Proprotein Convertase Subtilisin Kexin 9 (PCSK9) and nonHDL particles rise during normal pregnancy and differ by BMI.

Background: Serum lipids, including total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c), increase during pregnancy. Serum Proprotein Convertase Subtilisin Kexin 9 (PCSK9) is a vital regulator in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of liver cells inhibiting clearance of LDL-c.
Objective: To determine the influence of weeks of pregnancy and obesity on circulating levels of essential lipid lipoproteins and PCSK9 in women with normal, uncomplicated pregnancies and deliveries.
Methods: We performed a comprehensive lipid and lipoprotein profile during each trimester of pregnancy in 70 mostly Caucasian women with uncomplicated normal pregnancies and deliveries. Based on their first trimester BMI, we placed them into one of three categories: (<25 kg/m ² n=23, 25-30 kg/m ² n=25, or >30 n=22) kg/m ² . Cholesterol, triglycerides, LDL cholesterol (LDL-c), non-HDL particles, and lipoprotein(a) were measured by spectrophotometry, ion mobility, and immunoturbidimetric assays. Elisa assay determined PCSK9 (active and total). Homeostatic Model Assessment (HOMA-IR) assessed insulin resistance in the second and third trimesters of pregnancy.
Results: Total and active PCSK9, LDL-c, and nonHDL particle concentrations were higher than reported for non-pregnant normal values, increased after the first trimester of pregnancy, and were highest from mid-gestation to the last trimester of pregnancy in the overweight and the obese.
Conclusion: PCSK9 levels rise as normal pregnancy progresses. Levels are higher in persons who are obese, even after adjustment for insulin resistance. Defining normal PCSK9 levels during pregnancy must adjust for gestational age and BMI.
Competing Interests: Declaration of Competing Interest We confirm no known conflicts of interest associated with this publication, and there has been no financial support for this work that could have influenced the outcome. Dr Wren is Medical Director at Quest and Dr Lopez has a registered patent for the PCSK9 assay. Analysis and reporting was blind to the clinical data. We also confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that all have approved the order of our authors.
(Copyright © 2022. Published by Elsevier Inc.)