Abstract:Brain aging, many neurological diseases, and glaucoma are associated with neurodegenerative processes of varying degrees. Regular physical activity is one of the most successful non-pharmacological interventions for prevention and treatment. The mechanisms of neuroprotection through exercise and sport are becoming increasingly well understood. In addition to general anti-inflammatory and antioxidant effects, there are specific effects on neurogenesis, brain plasticity, and angiogenesis in the brain, which are also clinically associated with, among other things, reduced cognitive decline. Dozens of exerkines are now known. These are proteins or metabolites that are released during exercise and exert neuroprotective effects in the brain via specific mechanisms of action, e. g., BDNF (brain-derived neurotrophic factor) or VEGF (vascular endothelial growth factor). Intervention studies have shown that moderate endurance training, as well as specific strength training, can stimulate these and other neurobiologically relevant factors and positively influence atrophy processes in certain brain regions (e. g., the hippocampus).

Clinical guidelines for secondary cardiovascular (CV) prevention provide recommendations for medical treatment to improve patient prognosis. This retrospective German study aimed to identify the level of guideline implementation in patients suffering from myocardial infarction (MI), stroke or transient ischemic attack (TIA), and the impact of guideline-directed medical therapy (GDMT) adherence on CV outcomes or death. Data from an anonymized claims dataset from a German statutory health fund were analyzed regarding GDMT for the above patient population. Patients were followed for at least one year after their first MI and/or stroke/TIA. For clinical outcomes analysis, a 1:1 propensity score matching (PSM) was applied between patients receiving a GDMT and those with a treatment not in line with GDMT (nGDMT). Data from 56,671 patients with previous MI and 96,257 patients with previous stroke/TIA were included; 50.1

BACKGROUND:The effects of CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), on exercise capacity in people with cystic fibrosis (pwCF) remain unclear, with no data available on their impact within the context of an exercise intervention. Therefore, this study aimed to assess the effects of an exercise intervention on exercise capacity in adults with CF, comparing those treated with and without ETI. METHODS:A total of 56 adult pwCF participated in this quasi-experimental study as part of a rehabilitation program, which included a 3.5-week exercise intervention. The program involved five weekly 45-min sessions, including endurance training on a cycle ergometer. VO2 peak and Wpeak were the primary outcomes used to assess changes in exercise capacity. RESULTS:The intervention significantly increased VO2 peak and Wpeak in all pwCF, regardless of ETI use, with similar improvements between groups. PwCF with lower baseline fitness (VO2 peak ≤ 81%pred) showed greater improvements than those with higher fitness (VO2 peak ≥ 82%pred). ppFEV1 remained unchanged, while BMI increased in both groups. Notably, the ETI group spent significantly more time in physical activity (PA) at hard and very hard intensities compared to the non-ETI group. Additionally, a positive correlation was observed between PA intensity and VO2 peak and Wpeak in the ETI group. CONCLUSION:Independent of ETI treatment, adult pwCF improve their exercise capacity by participating in a regular exercise program. ETI treatment appears to enhance time spent in higher PA intensities. Despite the effectiveness of CFTR modulators, regular PA and exercise remain essential to maintain and improve exercise capacity in pwCF.

BACKGROUND:Patients with hypertension or dyslipidemia and patients in cardiovascular secondary protection usually require more pharmaceuticals to achieve the target values. For some years, a combination treatment with a single pill has been recommended for arterial hypertension and for most patients even from the beginning of treatment. OBJECTIVE AND METHODS:The aim of this review article is to present the current recommendations and illuminate the evidence with respect to cardiovascular outcomes for single pill treatment in comparison to loose combinations. RESULTS:The achievement of the target values in arterial hypertension, dyslipidemia and in secondary prevention is insufficient. Poor adherence plays a major role in this. This greatly depends on the number of pills, a simple treatment schedule and as few treatment changes as possible. For this reason, national and international scientific societies recommend an initial combination treatment when possible in a single pill. This concept is supported by a broad evidence base for an improved adherence. There are now also investigations that show significant reductions in cardiovascular outcomes, including the overall mortality, for single pill treatment in comparison to the use of the same substances in identical doses in the form of loose combinations. Simultaneously, the use of a single pill leads to a reduction of the total treatment costs due to improved adherence, a lower number of hospitalizations and a reduction of cardiovascular outcomes. The implementation of the recommended concept is insufficient as combinations are still used for the majority of patients, contrary to the guidelines and despite the availability of single pills with the selected substances and doses. CONCLUSION:The use of single pills in cardiovascular treatment improves the adherence, reduces cardiovascular outcomes and is widely recommended by specialist societies. The improvement of the insufficient implementation in the clinical practice needs comprehensive efforts.

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.

Patienten mit Hypertonie oder Fettstoffwechselstörungen und Patienten in der kardiovaskulären Sekundärprävention benötigen in der Regel mehrere Pharmaka zum Erreichen der Zielwerte. Seit einigen Jahren wird bei arterieller Hypertonie für die meisten Patienten schon zu Beginn der Therapie eine Kombinationstherapie mit einer Single Pill, also mit einer Tablette, empfohlen. Ziel der vorliegenden Übersicht ist es, die aktuellen Empfehlungen darzustellen und die Evidenz bezüglich kardiovaskulärer Endpunkte bei Single-Pill-Therapie im Vergleich zu losen Kombinationen zu beleuchten. Die Erreichung der Zielwerte bei arterieller Hypertonie, Fettstoffwechselstörungen und in der Sekundärprävention ist unzureichend. Dabei spielt eine schlechte Adhärenz eine zentrale Rolle. Diese hängt stark von der Tablettenzahl, einem einfachen Therapieschema und möglichst seltenen Therapieumstellungen ab. Aus diesem Grund empfehlen nationale und internationale Fachgesellschaften eine initiale Kombinationstherapie möglichst in einer Tablette, also mittels einer Single Pill. Dieses Konzept wird unterstützt durch eine breite Evidenz für eine verbesserte Adhärenz. Inzwischen gibt es auch Untersuchungen, die bei Single-Pill-Therapien signifikante Reduktionen kardiovaskulärer Endpunkte einschließlich der Gesamtmortalität zeigen im Vergleich zum Einsatz der gleichen Substanzen in identischer Dosis in Form loser Kombinationen. Gleichzeitig kommt es bei Einsatz von Single Pills zu einer Reduktion der Gesamttherapiekosten durch eine verbesserte Adhärenz, eine geringere Zahl von Hospitalisierungen und eine Reduktion kardiovaskulärer Endpunkte. Die Umsetzung der empfohlenen Konzepte ist unzureichend, denn bei der Mehrzahl der Patienten werden weiterhin lose Kombinationen eingesetzt – entgegen den Leitlinien und trotz Vorhandensein von Single Pills mit den gewählten Substanzen und Dosierungen. Der Einsatz von Single Pills in der kardiovaskulären Therapie verbessert die Adhärenz, reduziert kardiovaskuläre Endpunkte und wird von den Fachgesellschaften breit empfohlen. Die Verbesserung der unzureichenden Umsetzung in der klinischen Praxis bedarf umfangreicher Anstrengungen.

The purpose of this derivative version is to highlight and disseminate the core recommendations to clinicians, sports practitioners, and policy makers in the German-speaking health and sports sector.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 pre-participation evaluation (PPE) is designed to detect at-risk individuals and prevent potentially fatal events in apparently healthy adults. Therefore, a new guideline for conducting PPEs was developed through a consensus process involving 16 medical societies and sports associations based on previously published guidelines and consensus papers. Sports medicine physicians and potential participants were surveyed to assess the content, feasibility, and acceptability of the recommendations. Based on 20 recommendations developed and agreed upon by these entities, the PPE includes taking individuals’ personal, family, and sports histories, as well as a physical examination. The need for additional examinations (e.g., laboratory parameters, echocardiography, or stress tests) is determined based on the findings. The effect of implementing this guideline should be examined in future research.

AIMS:Our study aimed to assess whether a single pill concept (SPC) is superior to a multi-pill concept (MPC) in reducing cardiovascular (CV) events, all-cause death, and costs in CV patients. METHOD AND RESULTS:Anonymized medical claims data covering 2012-2018, including patients with hypertension, dyslipidaemia, and CV diseases who started a drug therapy either as SPC or identical MPC were analysed after 1:1-propensity score matching. Hospitalizations with predefined CV events, all-cause mortality, and costs were studied in 25 311 patients with SPC and 25 311 patients with MPC using incidence rate ratios (IRRs) and non-parametric tests for continuous variables.IRRs were significantly lower for SPC: stroke (IRR = 0.77; 95% CI 0.67-0.88; P < 0.001), transitory ischaemic attack (IRR = 0.61; 95% CI 0.48-0.78; P < 0.001), myocardial infarction (IRR = 0.76; 95% CI 0.63-0.90; P = 0.0016), coronary artery disease (IRR = 0.66; 95% CI 0.57-0.77; P < 0.001), heart failure (IRR = 0.59; 95% CI 0.54-0.64; P < 0.001), acute renal failure (IRR = 0.54; 95% CI 0.56-0.64; P < 0.001), all cause hospitalization (IRR = 0.72; 95% CI 0.71-0.74; P < 0.001), CV hospitalization (IRR = 0.63; 95% CI 0.57-0.69; P < 0.001), and all-cause mortality (IRR = 0.62; 95% CI 0.57-0.68; P < 0.001). Mean time to first events and time to death were also in favour of SPC. Mean total costs were 4708€ for SPC vs. 5.669€ for MPC, respectively (mean ratio 0.830, P < 0.001). CONCLUSION:SPC is associated with lower incidence rates of CV events, time to CV events, and all-cause death, and is superior regarding pharmacoeconomic parameters and should therefore become standard of care to improve outcomes and reduce healthcare costs.

In the management of overweight, the implementation of exercise helps to create a caloric deficit and to lose weight. Several studies have shown poor reporting quality of exercise interventions for other diseases. Thus, the purpose of this study was to assess the completeness of exercise intervention reporting in randomized controlled trials (RCTs) for the treatment of overweight and to evaluate potential differences between exercise modalities. Two independent reviewers applied two intervention reporting guidelines to 47 RCTs on the management of overweight. The completeness of intervention reporting was evaluated using descriptive statistics. Potential differences in reporting quality between studies using aerobic exercise (AE) vs. studies using combined aerobic and resistance exercise (ARE) were calculated with a χ2 test. Overall, studies completed 61% and 47%, respectively, of the guideline items. The χ2 analysis of exercise modalities showed a significant difference for two items regarding exercise progression (91% AE vs. 38% ARE, p<0.001) and detailed description of exercises (0% AE vs. 50% ARE, p<0.001). Reporting of exercise interventions in the treatment of overweight was found insufficient. The detected differences between exercise modalities imply the need for improved guidelines.

The benefits of exercise have been well described for the treatment of hypertension. Poor reporting quality impairs quality appraisal and replicability. High intensity interval training (HIIT) has been shown to be an effective alternative to traditional aerobic exercise in patients with hypertension. We evaluated the completeness of reporting of randomized controlled trials (RCTs) with HIIT for hypertension and to compare both exercise modes in reporting quality. RCTs of HIIT with a minimum duration of 6 weeks in adults with at least high normal blood pressure (≥130 mmHg/≥85 mmHg) were evaluated using the Consensus on Exercise Reporting Template (CERT). Nine RCTs conducting HIIT in hypertensive patients (N=718; 51.8 years) were evaluated. A mean of 62.6% of items were sufficiently described, compared with 49.2% in moderate intensity training interventions. Exercise dose was adequately reported in 8 out of 9 studies. Only one study reported information on adverse events. In a small sample of RCTs with HIIT in patients with hypertension we found a better reporting quality than in moderate intensity training interventions. However, reporting completeness is not optimal for a good replicability in clinical practice. The lack of reporting of adverse events in interventions using high intensities is particularly unfavourable.

Background:The SECURE trial demonstrated that the cardiovascular (CV)-polypill (acetylsalicylic acid [ASA] + atorvastatin + ramipril) reduces CV mortality by 33% in patients with acute myocardial infarction compared to standard care. The 2023 ACS ESC Guidelines recommend the polypill to improve outcomes and adherence. Objective:This study aims to establish a global consensus on the optimal use of the CV-polypill in secondary prevention. Methods:A two-round, modified Delphi method was used, featuring a 30-statement evidence-based questionnaire validated by eight renowned cardiologists. Fifty clinicians from 19 countries in Europe, Latin America, and Asia were invited to join the Delphi panel. Panelists ranked responses using a three-point Likert scale for agreement and importance. Consensus was defined as ≥80% agreement or rating statements 'very important' or 'important'. Statements without consensus after the first round were refined with evidence and feedback in the second round. Remaining disagreements were resolved in a face-to-face meeting. Descriptive statistics were applied. Results:Response rate was 76% (round 1) and 74% (round 2); 82% were cardiologists, with 74% frequently recommending the CV-polypill. Consensus was achieved on 93.3% of statements. Research showing a 24% relative risk reduction in major adverse CV events over a median of 3 years with the CV-polypill post-acute myocardial infarction, compared to usual care, reached 97.4% agreement for clinical implementation, and a 100% consensus supported polypill use at hospital discharge or first follow-up visits; 81.1% agreed on a prompt initiation after patient stabilization. There was agreement on algorithms for initiating (97.3%), considering patient preferences (97.4%) to the polypill and its cost savings over usual care (89.5%). Conclusion:The Delphi consensus on real-world use of a CV polypill (ASA, atorvastatin, and ramipril) for secondary prevention post-acute coronary syndrome supports early initiation (within 8 days or at discharge). The findings provide a foundation to inform practice and policy, identifying priorities for further research.

Color vision testing can be used to detect subtle disturbances in retinal function, which can often occur before clinical symptoms and, for the ophthalmologist, before visible changes in the fundus of the eye in general vascular diseases. This makes it possible to carry out rapid and inexpensive early diagnosis by detecting acquired color vision disorders, which can prevent further damage by optimizing therapy. Here it is particularly important to work closely with general practitioners and internists. Such aspects should be given greater consideration in occupational medicine. In many areas of industry, high demands are placed on color vision. In areas such as the textile industry, the chemical paint industry, the food industry, the automotive industry (paints) and in painting companies, normal color perception is of fundamental importance. Color vision testing is an inexpensive and easy-to-perform examination method that can provide an early indication of acquired color vision deficiency under standardized conditions. In addition to the detection of a generalized microcirculatory disorder, this determination is also useful in occupational medicine in order to better determine suitability for certain occupational groups. Keywords: color vision, vascular diseases, diabetes, arterial hypertension, migraine

Abstract Background The SECURE trial demonstrated that the CV-polypill strategy (acetylsalicylic acid [ASA]+atorvastatin+ramipril) reduces CV mortality by 33% in patients with acute myocardial infarction (MI) compared to standard care over 3 years (median). The 2023 ACS ESC Guidelines recommend the polypill strategy to improve outcomes and treatment adherence. The CV-polypill inclusion in the 2023 World Health Organization's essential medicines list signifies its effective and affordable response to a global secondary prevention healthcare requirement. Purpose To reach consensus among medical experts from various countries regarding key implementation aspects of the CV-polypill strategy (ASA+atorvastatin+ramipril) as baseline preventive treatment after a CV event (CVe) in routine clinical practice. Methods A two-round modified Delphi method was employed. A questionnaire consisting of 30 evidence-based statements was developed and validated with input from 8 distinguished cardiologists. The Delphi panel, 50 physicians from 19 countries across Europe, Latin America, and Asia, used a three-point Likert scale to establish their agreement and perceived importance of the statements. Consensus was reached when ≥80% agreed or deemed statements 'very important' or 'important. Statements without consensus in the first round underwent refinement based on evidence and panellists’ feedback in the second round. Persistent disagreements were resolved in a face-to-face meeting with experts. Descriptive statistics were applied. Results 38/50 panellists participated in round 1, and 37/50 in round 2. 31/38 were cardiologists. 28/38 routinely prescribed the CV-polypill strategy. 97.4% of panellists believed that the 24% relative risk reduction in major CVe over 3 years (median), attained with the CV-polypill strategy (ASA+atorvastatin+ramipril) compared to standard care could replicate in clinical practice while maintaining equal safety (97.4%). Unanimous consensus (100%) supported initiating the CV-polypill strategy as baseline preventive treatment upon hospital discharge or at first follow-up. Its efficacy and safety were also acknowledged for stroke (94.7%), peripheral artery disease (92.1%), and both genders (84.2%). 89.5% supported CV-polypill affordability for preventing CHD events and strokes. Algorithms for initiation (97.3%) and transition (97.4%) to the CV-polypill strategy from cardioprotective drugs, considering patient preferences (97.5%), were confirmed. A unanimous consensus (100%) affirmed the positive impact of the simplified CV-polypill treatment on patient satisfaction, with 94.7% recognizing its convenience (Figure 1). Conclusions Skilled medical experts across continents reached consensus on critical implementation aspects and strongly endorse the early use of the CV-polypill strategy (ASA+atorvastatin+ramipril). This adoption aims to reduce CVD recurrence, improve prognosis, and potentially enhance affordability in CVD treatment after a CVe.Consensus on CV polypill implementation

Primary open angle glaucoma is a primary mitochondrial disease with oxidative stress triggering neuroinflammation, eventually resulting in neurodegeneration. This affects many other areas of the brain in addition to the visual system. Aging also leads to inflammaging - a low-grade chronic inflammatory reaction in mitochondrial dysfunction, so these inflammatory processes overlap in the aging process and intensify pathophysiological processes associated with glaucoma. Actively counteracting these inflammatory events involves optimising treatment for any manifest systemic diseases while maintaining chronobiology and improving the microbiome. Physical and mental activity also provides support. This requires a holistic approach towards optimising neurodegeneration treatment in primary open angle glaucoma in addition to reducing intraocular pressure according personalised patient targets.

ZusammenfassungDas Glaukom ist mit zahlreichen Risikofaktoren und internistischen Erkrankungen wie Diabetes mellitus Typ 2 verbunden. Der Typ-2-Diabetes-mellitus führt peripher und im Gehirn zu neurodegenerativen Veränderungen. Möglicherweise liegt in der Neurodegeneration auch eine Gemeinsamkeit in der Pathophysiologie und Ätiologie beider Erkrankungen. Interessanterweise scheinen zahlreiche Medikamente zur Therapie des Diabetes mellitus unabhängig von der Senkung des Blutzuckers neuroprotektive Eigenschaften aufzuweisen. Obwohl prospektive, randomisierte klinische Studien dazu noch fehlen, scheinen besonders Metformin und Glucagon-like-Peptide-1-Receptor-Agonisten (GLP-1-RA) neuroprotektive Effekte aufzuweisen. Die immer noch sehr häufig eingesetzten Sulfonylharnstoffe (z. B. Glibenclamid, Glimepirid) senken zwar sehr potent den Blutzucker, haben bez. der Neuroprotektion wohl vergleichsweise weniger Effekte. In der vorliegenden Übersicht werden diese unterschiedlich ausgeprägten neuroprotektiven Befunde dargestellt und eine mögliche Differenzialtherapie für Diabetiker mit Glaukom oder erhöhtem Glaukomrisiko in der Praxis diskutiert.

Primary open-angle glaucoma (POAG) is no longer considered an isolated eye pressure-dependent optic neuropathy, but a neurodegenerative disease in which oxidative stress and neuroinflammation are prominent. These processes may be exacerbated by additional systemic diseases. The most common are arterial hypertension, dyslipidemia, and diabetes mellitus. Using diabetes mellitus as an example, it will be shown how far-reaching the influence of such a systemic disease can be on both the functional and the structural diagnostic methods for POAG. This knowledge is essential, since these interferences can lead to misinterpretations of POAG, which can also affect therapeutic decisions.

ZusammenfassungDas primäre Offenwinkelglaukom ist eine primäre Mitochondriopathie, die über den oxidativen Stress zu einer Neuroinflammation führt und später in eine Neurodegeneration übergeht. Dabei sind neben dem visuellen System zahlreiche weitere Hirnareale betroffen. Da es beim Altern im Rahmen einer mitochondrialen Dysfunktion ebenfalls zu einer niedriggradigen chronischen Entzündungsreaktion kommt (Inflamm-Aging), überlagern sich diese entzündlichen Prozesse im Alter und verstärken die glaukomassoziierten pathophysiologischen Vorgänge. Um aktiv diesen Entzündungsereignissen entgegenzuwirken, soll die Therapie von vorhandenen Systemerkrankungen optimiert, die Chronobiologie eingehalten und das Mikrobiom verbessert werden. Hierfür unterstützend sind eine erhöhte physische und mentale Aktivität. Somit ist neben einer personalisierten zieldruckorientierten Augeninnendrucksenkung auch eine holistische Sichtweise erforderlich, um der Neurodegeneration primäres Offenwinkelglaukom therapeutisch gerecht zu werden.