Abstract Background Subclinical atherosclerotic plaque (SAP) develops silently in older adults. Biological changes that predict plaque formation are not well defined. We examined whether circulating immunological, metabolic, and functional measures identify vascular vulnerability before clinical disease. Methods In a three-year longitudinal study, 49 healthy older adults (63.8 ± 3.8 years) underwent carotid ultrasound, T cell phenotyping, serum protein profiling, body composition assessment, and fitness testing at baseline and follow-up. At follow-up, participants were classified as no SAP, new SAP or persistent SAP. We analyzed baseline determinants and within-person changes to predict incident plaque formation. Results New SAP occurred in 30.3% of those initially plaque-free. At baseline, lower frequencies of CD8 + effector memory (EM) T cells and higher frequencies of CD8 + effector memory re-expressing CD45RA (EMRA) T cells and regulatory T cells (Tregs) were associated with higher odds of new SAP. Over time, expansion of CD8 + EM T cells was the most consistently associated independent variable of new SAP, accompanied by declines in Tregs and in the Treg/Teff ratio. Vascular cell adhesion molecule-1 (VCAM-1) at baseline was an additional independent predictor. Increases in visceral fat and declines in VO 2 peak were linked to new SAP, but immune markers were more robust than metabolic variables or serum cytokines. Conclusion Adaptive immune remodeling follows a phase-dependent pattern in which CD8 + EM reductions and later CD8 + EM expansion with Treg decline signal emerging vascular vulnerability. These immune signatures, together with VCAM-1, may help characterize vascular vulnerability during the subclinical phase of plaque development.

Cardiovascular diseases are still the leading cause of morbidity and mortality worldwide. Current research indicates that arterial stiffness is an independent risk factor for cardiovascular diseases and represents a potential target for personalized prevention and therapeutic approaches. Physical activity is a low-cost intervention for vascular prevention via pleiotropic mechanisms (e.g., reduced systemic inflammation, improved endothelial function, reduced arterial stiffness). In this clinical review we (i) highlight the clinical significance of arterial stiffness, (ii) recap current measurement methods, (iii) summarize the current evidence of the effects of physical activity on arterial stiffness and (iv) outline future directions for arterial stiffness research in sports medicine. Key Words: Prevention, Exercise, Vascular Aging, Cardiovascular Disease, Intervention, Inflammation, Cardiology

Aging is accompanied by functional decline and immune remodeling, yet the dynamics and early modifiability of these processes remain incompletely understood. Research suggests that lifestyle factors, particularly physical activity and fitness, influence immune aging. This study investigated longitudinal changes in physical performance and immune parameters in a well-characterized cohort of clinically healthy elderly. In this study, 49 clinically healthy elderly underwent repeated assessments of cardiorespiratory fitness, muscular strength, body composition, immune cell phenotypes, and serum cytokines at baseline, 1-year, and 3-year follow-up. We observed a shift toward an aged T cell profile, characterized by reductions in naïve and regulatory T cells (Tregs), alongside increases in differentiated and senescence-associated subsets. Treg subsets followed divergent trajectories, with resting Tregs (rTregs) declining and memory-like Tregs (mTregs) increasing. Serum levels of classical pro-inflammatory cytokines remained largely stable over the study period. Despite stable self-reported physical activity, participants showed declines in cardiorespiratory fitness and strength. Immune remodeling was primarily associated with declines in physical fitness, alongside an increase in highly differentiated CD4+ and senescent CD8+ T cell subsets, lower rTregs, higher mTregs, and increased CD4-CD8- lymphocyte frequencies, while habitual physical activity was independently related to effector T cell dynamics. Together, these findings indicate that subtle functional decline in clinically healthy older adults is paralleled by immune changes characteristic of early immunosenescence, occurring largely in the absence of overt systemic inflammation. These results highlight physical fitness as a potentially modifiable determinant of immune trajectories and immune resilience in healthy aging.

This expert opinion paper focuses on the clinical implementation, execution and interpretation of Cardiopulmonary Exercise Testing (CPET), providing comprehensive insights into its recognised prognostic, diagnostic and prescriptive value in everyday clinical practice. A practical guide offers step-by-step instructions on conducting and interpreting CPET, emphasising the importance of high-quality testing for the benefit of patients, healthy individuals and athletes. The approach considers test objectives, how to adapt procedures for different medical inquiries and reporting. A systematic method for interpreting CPET data is outlined, covering aerobic/exercise capacity evaluations with subsequent analyses of ventilatory, cardiovascular, cardiorespiratory gas-exchange and muscular-metabolic responses to exercise. Special attention is given to post-exercise recovery and other novel parameters for informed clinical decision-making. The outcomes emphasise the need for better implementation of CPET for prognostic evaluations and in diagnostic pathways. Barriers to its adoption are discussed, including logistical challenges or resource constraints, and strategies for integrating CPET into routine care pathways are proposed. The statement provides further details on how to utilise CPET outcomes to tailor exercise prescription based on identified functional limitations and adjust exercise intensity using different physiological and pathological thresholds for both patients and athletes. Finally, the latest advancements in CPET are explored, including novel portable systems and integration with transcutaneous blood-gas monitoring, imaging, and (non-)invasive haemodynamic measures, also addressing the potential for smaller clinics, improving accessibility in clinical practice. This expert opinion statement aims to offer a roadmap for making CPET a more standardised and accessible tool in clinical care.

Covert cerebrovascular disease is traditionally defined as microvascular brain injury. Whether non-culprit macrovascular abnormalities below conventional stenosis thresholds represent a clinically relevant form of vascular vulnerability remains unclear. We investigated the prevalence and prognostic significance of covert macrovascular disease (CMVD) in acute ischemic stroke and transient ischemic attack (TIA). In this prospective observational cohort, consecutive patients admitted with ischemic stroke or TIA underwent standardized vascular imaging. CMVD was defined as non-culprit macrovascular pathology not meeting TOAST criteria for large-artery atherosclerosis, including non-stenotic carotid or vertebral plaques (< 50

INTRODUCTION:The relationship between body mass index (BMI) and acute kidney injury (AKI) and mortality in infarction-related cardiogenic shock (CS) remains uncertain. We investigated the association between BMI and renal and short-term clinical outcomes in patients with infarction-related CS. METHODS:In this retrospective single-center cohort study, 369 consecutive patients with infarction-related CS were included. BMI was analyzed as the exposure variable and modeled both continuously and according to World Health Organization categories. AKI within 96 h, defined according to Kidney Disease: Improving Global Outcomes creatinine-based criteria, and in-hospital mortality were the primary outcomes; renal replacement therapy (RRT) was a secondary outcome. Associations were assessed using multivariable logistic regression adjusted for prespecified confounders, including age, sex, diabetes mellitus, chronic kidney disease, and baseline estimated glomerular filtration rate. Nonlinear relationships were explored using restricted cubic spline analyses. RESULTS:AKI occurred in 158 patients (42.8%). Higher BMI, modeled as a continuous variable, was associated with an increased risk of AKI (adjusted OR 1.34 per 5 kg/m2; 95% CI, 1.06-1.69; p = 0.012). RRT was more frequently required in patients with obesity than in those with normal weight (18.5% vs. 8.6%; p = 0.018). When analyzed categorically, overweight (BMI 25.0-29.9 kg/m2) was associated with lower in-hospital mortality compared with normal weight (adjusted OR 0.66; 95% CI, 0.45-0.95; p = 0.028), whereas obesity was not independently associated with mortality. Nonlinear modeling suggested a U-shaped relationship between BMI and both AKI and in-hospital mortality, with the lowest estimated risk at intermediate BMI levels. CONCLUSION:In patients with infarction-related CS, BMI was associated with both renal outcomes and in-hospital mortality. Higher BMI was linked to increased renal vulnerability, whereas overweight was associated with lower mortality. These findings should be interpreted cautiously given the observational design and the potential for residual confounding and reverse causation, particularly at lower BMI levels.

Zusammenfassung Die arterielle Hypertonie ist der weltweit bedeutendste veränderbare kardiovaskuläre Risikofaktor 1. Regelmäßiges körperliches Training senkt den Blutdruck nachhaltig, reduziert das kardiovaskuläre Risiko und ergänzt die Pharmakotherapie. Die Leitlinien 2 3 empfehlen 150–300 Minuten moderatintensives oder 75–150 Minuten hochintensives Ausdauertraining pro Woche, ergänzt durch 3 Krafttrainingseinheiten. Das Sportprogramm soll dabei nach dem „FITT-Prinzip“ individuell angepasst und progressiv gesteigert werden. Studien zeigen, dass Ausdauertraining, Krafttraining oder eine Kombination aus beiden blutdrucksenkend wirken 4 5. Dabei zeigen sich bei arterieller Hypertonie für das Ausdauertraining (bis −12 mmHg systolisch) und bei erhöhtem Blutdruck für das isometrische Krafttraining (bis −11 mmHg) die größten blutdrucksenkenden Effekte. Bei unkontrollierter Hypertonie (SBP > 160 mmHg) sollten Belastungen mit hoher Intensität vermieden werden, zunächst sollte eine Blutdruckkontrolle erfolgen.

Background/Objectives: Vitamin D has been implicated in lipid metabolism, but data regarding its association with atherogenic lipoproteins in elite athletes remain limited. Elite athletes represent a unique research model to investigate these associations with reduced confounding from obesity, chronic disease, smoking, and physical inactivity. Methods: This cross-sectional study included 773 male professional athletes from mixed sports disciplines (mean age 25.5 ± 5.0 years). Serum 25-hydroxyvitamin D [25(OH)D] concentrations and lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and lipoprotein(a) [Lp(a)], were assessed. Associations were analyzed using correlation analyses, subgroup comparisons according to predefined 25(OH)D categories (<30, 30-50, and >50 ng/mL), and multivariable linear regression models adjusted for age, body mass index, season, and training-related variables. Results: Higher serum 25(OH)D concentrations were independently associated with lower LDL-C (p = 0.028), triglyceride (p = 0.002), and Lp(a) concentrations (p = 0.036), whereas no independent association was observed with HDL-C (p = 0.559). Athletes with 25(OH)D concentrations ≥30 ng/mL demonstrated lower LDL-C, triglyceride, and Lp(a) levels compared with athletes below this threshold (all p < 0.05). Higher vitamin D status was additionally associated with greater peak exercise performance (4.29 ± 1.15 vs. 3.36 ± 0.68 W/kg; p < 0.001). Conclusions: Higher 25(OH)D concentrations were independently associated with a more favorable lipid profile in elite athletes, including lower LDL-C, triglyceride, and Lp(a) concentrations. Prospective studies are warranted to further investigate the relationship between vitamin D status and lipid metabolism in athletic populations.

AIMS:An exaggerated blood pressure response (eBPR) to exercise is associated with increased cardiovascular risk. The systolic blood pressure-to-achieved metabolic equivalent (SBP/METpeak) ratio was proposed as a fitness-indexed marker of eBPR in the general population, with > 18 mmHg/METpeak suggested as a pragmatic threshold. We aimed to define stage-specific SBP/METpeak reference limits in male elite athletes and examine this comparator. METHODS AND RESULTS:We examined 474 healthy male elite athletes (age 25.5 ± 5 y) from mixed sports who underwent a standardized maximal graded cycling test. SBP/METpeak was calculated as the quotient of SBP and peak METs at each workload stage and at peak exercise. Stage-specific percentiles, exceedance rates, and associations with fitness were analysed. Mean achieved workload was 360.7 ± 92.8 W, METpeak 13.1 ± 3.1, maximal SBP 196.9 ± 20.7 mmHg, and peak SBP/METpeak 15.68 ± 3.53 mmHg/METpeak. Stage-wise SBP/METpeak showed a non-linear pattern, increasing from 11.63 ± 2.79 at 100 W to 14.49 ± 3.59 at 250 W and 14.50 ± 3.43 at 300 W, then declining at 350 W (13.40 ± 3.01) and 400 W (12.14 ± 2.89). Stage-specific P75 values peaked at 16.7 mmHg/METpeak at 250-300 W, whereas P90 values reached 18.20-19.27 mmHg/METpeak at 200-300 W. Overall, 21.9% exceeded 18 mmHg/METpeak at least once up to 400 W. Fitness was strongly inversely associated with peak SBP/METpeak (r = -0.811, P < 0.001). CONCLUSION:In male elite athletes, SBP/METpeak is workload-dependent and closely linked to aerobic fitness. The 18 mmHg/METpeak comparator aligned primarily with moderate workloads, whereas upper reference values around 16 mmHg/METpeak may better describe the upper range during standardized exercise testing stages in athletes.

An exaggerated systolic blood pressure response to exercise (eBPR) is associated with future arterial hypertension and adverse cardiovascular outcomes, yet it remains an exercise-derived phenotype with heterogeneous definitions. We investigated whether resting cardiovascular biosignals can identify eBPR, defined by a workload-indexed systolic blood pressure-to-metabolic equivalent slope (SBP/MET slope) >6.2 mmHg/MET. In this retrospective study, 197 predominantly male professional athletes contributed 334 pre-season screening examinations comprising resting 12-lead electrocardiograms (ECG), radial pulse waves (RPW) and cycle ergometry. Convolutional neural networks were trained with group-stratified five-fold cross-validation and evaluated on a hold-out test set. The combined RPW-ECG model, via late fusion, achieved an area under the receiver operating characteristic curve of 0.79 (95% CI 0.65-0.90), slightly exceeding single-modality models (ECG: 0.77 [0.62-0.90]; RPW: 0.66 [0.50-0.80]). Explainable AI identified contributing signal regions. As proof of concept, resting biosignals could complement, not replace, exercise testing, pending external validation and prospective outcome studies.

Arterial hypertension is the most significant modifiable cardiovascular risk factor worldwide 1 . Regular physical exercise sustainably lowers blood pressure, reduces cardiovascular risk, and complements pharmacotherapy. The guidelines 2 3 recommend 150-300 minutes of moderate or 75-150 minutes of vigorous aerobic exercise per week, supplemented by three resistance training sessions. The exercise program should be individualized according to the "FITT principle" and progressively increased. Studies show that aerobic exercise, resistance training, or a combination of both have blood pressure-lowering effects 4 5 . Aerobic training (up to -12 mmHg systolic) shows the greatest blood pressure-lowering effects in arterial hypertension, while isometric resistance training (up to -11 mmHg) is most effective for elevated blood pressure. In uncontrolled hypertension (SBP > 160 mmHg), high-intensity exercise should be avoided, and blood pressure control should be prioritized initially.

Aging is associated with progressive deterioration of vascular function and cardiovascular risk. Cardiorespiratory fitness (CRF) is closely associated with cardiovascular health, yet longitudinal data in healthy older adults remain limited. This study examined 3-year changes in vascular and echocardiographic parameters in older adults and their associations with CRF and muscle strength. Forty-nine participants (mean age 63.8 ± 3.8 years) underwent vascular assessments (brachial/central blood pressure (BP), pulse wave velocity (PWV), augmentation index), echocardiography, CRF testing via spiroergometry to determine VO2peak, muscle strength testing, and carotid sonography at baseline and after 3 years. Participants were grouped by carotid plaque status: no atherosclerosis, existing atherosclerosis, or newly developed atherosclerosis. Over 3 years, CRF and muscle strength (grip strength, leg flexion) declined significantly (all p < 0.005), while systolic BP (p = 0.042), brachial-ankle PWV (p = 0.006), and echocardiographic parameters including aortic root diameter and ventricular dimensions increased (all p < 0.001). Participants with newly developed atherosclerosis showed the greatest CRF decline (p = 0.012). Changes in CRF were inversely associated with changes in systolic, diastolic, and central BP (all p < 0.01). Declines in leg flexion strength were also linked to larger BP increases. Participants maintaining > 90

INTRODUCTION:In acute heart failure (AHF), the factors associated with successful renal replacement therapy (RRT) discontinuation are largely undefined. We hypothesized that improvements in Doppler-derived renal venous flow (RVF) waveforms may serve as indicators of recovering cardiorenal function associated with successful liberation from RRT. METHODS:We performed a post hoc analysis of a prospective cohort study involving inpatients with AHF undergoing serial renal Doppler evaluations. Patients who received acute RRT were retained for analysis, with Doppler assessments conducted both before RRT initiation and after discontinuation. Successful RRT discontinuation was defined as RRT cessation without relapse for at least 14 days. Logistic regression was used to evaluate the association between changes in RVF markers - including intra-renal venous flow (IRVF) and the renal venous stasis index (RVSI) - and RRT discontinuation, along with echocardiographic and clinical data from pre- to post-RRT Doppler measurements. RESULTS:Overall, 10/53 (19%) patients successfully discontinued RRT. Increases in the severity of IRVF patterns and RVSI were negatively associated with RRT discontinuation (IRVF per 1-pattern increase in severity: OR 0.01, 95% CI, <0.001-0.11; p < 0.001; RVSI per 0.1-unit increase: OR 0.11, 95% CI, 0.03-0.48; p < 0.001). Additionally, improvements in right ventricular function markers, such as the TAPSE/sPAP ratio (per 0.1 mm/mm Hg increase: OR 1.83, 95% CI, 1.03-3.32; p = 0.049), were associated with higher odds of RRT discontinuation. CONCLUSIONS:In AHF patients requiring acute RRT, improvements in RVF were associated with successful RRT discontinuation. Serial RVF assessment may offer a noninvasive means of capturing dynamic changes in cardiorenal syndrome physiology and renal recovery. Larger studies with more frequent and appropriately timed Doppler assessments are needed to determine whether RVF monitoring may guide RRT management in AHF.

Background: Sleep disorders are prevalent conditions that may influence the progression of various heart diseases. However, the relationship between sleep disorders and the onset of heart failure (HF) remains unclear. Objective: The purpose of this study was to investigate whether sleep disorders are associated with an increased risk of developing HF. Methods: We conducted a retrospective cohort study using data from 1,293 general practices across Germany sourced from the IQVIA Disease Analyzer database. The study included patients with an initial diagnosis of HF (ICD-10 code: I50) between January 2010 and December 2022 (index data) These patients were matched with control subjects without HF based on age, sex, and pre-existing conditions. The primary outcome was the association between prior sleep disorder diagnoses and the subsequent development of HF. Data were available for 9,345,246 individuals, of which 406,265 had a history of HF. Results: The study analyzed data from 123,516 patients with HF and an equal number of matched controls. The mean age of participants was 73.3-73.4 (SD 12.4) years, with 53.2% being women. Sleep disorders diagnosed prior to the onset of HF were significantly associated with an increased risk of developing HF. This association was consistent across different types of sleep disorders overall (OR: 1.22; 95%CI: 1.19-1.24) as well as insomnia (OR: 1.26; 95%CI: 1.21-1.31), sleep apnea (OR: 1.20; 95%CI: 1.15-1.25), and unspecified sleep disorders (OR: 1.21; 95%CI: 1.18-1.25). Conclusion: In this large cohort of outpatients, a prior diagnosis of sleep disorders was linked to a higher incidence of HF. These findings suggest that sleep disorders may serve as a risk factor for the development of HF, highlighting the need for early identification and management of sleep disturbances in at-risk populations. Addressing these disorders in clinical practice could represent a pivotal step towards better cardiovascular health and patient care.

We aimed to characterize the burden of dysglycemia in acute stroke and evaluate whether HbA₁c, even below the diabetic threshold, is associated with neurological severity and embolic risk. We conducted a prospective study of patients with ischemic stroke or transient ischemic attack (TIA) over six months at a German stroke center. Glycemic status was defined by glycated hemoglobin (HbA₁c) and fasting glucose per American Diabetes Association (ADA) criteria. Associations with stroke subtype, age, sex, and severity were analyzed. Abnormal glucose metabolism was present in 449 of 714 patients (62.9

Dysphagia is as a common consequence of cerebral infarction affecting approximately 50 URL: https://clinicaltrials.gov/study/NCT06195501?term=TEDRAS rank=1 Registered June 2024.

The benefits of physical activity are undisputed. However, adverse events can occur in rare cases, particularly during high-intensity or prolonged exercise. During physical activity, at-risk patients can experience major cardiac events, whereas adverse events affecting the musculoskeletal system are more common but less severe. A sports preparticipation evaluation (PPE) for apparently healthy adults is designed to detect at-risk individuals and prevent potentially fatal events. This guideline for conducting PPEs was developed by consensus among 16 medical societies and sports associations and is based on previously published guidelines and consensus papers. Sports medicine physicians and potential participants were also surveyed to assess the recommendations' content, feasibility, and implementation. On the basis of the 20 recommendations developed and agreed upon by the abovementioned entities, PPE comprises individuals' personal, family, and sports histories, as well as a physical examination. The need for additional examinations (e.g., laboratory parameters, echocardiograms, or stress tests) is determined on the basis of the PPE findings. This approach's feasibility in various regions, including resource-limited settings, and the extent to which it prevents adverse or potentially fatal events, should be examined in future research.