Luiz Cláudio Martins

Characteristics of resistant hypertension: ageing, body mass index, hyperaldosteronism, cardiac hypertrophy and vascular stiffness

Resistant hypertension (RHTN) includes patients whose blood pressure (BP) is controlled with the use of four or more antihypertensive medications, and is referred to as ‘controlled resistant hypertension’ (CRH). While specifically comparing patients with CRH and uncontrolled resistant hypertension (UCRH), we hoped to identify distinguishing characteristics that would provide insight into factors contributing to resistance to antihypertensive therapies. RHTN patients were identified as controlled (CRH, n=43) or uncontrolled (UCRH, n=47). No statistical differences were observed between the CRH and UCRH subgroups with respect to age and gender. The body mass index, aldosterone–renin ratio and pulse wave velocity (PWV) were significantly higher in UCRH patients. Although both subgroups showed increased cardiac mass, left ventricular mass index was significantly higher in UCRH compared with CRH patients. Multivariate linear regression analysis indicated that PWV was significantly dependent on age in both UCRH and CRH patients; however, the influence of ageing was more pronounced in the former subgroup. Older age, greater vascular stiffness, higher aldosterone levels and greater left ventricular hypertrophy were significantly associated with lack of BP control in patients with RHTN. These findings suggest important possibilities in terms of preventing and better treating RHTN.

Vascular stiffness and endothelial dysfunction: Correlations at different levels of blood pressure

Abstract Resistant hypertensive (RHTN) patients have endothelial dysfunction and aldosterone excess, which contribute to the development of resistance to antihypertensive treatment and cardiovascular complications. Biophysical forces within the arterial wall provide functional regulation of arterial stiffness. Carotid–femoral pulse wave velocity (PWV) and flow-mediated brachial artery dilation (FMD) can be used to evaluate vascular stiffness and endothelial function. Although both techniques have been used in several studies in hypertensive patients, it is unknown whether endothelial dysfunction is also associated with vascular stiffness in RHTN patients. Methods. One hundred and ninety-three consecutive subjects were divided in three groups: 44 RHTN, 35 well-controlled hypertensive patients (HTN) and 25 normal healthy volunteers (NT). FMD was measured by high-resolution ultrasound and PWV was calculated from measurements of the pulse transit time and the distance traveled by the pulse between carotid and femoral arteries. Results. No significant differences were observed in respect to body mass index, age or other biochemical variables among the three groups. FMD (NO-dependent) values were statistically different when comparing RHTN and well controlled HTN patients (respectively, 8.3 ± 4.7% and 10.1 ± 5.9%) and 12.3 ± 6.3% in normal subjects (p < 0.05). One-way analysis of variance (ANOVA) showed a significant difference in BP-adjusted PWV between RHTN and HTN (13.9 ± 1.0 and 11.5 ± 1.1 m/s, respectively; p < 0.05). FMD (NO-dependent) and PWV-adjusted values were strongly correlated in well-controlled HTN and NT subjects (r = − 0.74 and − 0.83, respectively). Although statistically significant, this correlation was lower in RHTN patients (r = − 0.43). Conclusion. We found a close relationship among high BP levels, endothelial dysfunction and vascular rigidity in hypertensive patients, demonstrated by a significantly higher increase in carotid–femoral PWV and a decrease in brachial artery FMD in RHTN when compared with well-controlled hypertensive patients. Although this study was not designed to test the prognostic, the vascular damage differences observed between patients with controlled vs uncontrolled hypertension suggest that the latter group may have a worse cardiovascular prognosis, requiring prospective assessment tests.

Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients

BackgroundHypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance) could be a common root for RHTN (resistant hypertension) or RHTN plus type 2 diabetes (T2D) comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D), and its relationship with serum adiponectin concentration.MethodsTwenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years) were evaluated using the following parameters: BMI (body mass index), biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV) in time and frequency domains stratified into three periods: 24 hour, day time and night time.ResultsBoth groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone) and night periods (sympathetic > parasympathetic tone). T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m2 - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04), lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04) and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r = 0.37 [95% CI -0.04 - 1.00] p = 0.03), negatively with HbA1c levels (r = -0.58 [95% CI -1.00 - -0.3] p = 0.00) and also adiponectin correlated negatively with HbA1c levels (r = -0.40 [95% CI -1.00 - -0.07] p = 0.02).ConclusionType 2 diabetes comorbidity is associated with greater autonomic imbalance, lower adiponectin levels and greater BMI in RHTN patients. Similar circadian disruption was also found in both groups indicating the importance of lifestyle behavior in the genesis of RHTN.

Recomendações brasileiras de ventilação mecânica 2013. Parte I

Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associacao de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in Sao Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.

High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension

Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml−1, respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl−1, respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r2=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

Nested-PCR using MPB64 fragment improves the diagnosis of pleural and meningeal tuberculosis

Fluids in which Mycobacterium tuberculosis are seldom found, such as pleural and cerebrospinal liquids, are good candidates to be studied using PCR techniques. We detail our experience with a PCR assay applied to pleural and cerebrospinal fluids using the primer MPB64. Seventy three specimens were analyzed: 30 pleural fluids (PF), 26 pleural biopsies (PB) and 17 cerebrospinal fluids (CSF). The gold standard for the diagnosis of tuberculous meningitis was the positive culture for M. tuberculosis in CSF. Tuberculous pleural effusion was diagnosed when cultures of PF and/or PB were positive for M. tuberculosis, or the PB histology showed granulomas. Our results, compared to the gold standards employed, showed a sensitivity of 70%, specificity of 88%, positive predictive value of 82% and negative predictive value of 80%. The high specificity of the MPB64 fragment while still retaining a good sensitivity makes it very well suited for pleural and cerebrospinal tuberculosis diagnosis.

Non-dipping pattern relates to endothelial dysfunction in patients with uncontrolled resistant hypertension

Resistant hypertension (RHTN) includes both patients whose blood pressure (BP) is uncontrolled on three or more medications (uncontrolled RHTN (UCRH)) and patients whose BP is controlled with use of four or more drugs (controlled RHTN (CRH)). It is unknown whether endothelial function and nocturnal drop demonstrate a similar pattern in patients with CRH and UCRH. We examined circadian BP patterns and vascular function in these patients. In all, 40 CRH and 26 UCRH patients, and 25 normotensives underwent biochemical testing, ambulatory BP monitoring, determination of brachial artery responses to endothelial-dependent (flow-mediated; dilation (FMD)) and independent (nitroglycerin mediated) stimuli. The nighttime drop in systolic BP (SBP) and diastolic BP (DBP) was less pronounced in UCRH than in CRH (SBP, 1.9±1.6 versus 4.9±1.7%; DBP, 7.5±1.8 versus 10.9±1.8%, UCRH and CRH, respectively; P<0.05). FMD was greater in control group compared with RHTN patients. Patients with UCRH had significantly impaired FMD compared with CRH (5.9±2.3% versus 7.1±5.1%; P<0.0001). Therefore, UCRH patients have less nocturnal dipping and a more impaired endothelial response compared with CRH patients. These findings suggest that important differences among patients with RHTN may allow identify subgroups with increased cardiovascular risk.

Aldosterone excess or escape: Treating resistant hypertension.

Aldosterone excess or “escape” can occur after treatment with medications that block the renin‐angiotensin‐aldosterone system or in undiagnosed primary aldosteronism. Spironolactone is thought to be an important addition to resistant hypertension (RH) treatment. In this study, resistant (RH) and controlled (CH) hypertensives and normotensive patients were submitted to echocardiography, flow‐mediated vasodilation, carotid intima‐media wall thickness studies, renin plasma activity, and aldosterone plasma levels and plasma and urinary sodium and potassium concentrations at baseline (pre‐spironolactone phase). Subsequently, for only RH and CH groups, 25 mg/d spironolactone was added to preexisting treatments over 6 months. Afterwards, these parameters were reassessed (post‐spironolactone phase). The RH and CH groups achieved reductions in blood pressure (P<.001), decreases in left ventricular hypertrophy (P<.001), improved diastolic function (Kappa index RH: 0.219 and Kappa index CH: 0.392) and increases in aldosterone concentrations (P<.05). The RH group attained improved endothelium‐dependent (P<.001) and independent (P=.007) function. Optimized RH treatment with spironolactone reduces blood pressure and improves endothelial and diastolic function and left ventricular hypertrophy despite the presence of aldosterone excess or escape.

Thrombolysis in massive pulmonary embolism based on the volumetric capnography

This is the first report of a patient submitted to chemical thrombolysis due to massive pulmonary embolism (PE) during the postoperative period of neurosurgery, in whom due to the lack of adequate clinical conditions, no imaging assessment was performed. Clinical, gasometric and capnographic data allowed the decision to perform the thrombolysis with safety. The P(a-et)CO2 gradient decreased from 46.4 mmHg to 11.8 mmHg (normal < 5 mmHg) and the end-tidal alveolar dead space fraction decreased from 0.85 to 0.37 (normal < 0.15) from the pre-thrombolysis period to the 7th day post-thrombolysis. We conclude that the volumetric capnography (VC) was useful in the patients diagnosis and clinical follow-up.This is the first report of a patient submitted to chemical thrombolysis due to massive pulmonary embolism (PE) during the postoperative period of neurosurgery, in whom due to the lack of adequate clinical conditions, no imaging assessment was performed. Clinical, gasometric and capnographic data allowed the decision to perform the thrombolysis with safety. The P(a-et)CO2 gradient decreased from 46.4 mmHg to 11.8 mmHg (normal < 5 mmHg) and the end-tidal alveolar dead space fraction decreased from 0.85 to 0.37 (normal < 0.15) from the pre-thrombolysis period to the 7th day post-thrombolysis. We conclude that the volumetric capnography (VC) was useful in the patients diagnosis and clinical follow-up.

Leptin and aldosterone in sympathetic activity in resistant hypertension with or without type 2 diabetes

BACKGROUND The finding of adipocyte-derived hormone leptin as an overstimulator of sympathetic activity brought a new perspective to the pathophysiological mechanisms of obesity-hypertension. OBJECTIVES As aldosterone also increases sympathetic activity, we aimed to assess the relationship between sympathetic overactivity and plasma leptin and aldosterone levels in resistant hypertension (RHTN), comparing the groups with and without T2D. METHODS Twenty-five RHTN patients underwent ambulatory electrocardiography to analyze heart rate variability (HRV) in time and frequency domains, which were stratified into two periods: 24 hours and daytime (DT), comprising the records between 2:00 p.m to 6:00 p.m (time domain) and one hour at 3:00 p.m (frequency domain). RESULTS T2D group (n=10) had higher serum aldosterone and plasma leptin levels than the non-T2D (n=15) (26.0 ± 11.5 vs. 16.9 ± 7.0 ng/dL - p=0.021; 81.368.7 ± 47.086.1 vs 41.228.1 ± 24.523.1 pg/mL - p=0.048, respectively). Both groups had aldosterone correlated with HRV in frequency domain. Non-T2D had aldosterone correlated with DT low frequency in normalized units (LF nu) (r=0.6 [0.12-0.85] p=0.018) and DT high frequency in normalized units (HF nu) (r=-0.6 [-0.85- -0.12] p=0.018). Type-2-diabetes group had aldosterone correlated with DT LF nu (r=0.72 [0.16-0.93] p=0.019) and DT HF nu (r=-0.72 [-0.93- -0.16] p=0.019). However, despite of the importance of leptin in sympathetic overactivity in hypertension, leptin did not correlate with HRV. CONCLUSION Aldosterone seems to overdrive sympathetic activity in RHTN with and without T2D. This information combined with the clinical efficacy of mineralocorticoid receptor blocker in RHTN may reinforce that aldosterone is a major player to be a therapeutic target in RHTN.