title: The cardiovascular system in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene.
abstract: OBJECTIVE
  Loss-of-function variants in the gene encoding the calcium-sensing receptor (CASR) result in familial hypocalciuric hypercalcemia (FHH), causing hypercalcemia with high normal or elevated parathyroid hormone levels. The CASR may also influence electrolyte and water homeostasis. It is unknown whether FHH affects cardiovascular health. We, therefore investigated whether FHH is associated with changes in the regulation of the cardiovascular system by measuring 24-h blood pressure (BP), arterial stiffness and vasoactive hormones.
  
  
  METHODS
  Cross-sectional study comparing 50 patients with FHH to age- and gender-matched controls.
  
  
  RESULTS
  Studied subjects (69% women) had a mean age of 56years. A similar number of patients and controls (33%) were on treatment with antihypertensive drugs. Overall, no differences were found between groups in 24-h ambulatory BP or pulse wave velocity. However, compared with controls, diastolic BP during nighttime was lower in FHH females (60±5 vs 66±9mmHg, P<0.01) and higher in FHH males (69±6 vs 64±5mmHg, P=0.02). FHH was associated with a significantly higher plasma osmolality (P<0.01), higher plasma levels of vasopressin (P<0.01) and a higher renal excretion of epithelial sodium channels (ENaCs) (P=0.03), whereas urine aquaporin-2 and plasma sodium, aldosterone and renin did not differ between groups. FHH patients had a lower urinary volume with an increased osmolality if analyses were restricted to those not on treatments with antihypertensive drugs.
  
  
  CONCLUSIONS
  FHH does not seem to be associated with an increased risk of CVD.
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels Frederik
authors.initials: NF
authors.lastname: Breum Jakobsen
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, Denmark Danish Diabetes AcademyOdense University Hospital, Odense, Denmark Department of Clinical MedicineAarhus University, Aarhus, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Laugesen
authors.affiliation: Departments of Surgery.
authors.forename: Lars
authors.initials: L
authors.lastname: Rolighed
authors.affiliation: Clinical BiochemistryAarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nissen
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, Denmark.
authors.forename: Per Løgstrup
authors.initials: PL
authors.lastname: Poulsen
authors.affiliation: Department of Clinical MedicineAarhus University, Aarhus, Denmark University Clinic in Nephrology and HypertensionHolstebro Hospital, Hospital Jutland West, Holstebro, Denmark.
authors.forename: Erling Bjerregaard
authors.initials: EB
authors.lastname: Pedersen
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus, Denmark Department of Clinical MedicineAarhus University, Aarhus, Denmark lars.rejnmark@rm.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Rejnmark
mesh_terms: D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000502:physiology*; D002319:Cardiovascular System / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood; D059289:Vascular Stiffness / Q000502:physiology*; D014667:Vasopressins / Q000097:blood
chemical_list: D044169:Receptors, Calcium-Sensing; D014667:Vasopressins; D000450:Aldosterone; D012964:Sodium; D012083:Renin