LDL and non-HDL cholesterol with the lowest mortality in the general population in 1991-2018

Over the past few decades, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol levels in the general population have lowered. However, it is unclear whether these trends affected the U-shaped association of LDL and non-HDL cholesterol levels with risk of all-cause mortality.

Individuals without lipid-lowering therapy were selected from the Copenhagen City Heart Study in 1991-1994 (n = 9486) and from the Copenhagen General Population Study in 2003-2009 (n = 56,796) and in 2010-2018 (n = 48,105) and mortality was recorded until December 31, 2022. We analyzed the LDL and non-HDL cholesterol values with the lowest risk of mortality in each cohort.

The lowest risk of mortality was observed in individuals with LDL cholesterol levels of 4.0 (95% confidence interval, 3.8-4.3) mmol/L [155 (147-166) mg/dL] in the 1991-1994 cohort, which declined to 3.5 (3.4-3.7) mmol/L [135 (131-143) mg/dL] in the 2010-2018 cohort. The corresponding levels of non-HDL cholesterol were 4.8 (4.6-5.0) mmol/L [186 (178-193) mg/dL] and 4.2 (4.1-4.4) mmol/L [162 (159-170) mg/dL]. The median LDL cholesterol levels declined from 3.7 (interquartile range: 3.0-4.5) mmol/L [142 (115-173) mg/dL] to 3.2 (2.6-3.8) mmol/L [124 (101-148) mg/dL] while the corresponding non-HDL cholesterol levels declined from 4.5 (3.7-5.4) mmol/L [174 (143-209) mg/dL] to 3.9 (3.2-4.6) mmol/L [150 (123-178) mg/dL]. Parallel to these changes the absolute risk of all-cause mortality declined overtime.

The levels of LDL and non-HDL cholesterol with the lowest risk of all-cause mortality declined by 0.5 mmol/L (19 mg/dL) and 0.6 mmol/L (23 mg/dL) from 1991 through 2018 in the general population, while the absolute risk of all-cause mortality also declined over time.