Ortiz, A.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

The extent to which eGFR varies across populations, in the absence of risk factors and comorbidities associated with kidney disease, remains uncertain. We aimed to develop eGFR reference values in healthy American adults and to compare them with previously described European eGFR reference values. This cross-sectional study compared newly described age-specific and sex-specific creatinine-based eGFR reference values from over 9000 healthy Americans from National Health and Nutrition Examination Survey with previously described eGFR reference values from over 1.5 million healthy individuals in the European CKD Burden Consortium. Health status was based on 14 criteria related to comorbidities, lifestyle factors, and medication use. eGFR was calculated using the European Kidney Function Consortium equation and modeled over the age span and by sex using a generalized additive model. The median eGFR in both 20-year-old American and European men was 98 ml/min per 1.73 m 2 . In both 20-year-old American and European women, the median eGFR was 101 ml/min per 1.73 m 2 . eGFR started to decrease at age 40 years, a result of the structure of the European Kidney Function Consortium equation. By age 79 years, the median eGFR in American and European men was 68 and 67 ml/min per 1.73 m 2 , respectively. The median eGFR in 79-year-old American and European women was 63 and 64 ml/min per 1.73 m 2 , respectively. When removing the effect of comorbidities, lifestyle factors and medication use associated with kidney function, achieved by restricting the analyses to individuals who did not have a presence or history of certain criteria, the distribution of eGFR was similar between healthy Americans and Europeans. This supports the notion that eGFR reference values may be generalizable to populations they were not derived from.