Pulse transit time in pregnancy: a new way to diagnose and classify sleep disordered breathing?

STUDY OBJECTIVES: There are significant discrepancies between the prevalence of snoring and that of objectively defined sleep disordered breathing among pregnant women, suggesting subtle airflow limitations that may not be captured by conventional scoring. This study examined the performance of pulse transit time, an indirect measure of arterial stiffness and sympathetic activation, in pregnancy. METHODS: Pregnant women with obesity and snoring and a group of controls without symptoms of sleep disordered breathing were recruited in the first trimester. Women underwent a level III in-laboratory sleep monitoring study including an electrocardiogram and pulse oximetry, and pulse transit time was measured. Sleep disordered breathing was defined as an apnea-hypopnea index at least five events per hour of sleep. Statistical analysis was performed using Spearman correlation, Fisher's exact t-test, and univariate analysis. RESULTS: Of the 222 women, 38 met criteria for sleep disordered breathing. Pulse transit time drops were very prevalent (95% of participants with snoring had > 5 drops per hour). Median apnea-hypopnea index was 0.7 (interquartile range [IQR]: 2.6) events per hour whereas median pulse transit time drop index was 20.70 (IQR: 35.90) events per hour. Pulse transit time index was significantly higher in snorers with apnea-hypopnea index less than five events per hours and participants with apnea-hypopnea index greater than five events per hour compared to controls. Examination of random epochs with pulse transit time drops showed that 95% of pulse transit time drops were associated with airflow limitation. CONCLUSIONS: Pulse transit time ascertains frequent events of sympathetic activation in at-risk women with and without sleep disordered breathing beyond conventional apneas and hypopneas. Pulse transit time may be an important addition to the identification of clinically significant sleep disordered breathing in pregnant women, and may identify more sleep disordered breathing than apnea-hypopnea index.

Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences.

CONTEXT: Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous condition resembling primary hyperparathyroidism (PHPT) but not curable by surgery; FHH types 1, 2, and 3 are due to loss-of-function mutations of the CASR, GNA11, or AP2S1 genes, respectively. OBJECTIVE: This study aimed to compare the phenotypes of patients with genetically proven FHH types 1 or 3 or PHPT. DESIGN, SETTING, AND PATIENTS: This was a mutation analysis in a large cohort, a cross-sectional comparison of 52 patients with FHH type 1, 22 patients with FHH type 3, 60 with PHPT, and 24 normal adults. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: Abnormalities of the CASR, GNA11, and AP2S1 genes, blood calcium, phosphate, and PTH concentrations, urinary calcium excretion were measured. RESULTS: In 133 families, we detected 101 mutations in the CASR gene, 68 of which were previously unknown, and in 19 families, the three recurrent AP2S1 mutations. No mutation was detected in the GNA11 gene. Patients with FHH type 3 had higher plasma calcium concentrations than patients with FHH type 1, despite having similar PTH concentrations and urinary calcium excretion. Renal tubular calcium reabsorption levels were higher in patients with FHH type 3 than in those with FHH type 1. Plasma calcium concentration was higher whereas PTH concentration and urinary calcium excretion were lower in FHH patients than in PHPT patients. In patients with FHH or PHPT, all data groups partially overlapped. CONCLUSION: In our population, AP2S1 mutations affect calcium homeostasis more severely than CASR mutations. Due to overlap, the risk of confusion between FHH and PHPT is high.