High And Low LDL Increase Death Risk In General Population:
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This study aimed 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.

In this prospective cohort study, the Copenhagen General Population Study recruited in 2003-15 with a median follow-up of 9.4 years.

Baseline levels of LDL-C associated with risk of mortality were evaluated on a continuous scale (restricted cubic splines) and by a priori defined centile categories with Cox proportional hazards regression models. Main outcome was all cause mortality. Secondary outcomes were cause specific mortality (cardiovascular, cancer, and other mortality).

Results:
-- Among 108?243 individuals aged 20-100, 11?376 (10.5%) died during the study, at a median age of 81. The 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.

-- Compared with individuals with concentrations of LDL-C of 3.4-3.9 mmol/L, 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 and 1.15 for LDL-C concentrations of more than 4.8 mmol/L.

-- 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.

Conclusively, in 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).

Source: https://www.bmj.com/content/371/bmj.m4266#
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