (n=742) and diabetes (n=595). At 1 year, 731 patients (41.9%) experienced the primary outcome. Compared with HF alone, an increasing number of CKM conditions was associated with stepwise increases in the risk of the primary outcome (adjusted hazard ratios [HRs], 1.27 [95% CI, 1.01–1.59], 1.50 [95% CI, 1.19–1.89], and 2.10 [95% CI, 1.59–2.77] for 1, 2, and 3 CKM conditions). These associations remained consistent regardless of sex, age, and left ventricular ejection fraction ( P _interaction >0.05 for all). Conclusions: In this real‐world cohort of hospitalized patients with AHF, CKM multimorbidity was common and associated with a stepwise increase in the risk of adverse outcomes. These data underscore the importance of comprehensive CKM assessment in an AHF setting.

Aims: We aimed to develop the European Society of Cardiology (ESC) quality indicators (QIs) for myocardial infarction (MI), from 1 year after hospital discharge, corresponding to transition to the chronic coronary syndrome phases. Methods and results: We collaborated with the European Association of Preventive Cardiology (EAPC) and developed QIs for the long-term management of patients following MI. We applied the ESC methodology for QI development by (i) determining key domains of post-MI care; (ii) developing candidate QIs by performing a systematic review of the literature, and (iii) selecting the final set of QIs using a modified Delphi approach. In total, 18 QIs were identified across seven domains of care including (i) structural framework, (ii) risk assessment and follow-up, (iii) pharmacological management, (iv) rehabilitation, behavioural, and preventive interventions, (v) coronary revascularization, (vi) clinical outcomes, and (vii) patient-reported outcomes. Conclusion: We present the ESC QIs from 1 year after hospitalization for MI, to standardize and address gaps in care for this high-risk group. These QIs are supported by evidence from contemporary literature, endorsed by expert consensus, and aligned with the 2024 ESC guidelines on the management of chronic coronary syndromes. Lay summary: Measures to evaluate and improve the long-term management of patients following a heart attack are needed. In this paper, we identified key aspects of care that can help clinicians, decision-makers and patients improve the quality of care, from one year after a heart attack onwards, and help address inequalities and variations in clinical practice.

Background: Despite universal coverage, inequities persist in acute coronary syndrome (ACS) care. This study examines how educational levels impact the quality and outcomes of health care. Methods: A cohort of ACS patients hospitalized in five Swiss university hospitals was categorized into four educational levels (EL) with EL1 defined as lower than vocational school and EL4 as a university degree. The use of medical therapies, achievement of preventive targets and risk of clinical events were evaluated across ELs at baseline ( N = 6040), 1‐year ( N = 5756) and 5‐years ( N = 2253) and presented with adjusted marginal odds ratios (mOR), average marginal effect (AME) and hazard ratios (HRs). Results: Among 6040 patients, the mean age was 63 years, and 81% were male. Participants with lower EL had a greater burden of cardiovascular risk factors at baseline. Compared with EL4 participants EL1 participants had lower adherence to cardiac rehabilitation (mOR = .6 [95% CI .5–.8], AME = −10%) and were less likely to be followed by a cardiologist (mOR .6 [95% CI .5–.8], AME = −6%). Use of medical therapies did neither differ across EL at discharge nor during follow‐up. At 1 year, smoking cessation (mOR = .7 [95% CI .5–.9], AME = −10%) and weight reduction ≥5% among overweight or obese participants (mOR = .7 [95% CI .5–.9], AME = −6%) were less frequent in individuals with EL1 compared with EL4. At long term, achievement of LDL‐C <1.8 mmol/L (<70 mg/dL) (mOR = .6 [95% CI .4–.9], AME = −9%) was less frequent in individuals with EL1 compared with EL4. Lower EL was associated with an increased risk of major acute coronary event (MACE) at short‐ (aHR = 1.4 [95% CI 1.0–2.0] for EL1 vs. EL4) and long term (aHR = 1.3 [95% CI 1.0–1.6] for EL1 vs. EL4) and all‐cause death at long term (aHR = 1.6 [95% CI 1.1–2.2] for EL1 vs. EL4). Conclusion: In Switzerland, disparities in ACS care and outcomes remain across EL, emphasising the need for tailored interventions to reduce inequities.

Beta-blocker therapy reduced mortality and cardiovascular events following acute coronary syndromes (ACS) in the pre-reperfusion era. In the contemporary era of early mechanical reperfusion and modern secondary prevention, the benefit of beta-blockers after ACS without reduced left ventricular ejection fraction (LVEF) has been questioned. This review was based on PubMed database searches from inception to January 2025. The recent REDUCE-AMI and ABYSS trials were the first adequately powered contemporary randomized trials evaluating beta-blockers after ACS without reduced LVEF. Contemporary observational evidence is also discussed. Implications for different LVEF categories (41-49% versus ≥ 50%), ACS subtypes, beta-blocker therapy duration, optimal dose, and interaction with other secondary prevention therapies are addressed. We estimate that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LVEF ≥ 50%. Beta-blocker prescription should be individualized with shared decision-making, balancing the risk of cardiovascular event against potential benefits of deprescription. Factors favoring beta-blocker discontinuation include adverse effects, polypharmacy, >1-3 years of stability post-ACS, and specific comorbidities (e.g. heart failure with preserved LVEF). Factors favoring beta-blocker prescription/continuation (besides established indications such as LVEF ≤ 40%, arrhythmias, angina, and refractory hypertension) include good tolerance, LVEF 41-49%, and non-adherence to other secondary prevention therapies.