title: Cholecystokinin in plasma predicts cardiovascular mortality in elderly females.
abstract: BACKGROUND
  Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality.
  
  
  METHODS
  Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n=470). Primary care patients were followed for 13years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point.
  
  
  RESULTS
  In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p<0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p=0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p=0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p=0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk.
  
  
  CONCLUSIONS
  CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk assessment.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: JPG@dadlnet.dk.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: Department of Cardiology, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Urban
authors.initials: U
authors.lastname: Alehagen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000401:mortality*; D002766:Cholecystokinin / Q000097:blood*; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009026:Mortality / Q000639:trends; D011237:Predictive Value of Tests; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D015415:Biomarkers; D002766:Cholecystokinin
keywords: ANP; Atrial natriuretic peptide; B-type natriuretic peptide; BNP; Cholecystokinin; Heart failure; Prognosis