Blood pressure response to CPAP treatment in subjects with obstructive sleep apnoea: the predictive value of 24-h ambulatory blood pressure monitoring.

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h-1) were included; 28.4% had hypertension. 62 patients finished the study, and 60 were analysed. The daytime diastolic BP (-2 mmHg) and norepinephrine (-109.5 nmol·day-1) were reduced after CPAP, but no changes in the 24-h BP, night-time BP, dopamine, epinephrine, CRP, leptin or adiponectin were detected. The nocturnal normotension was associated with an increased night-time-BP (+4 mmHg) after CPAP, whereas nocturnal hypertension was associated with a reduction of 24-h BP (-3 mmHg). A multivariate linear regression model showed differential night-time BP changes after CPAP. Specifically, low night-time heart rate (<68 bpm) and BP dipper profile were associated with increased night-time BP and new diagnosis of nocturnal hypertension.Our results suggest that nocturnal hypertension, circadian BP pattern and night-time heart rate could be clinical predictors of BP response to CPAP and support the usefulness of 24-h ABPM for OSA patients before treatment initiation. These results need to be confirmed in further studies.

Role of local bioactivation of vitamin D by CYP27A1 and CYP2R1 in the control of cell growth in normal endometrium and endometrial carcinoma.

Vitamin D (VD) deficiency has been suggested as a risk factor for cancer. One recognized mechanism is that the low-serum 25-hydroxyvitamin D (25(OH)D) of VD deficiency reduces intratumoral 25(OH)D conversion to 1α,25-dihydroxyvitamin D (1,25D, the hormonal form of VD), compromising 1,25D-VD receptor (VDR) antitumoral actions. Reduced tumoral VDR and increased CYP24A1, the enzyme that degrades 1,25D and 25(OH)D, further worsen cancer progression. Importantly, in cells expressing CYP27A1 and/or CYP2R1, which convert inert VD into 25(OH)D, low-serum VD may reduce intratumoral 25(OH)D synthesis thereby compromising VDR antitumoral actions because 25(OH)D can activate the VDR directly and enhance 1,25D-VDR action. Therefore, this study examined whether abnormal endometrial expression of CYP27A1 and/or CYP2R1 may impair VDR-antiproliferative properties in endometrial carcinoma (EC). Immunohistochemical analysis of tissue microarrays of normal human endometrium (NE; n=60) and EC (n=157) showed the expected lower VDR expression in EC (P=0.0002). Instead, CYP24A1 expression was lower in EC compared with NE, while CYP27A1 and CYP2R1 expressions were higher (P=0.0002; P=0.03). Furthermore, in NE and EC, CYP2R1 and CYP27A1 expression correlated directly with nuclear VDR levels, an indicator of ligand-induced VDR activation, and inversely with the proliferation marker Ki67. Accordingly, in the endometrioid carcinoma cell lines IK, RL95/2 and HEC1-A, which express VDR, CYP27A1, and CYP2R1, VD efficaciously reduced cell viability and colony number, with a time course that paralleled actual increases in both intracellular 25(OH)D and nuclear VDR levels. Thus, VD may protect from EC progression in part through increased intratumoral 25(OH)D production by CYP27A1 and CYP2R1 for autocrine/paracrine enhancement of 1,25D-VDR-antiproliferative actions.

Comparison of pleural N-terminal pro-B-type natriuretic peptide, midregion pro-atrial natriuretic peptide and mid-region pro-adrenomedullin for the diagnosis of pleural effusions associated with cardiac failure.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the diagnostic utility of pleural fluid N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregion pro-atrial natriuretic peptide (MR-proANP) and midregion pro-adrenomedullin (MR-proADM) for discriminating heart failure (HF)-associated effusions. METHODS: NT-proBNP, MR-proANP and MR-proADM were measured by commercially available methodologies in the pleural fluid of a retrospective cohort of 185 consecutive patients with pleural effusions, of whom 95 had acute decompensated HF. Receiver-operating characteristic and area under the curve (AUC) analyses allowed comparisons of the discriminative properties of these biomarkers to be made at their optimal cut-off points. RESULTS: The diagnostic accuracy of NT-proBNP and MR-proANP for HF as quantified by the AUC was 0.935 and 0.918, respectively, whereas MR-proADM was of limited value (AUC = 0.62). A pleural fluid MR-proANP >260 pmol/L or NT-proBNP >1700 pg/mL argues for HF (likelihood ratio (LR) positive >5), while levels below these cut-off values significantly decrease the probability of having the disease (respective LR negative 0.19 and 0.10). The optimal cut-off points for natriuretic peptides were influenced by age, renal function and body mass index. Finally, both NT-proBNP and the albumin gradient correctly identified more than 80% of those cardiac effusions misclassified as exudates by standard criteria. CONCLUSIONS: MR-proANP is as valuable a diagnostic tool as NT-proBNP for diagnosing or excluding HF as the cause of pleural effusion.

Sympathetic Hyperactivity and Sleep Disorders in Individuals With Type 2 Diabetes.

Introduction: Many studies on the impact of type 2 diabetes mellitus (T2DM) on sleep breathing have shown a higher prevalence and severity of sleep apnea-hypopnea syndrome (SAHS) in those with T2DM. Moreover, an increased activity of the sympathetic nervous system has been described in both pathologies. This cross-sectional study aimed to assess sympathetic activity in patients with T2DM, and to investigate the relationship between sympathetic activity and polysomnographic parameters. Materials and Methods: Thirty-six patients with T2DM without known clinical macrovascular nor pulmonary disease and 11 controls underwent respiratory polygraphy, and their cardiac variability and 24-h urine total metanephrines were measured. Results: SAHS was highly prevalent with a mean apnea-hypopnea index (AHI) in the range of moderate SAHS. In patients with T2DM, the nocturnal concentration of total metanephrines in urine were higher than diurnal levels [247.0 (120.0-1375.0) vs. 210.0 (92.0-670.0), p = 0.039]. The nocturnal total metanephrine concentration was positively and significantly associatedwith the percentage of sleeping time spent with oxygen saturation <90%(CT90). In the entire population and in subjects with T2DM, the multivariate regression analysis showed a direct interaction between the nocturnal concentration of urine metanephrines and the CT90. Conclusion: These findings suggest that the increase in sympathetic activity previously described in patients with T2DM could be mediated through nocturnal breathing disturbances. The diagnosis and treatment of SAHS may influence sympathetic activity disorders and may contribute to an improvement in T2DM and cardiovascular risk.

Calcium Phosphate Product Is Associated with Subclinical Carotid Atherosclerosis in Type 2 Diabetes.

AIMS: To assess whether circulating 25-hydroxyvitamin D3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease. METHODS: We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. RESULTS: We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg2/dL2) product was positively associated with the presence of carotid plaques (ORadj = 1.078; 95% CI: 1.017-1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) (ßadj ± SE = -0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM.

Vitamin D Deficiency Is Associated with the Presence and Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

There is very few evidences on the role of vitamin D in the development of diabetic retinopathy. The aim of the current study was to explore whether there is an association of vitamin D status and diabetic retinopathy in type 2 diabetes. Two groups of patients were selected: 139 and 144 patients with and without retinopathy, respectively, as assessed by an experienced ophthalmologist. Subjects with advanced late diabetic complications were excluded to avoid confounding biases. 25-Hydroxy-vitamin D3 (25(OH)D) concentrations and vitamin D deficiency were associated with the presence of diabetic retinopathy. Additionally, patients with more advanced stages of retinopathy (grades 2-4) had lower concentrations of 25(OH)D and were more frequently vitamin D deficient as compared with patients not carrying this eye complication. In conclusion, our study confirms the association of vitamin D deficiency with the presence and severity of diabetic retinopathy in type 2 diabetes. Further experimental and prospective studies on this issue are clearly warranted.

A pilot study on the diagnostic accuracy of proadrenomedullin and proatrial natriuretic Peptide in lower respiratory tract infections.

BACKGROUND: Pneumonia is the leading cause of death among infectious diseases in developed countries. However, the severity of pneumonia requiring hospitalization often makes the initial diagnosis difficult because of an equivocal clinical picture or interpretation of the chest film. The objective of the present study was to assess the usefulness of the plasma levels of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) in differentiating pneumonia from other lower respiratory tract infections (LRTIs). METHODS: A retrospective study was conducted. The plasma levels of MR-proADM and MR-proANP were measured in 85 patients hospitalized for LRTIs, 56 of whom with diagnosis of pneumonia and 29 with other LRTIs. RESULTS: The patients with pneumonia had increased MR-proADM levels (median 1.46 nmol/L [IQR 25-75, 0.82-2.02 nmol/L]) compared with the patients with other LRTIs (median 0.88 nmol/mL [0.71-1.39 nmol/L]) (p= 0.04). However, the MR-proANP levels did not show differences between the groups. The optimal threshold of MR-proADM to predict pneumonia was 1.5 nmol/L, which yielded a sensitivity of 51.7% (95% CI, 38.0-65.3), a 79.3% specificity (95% CI, 60.3-92.0), and an odds ratio of 6.64 (95% CI, 1.32-32.85). The combination of this parameter with C-reactive protein in an "and" rule increased the specificity for detecting pneumonia significantly. CONCLUSION: MR-proADM levels (but not MR-proANP levels) are increased in patients with pneumonia although its discriminatory power is moderate.

Biomarkers of heart failure in pleural fluid.

BACKGROUND: The objective of this study was to compare the diagnostic accuracy of pleural fluid brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro-BNP) and ST2, which are biomarkers of myocyte stress, for diagnosing pleural effusions due to heart failure (HF). BNP and ST2 have not been previously evaluated in pleural fluid. METHODS: The three biomarkers were measured in the pleural fluid of 90 cardiac effusions and 91 noncardiac effusions by commercially available methodologies. The area under the curve (AUC) quantified the overall diagnostic accuracy of the tests. RESULTS: Pleural fluid NT-pro-BNP, BNP, and ST2 demonstrated AUCs of 0.96, 0.90 and 0.59, respectively, for diagnosing effusions due to HF. The cutoff values of 1,300 and 115 pg/mL, respectively, for NT-pro-BNP and BNP had the best discriminating properties. The reference level for BNP was particularly accurate in men > 75 years of age (AUC, 0.98), but age, gender, and serum creatinine level did not influence the NT-pro-BNP levels. Of the 20 patients whose cardiac effusions were misclassified as exudates by the criteria of Light et al, 18 patients (90%) and 14 patients (70%), respectively, would have been correctly categorized by NT-pro-BNP and BNP, whereas only 10 patients (50%) would have been appropriately classified by the serum-pleural protein gradient. CONCLUSIONS: The pleural fluid NT-pro-BNP level is very useful in establishing the diagnosis of HF-associated effusions, and it confirms this diagnosis better than pleural BNP levels. The measurement of NT-pro-BNP rather than the serum-to-pleural protein gradient is recommended for identifying mislabeled cardiac transudates. The pleural fluid ST2 level is not helpful in diagnosing HF.

Comparing serum and pleural fluid pro-brain natriuretic peptide (NT-proBNP) levels with pleural-to-serum albumin gradient for the identification of cardiac effusions misclassified by Light's criteria.

BACKGROUND AND OBJECTIVES: To assess the diagnostic performance of the amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in pleural fluid and serum for the identification of pleural effusions owing to heart failure, and to determine if these measurements allow better categorization of cardiac effusions that have been misclassified by Light's criteria, than do serum-pleural fluid albumin and protein gradients. METHODS: The study prospectively evaluated NT-proBNP in serum and pleural fluid from patients with effusions owing to heart failure (n = 53) and other causes (n = 40). Measurements were made of levels of NT-proBNP by an electrochemiluminiscence immunoassay, and serum-pleural fluid protein and albumin gradients. RESULTS: Using a cut-off value of 1500 pg/mL for serum and pleural samples, the accuracy of NT-proBNP for identifying pleural effusions from cardiac causes was 89% and 90%, respectively. The area under the receiver operating characteristic curve for the diagnosis of pleural effusions from heart failure was similar for pleural fluid (0.931, 95% CI: 0.871-0.991) and serum (0.919, 95% CI: 0.855-0.984) NT-proBNP. Six (75%) of eight patients with cardiac effusions that were misclassified as exudates by Light's criteria would have been correctly categorized by either NT-proBNP or the albumin gradient, whereas only four (50%) would have been correctly classified by the protein gradient. CONCLUSIONS: NT-proBNP is a useful marker for the diagnosis of pleural effusions from heart failure when measured in either serum or pleural fluid. At a cut-off of 1500 pg/mL, NT-proBNP is at least as accurate as the albumin gradient to correctly identify cardiac effusions misclassified as exudates by standard criteria, but at much higher cost.