Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients

Clin J Am Soc Nephrol. 2018 Apr 6;13(4):577-584. doi: 10.2215/CJN.07980717. Epub 2018 Mar 8.

Abstract

Background and objectives: Atherosclerosis is highly prevalent in CKD. The rate of progression of atherosclerosis is associated with cardiovascular events. Fibroblast growth factor 2 (FGF-2) is a member of the FGF family with potentially both protective and deleterious effects in the development of atherosclerosis. The role of circulating FGF-2 levels in the progression of atherosclerosis in CKD is unknown.

Design, setting, participants, & measurements: We used a multicenter, prospective, observational cohorts study of 481 patients with CKD. We determined the presence of atheroma plaque in ten arterial territories by carotid and femoral ultrasounds. Progression of atheromatosis was defined as an increase in the number of territories with plaque after 24 months. Plasma levels of FGF-2 were measured by multiplex analysis. A multivariable logistic regression analysis was performed to determine whether plasma FGF-2 levels were associated with atheromatosis progression.

Results: Average age of the population was 61 years. The percentage of patients in each CKD stage was 51% in stage 3, 41% in stages 4-5, and 8% in dialysis. A total of 335 patients (70%) showed plaque at baseline. Atheromatosis progressed in 289 patients (67%). FGF-2 levels were similar between patients with or without plaque at baseline (79 versus 88 pg/ml), but lower in patients with atheromatosis progression after 2 years (78 versus 98 pg/ml; P<0.01). In adjusted analyses, higher plasma FGF-2 was associated with lower risk of atheromatosis progression (odds ratio [OR], 0.86; 95% confidence interval [95% CI], 0.76 to 0.96; per 50 pg/ml increment). Analysis of FGF-2 in tertiles showed that atheroma progression was observed for 102 participants in the lowest tertile of FGF-2 (reference group), 86 participants in the middle tertile of FGF-2 (adjusted OR, 0.70; 95% CI, 0.40 to 1.20), and 74 participants in the lowest tertile of FGF-2 (adjusted OR, 0.48; 95% CI, 0.28 to 0.82).

Conclusions: Low FGF-2 levels are independently associated with atheromatosis progression in CKD.

Keywords: Atherosclerosis; Disease Progression; Fibroblast Growth Factor 2; Humans; Logistic Models; Plaque, Atherosclerotic; Prospective Studies; Renal Insufficiency, Chronic; arteries; cardiovascular disease; renal dialysis.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carotid Intima-Media Thickness
  • Disease Progression
  • Female
  • Femoral Artery / diagnostic imaging
  • Fibroblast Growth Factor 2 / blood*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / blood*
  • Plaque, Atherosclerotic / complications
  • Plaque, Atherosclerotic / diagnostic imaging
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors

Substances

  • Fibroblast Growth Factor 2