RESUMEN
Abstract Background: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). Objective: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. Methods: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. Results: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. Conclusion: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.
Resumo Fundamento: Evidências indicam que a inflamação sistêmica subclínica está presente na hipertensão arterial resistente (HAR). Objetivo: Desenvolver uma medida que integra citocinas envolvidas na fisiopatologia da HAR. Métodos: Indivíduos com HAR (n = 112) e indivíduos com hipertensão leve a moderada (HT) (n = 112) foram estudados em delineamento transversal. Valores de citocinas/adipocinas plasmáticas [TNF-alfa, interleucinas (IL)-6, -8, -10, leptina e adiponectina] foram divididos em tercis, e lhes atribuído um escore variando de 1 (tercil mais baixo) a 3 (tercil mais alto). O escore inflamatório (EI) de cada participante foi calculado como a soma do escore de cada citocina pró-inflamatória da qual subtraiu-se o escore de cada citocina anti-inflamatória (adiponectina e IL-10). O nível de significância aceito foi alfa = 0,05. Resultados: O EI foi mais alto nos indivíduos com HAR em comparação a indivíduos com HT [4 (2-6) vs. 3 (2-5); p = 0,02, respectivamente]. O EI correlacionou-se positivamente com parâmetros de gordura corporal, tais como índice de massa corporal (r = 0,40; p < 0,001), circunferência da cintura (r = 0,30; p < 0,001) e massa gorda avaliada por bioimpedância (r = 0,31; p < 0,001) em todos os indivíduos hipertensos. Análises de regressão logística mostraram que o EI foi um preditor independente de HAR (OR = 1,20; p = 0,02), independentemente de idade, sexo e raça; porém, o modelo perdeu significância estatística após ajuste para os parâmetros de gordura corporal. Conclusão: Um estado de inflamação subclínica definida pelo EI incluindo TNF-alfa, IL-6, IL-8, IL-10, leptina e adiponectina está associado com indivíduos obesos com HAR. Além disso, o escore correlaciona-se com parâmetros de obesidade, independentemente do grau de hipertensão. O EI pode ser usado na avaliação de condições que envolvem inflamação subclínica, tal como HAR relacionada à obesidade. O estudo também destaca a forte relação entre obesidade e inflamação.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Citocinas/sangre , Adipoquinas/sangre , Hipertensión/sangre , Estándares de Referencia , Índice de Severidad de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Índice de Masa Corporal , Modelos Logísticos , Tejido Adiposo , Estudios Transversales , Factores de Riesgo , Estadísticas no Paramétricas , Medición de Riesgo , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Obesidad/fisiopatología , Obesidad/sangreRESUMEN
BACKGROUND: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). OBJECTIVE: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. METHODS: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. RESULTS: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. CONCLUSION: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.
Asunto(s)
Adipoquinas/sangre , Citocinas/sangre , Hipertensión/sangre , Tejido Adiposo , Adulto , Anciano , Antihipertensivos/uso terapéutico , Índice de Masa Corporal , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/fisiopatología , Estándares de Referencia , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
Resumo: Introdução: Sabe-se que o risco cardiovascular (CV) aumenta com a falta de controle pressórico, além de outros fatores como diabetes mellitus, lesão em órgãos-alvo, obesidade, altas taxas de ingestão de sódio, sexo feminino e raça negra. Além disso, as doenças CV são causa de morte de 17,5 milhões de pessoas no mundo todos os anos, sendo a hipertensão arterial responsável por 14% das mortes no Brasil. Objetivos: O presente estudo avaliou (1) a ocorrência de eventos cardiovasculares ¿ acidente vascular cerebral (AVC), infarto do miocárdio (IM) e morte ¿ assim como, (2) os fatores associados à ocorrência de tais eventos, na população de hipertensos resistentes em ambulatórios especializados entre os anos de 1998 e 2017. Desenho de estudo e Métodos: Este estudo de coorte retrospectiva incluiu 156 pacientes com hipertensão arterial resistente (HAR) regularmente atendidos e acompanhados em ambulatórios especializados a partir de 1998 - Hospitais de Clínicas da Universidade Estadual de Campinas (UNICAMP) e Faculdade de Medicina de São José do Rio Preto (FAMERP). Foram avaliadas características gerais (idade, raça, gênero), exames bioquímicos, parâmetros antropométricos (índice de massa corporal), clínicos (pressão arterial ambulatorial e de consultório, hipertrofia cardíaca, microalbuminúria) e medicações em uso em dois períodos distintos, sendo a primeira e última consultas dos pacientes em seguimento. Resultados: Observou-se que, após a média de cinco anos de seguimento em ambulatórios especializados, 9% dos pacientes HAR apresentaram evento CV: AVC (6%); IM (3%) e morte (0,6%). Os pacientes HAR, ao final do seguimento, apresentaram um perfil clínico mais favorável em comparação ao momento inicial, quando foram observadas: (1) melhora do perfil pressórico de consultório (PAS: -18mmHg; PAD: -12mmHg) e 24h ( PAS 24h: -9mmHg; PAD 24h: -7mmHg) e (2) dos níveis de LDL-colesterol (-9,03mg/dL). A redução dos parâmetros pressóricos foi decorrente de alterações na conduta terapêutica, com aumento da prescrição de diferentes classes de anti-hipertensivos. De maneira interessante, o diabetes e uso de betabloqueadores no início do seguimento, foram associados, de maneira independente, à redução da pressão arterial sistólica no final do seguimento, assim como as estatinas. Por outro lado, a presença de obesidade foi associada inversamente à redução desses níveis. Os pacientes HAR que apresentaram algum evento CV tinham, tanto o nível pressórico de 24h quanto o de triglicérides, mais elevados em relação aos pacientes HAR que não apresentaram nenhum evento. Conclusão: Através do tratamento farmacológico otimizado, a redução dos parâmetros pressóricos e do perfil lipídico, pode ter sido favorável à baixa ocorrência de eventos CV na população estudada. Esses dados sugerem a importância de se prestar atendimento individualizado aos pacientes de alto risco CV. Além disso, o conhecimento dos fatores de risco CV pode contribuir para melhor se guiar a terapia farmacológica e, consequentemente, proporcionar maior sobrevida a grupos de alto risco CV, como o de pacientes HAR(AU)
Abstract: Background: It is known that cardiovascular (CV) risk increases with lack of blood pressure (BP) control, in addition to other factors such as diabetes mellitus, target organ damage, obesity, high sodium intake, female sex and black race. In addition, CV diseases are responsible for the deaths of 17.5 million people worldwide, it being known that hypertension accounts for 14% of deaths in Brazil. Objectives: This study evaluated (1) the occurrence of CV events - stroke, myocardial infarction (MI) and death - as well as (2) factors associated with the occurrence of such events in the population of hypertensive specialized outpatient clinics between 1998 and 2017. Design and Methods: This retrospective cohort study included 156 patients with resistant hypertension (RH) regularly attended and followed up in specialized outpatient clinics from 1998 ¿ in Clinical Hospital of the State University of Campinas (UNICAMP) and Medical School of São José do Rio Preto (FAMERP). General characteristics (age, race, gender), biochemical tests, anthropometric parameters (body mass index), clinical parameters (ambulatory and office BP, cardiac hypertrophy, microalbuminuria) and medications in use were evaluated in two distinct periods: at the beginning and at the end of this follow-up. Results: It was observed that, after a follow-up in specialized outpatient clinics that lasted, in average, five years, 9% of RH patients presented CV event: stroke (6%); MI (3%) and death (0.6%). At the end of the follow-up, the RH patients presented a more favorable clinical profile compared to the initial moment, when: (1) improvement of the office BP profile (SBP: -18mmHg; DBP: -12mmHg) and 24h: -9mmHg, DBP 24h: -7mmHg) and (2) LDL-cholesterol levels (-9.03mg/dL). The reduction in BP parameters was due to changes in therapeutic management, with an increase in the prescription of different classes of antihypertensives. Interestingly, diabetes and the use of beta-blockers at the beginning of follow-up were associated with a reduction in systolic BP in an independent way at the end of follow-up, as well as statins. On the other hand, the presence of obesity was inversely associated with the reduction of these levels. The RH patients who had a CV event had the 24h BP and the triglyceride levels higher than the RH patients who did not present any events. Conclusion: Through optimized pharmacological treatment the reduction of pressure parameters and lipid profile could have been favorable to the low occurrence of CV events in the study population. These data suggest the importance of providing individualized care to patients at high risk CV. In addition, knowledge of CV risk factors may contribute to better guiding pharmacological therapy and, consequently, providing greater survival rates to high-risk CV groups, such as in RH patients(AU)
Asunto(s)
Humanos , Masculino , Femenino , Anomalías Cardiovasculares , Hipertensión , Factores de Riesgo , Antihipertensivos , Antihipertensivos/administración & dosificación , Sistema Cardiovascular , Estudios de Cohortes , Diabetes Mellitus , Quimioterapia , Infarto del Miocardio , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular , Accidente Cerebrovascular/epidemiología , TerapéuticaRESUMEN
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.
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.
Asunto(s)
Quimiocina CCL2/análisis , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Remodelación Ventricular/fisiología , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
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.
Asunto(s)
Hipertensión/genética , Metaloproteinasa 2 de la Matriz/genética , Polimorfismo de Nucleótido Simple , Anciano , Brasil , Estudios de Casos y Controles , Femenino , Haplotipos , Humanos , Hipertensión/patología , Masculino , Persona de Mediana Edad , Pacientes AmbulatoriosRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hipertrofia Ventricular Izquierda/fisiopatología , Quimiocina CCL2/análisis , Remodelación Ventricular/fisiología , Hipertensión/fisiopatología , Índice de Severidad de la Enfermedad , Estudios Transversales , Monitoreo Ambulatorio de la Presión ArterialRESUMEN
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.
Asunto(s)
Resistencia a Medicamentos , Hipertensión/sangre , Hipertrofia Ventricular Izquierda/sangre , Metaloproteinasa 9 de la Matriz/sangre , Obesidad/sangre , Remodelación Vascular , Estudios Transversales , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Masculino , Metaloproteinasa 2 de la Matriz/sangre , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Inhibidor Tisular de Metaloproteinasa-1/sangreRESUMEN
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.
Asunto(s)
Antihipertensivos/uso terapéutico , Vasoespasmo Coronario/tratamiento farmacológico , Vasoespasmo Coronario/psicología , Diuréticos/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/psicología , Cumplimiento de la Medicación , Anciano , Antihipertensivos/administración & dosificación , Antihipertensivos/orina , Determinación de la Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Vasoespasmo Coronario/orina , Diuréticos/administración & dosificación , Diuréticos/orina , Estudios de Factibilidad , Femenino , Fluorometría , Humanos , Hipertensión/orina , Masculino , Persona de Mediana Edad , Proyectos Piloto , Sensibilidad y Especificidad , Triantereno/administración & dosificación , Triantereno/uso terapéutico , Triantereno/orinaRESUMEN
Resistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity. Low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated with RHTN. Single nucleotide polymorphisms (SNPs) -11377C/G (rs266729) and +276G/T (rs1501299) in ADIPOQ (adiponectin gene) were associated with hypertension. This study evaluated the association between two SNPs (-11377C/G and +276G/T) and adiponectin levels in RHTN. This study comprised 109 patients with RHTN genotyped for both polymorphisms. A cross-sectional study was designed to compare features of CC homozygous versus G allele carriers for -11377C/G and GG homozygous versus T allele carriers for +276G/T. Office and ambulatory BP measurements were similar among genotypes subgroups in both SNPs as well as the markers of target organ damage (arterial stiffness, left ventricular mass index and microalbuminuria). Adiponectin concentrations were significantly higher in CC compared to G carrier for -11377C/G (CC:7.0 (4.0-10.2) versus G allele:5.5 (2.5-7.9), p = 0.04) and lower in GG compared to T carrier for +276G/T (GG:5.3 (2.3-7.7) versus T allele:7.1 (3.6-10.5), p = 0.04). Adjusting for systolic ambulatory BP, body mass index, age, gender, race and presence of type 2 diabetes, multiple linear regression analyses revealed that the minor alleles G (ß-coefficient= -0.14, SE=0.07, p = 0.03) and T (ß-coefficient=0.12, SE=0.06, p = 0.04) were independent predictors of adiponectin. The -11377C/G and +276G/T SNPs in ADIPOQ were associated with adiponectin levels in RHTN individuals.