Abstract

We evaluated low-density lipoprotein (LDL) cholesterol patterns at the population level and quantified associated cardiovascular disease (CVD) morbidity and mortality for the Global Burden of Disease (GBD) 2020 study. Using all available high-quality data, we estimated the CVD burden attributable to elevated LDL (relative to the theoretical minimum risk exposure level of 1.3-1.7 mmol/L) by age, sex, country, and year among adults >25 years from 1990 - 2020. We used a spatiotemporal Gaussian process regression to estimate LDL mean and microdata to estimate standard deviation (SD) and characterize the global LDL distribution. In a meta-regression, we pooled data from 52 randomized control trials to estimate the relative risks for ischemic heart disease (IHD) and ischemic stroke. These were then used to calculate the population attributable fraction and the burden attributable to elevated LDL. We report SD and 95% uncertainty intervals (UI) in brackets. From 1990 to 2020, LDL levels measured in mmol/L increased globally from 1.4 [0.4] to 1.7 [0.4] in males, and from 1.5 [0.4] to 1.8 [0.5] in females. The highest LDL levels over the 30-year period were observed in high-income countries and Central and Eastern Europe and Central Asia. Sub-Saharan Africa had the lowest LDL levels. In 2020, a third (2.9 million [95% UI: 1.2-4.5 million]) and a fifth (1.5 million [919,750-2.1 million]) of deaths due to IHD and ischemic stroke, respectively, were attributable to elevated LDL. The estimated number of deaths and disability-adjusted life-years (DALYs) attributable to high LDL increased since 1990 reaching 4.5 million [2.6 - 6.2] deaths and 91.8 million [53.6 - 127] DALYs in 2020. More DALYs from elevated LDL were experienced by men than women (52.8 [29.7 - 73.4] vs 39 [23.9 - 53.5] million). Over the study period, the global all-age rates for deaths and DALYs per 100,000, remained unchanged at 58 [34-80] and 1,177 [688-1,629], respectively. Age-standardized deaths and DALYs due to high LDL levels decreased from 90 [55-123] to 57 [34-79] deaths per 100,000 and from 1,657 [981-2,251] to 1,610 [650-1,532] DALYs per 100,000. Age-standardized DALYs attributable to high LDL cholesterol were highest in Eastern Europe, Central Asia and North Africa and the Middle East. The lowest levels were observed in high-income Asia Pacific and Andean Latin America. The CVD burden attributable to LDL is increasing globally. In 2020, a fifth of CVD deaths and DALYs were associated with LDL. Differences between the trends of all-ages and age-standardized rates suggest that the LDL burden has been driven partially by population growth and aging. Measurement and estimation error must be considered when interpreting these trends. In addition to safe and cost-effective pharmacological and behavioral interventions, novel population level strategies are needed to reduce the LDL burden.

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