title: Synergistic effect of chronic kidney disease and high circulatory norepinephrine level on stroke risk in Japanese hypertensive patients.
abstract: OBJECTIVE
  Evidence is now available about the association between chronic kidney disease (CKD) and stroke. However, less is known about the underlying mechanisms, and there is currently no reliable marker for identifying stroke-prone high-risk patients among CKD patients.
  
  
  METHODS
  A total of 514 hypertensive patients aged >50 years (mean, 72.3 years; 37% men) underwent 24-h BP monitoring and measurement of circulatory high-sensitivity C-reactive protein (hs-CRP) and norepinephrine at baseline. CKD was defined as eGFR<60 ml/min/1.73 m(2) using the Cockcroft-Gault equation.
  
  
  CONCLUSIONS
  During an average of 41 months (1751 person-years), there were 43 stroke events. Compared with hypertensive patients without CKD, those with CKD (n=225) had higher levels of sleep systolic BP (SBP) (125 mmHg vs. 129 mmHg), circulatory hs-CRP (0.12 mg/L vs. 0.20 mg/L) and norepinephrine (332.2 pg/ml vs. 372.8 pg/ml; all P<0.05). On multivariable analysis, the hazard ratio (HR) (95% CI) for stroke in CKD vs. non-CKD was 2.7 (1.2-6.9) (P<0.05). CKD, as well as the baseline presence of silent cerebral infarction, sleep SBP increase, and high hs-CRP level (highest quartile: ≥0.42 mg/L) were independently and additively associated with stroke events; above all, there was a synergistic effect of CKD and high norepinephrine level (highest quartile: ≥538 pg/ml) on stroke risk (all P<0.05). Among hypertensive patients with CKD, those within the highest quartiles of norepinephrine had a greater stroke risk compared to those who were in the lower quartiles of norepinephrine (HR (95% CI): 2.2 (1.0-4.5); P=0.045). In conclusion, CKD is an independent predictor of stroke in Japanese hypertensive patients; in particular, hypertensive patients with CKD and a high norepinephrine level have a synergistically augmented stroke risk.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke Tochigi 329-0498, Japan.
authors.forename: Yuichirou
authors.initials: Y
authors.lastname: Yano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hoshide
authors.forename: Takuma
authors.initials: T
authors.lastname: Etoh
authors.forename: Noboru
authors.initials: N
authors.lastname: Tamaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Yokota
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002097:C-Reactive Protein / Q000032:analysis; D002544:Cerebral Infarction; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications; D007564:Japan; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology*
chemical_list: D002097:C-Reactive Protein; D009638:Norepinephrine