title: Arterial stiffness and endothelial dysfunction independently and synergistically predict cardiovascular and renal outcome in patients with type 1 diabetes.
abstract: OBJECTIVE
  To evaluate whether pulse pressure alone or with placental growth factor as estimates of arterial stiffness and endothelial dysfunction, predicts mortality, cardiovascular disease and progression to end-stage renal disease in patients with Type 1 diabetes.
  
  
  METHODS
  Prospective, observational study, median (range) follow-up 8 (0-13) years, 900 patients with Type 1 diabetes, 458 with diabetic nephropathy, mean ± SD age 44 ± 11 years.
  
  
  RESULTS
  During follow-up, we recorded 178 (20%) all-cause deaths, 109 (12%) cardiovascular deaths, 213 (24%) cardiovascular events and 73 (16%) progressed to end-stage renal disease. Elevated pulse pressure predicted all-cause and cardiovascular mortality and cardiovascular events [Hazard Ratio (HR) (95% CI) per 10 mmHg increase]: HR 1.2 (1.1-1.3), 1.3 (1.2-1.5) and 1.2 (1.1-1.3), P<0.001 (adjusted for sex, age, HbA(1c) , cholesterol, diastolic blood pressure, creatinine, smoking, previous cardiovascular disease and nephropathy status). Furthermore, pulse pressure predicted the development of end-stage renal disease in patients with diabetic nephropathy: HR 1.2 (1.1-1.4), P=0.011 (adjusted for sex, age, HbA(1c) , cholesterol, diastolic blood pressure, previous cardiovascular disease and glomerular filtration rate). In a two-hit model, patients with pulse pressure and placental growth factor levels above the median vs. below the median had increased risk of all-cause and cardiovascular mortality, cardiovascular events and progression to end-stage renal disease: adjusted HRs 2.3 (1.2-4.2), 4.2 (1.6-11.0), 2.3 (1.3-4.1) and 3.5 (1.0-11.8),P<0.05.
  
  
  CONCLUSIONS
  Elevated pulse pressure independently predicts mortality, cardiovascular events and progression to end-stage renal disease in patients with Type 1 diabetes. Placental growth factor adds to the predictive value of pulse pressure on cardiovascular and renal outcome.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. ktld@steno.dk
authors.forename: S
authors.initials: S
authors.lastname: Theilade
authors.forename: M
authors.initials: M
authors.lastname: Lajer
authors.forename: A
authors.initials: A
authors.lastname: Jorsal
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
authors.forename: P
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000401:mortality / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000401:mortality / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000401:mortality / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D011446:Prospective Studies; D059289:Vascular Stiffness / Q000502:physiology*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor