Editorial 

Global Low-Density Lipoprotein Cholesterol—Leveraging Estimation for Action

Mark D. Huffman, Victor G. Dávila-Román, Anubha Agarwal

JAMA Published Online: July 29, 2026

doi: 10.1001/jama.2026.10083

The Global Burden of Disease (GBD) 2023 study represents another step in the laudable, collective effort to better understand the causes of health, disease, and mortality around the world in a comprehensive and cohesive manner. The article in this issue of JAMA by the GBD 2023 LDL Cholesterol Collaborators¹ reports trends in the global, regional, and national burden of cardiovascular disease (CVD) attributed to elevated low-density lipoprotein cholesterol (LDL-C) from 1990 to 2023. The study addresses an important and arguably underrecognized problem in many parts of the world. The methods are consistent with other GBD reports and represent the best current global estimates of elevated LDL-C. Other reports using pooled demographic health survey and related data have been published.^2,3 This report extends the previous observations by linking findings to the global burden of CVD, namely ischemic heart disease and ischemic stroke, and by using the most contemporary data. Further refinement of these estimates is expected through future iterations of GBD and other large-scale pooling research.

Amid the wealth of numbers, discerning the proverbial forest through the trees is essential if these estimates are to be leveraged for action to improve global cardiovascular health. Several key points emerge from this report. First, the regional and national variability in the rate of change in elevated LDL-C in the study’s decomposition analysis led the authors to conclude that there is divergence in this burden across quintiles of sociodemographic index. For example, from 1990 to 2023, the highest quintile experienced a 54.2% decline in age-standardized LDL-C–attributable disability-adjusted life-years (DALYs) compared with an 8.9% increase in the lowest quintile. But globally, absolute LDL-C levels have risen modestly from 1990 to 2023 and are arguably converging across quintiles of sociodemographic index. Increases in elevated LDL-C are seen in many countries with a lower sociodemographic index (measured by education, income, and fertility), and decreases are seen in countries with a higher sociodemographic index due to a combination of changes in what people eat and what medicines they take. This global convergence has led to countries with an intermediate sociodemographic index bearing the highest burden of elevated LDL-C, especially in highly populous India and China. What seems more remarkable is how relatively modest changes in global estimates of elevated LDL-C have coincided with massive changes in dietary patterns around the world over this same time, including increased consumption of ultraprocessed foods and animal-source proteins that would be expected to raise LDL-C more substantially.

Second, while the age-standardized burden of CVD attributable to LDL-C has declined considerably over the study period (by 39.5% based on DALYs and by 45.6% based on deaths), the absolute attributable burden increased by 38.5% to 3.6 million premature deaths (95% uncertainty interval, 2.2 million to 5.4 million) and 90.7 million DALYs (95% uncertainty interval, 58.9 million to 123.2 million), largely due to population growth and aging. These demographic shifts to a growing and aging population have played an outsized yet almost imperceptible and inexorable influence on the global disease burden—and will continue to do so for decades to come—especially given the gains in life expectancy over the past 75 years.

Third, decomposition analyses show that risk-deleted DALYs declined by 41.3 million (95% uncertainty interval, 24.9 million to 63.4 million) from 1990 to 2023. Risk-deleted DALYs represent the remaining disease burden after accounting for population growth, aging, and temporal changes in elevated LDL-C exposure. This measure captures residual changes in health outcomes due to trends in other risk factors, implementation of public health policies, delivery of quality clinical care, and overall health care infrastructure strengthening. Despite these favorable trends, the cascade of lipid care is not as well documented as other CVD risk factors such as hypertension or diabetes, and population-based estimates of statin use are very low—only 21.9% (95% CI, 20.0%-24.0%) for secondary prevention among individuals who have experienced a previous CVD event and 8.0% (95% CI, 6.9%-9.3%) for primary prevention among high-risk individuals who have not.⁴

Fourth, the predominant types of CVD in many low-income countries are often different compared with middle- and high-income countries and include less atherosclerosis and more hypertensive heart disease. Competing risks from conditions that affect younger individuals likely drive at least some of this difference, as does long-standing exposure to poverty—rheumatic heart disease being an example that captures both phenomena.⁵ Vital registration systems are also less robust in low-income countries, raising the question of ascertainment bias or misclassification. However, recent research in East Africa explores the lower rates of atherosclerotic CVD and potential protective mechanisms that could partially explain why atherosclerosis is less common in some populations.⁶

A few limitations merit consideration of how closely these estimates reflect truth. First, this report focuses on LDL-C compared with other parameters, such as non–high-density lipoprotein cholesterol (non–HDL-C) or apolipoprotein B. This is an important limitation given the aforementioned changes in global dietary patterns and the rapidly rising prevalence of overweight and obesity, which is more likely to influence triglycerides and HDL-C. Nevertheless, the overall direction and magnitude of results are similar to previous reports that relied on non–HDL-C, such as the Noncommunicable Diseases Risk Factor Collaboration (NCD-RisC).³ Second, the theoretical minimum risk exposure level was set at 35 to 54 mg/dL based on randomized trial evidence demonstrating benefits of LDL-C at these levels. However, mendelian randomization studies suggest larger, compounding benefits from longer and earlier (including lifelong) reductions in LDL-C.⁷ Thus, these results may be underestimates of the true burden of elevated LDL-C. Third, the study focuses on ischemic heart disease and ischemic stroke, likely underestimating total LDL-C–attributable burden, excluding peripheral artery disease, vascular dementia, and other atherosclerotic manifestations. Fourth, the report relies on widespread use of spatiotemporal gaussian-process regression modeling to estimate LDL-C due to large data gaps. This common criticism of GBD estimates can hopefully continue to stimulate large and sustained efforts for better surveillance, something for which the GBD team has long advocated. That said, data from 806 population-based studies from 161 countries were included, and data availability is increasing in all parts of the world. Despite these limitations, the findings are novel, important, and valid.

With ever more data in hand demonstrating the large and rising burden of CVD and its risk factors, questions logically extend about how to move from estimation to action on elevated LDL-C. Population-wide elimination of artificial trans fatty acids through implementation of the World Health Organization’s REPLACE package provides an exemplar approach. Adopting policies that eliminate artificial trans fatty acids have been associated with reduction in CVD events posited to be driven by favorable lipid trends.⁸ Warning labels identifying foods high in unhealthy fats are increasingly implemented to raise consumer awareness, but other policies designed to lower LDL-C, such as Denmark’s short-lived tax on saturated fat,⁹ have less traction and sustainability. Broader efforts to improve the healthfulness, sustainability, and affordability of the food supply, including healthy fats, will require collective action, especially given the anticipated increase in burden of LDL-C with projected population growth, aging, and economic growth.

The findings of the GBD 2023 LDL Cholesterol Collaborators¹ arrive at a critical juncture. The United Nations Sustainable Development Goals target of reducing premature mortality from noncommunicable diseases by one-third by 2030 appears increasingly out of reach for CVD. On the health system side, the World Heart Federation’s Cholesterol Roadmap outlines barriers and facilitators to addressing elevated serum cholesterol, ranging from increasing public awareness to training health workers to reducing costs for testing and treatment.¹⁰ The World Health Organization’s Global Hearts Initiative is one of the largest platforms to integrate such cardiovascular services into routine primary care.¹¹ Hypertension has been the primary focus for most Global Hearts Initiative programs to date, with some beginning to incorporate diabetes care.^12,13 This stepwise approach is not ideal given the multifactorial nature of CVD, but blood pressure is cheaper to measure and diabetes is often prioritized over elevated cholesterol. However, the readiness of health systems for taking on new conditions for care remains limited. Scarcity abounds in terms of health workers, laboratory supplies to accurately measure serum cholesterol and its subfractions, and reliable accessibility of quality lipid-lowering medications. Simpler strategies such as polypills or even long-acting lipid-lowering medications taken twice annually offer the promise of new ways of easing strained systems and patients. Systems will need considerably more strengthening, including through collective action to lower costs of consumable testing supplies and medications to turn promises like this into reality. Pooled procurement mechanisms such as those conducted by the Pan American Health Organization’s HEARTS in the Americas initiative¹⁴ show how this can be done in what is now a new era of global health. As organizations such as the Gates Foundation have substantially increased spending¹⁵ in the wake of major declines in development assistance for health, data like these shine a light on urgent opportunities for action to reduce the burden of the leading cause of death around the world.