Physicians' Academy for Cardiovascular Education

U-shaped association between LDL-c levels and all cause mortality in the general population

Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study

Literature - Johannesen CDL, Langsted A, Mortensen MB et al., - BMJ. 2020 Dec 8;371:m4266. doi: 10.1136/bmj.m4266.

Introduction and methods

It has been clearly demonstrated that treatment with lipid lowering agents reduces the risk of atherosclerotic CV events [1-4]. This insight has led to a general perception that high levels of LDL-c are associated with a high risk of all cause mortality, while low levels are not. However, studies have shown conflicting results on the association between LDL-c and all cause mortality [5-11]. Most of these studies were conducted in historical population-based cohorts and in individuals aged over 65 years. This study determined the association between LDL-c levels and the risk of all cause mortality and cause specific mortality in a contemporary general population cohort.

The study included 108,243 individuals from the Copenhagen General Population study. Invited individuals were randomly selected from the national Danish Civil Registration System, reflecting the Danish general population. Participants were aged 20-100 years at baseline. All participants completed a questionnaire, underwent a physical examination, and gave (non-fasting) blood samples. Main outcome was all cause mortality. Secondary outcomes were cause specific mortality (CV, cancer, and other mortality). Median follow-up was 9.4 years. 11,376 people died during follow-up.

Main results


This study showed a U-shaped association between levels of LDL-c and risk of all cause mortality in the general Danish population; low and high levels of LDL-c were associated with increased risk of all cause mortality. A LDL-c level of 3.6 mmol/L (140 mg/dL) was associated with the lowest mortality risk. A U-shaped association was also observed for cancer mortality and other mortality. A positive association was found between LDL-c levels and MI risk; any increase of LDL-c was associated with increased risk of MI.


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