title: Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: dependent or independent risk factors?
abstract: BACKGROUND
  Vitamin D (Vit D) deficiency has been associated with prevalent and incident cardiovascular (CV) disease, suggesting a role for bioregulators of bone and mineral metabolism in CV health. Vitamin D deficiency leads to secondary hyperparathyroidism, and both primary and secondary hyperparathyroidism are associated with CV pathology. Parathyroid hormone (PTH) is an important regulator of calcium homeostasis, and its impact on CV disease risk is of interest. We tested whether elevated PTH is associated with CV disease and whether risk associations depend on Vit D status and renal function.
  
  
  METHODS
  Patients in the Intermountain Healthcare system with concurrent PTH and Vit D as 25-hydroxy-vitamin D (25[OH]D) levels were studied (N = 9,369, age 63 ± 16 years, 36% male). Parathyroid hormone levels were defined as low (<15 pg/mL), normal (15-75 pg/mL), or elevated (>75 pg/mL). Prevalence and incidence of hypertension, diabetes, hyperlipidemia, coronary artery disease/myocardial infarction, heart failure, stroke, and peripheral vascular disease were determined by the International Classification of Diseases, Ninth Revision codes documented in electronic medical records at baseline and, for incident events, during an average of 2.0 ± 1.5 years (maximum 7.5 years) of follow-up.
  
  
  RESULTS
  Parathyroid hormone elevation at baseline was noted in 26.1% of the study population. Highly significant differential CV prevalence/incidence rates for most CV risk factors, disease diagnoses, and mortality were noted for PTH >75 pg/mL (by 1.25- to 3-fold). Parathyroid hormone correlated only weakly (r = -0.15) with 25(OH)D and moderately with glomerular filtration rate (r = -0.36). 25(OH)D, standard risk factors, and renal dysfunction variably attenuated PTH risk associations, but risk persisted after full multivariable adjustment.
  
  
  CONCLUSIONS
  Elevated PTH is associated with a greater prevalence and incidence of CV risk factors and predicts a greater likelihood of prevalent and incident disease, including mortality. Risk persists when adjusted for 25(OH)D, renal function, and standard risk factors. Parathyroid hormone represents an important new CV risk factor that adds complementary and independent predictive value for CV disease and mortality.
authors.affiliation: Cardiovascular Department, Intermountain Medical Center, Murray, UT 84107-5701, USA. jeffrey.anderson@imail.org
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Vanwoerkom
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
authors.forename: Tami L
authors.initials: TL
authors.lastname: Bair
authors.forename: Heidi T
authors.initials: HT
authors.lastname: May
authors.forename: Donald L
authors.initials: DL
authors.lastname: Lappé
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Muhlestein
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D051437:Renal Insufficiency / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D014589:Utah / Q000453:epidemiology; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications* / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D014807:Vitamin D