The cardiovascular system in familial hypocalciuric hypercalcemia: A crosssectional 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. Design: Cross-sectional study comparing 50 patients with FHH to age- and gender-matched controls. Results: Studied subjects (69% women) had a mean age of 56 years. 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 ± 9 mmHg, P < 0.01) and higher in FHH males (69 ± 6 vs 64 ± 5 mmHg, 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. I.