title: Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD). Concurrently, CVD may promote CKD, resulting in a vicious cycle. We evaluated this hypothesis by exploring whether CKD and CVD have an additive or synergistic effect on future cardiovascular and mortality outcomes.
  
  
  METHODS
  Patients were pooled from 4 community-based studies: Atherosclerosis Risk in Communities, Framingham Heart, Framingham Offspring, and Cardiovascular Health Study. CKD is defined by an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) (<1 mL/s/1.73 m(2)). Baseline CVD included myocardial infarction, angina, stroke, transient ischemic attack, claudication, heart failure, and coronary revascularization. The primary outcome is a composite of cardiac events, stroke, and death. Secondary outcomes included individual components. Multivariable analyses using Cox regression examined differences in study outcomes. The interaction of CKD and CVD was tested.
  
  
  RESULTS
  The study population included 26,147 individuals. During 10 years, 4% (n = 2,927) of individuals with no CKD or CVD developed the primary outcome, 33% (n = 518) with only CKD, 37% (n = 1,260) with only CVD, and 66% (n = 459) with both. Both CKD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.16 to 1.35; P < 0.0001) and CVD (HR, 1.83; 95% CI, 1.72 to 1.95; P < 0.0001) were independent risk factors for the primary outcome. The interaction term CKD x CVD was not statistically significant (HR, 0.98; 95% CI, 0.85 to 1.13; P = 0.74). Similar results were obtained for secondary outcomes.
  
  
  CONCLUSIONS
  CKD and CVD are both strong independent risk factors for adverse cardiovascular and mortality outcomes in the general population. Although individuals with both risk factors are at extremely high risk, there does not appear to be a synergistic effect of CKD and CVD on outcomes.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Tufts-New England Medical Center, Boston, MA 02111, USA. dweiner@tufts-nemc.org
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weiner
authors.forename: Sayed
authors.initials: S
authors.lastname: Tabatabai
authors.forename: Hocine
authors.initials: H
authors.lastname: Tighiouart
authors.forename: Essam
authors.initials: E
authors.lastname: Elsayed
authors.forename: Nisha
authors.initials: N
authors.lastname: Bansal
authors.forename: John
authors.initials: J
authors.lastname: Griffith
authors.forename: Deeb N
authors.initials: DN
authors.lastname: Salem
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000150:complications / Q000209:etiology* / Q000401:mortality*; D002423:Cause of Death; D002908:Chronic Disease; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000502:physiology; D007674:Kidney Diseases / Q000150:complications* / Q000209:etiology / Q000401:mortality*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors