Association of aldosterone excess and apnea-hypopnea index in patients with resistant hypertension.

The present study was to investigate the association of aldosterone excess and apnea-hypopnea index (AHI) in patients with resistant hypertension. Patients with resistant hypertension were enrolled and baseline characteristics including plasma aldosterone concentration (PAC) and 24 h-urine aldosterone levels were collected and compared between groups with different degrees of AHI as assessed by polysomnography. Association of key variables and AHI was then evaluated by univariate and multiple linear regression analysis. A total of 534 patients with resistant hypertension were enrolled and mean age was 57 ± 11 years. Overall, mean number of AHI was 21.7 ± 9.6 and nearly 92.3% of resistant hypertensive patients had obstructive sleep apnea (OSA). Mean PAC and 24 h-urine aldosterone level was 12.4 ± 6.3 ng/dL and 13.1 ± 6.8 ug, respectively. Compared with other groups, participants in the severe OSA group (AHI ≥ 30) had significantly higher PAC and 24 h-urine aldosterone level. Multiple linear regression analysis showed that PAC and 24 h-urine aldosterone levels were positively associated with AHI, while spironolactone was negatively associated with AHI, independent of age, gender, body mass index, smoking, plasma renin activity and diuretics. OSA is highly prevalent in patients with resistant hypertension and both PAC and 24 h-urine aldosterone level are significantly associated with AHI.

Effects of continuous positive airway pressure treatment on aldosterone excretion in patients with obstructive sleep apnoea and resistant hypertension: a randomized controlled trial.

OBJECTIVE: Aldosterone excess has been equally associated with resistant hypertension (RHT) and obstructive sleep apnoea (OSA). We conducted a randomized controlled study to assess the effect of continuous positive airway pressure (CPAP) treatment on 24-h urinary aldosterone excretion in patients with RHT and moderate/severe OSA. METHODS: A total of 117 patients were randomized (57 CPAP and 60 control groups). Aldosterone excretion was determined by 24 h urine (24h-UAldo) collected at randomization and after 6 months of follow-up. Twenty-four hour UAldo differences were assessed by general linear model with the allocation group (CPAP or control) as a fixed factor adjusted for their respective baseline values. Both intention-to-treat and per-protocol (45 patients with optimal adherence to CPAP) analyses were performed. RESULTS: Baseline 24h-UAldo was higher in severe OSA than in moderate OSA patients. After CPAP treatment, there was a borderline significant reduction in 24h-UAldo [mean difference: -2.5 µg/24 h; 95% confidence interval (95% CI): -5.3 to +0.3 µg/24 h; P = 0.07] in intention-to-treat analysis, whereas in the per-protocol analysis, the CPAP group had a greater reduction in 24h-UAldo than the control group (mean difference: -3.3 µg/24 h; 95% CI: -6.1 to -0.4 µg/24 h; P = 0.027). This effect occurred solely in patients with uncontrolled ambulatory BPs, and was more pronounced in those with the nondipping pattern, not using spironolactone, less obese, and with lowest sleep SaO2 levels. CONCLUSION: Only optimal CPAP treatment reduced aldosterone excretion in patients with uncontrolled RHT, while on intention-to-treat the effect was borderline. Although nondefinitive, our results suggest that CPAP treatment might improve cardiovascular outcomes by reducing aldosterone excess in resistant hypertensive individuals with OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01508754.

Anesthetic management of a myotonic dystrophy patient with paraganglionoma.

Myotonic dystrophy (DM), though rare, can significantly complicate anesthesia due to muscular and extra-muscular involvement. When this condition is compounded by a pheochromocytoma, anesthetizing such patients becomes extra challenging. We present a case report of a 61-year-old lady with congenital DM, with the whole gamut of associated features, was diagnosed with a noradrenaline secreting paraganglionoma following investigation of refractory hypertension. We anesthetized her for an open resection of the lesion. The conduct of anesthesia and recovery of this patient is described. Our experience suggests that anesthetizing these patients though challenging can be safely managed with relaxant general anesthesia and epidural analgesia with meticulous care pre, intra and post-surgical intervention.

Severe and refractory hypertension in a young woman.

Refractory hypertension in a young person is an uncommon clinical problem, but one that may be referred to hypertension specialists. Factitious hypertension is fortunately quite rare but should be considered when evaluating patients who are refractory to numerous classes of antihypertensive therapies and have failed to achieve control despite input from multiple providers. A 19-year-old woman was referred to us after failing to achieve blood pressure control by a primary physician and two subspecialists in nephrology and hypertension; she also had numerous emergency department visits for symptomatic and severe hypertension. Exhaustive diagnostic testing for secondary causes and witnessed medication dosing in an outpatient setting was unrevealing. Subsequent inpatient admission demonstrated normalization of BPs with small doses of intravenous antihypertensive agents. During the hospitalization, she was observed "pocketing" her oral medications in the buccal folds and then discarding them in a trash container. Confrontation by psychiatrists and the hypertension specialists led to the admission that she had learned to start and stop beta-blockers and clonidine to induce severe, rebound hypertension. Factitious and induced hypertension is a rare cause of resistant or refractory hypertension. Nevertheless, hypertension specialists should suspect the diagnosis when there is a history of visits to multiple institutions and physicians, negative secondary workup, absence of overt target organ damage, history of psychiatric illness, and employment in the medical field.

A practical approach for measurement of antihypertensive medication adherence in patients with resistant hypertension.

Confirmation of medication adherence is a challenge in clinical practice and essential for the accurate diagnosis of resistant hypertension. Although it is well established that drug adherence is critical for controlling blood pressure, there are still difficulties applying a simple, inexpensive, and reliable assessment of adherence in the clinical setting. We aimed to test a simple method to assess adherence in resistant hypertensive (RH) patients. A pilot study with normotensives or mild/moderate hypertensive subjects was performed to provide a fluorescence cutoff point for adherence. After that, 21 patients referred to the Resistant Hypertension Clinic had triamterene prescribed and were monitored for a 30-day period. We conducted two unannounced randomly selected home visits for urine collection to test drug intake that day. Office, home and 24-hour ambulatory blood pressure, biochemical data, and the 8-item Morisky Medication Adherence Scale (MMAS-8) were systematically acquired. According to adherence indicated by urine fluorescence, subjects were divided into adherent and nonadherent groups. We found 57% of nonadherence. No differences were found between groups regarding baseline characteristics or prescribed medications; Kappa's test showed concordance between adherence through MMAS-8 items and fluorescence (kappa = 0.61; 95% confidence interval: 0.28-0.94; P = .005). Nonadherent patients had higher office (81 ± 11 vs. 73 ± 6 mm Hg, P = .03), 24-hour ambulatory blood pressure monitoring (75 ± 9 vs. 66 ± 7 mm Hg, P = .01), and home blood pressure measurement (77 ± 9 vs. 67 ± 8 mm Hg, P = .01) diastolic blood pressure than their counterparts. Nonadherence to antihypertensive therapy is high in patients with RH, even when assessed in clinics specialized in this condition. Fluorometry to detect a drug in the urine of RH patients is safe, easy, and reliable method to assess adherence.

Estimated GFR or albuminuria: which one is really associated with resistant hypertension?

Patients with resistant hypertension belong to a very high cardiovascular risk group and have a high prevalence of target organ damage. Microalbuminuria and low estimated glomerular filtration rate are associated with resistant hypertension, and could be a cause and/or complication of hypertension. In this review, we explore the relationship between these 2 markers of kidney disease and the prevalence of resistant hypertension. We identified different phenotypes of resistant hypertension that associate with microalbuminuria and/or low estimated glomerular filtration rate. These phenotypes suggest that high sympathetic activity associated with fluid overload and endothelial dysfunction may contribute differently to the development of resistant hypertension.

Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases after spasm provocation tests in patients with coronary spastic angina.

BACKGROUND: Bilirubin apparently functions as an antioxidant in vivo by reacting with reactive oxygen species, and, as a result, becomes oxidized. The urinary excretion of oxidative metabolites of bilirubin, biopyrrins, could be a biological marker for in vivo production of reactive oxygen species. The purpose of this study was to examine the extent of oxidative stress in patients with possible ischemic heart diseases (n=44) by measuring urinary biopyrrins by enzyme-linked immunosorbent assay before and after the spasm provocation test (SPT). METHODS: Spot urine samples were collected five times; 1 day before, in the morning just before, immediately after, 6 h after, and 1 day after the SPT. Nineteen patients were positive to SPT judged from the specific changes in electrocardiogram for myocardial ischemia following intracoronary injections of ergonovine. RESULTS: The baseline data such as age, sex, number of risk factors and concentrations of serum bilirubin, and the measured hemodynamic parameters of heart rate, blood pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction were not different between the positive and negative groups. The baseline concentrations of biopyrrins during the control period were not significantly different between the two groups. However, they increased significantly after the SPT, thereby the magnitude of increases immediately after and 6 h after the SPT were significantly (P<0.001 and P<0.01, respectively) greater in the positive group than in the negative. CONCLUSION: The present findings strongly suggest that coronary arterial occlusion augments production of biopyrrins, which indicates exposure to oxidative stress in patients with ischemic heart diseases.

Arterial and coronary sinus catecholamines in the course of spontaneous coronary artery spasm.

We studied plasma catecholamine levels in 10 patients with frequent spontaneous episodes of coronary artery spasm to evaluate the role of the sympathetic nervous system. Peripheral venous norepinephrine in supine and upright postures, urinary excretion of catecholamines, and functional testing of the sympathetic nervous system did not differ from the same measurements in control subjects. Arterial and coronary sinus levels of norepinephrine and epinephrine drawn early in ischemia were not elevated over baseline; coronary sinus norepinephrine levels were higher than those in arterial samples and rose from 315 +/- 32 (pg/ml +/- SE) at the onset of ST elevation to 490 +/- 49 pg/ml late in ischemia (p less than 0.05). Plasma epinephrine levels, higher in arterial than coronary sinus samples, also rose significantly only late in ischemia, from 44 +/- 14 pg/ml to 148 +/- 35 pg/ml (p less than 0.05) in arterial blood and from 33 +/- 10 pg/ml to 108 +/- 29 pg/ml in coronary sinus samples (p less than 0.05). Generalized sympathetic nervous system activation is not likely to be the sole cause of coronary artery spasm.