What are we missing to gain the battle against cardiovascular diseases?

Cardiovascular disease (CVD) remains a leading cause of premature morbidity and mortality worldwide, affecting the majority of adults after the age 60 years. When considering diagnostic aspects, CVD includes four major areas, i.e., coronary heart disease (CHD) as myocardial infarction, angina pectoris, heart failure, and coronary death; cerebrovascular disease, as stroke and transient ischemic attack; peripheral artery disease, as intermittent claudication, and aortic atherosclerosis and thoracic or abdominal aortic aneurysm. Already in 2012 and 2013, CVD resulted in 17.3 million death every year worldwide, approximately 31% of all deaths globally1-3. Recent epidemiological data from the Global Burden of Disease (GBD) studies point to concerning trends, and show escalating rates of CVDs that surpass the effects of population aging. From 1990 to 2019, the prevalence of total CVD nearly doubled, with cases rising from 271 million to 523 million. Concurrently, CVD-related deaths increased steadily from 12.1 million to 18.6 million. Disability-adjusted life years (DALYs) and years of life lost also saw significant increases, with years lived with disability doubling from 17.7 million to 34.4 million. DALYs attributed to ischemic heart disease (IHD) rose steadily to 182 million, with 9.14 million deaths in 2019 and 197 million prevalent cases of IHD. Similarly, DALYs due to stroke reached 143 million, with 6.55 million deaths in 2019 and 101 million prevalent cases of stroke4. In the ongoing battle against CVDs, remarkable progress in diagnosis and therapies has been made, pointing to improved patient outcomes. Nevertheless, CVDs continue to pose a significant global health challenge. The escalating burden of CVD requires substantial economic costs and is therefore a challenges to global health systems. There is urgent need for a comprehensive re-evaluation of strategies in combating CVD as an example of pervasive health threat. The ideal strategies should continue to target the best available and widely accessible medical treatments. A critical target should also be the implementation of public health policies oriented to markedly reduce the huge burden of environmental factors driving the onset and progression of CVD, independently from age. While individual risk assessment and targeted treatment strategies have been pivotal in managing CVDs, there exists a critical gap in addressing primary prevention measures. Environmental health, mainly in terms of detrimental effects of air pollution and climate change, has been largely overlooked in conventional medical paradigms. This oversight not only perpetuates inequities generating the burden of CV risk but also exacerbates the underlying drivers of CVDs. The first evidence linking clear relationships between air pollution and CVD has been published in the late ‘60 (i.e., the Nashville Pollution Study)5. In the last decades, consolidated epidemiological and experimental studies underlined a number of pathogenic mechanisms linking environmental pollutants with the onset and progression of atherogenesis, and with detrimental, direct effects on the cardiovascular system. These studies highlight the pressing need for a paradigm shift towards holistic preventive approaches. Yet, the integration of environmental health considerations into medical education and clinical practice remains inadequate, with a notable absence in mainstream curricula. This article delves into the multifaceted challenges impeding progress in the war against CVDs. By examining the critical role of environmental factors, the pervasive inequities in access to essential therapies, and the lack of awareness among healthcare professionals, we aim to shed light on the barriers that must be overcome to achieve meaningful advancements in cardiovascular health. Environmental factors such as pollution and climate change significantly impact the fight against CVDs (Figure 1). Despite notable progress in reducing ambient air pollution, studies from regions like Europe, North America, Australia, Canada, and the USA reveal adverse health effects even at low pollution levels. Impact of environmental factors on cardiovascular diseases This issue has become a matter of discussion for the WHO policy addressing at least 17 Sustainable Development Goals (SDG)(https://sdgs.un.org/goals), including SDG 3.4, i.e., non-communicable diseases and mental health, and SDG 3.9, i.e.. Mortality from environmental pollution. (https://www.who.int/data/gho/data/themes/sustainable-development-goals). Coronary heart disease and stroke, the most prevalent CVDs globally, are linked to various biological mechanisms affected by air pollution, including chronic systemic inflammation, epigenetic modulation of gene expression, oxidative stress, altered gluco-lipid homeostasis and autonomic nervous system imbalance, all contributing to the development of atherosclerosis and other cardiovascular issues. Large epidemiological cohort studies have consistently reported associations between cardiovascular disease incidence or mortality and both short- and long-term exposure to air pollutants as fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and black carbon6. Moreover, rising temperatures due to climate change pose another significant risk for CVDs. In fact, heat waves can exacerbate existing health conditions and increase morbidity and mortality rates, especially among vulnerable populations as older individuals and those with pre-existing chronic comorbidities. The GBD, Injuries, and Risk Factors Study underscores heat exposure as a significant contributor to cardiovascular disease related DALYs lost globally7. Despite mounting evidence linking environmental factors to cardiovascular outcomes, clinical practice and medical education have been slow to incorporate these considerations. Efforts to integrate planetary health principles into medical guidelines are underway globally, with initiatives such as the UK NHS aiming for climate neutrality by 20408. However, a systematic assessment of clinical guidelines from various medical associations reveals that planetary health issues are still largely absent. Furthermore, the absence of environmental health topics in medical curricula leaves healthcare professionals ill-equipped to address the complex interplay between environmental factors and cardiovascular health9-11. In addition to environmental factors, inequities in access to essential therapies pose significant challenges in the fight against CVDs. While advancements in medical technology and pharmaceuticals have expanded the armamentarium of treatments available for CVDs, disparities in access persist, particularly among marginalized and underserved populations. Statin therapies, which are widely used to lower cholesterol levels and reduce the risk of cardiovascular events, exemplify this issue. Despite being recommended as first-line therapy for individuals at high risk of CVDs, access to statins remains uneven across populations. Studies have shown that factors such as socioeconomic status, race, and geographic location influence the likelihood of receiving statin therapy, with disadvantaged groups often facing barriers to access12. These inequities in access to statin therapies contribute to disparities in cardiovascular outcomes, perpetuating cycles of illness and socioeconomic disadvantage. Addressing these disparities requires a multifaceted approach, including policies to improve healthcare access, initiatives to reduce medication costs, and targeted interventions to reach vulnerable populations. Central to overcoming the challenges in the war against CVDs is the role of healthcare professionals. Physicians, nurses, and other healthcare providers play a pivotal role in both preventing and managing CVDs, yet many remain unaware of the relevance of environmental factors and inequities in access to therapies. Efforts to improve awareness and education among healthcare professionals are essential in addressing these gaps. Clinicians should be adequately prepared to routinely engage in counselling patients on how to reduce the health risks derived from living in an unsafe environment. On the other hand, healthcare professionals should act as advocates, adequately presenting scientific evidence to policymakers to facilitate and to promote changes and transition towards sustainability. Integrating environmental health topics into medical curricula, providing continuing education on the latest research findings, and promoting interdisciplinary collaboration are critical steps in ensuring that healthcare providers are equipped to address the complex determinants of cardiovascular health. While significant progress has been made in the diagnosis and treatment of CVDs, the war is far from over. To achieve meaningful advancements in cardiovascular health, we must address the missing pieces in our current clinical approach, including the role of environmental factors, inequities in access to therapies, and the need for greater awareness among healthcare professionals. In other terms, the main missing piece is an effective primary prevention strategy. By embracing a holistic, patient-centred approach that considers the broader determinants of health, we can begin to turn the tide against CVDs. This will require collaboration across disciplines, innovative policy solutions, and a renewed commitment to health equity. H.S and A.D.C. conceived the idea for the manuscript, H.S wrote the draft and figures, P.P. and A.D.C reviewed the manuscript. P.P. is the coordinator of B4HT projects “Box for Health by Tradition & Innovation: promoting sustainable Mediterranean diet by Healthy Foods” funded by the PRIMA project, Section 2 – Multi-topic 2022. Project partners: University of Bari Aldo Moro (Italy), University of Genoa (Italy), Lebanese University (Lebanon), and University of Monastir (Tunisia). PP is recipient of HORIZON-HLTH-2022-STAYHLTH-01-05-two-stage Project 101080329 - PAS GRAS with the following partners Universidade De Coimbra, Portugal; Uppsala Universitet, Sweden; Universidade Nova De Lisboa, Portugal; Fundacio Eurecat (Eurecat), Barcelona, Spain; Consiglio Nazionale Delle Ricerche (Cnr), Roma Italy; Instituto Politecnico De Viana De Castelo, Viana Do Castelo 4900-347, Portugal; Technische Universitaet Muenchen (Tum), Muenchen, Germany; Instytut Biologii Doswiadczalnej Im. M. Nenckiego Polskiej Akademii Nauk (Nencki), Warszawa, Poland; Instituto Pedro Nunes Associacao Para A Inovacao E Desenvolvimento Em Ciencia E Tecnologia (Ipn), Coimbra, Portugal; The European Society For Clinical Investigation (Esci), Utrecht, Netherlands; Mediagnost Gesellschaft Fur Forschung Und Herstellung Von Diagnostika Gmbh (Mediagnost), Reutlingen, Germany; Martin-Luther-Universitat Halle-Wittenberg (Mlu), Halle, Germany; Associacao Protectora Dos Diabeticos De Portugal (Apdp), Lisboa 1250-203, Portugal; Agdcentro Associacao De Ginastica Do Centro (Agcentro), Coimbra, Portugal. PP is primary investigator in the grant PNRR-MAD-2022-12375639, project on Chronic non-communicable diseases. Involvement of neuroprotective mechanism(s) of neuroglobin on aberrant functions related to chronic neurological diseases. All the authors report having no relevant conflicts of interest for this article.

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