Effect of 3, 2-Drug Combinations of Antihypertensive Therapies on Blood Pressure Variability in Black African Patients: Secondary Analyses of the CREOLE Trial.

BACKGROUND: The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine plus perindopril (CCB+ACE [angiotensin-converting enzyme]-inhibitor), and perindopril plus hydrochlorothiazide (ACE-inhibitor+thiazide) on blood pressure variability (V) are unknown. METHODS: We calculated the blood pressure variability (BPV) in 405 patients (130, 146, and 129 randomized to ACE-inhibitor+thiazide, CCB+thiazide, and CCB+ACE-inhibitor, respectively) who underwent ambulatory blood pressure monitoring after 6 months of treatment in the Comparisons of Three Combinations Therapies in Lowering Blood Pressure in Black Africans trial (CREOLE) of Black African patients. BPV was calculated using the SD of 30-minute interval values for 24-hour ambulatory BPs and for confirmation using the coefficient of variation. Linear mixed model regression was used to calculate mean differences in BPV between treatment arms. Within-clinic BPV was also calculated from the mean SD and coefficient of variation of 3 readings at clinic visits. RESULTS: Baseline distributions of age, sex, and blood pressure parameters were similar across treatment groups. Participants were predominately male (62.2%) with mean age 50.4 years. Those taking CCB+thiazide had significantly reduced ambulatory systolic and diastolic BPV compared with those taking ACE-inhibitor+thiazide. The CCB+thiazide and CCB+ACE-inhibitor groups showed similar BPV. Similar patterns of BPV were apparent among groups using within-clinic blood pressures and when assessed by coefficient of variation. CONCLUSIONS: Compared with CCB-containing combinations, ACE-inhibitor plus thiazide was associated with higher levels, generally significant, of ambulatory and within-clinic systolic and diastolic BPV. These results supplement the differential ambulatory blood pressure-lowering effects of these therapies in the CREOLE trial.

The renin-angiotensin system in the synovium promotes periarticular osteopenia in a rat model of collagen-induced arthritis.

Periarticular osteopenia is the most specific hallmark of rheumatoid arthritis (RA). The renin-angiotensin system (RAS) in the synovium has been found to participate in the pathogenic process of RA. This study examined whether and how RAS regulates periarticular osteopenia in RA. The synovial tissues from patients with RA and osteoarthritis (OA) were prepared. Female Sprague-Dawley rats were treated with either saline, bovine type II collagen (CII) to induce arthritis (CIA), or CII combined with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). Expressions of RAS components, including AT1R, AT2R and ACE, in human and rat synovial tissues were detected. Bone mass of rat joints was examined. Levels of RANKL, OPG and DKK-1 in rat synovium and expressions of TRAF6 and ß-catenin in rat bone were examined. The results showed that AT1R, AT2R and ACE in human and rat synovium were up-regulated, but the increased ACE in rat synovial tissues was abrogated by perindopril. While CIA rats displayed increased bone resorption and decreased bone formation, perindopril treatment almost completely abrogated the RAS-mediated osteopenia, indicating that inhibition of ACE reduced the joint damages in rats. The expressions of RANKL and DKK-1 increased in CIA rats as compared with those in the control; TRAF6 was up-regulated and ß-catenin was down-regulated in the bone tissues of CIA rats. The changes were then reversed by the use of perindopril. Our findings demonstrate that RAS in the synovium promotes periarticular osteopenia by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK/TRAF6 and Wnt/ß-catenin pathways.

Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial.

BACKGROUND: Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. METHODS: Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including microRNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. DISCUSSION: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia. TRIAL REGISTRATION: ISRCTN, ISRCTN90094835 . Registered on 18 February 2015.

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.

Perindopril/amlodipine (Prestalia(®)): a review in hypertension.

Perindopril, an ACE inhibitor, and amlodipine, a dihydropyridine calcium channel blocker, are established antihypertensive agents with complementary mechanisms of action. Recently, a once-daily, orally-administered, fixed-dose combination (FDC) of perindopril arginine plus amlodipine besylate (Prestalia(®); hereafter referred to as perindopril/amlodipine FDC) was approved in the USA for the treatment of hypertension. This article reviews the efficacy and tolerability of perindopril/amlodipine FDC and briefly summarizes the agent's pharmacologic properties. As demonstrated in short-term randomized controlled trials, perindopril/amlodipine FDC was significantly more effective in reducing blood pressure (BP) than monotherapy with either of the component drugs, and it appeared to be more effective than an up-titration scheme using valsartan and valsartan/amlodipine. The FDC agent was generally well tolerated, with the most common adverse events (peripheral edema, cough, headache, and dizziness) being consistent with the well-defined tolerability profiles of the individual component drugs. Furthermore, perindopril/amlodipine FDC was associated with a numerically lower incidence of peripheral edema compared with amlodipine monotherapy. Thus, perindopril/amlodipine FDC represents a useful option for the treatment of hypertension, including as initial therapy for patients likely to require multiple drugs to achieve their BP targets.

A traditional Chinese medicine, Lujiao prescription, as a potential therapy for hypertrophic cardiomyocytes by acting on histone acetylation.

BACKGROUND: Chronic heart failure (CHF) is a complex clinical syndrome, and a serious stage of various heart diseases. Dysfunction of histone acetylation is involved in pathogenesis of CHF. Lujiao is a clinical and traditional prescription that has been previously used in the treatment of heart failure. The objective of our study was to explore the effects of traditional Chinese Medicine intervention with Lujiao prescription on hypertrophic cardiomyocytes with histone acetylation abnormality. METHODS: Myocardial cells from neonatal rats were stimulated via phenylephrine (PE) and then randomly divided into seven groups: normal group (without any treatment), model group (treated with saline), TSA group (treated with trichostatin A), perindopril group (treated with perindopril), and the high, medium, and low dose of Lujiao groups (treated with 2.4 g/mL, 1.2 g/mL, and 0.6 g/mL of Lujiao, respectively). The test drug of perindopril group or Lujiao group was derived from serum after drug treatment in rats. Real-time polymerase chain reaction and Western blot were performed to analyze expression of myocyte enhancer factor 2 (MEF-2), α-major histocompatibility complex (MHC), and ß-MHC and acetylation level of histone H3. RESULTS: Expressions of MEF-2 and ß-MHC were significantly increased after PE treatment and decreased after drug treatment. Expression of α-MHC mRNA was significantly reduced after PE treatment and increased after being treated with Lujiao prescription, perindopril, and TSA. The acetylation level of histone H3 decreased in rat myocardial cells stimulated by PE 48 for hours and this decrease was reversed after treatment with high and medium doses of Lujiao prescription, perindopril and TSA. CONCLUSION: Histone acetylation-MEF-2-α-MHC/ß-MHC axis was discovered in myocardial hypertrophy, and intervention of Lujiao prescription exhibited good effects.

Combination therapy in the extended cardiovascular continuum: a focus on perindopril and amlodipine.

The progression of cardiovascular disease could be regarded as following atherosclerosis-related and age-related pathways. The starting points for these pathways are different--risk factors or aortic ageing--but they conclude in the same way: end-stage heart disease. Together these interlinked pathways form the extended cardiovascular continuum. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been shown to interrupt or slow the progression of cardiovascular disease along one pathway, the cardiovascular atherosclerotic continuum. Cardiovascular protection with RAAS inhibitors varies; different RAAS inhibitors offer different levels of protection. Similarly, calcium channel blockers (CCBs) also have clearly shown protective effect of cardiovascular system, especially as it regards cerebrovascular disease risk. The AngloScandinavian Cardiac Outcomes Trial (ASCOT) showed that a combination of the angiotensin-converting enzyme (ACE) inhibitor perindopril and CCB amlodipine offered better cardiovascular protection in at-risk hypertensive patients than beta-blocker and thiazide. By attenuating the deleterious effects of cardiovascular disease at multiple stages of the extended cardiovascular continuum on top of lowering blood pressure (BP), perindopril and amlodipine could interrupt and slow the progression of cardiovascular disease. These antihypertensive agents have complementary vascular effects that enhance cardiovascular protection and reduce side-effects. Evidence from ASCOT shows that antihypertensive and vascular effects of amlodipine with and without perindopril have translated into real-life clinical benefits. A strategy using ACE inhibitors and CCBs, such as perindopril and amlodipine, to target multiple stages in both pathways of cardiovascular disease could effectively reduce cardiovascular risk and lower BP.

Inhibition of AAA in a rat model by treatment with ACEI perindopril.

BACKGROUND: The purpose of the present study was to evaluate the effect of a new angiotensin converting enzyme inhibitor perindopril on the formation of experimental abdominal aortic aneurysms (AAAs) in a rat model induced by intraluminal elastase infusion and extraluminal calcium chloride (CaCl2) application. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were randomly distributed into three groups (n = 12 per group): model (A), sham (B), and perindopril (C). Rats in model and perindopril groups underwent intra-aortic elastase perfusion and extraluminal CaCl2 application to induce AAAs. Rats in the sham group received aortic perfusion and extraluminal application of saline. A dose of 3 mg/kg/d of perindopril was fed orally in the perindopril group. The maximum abdominal aortic diameter was measured in vivo on days 0 and 28 and by ultrasound on days 7, 14, and 21. The arterial blood pressure was measured directly using a pressure transducer after cannulation in surgery and before death. AAA tissue samples were harvested at day 28 and evaluated using normal hematoxylin and eosin stain, Verhoeff-van Gieson stain for elastin, and image analysis technique. RESULTS: Aortic diameters of rats in the model group consistently increased within 28 d, coinciding with the development of a transmural inflammatory response, thickening of intima, and destruction of the elastic media. Without alteration in blood pressure, the AAA formation rate and mean maximal diameter of aorta at day 28 were significantly lower in the perindopril group compared with the control group (1.71 ± 0.20 versus 2.70 ± 0.69 mm, P < 0.001; 0% versus 90.91%, P < 0.001) and were similar to those in the sham group (1.79 ± 0.29 mm, P = 0.175; 0%, P = 1). The thickness of intima in the perindopril group was lower than that in the model group (20.68 ± 9.96 versus 58.49 ± 32.01 µm, P = 0.001), but higher than that in the sham group (7.23 ± 2.68 µm, P = 0.005). The intensity of elastin fiber showed the opposite trend (0.8541 ± 0.0495 in sham group versus 0.7376 ± 0.1024 in perindopril group versus 0.5413 ± 0.0912 in model group, P < 0.001). CONCLUSIONS: Perindopril inhibited the aortic degeneration and AAA formation in the experimental AAA model induced by elastase and CaCl2. This effect, which was independent of its influence on hemodynamics, appeared to be induced by the suppression of the inflammatory cell influx and intimal thickening and the preservation of aortic medial elastin.

Targeting different angiogenic pathways with combination of curcumin, leflunomide and perindopril inhibits diethylnitrosamine-induced hepatocellular carcinoma in mice.

No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of the anti-angiogenic agents: leflunomide; a disease modifying antirheumatic drug, perindopril; an angiotensin converting enzyme inhibitor (ACEI) and curcumin; the active principle of turmeric, on diethylnitrosamine (DEN)-induced HCC in mice. Eight weeks following DEN administration, there was a significant rise in immunohistochemical staining of CD31-positive endothelial cells and consequently hepatic microvessel density (MVD) as compared to normal liver. DEN treatment was associated with elevation in hepatic vascular endothelial growth factor (VEGF) level as compared to normal controls (P<0.05, 3842±72pg/ml and 2520.8±97pg/ml, respectively). Similarly, increased hepatic expression of hypoxia inducible growth factor-1α (HIF-1α) was observed in 100% of the DEN-treated animals compared to 0% in their normal counterparts. Treatment with leflunomide, perindopril or curcumin alone abrogated the DEN-induced increased MVD as well as the elevated expression of VEGF, while only curcumin inhibited HIF-1α hepatic expression. Combination of these agents showed further inhibitory action on neovascularization and synergistic attenuation of hepatic VEGF (1954.27±115pg/ml) when compared to each single agent. Histopathological examination revealed a more beneficial chemopreventive activity in the combination group compared to each monotherapy. In conclusion, the combination treatment of leflunomide, perindopril and curcumin targeting different angiogenic pathways, resulted in synergistic inhibition of angiogenesis and consequently more effective chemoprevention of HCC.

[Fixed dose combination perindopril-indapamide-amlodipine (Triplixam) for the treatment of arterial hypertension]. / Combinaison fixe périndopril-indapamide-amlodipine (Triplixam) pour le traitement de l'hypertension artérielle.

Triplixam is a fixed dose combination of three well known antihypertensive agents, with complementary activities, to control blood pressure in patients with arterial hypertension: perindopril, an angiotensin converting enzyme inhibitor, indapamide, a diuretic whith thiazide-like effects but also specific properties, and amlodipine, a long-acting calcium antagonist of the dihydropyridine family. The potential synergic action allows better control of blood pressure with once daily administration, while limiting the incidence of adverse events. Various presentations with different dosages are available to facilitate individualized therapy. Warnings and precautions for use of every molecule should of course be respected. Such a fixed dose combination should contribute to limit clinical inertia and to improve therapeutic compliance.

Which patients benefit the most from the perindopril/amlodipine combination.

Fixed-dose combinations have been strongly endorsed by European guidelines for first-line and second-line treatment of hypertension. Among recommended combinations, that of an angiotensin-converting enzyme inhibitor and a calcium channel blocker stands out because the mechanisms of action of these two therapeutic classes are complementary, leading to enhanced efficacy. In the large multicentre ASCOT-BPLA trial, treatment based on the combination of amlodipine and perindopril significantly reduced the risk of cardiovascular and all-cause death, stroke, coronary events and procedures, new-onset diabetes, and new-onset renal impairment in a wide range of patients with hypertension and other cardiovascular risk factors, when compared with atenolol/thiazide-based therapy. The perindopril/amlodipine single-pill combination was developed based on guideline recommendations for combination treatment, the indications of each component, and ASCOT-BPLA trial data. Several studies in real-life settings show that a wide range of hypertensive patients, including everyday hypertensives with common risk factors, would benefit from the perindopril/amlodipine combination.

Efficacy of Sevikar® compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study.

BACKGROUND AND RATIONALE: To date, few studies have investigated the effects of combined renin-angiotensin system blockade/calcium channel blockade on central aortic blood pressure. The Conduit Artery Function Evaluation (CAFE) sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) investigated the effects of amlodipine/perindopril and atenolol/bendroflumethiazide on central aortic blood pressure (CABP). Similar brachial blood pressure levels were achieved; however, there was a significant difference, in favor of the amlodipine/perindopril combination, on the effects of CABP. No study has investigated the effects of a combination of an angiotensin receptor blocker/calcium channel blocker compared to those of a calcium channel blocker/angiotensin-converting enzyme inhibitor combination. To confirm and support previous findings, the SEVITENSION study will assess the effects on CABP of treatment with the high dose combination of perindopril plus amlodipine as used in ASCOT-CAFE compared with the high dose combination of olmesartan/amlodipine in patients with moderate-to-severe hypertension uncontrolled on amlodipine monotherapy. OBJECTIVE: To demonstrate non-inferiority of fixed-dose olmesartan/amlodipine combination therapy compared with the combination of perindopril plus amlodipine on the mean change from baseline in central aortic systolic blood pressure. DESIGN: A multicenter, double-blind, parallel-group, non-inferiority study comprising a 2-4-week open-label run-in period with amlodipine and a 24-week active treatment period. CABP will be measured by the SphygmoCor® Vx Pulse Wave Velocity System. PATIENTS: 720 moderate-to-severe hypertensive patients aged ≥ 40 to ≤ 80 years and ≥ 3 additional risk factors will be enrolled. INTERVENTIONS: Study treatment will comprise orally-administered combination of olmesartan/amlodipine (40/10mg) or perindopril (8 mg) plus amlodipine (10mg), and matching placebos. (EudraCT number: 2009-012966-30; ClinicalTrials.gov identifier: NCT01101009).

[Efficacy of traditional therapy and chronotherapy using prestarium in elderly patients with polymorbid syndrome].

The aim of the work was to compare efficiency of traditional therapy with prestarium (tert-butylamine salt) and chronotherapy with prestarium A (arginine salt) in elderly patients with polymorbidity syndrome (diabetes mellitus, nephropathy, grade I-II chronic hepatic insufficiency). All patients underwent standard clinical and laboratory examination including measurement of glycemic profile, plasma urea, creatinine, K+ and Na+, AP monitoring, ECG, and echo-CG. The results suggest persistent hypotensive effect of prestarium and prestarium A within 4 days after the onset of therapy. However, in patients with a more severe disease, twice lower doses of prestarium A were needed to achieve positive effect and transform circadian AP rhythm from non-dipper to dipper pattern.

Clinical synergy of perindopril and calcium-channel blocker in the prevention of cardiac events and mortality in patients with coronary artery disease. Post hoc analysis of the EUROPA study.

BACKGROUND: The purposes of the study were to determine the effects of addition of perindopril to long-term continuous treatment with calcium-channel blocker (CCB) on cardiac outcomes in the stable coronary artery disease (CAD) population of EUROPA and to explore the presence of synergy between perindopril and CCB in secondary prevention. METHODS: We identified participants receiving CCB at every visit during the 4.2-year follow-up and analyzed the effect of addition of perindopril (n = 1,022 perindopril/CCB vs n = 1,100 placebo/CCB). RESULTS: Addition of perindopril to CCB significantly reduced total mortality by 46% (P < .01 vs placebo) and primary end point (a composite of cardiovascular mortality, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 35% (P < .05 vs placebo). There were 41%, 54%, and 28% reductions in cardiovascular mortality, hospitalization for heart failure, and myocardial infarction, respectively. Comparison of hazard ratios suggests the presence of a clinical synergy between perindopril and CCB, with a greater effect than addition of individual effects. CONCLUSION: Addition of perindopril to CCB in stable CAD patients had a significant supplementary impact on cardiac outcomes and mortality.

ACE-inhibitor suppresses the apoptosis induced by endoplasmic reticulum stress in renal tubular in experimental diabetic rats.

AIMS: The aim of the present study was to investigate the role of the endoplasmic reticulum stress and apoptosis in experimental diabetic nephropathy. The effects of ACE inhibitor on the endoplasmic reticulum stress and apoptosis were also assessed. METHODS: Diabetes was induced in male Sprague-Dawley rats by injection with streptozotocin at 60 mg/kg i .p. Diabetic rats were then randomly assigned into control (untreated) or treatment of an ACE inhibitor, perindopril, for 24 weeks. Tubulointerstitial injury was assessed by histopathology. Tubule apoptosis was detected by TUNEL assay. Endoplasmic reticulum stress associated proteins expression of glucose-regulated protein-78 (GRP78/BiP), phospho-eukaryotic initiation factor 2 alpha (eIF2 alpha), phospho-pancreatic ER kinase (PERK) and caspase-12 was assessed by immunohistochemistry and Western blots. RESULTS: There were more TUNEL-positive nuclei in diabetic kidneys than in control kidneys. At 24 weeks, experimental diabetes was associated with a considerable increase in protein expression of GRP78, phospho-eIF2 alpha, phospho-PERK, and caspase-12 in the tubulointestitium. ACE inhibitor not only attenuated the apoptosis but also reduced the overexpression of these endoplasmic reticulum stress associated proteins in tubulointestitium of diabetic rats. CONCLUSIONS: Increased tubular apoptosis in experimental diabetic rats is attenuated by blockade of the renin-angiotensin system with an ACE inhibitor, which might be in an association with reduced endoplasmic reticulum stress.

Omega-3 polyunsaturated fatty acid supplementation reduces hypertension in TGR(mRen-2)27 rats.

To establish the effect of dietary omega-3 PUFA on angiotensin II (ANG II)-mediated hypertension, male TGR (mRen-2)27 (Ren-2) rats (animals with high ANG II activity) were maintained on a diet either deficient or sufficient in omega-3 PUFA from conception. Half the animals on each diet were treated with the angiotensin-converting enzyme inhibitor, perindopril, from birth. Ren-2 rats fed the omega-3 PUFA deficient diet were significantly more hypertensive than those fed the omega-3 PUFA sufficient diet. Perindopril reduced the blood pressure of both omega-3 PUFA-deficient and omega-3 PUFA-sufficient diet-fed Ren-2 rats. Body weight, body fat and plasma leptin were reduced by perindopril treatment but not affected by omega-3 PUFA supply. Given that the elevated blood pressure of the Ren-2 rat is mediated by ANG II, the data suggest that omega-3 PUFA may reduce hypertension via the renin-angiotensin system.

Circadian blood pressure variation and antihypertensive medication adjustment in normoalbuminuric type 2 diabetes patients.

BACKGROUND/AIMS: The aim of the study was to assess the effect of an antihypertensive treatment adjustment on 24-hour blood pressure variation in type 2 diabetes patients. METHODS: The study group included 59 hypertensive type 2 diabetes patients subjected to a single one-step antihypertensive agent dose adjustment (increase or decrease). Ambulatory blood pressure monitoring was performed at baseline and 4-6 weeks after the treatment modification. Controls were 41 matched patients, in whom antihypertensive treatment remained unchanged. RESULTS: At baseline, 45 (76%) study group patients and 29 (71%) controls were 'non-dippers'; a similar number of patients in both groups converted to 'dipping' or vice versa: 11 (19%) from the study group and 7 (17%) controls. 'Converters' from the study group were significantly younger (47.5 +/- 3.9 vs. 56.4 +/- 12.2 years; p < 0.05) and had lower 24-hour systolic blood pressure than 'non-converters': 113.7 +/- 7.2 vs. 127.7 +/- 20.3 mm Hg (p < 0.01). CONCLUSION: A single one-step antihypertensive medication adjustment does not affect 'dipping' status in type 2 diabetes patients. However, the assessment of blood pressure variation should be made with greater caution in younger type 2 diabetes subjects with low systolic blood pressure.

[Influence of perindopril, rosuvastatin, or omega-3 polyunsaturated fatty acids on efficacy of antirecurrence therapy with sotalol in patients with persistent atrial fibrillation].

Patients (n=187) with symptomatic persistent atrial fibrillation at the background of ischemic heart disease after restoration of sinus rhythm were randomized for treatment with sotalol 80 - 160 mg/day (n=48), or with combinations of sotalol with perindopril 4 - 8 mg/day (n=48), rosuvastatin 5 - 20 mg/day (n=45), or omega-3 polyunsaturated fatty acids containing preparation 1 g/day (n=45). After 12 months sinus rhythm was maintained in 77.6, 93.8 (p < 0.05), 86.7, and 84.4% of cases, respectively, after conduction on the average 7.9 +/- 1.6, 4.3 +/- 1.0 (p < 0.05), 6.5 +/- 1.7, 7.2 +/- 1.8 pharmacological cardioversions per 1 patient in groups of comparison, respectively. Plasma level of high sensitivity C-reactive protein was lowered by all variants of combination therapy, while anterior-posterior left atrial diameter - only under the influence of perindopril. Antiinflammatory effect of nonarrhythmic drugs is able to play substantial role in prevention of atrial fibrillation, however antiremodeling and hemodynamic effects of therapy probably possess no less important significance.

[Comparison of noliprel and caposide efficacy in patients with arterial hypertension of high risk].

AIM: To compare clinical efficacy and tolerance of fixed combinations of perindopril and indapamide (noliprel), capoten+hydrochlorotiaside (caposide) in arterial hypertension stage I-II of high and very high risk which failed prior monotherapy. MATERIAL AND METHODS: A blind randomized trial in parallel groups recruited 40 patients (20 patients each). The patients received 1 tablet a day noliprel (2 mg/0.625 mg) or caposide (50 mg/25 mg) for 6 months. Target pressure patients were counted. Speed of the pulse wave, blood lipids and electrolytes, left ventricular myocardium posterior wall thickness were estimated. RESULTS: By antihypertensive efficacy and ability to reduce left ventricular hypertrophy and to improve arterial elasticity, low-dose fixed combination (noliprel) was not inferior to caposide (high-dose fixed combination) while by T/P noliprel was more effective than caposide, it lowered cholesterol more but potassium level--less. CONCLUSION: Noliprel has the the same with caposide antihypertensive efficacy and ability to diminish LVH. It has benefits by action on lipid and electrolyte indices.