1. There is a U-shaped association of LDL-C levels and risk of all-cause mortality with the lowest risk at LDL-C levels of 3.6 and 2.3 mmol/L in patients not on or on lipid lowering therapy, respectively.
2. There is a similar U-shaped association of LDL-C levels and risk of mortality due to cancer causes and other causes but not cardiovascular causes.
Evidence Rating Level: 2 (Good)
Low density lipoprotein cholesterol (LDL-C) is a well-known causal risk factor for cardiovascular disease and cardiovascular events. However, LDL-C’s association with all mortality is not as clear, with studies showing no association and, at times, inverse association. In this prospective cohort study, 108 243 participants from the Copenhagen General Population Study from the national Danish Civil Registration System were followed for a median of 9.4 years and data for all-cause mortality, cause specific mortality and LDL-C levels were extracted. The risk of all-cause mortality was U-shaped and compared to patients with LDL-C of 3.4-3.9 mmol/L. Multivariable analysis showed increased risk of mortality for individuals with LDL-C less than 1.25 mmol/L (aHR 1.25, 95%CI 1.15-1.36) and greater than 4.8 mmol/L (aHR 1.15, 95%CI 1.05-1.27). The LDL-C level associated with the lowest risk of all-cause mortality was 3.6 mmol/L in patients not receiving lipid lowering therapy and 2.3 mmol/L in patients receiving lipid lowering therapy. This association also existed for cancer mortality and other mortality but not for cardiovascular mortality where no association was found (though risk of fatal MI increased with increased LDL-C). These results can help healthcare professionals better define healthy LDL-C levels and guide guidelines on targets for the general population. Limitations of this study include a homogenous population in a single country, certain confounders could not be adjusted for, such as patients who discontinue or begin lipid-lowering therapy during follow-up or the impact of non-pharmacological interventions such as weight loss, and it is observational by design and cannot be used to infer causality.
©2020 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.