Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide [...].

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. This increases the demand for real-world evidence to complement findings from randomized controlled trials. The German IQVIA Disease Analyzer (DA) database, which is populated with anonymized electronic medical records from general practitioners and specialists, has become an increasingly valuable source for cardiovascular research. Over the past two decades, and especially between 2020 and 2025, numerous epidemiological studies have used this database to explore associations between cardiovascular risk factors, comorbidities, therapeutic patterns, and cardiovascular outcomes in large, broadly representative outpatient populations. This review synthesizes evidence from 13 selected DA-based studies examining atrial fibrillation, heart failure, cardiometabolic disease, lipid management, non-alcoholic fatty liver disease (NAFLD)-related cardiovascular risks, cerebrovascular complications, COVID-19-associated vascular events, and modifiable behavioral and anthropometric factors. These studies were selected based on predefined criteria including cardiovascular relevance, methodological rigor, large sample size, and representativeness of key disease domains across the 2000-2025 period. Eligible studies were identified through targeted searches of peer-reviewed literature using the German IQVIA Disease Analyzer database and were selected to reflect major cardiovascular disease domains, risk factors, and therapeutic areas. Across disease domains, the reviewed studies consistently demonstrate the DA database's capacity to identify reproducible associations between cardiometabolic risk factors, comorbidities, and cardiovascular outcomes in routine outpatient care. While causal inference is not possible, the database enables the identification of clinically meaningful associations that inform hypothesis generation, help quantify disease burden, and highlight gaps in prevention or treatment. The database's strengths include large sample sizes (often exceeding 100,000 patients), long follow-up periods, and high external validity, while limitations relate to coding accuracy, residual confounding, and the absence of detailed clinical measures. Collectively, the evidence underscores the importance of the DA database as a crucial platform for real-world cardiovascular research.

Cardiac sarcoidosis (CS) is associated with potentially serious complications, including heart failure and life-threatening arrhythmias. The diagnosis and management of CS is multifaceted, requiring a multi-disciplinary team (MDT)-based approach. A new regional CS clinical service was established in Sussex County (UK) in January 2025. This service is based on a core of cardiologists working with a wider MDT, including specialists in pulmonary sarcoidosis, nuclear medicine and cardiac electrophysiology. This study assessed the clinical performance of this new service.

Patients with suspected CS referred to the Sussex CS Service between January and December 2025 were included, as compared to a control cohort of patients referred for CS assessment before the service was conceived.

Of the 51 CS service referrals, 13 patients fulfilled the Heart Rhythm Society (HRS) criteria, all of whom were correctly diagnosed with CS, whilst only two out of seven HRS-positive control patients were correctly diagnosed. In the 38 HRS-negative CS service referrals, 8 patients (21%) were still given a clinical CS diagnosis compared to none in the HRS-negative controls. Of the 21 patients diagnosed with CS, 7 (33%) had active myocardial inflammation and 8 (38%) had LV systolic dysfunction. Where indicated, immunosuppressive and heart failure therapies were initiated in all patients. Eight CS patients (38%) underwent implantable cardioverter defibrillator implantation. No deaths or heart failure hospitalisations occurred within the first 11 months.

An MDT-based CS service model can provide multi-faceted care to patients, without major short-term adverse outcomes. The service model replicability and long-term outcomes require further assessment.

Obesity substantially increases cardiovascular risk and contributes to the accumulation of cardiometabolic risk factors. Achieving optimal control of body weight and guideline-recommended targets is essential in high-risk patients, particularly in secondary prevention following acute coronary events. This study aimed to evaluate treatment strategies and lifestyle modifications undertaken by patients with obesity during long-term follow-up.

This analysis included patients enrolled 6-18 months after acute coronary syndrome or coronary revascularization within the multicentre POLASPIRE II study. Standardized EUROASPIRE methodology was applied to collect clinical, anthropometric, and lifestyle-related data.

A total of 788 patients (mean age 65.4 ± 8.9 years; 25.8% women) were included, of whom 40.6% had obesity. No significant association between sex and BMI was observed (β = -0.48; 95% CI -1.30 to 0.31; p = 0.20). Increasing age was associated with lower BMI (β = -0.05; 95% CI -0.09 to -0.0001; p = 0.044), and higher education correlated with lower BMI (β = -1.10; 95% CI -2.00 to -0.22; p = 0.015). With advancing age (OR 1.02; 95% CI 1.002-1.033; p = 0.023) and increasing BMI (OR 1.11; 95% CI 1.076-1.138; p = 0.001), the number of risk factors and comorbidities increased. Higher BMI was associated with poorer control of medical risk factors (OR 1.06; 95% CI 1.03-1.10; p < 0.001), whereas patients with higher BMI demonstrated better control of lifestyle-related risk factors (OR 0.95; 95% CI 0.919-0.983; p = 0.003).

Obesity is highly prevalent among high-risk cardiovascular patients and is associated with a greater burden of comorbidities and poorer control of medical risk factors. These findings support the need for strengthened, risk-stratified secondary prevention strategies and more personalized therapeutic approaches in patients with obesity.

Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor and an indicator of hypolipidemic therapy effectiveness. However, direct and calculated methods for determining "LDL-C" present the sum of the cholesterol in all apoB-containing lipoproteins, including lipoprotein(a) [Lp(a)]. There has been an ongoing debate about the correctness of LDL-C in patients with elevated Lp(a) concentrations up to now. The aim of this study was to evaluate the effect of Lp(a) concentration on the LDL-C calculated by different equations.

The study included the results of fasting lipids and Lp(a) concentration of 566 measurements from 283 patients (before and after lipid-lowering therapy prescribing, after exclusion of 17 patients with incomplete data). LDL-C and LDL-C corrected for Lp(a)-cholesterol (LDL-C_corr) were calculated by Friedewald, Martin-Hopkins, and Sampson equations.

We assessed 566 measurements of lipids and Lp(a). The number of values reclassified to a higher risk category was 10% and 13% with Martin-Hopkins and Sampson equations compared to the Friedewald formula. The percentage of Lp(a)-cholesterol (Lp(a)-C) in the LDL-C calculated by three formulas was up to 90% or more depending on the concentration of LDL-C and Lp(a). When stratified by clinically significant LDL-C thresholds, the proportion of values LDL-C_corr reclassified to a lower risk category ranged from 30 to 59%.

Comparison of LDL-C concentrations calculated by Friedewald, Martin-Hopkins, and Sampson equations showed high consistency in patients without elevated triglycerides. The LDLcorr is reasonable to use in patients with Lp(a) concentration ≥ 30 and ≥41 mg/dL when using the Martin-Hopkins and Sampson equations, respectively. These data may help clinicians interpret LDL-C goal attainment in patients with elevated Lp(a) and avoid misclassification driven by the Lp(a)-cholesterol component.

Tankyrases (TNKS1 and TNKS2) are multifunctional enzymes of the poly(ADP-ribose) polymerase (PARP) family that regulate cellular homeostasis by catalyzing poly(ADP-ribosyl)ation and stabilizing protein-protein interactions through their ankyrin repeat clusters. By engaging with diverse sets of proteins, TNKSs act as central hubs that coordinate signaling and metabolic pathways. In this review, we discuss how TNKS -protein interactions underpin their roles across multiple biological pathways, including Wnt/β-catenin, YAP and SRC signaling, mTORC1 signaling, DNA damage repair (via PARP crosstalk and recruitment of repair factors), telomere maintenance, cell-cycle regulation, glucose metabolism, cytoskeleton rearrangement, autophagy, proteasomal degradation, and apoptosis. We highlight the structural basis of these interactions, emphasizing ankyrin repeat domain recognition motifs and the consequences of TNKS-mediated PARylation on protein stability and localization. By integrating findings from oncology, virology, and metabolism, we illustrate how TNKS functions as a nodal regulator linking genome stability, signaling fidelity, and metabolic control. The interplay between TNKS and these varied pathways is essential for the well-being of the organism, with its dysregulation having severe biological and clinical consequences, which are discussed here. Finally, we consider therapeutic implications of disrupting TNKS-protein interactions, with particular attention paid to selective small-molecule inhibitors and their translational potential in cancer, viral infections, and degenerative diseases.

Functional valve regurgitation (FVR) progression has traditionally been attributed to external anatomic alterations, without consideration of leaflet-intrinsic pathology. Emerging evidence now implicates valvular leaflets as active contributors rather than passive bystanders in FVR pathogenesis. Systematic investigations into leaflet-specific pathomechanisms remain absent for major FVR subtypes, particularly functional mitral regurgitation (FMR) and functional tricuspid regurgitation (FTR).

The association of FVR with clinical parameters was analyzed in a heart transplantation cohort. Comprehensive microscopic pathology evaluated fibrotic remodeling in mild, moderate, and severe FMR/FTR leaflets, validated in an independent bulk RNA sequencing cohort (FMR/FTR: n=41 each). Single-cell RNA sequencing was performed on 19 FVR leaflets (FMR: 3 mild/2 moderate/3 severe; FTR: 5 mild/3 moderate/3 severe). Subsequent analyses (cluster annotation, cellular proportions, trajectory inference, and cell-cell communication) explored cellular mechanisms of fibrotic remodeling in FVR, focusing on unique and shared changes between FMR and FTR. Histopathology and bulk transcriptomics validated single-cell RNA sequencing findings. Primary valvular endothelial cells and valvular interstitial cells from FVR patients underwent pharmacological intervention. A monocrotaline-induced rat pulmonary hypertension model established FTR, followed by pharmacological treatment to assess leaflet-directed therapy efficacy.

Fibrotic leaflet remodeling scores independently predicted FMR/FTR severity with high precision and significantly improved prediction beyond anatomic anomalies. Fibrotic remodeling showed divergent mechanisms between FMR and FTR. In FMR, suppressed retinoic acid metabolism drove antifibrotic-to-neutral valvular interstitial cell transition. In FTR, impaired IFN (interferon) signaling promoted antifibrotic-to-profibrotic valvular interstitial cell transdifferentiation, worsened by endothelial-to-mesenchymal transition-derived profibrotic valvular endothelial cells. Targeted PDK4 (pyruvate dehydrogenase kinase 4) upregulation or IFN signaling activation reduced FTR severity in vitro and in vivo.

Leaflet-specific organic fibrotic remodeling actively involves FVR beyond functional adaptation, with distinct fibrotic mechanisms in FMR versus FTR. PDK4 and IFN modulation demonstrate therapeutic potential for FTR.

Atrial cardiopathy often precedes atrial fibrillation (AF) and has emerged as an independent risk factor for cardiovascular outcomes. However, previous studies have been limited in size and have overlooked the right atrium.

In 51 693 UK Biobank participants without prevalent AF, we assessed biatrial volumes and emptying fraction from cardiac magnetic resonance imaging using deep learning segmentation. We evaluated associations with new-onset AF, ischemic stroke, heart failure, and dementia, conducted a genome-wide association study, and evaluated causal associations using Mendelian randomization.

Among 51 693 adults, the mean (SD) age was 65 (7.7) years, and 24 584 (48%) were male. During the 4-year follow-up, 964 (1.9%) developed AF, 266 (0.5%) developed ischemic stroke, 365 (0.7%) developed heart failure, and 72 (0.1%) developed dementia. After adjustment for clinical risk factors, both left and right atrial measures were associated with new-onset AF (left atrial minimal volume; hazard ratio, 1.55 [95% CI, 1.48-1.62]), ischemic stroke, and heart failure, with stronger associations in women. Left atrial minimal volume was also associated with dementia. Our genome-wide association study identified 51 (27 novel) genetic associations with atrial measures, many of which do not overlap with established AF loci. Genetic correlations revealed that each atrium had varying correlations with cardiometabolic risk factors, and Mendelian randomization demonstrated that left atrial measures had direct causal effects on AF and stroke risk. However, the stroke associations were attenuated after accounting for AF variants.

In this largest assessment of biatrial structure and function to date, both left and right atrial cardiopathies were independently associated with increased risk of adverse cardiovascular events. We identified several novel genetic loci for atrial traits and observed unique genetic correlations between left and right atrial traits and cardiovascular phenotypes, providing insight into chamber-specific remodeling. Several of these measures are likely to be causal determinants of cardiovascular complications previously attributed to AF.

The impact of intensive blood pressure (BP) control on cognitive function in East Asian populations remains uncertain. We aimed to assess the effect of a lower systolic BP target on global cognitive function in Chinese hypertensive adults.

This secondary analysis of a randomized trial involved hypertensive patients with high cardiovascular risk across 116 sites in China. Participants were assigned to receive intensive treatment (systolic BP target <120 mm Hg) or standard treatment (systolic BP target <140 mm Hg) for a median of 3.4 years. Cognitive function was assessed via MMSE (Mini-Mental State Examination) at baseline and the end of the study. Prespecified outcomes were a change in MMSE score and investigator-reported probable dementia.

Among 11 255 randomized participants, all completed cognitive assessment at baseline and 10 440 (92.8%) at the end of the study. The mean change in MMSE score was not significantly different between arms (difference, 0.05 [95% CI, -0.07 to 0.17]), with a mean change of -0.54 (95% CI, -0.63 to -0.46) in the intensive arm and -0.60 (95% CI, -0.68 to -0.51) in the standard arm. Results were robust across sensitivity analyses and consistent across most subgroups. Exceptions included subgroups of coronary heart disease or antiplatelet treatment. The incidence of probable dementia was too low for meaningful interpretation.

Intensive systolic BP lowering to a target of <120 mm Hg for 3 years did not adversely affect global cognitive function in Chinese hypertensive adults, irrespective of age, sex, BP level, and comorbidities, affirming the cognitive safety of this treatment strategy.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04030234.