Abstract
Background
PCSK9 is a key regulator of serum LDL-cholesterol levels. The relation of PCSK9 with other components of cardiovascular and coronary artery disease (CAD) risk is still debated.
Purpose
To evaluate the association of PCSK9 plasma levels with cardiovascular and coronary risk profile, in patients with symptoms of suspected stable CAD enrolled in the EVINCI study.
Methods
PCSK9 was measured in 522 patients (60.4±8.8 years, 318 males) with symptoms of stable CAD Individual risk was characterized by clinical and bio-humoral variables, including lipid/glucose/inflammatory profiles. Obstructive CAD was firstly ruled-in by multimodality non-invasive imaging and, subsequently, assessed by invasive coronary angiography.
Results
Patients were divided into groups according to PCSK9 quartiles: I (<138 ng/mL), II-III (138–264 ng/mL), and IV (>264 ng/mL) (Table). The prevalence of obstructive CAD at invasive angiography and statin treatment did not differ among groups. Compared with patients in quartile IV, patients in quartile I, had a higher prevalence of metabolic syndrome and higher values of body mass index. Among biomarkers, all cholesterol lipoproteins levels progressively increased from quartile I to IV, while insulin and HOMA index values decreased (Table). At multivariable analyses adjusted for medical treatment, the only clinical or bio-humoral variables independently associated with PCSK9 levels were presence of the metabolic syndrome (Coeff. −0.195, SE 0.05, p<0.0001) and HDL cholesterol levels (Coeff. 0.444, SE 0.06, p<0.0001), respectively.
Table 1 Clinical Variables Quartile I Quartile II–III Quartile IV Biomarkers Quartile I Quartile II–III Quartile IV <138 ng/L 138–264 ng/L >264 ng/L <138 ng/L 138–264 ng/L >264 ng/L (n=130) (n=261) (n=131) (n=130) (n=261) (n=131) Age, years 61±9 60±9 61±8 Glucose, mg/dL 110±30 117±41 109±29 Male gender 86 (66) 161 (62) 71 (55) Insulin, mUI/mL 13.3±12.5* 11.3±10.1 10.3±10.1 Family history 38 (29)# 86 (33) 58 (44) HOMA index 3.9±4.5* 3.5±4.1 2.9±3.3 Hypertension 78 (60) 164 (63) 88 (67) Tryglicerides, mg/dL 128±86 128±87 118±68 Hypercholesterolemia 72 (55) 158 (61) 81 (62) Total cholesterol, mg/dL 171±43* 181±45 203±55 Diabetes mellitus 43 (33) 91 (35) 37 (28) LDL, mg/dL 99±36* 104±38 119±45 Metabolic Syndrome 45 (35)# 72 (28) 19 (15) HDL, mg/dL 46±13* 52±15 61±19 BMI, kg/m2 28.02±4.00* 28.03±4.25 26.95±4.56 Total/HDL cholesterol 3.8±1.2* 3.7±1.2 3.5±1.1 Significant CAD at ICA 18 (14) 46 (18) 24 (18) hs-CRP, mg/dL 0.41±0.61 0.39±1.38 0.41±0.83 Statins treatment 68 (52) 143 (55) 58 (44) Interleukin 6, ng/L 1.60±2.75 1.30±2.49 1.30±1.68 Chi square test: #p<0.05. ANOVA: I vs. IV Quartile: *p<0.05.
Conclusion
In patients with stable CAD, low plasma levels of PCSK9 are associated with the prevalence of metabolic syndrome and its individual components, including, in particular, HDL cholesterol.
Acknowledgement/Funding
AMGEN grant, EU FP7-CP-FP506 2007 project (grant agreement no. 222915)
Association of Cholesteryl Ester Transfer Protein-TaqIB Polymorphyisms with HDL Cholesterol Levels and the Risk of Coronary Artery Disease