R3i Editorials

R3i editorials, created by members of the R3i board, focus on addressing the persistent challenges of residual cardiovascular risk. These editorials serve to educate healthcare professionals about emerging insights and therapeutic strategies related to lipid-related risk factors, such as triglyceride-rich lipoproteins and lipoprotein(a).

Latest Editorial

October 2026
Global burden of cardiovascular disease: a continuing challenge
Prof. Peter Libby, Prof. Michel Hermans, Prof. Pierre Amarenco, Prof. Lale Tokgözoglu 

Cardiovascular disease is the leading cause of death globally, responsible for about one-third of all deaths, with most due to myocardial infarction or stroke (1). Cardiovascular diseases also cause substantial morbidity and disability, with the global burden surging due to population growth and aging (2,3). Most of this cardiovascular disease burden (about 80%) is attributable to modifiable risk factors, with elevated blood pressure and low-density lipoprotein cholesterol (LDL-C), high body mass index, high fasting plasma glucose, and low physical activity identified as major contributors (1). However, as no single risk factor fully explains this burden, understanding how these major risk factors change over time provides a better assessment of global trends in cardiovascular risk.

Recent studies provide insights into the evolving picture of the global cardiovascular burden. Findings from the WHO Global Health Observatory which includes data from over 190 countries, showed improvements in hypertension and tobacco use but rising metabolic risk (4). Indeed, estimates from the Global Burden of Disease Study identify metabolic risk as a major contributor to the escalating challenge of cardiovascular-kidney-liver-metabolic syndrome, responsible for nearly half of the associated global disease burden. This burden is also unequal, with low- and middle-income countries shouldering an increasingly greater share (5). Trends for cholesterol were less clear, with analysis from the WHO Global Health Observatory indicating a downward trend in elevated total cholesterol prevalence in some but not all regions, a possible reflection of access to efficacious lipid-lowering therapies (4). 

Recently, the Global Burden of Disease Study 2023 investigated the cardiovascular burden attributable to elevated LDL-C (discussed in this month’s Focus report) (6). The study period 1990-2023 oversaw advances in the management of high LDL-C, with the introduction of novel highly efficacious treatments that target PCSK9, proven to reduce cardiovascular events in secondary prevention settings in the FOURIER and the ODYSSEY OUTCOMES trials (7,8).  Latterly, VESALIUS-CV with evolocumab extended the profile of cardiovascular efficacy with PCSK9-targeted inhibition to high-risk patients without prior myocardial infarction or stroke, demonstrating comparable benefit to that seen in the secondary prevention trials (9), thereby establishing the value of early upstream intervention for vulnerable populations. Clinical guidelines have also shifted, with combination LDL-C-lowering therapy essential to achieve increasingly stringent LDL-C goals among high-risk patients (10,11).

Thus, the question addressed indirectly by the Global Burden of Disease Study is whether this heightened focus on LDL-C management has impacted the burden of LDL-C-attributable atherosclerotic cardiovascular disease. The results, however, highlight an escalating clinical and socioeconomic challenge. Despite decreases in global age-standardized rates for death and disability-adjusted life years (DALYs) related to elevated LDL-C, the absolute burden of LDL-C-attributable cardiovascular disease increased over this period, largely driven by population growth and aging (4).

Importantly, this persistent cardiovascular burden due to elevated LDL-C was increasingly borne by low-and middle-SDI regions (4). These findings underline inequities in LDL-C management, encompassing prevention, detection, and treatment. For example, suboptimal use of statin treatment is prevalent; only about one in ten eligible people for the primary prevention of cardiovascular diseases and one in five eligible people for secondary prevention receive statin treatment (12), far below the WHO target of at least 50%.  Even with a generic fixed-dose combination polypill combining treatments that lower blood pressure, a statin, and aspirin, access and affordability remain significant barriers to their use (13). Overcoming these barriers will require comprehensive strategies that address both implementation by global agencies, as well as reimbursement by governments and other payers.

This latest report from the Global Burden of Disease Study highlights the enormity of the continuing cardiovascular burden attributable to elevated LDL-C.  Addressing the persistent inequities in treatment access and affordability is crucial. Furthermore, real change also necessitates broader, long-term strategies that not only support clinical care, but are also relevant to local environments and behaviours in cardiovascular health. All perspectives are essential to counter the burgeoning global burden of cardiovascular disease associated with elevated LDL-C.

References

  1. World Health Organization. Cardiovascular diseases. https://www.who.int/news-room/fact-sheets
  2. Chong B, Jayabaskaran J, Jauhari SM, et al. Global burden of cardiovascular diseases: projections from 2025 to 2050. Eur J Prev Cardiol 2025;32:1001-15.
  3. Global Burden of Cardiovascular Diseases and Risks 2023 Collaborators. Global, regional, and national burden of cardiovascular diseases and risk factors in 204 countries and territories, 1990-2023. JACC 2025; 86:2167-243.
  4. Candelaria D, Atkins T, Briffa T, Redfern J. Global trends in key modifiable cardiovascular risk factors: A joinpoint analysis across WHO regions (1990–2022). Eur J Prev Cardiol 2026; doi: 10.1093/eurjpc/zwag401.
  5. Jayabaskaran J, Nagarajan S, Raden Himan H, et al. Global and regional projections of atherosclerotic cardiovascular-kidney-liver-metabolic disease burden to 2050: a forecasting analysis for the global burden of disease study 2023. Metabolism 2026;183:156716.
  6. GBD 2023 LDL Cholesterol Collaborators. Global Burden of Elevated LDL-C. Findings from the Global Burden of Disease Study 2023. JAMA doi:10.1001/jama.2026.8628.
  7. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22.
  8. Schwartz GG, Steg PG, Szarek M et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-107.
  9. Bohula EA, Marston N, Bhatia AK, et al. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med 2026;394:117-27.
  10. Blumenthal RS, Morris PB, Gaudino M, et al. 4

2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026;87:2624-757.

  1. Mach F, Koskinas KC, Roeters van Lennep JE, et al. Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2025;46:4359-78.
  2. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88.
  3. Marcus ME, Manne-Goehler J, Theilmann M, et al. Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data. Lancet Glob Health 2022;10(3):e369-e379.
  4. Satheesh G, Gyawali B, Sun MFC, et al. A survey of availability and affordability of polypills for cardiovascular disease in selected countries. Global Heart 2024;19(1): 56.

 

Key words: LDL-C; low-density lipoprotein cholesterol; global cardiovascular disease burden; residual cardiovascular risk