Both High and Low LDL-C Levels Associated With Increased All-Cause Mortality Risk

In a massive prospective cohort study, investigators reported that both high and low levels of low density lipoprotein cholesterol (LDL-C) were associated with an increased risk of all-cause mortality among the general population.

Investigators at the University of Copenhagen and Copenhagen University Hospital in Denmark wrote in the article published in the British Medical Journal that they initiated the study because, since

lowering levels of LDL-C reduces cardiovascular disease outcomes,
“the general perception is that high levels of LDL-C are associated with an increased risk of mortality, but low levels are not.”

“Studies on the association between LDL-C levels and the risk of all- cause mortality, however, have provided conflicting results, with some studies showing a counterintuitive inverse association (lower mortality with increasing levels of LDL-C) and some showing no association,” they added.

For the study, the investigators randomly selected people from the national Danish Civil Registration System from 2003-2015, encompassing more than 108,000 individuals with a median follow-up of 9.4 years.

All participants completed a self-administered questionnaire, including questions on lifestyle factors and medical treatment, underwent a physical examination, and gave blood samples for biochemical measurements.

More than 11,000 (10.5%) patients died during follow-up, with a median age of 81 years old at the time of deaths.

The multivariable adjusted hazard ratio for all-cause mortality was 1.25 for individuals with LDL-C concentrations of less than 1.8 mmol/L (<70 mg/dL; 1st-5th centiles) and 1.15 (1.05 to 1.27) for LDL-C concentrations of more than 4.8 mmol/L (>189 mg/dL; 96th-100th centiles).

The 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,” the investigators wrote.

Reference

1. Ditlev Lindhardt Johannesen C, Langsted A, Bødtker Mortensen M, et al. Association between low density lipoprotein and all cause and cause specific mortality in Denmark: prospective cohort study. The British Medical Journal. December 8, 2020. https://doi.org/10.1136/bmj.m4266