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Proprotein Convertase Subtilisin Kexin 9 (PCSK9) and nonHDL particles rise during normal pregnancy and differ by BMI
1University of Oklahoma Health Sciences Center, Department of Obstetrics and Gynecology, Oklahoma City, OK, USA (Wild, Weedin, Cox, Myers and Hansen); Department of Biostatistics and Epidemiology, Oklahoma City, OK, USA (Wild and Zhao).
Insights
Serum Proprotein Convertase Subtilisin Kexin 9 (PCSK9) levels increase during pregnancy, particularly in overweight and obese individuals. Normal PCSK9 levels during gestation must account for gestational age and body mass index (BMI).
Area of Science:
- Reproductive biology
- Metabolic disorders
- Cardiovascular health
Background:
- Serum lipids like cholesterol and triglycerides naturally rise during pregnancy.
- Proprotein Convertase Subtilisin Kexin 9 (PCSK9) is crucial in lipoprotein metabolism, regulating LDL receptor levels and influencing LDL cholesterol clearance.
- Elevated PCSK9 can inhibit the liver's ability to remove LDL cholesterol from circulation.
Purpose of the Study:
- To investigate how gestational weeks and obesity affect lipid profiles and PCSK9 levels in pregnant women.
- To compare these levels in women with normal, uncomplicated pregnancies and deliveries.
Main Methods:
- A cohort of 70 women with uncomplicated pregnancies underwent comprehensive lipid and lipoprotein profiling across trimesters.
- Participants were categorized by pre-pregnancy BMI into normal weight, overweight, and obese groups.
- Measurements included cholesterol, triglycerides, LDL cholesterol, non-HDL particles, lipoprotein(a), and both active and total PCSK9 via Elisa assay. Insulin resistance was assessed using HOMA-IR.
Main Results:
- Concentrations of total and active PCSK9, LDL cholesterol, and non-HDL particles were elevated compared to non-pregnant norms.
- These levels increased significantly after the first trimester, peaking in mid-to-late gestation.
- Overweight and obese participants exhibited higher PCSK9 levels, even after adjusting for insulin resistance.
Conclusions:
- Circulating PCSK9 levels naturally increase as pregnancy progresses.
- Obesity is associated with higher PCSK9 levels during pregnancy, independent of insulin resistance.
- Establishing normal PCSK9 reference ranges in pregnancy requires consideration of both gestational age and maternal 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/m2 n=23, 25-30 kg/m2 n=25, or >30 n=22) kg/m2. 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.
