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ObjectivesBempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients.Data sourcesMEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched.Study selectionRandomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included.Main outcomes and measuresPrimary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function.ResultsSix RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39).ConclusionBA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.

Objective This study was performed to evaluate the general health status of employees aged 45–59 years using data from the Ü45-Check study (2021–2024). In addition, the health status of individual occupational groups was assessed to investigate potential associations within these groups. Methods Clinical and occupational data were collected from 1,040 employees aged 45–59 years from Berlin and Brandenburg, Germany, who participated in the Ü45-Check study. The data were derived from a preventive health examination conducted to identify potential preventive or rehabilitation needs. The clinical examination included anthropometric measurements, bioelectrical impedance analysis, handgrip strength, 12-lead resting electrocardiogram, systolic and diastolic blood pressure, anamnesis, and blood analyses. To categorize health status by occupation, the International Standard Classification of Occupations 2008 (ISCO-08) was applied. Results Data from 1,040 participants ( n  = 631 male, 61%) revealed occupational and sex-related disparities. The mean body mass index (BMI) of the total sample was 26.89 kg/m 2 (sd = 4.90). Plant and Machine Operators and Assemblers had a mean BMI of 28.25 kg/m 2 (sd = 5.19), while those in Elementary Occupations had a mean BMI of 28.45 kg/m 2 (sd = 4.88), which was the highest among the occupational groups. In terms of percent body fat, the highest means were found in Elementary Occupations , 31.03% (sd = 8.65), and Service and Sales Workers , 32.35% (sd = 8.73). Mean systolic blood pressure values were also elevated: Elementary Occupations (139.02 mmHg, sd = 15.92), Skilled Agricultural , Forestry , and Fishery Workers and Craft and Related Trades Workers (139.63 mmHg, sd = 15.60), and Plant and Machine Operators and Assemblers (139.78 mmHg, sd = 17.90). Resting electrocardiograms and clinical examinations were largely unremarkable. However, blood analyses revealed elevated total cholesterol (mean = 204.03 mg/dL, sd = 40.18) and low-density lipoprotein (mean = 126.28 mg/dL, sd = 35.30) in both women and men, exceeding reference ranges. Conclusion These results highlight occupational and sex-based disparities in anthropometric and clinical measures, pointing to significant health concerns such as obesity and increased cardiovascular risk. The findings underscore the importance of occupational health initiatives tailored to specific job demands and sex differences. Clinical trial registration DRKS ID: DRKS00030982.

To evaluate whether CMR-derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair (TMVR). In patients undergoing TMVR, only limited data exist regarding the role of RV function. Previous studies assessed the impact of pre-procedural RV dysfunction stating that RV failure may be associated with increased cardiovascular mortality after the procedure. Sixty-one patients underwent CMR, echocardiography and right heart catheterization prior TMVR. All-cause mortality and heart failure hospitalizations were assessed during 2-year follow-up. According to RV ejection fraction (RVEF) <46%, 23 patients (38%) had pre-existing RV dysfunction. By measures of RV end-diastolic volume index (RVEDVi), 16 patients (26%) revealed RV dilatation. Nine patients (15%) revealed both. RV dysfunction was associated with increased right and left ventricular volumes as well as reduced left ventricular (LV) ejection fraction (all p<0.05). During follow-up, 15 patients (25%) died and additional 14 patients (23%) were admitted to hospital due to heart failure symptoms. RV dysfunction predicted all-cause mortality even after adjustment for LV function. Similarly, RVEDVi was a predictor of all-cause mortality even after adjustment for LVEDVi. Kaplan-Meier survival analysis unraveled that, among patients presenting with CMR indicative of both, RV dysfunction and dilatation, the majority (78%) experienced an adverse event during follow-up (p<0.001). In patients undergoing TMVR, pre-existing RV dysfunction and RV dilatation are associated with reduced survival, in progressive additive fashion. The assessment of RV volumes and function by CMR may aid in risk stratification prior TMVR in these high-risk patients.

Background: Congenital heart disease (CHD) affects approximately 9 per 1000 live births worldwide, with increasing prevalence due to improved survival. Today, over 90% of individuals with CHD reach adulthood, resulting in a growing population of adults with congenital heart disease (ACHD). Despite its clinical relevance, iron deficiency (ID) and anemia have been insufficiently studied in this group. Objectives: To evaluate the prevalence and clinical impact of iron deficiency and anemia in ACHD, particularly their relationship with exercise capacity. Methods: We retrospectively analyzed 310 ACHD patients at University Hospital Düsseldorf between January 2017 and January 2019. Iron status was assessed using serum ferritin, transferrin saturation (TSAT), and hemoglobin levels. Exercise capacity was measured by cardiopulmonary exercise testing (VO2 max). Prevalence and clinical associations were compared with those reported in heart failure populations, using ESC guideline criteria. Analyses were adjusted for age, sex, and defect complexity. Results: Iron deficiency (ID) was present in 183 patients (59.0%). Anemia was observed in 13 patients (4.2%), with 6 (46.2%) classified as microcytic and 5 (38.5%) as normocytic. Reduced exercise capacity, defined as VO2 max <80% of predicted, was present in 51 patients (16.5%), occurring more frequently in those with complex CHD (31.3% vs. 11.3%, p < 0.001). ID was associated with a trend toward lower VO2 max (21.3 vs. 23.5 mL/min/kg, p = 0.068), while anemia correlated with significantly reduced performance (19.8 ± 4.1 vs. 22.9 ± 6.3 mL/min/kg, p = 0.041). Conclusions: Iron deficiency is highly prevalent, and anemia—though less common—was consistently associated with reduced functional capacity in ACHD. These findings highlight the need for targeted screening and management strategies in this growing patient population.

Background and purposeThe National Cardiovascular Data Registry (NCDR) risk scores for mortality, bleeding and acute kidney injury (AKI) are accurate outcome predictors of coronary catheterization procedures in North American populations. However, their application in German clinical practice remained elusive and we thus aimed to verify their use.MethodsNCDR scores for mortality, bleeding and AKI and corresponding clinical outcomes were retrospectively assessed in patients undergoing catheterization for ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or for elective coronary procedures at a German Heart Center from 2014 to 2017. Risk model performance was assessed using receiver-operating-characteristic curves (discrimination) and graphical analysis/logistic regression (calibration).ResultsA total of 1637 patients were included, procedures were performed for STEMI (565 patients, 34.5%), NSTEMI (572 patients, 34.9%) and elective purposes (500 patients, 30.5%); 6% (13% of STEMI and 5% of NSTEMI patients) presented in cardiogenic shock and 3% with resuscitated cardiac arrest. Radial access was used in 38% of procedures and cross-over was necessary in 5%; PCI was performed in 60% of procedures. In-hospital mortality was 6.3% (STEMI 14.5%; NSTEMI 3.7%; elective 0%) and major bleedings occurred in 5.6% (STEMI 10.6%; NSTEMI 5.4%; elective 0.2%); AKI was detected in 18.1% of patients (STEMI 23.7%; NSTEMI 27.3%; elective 1.4%), amounting to KDIGO stage I/II/III in 11.5%/3.5%/3.2%. NCDR risk models discriminated very well for mortality [AUC 0.93 with 95% confidence interval (CI) 0.91–0.95] and well for major bleeding (AUC 0.82, CI 0.78–0.86) and any AKI (AUC 0.83, CI 0.81–0.86). Discrimination in the subgroup of patients with PCI was comparable (mortality: AUC 0.90; major bleeding: AUC 0.78; any AKI: AUC 0.79). However, calibration showed considerable underestimation of mortality and AKI in high-risk patients, while major bleeding was consistently overestimated (Hosmer–Lemeshow p < 0.02 for all outcomes).ConclusionsThe NCDR risk models showed excellent performance in discriminating high-risk from low-risk patients in contemporary German interventional cardiology. Model calibration for adverse event probability prediction, however, is limited and demands recalibration, especially in high-risk patients.Graphic abstract

This study was designed to identify the multivariate effect of clinical risk factors on high on-treatment platelet reactivity (HPR) and 12 months major adverse events (MACE) under treatment with aspirin and clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI). 739 consecutive patients with stable coronary artery disease (CAD) undergoing PCI were recruited. On-treatment platelet aggregation was tested by light transmittance aggregometry. Clinical risk factors and MACE during one-year follow-up were recorded. An independent population of 591 patients served as validation cohort. Degree of on-treatment platelet aggregation was influenced by different clinical risk factors. In multivariate regression analysis older age, diabetes mellitus, elevated BMI, renal function and left ventricular ejection fraction were independent predictors of HPR. After weighing these variables according to their estimates in multivariate regression model, we developed a score to predict HPR in stable CAD patients undergoing elective PCI (PREDICT-STABLE Score, ranging 0-9). Patients with a high score were significantly more likely to develop MACE within one year of follow-up, 3.4% (score 0-3), 6.3% (score 4-6) and 10.3% (score 7-9); odds ratio 3.23, P=0.02 for score 7-9 vs. 0-3. This association was confirmed in the validation cohort. Variability of on-treatment platelet function and associated outcome is mainly influenced by clinical risk variables. Identification of high risk patients (e.g. with high PREDICT-STABLE score) might help to identify risk groups that benefit from more intensified antiplatelet regimen. Additional clinical risk factor assessment rather than isolated platelet function-guided approaches should be investigated in future to evaluate personalized antiplatelet therapy in stable CAD-patients.

Chronic inflammation promotes atherosclerosis in cardiovascular disease and is a major prognostic factor for patients undergoing percutaneous coronary intervention (PCI). Macrophage migration inhibitory factor (MIF) is involved in the progress of atherosclerosis and plaque destabilization and plays a pivotal role in the development of acute coronary syndromes (ACS). Little is known to date about the clinical impact of MIF in patients with symptomatic coronary artery disease (CAD). In a pilot study, 286 patients with symptomatic CAD (n = 119 ACS, n = 167 stable CAD) undergoing PCI were consecutively evaluated. 25 healthy volunteers served as control. Expression of MIF was consecutively measured in patients at the time of PCI. Baseline levels of interleukin 6 (IL-6), \"regulated upon activation, normal T-cell expressed, and secreted\" (RANTES) and monocyte chemoattractant protein-1 (MCP-1) were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Patients with ACS showed higher plasma levels of MIF compared to patients with stable CAD and control subjects (median 2.85 ng/mL, interquartile range (IQR) 3.52 versus median 1.22 ng/mL, IQR 2.99, versus median 0.1, IQR 0.09, p<0.001). Increased MIF levels were associated with CRP and IL-6 levels and correlated with troponin I (TnI) release (spearman rank coefficient: 0.31, p<0.001). Patients with ACS due to plaque rupture showed significantly higher plasma levels of MIF than patients with flow limiting stenotic lesions (p = 0.002). To our knowledge this is the first study, demonstrating enhanced expression of MIF in ACS. It is associated with established inflammatory markers, correlates with the extent of cardiac necrosis marker release after PCI and is significantly increased in ACS patients with \"culprit\" lesions. Further attempts should be undertaken to characterize the role of MIF for risk assessment in the setting of ACS.

BackgroundPrevious randomized controlled trials (RCT) failed to demonstrate benefits of patent foramen ovale (PFO) closure (PFO-C) over medical therapy (MT) for secondary prevention of cryptogenic ischemic stroke. Three recently published RCTs, however, turned out positive for PFO-C and warrant an updated meta-analysis.MethodsData from all available RCTs on PFO-C vs. MT for secondary prevention of cryptogenic ischemic stroke up until October 2017 were abstracted and analyzed in a comprehensive meta-analysis. Clinical efficacy outcomes were recurrent stroke, recurrent TIA, and their combination; safety outcomes were mortality, major bleeding, venous thromboembolism (VTE), and new-onset atrial fibrillation/flutter (NOAF).ResultsFive trials including a total of 3440 patients were included in the meta-analysis. PFO-C significantly reduced recurrent stroke [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.19–0.90; p = 0.03] and the combination of recurrent stroke + TIA (OR 0.53, CI 0.36–0.80; p = 0.002) compared to MT; recurrent TIA alone showed no differences (OR 0.77; CI 0.51–1.14; p = 0.19). NOAF was significantly more frequent after PFO-C (OR 5.75, CI 3.09–10.70; p < 0.00001). Mortality (OR 0.80, CI 0.39–1.67), major bleeding (OR 0.96, CI 0.48–1.92), and VTE (OR 2.45, CI 0.75–7.99) remained neutral. Trials with superior patient selection for PFO-C showed advantageous results compared to MT.ConclusionsPFO-C after cryptogenic ischemic stroke is safe and effective to reduce the risk of recurrent stroke and recurrent stroke + TIA, albeit with an increased risk for NOAF.

Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. \"poor responders\" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Routine platelet function testing identifies patients with high residual platelet reactivity (\"poor responders\") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit. ClinicalTrials.gov NCT01339026.

Short bowel syndrome after extensive surgical resection of the intestine is characterised by inadequate digestion and absorption of nutrients. Additional clinical problems include impaired absorption and metabolism of diverse drugs requiring individualised medical therapy or alternative treatments. We report a case of individualised dual antiplatelet therapy in a patient who underwent an extensive intestinal resection complicated by acute myocardial infarction requiring percutaneous coronary intervention and stent implantation. Genetic testing of CYP2C19 gene polymorphisms and platelet aggregation testing were used to assess responses to aspirin, clopidogrel, prasugrel and ticagrelor. Given its unique pharmacokinetics with good absorption and without need of metabolism to an active substance, ticagrelor appears to be the best for patients with short bowel syndrome who require dual antiplatelet therapy after coronary stent implantation.