The growing importance of non-traditional cardiovascular risk factors: global warning, infections, and extreme sports

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on epidemiology, prevention, and healthcare policies contains a Special Article entitled ‘Heat extremes and cardiovascular diseases: a scientific statement of the Association of Cardiovascular Nursing & Allied Professions, Association for Acute Cardiovascular Care, European Association of Preventive Cardiology, Heart Failure Association, European Heart Rhythm Association of the ESC, the ESC Council on Hypertension, the ESC Council on Stroke, and the ESC Working Group on Cardiovascular Pharmacotherapy’ by Georgia K. Chaseling from The University of Sydney, Australia, and colleagues which provides a comprehensive discussion on the epidemiological evidence of heat-related cardiovascular disease (CVD), the human physiological responses to hot environments, the impact of heat on cardiovascular health, and the relative impact of social inequalities.1 Globally, hot weather and heatwaves are claiming lives, and are predicted to become increasingly deadly under all future climate change scenarios.2,3 Rising global temperatures pose a significant risk to cardiovascular health, disproportionately impacting the elderly and people with CVD. However, despite convincing epidemiological data demonstrating this increased cardiovascular risk, the physiological mechanisms that underpin this risk are less known. Exposure to elevated temperatures leads to increased inflammation, myocardial oxygen demand, and dehydration, predisposing people to myocardial stress. Additionally, health and social inequities such as low income, poor housing, and limited access to cooling further exacerbate the health risks during heatwaves. This scientific statement aims to inform clinicians, researchers, and policymakers by addressing the current evidence regarding the epidemiology and physiology of heat-related CVD. Cardiovascular disease is the leading cause of deaths worldwide, with 80% occurring in low- and middle-income countries. These countries are characterized by rapid urbanization, poorly funded health systems, poor access to prevention and treatment strategies, and increasing age and a higher prevalence of chronic disease.4–6 In a State of the Art Review article entitled ‘Social factors, health policy, and environment: implications for cardiovascular disease across the globe’, Scott A. Lear from Simon Fraser University, British Columbia, Canada, and colleagues aim to understand the environmental, social, and policy determinants of cardiovascular health in countries across varying levels of economic development through an urban/rural lens.7 Rapid urbanization has contributed to the significant environmental and societal changes affecting daily life habits and cardiovascular health. There is growing awareness that environmental and social exposures and policies can influence CVD directly or through behavioural risk factors. However, much of this knowledge comes from studies in high-income countries and is applied to low- and middle-income countries without evidence to indicate that this is appropriate. This state-of-the-art review presents and synthesizes key findings from the Prospective Urban Rural Epidemiology study and related studies. Emerging from these findings are future policy and research recommendations to accelerate the reduction of the global burden of CVD. Hypertension is a key modifiable cardiovascular risk factor.8–16 In a Clinical Research article entitled ‘Ambulatory blood pressure monitoring, European guideline targets, and cardiovascular outcomes: an individual patient data meta-analysis’, Dong-Yan Zhang from Shanghai Jiao Tong University School of Medicine in China, and colleagues assess the association of risk with the percentage of time that the ambulatory blood pressure (ABP) is within the target range (PTTR) proposed by the 2024 European Society of Cardiology (ESC) guidelines for blood pressure (BP) management.17 In a person-level meta-analysis of >14 000 individuals enrolled in 14 population cohorts, systolic and diastolic ABPs were combined to assess 24 h, daytime, and night-time PTTR. During 10.9 years median follow-up, deaths (n = 3117) and cardiovascular endpoints (n = 2265) decreased across increasing 24 h PTTR quartiles from 21.3 to 16.1 and from 20.3 to 11.3 events per 1000 person-years, respectively. The standardized multivariable-adjusted hazard ratios (HRs) for 24 h PTTR were 0.57 for mortality and 0.30 for cardiovascular endpoints. Analyses of daytime and night-time ABP, cardiovascular mortality, coronary endpoints and stroke, and subgroups produced confirmatory results. The 2024 ESC non-elevated 24 h PTTR, compared with the 2018 ESC/European Society of Hypertension non-hypertensive 24 h PTTR, shortened the interval required to reduce relative risk for adverse outcomes from 60% to 18%. Office BP, compared with 24 h PTTR, misclassified most participants with regard to BP control. The authors conclude that a longer time with ABP within the 2024 ESC target range is associated with reduced adverse outcomes; PTTR derived from ABP refines risk prediction and, compared with office BP, avoids misclassification of individuals with regard to BP control. The manuscript is accompanied by an Editorial by Ruth Campbell and John W. McEvoy from the University of Galway in Ireland.18 The authors note that while Zhang and colleagues should be commended for their rigorous meta-analysis, it is worth considering its limitations. Residual confounding remains a concern, and the generalizability may be limited by the under-representation of Black individuals. Additionally, the applicability of these findings to frail elderly populations is uncertain. Finally, only clinical trials (which have been done) can truly confirm the value of BP treatment targets recommended by the 2024 ESC Guidelines and, as such, these observational data are simply indirectly confirmatory. Despite these limitations, the meta-analysis of Zhang and colleagues provides compelling motivation for a paradigm shift in hypertension management by supporting the lower BP treatment control targets recommended in the 2024 ESC BP Guidelines. These findings also underscore the need for a more dynamic approach to BP control—one that prioritizes PTTR over static BP measurements. As wearable BP-monitoring technology continues to evolve, the ability to achieve and sustain optimal PTTR may become increasingly feasible, paving the way for more effective and individualized hypertension treatment strategies that may help to overcome the major challenges we currently face. The future, we hope, is bright. Vaccinations are playing a growing role in cardiovascular prevention.19,20 Despite the potential association between herpes zoster infection and cardiovascular events, limited studies have investigated the relationship between live zoster vaccination and cardiovascular outcomes. In a Clinical Research article entitled ‘Live zoster vaccination and cardiovascular outcomes: a nationwide, South Korean study’, Sooji Lee from Kyung Hee University in Seoul, South Korea, and colleagues present the results from a large-scale, population-based cohort study with a long-term follow-up aimed to investigate the association between live zoster vaccination and the risk of various cardiovascular events.21 Data on comprehensive information of individuals aged ≥50 years from South Korea (n = 2 207 784) were included from 1 January 2012 to 31 December 2021. National insurance information from the Korea Health Insurance Review and Assessment Service, the national health examination results from the Korean National Health Insurance Service, and the live zoster vaccination data from the Korea Disease Control and Prevention Agency were merged. The risk of incident cardiovascular outcomes after live zoster vaccination was compared with that of unvaccinated individuals. The primary outcome was the risk of CVDs. In propensity score-based overlap weighted cohorts, Cox proportional hazard models were used to estimate HRs for overall and specific cardiovascular outcomes, while calculating restricted mean survival time for each outcome. After applying propensity score-based overlap weighting, ∼1 270 000 individuals were included (mean age, 61 years; 43% male; median follow-up time, 6.0 years) in the overlap-weighted cohort. Live zoster vaccination was associated with significantly lower risks of overall cardiovascular events (HR 0.77), particularly major adverse cardiovascular events (HR 0.74), heart failure (HR0.74), cerebrovascular disorders (HR 0.76), ischaemic heart disease (HR 0.78), thrombotic disorders (HR 0.78), and dysrhythmia (HR 0.79) (Figure 1). The protective association persisted up to 8 years, with the greatest reduction observed 2–3 years post-vaccination. The decrease in CVD risk was more pronounced among males, individuals aged <60 years, those with unhealthy lifestyle habits, those from low-income households, and rural residents. Structured Graphical Abstract21 The authors conclude that the findings suggest that live zoster vaccination may be beneficial as a public health strategy, with potential implications for CVD burden in the general population. The manuscript is accompanied by an Editorial by Christian Torp-Pedersen and Tor Biering Sørensen from the University of Copenhagen in Denmark.22 The authors highlight that due to the sparsity of safety data and methodological challenges, herpes zoster vaccination cannot be currently recommended for indications other than avoidance of shingles. Observational studies have indicated herpes zoster vaccination not only to protect against CVD, but also to be protective against dementia. While anything is possible, such a result increases the risk of a healthy survivor bias. It is therefore necessary that these observational results are tested in a properly conducted randomized trial. Vaccines stand as one of the greatest achievements of evidence-based medicine, preventing millions of infections and premature deaths worldwide. However, vaccinations of many types are also associated with rare, but serious side effects. Consequently, establishing a herpes zoster vaccine as a recommendation to reduce the risk of CVD requires a very large-scale randomized trial which not only shows a benefit of reducing CVD, but which can also convince the community of safety. The time is ripe for such a study. Premature deaths of bodybuilders have raised questions about the safety and associated risks of this discipline. In a Clinical Research article entitled ‘Mortality in male bodybuilding athletes’, Marco Vecchiato from the University of Padova in Italy, and colleagues analyse mortality risk in a large international population of bodybuilders.23 Male athletes who took part in International Federation of Bodybuilding and Fitness (IFBB) competitions between 2005 and 2020 were identified and classified according to age, division, and level. A standardized web search, tailored to detect deaths, was performed for each athlete using specific keywords, with follow-up through July 2023. Mortality rates were calculated both as the overall incidence rate during the monitored period and as the annual incidence rate of those who participated in at least one competition within the previous year, i.e. currently competing athletes. A total of ∼20 200 athletes competing in 730 IFBB events were identified, with an average follow-up of 8.1 years. During the study period, 121 deaths were identified: 73 were considered sudden deaths, of which 46 were classified as sudden cardiac deaths, including 11 currently competing athletes. The incidence of SCD in currently competing athletes was 32.83 cases per 100 000 athlete-years. Available autopsies of SCD cases consistently showed cardiomegaly and ventricular hypertrophy. Professional bodybuilders had a much higher risk of SCD than amateurs (HR 5.23) (Figure 2). Structured Graphical Abstract23 The authors conclude that the results of this study should alert the bodybuilding and medical communities to the need for improved preventive measures to promote safer sports participation. The manuscript is accompanied by an Editorial by James M. Smoliga from Tufts University School of Medine in Boston, MA, USA.24 The authors note that the findings of Vecchiato et al. underscore that competitive bodybuilding is associated with a disproportionately high mortality rate and SCD risk. Although parallels can be drawn to other high-risk sports, the unique goal of extreme hypertrophy and the culture of open drug use demand specialized interventions. Heightened doping control, comprehensive screening, and honest athlete–clinician dialogues all have potential to improve bodybuilder safety. However, these may not fully mitigate risk, especially if stakeholders accept the sport’s dangers as part of its ethos. Ultimately, efforts to reduce the mortality rate must balance the sport’s inherent pursuit of extreme physiques with a commitment to athlete safety. Bodybuilders, their healthcare providers, and the IFBB must work collaboratively to develop evidence-based strategies that both respect the sport’s culture and address the very real health risks that bodybuilders face. The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Unaddressed questions on the benefits of nationwide abdominal aortic aneurysm screening in Sweden’, Heng Wang, Honglin Dong, and Guoping Zheng from The University of Sydney, Australia and The Second Hospital of Shanxi Medical University in China comment on the recently published paper entitled ‘Abdominal aortic aneurysm repair in Sweden vs. Finland: benefits of population-wide screening’ by Matti T. Laine from the University of Helsinki and Helsinki University Hospital in Finland, and colleagues.25,26 Laine et al. reply in a separate contribution.27 The editors hope that this issue of the European Heart Journal will be of interest to its readers. Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, BMS, Chiesi, Daiichi Sankyo, Menarini outside the submitted work. With thanks to Lindsay Washington, Johanna Huggler, Amelia Meier-Batschelet, and Martin Meyer for help with compilation of this article.