Key result
Global LDL-C-related ischemic stroke deaths rose ~43% since 1990 despite falling age-standardized mortality.
Why the study?
Despite advances in lipid-lowering therapies, substantial inequalities in the burden of LDL-C-associated ischemic stroke persist across geographical areas and socioeconomic strata.
Observational
Yes
Although global age-standardized mortality and DALY rates for LDL-C-related ischemic stroke declined between 1990 and 2021, absolute case counts rose by over 43% due to population aging and growth, accompanied by a socioeconomic shift transferring disproportionate disease burden to lower-income regions.
Answers are grounded in this paper and cite their sources.
Rising absolute deaths despite rate declines signal need for population-level prevention in aging and low-SDI regions; leaves open drivers of cohort and regional disparities.
BACKGROUND: Ischemic stroke persists as a primary driver of global disease burden and death, wherein heightened levels of low-density lipoprotein cholesterol (LDL-C) constitute a critical, alterable risk determinant. Despite advances in lipid-lowering therapies, substantial inequalities in the burden of LDL-C-associated ischemic stroke (HLIS) continue to exist across different geographical areas and socioeconomic strata. METHODS: Drawing upon data from the 2021 Global Burden of Disease Study, we comprehensively assessed the burden of HLIS spanning 1990 through 2021. This evaluation encompassed 204 distinct countries and territories, stratified by biological sex and divided into 25 specific age cohorts. Key metrics analyzed included the age-standardized mortality rate (ASMR) alongside the disability-adjusted life year (DALY) rate. Furthermore, to elucidate the underlying drivers of observed temporal trends, we performed decomposition analyses, age-period-cohort modeling, and assessments of health inequity. RESULTS: From 1990 to 2021, global HLIS-related deaths increased by 43.03% (654,503 to 936,192), while age-standardized rates declined annually (ASMR: -2.06%; DALYs: -1.72%). The steepest declines occurred in high-SDI regions (e.g., Western Europe [ASMR: -4.65%/year]). In contrast, low-SDI regions, particularly Southern Sub-Saharan Africa, experienced rising burdens (ASMR: +1.03%/year). A socioeconomic reversal was observed, with burden shifting toward lower-income populations (Concentration Index changed from 0.08 to -0.09). Population aging and growth drove the absolute rise in cases, especially in low-resource settings. Sex disparities were notable, with higher mortality in elderly women and greater DALYs in middle-aged men. Birth cohort analysis suggested slowing improvements among younger generations. CONCLUSIONS: Although age-standardized HLIS burden has declined globally, persistent inequalities across regions, sexes, and socioeconomic groups reflect ongoing disparities in healthcare access and lipid management. Targeted interventions addressing demographic shifts and strengthening primary prevention in resource-limited settings are urgently needed to reduce future disease burden.
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Yu et al. (2026) conducted an observational in High LDL-C-related ischemic stroke (HLIS). Elevated low-density lipoprotein cholesterol (LDL-C >=2.6-3.0 mmol/L; above TMREL of 0.7-1.3 mmol/L) vs. Theoretical minimum risk exposure level (TMREL) of LDL-C (0.7-1.3 mmol/L) and comparisons across Socio-demographic Index (SDI) quintiles, sexes, and 1990 vs. 2021 periods was evaluated on Age-standardized mortality rate (ASMR) and estimated annual percentage change (EAPC) of high LDL-C-related ischemic stroke from 1990 to 2021 (EAPC -2.06%, 95% CI -2.16 to -1.96, p=<0.05). High LDL-C-related ischemic stroke deaths rose 43.03% (654,503 to 936,192) from 1990 to 2021, while age-standardized mortality declined annually by 2.06%.
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