RESUMO
Systemic blood pressure (BP) may oscillate for homeostatic needs (equilibrium by constancy) or just as shifts in other intrinsic and extrinsic variables known as allostatic changes. This transitory pressure often rises alerts physicians to out-of-control hypertension or even hypertensive crisis. There is a very complex theory underlying these stochastic phenomena, which physicists and mathematicians translate into a single word: chaos. These changes happen according to a stochastic probabilistic pattern that presumes chaotic but somewhat predictable and nonlinear modeling of BP-related dynamics as a mathematical approach. Based on the chaos theory, small changes at the initial BP (baseline overtime) values could disturb the homeostasis leading to extreme BP chaotic shifts. These almost insignificant oscillations may also affect other variables and systems, leading to the misdiagnosis of hypertension, "out-of-control" BP levels, and resistant hypertension (RHT). Thus, these unpredictable and transient increases in BP values may be improperly diagnosed as the white coat and masked or resistant hypertension. Indeed, the interference of the chaos in any phenotype of (true or false) hard to control BP is not considered in clinical settings. This review provides some basic concepts on chaos theory and BP regulation. Besides pseudoresistant hypertension (lack of adherence, circadian variations, and others (white-coat, masked, early morning effects or hypertension), chaotic changes can be responsible for out-of-control hypertension.
Assuntos
Hipertensão , Hipertensão Mascarada , Hipertensão do Jaleco Branco , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão Mascarada/diagnóstico , Hipertensão do Jaleco Branco/diagnósticoRESUMO
Coarctation of the abdominal aorta is a rare etiology of intermittent claudication and refractory hypertension. Treatment is complex and requires knowledge of several vascular reconstruction techniques. We report a case of aortic coarctation at the level of the renal arteries, describing its treatment and presenting a literature review. Female patient, 65 years old, with refractory hypertension since the age of 35, using five antihypertensive medications at maximum doses. Blood pressure was 260/180mmHg and she had disabling claudication (less than 20 meters). Computed tomography angiography showed a 4mm coarctation in the juxtarenal aorta, with circumferential calcification at the stenosis site, and tortuous infrarenal aorta. Hybrid repair was performed with an iliac-birenal bypass and implantation of an Advanta V12 stent at the stenosis site. The patient's postoperative course was satisfactory, she was free from claudication, and her blood pressure 60 days after surgery was 140/80mmHg, taking two antihypertensive medications.
RESUMO
PURPOSE OF REVIEW: To perform a narrative systematic review on refractory hypertension (RfHT) with particular emphasis on prognosis. RECENT FINDINGS: There were 37 articles on RfHT, 13 non-systematic reviews, and 24 original studies. RfHT, a recently described extreme phenotype of anti-hypertensive treatment failure, shall be defined as uncontrolled out-of-office blood pressure (BP) levels despite the use of at least 5 anti-hypertensive drugs, including a long-acting diuretic and a mineraloreceptor antagonist. Its prevalence ranges from 0.5 to 4.3% of general treated hypertensives and between 3.6 and 51.4% of patients with resistant hypertension (RHT). RfHT is associated with younger age, African ancestry, obesity, hypertension-mediated organ damage and clinical cardiovascular diseases, and with some comorbidities, such as diabetes and obstructive sleep apnea. Its physiopathological mechanisms probably involve sympathetic overactivity and not volume overload. Patients with RfHT have a worse prognosis than non-refractory RHT individuals, with higher risks of adverse cardiovascular and renal outcomes and of mortality. RfHT represents a rare but true extreme phenotype of anti-hypertensive treatment failure distinct from RHT and with a significantly worse prognosis. Identifying such individuals is important to tailor specific interventions.
Assuntos
Hipertensão , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Diuréticos/uso terapêutico , Humanos , PrognósticoRESUMO
Resumo Coarctação da aorta abdominal é uma causa rara de claudicação de membros inferiores e hipertensão refratária. O tratamento é complexo e exige conhecimento de diversas técnicas de reconstrução vascular. Apresentamos um caso de coarctação ao nível das artérias renais, seu tratamento e revisão da literatura. Paciente feminina, 65 anos, com hipertensão refratária desde os 35 anos, utilizando cinco medicações anti-hipertensivas em dose máxima. Pressão arterial média de 260/180mmHg e claudicação incapacitante (menos de 20 metros) bilateral. Angiotomografia computadorizada demonstrou coarctação de aorta justarrenal de 4 mm de maior diâmetro, calcificação circunferencial no local da estenose e tortuosidade da aorta infrarrenal. Foi submetida a tratamento híbrido, com ponte ilíaco-birrenal e implante de stent Advanta V12 no local da estenose. A paciente evoluiu satisfatoriamente e, 60 dias depois da cirurgia, apresentava-se com uma pressão arterial de 140/80mmHg, em uso de apenas duas medicações anti-hipertensivas e sem claudicação.
Abstract Coarctation of the abdominal aorta is a rare etiology of intermittent claudication and refractory hypertension. Treatment is complex and requires knowledge of several vascular reconstruction techniques. We report a case of aortic coarctation at the level of the renal arteries, describing its treatment and presenting a literature review. Female patient, 65 years old, with refractory hypertension since the age of 35, using five antihypertensive medications at maximum doses. Blood pressure was 260/180mmHg and she had disabling claudication (less than 20 meters). Computed tomography angiography showed a 4mm coarctation in the juxtarenal aorta, with circumferential calcification at the stenosis site, and tortuous infrarenal aorta. Hybrid repair was performed with an iliac-birenal bypass and implantation of an Advanta V12 stent at the stenosis site. The patient's postoperative course was satisfactory, she was free from claudication, and her blood pressure 60 days after surgery was 140/80mmHg, taking two antihypertensive medications.
Assuntos
Humanos , Feminino , Idoso , Coartação Aórtica/cirurgia , Coartação Aórtica/complicações , Aorta Abdominal , Coartação Aórtica/diagnóstico , Artéria Renal , Stents , Angioplastia com Balão , Hipertensão Renovascular/cirurgia , Hipertensão Renovascular/etiologia , Claudicação Intermitente/cirurgia , Claudicação Intermitente/etiologiaRESUMO
Caso clínico de uma paciente com quadro de hipertensão arterial refratária, sendo inicialmente atribuída como etiologia a displasia de artéria renal. Os níveis pressóricos mantiveram elevados após a angioplastia de artéria renal, mantendo descontrole pressórico apesar do uso de 10 classes de anti-hipertensivos. Foi indicada a denervação de artéria renal e após tal, foi possível redução das medicações e êxito no controle de seus níveis tensionais. Destaca-se a importância do adequado diagnóstico de hipertensão arterial refratária, a exclusão de hipertensão secundária, somado à otimização terapêutica e indicação de procedimentos quando necessário, tendo como objetivo o melhor controle pressórico e consequente redução de lesões de órgãos-alvo e eventos cardiovasculares graves (AU).
It will be explained the patient clinical case of with refractory hypertension, which was initially attributed to renal artery dysplasia, but after the renal artery angioplasty, remained with high blood pressure levels despite adequate anti-hypertensive drugs administration. Renal denervation was indicated and after medications was reduced, with adequate blood pressure level control. It emphasizes the importance of secondary hypertension diagnosis, therapeutic optimization and specific therapies, if necessary, with the aim to take blood pressure control and the consequent reduction of target-organ damage and severe vascular events (AU).
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Artéria Renal/cirurgia , Artéria Renal/inervação , Hipertensão RenalRESUMO
Background The long-term prognosis of refractory hypertension (RfHT), defined as failure to control blood pressure (BP) levels despite an antihypertensive treatment with ≥5 medications including a diuretic and mineraloreceptor antagonist, has never been evaluated. Methods and Results In a prospective cohort study with 1576 patients with resistant hypertension, patients were classified as refractory or nonrefractory based on uncontrolled clinic (or office) and ambulatory BPs during the first 2 years of follow-up. Multivariate Cox analyses examined the associations between the diagnosis of RfHT and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular and all-cause mortality, after adjustments for other risk factors. In total, 135 patients (8.6%) had RfHT by uncontrolled ambulatory BPs and 167 (10.6%) by uncontrolled clinic BPs. Over a median Follow-Up of 8.9 years, 338 total CVEs occurred (288 major adverse CVEs, including 124 myocardial infarctions, and 96 strokes), and 331 patients died, 196 from cardiovascular causes. The diagnosis of RfHT, using either classification by clinic or ambulatory BPs, was associated with significantly higher risks of major adverse CVEs, cardiovascular mortality, and stroke incidence, with hazard ratios varying from 1.54 to 2.14 in relation to patients with resistant nonrefractory hypertension; however, the classification based on ambulatory BPs was better in identifying higher risk patients than the classification based on clinic BP levels. Conclusions Patients with RfHT, particularly when defined by uncontrolled ambulatory BP levels, had higher risks of major adverse CVEs and mortality in relation to patients with resistant but nonrefractory hypertension, supporting the concept of refractory hypertension as a true extreme phenotype of antihypertensive treatment failure.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/mortalidade , Hipertensão/complicações , Acidente Vascular Cerebral/mortalidade , Idoso , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Monitorização Ambulatorial da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial/estatística & dados numéricos , Brasil/epidemiologia , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/classificação , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Falha de TratamentoRESUMO
PURPOSE OF REVIEW: To gather data from studies evaluating the pro-inflammatory profile of individuals with resistant hypertension (RH), and bring a clinical update of new and potential complementary therapies to treat inflammation in RH. RECENT FINDINGS: Increases in pro-inflammatory cytokines are related to elevated blood pressure and target organ damage in RH patients. Clinical and experimental studies have shown that some biological therapies, especially TNF-α inhibitors, regulated pro- and anti-inflammatory cytokines associated with improvements in clinical outcomes, although they are not yet reported in RH. New emerging therapies to treat inflammation in RH, although promising, are still hypotheses that have not been scientifically confirmed in clinical trials. For this reason, inflammation-target treatments, such as the TNF-α and IL-6 inhibitors, should be encouraged for testing as complementary therapies in RH in order to elucidate their potential benefits.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Citocinas/imunologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Inflamação/imunologia , Citocinas/sangue , Humanos , Hipertensão/sangue , Inflamação/sangue , Inflamação/tratamento farmacológicoRESUMO
Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.
Resumo A Hipertensão Arterial Refratária (HARf) representa um fenótipo extremo da hipertensão arterial resistente (HAR), sendo considerada a falência ao tratamento apesar do uso de 5 ou mais classes de anti-hipertensivos, incluindo um diurético tiazídico de longa ação e um antagonista mineralocorticoide. A HAR é comum (10-20%) entre os hipertensos em geral, sendo decorrente de hiperatividade do Sistema Renina Angiotensina Aldosterona e retenção hidrossalina. Aqueles com HARf correspondem a 5-8% dos resistentes e parecem sofrer maior influência catecolaminérgica. Os resistentes tendem a ter maior idade, ao sobrepeso e à obesidade. Comorbidades incluem diabetes, apneia obstrutiva do sono e status de hiperaldosteronismo. Refratários são afro-americanos em maior proporção, mais jovens e, predominantemente, mulheres. Ambos são fortemente associados à elevada albuminúria, HVE, doenças cardio e cerebrovasculares, além da doença renal crônica. O fenômeno do jaleco branco parece ser mais evidente nos resistentes. Quanto ao tratamento, a intensificação da terapia diurética está indicada nos resistentes, enquanto na HARf, a falência à terapia impôs novas alternativas de tratamento ("simpaticolíticas"). Em conclusão, tanto a HAR quanto a HARf constituem-se desafios na prática clínica e devem ser abordadas como entidades clínicas distintas por profissionais especialistas que identifiquem comorbidades e venham a prover um tratamento específico, diversificado e individualizado.
Assuntos
Humanos , Resistência a Medicamentos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Fenótipo , Simpatolíticos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Terapias Complementares , Consumo de Bebidas Alcoólicas/efeitos adversos , Exercício Físico , Fumar/efeitos adversos , Prevalência , Monitorização Ambulatorial da Pressão Arterial , Dieta Hipossódica , Diuréticos/farmacologia , Abordagens Dietéticas para Conter a Hipertensão , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Anti-Hipertensivos/farmacologiaRESUMO
PURPOSE OF REVIEW: Resistant hypertension (RHTN) is a condition in which besides the antihypertensive therapy using at least three different drugs (including a diuretics), brachial blood pressure does not reach the target (e.g., 140/90 mmHg). RECENT FINDINGS: Despite the diversity of clinical presentations, we divide RHTN in two major groups according to blood pressure and number of drugs taken: controlled (C-RHTN) and uncontrolled (UC-RHTN) resistant hypertension, with refractory hypertension (RfHTN) included in the latter subgroup. Both C-RHTN and UC-RHTN are heterogenic and complex syndromes. To better approach this matter, the some pathophysiological mechanisms (increased volemia, hyperactivity, plasma cortisol, adipocitokines, and other pro-inflammatory factors), have a pivotal clinical role. Some features (African ethnic, obesity, age > 60, LV hypertrophy, and vascular stiffness) increase the risk of refractoriness as well as worst prognosis. Based on increased target organ damage, cardiovascular risk and events will be addressed in this review. Our conclusion is that although both C-RHTN and UC-RHTN are extreme phenotypes of hard-to-control BP, some mechanisms of the disease and clinical expressions are distinct. According to these differences, "UC-RHTN and C-RHTN are not in the same bag."
Assuntos
Hipertensão/fisiopatologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológicoRESUMO
BACKGROUND: Takayasu arteritis is a rare, chronic, granulomatous systemic vasculitis of unknown etiology and a few cases have been reported in pregnancy. In pregnancies concomitant with Takayasu arteritis or after diagnosis, Takayasu arteritis negatively affects pregnancy by increasing 13-fold the odds of complications such as hypertensive disorders. The best recommendations in this scenario are still to be made. CASE PRESENTATION: We present a case of 21-year-old, gravid 1, Mexican woman of Mestizo descent with chronic hypertension diagnosed since she was 15-years old who presented severe hypertension during pregnancy (early second trimester); the diagnosis of hypertensive disorder of pregnancy was ruled out requiring first-line and second-line antihypertensive therapy without serious associated maternal or fetal morbidity. CONCLUSIONS: Takayasu arteritis and pregnancy play an important role in maternal and fetal outcomes. Efforts should be made to further investigate the Takayasu arteritis diagnosis in pregnant women with refractory hypertension.
Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/etiologia , Nitroprussiato/administração & dosagem , Arterite de Takayasu/complicações , Antirreumáticos/uso terapêutico , Cesárea , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Período Pós-Parto , Gravidez , Rituximab/uso terapêutico , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) are enzymes involved in cardiovascular (CV) remodeling and hypertension-mediated target organ damage (TOD). Genetic polymorphisms in matrix metalloproteinase 2 (MMP-2) gene [-1575G/A (rs243866); -1306C/T (rs243865); and -735C/T (rs2285053)] are associated with several CV conditions, however the relationship between MMP-2 polymorphisms and resistant hypertension (RH) is unknown. We evaluated whether these genetic single nucleotide polymorphisms (SNPs) in MMP-2 gene are associated with 1) MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) levels in RH and mild to moderate hypertensive (HT) subjects, 2) left ventricular hypertrophy (LVH) and arterial stiffness and 3) the presence of RH. METHODS: One hundred and nineteen RH and 136 HT subjects were included in this cross-sectional study. Genotypes were determined by real-time PCR using TaqMan probes. Haplotypes were estimated using Bayesian method. RESULTS: The levels of MMP-2 and TIMP-2 were similar among genotypes and haplotypes for the three studied polymorphisms in HT and RH groups. RH showed higher frequency for GCC haplotype and lower frequency of GCT and ATC haplotypes (-1575G/A, -1306C/T and -735C/T, respectively) compared to HT (0.77 vs. 0.64; 0.09 vs. 0.17; 0.13 vs. 0.19, p=0.003 respectively). GCC haplotype was associated to RH apart from potential confounders (odds ratio (OR)=2.09; 95% confidence interval (CI)=1.20-3.64; p=0.01). In addition, CC genotype (OR=2.93; 95% CI=1.22-7.01; p=0.02) and C allele (OR=2.81; 95% CI=1.26-6.31; p=0.01) for -735C/T polymorphism were independently associated with RH. GCT haplotype was associated with reduced probability of having RH (OR=0.35; 95% CI=0.16-0.79; p=0.01). Finally, no relationship was found between studied MMP-2 SNPs and left ventricular hypertrophy and arterial stiffness in both groups. CONCLUSION: GCC haplotype carriers showed higher probability to have RH (odds ratio>1), while the GCT haplotype carriers showed lower probability to have RH, suggesting that the GCT haplotype may represent a protective genetic factor for the development of RH. These finds suggest that GCC and GCT haplotypes, and C allele and CC genotype of the -735C/T MMP-2 gene polymorphism may have a role in RH.
Assuntos
Hipertensão/genética , Metaloproteinase 2 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Idoso , Brasil , Estudos de Casos e Controles , Feminino , Haplótipos , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Pacientes AmbulatoriaisRESUMO
Abstract Background: Hypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood. Objective: This study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects. Methods: We enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography. Results: We found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population. Conclusion: Since MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata.
Resumo Fundamentos: A hipertensão arterial é um processo crônico de baixo grau inflamatório, associado com liberação de citocinas e desenvolvimento de lesão em órgãos-alvo. A desregulação dos níveis de proteína quimiotática de monócitos-1 (MCP-1) tem sido associada com elevação da pressão arterial e complicações cardiovasculares; porém, os mecanismos envolvidos são complexos e ainda não foram inteiramente elucidados. Objetivo: O objetivo deste estudo foi comparar os níveis de MCP-1 em pacientes com hipertensão resistente (HR) versus pacientes com hipertensão de grau leve a moderado (HAS) e sua associação com a presença ou ausência de hipertrofia ventricular esquerda (HVE) em todos os indivíduos hipertensos. Métodos: Foram incluídos 256 indivíduos hipertensos: 120 com HR e 136 com HAS. Foi investigada a relação entre os níveis circulantes de MCP-1 e pressão arterial, dados bioquímicos, perfil hematológico e dano cardíaco nos grupos HR e HAS. Os níveis plasmáticos de MCP-1 foram medidos por ELISA e a HVE foi avaliada por ecocardiografia. Resultados: Não encontramos diferença nos níveis de MCP-1 entre indivíduos com HR e HAS. Por outro lado, encontramos níveis mais baixos de MCP-1 em pacientes com HVE (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL [100 - 200 pg/mL], respectivamente, p = 0,005] em comparação a pacientes sem HVE. Um modelo de regressão logística ajustado para o índice de massa corporal (IMC), idade, raça, níveis de aldosterona e presença de diabetes e HR mostrou que os níveis medianos de MCP-1 (2,55 pg/mL [1,22 - 5,2 pg/mL], p = 0,01) estiveram independentemente associados com HVE em toda a população de hipertensos. Conclusão: Como os níveis de MCP-1 foram semelhantes em indivíduos tanto com HR quanto HAS e estiveram diminuídos em pacientes hipertensos com HVE, nosso estudo sugere uma possível redução nos níveis de MCP-1 em indivíduos hipertensos com HVE, independe do grau da hipertensão.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hipertrofia Ventricular Esquerda/fisiopatologia , Quimiocina CCL2/análise , Remodelação Ventricular/fisiologia , Hipertensão/fisiopatologia , Índice de Gravidade de Doença , Estudos Transversais , Monitorização Ambulatorial da Pressão ArterialRESUMO
Leptin is associated to the lack of blood pressure control as well as target organ damage in resistant hypertensive (RH) subjects. Single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) genes, respectively, are associated with cardiovascular disease and metabolic syndrome. We evaluated the association of these two SNPs with clinical and biochemical features in 109 apparent treatment-RH subjects (aTRH) and 125 controlled hypertensives. Homozygous genotypes GG (n = 43) vs. AA (n = 14) for rs7799039 and AA (n = 34) vs. GG (n = 26) genotypes for rs1137101 were compared in aTRH subjects. There was no difference in leptin levels among both SNPs. On the other hand, LEP SNP (GG vs. AA) associated with the levels of glycated haemoglobin (6.4 ± 1.4 vs. 7.8 ± 2.3%, p = 0.03), insulin (8.6 ± 4.6 vs. 30.6 ± 27.7 uUI/mL, p = 0.01), HDL-cholesterol (51 ± 16 vs. 39 ± 11 mg/dL, p = 0.001) and PWV (9.5 ± 2.1 vs. 11.2 ± 2.8 m/s, p = 0.03). LEPR SNP (AA vs. GG), associated with heart rate (69 ± 12 vs. 67 ± 12 bpm, p = 0.03), fat mass (31 ± 11 vs. 24 ± 8 kg, p = 0.03) and triglycerides levels (175 ± 69 vs. 135 ± 75 mg/dL, p = 0.03). These findings may be clinically useful for identifying a group of aTRH who may have a LEP and/or LEPR gene variants, which may predispose this specific group to worse or better outcomes.
Assuntos
Resistência a Medicamentos , Hipertensão , Leptina/genética , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Receptores para Leptina/genética , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores para Leptina/metabolismoRESUMO
The balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) plays a key role in the development of hypertension and obesity. We aimed to evaluate the levels of MMP-2 and 9 and TIMP-2 and -1 in obese and non-obese apparent treatment-resistant hypertensive subjects (aTRH) and its association with cardiac hypertrophy. This cross-sectional study enrolled 122 subjects and divided into obese aTRH (n = 67) and non-obese (n = 55) group. Clinical and biochemical data were compared between both groups, including office BP, ambulatory BP, plasma MMP-2 and 9, TIMP-2 and 1 and left ventricular mass index (LVMI). We found higher MMP-9 levels and MMP-9/TIMP-1 ratio in obese aTRH subjects but no difference in MMP-2 and TIMP-1 levels. Obesity influenced MMP-9 levels [ß = 20.8 SE =8.6, p = 0.02) independently of potential confounders. In addition, we found a positive correlation between MMP-9 and anthropomorphic parameters. Finally, obese aTRH subjects with left ventricular hypertrophy (LVH) had greater MMP-9 levels compared with non-obese with LVH. Our study suggests that MMP-9 levels are influenced by obesity and may directly participate in the progressive LV remodelling process, suggesting a possible role for a higher cardiovascular risk in apparent resistant hypertensive subjects.
Assuntos
Resistência a Medicamentos , Hipertensão/sangue , Hipertrofia Ventricular Esquerda/sangue , Metaloproteinase 9 da Matriz/sangue , Obesidade/sangue , Remodelação Vascular , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológico , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
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.
Assuntos
Anti-Hipertensivos/uso terapêutico , Vasoespasmo Coronário/tratamento farmacológico , Vasoespasmo Coronário/psicologia , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Adesão à Medicação , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/urina , Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Vasoespasmo Coronário/urina , Diuréticos/administração & dosagem , Diuréticos/urina , Estudos de Viabilidade , Feminino , Fluorometria , Humanos , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e Especificidade , Triantereno/administração & dosagem , Triantereno/uso terapêutico , Triantereno/urinaRESUMO
La hipertensión arterial afecta a más de 1.200 millones de personas en el mundo y constituye uno de los factores de riesgo más importantes en la incidencia del infarto agudo de miocardio y el accidente cerebrovascular. Solo el 35% de los pacientes hipertensos se encuentran con valores de la presión arterial (PA) controlados con el uso de medicamentos antihipertensivos. Surge una alternativa, la denervación renal como técnica invasiva, la cual ha demostrado disminuir significativamente los valores de la PA en pacientes con hipertensión arterial resistente, y aunque ha sido debatida y controvertida luego de la publicación del estudio SYMPLICITY HTN-3, en el que no se apreció reducción significativa de las cifras de la presión arterial utilizando el Monitoreo Ambulatorio de Presión Arterial (MAPA), como herramienta de evaluación, surgen muchos interrogantes por resolver sobre esta nueva técnica y su aplicación en el campo clínico. El objetivo del presente reporte es describir detalladamente dos casos de hipertensión arterial resistente, tratados mediante ablación con radiofrecuencia con el nuevo dispositivo Vessix® de la compañía Boston Scientific.
Hypertension affects more than 1,200 people in the world, and constitutes one of the most important risk factors for the incidence of acute myocardial infarction and cerebrovascular accident. Only 35% of hypertensive patients show controlled blood pressure (BP) values with the use of hypertensive drugs. Al alternative becomes available: renal denervation as an invasive technique. It has shown to significantly reduce the BP levels in patients with resistant hypertension, and though it was discussed and controversial after the publication of the SYMPLICITY HTN-3 trial, where no significant reduction of BP values using the ambulatory blood pressure monitoring (ABPM) was noted, many questions have yet to be answered regarding this new technique and its application in the clinical field. The motivation for this report is to accurately describe two cases of resistant hypertension treated with radiofrequency ablation with the new Vessix® device from the company Boston Scientific.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Hipertensão Arterial Pulmonar , Ablação por Cateter , Angioplastia com BalãoRESUMO
BACKGROUND: Impaired endothelial function and arterial stiffness are associated with hypertension and are important risk factors for cardiovascular events. Reactive oxygen species reduce nitric oxide bioavailability and have a pivotal role in endothelial function. Resistant hypertension (RHTN) is characterized by blood pressure (BP) above goal (140/90mmHg) in spite of the concurrent use of ≥3 antihypertensive drugs of different classes. This study evaluated the association between 8-isoprostane levels, an oxidative stress marker, endothelial function and arterial stiffness, in RHTN. METHODS: Ninety-four RHTN and 55 well-controlled hypertensive (HT) patients were included. Plasma 8-isoprostane levels were determined by ELISA. Also, flow-mediated dilation (FMD) and pulse wave velocity (PWV) were evaluated to determine endothelial function and arterial stiffness, respectively. RESULTS: Levels of 8-isoprostane were markedly higher in RHTN compared to HT patients (22.5±11.2 vs. 17.3±9.8pg/ml, p<0.05, respectively). A significant inverse correlation was observed between FMD and 8-isoprostane (r=-0.35, p=0.001) in RHTN. Finally, multiple logistic regression revealed that 8-isoprostane was a significant predictor of endothelial dysfunction (FMD≤median) in RHTN group. CONCLUSION: RHTN showed markedly higher oxidative stress measured by 8-isoprostane, compared to HT patients. Taken together, our findings suggest the involvement of oxidative stress in endothelial function in RHTN.
Assuntos
Dinoprosta/análogos & derivados , Resistência a Medicamentos , Endotélio Vascular/patologia , Hipertensão/sangue , Hipertensão/patologia , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Dinoprosta/sangue , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Rigidez Vascular/efeitos dos fármacosRESUMO
JUSTIFICATIVA E OBJETIVOS: A grande maioria dos pacientes portadores de hipertensão arterial sistêmica (HAS) apresenta a forma primária. O diagnóstico de hipertensão arterial (HA) secundário sempre deve ser considerado, correspondendo à prevalência de até 5% dos pacientes hipertensos.O objetivo deste estudo foi ressaltar a importância do reconhecimento clínico precoce da HA secundária, através de anamnese, observação clínica e exame físico minudentes, no exame médico habitual.RELATO DO CASO: Paciente do sexo feminino, 49 anos, portadora de HA refratária a todos os tratamentos farmacológicos instituídos, com diagnóstico tardio de HA secundária. Como sintomas, apresentava cefaleia e precordialgia associada aos esforços. Foi tratada por quase toda vida como HA primária.CONCLUSÃO: Diagnosticar uma causa específica de HA secundária, embora pouco frequente, apenas com um exame físico e anamnese adequados, pode ser necessário para realizar um tratamento definitivo, resolvendo a hipertensão de difícil controle.Ressalta-se também a importância de uma propedêutica qualificada no pré-operatório para evitar complicações cirúrgicas, pós-cirúrgicas e causas secundárias que necessitem correções.
BACKGROUND AND OBJECTIVES: Although the vast majority of patients with secondary systemic blood pressure (SBP) have the primary form, the diagnosis of secondary hypertension should always be evaluated, corresponding to 5% of hypertensive patients. The aim of this study is to highlight the importance of early clinical recognition of secondary hypertension by accurate history, physical examination and clinical observations in theu sual medical examination.CASE REPORT: Female, 49 year-old patient, with hypertension refractory to all drug treatments, with late diagnosis of secondary hypertension. The symptoms were headache and exercise-related chest pain. She has been treated for primary hypertension almost all her life long.CONCLUSION: Making the diagnosis of a specific cause of secondary hypertension, only with physical examination and history, although uncommon, may be necessary in order to givea definitive treatment, solving difficult-to-control hypertension.We also emphasize the importance of a qualified preoperative workup to prevent surgical, post-surgical complications and secondary causes that require corrections.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Pressão Arterial , Hipertensão/diagnósticoRESUMO
Se reporta el caso de una paciente con hipertensión paroxística asociada a síntomas adrenérgicos, en quien se encontraron niveles elevados de metanefrinas totales en orina de 24 horas, hipopotasemia persistente y nódulo en la glándula suprarrenal. Fue llevada a cirugía en la que se identificaron dos masas suprarrenales, una con características histológicas de feocromocitoma y otra de adenoma suprarrenal.
We report the case of a female patient with paroxysmal hypertension associated with adrenergic symptoms. Elevated levels of total metanephrines in 24 hour urine were found, as well as persistent hypokalemia and a nodule in the adrenal gland. She was taken to surgery, and two adrenal masses were identified, one with histological characteristics of pheochromocytoma and another one of adrenal adenoma.
Assuntos
Hipertensão , NeoplasiasRESUMO
Electrical stimulation of baroreceptor afferents was used in the 1960's in several species, including human beings, for the treatment of refractory hypertension. This approach bypasses the site of baroreceptor mechanosensory transduction. Chronic electrical stimulation of arterial baroreceptors, particularly of the carotid sinus nerve (Hering's nerve), was proposed as an ultimate effort to treat refractory hypertension and angina pectoris due to the limited nature of pharmacological therapy available at that time. Nevertheless, this approach was abandoned in the early 1970's due to technical limitations of implantable devices and to the development of better-tolerated antihypertensive medications. More recently, our laboratory developed the technique of electrical stimulation of the aortic depressor nerve in conscious rats, enabling access to hemodynamic responses without the undesirable effect of anesthesia. In addition, electrical stimulation of the aortic depressor nerve allows assessment of the hemodynamic responses and the sympathovagal balance of the heart in hypertensive rats, which exhibit a well-known decrease in baroreflex sensitivity, usually attributed to baroreceptor ending dysfunction. Recently, there has been renewed interest in using electrical stimulation of the carotid sinus, but not the carotid sinus nerve, to lower blood pressure in conscious hypertensive dogs as well as in hypertensive patients. Notably, previous undesirable technical outcomes associated with electrical stimulation of the carotid sinus nerve observed in the 1960's and 1970's have been overcome. Furthermore, promising data have been recently reported from clinical trials that evaluated the efficacy of carotid sinus stimulation in hypertensive patients with drug resistant hypertension.