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Introduction Hypertension control reduces cardiovascular and renal risks in type 2 diabetes. Sodium-glucose cotransporter-2 inhibitors prevent renal glucose reabsorption and decrease glucose plasma levels, blood pressure (BP) and weight reduction. Treatment of hypertension and sodium-glucose cotransporter-2 are able to improve arterial stiffness. Aims To evaluate, in patients with type 2 diabetes and hypertension, the effects of 6 months treatment with canagliflozin, or perindopril, an angiotensin converting enzyme inhibitor, on central BP and carotid-femoral pulse wave velocity (cfPWV). Methods Thirty type 2 diabetic patients with hypertension taking amlodipine, 10 mg daily, and metformin, 750-2000 mg daily, were randomized and a third medication was added: canagliflozin, 300 mg daily (n = 15, nine women, mean age: 63 ± 8 years), or perindopril, 10 mg daily (n = 15, five women, mean age 59 ± 4 years), for 6 months. Ambulatory BP monitoring was assessed at baseline and after 3 and 6 months of treatment, whereas cfPWV was measured before and after 6 months of treatment. Plasma fasting glucose, glycated hemoglobin, creatinine, plasma and urinary sodium and potassium were also measured. Results Both treatments significantly reduced BP and cfPWV. Only canagliflozin maintained the PWV action after adjusting for BP values and reduced glycemia, glycated hemoglobin and 24 h urinary sodium. Other security laboratory parameters, including gluthamic oxaloacetic transaminase, gluthamic piruvic transaminase; and bilirubin failed to show any change. Conclusion Canagliflozin reduced BP and improve arterial stiffness, independently of the BP effect. These two conditions could explain the cardiovascular protection observed with canagliflozin compared with perindopril.

Introduction: Silent coronary heart disease is frequently undetected in type 2 diabetes mellitus (DM2) and pre-diabetes determined by glucose intolerance (GI). Pulse wave velocity (PWV) and albumin-creatinine ratio (ACR) have been considered markers of cardiovascular mortality, coronary heart disease and chronic renal failure. Aims: To evaluate the incidence of coronary artery disease (CAD) and the relationship between urinary albumin-creatinine ratio, glomerular filtration rate (GFR) and PWV in type 2 DM with silent CAD. Methods: We analyzed 92 individuals (44 male), 49 (60±7y) type 2 DM non-insulin dependents and 43 prediabetics (43±4y), with Grade I-II hypertension and no symptoms of CAD. : All type 2 DM patients were under antidiabetic treatment with A1C hemoglobin between 5.5 and 6.5%. : Every patient underwent a myocardial perfusion SPECT scan. In those subjects with ischemic patterns, coronary angiography was performed. In addition, PWV, glomerular filtration rate, and ACR were evaluated. Statistics: mean±SEM, and ANOVA among groups. Results: 48.59% of DM2 and 25.58% of GI patients had silent coronary artery had silent coronary artery disease and higher ACR, PWV and reduced GFR. Higher ACR and PWV and reduced GFR. DM2 and GI showed a negative relationship between GFR and ACR. Moreover, this relation was also observed in different levels of GFR (>60 ml/min and Conclusions: Higher PWV, lower GFR and ACR predict the incidence of CAD in DM2. Dysglycemic individuals also represent a group of higher risk for coronary artery disease with similar predictors as in DM2. Diabetic and prediabetics still develop renal microalbuminuria. Thus, PWV seems to represent a reliable marker of renal impairment and coronary artery disease.

Introduction: Chronic serum uric acid elevation (SUA) is known to be induced by dyslipidemia, hypertension, inflammation, and insulin resistance. Therefore, it has been associated with higher risk for coronary artery disease and cardiovascular mortality. Also, increased levels of SUA have been associated with regional arterial stiffness, assessed by pulse wave velocity (PWV). Aims: To evaluate the relationships of PWV, SUA and different metabolic parameters in essential hypertensive patients. Material and Methods: We evaluated 445 essential hypertensive patients, by measuring office blood pressure (BP), weight, height, and waist circumference. In each patient, blood samples were drawn for biochemical evaluations and 24h urine collection. Body Mass Index (BMI) and Glomerular Filtration Rate (GFR) were calculated. Carotid-Femoral PWV and Left Ventricular Mass Index (LVMI) were measured in all patients. Results: All subjects (n=402), 242 males (55±0.9 yrs.; BMI: 28.9±0.3 Kg/m2) and 160 females (58±1 yrs.; BMI: 28.1±0.4 Kg/m2) had normal renal function. PWV values showed a significant association with SUA (p Conclusions: In this population of essential hypertensive patients, SUA was associated to increased arterial stiffness and to components of the Metabolic Syndrome. These results raise the possibility that a new approach to the role of SUA, linked to cardiovascular stratification, and a most appropriate treatment might be considered.

Introduction: Silent coronary heart disease is frequently undetected in type 2 diabetes mellitus (DM2) and prediabetes determined by glucose intolerance (GI). Pulse wave velocity (PWV) and albumin-creatinine ratio (ACR) have been considered markers of cardiovascular mortality, coronary heart disease and chronic renal failure. Aims: To evaluate the incidence of coronary heart disease (CHD) and its relationship with urinary albumin-creatinine ratio, glomerular filtration rate (GFR) and PWV in type 2 DM with silent CHD. Methods: We analyzed 92 individuals (44 male), 49 (60±7y) type 2 DM non-insulin dependents and 43 prediabetics (43±4y), with Grade I-II hypertension and no symptoms of CHD. All type 2 DM patients were under hypoglycemic treatment with an A1C hemoglobin between 5.5 and 6.5%. Every patient underwent a myocardial perfusion SPECT scan. In those subjects with ischemic patterns, a coronary angiography was performed. In addition, a PWV, glomerular filtration rate (CrCl), and ACR were evaluated. Statistics: mean±SEM, and ANOVA followed by Post Hoc analysis among groups. Results: Silent CHD was found in 48.59% of DM2 and 25.58% of GI. DM2 and GI patients with CHD had higher ACR and PWV and reduced glomerular filtration rate (p Conclusions: Higher PWV, lower GFR and ACR predict the incidence of CHD in DM2. GI also represent a group of higher risk for coronary heart disease with the same predictors showed in DM2. PWV seems to represent a reliable marker. Disclosure R.A. Sanchez: None. M.J. Sanchez: None. A.J. Ramirez: None.

Since 1966, a large number of trials of blood pressure (BP) lowering drugs compared with placebo (or no treatment) in hypertensive patients, complemented by trials of more versus less intense BP lowering, have shown that antihypertensive treatment can significantly reduce the incidence of fatal and nonfatal events associated with hypertension.1 A meta-analysis of all BP-lowering trials from 1966 to end of 2013 (68 trials in 245 885 individuals) has calculated that a 10/5 mm Hg systolic BP/diastolic BP (SBP/DBP) reduction significantly decreases stroke by 36%, heart failure by 38%, coronary events by 20%, cardiovascular mortality by 16%, and all-cause mortality by 10%.2 In addition, head-to-head comparisons between treatments based on different antihypertensive drugs (meta-analyses of 50 trials with 58 two-drug comparisons in 247 006 individuals) have shown that what really matters for preventing cardiovascular events is lowering of BP, and how BP is lowered (ie, the types of drugs used) is of minor importance.3 Despite the very large number of trials of antihypertensive treatment, it must be recognized that, except for the benefits of reducing high BP and for the equivalence of the various classes of antihypertensive agents, the majority of questions of practical importance that doctors ask themselves every day when treating hypertension have not been approached by randomized controlled trials or have remained unanswered.1–4 Examples of these unanswered questions are those to be discussed below such as initiation of drug treatment of hypertension, the BP targets to be aimed at, and the role of overall cardiovascular risk in treatment decisions. Although the safest decisions are those that can be found according to results of randomized trials, their concordance, and/or meta-analyses, other decisions should necessarily be taken on the basis of other criteria such as post hoc analysis of trials, observational studies, pathophysiological and pharmacological knowledge, …

We have previously shown a strong relation between high serum uric acid and pulse wave velocity (PWV) as expression of arterial stiffness. This relation was even stronger than with blood pressure. In addition to its hypoglycemic effect, sodium-glucose transport protein 2 inhibitors (SGLT2i) may reduce serum uric acid (SUA) by a uricosuric effect. Aims: to evaluate in type 2 diabetic patients with hypertension and normal renal function the effect of canagliflozin on SUA and carotid femoral PWV. Methods: 20 patients with type 2 diabetes mellitus (DM) 10 females, 59±4y received metformin 2000mg, canagliflozin 100-300mg and amlodipine 10mg daily during 6 months. Laboratory parameters including HbA1C, fasting blood glucose level, glomerular filtration rate, SUA, 24h ambulatory blood pressure monitoring (ABPM) and PWV were determined at baseline and after a 6-month treatment course with canagliflozin 100-300mg. Results: After 6 months of treatment, PWV dropped from 12±3 to 8.5±4 m/sec, p Conclusions: Canagliflozin ameliorates arterial stiffness in patients with type 2 DM and hypertension. This effect seems to be related, among other mechanisms, such as blood pressure drop and plasma volume contraction to the reduction in serum uric acid level. Since SUA has been shown to predict the risk of cardiovascular morbidity and mortality in hypertension and DM, lowering serum uric acid by SGLT2i might be contributing to cardiovascular protection. Disclosure R.A. Sanchez: None. M.J. Sanchez: None. A.J. Ramirez: None.

Epidemiological and clinical evidence have shown a close association between hypertension, obesity, IGT or NIDDM, and dyslipidemia. The activation of sympathetic nervous system plays a role in the pathogenesis of essential hypertension and its inhibition is of a therapeutic value. Rilmenidine is an oxazoline compound with antihypertensive properties that acts mainly on the brain stem but also in the kidneys, where it selectively binds to I1 imidazoline receptors, distinguishing it from reference α2-agonists. As a consequence, anti-hypertensive treatments that reduce the sympathetic response could also have effects on the metabolic abnormalities of hypertensive patients with metabolic disorders. The aim of the present study was to evaluate the effect of rilmenidine or placebo on insulin resistance and sympathetic activity, in essential hypertensive patients untreated or non-adequately treated. Our results have shown that Rilmenidine was able to decrease sympathetic activity expressed by both a decrease in SBP variability and an increase in baroreflex sensitivity. Together with these effects a significant improvement of insulin resistance index (HOMA), which was not obtained by the adjusted conventional treatment, was also observed. In conclusion, these beneficial effects observed support the idea that Rilmenidine could be comparable to established drugs for first-line therapy in hypertension.

Introduction: Hypertension may increase the risk for stroke and is frequently associated with subcortical and periventricular white matter lesions (WML). This is considered a prognostic factor for the development of stroke and cognitive impairment, particularly in attention processes. Additionally, in elderly subjects, it is known the implications of alterations in the neural cardiovascular regulation and the cardiovascular risk. Aims: To evaluate, in asymptomatic elderly hypertensives, the association of ambulatory blood pressure values and autonomic activity with neurocognitive impairment and WML. In addition, we also evaluated the role of the autonomic nervous system particularly the vagal component, in the pathogenesis of white matter lesions. Methods: We studied 22 elderly essential hypertensive patients (69±1.1y) and as control group, 16 normotensive elderly subjects (age 67±3.2y) were also enrolled. To each one of them, a cerebral MRI was performed to classify them, by a neuro-radiologist blinded of the subject clinical status, using a 0 to 9 scale where 0 denoted no WML and 9 the most severe lesions. Twenty four hours arterial blood pressure monitoring was performed to each one of the subjects under study. Office blood pressure was measured 3 times and the mean value reported. Beat to beat finger arterial pressure monitoring (Finapres) was performed for a 2h period. During the first hour the patient remained lying supine in a quiet darkened room and during the second hour four manoeuvres: stand-up, cold pressor test, handgrip and quiet activity were randomly performed. Mean blood pressure and pulse interval values, from the two periods, and their respective variabilities, baroreflex sensitivity and power spectral analysis were calculated. Regarding neuropsychological assessment: Minimental test, attention evaluation, RAVLT, visual memory, language and executive function, geriatric depression scale, cognitive deficit rate tests were performed in all subject.....

Renal function and outcome of PTRA and stenting for atherosclerotic renal artery stenosis.BackgroundPrior studies of percutaneous transluminal renal artery angioplasty and stenting (PTRAS) for atherosclerotic renal artery stenosis (RAS) have shown that renal function is improved in about 25%, stabilizes in about 40%, but worsens in about 25% of patients. The factors predicting benefit remain controversial. We tested the hypothesis that the baseline glomerular filtration rate (GFR) predicts the changes in GFR and blood pressure (BP) after PTRAS.MethodsTreated hypertensive patients with positive renal color-coded duplex Doppler velocimetry and clinical criteria were screened by arteriography. Patients (N = 105) were included if they had an RAS ≥70%, a transluminal pressure gradient ≥30mm Hg and, they had more than 100 days of follow-up. GFR was calculated from the serum creatinine concentration (SCr). Patients were divided by baseline GFR into subgroups with normal to mildly impaired (N = 52) or moderately to severely impaired (N = 53) initial GFR, according to a GFR ≥50 or

Background: Nocturnal hypertension, male gender, age and arterial stiffness are important risk factors for cardiovascular morbidity and mortality. The objective of this study was to assess arterial stiffness in nocturnal hypertensive or normotensive men and women >40 years of age. Methods: Twenty-four-hour ambulatory blood pressure monitoring was performed in 144 men and 137 women. Eighty-eight subjects were between 40 and 49 years old (53% men), 98 were between 50 and 59 years old (55% men) and 95 were >60 years old (45% men). They were classified as nocturnal hypertensive if their average night systolic blood pressure and/or diastolic blood pressure was >120/70 mm/Hg. Arterial stiffness was assessed by the Ambulatory Arterial Stiffness Index (AASI), which is calculated as 1 minus the slope of diastolic on systolic blood pressure during the 24-hour recording period. Results were analyzed by analysis of covariance and were adjusted for 24-hour mean arterial pressure, the presence of antihypertensive treatment, height and heart rate. Results: Women showed a higher AASI compared to men, independently of age. In men, the AASI increased with age, being higher in nocturnal hypertensive than in nocturnal normotensive subjects, independently of age. Nocturnal hypertensive women showed higher AASI values than their respective nocturnal normotensive controls in the 50- to 59-year and >60-year age groups only. Conclusion: The results show that arterial stiffness is higher among nocturnal hypertensive subjects, especially in women >50 years old. Fil: Drucaroff, Lucas Javier. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ramirez, Agustin Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Favaloro; Argentina Fil: Sanchez, Ramiro. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Perez Lloret, Santiago. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina

Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (η) using the hysteresis loop elimination criteria. In NTA, η was 2.73±1.66 (mm Hg · s/mm) and IMT was 0.58±0.08 (mm), whereas in HTA, η was 5.91±2.34 ( P P r =.71 ( P r =.59 ( P

El presente documento ha sido preparado por un grupo de expertos, miembros de las sociedades de cardiología, endocrinología, medicina interna, nefrología y diabetes de los países de América Latina, para que sirvan de guía a los médicos que cuidan a pacientes con diabetes, hipertensión y enfermedades concomitantes o complicaciones de ambas condiciones. Aunque el concepto de síndrome metabólico actualmente es discutido, la alta prevalencia en América Latina del conjunto de alteraciones metabólicas que lo conforman sugiere que el síndrome metabólico es una entidad nosográfica común en el contexto de la medicina latinoamericana. Por lo tanto, en el presente documento se presta especial atención a este síndrome con el fin de alertar a los médicos de una particular población de alto riesgo, en la que por lo general es subestimada y no se tratan en forma optima los factores de riego que constituyen el síndrome metabólico. Las presentes recomendaciones son el resultado de las presentaciones y los debates en los paneles de discusión durante una reunión de dos días celebrada en Bucaramanga en octubre de 2012. Todos los participantes han aprobado las conclusiones finales. Los autores reconocen que la publicación y difusión de las guías no serán suficientes para alcanzar los cambios recomendados tanto en las estrategias diagnósticas como terapéuticas, por lo que se ha programado intervenciones que permitan identificar las barreras del conocimiento, de las actitudes y de comportamiento, lo que permitirá tanto a los médicos como a los pacientes una adecuada adherencia a las recomendaciones de las guías. (Acta MedColomb 2013; 38: 154-172). The present document has been prepared by a group of experts, members of cardiology, endocrinology, internal medicine, nephrology and diabetes societies of Latin American Countries, to serve as a guide to physicians taking care of patients with diabetes, hypertension and comorbidities or complications of both conditions. Although the concept of metabolic syndrome is currently disputed, the higher prevalence in Latin America of that cluster of metabolic alterations has suggested that metabolic syndrome is useful nosography entity in the context of Latin American medicine. Therefore, in the present document, particular attention is paid to this syndrome in order to alert physicians on a particular high- risk population, usually underestimated and undertreated. These recommendations results from presentation and debates by discussion panels during a 2-day conference held in Bucaramanga, in October 2012, and all the participants have approved the final conclusions. The authors acknowledge that the publication and diffusion of guidelines do not suffice to achieve the recommended changes in diagnostic or therapeutic strategies, and plan suitable interventions overcoming both physicians and patients from effectively adhering to guideline recommendations. Documento licenciado en la revista Acta Médica Colombiana con licencia de atribución. Compartir - copiar y redistribuir el material en cualquier medio o formato. Adaptar - remezcla, transformar y construir sobre el material para cualquier propósito, incluso en el comercio.

The diagnosis and management of secondary hypertension has improved in the last decade as a result of the advances in the acknowledgment of some physiopathologic mechanisms and mainly by the development of new diagnostic methods. Furthermore, the treatment of some types of secondary hypertension may be solved by noninvasive techniques. Hypertension of renal and renovascular origin, coarctation of the aorta, primary hyperaldosteronism, and adrenal medullary tumors are analyzed. The main results of some relevant studies on diagnostic and treatment of those diseases are presented. Also, some experimental methods are mentioned, taking into account the possibility of clinical use in the near future.

Type 2 Diabetes Mellitus (DM), or adult-onset diabetes, is being considered as a new pandemic. Cardiovascular disease is the major cause of morbidity and mortality in type 2 DM, due to arterial structure and functional changes. Assessment of arterial structure and biomechanics, by non-invasive methods and parameters, can be used to detect early alterations related to DM. Three markers of vascular disease may help to a better evaluation of vascular dysfunction in type 2 DM patients: carotid intimamedia thickness (IMTc), arterial stiffness, assessed by pulse wave velocity (PWV), and endothelial function, evaluated through the brachial artery flow-mediated dilation (FMD). Among these parameters, IMTc is considered a marker of structural vessel wall properties, and arterial stiffness reflects functional wall properties. Endothelial function represents the arterial way to actively regulate its diameter (smooth muscle-dependent actions) and its visco-elastic properties (wall elasticity and viscosity). IMTc is increased in patients with type 2 DM and other independent risk factors, such as: age, hyperlipidemia and duration of DM. Subjects with DM have shown increased arterial stiffness. Type 2 DM is associated with reductions in FMD (endothelial dysfunction), which has already been reported to be inversely and strongly related to the extent of hyperglycemia. The underlying patho-physiological mechanisms are complex and remain to be fully elucidated. A complete understanding of the association between arterial alterations and early detection, and type 2 DM, may be critical for the primary prevention of DM-related macro-vascular disease.

30 patients (20 male and 10 female, mean age 53 years) with mild to moderate essential hypertension took part in a double-blind randomised study to evaluate the effects of nebivolol (5 mg/day) vs atenolol (100 mg/day). Systolic and diastolic blood pressure (BP) were recorded by 24-hour ambulatory BP monitoring after 4 weeks’ placebo and 8 weeks’ active treatment. Systolic and diastolic left ventricular function were measured using a 2-dimensional ECG and PW Doppler transmitral blood flow velocity recordings. The 2 drugs produced similar reductions in BP, whereas only atenolol significantly decreased heart rate. Cardiac index was unchanged with both drugs. An improvement was observed in different indices of diastolic left ventricular function with both treatments. However, only nebivolol enhanced the peak filling rate normalised to mitral stroke volume, from 5.4 to 6.5 sec−1 (p < 0.05).

Diabetes mellitus and hypertension, responsible of a major burden of cardiovascular complications, are increasing their incidence in Latin America in similar proportions to the rest of the world. The metabolic syndrome, a strong predictor of both diabetes and hypertension deserves more attention from the primary care physicians. Evidence based and updated guidelines on detection, prevention and treatment of diabetes and hypertension, issued by local experts, are willing to inform and translate these recommendations to the clinical practice of physicians assisting these patients throughout Latin America.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP ≥140 mm Hg, 20 and P =0.012; systolic BP −1.5 [95% CI −3.0, −0.1] diastolic BP P =0.019) and AER −42% (95% CI −50%, −33%) versus −27% (95% CI −37%, −16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

Angiotensin II has many actions in the kidney, including regulation and distribution of renal circulation and glomerular filtration, as well as effects on mesangial contraction and on the filtration coefficient. The reduction in circulating and intrarenal angiotensin II by angiotensin converting enzyme (ACE) inhibitors in essential hypertension is associated with a significant increase in renal blood flow and a decrease in filtration fraction, without changes in glomerular filtration rate. In addition, administration of ACE inhibitors can reduce proximal sodium reabsorption via changes in peritubular hydrostatic and oncotic forces resulting from the fall in postglomerular capillary resistance. In severe hypertension the state of the renal vasculature does not allow ACE inhibition to induce similar haemodynamic changes and, therefore, it cannot contribute to renal sodium handling that requires the recruitment of alternate mechanisms. In spite of this, ACE inhibitors may exert a protective effect on the renal function of patients with severe hypertension as well as in those with renal impairment, by lowering systemic and, probably, intraglomerular pressure, reducing proteinuria and slowing the progression of renal failure.

OBJECTIVE: To study the effect of treatment with cilazapril versus nifedipine on the glomerular filtration rate (GFR), microalbumin excretion rate (mu Alb) and baseline plasma renin activity (PRA) levels in non-diabetic or diabetic essential hypertension. DESIGN AND METHODS: Thirty-four moderate essential hypertensives and thirty-two type II diabetic hypertensives with currently normal renal function completed the study, receiving treatment with a converting enzyme inhibitor (CEI, 5-10 mg/day cilazapril) or a non-CEI (20-40 mg slow-release nifedipine three times a day) during a 12-month controlled follow-up study. RESULTS: Either treatment induced a similar reduction in blood pressure. Patients with PRA > 3 ng/ml per h treated with cilazapril showed a proportional increase in GFR, whereas in those treated with a non-CEI there was a decline in GFR after 8 and 12 months. Only diabetic patients treated with cilazapril showed a mu Alb reduction associated with a stable GFR. CONCLUSION: PRA predicts the effect of CEI preserving renal function in essential and diabetic hypertension.

The blood pressure decrease after beta-blockade is delayed and there are little data on the hemodynamic events associated with the initial decrease in blood pressure. The present study measured the hemodynamics of the initial hypotensive action of timolol maleate, a nonselective beta-adrenoreceptor blocking agent, in 10 patients with essential hypertension. Frequent measurements were made for the first 30 hours of treatment, and follow-up measurements made at 3 and 6 weeks. Before treatment, mean arterial blood pressure, cardiac output, and arteriovenous oxygen difference were 115.9 +/- 9.1 mm Hg, 4.65 +/- 1.05 liter/min, and 55.0 +/- 9.6 ml/liter, respectively. At 3 hours after the first dose of timolol, blood pressure had fallen 13.5 +/- 8.2 mm Hg (p less than 0.05). This was preceded by an initial decrease in cardiac output, which was not associated with a simultaneous decrease in blood pressure, and by an increase of arteriovenous oxygen difference. The early, statistically significant, decrease in cardiac output was followed by a return to normal output, which coincided with the onset of blood pressure reduction. The magnitude of the initial decrease of cardiac output and of the initial increase in arteriovenous oxygen difference was significantly correlated to the later decrease in blood pressure (7 hours after first dose). These hemodynamic observations are consistent with the notion that early underperfusions of tissue play a role in the initial hypotensive action of beta-blockers. After 6 weeks, the blood pressure remained lower but the cardiac output was again decreased at that point. As with many antihypertensive agents, there was a difference between the early and late hemodynamic pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy and safety of cilazapril monotherapy was evaluated in a multicenter, open-label, ascending-dose titration study in 83 elderly essential hypertensive patients. After a four-week, single-blind, placebo run-in period, patients received 1 mg of cilazapril once daily for the first four weeks. This dose was then increased to 2.5 mg once daily for the next four weeks for patients whose pre-dose sitting diastolic blood pressure was above 90 mm Hg. Similarly, at Week 8 the dose was increased in such patients from 1 to 2.5 mg or from 2.5 to 5 mg once daily. A 12-hour blood pressure profile was performed on the first day of active treatment and of each dose increase. Mean decrease of sitting diastolic blood pressure from baseline (102.7 ± 0.4 mm Hg) at Week 12 was 13.3 ± 1.1 mm Hg (p

The antihypertensive activity of cilazapril, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor was evaluated in 20 outpatients (13 women, 7 men; mean age, 49 +/- 2.4 years) with mild to moderate essential hypertension, by means of an open dose-finding study of 10 weeks' duration. Cilazapril, 0.5 mg/day, was given, and the dose increased up to 10 mg/day if sitting diastolic blood pressure (SDBP) was not normalized (less than or equal to 90 mm Hg). Blood pressure measurements were carried out every 2 weeks before and 2 h after dosing. Predose and 2-h postdose measurements of plasma renin activity (PRA), angiotensin II (AII), plasma aldosterone (PA), and enzyme converting activity (ECA) were performed on the 1st day of active treatment and after 2 weeks of therapy. The SDBP decreased from 107.6 +/- 2 to 97.2 +/- 3 mm Hg 2 h after the initial dose (p less than 0.01). At the same time, ECA was inhibited 84.2 +/- 5% (p less than 0.01), AII decreased from 21.2 +/- 3 to 13.6 +/- 2 pg/ml (p less than 0.05), and PA from 208 +/- 29 to 119 +/- 14 pg/ml (p less than 0.01). After 2 weeks of therapy, ECA remained markedly reduced, by 68 +/- 6%, 24 h after the preceding cilazapril dose (p less than 0.01). The mean SDBP decreased from baseline to the end of treatment by 14.6 +/- 3 mm Hg (p less than 0.01). Cilazapril seems to be an effective antihypertensive drug which exerts potent and long-lasting ACE inhibition.

The effect of cilazapril as monotherapy or in combination with hydrochlorothiazide was assessed in 30 severely hypertensive patients, 23 men and seven women, aged 38 to 68 years, with sitting diastolic blood pressure of more than 115 mmHg. Fifteen patients had left ventricular hypertrophy documented by two-dimensional echocardiography. Sitting systolic blood pressure was reduced from 175.8 ±2.0 to 143.3 ±3.0 mmHg within 25 days of therapy (p

The efficacy and safety of cilazapril monotherapy was evaluated in a multicenter, open-label, ascending-dose titration study in 83 elderly essential hypertensive patients. After a four-week, single-blind, placebo run-in period, patients received 1 mg of cilazapril once daily for the first four weeks. This dose was then increased to 2.5 mg once daily for the next four weeks for patients whose pre-dose sitting diastolic blood pressure was above 90 mm Hg. Similarly, at Week 8 the dose was increased in such patients from 1 to 2.5 mg or from 2.5 to 5 mg once daily. A 12-hour blood pressure profile was performed on the first day of active treatment and of each dose increase. Mean decrease of sitting diastolic blood pressure from baseline (102.7 +/- 0.4 mm Hg) at Week 12 was 13.3 +/- 1.1 mm Hg (p less than 0.001). Seventy-five percent of patients had a decrease of 10 mm Hg or more from baseline sitting diastolic blood pressure, and in 60 percent sitting diastolic blood pressure normalized. Unexpectedly large decreases of blood pressure after the first dose were seen only in three patients and none had clinical symptoms. Fourteen patients (16.9 percent) reported adverse events, but most of these were judged unlikely to be related to therapy. Four patients with predisposing underlying diseases experienced potentially serious adverse events (angina pectoris, myocardial infarction, arrhythmia, and blood pressure elevation) whose relationship to therapy was judged remote or only possible. There was no particular pattern of changes in laboratory values. The results indicate that cilazapril is an effective, safe, and well-tolerated antihypertensive drug for the elderly.

The purpose of this study was to evaluate the natriuretic effect and renal haemodynamic changes induced by enalapril in patients with essential hypertension. In a group of 11 patients with mild to moderate hypertension with normal renal function, and on a controlled sodium intake (80 mmol/day), a decrease in systolic and diastolic blood pressure was observed (p less than 0.001) after 16 weeks of enalapril treatment (20 mg/day), without a change in heart rate. An increase in plasma renin activity (p less than 0.05) without changes in serum aldosterone, and a decrease in exchangeable sodium (p less than 0.001) were present at the end of the treatment period. In 10 hypertensive patients also taking a dietary sodium of 80 mmol/day, the renal haemodynamics, humoral changes, and urinary sodium excretion were measured during 4 days of enalapril treatment (20 mg/day). There was an increase in urinary sodium excretion on the 3rd and 4th days of treatment (p less than 0.01). The effective renal plasma flow and fractional sodium excretion increased 72 hours after the beginning of treatment (p less than 0.01); the glomerular filtration rate did not change, and filtration fraction decreased at 72 hours. Mean blood pressure fell 2 hours after the first dose (p less than 0.01), and the maximum drop in intrarenal vascular resistance occurred after 72 hours of treatment (p less than 0.01). Plasma renin activity increased (p less than 0.05) and serum aldosterone decreased (p less than 0.01) 2 hours after the first dose. Thereafter, serum aldosterone increased progressively until it reached values similar to those with placebo at 48 and 72 hours of treatment. Urinary kallikrein fell during the 2nd and 3rd day of treatment (p less than 0.01). It was concluded that the decrease in exchangeable sodium was due to a natriuretic effect of enalapril. This effect presumably results from renal haemodynamic changes due to the reduction of angiotensin II. Other mechanisms, such as the reduction of aldosterone and accumulation of kinins, could be contributory factors.