title: Insulin resistance, inflammation, and blood pressure determine vascular dysfunction in CKD.
abstract: BACKGROUND
  Conventional cardiovascular risk equations underestimate the risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD), implying a role for novel risk factors. Our aim was to compare vascular function and arterial compliance, known markers of CVD, between patients with CKD and healthy controls and examine their association with traditional and novel CVD risk factors.
  
  
  METHODS
  Vascular function was determined by using high-resolution ultrasonography to measure brachial artery endothelial-dependent flow-mediated dilatation (FMD) and endothelial-independent glyceryl trinitrate (GTN)-mediated dilatation. Arterial compliance was measured by using pulse contour analysis to generate large-artery (C1) and small-artery (C2) compliance. We also examined the relationship between vascular function, arterial compliance and blood pressure, lipid and lipoprotein levels, insulin resistance, inflammation, oxidative stress, and calcium and phosphate levels in 105 patients with CKD and 40 healthy controls.
  
  
  RESULTS
  Vascular function and arterial compliance were significantly impaired in patients with CKD compared with healthy controls: mean FMD, 3.8% +/- 0.3% (SE) versus 5.7% +/- 0.6%; GTN-mediated dilatation, 15.7% +/- 0.9% versus 19.6% +/- 1.0%; C1, geometric mean, 12.1 mL/mm Hg; 95% confidence interval (CI), 11.2 to 13.1 versus 15.1 mL/mm Hg; 95% CI, 13.7 to 16.5; and C2, 3.8 mL/mm Hg; 95% CI, 3.4 to 4.3 versus 5.0 mL/mm Hg; 95% CI, 4.2 to 6.0; all P < 0.05. Patients with CKD had greater waist-hip ratios, systolic blood pressures (SBPs), pulse pressures, triglyceride levels, oxidized low-density lipoprotein levels, high-sensitivity interleukin 6 levels, and Homeostasis Model Assessment (HOMA) scores (all P < 0.05) and lower high-density lipoprotein levels (P < 0.001). In patients with CKD, HOMA score and SBP were associated negatively with FMD (model R(2) = 0.28; P < 0.001), and SBP and waist-hip ratio were associated negatively with GTN-mediated dilatation (model R(2) = 0.25; P < 0.001). Pulse pressure was associated negatively with C1 (R(2) = 0.37; P < 0.001), and pulse pressure and high-sensitivity interleukin 6 level were associated negatively with C2 (model R(2) = 0.36; P < 0.001).
  
  
  CONCLUSIONS
  Insulin resistance, inflammation, systolic hypertension, and increased pulse pressure, but not dyslipidemia, were associated with vascular dysfunction and may be targets for future interventional strategies to reduce CVD risk in patients with CKD.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia. sdogra@meddent.uwa.edu.au
authors.forename: Gursharan
authors.initials: G
authors.lastname: Dogra
authors.forename: Ashley
authors.initials: A
authors.lastname: Irish
authors.forename: Dick
authors.initials: D
authors.lastname: Chan
authors.forename: Gerald
authors.initials: G
authors.lastname: Watts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress; D011674:Pulse; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D012307:Risk Factors; D014463:Ultrasonography; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D008055:Lipids; D008074:Lipoproteins; D014665:Vasodilator Agents; D005996:Nitroglycerin