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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelets are intimately involved in atherosclerosis, and hypertension is a known risk factor for coronary artery disease. The angiotensin-converting enzyme (ACE) inhibitors were demonstrated to reduce hypertension and attenuate atherosclerosis. Because increased platelet aggregation was shown in hypertensive patients, the effect of a new ACE inhibitor, fosinopril, on platelet aggregation was studied. Fosinopril therapy (10 mg/day for 4 weeks) in 18 male hypertensive patients showed > or = 31% reduction in ADP-induced platelet aggregation. In vitro studies showed that fosinopril had similar inhibitory effect on ADP-induced platelet aggregation. No inhibitory effect could be detected with collagen as the aggregating agent. Finally, inhibition of platelet aggregation by fosinopril was less effective in platelets derived from hypertensive patients as compared with platelets derived from normal subjects. We conclude that fosinopril possesses a significant inhibitory activity on ADP-induced platelet aggregation both in vitro and in vivo.
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PMID:Fosinopril reduces ADP-induced platelet aggregation in hypertensive patients. 872 Apr 15

Recent trials in hypertensive patients with type 2 diabetes reveal important differences in the risk for major cardiovascular events when individual agents are compared. In the Fosinopril Amlodipine Cardiovascular Events Trial (FACET), 380 patients with hypertension and type 2 diabetes were randomized to fosinopril or amlodipine and followed for up to 3.5 years to assess effects on serum lipids. Although both agents effectively controlled blood pressure, amlodipine caused a significantly greater decrease in systolic pressure. At the end of the trial, serum cholesterol, high-density lipoprotein cholesterol, triglycerides, HbA1c, serum glucose, plasma insulin, serum creatinine, and microalbuminuria were similar in both groups. The patients randomized to fosinopril were significantly less likely to experience the prospectively defined combined outcome of acute myocardial infarction (MI), hospitalized angina, or stroke compared to those randomized to amlodipine (RR 0.49; 95% CI 0.26-0.95). In the Appropriate Blood pressure Control in Diabetes (ABCD) trial, 470 patients with hypertension and type 2 diabetes who were randomized to long-acting nisoldipine had an adjusted sevenfold increased risk for acute MI compared to those randomized to enalapril (RR 7.0; 95% CI 2.3-21.4). In the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) trial, the patients with hypertension and above the median of HbA1c (> or =6.7%) randomized to isradipine had a threefold increased risk for major cardiovascular events compared to those randomized to hydrochlorothiazide (RR 2.81; 95% CI 1.09-7.26). These findings are supported by several observational studies. Therefore, evidence is emerging that angiotensin-converting enzyme inhibitors and low-dose diuretics may be more effective than calcium antagonists for prevention of cardiovascular events in hypertensive patients with diabetes or impaired glucose control.
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PMID:New evidence on the prevention of cardiovascular events in hypertensive patients with type 2 diabetes. 973 37

Angiotensin II (Ang II) was shown to be an important risk factor for accelerated atherosclerosis. Inhibition of Ang II action on the arterial wall by blocking its production with angiotensin converting enzyme (ACE) inhibitors, or by blocking binding to its receptors on cells with antagonists was shown to attenuate atherogenesis in animal model of atherosclerosis. We questioned whether Ang II atherogenicity is related to a stimulatory effect of Ang II on macrophage cholesterol biosynthesis. Angiotensin II injected intraperitoneally once a day (0.1 ml of 10(-7) M per mouse) for a period of 30 days, to the apolipoprotein E deficient mice increased the atherosclerotic lesion area by 95% (P < 0.01 vs. control), compared to placebo-injected mice, with no significant effect on blood pressure or on plasma cholesterol levels. On using mouse peritoneal macrophages (MPMs) that were harvested after intraperitoneally injection of Ang II, an increased rate of cellular cholesterol biosynthesis (measured as incorporation of [3H]acetate into cholesterol) by up to 90% (P < 0.01 vs. control) was observed. In mice treated with the ACE inhibitor, Fosinopril (25 mg/kg per day) a reduction in their MPM's cholesterol synthesis by up to 70% (P < 0.01 vs. control) was obtained. In vitro studies in human monocyte-derived macrophages (HMDM), in MPMs from control BALB/c mice, and in J-774 A.1 macrophage-like cell line demonstrated up to 44, 34 and 30% stimulation of macrophage cholesterol biosynthesis, respectively, following cell incubation with 10(-7) M Ang II for 18 h at 37 degrees C. The stimulatory effect of Ang II on macrophage cholesterol biosynthesis could be related to its interaction with the macrophage AT1 receptor, as Losartan (10(-5) M), an AT1 blocker, but not PD 123319 (10(-5) M), an AT2 blocker, prevented the stimulatory effect on macrophage cholesterol synthesis. Furthermore, in cells that lack the AT1 receptor (RAW macrophages), Ang II did not increase cellular cholesterol synthesis. Ang II increased macrophage 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase mRNA levels in a dose dependent manner in J-774 A.1 macrophages and in MPM. Losartan, the AT1 receptor antagonist clearly attenuated this mRNA induction. We thus conclude that Ang II stimulation of macrophage cholesterol biosynthesis is related to its interaction with the AT1 receptor, followed by stimulation of macrophage HMG CoA reductase gene expression, which leads to increased cellular cholesterol biosynthesis, and can possibly result in macrophage cholesterol accumulation and foam cell formation.
Atherosclerosis 1999 Oct
PMID:Angiotensin II atherogenicity in apolipoprotein E deficient mice is associated with increased cellular cholesterol biosynthesis. 1053 81

The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matching placebo and to fosinopril 20mg or matching placebo. Using high resolution ultrasound, flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) was assessed at baseline and after 4 years of treatment in a total of 276 subjects. At baseline, mean+/-standard error FMD was 4.73+/-0.49% and NID was 10.86+/-0.67%. Pravastatin significantly reduced total cholesterol and LDL cholesterol (p<0.01) and randomization to pravastatin was associated with a non-significant improvement of 18.9% in FMD (+0.80+/-0.95, p=0.09), without a significant change in NID. Interestingly, pravastatin significantly increased FMD by 34.9% in men (+1.23, p=0.04), but only 1.1% in women (+0.06, p=0.95). Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion, systolic and diastolic blood pressure (all p<0.01). In conclusion, after 4 years of follow-up, pravastatin treatment tended to increase FMD and this effect was predominantly present in men. Fosinopril treatment did not modify FMD during long-term follow-up.
Atherosclerosis 2008 Jan
PMID:Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects. 1714 Dec 45

Inflammation is an important factor in the development and progression of atherosclerosis. Observational studies have suggested that renin-angiotensin system inhibition might lower C-reactive protein (CRP). The aim of this study was to test the hypothesis that angiotensin-converting enzyme inhibition with fosinopril would reduce inflammation in a placebo-controlled trial involving 621 subjects. CRP was determined using a high-sensitivity assay at baseline and after 3 months of fosinopril treatment. The median CRP level at baseline was 1.38 mg/dl (interquartile range 0.64 to 2.86) and did not significantly differ between treatment groups. CRP levels at baseline were significantly associated with future cardiovascular events, even after adjustment for age and gender (odds ratio 1.76, 95% confidence interval 1.16 to 2.67, p = 0.008). Fosinopril treatment during 3 months did not result in a significantly higher reduction of CRP levels compared with placebo (difference -0.11, p = 0.20). Exploratory analysis suggested an interaction between gender and fosinopril treatment on CRP reduction (p = 0.07). Male gender was associated with a significantly larger reduction in CRP compared to female gender. In conclusion, contrary to previous observational studies, no effect of angiotensin-converting enzyme inhibition on CRP levels was found.
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PMID:Effect of fosinopril treatment on serum C-reactive protein levels in patients with microalbuminuria. 1860 26