RESUMO
AIMS: The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function. MAIN METHODS: Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies. KEY FINDINGS: All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (ß -0.347; P<0.05). SIGNIFICANCE: These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Imunidade Inata/efeitos dos fármacos , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Feminino , Humanos , Hidroclorotiazida/farmacologia , Hipertensão/imunologia , Imunidade Inata/imunologia , Indapamida/farmacologia , Masculino , Pessoa de Meia-Idade , Perindopril/farmacologia , Método Simples-CegoRESUMO
Obesity and hypertension have been recognized as inflammatory diseases capable of activating the immune system, thus contributing to an increased cardiovascular risk. However, the link between adaptive immunity, obesity, and hypertension is poorly understood. We investigated the relationship of the body mass index (BMI) on the inflammatory, vascular, and immune responses in patients with hypertension naïve of anti-hypertensive treatment. Hypertensive patients (N = 88) were divided into three groups: normal weight (NW), overweight (OW), and obese (OB) subjects. Anti-oxidized LDL autoantibodies (anti-oxLDL Abs), anti-ApoB-D peptide (anti-ApoB-D) Abs, interleukin (IL)-8 and IL-10, flow-mediated dilation (FMD) of the brachial artery, and 24-h ambulatory blood pressure monitoring (ABPM) were assessed. OB patients presented lower levels of anti-oxLDL Abs and IL-10, higher levels of IL-8, and impaired FMD, when compared to NW and OW (P < 0.05), without differences between groups regarding anti-ApoB-D Abs. After adjusting for age, systolic and diastolic blood pressure, anti-oxLDL Abs were inversely correlated with BMI and waist circumference (r = -0.24, P = 0.02 and r = -0.25, P = 0.02, respectively), whereas ApoB-D correlated with 24-h ABPM (r = 0.22, P = 0.05 for systolic, and r = 0.29, P = 0.01 for diastolic blood pressure). Regression analyses showed inverse associations of anti-oxLDL Abs with BMI (ß = -0.05, P = 0.01) and waist circumference (ß = -0.01, P = 0.02); anti-ApoB-D Abs were associated with systolic and diastolic 24-h ABPM (ß = 0.96, P = 0.04; ß = 1.02, P = 0.005, for systolic and diastolic 24-h ABPM, respectively). Among hypertensive patients, obesity modulates the immune and inflammatory milieu, determining an unfavorable balance of cytokines and reduction in titers of anti-oxLDL Abs. Twenty-four hour ABPM is associated with titers of anti-ApoB-D Abs.
Assuntos
Hipertensão/complicações , Hipertensão/imunologia , Lipoproteínas LDL/imunologia , Obesidade/imunologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Apolipoproteínas B/imunologia , Apolipoproteínas D/imunologia , Autoanticorpos/sangue , Pressão Sanguínea , Índice de Massa Corporal , Feminino , Humanos , Hipertensão/tratamento farmacológico , Interleucina-10/sangue , Interleucina-8/sangue , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Obesidade/complicações , Obesidade/metabolismoRESUMO
A hipertensão arterial (HA) é um dos principais fatores de risco para a morbimortalidade cardiovascular. Os polimorfismos do sistema renina-angiotensina-aldosterona (SRAA) estão envolvidos na fisiopatologia da HA. Estudos mostram que afrodescendentes tendem a ser hipertensos com taxa mais alta de complicações. Este estudo teve por objetivo avaliar a prevalência dos polimorfismos do SRAA - da enzima conversora de angiotensina (ECA I/D), do antagonista do receptor da angiotensina II (AT1R A/C1166) e da aldosterona sintase (CYP11B2-344T/C) - em pacientes hipertensos afrodescendentes em tratamento. Vinte e três pacientes hipertensos afrodescendentes foram avaliados clinicamente (pressão arterial - PA e índice de massa corporal - IMC), laboratorialmente (perfil lipídico, creatinina e glicemia) e foram analisados os polimorfismos da ECA, AT1R e CYP por PCR. Os dados obtidos foram comparados com os de 21 hipertensos não afrodescendentes. Não houve diferença significativa na PA, IMC e perfil metabólico entre os grupos. Entretanto, o estudo dos polimorfismos do SRAA revelou diferenças significativas na distribuição dos genótipos (grupo I afro e II não afro): a frequência para os genes da ECA foi 47,8% DD, 43,5% DI e 8,7% I vs. 14,3% DD, 47,6% DI e 38,1% II (p=0,0017); para genes do AT1R: 100% AA, 0% AC e 0% CC no I vs. 33,3,% AA, 22,2% AC e 44,4% CC no II (p <0,0001); e, para o gene CYP11B2: 56% TT, 21,7% TC e 4,3% CC no I vs. 33% TT, 77,7% TC e 5,5% CC no II (p=0,034) entre os afrodescendentes e controles, respectivamente. Os resultados sugerem diferenças genéticas entre os pacientes hipertensos afrodescendentes no grupo estudado.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hipertensão/complicações , Hipertensão/mortalidade , Polimorfismo Genético/genética , Sistema Renina-Angiotensina , Fatores de RiscoRESUMO
BACKGROUND: Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of antihypertensive therapeutic regimens. METHODS: Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of antihypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS: Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS: We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.
Assuntos
Anti-Hipertensivos/uso terapêutico , Autoanticorpos/metabolismo , Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Lipoproteínas LDL/imunologia , Idoso , Apolipoproteínas/sangue , Biomarcadores , Análise Química do Sangue , Pressão Sanguínea/efeitos dos fármacos , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Endotélio Vascular/fisiologia , Feminino , Humanos , Inflamação/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Vasodilatação/fisiologiaRESUMO
BACKGROUND: Oxidized lipoproteins and antibodies anti-oxidized low-density lipoprotein (anti-oxLDL) have been detected in human plasma and in atherosclerotic lesions. However, the role of these autoantibodies in the maintenance of vascular health or in the pathogenesis of acute vascular insults remains unclear. We examined the relationship of human immunoglobulin G (IgG) anti-oxLDL antibodies with cardiovascular disease risk markers in stable subjects and in patients after an acute coronary syndrome (ACS). METHODS: Titers of human anti-oxLDL antibodies were measured in hypertensive subjects in primary prevention (n=94), without other risk factors, and in individuals after a recent ACS event who also had metabolic syndrome (n=116). Autoantibodies against copper ion oxidized LDL were measured by enzyme-linked-immunosorbent assay. RESULTS: Anti-oxLDL titers were higher in hypertensive patients and these subjects presented lower high sensitivity C-reactive protein (hs-CRP) than those with ACS (p<0.0001). We found significant correlations between anti-oxLDL and hs-CRP (r=-0.284), body mass index (r=-0.256), waist circumference (r=-0.368), apolipoprotein B (r=-0.191), glucose (r=-0.303), systolic blood pressure (r=0.319), diastolic blood pressure (r=0.167), high-density lipoprotein cholesterol (r=0.224) and apolipoprotein A1 (r=0.257) (p<0.02 for all). After multiple linear regression hs-CRP, fasting glucose and waist circumference remained independently and inversely associated with anti-oxLDL. CONCLUSIONS: Acute inflammatory and metabolic conditions decrease titers of human antibodies of IgG class against oxidized LDL, and that circulating anti-oxLDL antibodies could be associated with a protective role in atherosclerosis.
Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Lipoproteínas LDL/imunologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/imunologia , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/imunologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
O melhor conhecimento da história natural da aterosclerose revelou a importância crucial dos lipídeos. Dessa forma , têm sido propostas intervenções mais agressivas sobretudo para os pacientes em prevenção ou sob alto ou muito alto risco de eventos coronários. Hoje, com os fármacos disponíveis, essas metas têm sido alcançadas com maior facilidade. Embora esses fármacos sejam muito seguros , segundo cuidados, especialmente para doses elevadas ou quando associados, são importantes.