Antihypertensive therapy increases natural immunity response in hypertensive patients.

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.

Perindopril and barnidipine alone or combined with simvastatin on hepatic steatosis and inflammatory parameters in hypertensive patients.

UNLABELLED: The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree. One hundred and forty nine mild to moderate hypertensive, normocholesterolemic, overweight or obese outpatients with hepatic steatosis were enrolled. They were treated with perindopril 5mg/day, or barnidipine, 20mg/day, for 6 months; subsequently simvastatin, 20mg/day was added to both treatments for further 6 months. Blood pressure variation was recorded. Patients also underwent an ultrasound examination, at baseline and after 6, and 12 months. We also assessed: fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), tumor necrosis factor-α (ΤΝF-α), interleukin-6 (IL-6), high-sensitivity C reactive protein (Hs-CRP). Both perindopril and barnidipine reduced blood pressure, with barnidipine being more effective. Barnidipine, but not perindopril, slightly decreased total cholesterol and triglycerides after 6 months compared to baseline; lipid profile improved in both groups when simvastatin was added. Regarding inflammatory parameters, barnidipine reduced TNF-a, IL-6, and Hs-CRP, both in monotherapy, and after simvastatin addition. Hepatic steatosis parameters improved only when simvastatin was added. We can conclude that barnidipine better reduced blood pressure compared to perindopril and inflammatory parameters. Regarding hepatic steatosis parameters, only the addition of simvastatin improved them. REGISTRATION NUMBER: NCT02064218, ClinicalTrials.gov.

Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients.

OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45-/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05) and better left ventricle function (p<0.01). CONCLUSIONS: The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients.

Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients

OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (p<0.05) and better left ventricle function (p<0.01). CONCLUSIONS: The use of angiotensin-converting enzyme inhibitors represents a novel approach for improving cardiovascular repair after acute myocardial infarction in T2DM patients. .

Hypertensive urgencies in the emergency department: evaluating blood pressure response to rest and to antihypertensive drugs with different profiles.

To study the efficacy of a treatment strategy for the management of hypertensive urgencies, the authors evaluated 549 patients admitted to the emergency department. They were first assigned to a 30-minute rest period, then a follow-up blood pressure measurement was carried out. Patients who did not respond to rest were randomly assigned to receive an oral dose of an antihypertensive drug with different mechanisms of action and pharmacodynamic properties (perindopril, amlodipine, or labetalol), and blood pressure was reassessed at 60- and 120-minute intervals. A satisfactory blood pressure response to rest (defined as postintervention systolic blood pressure < 180 mm Hg and diastolic blood pressure < 110 mm Hg, with at least a 20 mm Hg reduction in basal systolic blood pressure and/or a 10-mm Hg reduction in basal diastolic blood pressure) was observed in 31.9% of population. Among nonresponders, 79.1% had a satisfactory blood pressure response to the antihypertensive drug treatment in a 2-hour average follow-up period. No major adverse events were observed. This treatment strategy, based on standardized rest as an initial step and different antihypertensive drugs, can be effective and safe for the management of patients with hypertensive urgencies.

Effects of dual blockade of the renin angiotensin system in hypertensive type 2 diabetic patients with nephropathy.

AIM: To evaluate the effects of combined treatment of an ACE inhibitor and an angiotensin II receptor antagonist on parameters related to the progression of renal disease in type 2 diabetic patients. METHODS: 20 hypertensive type 2 diabetic patients with non-nephrotic proteinuria (0.5 - 3.0 g/day) and estimated creatinine clearance > or = 40 ml/min/1.73m2 were randomly assigned to be treated with perindopril 8 mg/day (Per), irbesartan 300 mg/day (Irb) or a combination of both with the same doses (Per + Irb). Each treatment phase lasting 16 weeks was preceded by a four-week washout period. Diuretics, clonidine and hydralazine were used as supplementary drugs for blood pressure control. Patients were evaluated at baseline and at the end of each treatment phase. RESULTS: 15 (3M/12F) patients completed all the phases. Use of Per, Irb and Per + Irb led to a reduction in 24-hour mean blood pressure of 6 mmHg, 4 mmHg and 4 mmHg, respectively. Changes in glomerular filtration rate were not significant at any phase. Renal plasma flow was significantly more elevated with Irb than Per. Treatment with both Irb and Per + Irb induced similar plasma renin elevation, but treatment with Per did not, suggesting escape. Plasma aldosterone was reduced only by treatment with Per + Irb (-36%, p < 0.02). Reduction in proteinuria during Per + Irb (-33%) was not significantly different from Per (-34%) or Irb (-22%). Urinary transforming growth factor beta1 (TGF-beta1) excretion was significantly reduced with both Irb (-24%, p < 0.05) and Per + Irb (-36%, p < 0.05) but not with Per (-11%, p = 0.60). CONCLUSION: Only combined therapy with irbesartan plus perindopril concurrently reduces plasma aldosterone, proteinuria and urinary TGF-beta1.

Angiotensin-converting enzyme inhibition and angiogenesis in myocardium of obese Zucker rats.

BACKGROUND: Obesity, hypertension, and non-insulin-dependent diabetes mellitus (NIDDM) are associated with microvascular rarefaction in the myocardium and this contributes to increase cardiovascular morbidity and mortality. At present, controversial data exist in medical literature regarding the specific role of angiotensin-converting enzyme (ACE) inhibitors concerning angiogenesis in different tissues. The present study was designed to determine the possible beneficial effects of an ACE inhibitor perindopril on myocardial angiogenesis in an animal model of obesity, hypertension, and NIDDM, such as the obese Zucker rat (OZR) and control lean Zucker rats (LZR). METHODS AND RESULTS: Ten-week-old male OZR (fa/fa) and LZR (Fa/fa) were used in this study: OZR group (G1, n = 10), OZR with perindopril group (G2, n = 10); LZR group (G3, n = 10). For 6 months, G2 received a daily dose of 3 mg/kg of perindopril, by gavage, and G1 and G3 received an equal volume of vehicle throughout the experiment. After 6 months of treatment, all rats were killed, hearts were harvested for pathology studies, including immunohistochemistry, using monoclonal antibodies against rat endothelial cell (RECA-1) and endothelial nitric oxide synthase. At the end of the study, OZR treated with perindopril presented: 1) lower blood pressure (BP) (127 +/- 3.2 v 152.4 +/- 3 mm Hg, P <.01) and 2) lower heart weight/100 g body weight (0.22 +/- 0.02 v 0.36 +/- 0.04 g, P <.01) than OZR untreated. Moreover, OZR that received perindopril showed higher: 1) myocyte density (2044 +/- 67 v 847 +/- 91 myocytes/mm(2), P <.01) and 2) capillary density (1348 +/- 118 v 436 +/- 78 capillaries/mm(2), P <.01); higher amount of: 1) vascular endothelial growth factor (VEGF) in the myocardium (P <.01) and higher percentage of capillaries with positive immunostaining for eNOS (P <.01), compared with untreated OZR. There was a correlation between both the amount of VEGF in myocardium and the number of capillaries (r = 0.88; P <.01) and VEGF and eNOS expression in myocardial capillaries (r = 0.93; P <.01) in OZR treated with perindopril. Finally, OZR that received P showed an improvement in insulin/glucose ratio (P <.01) when compared with untreated OZR. CONCLUSIONS: These results suggest that ACE inhibition by perindopril improves myocardial angiogenesis in this animal model of human metabolic syndrome. The pathway that involves bradykinin, eNOS, and VEGF could be involved in this effect; however, because no additional antihypertensive treatment group was included in our study, the BP-lowering effect cannot be excluded.

[Pulse wave velocity and urinary albumin excretion in hypertensive patients treated with perindopril]. / Velocidad de la onda de pulso y la excreción urinaria de albúmina en pacientes hipertensos tratados con perindopril.

Systolic and diastolic blood pressures and urinary albumin excretion (UAE) have been recognized as predictors for cardiovascular risk. Furthermore, arterial compliance (AC) disorders assessed by increased aortic pulse wave velocity (PWV) are closely related to changes in blood pressure and strongly correlated with cardiovascular mortality and presence or extent of atherosclerosis. Our purpose in the present study was to determine a relationship between AC using PWV and UAE in a group of non-smoking patients with essential hypertension, and the level of interaction of ACE inhibition on these two variables. A total of 70 non-smoking never treated hypertensive patients (33 men and 37 women), aged 50 +/- 7 years (range 35-69), have been enrolled in this study. All of them underwent PWV by a computerized device (Complior) and UAE determination by radial immunodiffusion method, on baseline and after six months of treatment with perindopril (4.6 +/- 1.4 mg/day). We have found a significant decrease of systolic blood pressure (160.2 +/- 10.6 vs. 131.9 +/- 7.1 mmHg, p < 0.01), diastolic blood pressure (100.6 +/- 5 vs. 81.6 +/- 4.8 mmHg, p < 0.01), PWV (13.4 +/- 1 vs. 9.1 +/- 0.9 m/sec, p < 0.01), and UAE (42.2 +/- 19.3 vs. 11.1 +/- 3.6 mg/day, p < 0.01) at the end of the sixth month when they were compared to baseline values. Furthermore, renal function was also improved by the treatment at the end of the study as illustrated by creatinine clearance (87.5 + 22.5 vs. 102.1 + 23.5 ml/min, p < 0.01). Moreover, a high positive correlation between UAE and PWV at the beginning of the study (r = 0.81; p < 0.01) and after six months of treatment (r = 0.66; p < 0.01) was observed. In addition, PWV vs. UAE, differences between sixth month and baseline have shown a high correlation (r = 0.67; p < 0.01) and using a multiple regression test we found that PWV (t ratio 5.76; p < 0.001) was the most important and significant independent variable that correlates with UAE. These results suggest the existence of a real link between UAE and AC in non-smoking patients with arterial hypertension, and that ACE inhibition can similarly modify these two parameters.

Velocidad de la onda de pulso y la excrecion urinaria de albumina en pacientes hipertensos tratados con perindopril / Pulse wave velocity and urinary albumin excretion in hypertensive patients treated with perindopril

La presión arterial sistólica, la presión arterial diastólica y la excreción urinaria de albúmina (EUA)han sido reconocidas como predictores de riesgo cardiovascular. Además, los trastornos de la compliancearterial (CA) evaluados mediante la velocidad de la onda de pulso elevada (VOP) están estrechamente relacionadoscon los cambios de la presión arterial y correlacionados con la mortalidad cardiovascular y la presencia deateroesclerosis. El objetivo primario de este estudio ha sido determinar la relación entre la VOP y la EUA en un grupo de pacientes no fumadores con hipertensión esencial y secundariamente evaluar los cambios producidos por un inhibidor de la enzima convertidora de angiotensina (perindopril) sobre estas dos variables. En el estudio participaron setenta pacientes (33 hombres y 37 mujeres) hipertensos no fumadores, sin tratamiento previo, de 50 ± 7 años (entre 35-69). La VOP de todos los pacientes fue estudiada por medio de un dispositivo computarizado (Complior O ) en el período basal y a los seis meses de tratamiento con perindopril. También se determinó la EUA por el método de inmunodifusión radial al inicio del tratamiento y luego de seis meses de tratamiento con perindopril (4.6 ± 1.4 mg/día). Al finalizar el estudio se observó una reducción significativa de la presión arterial sistólica (PAS) (160.2 ± 10.6 vs. 131.9 ± 7.1 mmHg, p<0.01), presión arterial diastólica (PAD) (100.6 ± 5 vs. 81.6 ± 4.8 mmHg, p<0.01), VOP (13.4 ± 1 vs. 9.1 ± 0.9 m/seg, p<0.01) y EUA (42.2 ± 19.3 vs.11.1 ± 3.6 mg/día, p<0.01) al comparar estos valores con los del período basal. Por otra parte, la función renal evaluada por clearance de creatinina mostró una significativa mejoría en relación a losvalores iniciales (87.5 ± 22.5 vs. 102.1 ± 23.5 ml/min, p<0.01). Asimismo, se apreció una significativa correlación po-sitiva entre la EUA y la VOP al inicio del estudio (r = 0.81; p<0.01) y después de seis meses de tratamiento (r = 0.66; p<0.01). Además, en la VOP vs. la EUA, las diferencias entre el sexto mes y el punto de partida, también, demostra-ron una significativa correlación (r= 0.67; p<0.01); y, con el análisis de regresión múltiple, se evidenció que la VOP (relación t 5.76; p<0.001) fue la variable independiente más significativa asociada con la EUA (AU)