Abstract:Nicotine is an independent and frequently underestimated cardiovascular risk factor. While prevention strategies have long focused on tobacco smoke and combustion products, current evidence clearly shows that nicotine itself is vasculotoxic, regardless of the delivery mode. Through sympathetic activation, blood pressure elevation, oxidative stress, endothelial dysfunction, and prothrombotic effects, nicotine drives the initiation and progression of cardiovascular disease. Most nicotine-associated mortality is cardiovascular and often occurs earlier than cancer outcomes. New nicotine products such as e-cigarettes, heat-not-burn devices, and oral nicotine pouches do not reduce this risk but increasingly shift exposure toward younger populations. A consistent, product-spanning early warning signal is the endothelial dysfunction, a validated predictor of future cardiovascular events, which is reversible only with complete nicotine abstinence. Unified, risk-based regulation of all nicotine-containing products is therefore a central pillar of effective cardiovascular prevention.

Traffic-related environmental noise represents a widespread and relevant environmental factor in Europe that is associated with a substantial burden of disease. Current estimates indicate that a significant proportion of the population is exposed to noise levels linked to adverse health effects. Cardiovascular diseases are among the most extensively studied outcomes in this context. Epidemiological studies consistently demonstrate associations between long-term exposure to traffic noise and an increased risk of arterial hypertension, ischemic heart disease, myocardial infarction, heart failure and arrhythmias. These associations are often dose-dependent and also remain even after adjustment for air pollution. Experimental human studies provide complementary mechanistic evidence, showing that even short-term noise exposure can impair endothelial function, activate autonomic stress responses and disrupt sleep. Underlying mechanisms include activation of the sympathetic nervous system, dysregulation of the hypothalamic-pituitary-adrenal axis, oxidative stress and inflammatory processes. Overall, the available evidence supports a stronger consideration of traffic noise as a modifiable risk factor for cardiovascular disease. In addition to individual-level measures to reduce exposure, population-based strategies for noise reduction are essential.

Loneliness has emerged as a significant and independent risk factor for cardiovascular disease (CVD), with epidemiological studies reporting an estimated 15%–30% increased risk across diverse populations and settings. This review synthesizes current evidence linking loneliness to major cardiovascular outcomes including coronary artery disease, heart failure, stroke, and all-cause mortality. This review is organized using a bio-psycho-social framework, examining biological mechanisms, psychological vulnerability, and social determinants contributing to cardiovascular risk. Within this framework, we examine biological mechanisms underlying this association, including chronic activation of stress response systems (hypothalamic–pituitary–adrenal axis and sympatho-adrenomedullary system), endothelial dysfunction, systemic inflammation, oxidative stress, and sleep disturbances. Among patients with established CVD, loneliness is highly prevalent (36%–45%) and associated with poor prognosis, reduced treatment adherence, and lower cardiac rehabilitation participation. We outline practical approaches for screening loneliness in clinical settings and discuss intervention strategies addressing social, emotional, and cognitive pathways. Recognition of loneliness as a modifiable cardiovascular risk factor represents an important opportunity for comprehensive patient care and secondary prevention strategies.

Healthy soils and clean water are essential for human survival, yet, both are increasingly compromised by chemical and plastic pollution. This preventable crisis causes an estimated 9 million premature deaths each year, including about 0.9 million linked to soil pollution and 1.3 million to water pollution. In 2019 alone, pollution contributed to 5.5 million cardiovascular deaths, underscoring its role in the global burden of non-communicable disease. A key underrecognized driver is the rapid rise in plastic production and plastic-associated chemicals. Global plastic output has increased more than 250-fold since 1950 and is projected to nearly triple by 2060, while less than 10% is effectively recycled. As highlighted by the Lancet Countdown on health and plastics, plastics threaten human health across their lifecycle, from fossil fuel extraction to waste, fragmentation, and environmental persistence. Soils and water systems are increasingly contaminated by heavy metals, pesticides, persistent synthetic chemicals, and micro- and nanoplastics. These pollutants degrade soil, reduce agricultural productivity, contaminate food chains, and spread through aquatic ecosystems, thereby amplifying disease risk. Micro- and nanoplastics have been detected in human blood, placenta, brain, and cardiovascular tissues, raising concern about biological effects. These exposures are drivers of cardiovascular disease. Despite their chemical diversity, they converge on shared mechanisms, including oxidative stress, inflammation, endocrine disruption, and circadian dysregulation. Their persistence reflects policy failure. Reducing soil, water, and plastic pollution must become a central pillar of cardiovascular prevention through enforceable, lifecycle-based policies that protect human health. #These authors contributed equally and should be considered as joint first and joint last authors.

Cardiogenic shock complicates takotsubo syndrome (TTS) in approximately 10

Non-communicable diseases (NCDs) account for 70% of global mortality and are responsible for over 38 million deaths annually, with cardiovascular disease (CVD) constituting most of these fatalities. While traditional risk factors for CVD have long been recognized, there is growing evidence that a rising prevalence of ubiquitous environmental risk factors (ERFs) may play an increasingly significant role in the genesis and rising prevalence of NCDs. ERFs include many interconnected anthropogenic exposures with cumulative compound health impacts, including air pollution, noise exposure, artificial light at night, plastic pollution, chemical pollution and the various effects of climate change, such as heat extremes, desert storms, floods and wildfires. Urbanization has intensified the impact of many ERFs and created intense exposure environments, highlighting the urgency and the opportunity to address these for maximum public health benefit. Impactful intervention often requires regulatory and policy-driven efforts addressing the genesis of exposures and minimizes their health impact, particularly in vulnerable populations who may contribute the least but may be impacted the most. Solutions must involve the development of resiliency and adaptation measures to a changing world, where the probability of sudden catastrophic and cascading events is much more likely. Political will and international cooperation are essential in establishing and enforcing regulations that promote cleaner air and water, quieter and natural biodiverse environments, and sustainable infrastructure in urban, and rural medical facilities. Integration of planetary and environmental health into cardiovascular care will be vital in reducing the burden of NCDs globally. By addressing the root causes of environmental stressors, it is possible to reduce the incidence of CVDs and promote healthier, just and sustainable societies.

BACKGROUND:Peripheral artery disease (PAD) is the third leading cause of atherosclerotic morbidity. The influence of comorbidity burden on the prognosis of PAD patients is still underestimated. The Charlson Comorbidity Index (CCI) is an established tool for evaluating patients' comorbidity burden. METHODS:We used the German nationwide inpatient statistics including all hospitalizations of patients admitted due to PAD in Germany 2005-2022 and categorized according CCI classes (mild: CCI=1-2points, moderate: CCI=3-4points, high severity: CCI>4points). RESULTS:Overall, 3,167,987 hospitalizations of PAD patients were included in our study. Of these, 10.3% were categorized as mild, 34.3% as moderate and 55.4% as high-severity CCI class. Comorbidity burden and particularly frequency of high-severity CCI class increased from 51.2% (2006) to 58.5% (2022).An increase in the CCI class was associated with increased likelihood of being treated endovascularly (OR 1.48, 95%CI 1.48-1.49, P<0.001) rather than surgically (OR 0.87, 95%CI 0.87-0.88, P<0.001). An increase in the CCI class was associated with an elevated risk for major adverse cardiovascular and cerebrovascular events (MACCE) (OR 9.66, 95%CI 9.45-9.88, P<0.001), amputation (OR 2.82, 95%CI 2.80-2.84, P<0.001) and in-hospital case-fatality (OR 9.87, 95%CI 9.62-10.12, P<0.001). CONCLUSION:PAD patients' comorbidity burden increased during the observational period between 2005 and 2022 in Germany. Higher comorbidity burden mirrored by higher CCI class was associated with an approximately 10-fold increased risk for MACCE and in-hospital mortality. Physicians have to be aware for the impact of comorbidity burden and optimization of the comorbidities is an important focus to improve outcomes and prevent complications.

Background: Peripheral artery disease (PAD) constitutes a major global burden of disease. Regarding patient-cases of patients with PAD, it is of outstanding interest to identify patients with a high risk for adverse in-hospital events. Thus, risk stratification tools including scores are of key interest for prognosis prediction. Materials and methods: The German nationwide inpatient statistics 2005-2018 was used for this analysis. Patient-cases of PAD patients were stratified according to a modified Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class and compared. The predictive performance of this score was evaluated to predict adverse in-hospital events with the help of unadjusted and adjusted logistic regressions. Results: Overall, 2,462,085 patient-cases (36.8% females; 57.4% ≥ 70 years) of patients hospitalised due PAD were included in Germany 2005-2018. According to the Mansoor's self-report tool for cardiovascular risk assessment, 1,101,123 (44.7%) of the PAD patient-cases were classified as low-risk and 1,360,962 (55.3%) as high-risk. High-risk class was predictive for major adverse cardiovascular and cerebrovascular events (MACCE; odds ratio [OR] 1.09 [95% confidence interval [CI] 1.07-1.10], p < .001), acute kidney injury (OR 1.33 [95% CI 1.30-1.36], p < .001) and amputations (OR 1.46 [95% CI 1.44-1.47], p < .001). In contrast, high risk class was not associated with increased rate of arterial and venous embolism/thrombosis and in-hospital death (OR 0.97 [95% CI 0.96-0.99], p < .001). High risk class was associated with coronary revascularization treatments. Conclusions: The modified Mansoor's Self-Report Tool for Cardiovascular Risk Assessment score is a new and effective risk stratification tool to predict individual risk regarding MACCE, acute kidney injury and amputations in PAD patients during their hospitalisation, but the score failed to predict for in-hospital mortality.

AIMS: Ultrafine particles (UFPs) smaller than 100 nm are ubiquitous in polluted air. Although they carry little mass, UFPs have a large exposure surface area, can bypass respiratory defences, translocate into the brain and bloodstream, and impact the heart and other organs. Here, we assess the role of UFPs in air quality and the health burden they impose. METHODS AND RESULTS: We integrated Earth observations with machine learning to estimate long-term UFP exposure at 1 km resolution, demonstrating that they pose a major air quality concern in urban environments, with annual mean concentrations typically ranging between 10,000 and 30,000 particles/cm-3. Model calculations suggest that black and organic carbon are primary components of pollution UFPs. Based on a meta-analysis of epidemiological cohort studies in Europe and North America, we derived a pooled hazard ratio for mortality and combined it with our UFP data. We estimate a mortality density of 35.7 (15.8-65.5) per 100,000 people annually in Europe, and 27.4 (12.9-47.4) per 100,000 in North America, the latter being close to the global mean. We find that UFP exposure and mortality densities are particularly high in South and Eastern Europe. Since observational data for other regions are limited, global calculations primarily depend on modelling. We indicatively estimate that 1.99 (0.81-3.89) million excess deaths per year are attributable to UFP exposure. This could account for approximately 5% of total mortality from non-communicable diseases, to a large degree (about half) due to cardiovascular conditions. Globally, about 91% of UFP-related excess mortality occurs in urban and suburban environments, and much of that (78%) in densely populated urban areas. CONCLUSION: Health-improving interventions should target combustion sources in cities, particularly those related to energy consumption, industry, and traffic. An annual air quality limit of 5,000 cm-3 could reduce global excess mortality by about 45%.

Particulate matter (PM) is a significant contributor to air pollution-associated negative health effects, and cardiovascular disease patients are more susceptible to air pollution-mediated damage of the heart and vessels. The present study investigated the protective effects against PM-induced cardiovascular damage by classic cardiovascular drugs, as used for the standard therapy of cardiovascular disease patients. Male C57BL/6J mice were exposed to ambient PM2.5 (<2.5 µm) for 3 days with or without treatment with the cholesterol-lowering drug atorvastatin (20 mg/kg/d) or the angiotensin-converting enzyme (ACE) inhibitor captopril (50 mg/kg/d). Both drugs mitigated PM2.5-induced systolic blood pressure increases and partially prevented endothelial dysfunction, as reflected by a mixed effect on endothelial nitric oxide synthase phosphorylation. Both drugs ameliorated reactive oxygen species (ROS) formation and phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-2) expression in the vasculature of PM2.5-exposed mice. Pulmonary ROS levels showed a minor improvement by the treatments, whereas Nox2 mRNA expression was not diminished. Only captopril showed some anti-inflammatory effects in the heart and lung of PM2.5-exposed mice, whereas both drugs failed to reduce systemic inflammation measured in plasma. These findings offer new insights into potential mitigation strategies for PM2.5-induced cardiovascular complications, particularly for patients at higher cardiovascular risk, like those with coronary artery or ischemic heart disease or hypertension.

Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m2. Patients with an eGFR < 30 ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1 year. In MULTISTARS AMI, 108 (13

Ambient air pollution is a leading modifiable environmental determinant of cardiovascular morbidity and mortality worldwide. Long-term and short-term exposure to fine particulate matter and traffic-related pollutants is consistently associated with an increased risk of ischemic heart disease, stroke, heart failure, arrhythmia and cardiovascular death. Mechanistic studies demonstrate that inhaled pollutants induce pulmonary and systemic oxidative stress, inflammation, endothelial dysfunction, autonomic imbalance and prothrombotic changes, providing biological plausibility for these associations. Air pollution rarely acts in isolation but clusters with other environmental stressors, such as transportation noise, heat and limited access to green space and disproportionately affects socioeconomically disadvantaged and medically vulnerable groups. This review summarizes the current evidence on the cardiovascular effects of air pollution, highlights high-risk populations and discusses clinical, public health and policy strategies to reduce exposure and vulnerability. We argue that contemporary cardiovascular prevention must adopt an exposome-oriented perspective and engage with transport, energy, housing and urban planning policies to effectively protect vulnerable patients and communities.

Environmental pollution-including air, noise, and light-and progressive climate change are major contributors to global health burdens, responsible for over 9 million premature deaths annuallysa. Among environmental exposures, air and noise pollution show the strongest epidemiological links to hypertension and cardiovascular disease, while emerging evidence also implicates light pollution, toxic metal exposure, and climate-related factors. Hypertension, the leading global cause of mortality, is increasingly recognized as a sentinel marker of environmental damage. Fine particulate matter (PM2.5) and road traffic noise exposure are associated with significant increase in hypertension prevalence and incidence. While historical guidelines overlooked environmental contributors, recent updates by the European Society of Hypertension (ESH) and European Society of Cardiology (ESC) have integrated environmental risk factors into hypertension management frameworks. This position paper from the ESH Working Group on Environment and Hypertension synthesizes current evidence on the epidemiology and pathophysiology of environmental pollution in the development of hypertension. It highlights the mechanistic pathways involving oxidative stress, vascular dysfunction, and neurohormonal dysregulation triggered by pollution exposure. Importantly, the paper outlines mitigation strategies at both population and individual levels, including legislative initiatives, urban planning, and personal exposure reduction techniques. Considering hypertension as an early manifestation of environmental harm offers a critical opportunity for preventive intervention. It is vital to emphasize strict blood pressure control, enhanced screening in high-risk populations and the integration of environmental exposure monitoring into clinical practice. This comprehensive document seeks to raise awareness among healthcare professionals and inform evidence-based strategies for reducing pollution-related hypertension and cardiovascular morbidity.