title: The blood pressure lowering potential of sulodexide--a systematic review and meta-analysis.
abstract: OBJECTIVE
  Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of sulodexide treatment.
  
  
  METHODS
  We selected randomized controlled trials that investigated sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data.
  
  
  RESULTS
  Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P < 0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r(2)=0.83, P < 0.001) and diastolic BP (r(2)=0.41, P = 0.02) reductions after sulodexide treatment. In addition, systolic (r(2)=0.41, P = 0.03) and diastolic BP reductions (r(2)=0.60, P = 0.005) were significantly associated with albuminuria reduction.
  
  
  CONCLUSIONS
  Our data suggest that sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of sulodexide.
authors.affiliation: Division of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam.
authors.forename: Rik H G
authors.initials: RH
authors.lastname: Olde Engberink
authors.affiliation: Division of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam.
authors.forename: Nienke M G
authors.initials: NM
authors.lastname: Rorije
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen.
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen.
authors.forename: Dick
authors.initials: D
authors.lastname: De Zeeuw
authors.affiliation: Division of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Bert-Jan H
authors.initials: BJ
authors.lastname: van den Born
authors.affiliation: Division of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam.
authors.forename: Liffert
authors.initials: L
authors.lastname: Vogt
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis
chemical_list: D000959:Antihypertensive Agents; D006025:Glycosaminoglycans; D009569:Nitric Oxide; C007858:glucuronyl glucosamine glycan sulfate
keywords: albuminuria; blood pressure; cardiovascular; glycosaminoglycan; hypertension; sulodexide