Nutr Metab Cardiovasc Dis. 2026 Feb 10:104622. doi: 10.1016/j.numecd.2026.104622. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: High low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular diseases (CVDs), contributing substantially to global disease burden. We aimed to quantify the global burden of LDL-C-related CVDs and establish causal relationships through integrated Global Burden of Disease(GBD) and Mendelian randomization(MR) analyses.
METHODS AND RESULTS: We analyzed the impact of high LDL-C on CVDs burden using GBD 2021. Estimated Annual Percentage Change(EAPC) was used to delineate trends, while frontier analysis compared national performances against the minimum risk level adjusted for sociodemographic factors. BAPC modeling projected trends to 2036. MR examined the causal relationship between LDL-C (and its subtypes) and CVDs (ischemic heart disease(IHD) and ischemic stroke).The absolute increase in DALYs (45.7% increase from 1990 to 2021) contrasts sharply with the decline in ASDR (-33.2%), with a global EAPC of -1.47. This downward trend is consistent with that of the age-standardized mortality rate (ASMR) and is particularly pronounced among older individuals.In 2021, Nauru had the highest ASMR, while Israel showed the most significant reduction.Frontier analysis highlighted improvements in Somalia, Ethiopia, Rwanda, Burkina Faso, and Niger, but Lithuania, the US, Germany, Finland, and Monaco need more progress. Projections indicate ASMR will decrease by 2036 without targeted measures. MR analysis revealed a causal link between LDL-C and IHD, but not ischemic stroke.
CONCLUSION: High LDL-C is a modifiable risk factor for CVDs (IHD). Despite declining ASDR and ASMR globally from 1990 to 2021, the absolute burden is rising. MR and GBD findings call for immediate targeted LDL-C interventions to reduce the burden on vulnerable populations.
PMID:41862301 | DOI:10.1016/j.numecd.2026.104622