title: Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study.
abstract: OBJECTIVE
  To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population.
  
  
  METHODS
  Prospective population based cohort study.
  
  
  METHODS
  Reykjavik, Iceland.
  
  
  METHODS
  16 958 people aged 33-81 years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry.
  
  
  METHODS
  Hazard ratios for time to major coronary heart disease outcomes and mortality.
  
  
  RESULTS
  1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 4010 coronary heart disease outcomes, 559 deaths from stroke, and 3875 deaths from non-vascular causes were recorded. Compared with the reference group (estimated glomerular filtration rate 75-89 ml/min/1.73 m(2) and no proteinuria), people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease. By contrast, in 1210 (7%) participants with chronic kidney disease at entry, hazard ratios for coronary heart disease, adjusted for several conventional cardiovascular risk factors, were 1.55 (95% confidence interval 1.02 to 2.35) for stage 1, 1.72 (1.30 to 2.24) for stage 2, 1.39 (1.22 to 1.58) for stage 3a, 1.90 (1.22 to 2.96) for stage 3b, and 4.29 (1.78 to 10.32) for stage 4. Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors (P<0.01). The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking (C index increases of 0.0015, 0.0024, and 0.0124 respectively). Hazard ratios with chronic kidney disease were 0.97 (0.82 to 1.15) for cancer mortality and 1.26 (1.07 to 1.50) for other non-vascular mortality.
  
  
  CONCLUSIONS
  In people without manifest vascular disease, even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease. Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population. Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer.
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. emanuele.diangelantonio@phpc.cam.ac.uk
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chowdhury
authors.forename: Nadeem
authors.initials: N
authors.lastname: Sarwar
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.forename: John
authors.initials: J
authors.lastname: Danesh
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors