Longitudinal Monitoring of Hair Cortisol Using Liquid Chromatography-Mass Spectrometry to Prevent Hypercortisolism in Patients Undergoing Glucocorticoid Replacement Therapy.

OBJECTIVE: Currently available methods for endogenous cortisol monitoring in patients with hormonal insufficiency rely on measurements of plasma levels only at a single time point; thus, any kind of chronic exposure to cortisol is challenging to evaluate because it requires collecting samples at different time points. Hair cortisol levels acquired longitudinally better reflected chronic exposure (both cortisol synthesis and deposition) and may significantly contribute to better outcomes in glucocorticoid replacement therapies. DESIGN: Twenty-two patients on cortisol substitution therapy were monitored for plasma, urinary, and hair cortisol levels for 18 months to determine whether hair cortisol may serve as a monitoring option for therapy setting and adjustment. METHODS: Plasma and urinary cortisol levels were measured using standardized immunoassay methods, and segmented (∼1 cm) hair cortisol levels were monitored by liquid chromatography coupled to mass spectrometry. A log-normal model of the changes over time was proposed, and Bayesian statistics were used to compare plasma, urinary, and hair cortisol levels over 18 months. RESULTS AND CONCLUSIONS: Hair cortisol levels decreased over time in patients undergoing substitutional therapy. The residual variance of hair cortisol in comparison to plasma or urinary cortisol levels was much lower. Thus, longitudinal monitoring of hair cortisol levels could prove beneficial as a noninvasive tool to reduce the risk of overdosing and improve the overall patient health.

The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure.

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

Long-term relationship between unattended automated blood pressure and auscultatory BP measurements in hypertensive patients.

AIMS: Unattended automated office blood pressure (uAutoOBP) has attracted more attention since SPRINT trial had been published. However, its long-term relationship to attended office blood pressure (AuscOBP) is not known. MATERIAL AND METHODS: Stable treated hypertensive subjects were examined in four Czech academic hypertension centers. All subjects attended four clinical visits three months apart. uAutoOBP was measured with the BP Tru device; AuscOBP was measured three times with auscultatory method by the physician. 24-hour ambulatory blood pressure monitoring (ABPM) was performed within one week from the second clinical visit. RESULTS: Data on 112 subjects aged 65.6 ± 10.8 years with mean AuscOBP 128.2 ± 12.2/78.5 ± 10.3 mm Hg are reported. Across the four clinical visits, the uAutoOBP was by 10.1/3.7 mm Hg lower than AuscOBP and the mean difference was similar during all four visits (P≥.061). Both uAutoOBP and AuscOBP had similar intra-individual variability during study follow-up as demonstrated by similar intraclass correlation coefficients (ICC, for systolic ICC = 0.50, for diastolic ICC = 0.72). However, the intra-individual variability of the systolic AuscOBP and uAutoOBP difference was high as demonstrated by low ICCs for absolute (ICC = 0.17 [95%CI, 0.09 - 0.25]) and low κ coefficients for categorized differences (κ ≤ 0.16). The main determinant of AuscOBP-uAutoOBP difference was AuscOBP level. The AuscOBP-uAutoOBP difference was poor tool to identify hypertension control categories defined on the basis of AuscOBP and ABPM. CONCLUSIONS: Although mean AuscOBP-uAutoOBP differences were relatively similar across the four clinical visits, intra-individual variability of this difference was high. The AuscOBP-uAutoOBP difference was poor tool to identify hypertension control categories defined on the basis of AuscOBP and ABPM. Therefore, uAutoOBP cannot be used as a replacement for ABPM.

A multicentre study on unattended automated office blood pressure measurement in treated hypertensive patients.

AIMS: Unattended automated office blood pressure (uAutoOBP) may eliminate white-coat effect. In the present study, we studied its relationships to attended office blood pressure (BP) and ambulatory BP monitoring (ABPM). MATERIAL AND METHODS: Stable treated hypertensive subjects were examined in four Czech academic hypertension centres. uAutoOBP was measured with the BP Tru device; attended BP was measured six times: three times with auscultatory method (AuscOBP) by the physician followed optionally by three oscillometric measurements (OscOBP). ABPM was performed within one week from the clinical visit. RESULTS: Data on 172 subjects aged 63.7 ± 12.4 years with AuscOBP 127.6 ± 12.1/77.6 ± 10.0 mm Hg are reported. uAutoOBP was by 8.5 ± 9.0/3.0 ± 6.1 mm Hg lower than AuscOBP. The AuscOBP-uAutoOBP difference increased with the AuscOBP level and it did not depend on any other factor. OscOBP differed by 8.6 ± 8.6/1.9 ± 5.7 mm Hg from uAutoOBP. 24-hour mean BP was by 4.2 ± 12.1/3.5 ± 7.8 mm Hg lower than AuscOBP and by 4.3 ± 11.0/0.5 ± 6.9 mm Hg higher than uAutoOBP; the correlation coefficients of 24-hour mean BP with AuscOBP and with uAutoOBP did not differ (p for difference ≥.13). In the lowest BP group (systolic AuscOBP <120 mm Hg or diastolic AuscOBP <70 mm Hg), both AuscOBP and uAutoOBP were lower than 24-hour mean BP, while in the highest BP group (systolic AuscOBP ≥140 mm Hg or diastolic AuscOBP ≥90 mm Hg), they were higher. CONCLUSIONS: Compared to uAutoOBP, attended BP measurement gives higher values, both when measured with auscultatory or oscillometric method. Inter-individual variability of AutoOBP - uAuscOBP difference, as well of uAutoOBP - ABPM difference, is large. We did not prove that uAutoOBP would be associated to 24-hour ambulatory BP more closely than attended BP.

[SPRINT study: far lower systolic blood pressure]. / Studie SPRINT: Kam az snizovat systolický krevní tlak.

There is still no consensus, which blood pressure value is the most profitable for the patients when treating the systolic hypertension in the context of reduction of cardiovascular events and cardiovascular and overall mortality.Researchers of the ACCORD study were comparing intensive treatment of systolic blood pressure bellow 120 mmHg and standard treatment reaching bellow 140 mmHg and showed no influence of intensive treatment on the primary goal in individuals with diabetes mellitus.Last autumn, SPRINT study was presented and published showing the favourable effect of intensive (i. e. bellow 120 mmHg) blood pressure lowering on combined primary goal which was myocardial infarction, other acute coronary syndromes, ischemic stroke, heart failure or death from cardiovascular reasons. On the other hand, intensive treatment also resulted in statistically significant occurrence of adverse events (hypotension, syncope, renal injury of failure).

Chronobiological changes in arterial blood pressure in participants of the 5th and 6th Czech Antarctic Scientific Expeditions.

OBJECTIVE: To evaluate potential changes in arterial blood pressure (ABP) and heart rate (HR) during a 2-month stay in Antarctica, using chronobiological analysis. METHODS: An observational study performed at Mendel research base, Antarctica, during 2011 and 2012. The studied group consisted of 24 participants of the 5th and 6th Czech Antarctic Scientific Expeditions. Three series of 24-hour ABP monitoring were performed, of these two in Antarctica and one in the Czech Republic. Chronobiological analyses of the data were performed (Halberg Chronobiology Center, Minnesota) using population-mean cosinor. The values of MESOR (Midline Estimating Statistic Of Rhythm), double amplitude and the acrophase were obtained for SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure) and HR. These rhythm characteristics were compared between the two locations by parameter tests and by the paired t-test. RESULTS: On the average, the MESORs of SBP, DBP and HR were significantly higher in Antarctica than in the Czech Republic, as were the double amplitudes of the 12-hour component of SBP and DBP. High prevalence of CHAT (Circadian Hyper-Amplitude-Tension) was detected in Antarctica (8/24 = 33%); only 2 persons had CHAT in the Czech Republic (χ²=3.945, p=0.047). CONCLUSIONS: A prolonged stay in Antarctica clearly affected certain chronobiological parameters of ABP and HR.

A comparison of the trough-to-peak ratio of cardio-selective beta-blockers in patients with newly diagnosed hypertension.

INTRODUCTION: The drug can be administered once a day, if the trough-to-peak ratio (T/P) exceeds 50-66%. The objective of this work was to determine and compare the T/P ratio for betaxolol hydrochloride and for extended-release metoprolol tartrate. METHODS: An open, randomized, prospective, comparative clinical study. The 24-h ambulatory blood pressure was measured with a SpaceLab 90207 automatic instrument (Redmond, Washington, USA) before and after 3 months of beta-blocker treatment. In order to determine the peak value, the individual maximum hourly mean blood pressure reduction was determined in the 3 to 6-h post-dose interval. For the determination of the trough value, the individual hourly mean blood pressure decrease in the 23-h post-dose interval, minimal 30 min after getting up in the morning was used. The T/P ratio was calculated as the mean of individual T/P ratios with statistical description of standard deviation (SD) and 95% confidence intervals (CIs). RESULTS: Betaxolol hydrochloride reduced the mean peak systolic blood pressure value by 17.87+/-8.32 mmHg, the mean peak diastolic blood pressure value by 16.07+/-6.65 mmHg, the mean trough systolic blood pressure value by 11.83+/-5.98 mmHg and the mean trough diastolic blood pressure value by 11.33+/-6.74 mmHg. The mean T/P ratio was calculated as 72.84+/-33.32% (95% CI, 60.40-85.285%) for systolic blood pressure and as 71.57+/-29.35% (95% CI, 60.62-82.53%) for diastolic blood pressure. Metoprolol reduced the mean peak systolic blood pressure value by 16.70+/-10.54 mmHg, the mean peak diastolic blood pressure value by 14.20+/-8.67 mmHg, the mean trough systolic blood pressure value by 11.30+/-9.12 mmHg and the mean trough diastolic blood pressure value by 10.00+/-8.38 mmHg. The mean T/P ratio was calculated as 70.59+/-31.66% (95% CI, 58.76-82.41%) for systolic blood pressure and as 66.95+/-31.60% (95% CI, 55.15-78.75%) for diastolic blood pressure. CONCLUSION: The T/P ratio determined for betaxolol hydrochloride and extended-release metoprolol tartrate is higher than 66%. This ratio guarantees a satisfactory 24-h effect of both the above-mentioned drugs.

24 hour ambulatory blood pressure values corresponding to office blood pressure value of 130/80 mm Hg.

BACKGROUND: 24 hour ambulatory blood pressure monitoring (ABPM) values for patients who have office BP of 130/80 mm Hg have not been clearly reported. AIM: The determination of ABPM values in treated hypertensive subjects corresponding to a mean office BP of 130/80 mm Hg. METHODS: BP measurement in subjects 40-70 years old, by ABPM and mercury sphygmomanometer. The inclusion criteria were: mean office BP systolic (SBP) 128-132 mm Hg and diastolic (DBP) 78-82 mm Hg. Seventy six subjects met all study inclusion criteria. RESULTS: Mean office BP: SBP 129.5 ± 1.1 mm Hg, DBP 79.9 ± 1.3 mm Hg. Mean 24 hour BP: SBP 121.9 ± 2.0 mm Hg, DBP 73.1 ± 1.9 mm Hg. Mean awake BP: SBP 124.9 ± 2.4 mm Hg, DBP 75.5 ± 2.2 mm Hg. Mean asleep BP: SBP 109.1 ± 3.9 mm Hg, DBP 63.3 ± 4.0 mm Hg. CONCLUSIONS: The target values of ABPM identified in this study can be used in clinical practice and will contribute to risk stratification and treatment of hypertension.

The effect of short-term isometric muscle contraction and the Valsalva maneuver on systemic and pulmonary hemodynamics in patients with severe heart failure.

BACKGROUND: Chronic heart failure is characterized by high mortality, frequent hospitalization, and reduced quality of life. Patients with severe heart failure are often in very poor physical condition, they are unable to take part in the usual exercise programs, and therefore need an individual approach. HYPOTHESIS: To assess the systemic and pulmonary hemodynamic responses to maximum voluntary contraction of the lower extremity muscles (MVC-LEM) with persistent physiologic breathing, the Valsalva maneuver, and the combination of Valsalva with MVC-LEM. METHODS: Seventeen patients with severe heart failure (ejection fraction 20%) were exposed to 3 types of load for a period of 10 seconds: 1) MVC-LEM with persistent physiologic breathing, 2) the Valsalva maneuver, and 3) a combination of MVC-LEM with the Valsalva maneuver. During each measurement, a continuous, time-synchronized record was taken of the electrocardiogram, and the pulmonary and systemic blood pressures. RESULTS: There were slight changes in the heart rate and systemic blood pressure when comparing resting versus MVC-LEM values. There were much greater and significant changes (P < .01) in the systemic and pulmonary blood pressures when comparing resting versus the Valsalva maneuver or the combination of the MVC-LEM plus the Valsalva maneuver values. CONCLUSIONS: A short maximum voluntary contraction of the muscles of the lower extremities with persistent physiologic breathing did not have an abnormal effect on the systemic and pulmonary hemodynamics in patients with severe chronic heart failure. The Valsalva maneuver caused significantly higher hemodynamic changes in the systemic and pulmonary system with possible negative effects.