Copenhagen General Population Study - LDL-C and all-cause mortality risk

Copenhagen General Population Study

A prospective cohort study was undertaken to determine the association between levels of low density lipoprotein cholesterol (LDL-C) and all cause mortality, and the concentration of LDL-C associated with the lowest risk of all cause mortality in the general population (1)

The study setting:

• Denmark; the Copenhagen General Population Study recruited in 2003-15 with a median follow-up of 9.4 years

Study Results:

• among 108243 individuals aged 20-100, 11376 (10.5%) died during the study, at a median age of 81
  • association between levels of LDL-C and the risk of all cause mortality was U shaped, with low and high levels associated with an increased risk of all cause mortality
    • concentration of LDL-C associated with the lowest risk of all cause mortality was 3.6 mmol/L (140 mg/dL) in the overall population and in individuals not receiving lipid lowering treatment, compared with 2.3 mmol/L (89 mg/dL) in individuals receiving lipid lowering treatment
    • similar results were seen in men and women, across age groups, and for cancer and other mortality, but not for cardiovascular mortality. Any increase in LDL-C levels was associated with an increased risk of myocardial infarction

Study conclusions:

• the general population, low and high levels of LDL-C were associated with an increased risk of all cause mortality, and the lowest risk of all cause mortality was found at an LDL-C concentration of 3.6 mmol/L (140 mg/dL)

Discussion:

Possible explanation of findings:

• association between low levels of LDL-C and an increased risk of all cause mortality could be explained by reverse causation (1)

Lipid lowering therapy and all-cause mortality (1):

• in individuals receiving lipid lowering treatment, the association between low levels of LDL-C and an increased risk of all cause, cancer, and other mortality was weaker than for individuals not receiving lipid lowering treatment
  • it is incorrect to use this study data as an argument against the use of lipid lowering treatment in the prevention of atherosclerotic cardiovascular disease and mortality
    • association between low levels of LDL-C and cancer mortality together with the association between very low levels of LDL-C and an increased risk of cancer (fatal and non-fatal) supports the hypothesis of a decrease in LDL-C levels because of debilitation and illness

Reference:

• Johannesen CDL et al. Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study. BMJ 2020;371:m4266http://dx.doi.org/10.1136/bmj.m4266