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We studied the effects of apoptotic bodies of cardiomyocytes (ApBc) and fibroblasts (ApBf) on myocardial regeneration and contractility in rats and the dynamics of RNA concentrations in cardiomyocytes and fibroblasts at different stages of apoptosis. ApBc increase the contractility of rat myocardium, while ApBf reduce it. ApBc stimulate the development of clones of cardiomyocyte precursors in the myocardium, while ApBf stimulate the formation of endothelial precursor clones. In doxorubicin cardiomyopathy, ApBc, similar to the reference drug (ACE inhibitor) improve animal survival, while ApBf produce no such effect. RNA concentrations in cardiomyocytes and fibroblasts before apoptosis and at the beginning of cell death significantly differed, while in apoptotic bodies of these cells, it was practically the same. It has been hypothesized that RNA complex present in ApBc and ApBf represents an "epigenetic code" of directed differentiation of cardiac stem cells.

Renal fibrosis (RF) is the common pathway for a variety of chronic kidney diseases that progress to end-stage renal disease. Chitosan oligosaccharide (COS) has been identified as possessing many health functions. However, it is not clear whether COS can prevent RF. The purpose of this paper was to explore the action and mechanism of COS in alleviating RF. First, an acute unilateral ureteral obstruction operation (UUO) in male BALB/c mice was performed to induce RF, and COS or fosinopril (positive control drug) were administered for 7 consecutive days. Data from our experiments indicated that COS treatment can significantly alleviate kidney injury and decrease the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) in the UUO mouse model. More importantly, our results show that COS can reduce collagen deposition and decrease the expression of fibrosis proteins, such as collagen IV, fibronectin, collagen I, α-smooth muscle actin (α-SMA) and E-cadherin, ameliorating experimental renal fibrosis in vivo. In addition, we also found that COS suppressed oxidative stress and inflammation in RF model mice. Further studies indicated that the mechanism by which COS alleviates renal fibrosis is closely related to the regulation of the TGF-β1/Smad pathway. COS has a therapeutic effect on ameliorating renal fibrosis similar to that of the positive control drug fosinopril. Taken together, COS can alleviate renal fibrosis induced by UUO by reducing oxidative stress damage and regulating the TGF-β1/Smad pathway.

Fosinopril diacid is an angiotensin converting enzyme inhibitor with efficient antihypertensive action. It is an active metabolic product formed in the body from hydrolysis of its prodrug Fosinopril. A sensitive, rapid method with high recovery for Fosinopril diacid from human plasma was developed. Solid-phase extraction technique employing Waters Oasis SPE cartridges gave clean samples with very high recovery of 97%. The analyte along with its internal standard (Benazepril hydrochloride) were chromatographed on an XTerra RP8 column (4.6 × 50 mm, 5 μm) using methanol-ammonium acetate buffer (10 mm; 90:10, v/v) as the mobile phase. A triple quadrupole mass spectrometer equipped with electrospray ionization source operated in the negative ion mode was used for detection. Multiple reaction monitoring scan mode was used for monitoring the transitions from m/z 434.00 → 237.15 for Fosinopril diacid and m/z 423.10 → 174.00 for Benazepril hydrochloride. Beer-Lambert's law was obeyed in the range of 0.50-1,500.00 ng/ml (r = 0.9993). The stability of the drugs in human plasma and in stock solution was proved by performing stability tests as per US Food and Drug Administration guidelines. The method was successfully applied for a bioequivalence study of Fosinopril diacid in 36 healthy, adult, male volunteers under fasting conditions.

Rationale: The most common cardiac involvement of Fabry disease (FD) is left ventricular hypertrophy (LVH), which usually occurs in male patients over the age of 30. In rare cases, it can progress to ventricular dilation in the late stage of the disease. Patient concerns: A 16-year-old boy presenting with recurrent extremity pain and chest distress was admitted to our hospital. Imaging examinations revealed ventricular dilation. Diagnosis: α-Galactosidase A enzyme assay and GLA gene sequencing confirmed the diagnosis of FD and revealed a novel mutation c.76_77insT. Interventions: The patient was treated using metoprolol (23.75 mg qd) and angiotensin-converting enzyme inhibitor (fosinopril sodium 5 mg qd). He refused enzyme replacement therapy for financial reasons. Outcomes: The echocardiography, electrocardiography, renal function, and routine blood and urine tests performed 20 months after the patients discharge from hospital showed no significant changes. The patient reported a slow and gradual decrease in the frequency and degree of pain and chest distress, starting approximately 24 months after discharge. Lessons: Cardiac involvement of FD can progress rapidly in some cases. Screening for FD should be considered in patients with unexplained ventricular dilation, especially in those with a history of typical FD manifestations.

Background Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection on cardiovascular diseases like hypertension and myocarditis. Purpose To elucidate the protective effects of XJEK on heart failure (HF) induced by myocardial infarction (MI) through the amelioration of inflammation, oxidative stress (OS) and endothelial dysfunction(ED). Materials and methods Fifty-seven male KM mice were randomized into the following six groups (n = 9–10 for each): control group, model group, MI+XJEK low dose group(XJEKL) group, MI+XJEK middle dose group(XJEKM), MI+XJEK high dose group(XJEKH), and MI+fosinopril group (positive control group). After treatment for four weeks, electrocardiography (ECG) and haemodynamics were recorded. Serum and tissues were collected for further analysis. Endothelium-dependent relaxation induced by acetylcholine was assessed in isolated thoracic aorta ring experiment. Hematoxylin and eosin (HE) and Van Gieson (VG) staining were used to detect the pathological changes of heart and thoracic aorta. Colorimetric analysis was employed to determine serum nitric oxide level (NO), malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. ELISA was used to detect serum B-type natriuretic peptide (BNP) and serum inflammatory cytokines, as well as endothelial NO synthetase (eNOS), angiotensinII (Ang II) and endothelin-1(ET-1) concentration in both serum and cardiac tissues. Immunohistochemistry and Western blotting (WB) were employed to detect eNOS and inflammatory cytokine expressions in cardiac tissues. Results XJEK administration markedly ameliorated cardiac dysfunction and abnormal ECG manifested by decreased weight/body weight (HW/BW) ratio, BNP and remedied hypertrophy of cardiomyocytes and deposition of collagen, which might be in part attributed to the increased SOD and decreased MDA in serum. Furthermore, XJEK administration improved ED with boosted eNOS activities in serum and cardiac tissues, as well as up-regulated NO levels in serum, down-regulated Ang II and ET-1 content in serum and cardiac tissues. Lastly, protein expression of pro-inflammation cytokines significantly decreased, and anti-inflammatory cytokine was significantly enhanced in serum and cardiac tissues compared to model group. Conclusion XJEK may exert beneficial effects on HF induced by MI in mice, and the underlying mechanism may be attributable to the amelioration of ED, anti-OS and anti-inflammation effects.

Ethnopharmacological relevance Diabetic nephropathy (DN) is an acute and serious diabetic complication characterized by renal hypertrophy and renal fibrosis with the expansion of extracellular matrices. Diabetic nephropathy has become a major cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound prescription which has been widely applied in clinical medicine for the prevention and treatment of diabetic nephropathy as well as for acute and chronic kidney injuries. However, the mechanism of protective effects of SZGB in DN remains unclear. Materials and methods In this research, we investigated the effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by performing a right uninephrectomy along with a single intraperitoneal injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D, SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage for 12 weeks. Samples from urine, blood and kidneys were collected for biochemical, histological, immunohistochemical and western blot analyses. Results We found that rats treated with SZGB showed reduced 24-h urinary protein excretion along with reduced serum total cholesterol (TC) and triglyceride (TG) levels. SZGB was also shown to prevent the disruption of catalase activity and reduce serum urea, creatinine, and renal malondialdehyde while increasing glutathione levels. Moreover, SZGB administration markedly improved the expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased the expression levels of Vimentin, α-SMA and Cleaved caspase-3 in the kidneys of diabetic rats. The renoprotective effects of SZGB was believed to be mediated by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Conclusions Therefore, it is suggested that SZGB can restrain epithelial-mesenchymal transition (EMT) through stimulating the Nrf2 pathway, which improves renal interstitial fibrosis in DN.

Diabetes mellitus (DM) is a systemic, chronic metabolic disease that is related to heredity and autoimmunity and is often accompanied by complications of retinopathy. However, the causative mechanism involved in the pathological process remains unclear. In this research, treatment with fosinopril or LY2109761 was found to be responsible for the improvement of the pathological processes, serum biochemical indexes and retinopathy in rats with streptozotocin-induced diabetes. In addition, the upregulation of angiotensin-converting enzyme (ACE) in the serum and the increased expression of TGF-β1 in the pathological outer nuclear layer (ONL) and inner nuclear layer (INL) of the retina were also reduced. In vitro experiments demonstrated that ACE enhanced cell damage and TGF-β1/Smad signaling pathway activation in retinal capillary endothelial cells (RCECs) under high glucose conditions. In addition, the activity of ACE was also considered to be related to the increasing levels of activated TGF-β1 in both rat retinal Muller cells (RMCs) and RCECs, but ACE activity had no effect on the high glucose-mediated upregulation of total TGF-β1 in RMCs. Coculture experiments with RCECs and RMCs showed that the barrier that was established under normal conditions was significantly impaired when exposed to high glucose combined with ACE, and damage of barrier can be prevented by adding fosinopril or LY2109761. Finally, a similar auxiliary effect of ACE was also observed in the activated TGF-β1-mediated barrier damage in blood-retinal barrier model in vitro. In summary, ACE-mediated TGF-β1/Smad signaling pathway activation was found to be involved in the destruction of the blood-retina barrier during diabetic retinopathy in a model of streptozotocin-induced diabetes, and these data may provide evidence to guide the treatment of the complications of diabetes mellitus.

The study aimed to investigate the effects of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on chronic heart failure (HF) in normoglycemic rats. The effects of empagliflozin were compared with the standard medications for HF, e.g., angiotensin-converting enzyme (ACE) inhibitor fosinopril, beta-blocker bisoprolol, and aldosterone antagonist spironolactone. Myocardial infarction (MI) was induced in male Wistar rats via permanent ligation of the left descending coronary artery. One-month post MI, 50 animals were randomized into 5 groups (n = 10): vehicle-treated, empagliflozin (1.0 mg/kg), fosinopril (10 mg/kg), bisoprolol (10 mg/kg), and spironolactone (20 mg/kg). All medications except empagliflozin were titrated within a month and administered per os daily for 3 months. Echocardiography, 24-hour urine volume test, and treadmill exercise tests were performed at the beginning and at the end of the study. Treatment with empagliflozin slowed the progression of left ventricular dysfunction: LV sizes and ejection fraction were not changed and the minute volume was significantly increased (from 52.0 ± 15.5 to 61.2 ± 21.2 ml/min) as compared with baseline. No deaths occurred in empagliflozin group. The 24-hour urine volume tends to be higher in empagliflozin and spironolactone groups than in vehicle and fosinopril group. Moreover, empagliflozin exhibited maximal physical exercise tolerance in comparison with all investigated groups (289 ± 27 s versus 183 ± 61 s in fosinopril group, 197 ± 95 s in bisoprolol group, and 47 ± 46 s in spironolactone group, p = 0.0035 for multiple comparisons). Sodium-glucose co-transporter 2 inhibitor empagliflozin reduced progression of left ventricular dysfunction and improved tolerance of physical exercise in normoglycemic rats with HF. Empagliflozin treatment was superior with respect to physical tolerance compared with fosinopril, bisoprolol, and spironolactone.

Systematic review of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) in the prophylactic treatment of adults with migraine. To identify gaps in research and provide guidance for future clinical trials. A search was completed using PubMed, MEDLINE, Embase, and the Cochrane Library January 1, 1990 through December 31, 2017. The following are keywords used in the search: migraine, migraine prophylaxis/prevention, renin-angiotensin-aldosterone system, RAAS, ACE inhibitors, angiotensin-converting enzyme inhibitors: quinapril, perindopril, ramipril, captopril, enalapril, lisinopril, benazepril, fosinopril. Angiotensin receptor blockers, ARB, angiotensin II receptor antagonists: candesartan cilexetil, irbesartan, olmesartan, valsartan, losartan, azilsartan medoxomil, telmisartan, and eprosartan. The search included randomized controlled trials (RCT), systemic reviews and open-label studies of ACE inhibitors and ARB for the prevention of migraine attacks in adults 18–70 years old. Of 2461 retrieved articles, 18 included RCT, meta-analysis, systemic reviews, or guidelines published on ACE inhibitors or ARB in the prevention of migraine. Three RCT with telmisartan 80 mg, candesartan 16 mg, and enalapril 10 mg, and two open-label trials with lisinopril 5 mg and ramipril 5 mg found a high number of responders with greater than 50 % reduction in migraine attack frequency when compared to a 4-week baseline period. Candesartan was superior to placebo while telmisartan and enalapril were not. Lipophilic ACE inhibitors and ARBs can be effective prophylactic agents for reduction of migraine frequency in adults. Based on the limited number of published trials and small sample size, they are not recommended as first-line prophylactic agents. However, in populations with co-morbidities such as hypertension, they may be useful as first- or second-line prophylactics. Additional trials following the International Headache Society’s guidelines on RCT are warranted.

Background Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. Methods Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. Results The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. Conclusion Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.

The present study was designed to elucidate the beneficial effects of XJEK on myocardial infarction (MI) in rats, especially through the amelioration of endothelial dysfunction (ED). 136 Sprague-Dawley rats were randomized into 13 groups: control group for 0wk (n = 8); sham groups for 2, 4, and 6 weeks (wk); MI groups for 2, 4, and 6 wk; MI+XJEK groups for 2, 4, and 6w k; MI+Fosinopril groups for 2, 4, and 6 wk (n = 8~10). In addition, 8 rats were treated for Evans blue staining and Tetrazolium chloride (TTC) staining to determine the infarct size. Cardiac function, ECG, and cardiac morphological changes were examined. Colorimetric analysis was employed to detect nitric oxide (NO), and enzyme-linked immunosorbent assay (ELISA) was applied to determine N-terminal probrain natriuretic peptide (NT-ProBNP), endothelin-1 (ET-1), angiotensin II (Ang II), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4), and endothelial NO synthase (eNOS) content. The total eNOS and eNOS dimer/(dimer+monomer) ratios in cardiac tissues were detected by Western blot. We found that administration of XJEK markedly ameliorated cardiovascular remodeling (CR), which was manifested by decreased HW/BW ratio, CSA, and less collagen deposition after MI. XJEK administration also improved cardiac function by significant inhibition of the increased hemodynamic parameters in the early stage and by suppression of the decreased hemodynamic parameters later on. XJEK also continuously suppressed the increased NT-ProBNP content in the serum of MI rats. XJEK improved ED with stimulated eNOS activities, as well as upregulated NO levels, BH4 content, and eNOS dimer/(dimer+monomer) ratio in the cardiac tissues. XJEK downregulated ET-1, Ang II, and ADMA content obviously compared to sham group. In conclusion, XJEK may exert the protective effects on MI rats and could continuously ameliorate ED and reverse CR with the progression of MI over time.

Background Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula that has beenreported to exert effective protection against cardiovascular diseases, such as hypertension and myocarditis. Objective The aim of the present study was to investigate the effect of XJEK on high-salt-induced hypertensive mice and its possible mechanism. Methods The model of hypertension was established through a high-salt diet. Sixty male Kunming mice were randomized into six groups, namely the Control, Model, Low-dose XJEK, Middle-dose XJEK, High-dose XJEK and Fosinopril groups (n=10 per group). Different steady interventions were given to each group: 0.9% Sodium chloride was added to the diet of the Control group and 8% sodium chloride to the diet of the other five groups from the very beginning. An additional 4, 8 and 12 g/kg/day XJEK were intragastrically administered to the Low-dose, Middle-dose and High-dose XJEK groups, respectively, and 2 mg/kg/day fosinopril to the fosinopril group, from the start of week 5. Systolic blood pressure (SBP) was measured weekly from weeks 1 to 8 using the tail-cuff method. At the end of week 8, left ventricular (LV) systolic pressure, LV end-diastolic pressure and rate of rise of LV pressure were examined using a TransonicScisense catheter (Transonic Systems Inc,Ithaca, NY,USA). Endothelium-dependent relaxations induced by acetylcholine were observed in an isolated thoracic aorta ring. Serum and heartsweresampled for the measurement of the following indexes:Serum nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content (determined by colorimetricanalysis); serum angiotensin II(Ang II), endothelin-1, endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4) concentration and l -arginine (determined by enzyme-linked immunosorbent assay); heart to body weight (HW/BW) ratio; myocardial morphological change (determined by HE and VG staining); myocardial eNOS expression (determined by immunofluorescence), and myocardial endothelin receptor A (ETA) expression (determined by western blotting). Results:Statistical data showed that the HW/BW ratio was significantly decreased in the drug treatment group. XJEK treatment could improve the heart systolic and diastolic function and ameliorate hemodynamic parameters and vascular remodeling indexes. Colorimetric results showed that, compared with the model group, XJEK increased serum SOD, NOlevels, and decreased those of serum MDA and Ang II. XJEK reverted changes in cardiac pathology, decreased the myocardial cross-sectional area, collagen volume fraction and perivascular collagen area and improved endothelial dysfunction (ED) by promoting eNOS activity, enhancing NO bioavailability, increasing the expression of BH4 and decreasing ETA content. In addition, treatment with XJEK decreased ADMA content in the myocardium. Conclusion:In conclusion, XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. The potential mechanism involves improved oxidative stress and endothelial dysfunction, independently of ameliorating BP.

The aim of the study was to determine the effect of carboxylesterase 1 (CES1) genetic variation on the activation of angiotensin-converting enzyme inhibitor (ACEI) prodrugs. In vitro incubation study of human liver, intestine and kidney s9 fractions demonstrated that the ACEI prodrugs enalapril, ramipril, perindopril, moexipril and fosinopril are selectively activated by CES1 in the liver. The impact of CES1/CES1VAR and CES1P1/CES1P1VAR genotypes and diplotypes on CES1 expression and activity on enalapril activation was investigated in 102 normal human liver samples. Neither the genotypes nor the diplotypes affected hepatic CES1 expression and activity. Moreover, among several CES1 nonsynonymous variants studied in transfected cell lines, the G143E (rs71647871) was a loss-of-function variant for the activation of all ACEIs tested. The CES1 activity on enalapril activation in human livers with the 143G/E genotype was approximately one-third of that carrying the 143G/G. Thus, some functional CES1 genetic variants (for example, G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs.

Ethnopharmacological relevance Chaihuang-Yishen formula (CHYS) is a Chinese herbal formula that has been shown clinically to effectively treat chronic kidney disease including diabetic nephropathy (DN), also known as diabetic kidney disease. Our previous animal studies showed that numerous intrarenal metabolites were associated with the development of DN. In the present work, an integrated metabolomic and lipidomic analysis was used to further examine whether CHYS could attenuate the development of DN by regulating the disordered metabolic pathways. Method Progressive diabetic kidney disease was induced in Wistar rats by uninephrectomy and a single intraperitoneal injection of streptozocin. Over 20 weeks, one group of animals was treated with CHYS and another group went untreated. Effects of CHYS on metabolomic and lipidomic changes in the renal cortex of diabetic rats were studied using gas chromatography/time-of-flight mass spectrometry, ultra-performance liquid chromatography/time-of-flight mass spectrometry, and tandem MS-based metabolomic and lipidomic. The well-established drug fosinopril was used as positive control throughout the experiment. Results Like fosinopril, treatment with CHYS produced a renoprotective effect against DN. Metabolomic and lipidomic analyses showed that the therapeutic effect of CHYS on DN was significantly associated with inhibition of the elevated organic toxins including several uremic toxins and glucuronides, and normalization of diminished phospholipids, especially sphingomyelins. Conclusion Improved abnormal metabolic and lipidomic disorders, such as accumulation of uremic toxins and glucuronides and phospholipids, may be mechanisms by which treatment of CHYS inhibits DN. Results from this study provide new evidence for the pharmacologic characteristics of CHYS on DN.

Hepatocellular carcinoma (HCC) is a major global health problem. Therapeutic interventions of HCC are still limited because of its complicated molecular pathogenesis. Many reports showed that renin-angiotensin system (RAS) contributes to the development of different types of malignancies. Therefore, the present study aimed to examine the effect of RAS inhibition using perindopril (1 mg/kg), fosinopril (2 mg/kg), or losartan (10 mg/kg) on diethylnitrosamine-induced HCC compared to sorafenib (30 mg/kg). The administration of RAS inhibitors resulted in improved liver function and histologic picture with a reduction in AFP levels. These effects found to be mediated through inactivation of NFкB pathway by the inhibition of NFĸB p65 phosphorylation at the Ser536 residue and inhibition of the phosphorylation-induced degradation of NFĸBia. Consequently, expression levels of cyclin D1 mRNA were significantly lowered. In addition, NFкB-induced TNF-α and TGF-β1 levels were reduced leading to lower levels of MMP-2 and VEGF. We concluded that RAS inhibition either through inhibiting the ACE or the blockade of AT1R has the same therapeutic benefit and that the tissue affinity of the ACEIs has no impact on its anti-tumor activity. These results suggest that ACEIs and ARBs can serve as promising candidates for further clinical trials in the management of HCC.

Background/Aims: Some angiotensin converting enzyme (ACE) inhibitors are efficiently removed from circulation by hemodialysis (‘high dialyzability'), whereas others are not (‘low dialyzability'). In patients receiving hemodialysis, this may influence the effectiveness of ACE inhibitors. Methods: Using linked healthcare databases we identified older patients receiving chronic hemodialysis who filled new ACE inhibitor prescriptions. The low dialyzability group (n = 3,369) included fosinopril and ramipril. The high dialyzability group (n = 5,974) included enalapril, lisinopril, and perindopril. The primary outcome was all-cause mortality within 180 days of first ACE inhibitor prescription. Results: There were 361 deaths among 5,974 patients (6.0%) prescribed with low dialyzability ACE inhibitors and 179 deaths among 3,369 patients (5.3%) prescribed with high dialyzability ACE inhibitors (relative risk 1.1, 95% CI 0.9-1.3, p = 0.6). Conclusion: In this study of older patients receiving hemodialysis, the dialyzability of ACE inhibitors was not associated with mortality or cardiovascular outcomes.

Pseudo-Sezary syndrome is a benign lymphoproliferative disorder, which clinically and pathologically mimics true Sezary syndrome. In this article, a case of pseudo-Sezary syndrome and review the literature has been reported. The patient was a 51-year-old man who developed erythroderma and palmoplantar keratoderma. The patient's medication history included fosinopril and combination metoprolol/hydrochlorothiazide. Flow cytometry showed a population of 2500 "Sezary-like" CD4726 T cells per microliter in the peripheral blood. Skin biopsy showed numerous atypical lymphocytes with epidermotropism, and there was matching dominant T-cell clonality in the skin and peripheral blood. After stopping all antihypertensive medications, the eruption resolved in its entirety.

Objective.To investigate the renal protective effects of early renin-angiotensin-aldosterone system (RAAS) blockade with renin-angiotensin system inhibitors (RASI) in systemic lupus erythematosus (SLE) patients with antiphospholipid-associated nephropathy (aPLN).Methods.Medical data of 57 SLE patients with biopsy-proven aPLN were analyzed. Early RAAS blockade was defined as administration of RASI within 3 months after kidney biopsy and continued for ≥ 12 months.Results.There was no significant difference in demographic data, laboratory findings, and renal histology by the time of kidney biopsy, except that the RASI group had higher proteinuria levels vs the non-RASI group [5.2 (2.8–8.8) vs 1.9 (0.6–2.8) g/d, p = 0.005, respectively] and higher prevalence of hypertension (75% vs 29%, p = 0.001, respectively). No significant difference between the 2 groups was observed in estimated glomerular filtration rate (eGFR), mean arterial pressure, and proteinuria level at 12 months after kidney biopsy. The improvement ratio of eGFR at 12 months was significantly higher in the RASI group versus the non-RASI group [26% (−5 to 86) vs −2% (−20 to 20), p = 0.028, respectively], and the rate of change in eGFR beyond 12 months was similar between the 2 groups. During a mean followup of 80 months, 4 (23%) patients in the non-RASI group and 3 (8%) patients in the RASI group developed kidney disease progression. Early RAAS blockade significantly decreased the risk of kidney disease progression [HR = 0.11 (0.02–0.59); p = 0.010]. Proteinuria and hypertension controls were similar between the 2 groups.Conclusion.Early RAAS blockade improved the short-term and longterm renal outcomes in SLE patients with aPLN. The renal protective effect of RASI was independent of its antihypertensive and antiproteinuric effects.

Purpose - to improve antihypertensive therapy on the basis of studying the antioxidant properties of an angiotensin-converting enzyme (ACE) inhibitor (fosinopril sodium) and a diuretic (hydrochlorothiazide), their impact on endothelial dysfunction and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. A combination of fosinopril sodium 20 mg/day and hydrochlorothiazid 12.5 mg/day was prescribed to 54 patients with essential hypertension of 1-3 grades, 30 to 65 years old . The control group included 10 healthy subjects matched for age and sex. During the course of combined antihypertensive therapy we observed a significant decrease of i-NOS activity, reduce of TNF-α type I of its soluble receptor (sTNF-αRI), and 8-iso-PgF2α in the patients. Activity of e-NOS, superoxide dismutase and catalase, in contrast, were increased in patients with hypertension and concomitant obesity. Thus, the improvement of endothelial function, a significant decrease autoimmune activation due to lower tension of oxidative stress in the examined patients optimizes use of a combination of fosinopril sodium and hydrochlorothiazid for differentiated therapy in hypertensive patients with obesity.

Background Myocardial infarction (MI) is a major risk factor responsible for morbidity and mortality. Xinji′erkang (XJEK) has been clinically used as an effective medication in the treatment of coronary heart disease and myocarditis. The purpose of this study was to investigate the cardioprotective effect of Xinji′erkang on MI mice. Methods Forty male mice were randomly assigned into four groups as follows (n = 10): sham, model, MI with administration of XJEK and fosinopril for four weeks. At the end of studies, hemodynamic parameters and electrocardiography (ECG) were recorded. Heart and body mass were measured and heart weight/body weight (HW/BW) ratio was calculated as index of hypertrophy. The hypertrophy of heart and aorta was examined using the hematoxylin and eosin (HE) staining, and the collagen deposition was evaluated using Van Gieson (VG) staining. Serum nitric oxide level (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were assayed by colorimetric analysis. The expressions of endothelial NO synthetase (eNOS) expression in serum and cardiac tissues were determined using ELISA assay and immunohistochemistry. Angiotensin II (Ang II) in serum and cardiac tissues was measured using ELISA assay. Besides, tumor necrosis factor-α (TNF-α), interleukin1β (IL-1β) and interleukin10 (IL-10) were observed in cardiac tissues with ELISA assay as well. Results The administration of XJEK significantly improved cardiac dysfunction and abnormal ECG with reduced HW/BW ratio and ameliorated cardiomyocyte hypertrophy and collagen deposition compared to MI, which was partly due to the decreased SOD and increased MDA in serum. Moreover, XJEK treatment also improved endothelial dysfunction (ED) with not only enhanced eNOS activities in serum and cardiac tissues and elevated NO levels in serum, but also decreased Ang II content in serum and cardiac tissues. Finally, protein expressions of pro-inflammation cytokines, TNF-α and IL-1β in the cardiac tissues with XJEK treatment were significantly decreased compared to model. On the contrary, IL-10, an anti-inflammatory cytokine concentrated in cardiac tissues was significantly enhanced compared to model. Conclusion Xinji′erkang exerts cardioprotective effect on myocardial infarction in mice, which may be due to the improvement of endothelial dysfunction and the reduction of oxidative stress and inflammation response.

Introduction Co-administration of a diuretic or calcium channel blocker with an ACE inhibitor are both preferred combinations in patients with hypertensive chronic kidney disease (CKD). According to the available evidence, it is still unknown which combination plays a more active role in renal protection. We hypothesised that a combination of fosinopril and benidipine may delay the progression of CKD more effectively than a combination of fosinopril and hydrochlorothiazide (HCTZ). Methods and analysis This study will be a multicentred, prospective, double-blind, randomised parallel controlled trial for hypertensive CKD patients in China. Patients will be randomised to one of two treatment groups: a combination of benidipine 4–8 mg/day and fosinopril 20 mg/day; or a combination of HCTZ 12.5–25 mg/day and fosinopril 20 mg/day. Patients will be followed up for 24 months after a month's fosinopril run-in. There will be dose-titration after 1 and 2 months. The primary endpoint is changes in estimated glomerular filtration rate (eGFR) from baseline to month 24. Secondary endpoints include changes in home blood pressure (BP), ambulatory BP, proteinuria, urinary albumin/creatinine ratio, and composite renal events in 24 months. Inclusion criteria are: age 18–80 years, non-dialysis CKD patients with eGFR >30 mL/min/1.73 m2, home BP >130 mm Hg systolic or BP >80 mm Hg diastolic at the screening and randomisation, and 24 hour proteinuria

Background Angiotensin-converting enzyme (ACE) inhibitors have been widely used in the treatment of hypertension, but the comparative effectiveness in reducing mortality among different drugs is seldom reported. Methods We identified hypertensive patients who started captopril, enalapril, lisinopril, fosinopril, perindopril, ramipril, or imidapril therapy from Taiwan's National Health Insurance database between 1 January 2004 and 31 December 2009. Overall and cause-specific mortalities were ascertained through a linkage to Taiwan's National Death Registry. Patients were followed from the initiation of ACE inhibitors to death, disenrollment, or study termination (31 December 2010). A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), using ramipril as the reference group. Results A total of 989,489 hypertensive patients were included, with a mean follow-up ranging from 3.5 years for imidapril to 4.5 years for enalapril. Captopril initiators had the highest overall mortality rate (117.8 per 1,000,000 person-days) as compared to other ACE inhibitors (54.3-79.4 per 1,000,000 person-days). Patients who started captopril therapy had a significantly increased risk of overall mortality (HR: 1.28, 95% CI: 1.24-1.31) when compared with ramipril. Enalapril (HR: 1.08, 95% CI: 1.05-1.11) and fosinopril (HR: 1.08, 95% CI: 1.05-1.12) were also associated with a modestly increased risk. No difference in mortality was found for lisinopril, perindopril, and imidapril, as compared with ramipril. Conclusions There are differences in the mortality risk associated with different ACE inhibitors. However, potential residual confounding effects might still exist.

BACKGROUND: Skeletal muscle impairment is a recognized complication of COPD, predicting mortality in severe disease. Increasing evidence implicates the renin-angiotensin system in control of muscle phenotype. We hypothesized that angiotensin-converting enzyme (ACE) inhibition would improve quadriceps function and exercise performance in COPD. METHODS: This double-blind, randomized placebo-controlled trial investigated the effect of the ACE inhibitor, fosinopril, on quadriceps function in patients with COPD with quadriceps weakness. Primary outcomes were change in quadriceps endurance and atrophy signaling at 3 months. Quadriceps maximum voluntary contraction (QMVC), mid-thigh CT scan of the cross-sectional area (MTCSA), and incremental shuttle walk distance (ISWD) were secondary outcomes. RESULTS: Eighty patients were enrolled (mean [SD], 65 [8] years, FEV1 43% [21%] predicted, 53% men). Sixty-seven patients (31 fosinopril, 36 placebo) completed the trial. The treatment group demonstrated a significant reduction in systolic BP (Δ−10.5 mm Hg; 95% CI, −19.9 to −1.1; P = .03) and serum ACE activity (Δ−20.4 IU/L; 95% CI, −31.0 to −9.8; P < .001) compared with placebo. No significant between-group differences were observed in the primary end points of quadriceps endurance half-time (Δ0.5 s; 95% CI, −13.3-14.3; P = .94) or atrogin-1 messenger RNA expression (Δ−0.03 arbitrary units; 95% CI, −0.32-0.26; P = .84). QMVC improved in both groups (fosinopril: Δ1.1 kg; 95% CI, 0.03-2.2; P = .045 vs placebo: Δ3.6 kg; 95% CI, 2.1-5.0; P < .0001) with a greater increase in the placebo arm (between-group, P = .009). No change was shown in the MTCSA (P = .09) or ISWD (P = .51). CONCLUSIONS: This randomized controlled trial found that ACE inhibition, using fosinopril for 3 months, did not improve quadriceps function or exercise performance in patients with COPD with quadriceps weakness. TRIAL REGISTRY: Current Controlled Trials; No.: ISRCTN05581879; URL: www.controlled-trials.com

Xin-Ji-Er-Kang (XJEK), a Chinese herbal formula, is effective against hypertension induced coronary heart disease, viral myocarditis and toxic myocarditis. In this study, the effect of XJEK on cardiovascular system was investigated. To test the hypothesis that Xin-Ji-Er-Kang (XJEK) has an anti-hypertensive effect mediated through attenuation of cardiac remodeling, and amelioration of vascular endothelial dysfunction and oxidative stress.Hypertension was induced in Wistar rats by 2 kidney 1 clip (2K1C) treatment. The hypertensive rats were then randomly assigned into four groups and treated as follows: group 1 (Sham-operated [Sh-Op] group received only drinking water), group 2 (induced hypertensive model+no treatment), and group 3 (induced hypertensive+a single daily oral dose of 24 g kg(-1) XJEK treatment) and group 4 (induced hypertensive+a single oral dose of 15 mg kg(-1) Fosinopril treatment). The rats in all the defined groups were respectively treated for a period of 4 weeks. Cardiovascular parameter such as systolic blood pressure (SBP) was measured weekly by using tail-cuff apparatus; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the rate of the rise in left ventricular pressure (±dp/dt max) were measured by using a PowerLab 8/30 apparatus (AD Instruments, Australia) at the end of the 8th week; heart weight/body weight (HW/BW) was determined as an index of myocardial hypertrophy (MH). Hematoxylin and eosin (HE) and Van Gieson (VG) stain were used to assess the cardio-histological changes. Colorimetric analysis was used to assay serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), nitric oxide (NO), and hydroxyproline (Hyp) contents in cardiac tissue. Angiotensin II (Ang II) content in serum was assessed by radioimmunoassay; tetrahydrobiopterin (BH4) content in cardiac tissue, BNP and endothelial NOS (eNOS) in serum were determined by using ELISA, and the protein expressions of c-Jun NH2-terminal kinase (JNK), P-JNK, p38, P-p38, and NADPH oxidases-2 (Nox-2) were measured by western blot.XJEK therapy could impair the heart systolic and diastolic function, potently improve the heart weight index, inhibit the elevation of HW/BW ratio, and markedly ameliorate hemodynamic indices and vascular remodeling index. It has blunted the decrease of SOD, NO and the increase in MDA and Ang II serum contents, myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) compared to the hypertensive model group. It also reduced the serum content of Hyp while increased BH4 levels in cardiac tissue. In addition, the expressions of Nox-2, P-JNK and P-p38MAPK were all suppressed compared to the hypertensive model group. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting eNOS activities and enhancing the NO activity in serum.The results of the present study show that XJEK attenuates 2K1C-induced hypertension in rats, which confirms our hypothesis that XJEK has an anti-hypertensive and cardiovascular remodeling effect via attenuation of cardiac remodeling and improvement of endothelial dysfunction and oxidative stress.

We tested five different angiotensin converting enzyme inhibitors (ACEI) as mitigators of experimental radiation nephropathy at drug doses calibrated to the plasma renin activity (PRA). This was done to determine whether all ACEI had the same efficacy as mitigators of radiation nephropathy when used at drug doses that gave equivalent suppression of the renin angiotensin system.10 Gy total body irradiation with bone marrow transplantation was used to cause radiation nephropathy in barrier-maintained rats. Equivalent ACEI doses were determined based on their effect to inhibit angiotensin converting enzyme (ACE) and raise the PRA in unirradiated animals.PRA-equivalent doses were found for captopril, lisinopril, enalapril, ramipril and fosinopril. These doses overlap the human doses of these drugs on a body surface area basis. All ACE inhibitors, except fosinopril, mitigated radiation nephropathy; captopril was a somewhat better mitigator than lisinopril, enalapril or ramipril.Most, but not all, ACEI mitigate radiation nephropathy at doses that overlap their clinically-used doses (on a body surface area basis). Fosinopril is known to be an ineffective mitigator of radiation pneumonitis, and it also does not mitigate radiation nephropathy. These pre-clinical data are critical in planning human studies of the mitigation of normal tissue radiation injury.

Rationale: Pulmonary hypertension (PH) is a complicated disease which has complex causes and poor outcome. Many factors are involved in the increase of pulmonary artery pressure. It is often difficult to identify the specific cause of a particular patient. However, identifying the etiology is of great importance for specifying treatment strategies and improving the prognosis of patients. Patient concerns: A 58-year-old male was admitted because of fatigue, breath shortness for 6 months, which got worse in the last 3 months. The ultrasound cardiogram (UCG) indicated a remarkably elevated pulmonary artery systolic pressure (PASP = 82 mm Hg). He had hypertension for 15 years. Besides, his spleen was found to be enlarged since 15 years ago. Bone marrow biopsy of the patient revealed myeloproliferative neoplasm (MPN) with severe myelofibrosis (MF). Diagnosis: Myeloproliferative neoplasm (MPN) with severe myelofibrosis (MF) which in turn caused PH and portal vein hypertension (PVH). Interventions: We treated the patient with diuretics and fosinopril, and also steroids and thalidomide for his MPN/MF. Outcomes: Two weeks later, the pulmonary artery pressure (PAP) was remarkably decreased (PASP = 53.1 mm Hg by UCG, mean PAP = 21 mm Hg by right cardiac catheterization). Within 2 years’ follow-up, his circulatory state and hematological state remained stable. Lessons: It is often difficult to define the cause of PH, but it is important for making the appropriate treatment at the same time.

To investigate fosinopril’s effect on the transient outward potassium current (Ito) of differing degrees of hypertrophied myocytes in the spontaneously hypertensive rat (SHR). Ten- and 24-week-old SHRs were used as models for cardiac hypertrophy. Hypertrophied ventricular myocytes were exposed to 1, 10, and 100 μmol/L fosinopril; the whole-cell patch-clamp technique was used to study the effects on the transient outward potassium current. Ito current density was decreased in SHR myocytes relative to controls (14.17 ± 0.31 and 11.62 ± 0.08 pA/pF in 10- and 24-week-old SHR versus 16.73 ± 0.15 pA/pF, p < 0.01). Higher concentrations of fosinopril (10 and 100 μmol/L) increased Ito peak current density in 10-week-old SHR myocytes compared with controls (14.92 ± 0.14 and 15.27 ± 0.13 pA/pF versus 14.17 ± 0.31 pA/pF, p < 0.01). Fosinopril increased Ito peak current density in 24-week-old SHR myocytes at all doses (12.70 ± 0.07, 13.74 ± 0.10, and 14.53 ± 0.13 versus 11.62 ± 0.08 pA/pF for controls, p < 0.01). Fosinopril had a greater Ito elevation potential on hypertrophied myocytes in 24-week-old compared with 10-week-old SHR for each dose (1.08 ± 0.09 versus 0.37 ± 0.26 pA/pF, p < 0.01; 2.13 ± 0.05 versus 0.75 ± 0.35 pA/pF, p < 0.01; 2.92 ± 0.07 versus 1.10 ± 0.40 pA/pF, p < 0.01). Fosinopril increased Ito current density in hypertrophied myocytes. This effect was more pronounced in myocytes with a greater degree of hypertrophy.

OBJECTIVES: Recurrent urinary tract infections (UTIs) are a problem affecting both women and men. Animal experiments and in vitro studies indicate that statins might prevent recurrent UTIs. We assessed the effects of pravastatin on UTI antibiotic prescribing among adults.METHODS: A post hoc analysis was conducted with data from PREVEND IT, a trial among participants randomized to receive pravastatin, fosinopril or placebo in a 2 × 2 factorial design over 4 years. Trial data were linked to the pharmacy prescription database IADB.nl. The primary outcome was the number of prescriptions with a nitrofuran derivate, a sulphonamide or trimethoprim as a proxy for UTI antibiotic prescribing. Generalized estimating equations were used to estimate the effect on the number of UTI antibiotic prescriptions. Cox regression was used to determine the effect on first and second (recurrent) UTI antibiotic prescriptions.RESULTS: Of the 864 trial participants, 655 were eligible for analysis. During an average follow-up of 3.8 years, 112 (17%) participants received at least one UTI antibiotic prescription. Intention-to-treat analyses showed that pravastatin was associated with a reduced total number of UTI antibiotic prescriptions (relative risk, 0.43; 95% CI, 0.21-0.88) and occurrence of second UTI antibiotic prescriptions [hazard ratio (HR), 0.25; 95% CI, 0.08-0.77]. No significant effect on occurrence of first UTI antibiotic prescriptions was found (HR, 0.83; 95% CI, 0.57-1.20). Fosinopril was associated with an increased occurrence of first UTI antibiotic prescriptions (HR, 1.82; 95% CI, 1.16-2.88). Combination therapy with fosinopril and pravastatin did not significantly influence the number of UTI antibiotic prescriptions.CONCLUSIONS: This study suggests that pravastatin can reduce the occurrence of recurrent UTIs. Larger studies among patients with recurrent UTIs are warranted.

Worldwide, diabetic nephropathy is one of the leading causes of end-stage renal failure. This hospital-based single-center prospective open-label randomized case-control interventional study was performed to evaluate and compare the native drug Dioscorea bulbifera with fosinopril in the management of diabetic nephropathy. Patients with diabetic nephropathy with proteinuria >500 mg/day or albuminuria >300 mg/ day, S Cr ≤2.5 mg/dL and hypertension controlled with a single drug were included into the study and were divided into three groups according to the interventional drugs that they were given; group A (n = 46) on fosinopril (5-40 mg/day), group B (n = 45) on Dioscorea bulbifera (500 mg BD) and group C (n = 46) on neither of these drugs. All necessary laboratory investigations needed to assess the effect of both the drugs were carried out. Patients were followed-up for six months. The study included 137 patients (M:F 2.61:1) with an age range of 19-76 years. At the sixth-month follow-up, a significant decrease in the systolic blood pressure was noted in all three groups whereas the diastolic blood pressure decreased significantly only in group B. There was significantly better control of both systolic and diastolic blood pressures in group B than in the other groups. Although fasting blood sugar was poorly controlled in the initial visit in all three groups, there was a significant decrease at the sixth-month follow-up in all three groups. Moreover, the decrease was significantly more pronounced in group B than in the other two groups. Low-density lipoprotein decreased significantly only in group B. Proteinuria, serum transforming growth factor-β, interleukin-6 (IL-6) and C-reactive protein decreased in both group A and group B, more so in the latter, but the differences between the groups were not statistically significant. Importantly, proteinuria and serum IL-6 showed an increasing trend in group C. It can be concluded that Dioscorea bulbifera was more effective than fosinopril in controlling blood pressure, glycemia, cholesterolemia and inflammatory state in diabetic nephropathy. Both agents decreased proteinuria. However, creatinine clearance significantly decreased with both the drugs, more so with Dioscera, and thus further evaluation with a larger trial is needed.

Fosinopril, an angiotensin-converting enzyme inhibitor, is known to attenuate cardiomyopathy induced by doxorubicin (DOX); however, the mechanisms of this cardioprotection are not fully elucidated yet. In the present study, experimental cardiomyopathy was induced in rats by administration of DOX with or without co-treatment with fosinopril. Fosinopril was utilized on day 1 or 14 of the treatment with DOX to compare efficacies of early versus late co-treatments. We observed that fosinopril attenuated changes induced by DOX (e.g., less increased heart and left ventricular weights, diminished lung congestion and ascites, attenuated LVEDP and LVSP, and less decreased +dP/dt and -dP/dt). Further, fosinopril diminished the levels of markers of cardiac toxicity (i.e., plasma levels and activities of cardiac enzymes and proteins AST, LDH, CPK, cTnI, and BNP). Fosinopril also prevented DOX-induced decreases in Ca(2+) uptake and restored activity of Ca(2+)-stimulated ATPase in left ventricular sarcoplasmic reticulum. We next tested whether the improved Ca(2+) transport activity in sarcoplasmic reticulum was due to modulation of SERCA2 and phospholamban expressions by fosinopril. Fosinopril attenuated the decrease in SERCA2 and phospholamban expressions caused by DOX. In conclusion, cardioprotective effects of fosinopril in the DOX-induced cardiomyopathy appear to be due to its ability to prevent remodeling of the cardiac sarcoplasmic reticulum membrane.

Evidence is currently equivocal on the added benefits of dual blockade of the renin-angiotensin-aldosterone system with the combination of either an ACE inhibitor (ACEI) plus an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) or aliskiren, the first-in-class direct renin inhibitor, plus an ARB. To compare the compliance, persistence, healthcare resource utilization, and healthcare costs associated with aliskiren plus ARB versus ACEI plus ARB combination therapies among adult patients diagnosed with hypertension. Patients (aged ≥18 years) initiated on either combination therapy were identified in the Market-Scan Commercial and Medicare Supplemental Databases (1 July 2007 to 30 June 2008). The ARB components considered were candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan. The ACEI components included benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. Outcomes measured during the 6-month study period included the proportion of days covered (PDC), treatment discontinuation, healthcare resource utilization, and changes in healthcare costs (study period minus 6-month baseline values). Risk-adjusted differences in outcomes between treatments and associated 95% confidence intervals (CIs) were estimated using multivariate regression models, controlling for demographics, region, co-morbidities, prescription drug use, and resource utilization during the baseline period. Adjusting for baseline characteristics, aliskiren plus ARB patients (n= 1395) demonstrated a significantly higher PDC (67.0% vs 54.3%; difference 12.7%; 95% CI 10.6, 14.7) and a significantly lower discontinuation rate (50.4% vs 68.6%; odds ratio 0.46; 95% CI 0.40, 0.54) than ACEI plus ARB patients (n=16 507). Aliskiren plus ARB patients had significantly fewer all-cause hospitalizations (adjusted incidence rate ratio [IRR] 0.73; 95% CI 0.61,0.86) and significantly fewer all-cause emergency room (ER) visits (adjusted IRR 0.72; 95% CI 0.61, 0.85) than ACEI plus ARB patients. Compared with ACEI plus ARB therapy, aliskiren plus ARB therapy was associated with significantly larger increases in prescription costs by $US264 post therapy initiation (95% CI 153, 375), but with non-significantly greater reductions in total healthcare costs by -$583 (95% CI −2409, 1242) [2008 values]. In adult hypertensive patients, treatment with aliskiren plus ARB was associated with significantly better compliance/persistence and fewer hospitalizations and ER visits compared with ACEI plus ARB therapy. Reductions in total healthcare costs were non-significantly different between patients treated with aliskiren plus ARB versus ACEI plus ARB, despite the increased prescription costs associated with aliskiren plus ARB therapy.

The present study evaluates the effects of a 6-month treatment with an ACE-inhibitor (ie, fosinopril) on serum concentrations of total IGF-1 and IGF binding protein (IGFBP)-3 in older adults at high risk for cardiovascular disease.Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial.Participants were recruited from the communities of Winston Salem, NC, and Greensboro, NC.Subjectsor = 55 years old with high cardiovascular disease risk profile.The intervention consisted of 6-month administration of fosinopril vs. placebo.Serum concentrations of total IGF-1 and IGFBP-3 were measured in 100 participants of the TRAIN study at baseline, 6-month and 12-month follow-up visits. Differences in total IGF-1 and IGFBP-3 concentrations were assessed using two-sided paired ttests.The mean age of participants (47% women) was 66.5 (standard deviation 7.2) years. Serum concentrations of total IGF-1 were significantly higher after 6-month treatment with fosinopril compared to placebo (203.73 ng/mL vs 194.24 ng/mL; p=0.02): After ACE-inhibitor intervention, significantly higher serum IGFBP-3 concentrations compared to controls (4308.81 ng/mL vs 4086.93 ng/mL; p=0.03) were also reported.A six-month treatment with fosinopril increases systemic levels of total IGF-1 and IGFBP-3 in older adults with high cardiovascular risk profile. This may represent a potential biological explanation to the beneficial effects of ACE-inhibition on stroke, ischemic heart disease and insulin resistance.

Aim: A possible link between the renin–angiotensin–aldosterone system (RAAS) and fibrinolysis has recently been suggested. Systemic infusion of angiotensin II results in an increase in plasminogen activator inhibitor type 1 (PAI-1) levels and angiotensin-converting enzyme inhibitors (ACEI) have been shown to decrease PAI-1 levels. Moreover, recent data indicated that plasma aldosterone levels were positively correlated with plasma PAI-1 levels. This study was designed to compare the effects of an ACEI with an ACEI in combination with an aldosterone antagonist on PAI-1 levels in chronic hypertensive patients. Methods: Patients were randomized into two groups and were treated with either low salt diet plus fosinopril (group 1, n = 43) or low salt diet plus fosinopril plus spironolactone (group 2, n = 42). Plasma PAI-1, tissue plasminogen activator (tPA) and plasma renin activity (PRA) levels were measured before and after 24 week treatment in both groups. Results: The mean basal PRA levels were similar in both groups. After antihypertensive therapy, the mean PRA increased significantly in both groups (P

Elevated blood glucose (BG) induced by antihypertensive agents increases the risk of cardiovascular events. This study was designed to investigate whether fosinopril+indapamide combination therapy has any effect on glucose tolerance (GT), and if it did, whether conversion to fosinopril alone could reverse the impaired GT.Included in the present study were 124 hypertensive patients, of whom 62 patients were treated with fosinopril plus indapamide (F/I group) and the remaining 62 patients were treated with fosinopril alone (F group). Of them, 89 patients completed a mean of 14-month follow-up. In the F/I group, 29 patients were converted to the use of fosinopril for 4-12 months after they completed the follow-up.In the F group, fasting BG decreased significantly from 5.1+/-0.5 to 4.8+/-0.7 mmol/l (p0.01), and 2-h postprandial BG decreased significantly from 7.2+/-1.6 to 6.4+/-1.4 mmol/l (p0.01), while in the F/I group, fasting BG increased significantly from 5.1 +/-0.6 to 5.3+/-0.9 mmol/l (p0.05), and 2-h postprandial BG increased significantly from 7.2+/-1.7 to 7.7+/-1.8 mmol/l (p0.05). In 29 patients of the F/I group who completed the follow-up and were converted to fosinopril, fasting BG decreased significantly from 5.5+/-1.0 to 5.3+/-1.0 mmol/l (p0.05), and 2-h postprandial BG decreased significantly from 7.5+/-2.0 to 7.0+/-2.7 mmol/l (p0.05).Fosinopril+indapamide combination therapy impaired GT in Chinese hypertensive patients, and fosinopril alone was able to reverse fosinopril+indapamide-induced GT impairment in part of these patients.

1. Angiotensin-converting enzyme inhibitors (ACEI) are hypotensive drugs that have been shown to prevent Type 2 diabetes mellitus (T2DM) in high-risk individuals. However, in T2DM, the effects of ACEI on hepatic steatosis are not known. The aim of the present study was to examine the effects of ACEI on changes in liver histology and hepatic mRNA expression of adipokines in rats with T2DM. 2. Thirty-six rats were divided into a normal control group, a T2DM group and a fosinopril-treated group. After six weeks of treatment with 5 mg/kg per day fosinopril, an ACEI, changes in liver histology, serum fasting glucose (FG), insulin, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin were evaluated, as was hepatic TNF-alpha, IL-6 and adiponectin receptor-2 (adipoR2) mRNA expression. 3. The degree of hepatic steatosis and inflammation, serum FG, insulin, TG, TC, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression were significantly higher in rats with T2DM than in normal controls. Serum adiponectin concentrations and hepatic adipoR2 mRNA expression in rats with T2DM were significantly lower than in normal controls. Fosinopril significantly reduced the degree of hepatic steatosis, serum FG, insulin, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression. Fosinopril significantly increased serum adiponectin concentrations and hepatic adipoR2 mRNA expression. 4. In conclusion, the ACEI improved insulin sensitivity and hepatic steatosis in rats with T2DM by increasing circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokine levels in the circulation and liver.

Gait ignition failure (GIF) classifications all had major limitations. Few years ago, a new and simpler classification was proposed by Liston. The aim of this paper is to discuss three GIF patients with respect to this new classification. All three patients presented with hesitation to start walking and turning and their neurological examination revealed start and turn hesitation without any other abnormality. We classified our patients according to Liston's classification as ignition apraxia, which enabled us to approach the patients in a practical way. This classification helps to understand the underlying pathologies and combines clinical characteristics and pathophysiology. We reported our experience with pergolide in the treatment of patients suffering from primary GIF and underline the fact that more research is needed on the treatment of this condition.

Objective: To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange. Case Summary: A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patient's jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment. Discussion: Angiotensin-converting enzyme (ACE) inhibitor–induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor–induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure. Conclusions: Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.

The ideal therapy for patients with isolated systolic hypertension remains unclear; diuretics, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors are all used in clinical practice. The aim of this study was to determine whether a fixed-dose ACE inhibitor/diuretic combination would reduce ambulatory blood pressures (BP) and arterial stiffness in isolated systolic hypertension more than antihypertensive monotherapy. In this randomized, double-blind study, 8 weeks of fosinopril/hydrochlorothiazide combination (10/12.5 mg titrated up to 20/12.5 mg) was compared with the calcium channel blocker (amlodipine, 5 mg titrated up to 10 mg) and diuretic (indapamide, 2.5 mg) monotherapy in 28 patients with isolated systolic hypertension. Each patient received all 3 therapies. Assessments included 24-hour ambulatory BP, clinic BP, and applanation tonometry-derived augmentation index. At 8 weeks, the fall in average 24-hour systolic BP and night time systolic BP were significantly greater in the fosinopril-hydrochlorothiazide group, compared to amlodipine and indapamide. The decrease in augmentation index and central aortic systolic BP was also greater in the fosinopril-hydrochlorothiazide group, compared to either amlodipine or indapamide. There was no difference between therapies in decrease in clinic systolic or diastolic BP, or diastolic ABP (average 24-h, diurnal, or nocturnal). Compared with either calcium channel blocker or diuretic therapy, a fixed-dose ACE inhibitor-diuretic combination induces greater reductions in systolic ABP, particularly at night, favorable effects that may be related to a decrease in the intensity of or delay in arterial wave reflections. ACE inhibitor-diuretic combination therapy is a useful approach to cardiovascular risk reduction in isolated systolic hypertension.

To study the effects of fosinopril on sinoaortic denervation (SAD)-induced pulmonary vascular remodeling and on phosphodiesterases (PDE) 1 in rats.SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. The experiment included sham-operated (Sham), SAD, and fosinopril-treated SAD groups. Fosinopril (15 mg/kg/d) was given in rat chow. After 16 weeks of treatment, the pulmonary arteries were taken for investigations, including pharmacological study, measurement of cGMP, light microscopy, immunohistochemistry, Western blotting, and quantitative real-time RT-PCR.Compared with Sham rats, blood pressure variability (BPV) was significantly increased in the SAD group. However, the mean pulmonary artery pressure (mPAP) was not significant change among 3 groups. After SAD, maximal contraction of pulmonary artery rings to phenylephrine was markedly decreased; the most prominent morphological change in the lung included thickening vascular walls, increasing number of smooth muscle cells, and greater wall-to-lumen ratio; the tissue concentrations of cGMP was reduced significantly; PDE1A or PDE1C expression was upregulated significantly, and endothelial nitric oxide synthase (eNOS) expression was downregulated significantly. Fosinopril treatment prevented these changes induced by SAD.Pulmonary artery remodeling (structural and functional abnormalities) was induced by SAD. Fosinopril, an angiotensin-converting enzyme inhibitor, mainly via potentiating eNOS pathway and inhibiting AngII formation, effectively prevented increased blood pressure variability and vascular remodeling of the pulmonary artery after SAD by regulating the activity levels or expression of eNOS, cGMP, and PDE1s.

Objective On average, 50% of patients are noncompliant with drugs for chronic health problems, despite their proven efficacy. It is therefore essential to have real-world data to devise suitable methods for improving persistence with these therapies. To measure and compare persistence rates with the angiotensin-converting enzyme inhibitors (ACEIs) in primary and secondary prevention and their determinants. Methods Two cohorts were reconstructed from the Regie de l'assurance maladie du Quebec's databases. The subjects had to be newly treated with ACEIs between January 1, 1998 and December 31, 2000. The primary prevention cohort consisted of 4596 hypertensive patients and the secondary prevention cohort of 1620 patients. The cumulative persistence rates were determined by the Kaplan–Meier method. The determinants of nonpersistence were evaluated with a Cox regression model. Results The 1-year persistence rates for the nonexclusive use of antihypertensive agents by initial prescribed agent: enalapril, fosinopril, lisinopril, quinapril, and ramipril were 66%, 64%, 69%, 65%, and 72% in the secondary prevention cohort, and of 66%, 72%, 71%, 72%, and 75% in the primary prevention cohort. The adjusted 1.5-year nonpersistence rates in primary prevention were higher for quinapril and enalapril than for ramipril. In secondary prevention all of the ACEIs were equivalent in nonpersistence rate. In secondary prevention cohort, having dyslipidemia, respiratory disease, ≥4 different classes of drugs/month increase the rate of persistence. Among, the primary prevention cohort, the fact of having diabetes, dyslipidemia, respiratory disease, using ≥4 different classes of drugs/month or prior hospitalization increased significantly the rate of persistence. For both cohorts, the fact of having high number of oral doses/day or elevated health-care resource utilization decreased significantly the rate of persistence. Conclusion The 1.5-year persistence rate was low compared with the threshold of 80% generally accepted. The high-risk patients were less likely to discontinue their treatment. These results can be of help in devising methods for improving the effectiveness of these drugs in routine practice.

Background In animal models, pretreatment with angiotensin-converting enzyme inhibitor (ACEI) can reduce no-reflow. In the present study, we investigated whether pretreatment with ACEI may prevent no-reflow in patients who underwent primary coronary intervention for AMI. Method and Results A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. No-reflow was defined as a TIMI flow grade < 3. The no-reflow phenomenon was found in 33 of 259 patients. There were no significant differences in clinical characteristics between the patients with and without ACEI pretreatment. However, the 47 patients receiving chronic ACEI treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, p < 0.05). Multivariable logistic regression analysis revealed that absence of ACEI pretreatment was a significant predictor of the no-reflow along with absence of preinfarction angina, complete occlusion of the culprit lesion, high-burden thrombus, ejection fraction on admission, number of Q-waves, absence of statin pretreatment, and anterior AMI. Conclusion Pretreatment with ACEI could preserve the microvascular integrity after acute myocardial infarction in humans. Copyright © 2007 Wiley Periodicals, Inc.

The article presents the evaluation of the influence of complex application of monopril, propranolol and heparin and percutaneous coronary intervention (PCI); monopril, propranolol with methylase in combination with PCI and PCI only on hemddynamics, cardiohemodynamics and clinical course in acute myocardial infarction (MI), as well as the monitoring of these patients. A comparison of the results of the complex medical and mechanical revascularization. The study involved 63 patients with acute coronary syndrome (ACS): anterior MI with Q wave and ST-segment with the rise in age from 30 to 70 years, the average age (56.7 +/- 1.2) years old, who were randomly divided into three groups with 21 in each. Patients in group I received heparin, propranolol with monopril and PCI; II--methylase (tenakteplaza) and propranolol, monopril and after 1 day they performed PCI; group III patients performed only PCI. With the help of echocardiography and Doppler echocardiometry values studied endsystolic (ESV) and end-diastolic (EDV) volume, ejection fraction (EF), stroke (SI) and heart (HI) index, index of local contractility disturbance of the left ventricle (LV ILCD) as well as the dynamics of systolic, (SBP) and diastolic (PBP) blood pressure, clinical features of myocardial infarction during follow-up. Injection of methylase, infusion of propranolol, receiving per os of monopril and conduct after 1 day of PCI accelerate the stabilization of central hemodynamics. ESV, EDV and ILCD reduce, systolic function of LV improves, ejection fraction increases. When there was no restenosis, myocardial infarction relapse and mortality 1 patient on 5th day was recorded acute heart failure (AHF). When treating by monopril, propranolol and heparin and conduct of PCI also stabilize central hemodynamics. ESV, EDV and ILCD reduce, EF increases and systolic function of LV improves (I group). However, in one patient on the 3rd day were recorded acute heart failure (AHF). Restenosis, recurrent myocardial infarction, and mortality were not observed. During the PCI only treatment 4 patients relapsed MI, 4 patients had restenosis, 2 patients had AHF and 2 patients died. Observations have shown that the combined application of drug therapy with PCI provides a positive predictive as opposed to using only PCI.

As the most common and severe complication of diabetes, diabetic nephropathy (DN) has been known to be related with angiotensin converting enzyme inhibitor (ACEI), which can reduce proteinuria and protect renal function. This study analyzed the effect of ACEI analog-fosinopril-on the expression of chemerin and vascular epithelial growth factor (VEGF), in an attempt to reveal the mechanism of ACEI analog on renal protection. A total of 45 SD rats were induced by sreptozotocin for diabetes and were given fosinopril via intragastric cannulation for 12 weeks. After sacrifice, serum and renal chemerin and VEGF contents were quantified by enzyme linked immunosorbent assay (ELISA) and Western blot method, in addition to biochemical laboratory examinations. In diabetic model rats, blood glucose, creatinine, urea nitrogen, 24-hour urinary protein, chemerin and VEGF protein contents were all significantly elevated when compared to those in control group (P

The aim of this study was to evaluate fosinopril-induced changes in hemodynamic parameters and tactile allodynia in a rat model of diabetes. Diabetes was induced by streptozotocin (STZ; 50 mg/kg, i.p.) in male Wistar rats. STZ produced hyperglycemia, weight loss, polydipsia, polyphagia, and polyuria as well as long-term arterial hypotension, bradycardia, and tactile allodynia at 10-12 weeks. Daily administration of the angiotensin converting enzyme inhibitor, fosinopril (25 mg/kg, p.o., for 11 weeks) partially reduced the loss of body weight, decreased hyperglycemia, and systolic blood pressure in diabetic rats. Likewise, systemic administration of fosinopril prevented the development and maintenance of tactile allodynia in STZ-induced diabetic rats. These data suggest that fosinopril may have a role in the pharmacotherapy of diabetic neuropathic pain.

Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric patients were included. Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded, randomized treatment (fosinopril 20 mg or placebo). Mean age was 51.1±11.5 years, and 65.6% were male. Median urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial pressure (β standardized =0.161; P =0.006), urinary sodium excretion (β standardized =0.154; P =0.011), and estimated renal function were independently associated with albumin excretion. In these predominantly normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by 18.5% versus a 6.1% increase on placebo after 3 months ( P standardized =−0.303; P

To investigate the effect of leflunomide for treatment of immunoglobulin A (IgA) nephropathy.Sixty IgA nephropathy patients were divided into two groups at random. Patients in the test group received leflunomide and patients in the control group received fosinopril. Clinical data were obtained at weeks 2, 4, 6, 8, 12, 16, 20, 24 and 28.The complete remission rate was 62.1% and the total effectiveness rate was 72.4%. In the leflunomide group, proteinuria significantly decreased from 1.66 +/- 0.42 g to 0.60 +/- 0.68 g (P0.05). The efficacy rate of leflunomide compared with fosinopril in treating IgA nephropathy was not statistically different (P0.05). Side-effects were mild in both treatment groups.These preliminary results are encouraging, but further randomised studies are required before leflunomide can be recommended for the treatment of IgA nephropathy.

Introduction. The aim of this study was to evaluate short-term clinical, bio?chemical and functional effects of fosinopril versus enalapril in patients with heart failure. Material and methods. 59 consecutive patients (mean age 57?8 years, EF 18.9?6.3%, NYHA III or IV class 19/59) -were randomized to receive fosinopril or enalapril for three months. All patients underwent echocardiography, metabolic testing, and a 6-minute walk test and completed the Minnesota questionnaire on inclusion and three months later. Additionally, serum creatinine, BUN, total cholesterol and triglycerides were measured. Kaplan-Meier curve was created to assess event-free survival for cardiac death and hospitalization for heart failure. Results. There was no statistically significant difference in event-free survival between patients on fosinopril and enalapril (86.7% vs. 82.8%, log rank 4.21 p=0.43). However, time to the event was longer in patients on fosinopril (77.0?25.35 vs. 40.2?6.8days, p=0.04). At the end of the study, no difference between fosinopril and enalapril group existed with respect to maximal oxygen consumption (20.90?4.47 vs. 20.89?6.86 ml/kg/mm), ejection fraction (20.5?7.4 vs. 2L4?7.8%), distance during the 6-minute test walk (313?74 vs. 352?129 meters) and quality of life (23.8?15.8 vs. 25.6?20.3 points), but patients on enalapril had higher creatinine (99?13 vs. 113?17 umol/L, p=0.002) and BUN (7.28?1.7vs. 8.89?2.39 mmol/L, p=0.01) levels. Increase in fosinopril dose during the study was higher than increase in enalapril dose (24.1%?23.8% vs. 9.5?24.5%, p=0.04). Conclusions. Fosinopril and enalapril have similar short-term effects on event-free survival, ejection fraction, functional capacity and quality of life in patients with heart failure. Patients on fosinopril presented with longer survival without event and had lower creatinine and BUN at the end of the follow-up. Additionally, fosinopril can be easily titrated to the maximum therapeutic dose. .

INTRODUCTION The cardiovascular changes (vascular structure changes, hypertrophy of the left ventricle) contribute to both the increased cardiovascular morbidity and the mortality of essential hypertension. Therefore, modern treatment strategies should not only target blood pressure (BP) reduction but also normalize cardiovascular structure and function. OBJECTIVE Aim of the study was to determine the effect of the ACE inhibitor Fosinopril on the Intima-media thickness of the common carotid artery and on the left ventricle mass after 9-month treatment of hypertensive patients. METHOD The study included 40 patients with the arterial hypertension and the left ventricle hypertrophy verified by echocardiography. The patients were randomized on A) ACE-inhibitor - Fosinopril and 6) without ACE inhibitor - atenolol, and they were followed up 9 months. The groups were not different by age, sex, and metabolic status. Color Duplex ultrasonography of the carotid arteries was performed by Acuson Sequia C236 with high-frequency linear probe of 8 MHz. The Intima-media thickness of the common carotids on the left and the right was measured in diastole at 1.5. cm from the highest point of bifurcation under maximal magnification. Using the same device, the left ventricle mass and other parameters of the left ventricle were determined in M-mode and by means of 2D image. RESULTS After 9 months, BP In both groups Was reduced In similar range (group A: systolic BP from 158 to 137 mmHg, and diastolic BP from 94 to 85 mmHg, and group B; systolic BP from 164 to 137 mmHg, and diastolic BP from 87 to 84 mmHg). The thickness of the intimomedial complex in patients using Fosinopril was decreased by 0.0278 ? 0.03 mm, while in the group of patients that did not use the ACE-inhibitor, it was increased by 0.078 ?0.13 mm. The left ventricle mass in patients using Fosinopril was decreased by 5 grams (312 ? 72 g vs. 307 ? 77 g), while in group B patients, it was increased by 15 grams (323 ? 79 g vs. 328 ? 58 g. Diastolic function expressed through relation E/A was improved minimally in the group A, while it worsened by 0.1 in the group B. After 9 months, serious cardiovascular events were recorded (one infarction of myocardium and one hospitalization due to the unstable angina pectoris) in two patients of the group A, while four patients of the group B. had serious CV events (1 cerebrovascular stroke and 3 hospitalizations due to unstable angina pectoris). CONCLUSION The results of our study showed that the application of Fosinopril in patients with the arterial hypertension and the left ventricle hypertrophy could efficiently block further progression of the intima-medial thickness of the common carotid artery, reduce the left ventricle mass, and improve. diastolic function of the left ventricle.

Aims Microalbuminuria frequently clusters with the metabolic syndrome and may identify subjects at increased coronary risk. Statin treatment may reduce the incidence of major adverse cardiac events in subjects with the metabolic syndrome, but evidence is limited. We evaluated the impact of pravastatin treatment on the incidence of major adverse cardiac events in microalbuminuric subjects with the metabolic syndrome. Methods and results This substudy of the PREVEND Intervention Trial (a randomized, placebo-controlled trial with a 2� 2 factorial design) included 864 microalbuminuric subjects, who were randomized to fosinopril 20 mg or matching placebo and pravastatin 40 mg or matching placebo (mean follow-up 46 months). The metabolic syndrome was defined according to the NCEP ATPIII-report. Subjects with or without the metabolic syndrome were characterized by a higher age, male sex, and increased albuminuria. The incidence of major adverse cardiac events in subjects with the metabolic syndrome [9.1%; 95% confidence interval (CI) 6.0–13.0%] was increased vs. those without [3.6%; 95% CI 2.3–5.5%; P ¼ 0.007). Pravastatin treatment lowered the incidence of major adverse cardiac events in subjects with the metabolic syndrome after adjustment for age and sex (hazard ratio ¼ 0.39; 95% CI 0.17–0.89; P ¼ 0.025). Conclusion This study supports the use of statins in microalbuminuric subjects with the metabolic syndrome to reduce the incidence of major adverse cardiac events.

There is a small body of literature on the interactions between lithium and angiotensin-converting enzyme inhibitors (ACEIs), but little data documenting the differences between these agents in their impact on serum lithium levels. We present the case of a 46-year-old male who sustained a five-fold increase in his serum lithium level after switching from fosinopril to lisinopril, with a peak serum lithium level of 3.4 meq/l. There was also an increase in serum creatinine from 1.1 on fosinopril to 1.4 after switching to lisinopril. The patient was hospitalized, and intravenously hydrated with 0.5 normal saline, with a reduction of the serum lithium level to 0.7 meq/l by 72 h after admission. The hospital course was marked by two episodes of bradycardia, but was otherwise uneventful, and the patient was discharged without any neurological sequelae. This case demonstrates that ACEIs may have differential effects on renal function, and the potential for significant alterations in lithium clearance that may not be clinically evident for several weeks. Lithium-treated patients who have a change in ACEI, especially those who are older or have below average renal function, must have diligent monitoring for the first 4-6 weeks after switching to detect potentially serious changes in serum lithium levels.