Abstract
Objective
The clinical significance of the measurement of serum PCSK9 (proprotein subtilisin
kexin type 9) is not well defined. This study investigated the association between
serum PCSK9 levels and atherosclerosis assessed by carotid intima media thickness
(IMT) in hypertensive patients.
Methods
A total of 126 hypertensive patients over the age of 45 were enrolled. The maximum
carotid IMT (max-IMT) and the mean carotid IMT (mean-IMT) were measured at the time
of enrollment. Clinical and laboratory parameters including serum PCSK9 were analyzed.
Results
Patients were divided into tertiles based on serum PCSK9 levels. After adjusting for
age, sex, total cholesterol, HDL-cholesterol and triglyceride, max-IMT was significantly
increased in the highest tertile of serum PCSK9 (0.969±0.033 vs 0.959±0.033 vs 1.077±0.033 mm, respectively; P=0.026). Mean-IMT showed a tendency to increase across the tertile groups (0.773±0.025 vs 0.790±0.026 vs 0.856±0.025 mm, respectively; P=0.059). Multivariate regression analysis revealed that serum PCSK9 was independently
associated with carotid IMT (max-IMT: β=0.212, P=0.016; mean-IMT: β=0.184, P=0.04).
Conclusion
The present study is the first to report the association between serum PCSK9 levels
and carotid IMT in hypertensive patients. These results suggest that serum PCSK9 may
have a certain role in early pathogenesis of atherosclerosis.
Abbreviations:
ANCOVA (analysis of covariance), ANOVA (analysis of variance), SD (standard deviation), BMI (body mass index), SBP (systolic blood pressure), DBP (diastolic blood pressure), DM (diabetes mellitus), IMT (intima media thickness), LDLR (low-density lipoprotein receptor), PCSK9 (proprotein convertase subtilisin/kexin type 9)Keywords
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References
- Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation.J Biol Chem. 2007; 282: 18602-18612
- Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice.J Clin Invest. 2006; 116: 2995-3005
- Plasma PCSK9 preferentially reduces liver LDL receptors in mice.J Lipid Res. 2008; 49: 1303-1311
- Secreted proprotein convertase subtilisin/kexin type 9 reduces both hepatic and extrahepatic low-density lipoprotein receptors in vivo.Biochem Biophys Res Commun. 2008; 370: 634-640
- Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking outside the box.Metabolism. 2012; 61: 3-11
- Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.Nat Genet. 2003; 34: 154-156
- Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.Nat Genet. 2005; 37: 161-165
- Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.N Engl J Med. 2006; 354: 1264-1272
- Genetic and metabolic determinants of plasma PCSK9 levels.J Clin Endocrinol Metab. 2009; 94: 2537-2543
- Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment.Clin Chem. 2008; 54: 1038-1045
- Serum PCSK9 is associated with multiple metabolic factors in a large Han Chinese population.Atherosclerosis. 2010; 213: 632-636
- PCSK9: a convertase that coordinates LDL catabolism.J Lipid Res. 2009; 50: S172-S177
- Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles.Atherosclerosis. 2010; 208: 177-182
- Measurement of arterial wall thickness as a surrogate marker for atherosclerosis.Circulation. 2004; 109: III33-III38
- Prediction of clinical cardiovascular events with carotid intima–media thickness: a systematic review and meta-analysis.Circulation. 2007; 115: 459-467
- High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol.J Lipid Res. 2010; 51: 2714-2721
- Insulin resistance as an independent risk factor for carotid wall thickening.Hypertension. 1996; 28: 593-598
- Factors underlying the increase in carotid intima–media thickness in borderline hypertensives.Arterioscler Thromb Vasc Biol. 1999; 19: 1231-1237
- Metabolic syndrome and preclinical atherosclerosis: focus on femoral arteries.Metabolism. 2007; 56: 541-546
- Plasma lipoprotein(a) is an independent factor associated with carotid wall thickening in severely but not moderately hypercholesterolemic patients.Stroke. 1996; 27: 1044-1049
- Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue.Arterioscler Thromb Vasc Biol. 2011; 31: 785-791
- Impact of low-density lipoprotein particle size on carotid intima–media thickness in patients with type 2 diabetes mellitus.Metabolism. 2007; 56: 608-613
- Carotid intima–media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (Atherosclerosis Risk In Communities) study.J Am Coll Cardiol. 2010; 55: 1600-1607
Article info
Publication history
Published online: February 04, 2013
Accepted:
January 7,
2013
Received:
July 16,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.