The Lancet Commission on rethinking coronary artery disease: moving from ischaemia to atheroma

Abstract

Coronary artery disease has long been understood through the paradigm of epicardial coronary artery obstruction, causing myocardial ischaemia (a mismatch between myocardial blood supply and demand). However, this model, which focuses on diagnosing and managing coronary artery disease based on ischaemia and cardiovascular events, is flawed. By the time ischaemia manifests, it is often too late for optimal intervention, limiting the effectiveness of treatment options. Despite decades of medical advances, coronary artery disease continues to be a leading cause of morbidity and mortality globally, highlighting the inadequacy of this traditional ischaemic-centric approach.

The central limitation of current approaches is the focus on the temporary solutions of restoring myocardial blood flow after obstruction, rather than tackling the underlying disease. Coronary artery disease, caused by atherosclerosis, often results in myocardial infarction through mechanisms that emerge earlier in the progression of disease. The focus of medical care has predominantly been on the recognition of symptoms and treatment of acute events, missing opportunities for early detection and prevention of disease. Billions of dollars in health-care funding continue to be spent on identifying and managing coronary ischaemia; yet, the dominant mechanisms for myocardial infarction are atherosclerotic plaque rupture or erosion and, to a lesser extent, erupted calcified nodules that can emerge at a much earlier stage of the disease.

This Commission advocates for a shift in the conceptual framework of coronary artery disease. We suggest reclassifying the condition as atherosclerotic coronary artery disease (ACAD), moving away from the traditional emphasis on ischaemia and acute cardiac events towards a more systematic understanding of atherosclerosis. This reframing will enable the identification and management of the disease much earlier in its course, potentially saving millions of lives worldwide.

Risk of ACAD develops over a lifetime, beginning in utero, progressing through childhood and adolescence, and continuing into older age. The early stages of disease, which involve the formation of atherosclerotic plaques, are often undetected. A major shift is needed from acute event-centred care to strategies focused on early diagnosis, prevention, and management of atherosclerosis. In this new framework, ACAD should be recognised across all stages, from the earliest signs of atheroma formation to the advanced stages of disease. Our goals should not just to be to manage symptoms and events but to prevent the disease from developing in the first place and, where possible, reverse its course.

Early detection and prevention of ACAD: The prevention of ACAD must begin with early detection and modification of risk factors. If behavioural and metabolic risk factors, such as smoking, hypertension, high cholesterol, and poor diet, were eliminated or controlled early in life, the global burden of ACAD could be dramatically reduced. Eliminating these risk factors by 2050 could decrease the rate of ACAD deaths by 82·1%, potentially saving 8·7 million lives annually. Public health initiatives should emphasise lifestyle changes and the management of metabolic disorders to prevent the onset of atherosclerosis.

Early detection and effective prevention remain a challenge. The implementation of screening strategies to identify individuals at risk of developing ACAD is crucial. Targeted screening programmes, integrated into health-care systems, can detect early signs of atherosclerosis and enable timely intervention. Such interventions, if applied early, have the potential to halt, delay, or even reverse the progress of the disease, reducing the risk of cardiovascular events in later life.

Addressing the global burden of ACAD: ACAD is not a uniform problem across the globe. Disparities exist between high-income countries and low-income to middle-income countries in terms of prevention, diagnosis, and treatment. These differences contribute to variations in health outcomes. Between 2022 and 2050, mortality rates from ACAD are forecasted to increase by 19·2% in lower-middle-income countries and 4·2% in upper-middle-income countries. This global disparity underscores the importance of equitable access to prevention, diagnosis, and treatment to reduce the global burden of ACAD.

Health-care systems must be designed to prioritise prevention and early detection of ACAD rather than simply treating advanced disease. This prioritisation requires a fundamental shift in the education and training of health-care providers, with a focus on the early stages of the disease and the integration of prevention strategies into clinical practice.

A comprehensive international approach to ACAD treatment requires increased research funding, the development of novel treatments, and investment in early detection methods. The development of new therapies to prevent, reverse, and eradicate atherosclerosis is crucial. Research funding must be increased to support these efforts, particularly in the development of transformative therapies and imaging technologies that can accurately assess disease progression at all stages.

Current research is insufficient and does not match the global burden of the disease. Research is not representative of diverse populations, often neglecting the specific needs of low-income and middle-income countries. More research is needed to ensure that clinical pathways for the prevention and treatment of ACAD are adaptable and effective across all health-care settings.

The reframing of coronary artery disease as ACAD represents a crucial shift in the way we approach the disease. By recognising ACAD as a lifelong condition, from early atherosclerotic plaques to advanced disease, and shifting priority towards early detection, prevention, and treatment, the potential to save millions of lives annually is substantial. Implementing these changes will require global collaboration, increased investment, and a commitment to equitable health-care delivery. Stakeholders should work together towards the stabilisation, reversal, and ultimate elimination of ACAD, reducing the global burden of this preventable disease.

Figure 1:. Number of deaths from ACAD from 1990 to 2021 and projection to 2050 with and without elimination of metabolic and behavioural risk factors

Raw data were acquired from the Institute for Health Metrics and Evaluation through the Global Burden of Disease Foresight and Results tools. Data from 1990 to 2021 are based on past observations. Data from 2022 to 2050 are forecasted. The forecasted data consists of two scenarios: a reference scenario and an improved behavioural and metabolic risks scenario (with 5-year delay). In both scenarios, the risk, demographic, and environmental factors were first forecasted until 2050 and then used to regress the mortality trends. Under the improved behavioural and metabolic risks scenario, the original study assumed that: (1) metabolic risks, high adult BMI, high systolic blood pressure, high LDL-cholesterol, and high fasting plasma glucose, are linearly eliminated by 2050; (2) exposure to non-optimal diet is eliminated by 2050; (3) the number of smokers reduces linearly until reaching zero in 2050; and (4) there are no new smokers after 2022. For each measurement, the mean value and the 95% uncertainty interval (from percentile 2·5–97·5; shown as shaded areas) were used. Data were visualised using the Matplotlib, Seaborn, and GeoPandas packages in Python programming. No imputation and alteration of the data was performed. ACAD=atherosclerotic coronary artery disease.

Figure 2:. Projected change in number of ACAD deaths from 2021 to 2050

(A) Number of global deaths from ACAD per 100 000 population in 2021. (B) Projected change in global deaths from ACAD per 100 000 population from 2021 to 2050. Global Burden of Disease estimates for ischemic heart disease were used to construct choropleth maps. ACAD=atherosclerotic coronary artery disease.

Figure 3:. Absolute number of deaths from ACAD by income and geographical region, current and projected to 2050

(A) Deaths by income level. (B) Deaths by geographical region. Estimates are from the GBD model and definitions. ACAD=atherosclerotic coronary artery disease. GBD=Global Burden of Disease.

Figure 4:. Number of deaths from ACAD per 100 000 population by income and geographicalregion, current and projected to 2050

(A) Deaths by income level. (B) Deaths by geographical region. Data are from GBD estimates. ACAD=atherosclerotic coronary artery disease. GBD=Global Burden of Disease.

Figure 5:. Projected changes in absolute numbers of deaths from ACAD by geographical regions from 2021 to 2050

Dark-coloured circles indicate number of deaths in 2021 from ACAD. Light-coloured circles indicate the projected change over time to 2050. Population size in each geographical region is represented by size of circle. Data from Global Burden of Disease models. ACAD=atherosclerotic coronary artery disease.

Figure 6:. Contribution of leading risk factors to global ACAD deaths between 1990 and 2021

Data are from Global Burden of Disease models. ACAD=atherosclerotic coronary artery disease. Dietary risk is defined as a diet low in fruits, vegetables, legumes, whole grains, fibre, nuts and seeds, seafood omega-3 fatty acids, calcium, polyunsaturated acids, and milk, as well as a diet high in red meat, processed meat, sugar-sweetened beverages, sodium, and trans fatty acids.

Figure 7:. Leading risk factor contributions to ACAD DALYs by income level for 2021

Data are from Global Burden of Disease models. ACAD=atherosclerotic coronary artery disease. DALYs=daily-adjusted life-years.

Figure 8:. Global prevalence of leading risk factors contributing to all causes of death between 2021 and projected to 2050

SEV is the ratio between the weighted average of the excess risks among individuals in the global population and the maximum excess risk. Data are from Global Burden of Disease models. This metric includes both the prevalence of the exposure and the extent to which such exposure would affect the disease. SEV is 0% when everyone in the population has no excess risk and 100% when everyone is at maximum risk. For a dichotomous risk factor, SEV is equivalent to the prevalence. SEV=summary exposure value.

Figure 9:. Opportunities and strategies to prevent atherosclerotic coronary artery disease over the life course

Early life defined as age 0–3 years. Young life defined as age 4–17 years. Adult life defined as age 18 years and older. ACAD=atherosclerotic coronary artery disease.

Figure 10:. Summary of evidence on risk factor exposure with ACAD according to primordial, primary, and secondary prevention interventions

Green=modifiable risk factors with multiple studies showing that intervention on this risk factor leads to improved cardiovascular outcomes. Yellow=risk factors with some data, but the efficacy of an intervention on cardiovascular outcomes has not been established. Red=minimal or no supporting data. ACAD=atherosclerotic coronary artery disease. DASH=Dietary Approaches to Stop Hypertension. NA=not applicable.

Figure 11:. Guidance on screening and investigation of atherosclerotic coronary artery disease

Figure 12:. Recommended actions to lower mortality and morbidity from atherosclerotic coronary artery disease