title: Risk of diabetes and cardiovascular disease in patients with primary sclerosing cholangitis.
abstract: OBJECTIVE
  Primary sclerosing cholangitis (PSC) is associated with increased mortality. Cardiovascular disease is a leading cause of death in the Western world. We examined the risk of cardiovascular disease and diabetes (type 1 and type 2) in patients with PSC and their first-degree relatives.
  
  
  METHODS
  This prospective multicentre cohort study included 678 individuals with PSC diagnosed between 1970 and 2004, and 6347 non-PSC reference individuals matched for age, and sex. Through linkage of the Swedish Multigeneration Register we identified 3139 first-degree relatives to PSC patients and 30,953 first-degree relatives to the matched comparison cohort. We retrieved data on cardiovascular disease and type 1 and type 2 diabetes (T1D and T2D) from the National Patient Register, and then examined the association with PSC or having a family history of PSC using Poisson regression.
  
  
  RESULTS
  During 125,127 person-years of follow-up, 203 individuals with PSC had a diagnosis of cardiovascular disease. This corresponded to a 3.34-fold increased relative risk (RR) of cardiovascular disease in individuals with PSC (95% CI=2.86-3.91). The highest risk estimates were seen for diseases of the arteries, veins, and lymphatic vessels while the RR was neutral for ischemic heart disease (0.90) or only slightly elevated for cerebrovascular disease (1.74). Meanwhile, PSC first-degree relatives were at no increased risk of cardiovascular disease (RR=0.87; 95% CI=0.80-0.95). Individuals with PSC (RR=7.95; 95% CI=4.82-13.12), and to some extent also their first-degree relatives (RR=1.73; 95% CI=1.19-2.52) were at increased risk of T1D. Also for T2D were the RR is higher in individuals with PSC (RR=2.54; 95% CI=1.56-4.13) than in PSC first-degree relatives (RR=0.81; 95% CI=0.65-1.02).
  
  
  CONCLUSIONS
  PSC was associated with T1D, T2D, and non-ischemic cardiovascular disease. In contrast, first-degree relatives to PSC patients were only at a moderately increased risk of T1D, and at no increased risk of either cardiovascular disease or T2D.
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Sweden; Department of Pediatrics, Örebro University Hospital, Sweden.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Ludvigsson
authors.affiliation: Department of Gastroenterology and Hepatology, Karolinska University Hospital and Karolinska Institutet, Sweden. Electronic address: Annika.Bergquist@ki.se.
authors.forename: Annika
authors.initials: A
authors.lastname: Bergquist
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Sweden; Clinical Epidemiology and Biostatistics, Örebro University Hospital & Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, UK.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Montgomery
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Bahmanyar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics; D002648:Child; D015209:Cholangitis, Sclerosing / Q000150:complications* / Q000235:genetics; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden; D055815:Young Adult
keywords: Bile duct diseases; Diabetes; Heart; Liver; Primary sclerosing cholangitis