Association Between Low-density Lipoprotein Cholesterol and Cardiovascular Mortality in Statin Non-users: a Prospective Cohort Study in 14.9 Million Korean Adults

Background: Limited information is available on detailed sex/age-specific associations between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) mortality and 'the optimal range' associated with the lowest CVD mortality in the general population.

Methods: Korean adults (N = 14 884 975) who received routine health screenings during 2009-2010 were followed until 2018 for CVD mortality.

Results: During 8.8 years (mean) of follow-up, 94 344 individuals died from CVD. LDL-C had U-curve associations with mortality from CVD and its subtypes, except haemorrhagic stroke. Optimal range was 90-149 mg/dL for CVD; 70-114 for ischaemic heart disease; 85-129 for ischaemic stroke; ≥85 for subarachnoid haemorrhage; ≥130 for intracerebral haemorrhage; 115-159 for hypertension and heart failure; and 100-144 for sudden cardiac death. Assuming linear associations between 100 and 300 mg/dL, LDL-C was positively associated with CVD mortality [hazard ratio (HR) per 39-mg/dL (1-mmol/L) higher LDL-C = 1.10], largely due to ischaemic heart disease (HR = 1.26), followed by sudden cardiac death (HR = 1.13), ischaemic stroke (HR = 1.11) and heart failure (HR = 1.05). Intracerebral haemorrhage (HR = 0.90), but not subarachnoid haemorrhage, had inverse associations. Women and older adults had weaker positive associations than men and younger adults (Pinteraction < 0.001 for both sex and age). Individuals aged 75-84 years had modest positive associations with CVD mortality, especially ischaemic heart disease and ischaemic stroke.

Conclusion: LDL-C had U-curve associations for CVD mortality. The associations and optimal ranges differed across CVD subtypes. Women and older adults had weaker positive associations than men and younger adults. Positive associations with ischaemic heart disease and ischaemic stroke were maintained in adults aged 75-84 years.