Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study.
Level 3 - non-randomized controlled study
Prospective observational cohort study
PubMed 33293274 · doi:10.1136/bmj.m4266
What was done
A prospective cohort study evaluated 108,243 individuals aged 20–100 years randomly sampled from the Danish Civil Registration System into the Copenhagen General Population Study (recruited 2003–2015). Participants were followed for a median of 9.4 years. The association between baseline low-density lipoprotein cholesterol (LDL-C) and mortality was assessed using Cox proportional hazards regression models with restricted cubic splines and predefined centile categories. The primary outcome was all-cause mortality; secondary outcomes included cause-specific mortality (cardiovascular, cancer, and other) and myocardial infarction.
What was found
During follow-up, 11,376 participants (10.5%) died at a median age of 81 years. The association between LDL-C and all-cause mortality was U-shaped. Compared with individuals with LDL-C concentrations of 3.4–3.9 mmol/L (132–154 mg/dL; 61st–80th centiles), multivariable-adjusted hazard ratios for all-cause mortality were 1.25 (95% CI 1.15 to 1.36) for LDL-C < 1.8 mmol/L (< 70 mg/dL; 1st–5th centiles) and 1.15 (95% CI 1.05 to 1.27) for LDL-C > 4.8 mmol/L (> 189 mg/dL; 96th–100th centiles). The LDL-C concentration associated with lowest all-cause mortality was 3.6 mmol/L (140 mg/dL) overall and in untreated individuals, versus 2.3 mmol/L (89 mg/dL) in individuals receiving lipid-lowering treatment. Similar patterns were seen across sexes, age groups, and for cancer and other mortality, but not for cardiovascular mortality. Any increase in LDL-C was associated with increased risk of myocardial infarction.
Why it matters
In a general population cohort, both low and high LDL-C concentrations are associated with increased all-cause mortality, even while risk of myocardial infarction increases linearly with higher LDL-C.
Limits
The observational design cannot establish causality and remains susceptible to reverse causation (e.g., severe illness lowering cholesterol). The study evaluated a single Danish population, limiting generalizability to other demographic or ethnic groups. Only baseline LDL-C measurements were evaluated.
Cited by
- supports Elevated LDL cholesterol levels are associated with a 10% to 30% increased risk of mortality.