Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case is presented of a 70 year old woman with mild hypercholesterolaemia and hypertension who was readmitted to hospital six months after a previous admission for angina pectoris. The patient was treated with verapamil, nifedipine, and aspirin, and had been receiving bezafibrate (400 mg every 12 hours) for the previous 40 days. Twenty four hours after admission she developed podagra, which was treated with indomethacin (100 mg daily). Eight days after admission myocardial infarction was suspected, and the next day she presented with symptoms of rhabdomyolysis, which was confirmed by laboratory tests. Bezafibrate was withdrawn and the patient became asymptomatic after seven days. It is recommended that doctors should be aware of the possibility of patients, especially those with impaired renal function, developing rhabdomyolysis while being treated with bezafibrate.
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PMID:Bezafibrate induced rhabdomyolysis. 158 57

The benefit of aspirin therapy among women with coronary artery disease (CAD) is not well established. Previous studies have shown conflicting results among women. Data from 2,418 women with CAD screened for participation in the ongoing Bezafibrate Infarction Prevention (BIP) study were analyzed: 45% reported aspirin therapy. Baseline characteristics were similar in both groups. Cardiovascular mortality at 3.1 +/- 0.9 years of follow-up was 2.7% in the aspirin treated group versus 5.1% in the non-aspirin-treated women (p = 0.002). All cause mortality was 5.1% and 9.1%, respectively (p = 0.0001). Treatment with aspirin emerged as an independent predictor of reduced cardiovascular (RR = 0.61, 95% confidence interval [CI] 0.38 to 0.97) and all cause (RR = 0.66, 95% CI 0.47 to 0.93) mortality after multiple adjustment for possible confounders such as age, history of myocardial infarction, systemic hypertension, diabetes mellitus, peripheral vascular disease, current smoking, New York Heart Association classification, and concomitant treatment with digitalis. Women who benefited the most from aspirin therapy were older, diabetic, symptomatic, or had a previous myocardial infarction. Thus, treatment with aspirin was associated with reduced mortality among women with CAD. This study suggests that women with CAD should be treated with aspirin, unless specific contraindications exist.
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PMID:Effect of aspirin on mortality in women with symptomatic or silent myocardial ischemia. Israeli BIP Study Group. 896 May 77

Previous reports have yielded contradictory conclusions regarding the safety of digoxin therapy in patients with acute myocardial infarction. The purpose of our study was to determine whether digoxin therapy is associated with increased mortality in patients with chronic coronary artery disease. We analyzed data from 8173 patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) trial and who survived an acute myocardial infarction at least 6 months prior to the study. Three-year overall mortality of the 451 (15.5%) patients receiving digoxin (according to the judgement of their treating physician) at the time of screening for BIP participation, was 22.4% compared to 8.3% in the patients who did not receive digoxin. Cardiac mortality was 16.2% in the digoxin-treated group, compared to 4.9% in the non-treated patients. The increased risk associated with digoxin remained statistically significant when patients were stratified according to sex, age groups, functional capacity and the presence of hypertension, diabetes or angina. The administration of digoxin to survivors of an acute myocardial infarction in the chronic phase of their disease, is statistically associated with a 30-50% increase in the risk of overall and cardiac mortality during long-term follow-up. A propensity of increased risk of arrhythmias in ischemic coronary patients may explain this finding.
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PMID:Are coronary patients at higher risk with digoxin therapy? An ongoing controversy. 1018

The natural history of non-insulin-dependent diabetes mellitus (NIDDM) differs markedly between patients with diet treated and pharmacologically treated disease. However, the interrelationship between hypertension and these common diabetes types has not been specifically addressed in previous studies. This study was designed to evaluate the prognostic significance and prevalence of hypertension in coronary patients with diet versus pharmacologically treated NIDDM over a 5-year follow-up period. The study sample comprised 11 515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who had been screened but were not included in the Bezafibrate Infarction Prevention study. Among them, 9033 were nondiabetics and 2482, diabetics (987 diet treated and 1495 pharmacologically treated). The prevalence of hypertension among nondiabetics, diet-treated diabetics, and pharmacologically treated diabetics was 31%, 42%, and 43%, respectively. Crude all-cause mortality (CM) was lower in the nondiabetic patients (11.2% versus 22.0%; P<0.001). Among diabetics, 548 patients died: 81 diet treated normotensives (CM 14%); 100 diet-treated hypertensives (CM 24.4%); 205 pharmacologically treated normotensives (CM 24.2%); and 162 pharmacologically treated hypertensive patients (CM 25.0%). Age-adjusted mortality was lowest for the normotensive patients in the diet-treated group and highest for the hypertensive pharmacologically treated patients. Multivariate analysis shows that hypertension is a strong and independent predictor of increased CM in diet-treated but not in pharmacologically treated NIDDM: hazard ratio (HR) was 1.68 (95% confidence interval [CI] 1.24 to 2.29) for the diet-treated versus 1. 01 (95% CI 0.82 to 1.26) for the pharmacologically treated diabetics. The contribution of hypertension to stroke mortality was substantial for both diet treated and pharmacologically treated NIDDM: hazard ratios were 3.17 (95% CI 1.12 to 8.98) and 2.21 (95% CI 0.72 to 6.77), respectively. The increased risk of mortality associated with hypertension in relatively mild diet-treated NIDDM strongly supports the clinical benefit of early blood pressure control among diabetic patients with ischemic heart disease.
Hypertension 1999 Apr
PMID:Hypertension in diet versus pharmacologically treated diabetics: mortality over a 5-year follow-up. 1020 38

Few data are available regarding the prevalence and prognostic significance of the triple coexistence of undiagnosed systemic hypertension, diabetes mellitus, and coronary heart disease. This study aimed to evaluate the prevalence and prognostic significance of unrecognized hypertension in cardiac diabetic patients previously defined as "normotensives" over a 5-year follow-up period. The study sample comprised 11,515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who were screened but not included in the Bezafibrate Infarction Prevention study. Among them, 9,033 were nondiabetics and 2,482, diabetics. The diabetics were divided into 3 groups: (1) 1,272 normotensives, (2) 152 patients without history of hypertension but with elevated blood pressure ("unrecognized hypertensives"), and (3) 1,058 hypertensives with established diagnosis. The prevalence of both diagnosed and unrecognized hypertension in diabetics pooled together increased from 49% to 69% when World Health Organization and new Joint National Committee-VI criteria were compared. Crude all-cause mortality was lower in nondiabetics than in diabetics (11.2% vs 22.0%; p <0.001). Among diabetics the lowest all-cause mortality was documented for normotensives (19.3%), whereas the highest mortality was observed in unrecognized hypertensives (26.3%, p = 0.003). Both unrecognized and established hypertensives demonstrated a significant stroke-related mortality excess: about four- and threefold increases in cerebrovascular accident-related death, respectively, were observed (p = 0.002). On multivariate analysis, both unrecognized and diagnosed hypertension were consistent predictors of increased all-cause mortality, with a hazard ratio of 1.28 (95% confidence interval 0.90 to 1.82) and 1.24 (95% confidence interval 1.03 to 1.49), respectively. Our findings demonstrate widespread undiagnosed hypertension in diabetic coronary patients; their 5-year mortality was significantly increased compared with normotensives, and tended to be even higher than in diabetics previously identified as hypertensives.
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PMID:Prevalence and prognostic significance of unrecognized systemic hypertension in patients with diabetes mellitus and healed myocardial infarction and/or stable angina pectoris. 1049 38

Mortality rates are considerably higher in chronic ischemic heart disease (IHD) patients with non-insulin-dependent diabetes mellitus (NIDDM) than in those who are nondiabetics. The relationship between different types of antihyperglycemic pharmacological therapy and mortality rate in this NIDDM population is uncertain. We aimed to examine the survival in NIDDM patients with IHD using various types of oral antidiabetic treatments over a 5-year follow-up period. The study sample comprised 11,440 patients with a previous myocardial infarction and/or stable anginal syndrome, aged 45-74 years, who were screened, but not included in the Bezafibrate Infarction Prevention study. Among them, 9,045 were nondiabetics and 2,395 diabetics. The diabetic patients were divided into four groups on the basis of their therapeutic regimen at screening: diet alone (n = 990), sulfonylureas (n = 1,041), metformin (n = 78) and a combination of a sulfonylurea and metformin (n = 266). All NIDDM groups were similar with regard to age, gender, hypertension, smoking, heart failure, angina and prior myocardial infarction. Crude mortality rate was lower in the nondiabetic group (11.21 vs. 21.8%; p < 0.001). In the diabetic group, mortality was 18.5% for patients on diet alone, 22.5% for those on sulfonylureas, 25.6% for patients on metformin, and 31.6% for the combined sulfonylurea/metformin group (p < 0.01). When analyzing age-adjusted mortality rate and actuarial survival curves, the lowest mortality was found in patients on diet alone and the highest in patients on metformin (alone or in combination with sulfonylureas). After adjustment for variables connected with long-term prognosis, the use of metformin was associated with increased relative risk (RR) for all-cause mortality of 1.42 (95% CI 1.10-1.85), whereas the use of sulfonylureas alone was not [RR 1.11 (95% CI 0.90-1.36)]. NIDDM patients with IHD using metformin, alone or in combination with sulfonylureas, exhibited a significantly increased mortality. Until the results of problem-oriented prospective studies on oral control of NIDDM will be available, alternative therapeutic approaches should be investigated in these patients.
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PMID:Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up. 1051 15

A high fructose diet induces hypertension, hyperinsulinemia - insulin resistance, and hypertriglyceridemia (syndrome X). In this study, we investigated the role of an abnormal lipid profile in mediating fructose-induced hypertension. We hypothesized that bezafibrate, a lipid-lowering drug, would reduce elevated blood pressure and inhibit increased vascular reactivity in fructose-fed rats. Male rats were placed on four different diets: group 1 was fed standard chow (n = 6); group 2 was fed 60% fructose (n = 5); group 3 was fed fructose plus bezafibrate (30 mg x kg(-1) x day(-1); drinking water; n = 5); and group 4 was fed standard chow plus bezafibrate (n = 6). In addition, the direct effects of very low density lipoprotein (VLDL) on vascular reactivity were examined. Bezafibrate treatment lowered blood pressure, free fatty acids, and triglycerides in the fructose-fed group, suggesting that lipid abnormalities play a role in the elevation of blood pressure in the fructose-induced hypertensive rat. Aortae from fructose-fed rats were hyperresponsive to the calcium channel agonist Bay K 8644, which was normalized with bezafibrate treatment. Incubation of aortae in a VLDL medium resulted in increased responsiveness to Bay K 8644, lending further support to lipid abnormalities altering vascular reactivity. An altered lipid profile evidenced by elevated triglycerides and free fatty acids is causally related to the development of high blood pressure and increased vascular reactivity in the fructose-induced hypertensive rat.
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PMID:Bezafibrate, an anti-hypertriglyceridemic drug, attenuates vascular hyperresponsiveness and elevated blood pressure in fructose-induced hypertensive rats. 1058 79

This paper reviews the clinical trial data that offer insight into the question of whether, and in what groups of people, triglycerides might be an appropriate therapeutic target for the primary or secondary prevention of atherosclerotic cardiovascular disease. Two angiographic trials (the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial) and three clinical endpoint trials (the Helsinki Heart Study, the Bezafibrate Infarction Prevention Study, and the VA HDL Intervention Trial) are reviewed. Hypertriglyceridemia per se is probably not an appropriate therapeutic target for the prevention of atherosclerotic cardiovascular disease because it is a poor marker of atherogenic risk and because there have been no clinical trials that have directly addressed the question of whether lowering the triglyceride level reduces the number of clinical events. The studies reviewed here, however, suggest that patients with established coronary heart disease and a high triglyceride level, in association with either a low high-density lipoprotein-cholesterol level or perhaps other features of the metabolic syndrome, such as obesity, diabetes, or hypertension, may benefit from fibrate therapy. For patients without established coronary heart disease, it is reasonable to consider hypertriglyceridemia as a risk marker prompting the aggressive treatment of other risk factors such as hypertension, diabetes, high low-density lipoprotein-cholesterol, and obesity.
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PMID:Triglycerides and coronary heart disease: implications of recent clinical trials. 1114 64

The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet (FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (+198%) and hepatic cholesterol (+89%), but a decrease in hepatic phospholipids (-36%), hypertriglyceridemia (+223%), and hypertension (+15%), without increase in HIC. Amlodipine reduced blood pressure (-18%), plasma triglycerides (-12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (-24%), plasma triglycerides (-36%), hepatic triglycerides (-51%), and hepatic macrovesicular fat (-51%), but increased HIC (+23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (-49%), hepatic triglycerides (-78%), hepatic macrovesicular fat (-90%), and blood pressure (-11%). We conclude that FED rats can be a suitable model for human NAFLD. Drugs administered to treat various aspects of the metabolic syndrome could have hepatic effects. An increase in HIC in rats with NAFLD could be associated with increased hepatic fibrosis.
Hypertension 2005 May
PMID:Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. 1582 94

Activation of peroxisome proliferator activated receptor (PPAR)alpha and its protective role in cardiovascular function has been reported but the exact mechanism(s) involved is not clear. As we have shown that PPARalpha ligands increased nitric oxide (NO) production and cardiovascular function is controlled by a balance between NO and free radicals, we hypothesize that PPARalpha activation tilts the balance between NO and free radicals and that this mechanism defines the protective effects of PPARalpha ligands on cardiovascular system. Systolic blood pressure (SBP) was greater in PPARalpha knockout (KO) mice compared with its wild type (WT) litter mates (130+/-10 mmHg versus 107+/-4 mmHg). L-NAME (100mg/L p.o.), the inhibitor of NO production abolished the difference between PPARalpha KO and WT mice. In kidney homogenates, tissue lipid hydroperoxide generation was greater in KO mice (11.8+/-1.4 pM/mg versus 8.3+/-0.6 pM/mg protein). This was accompanied by a higher total NOS activity (46+/-6%, p<0.05) and a approximately 3 fold greater Ca2+-dependent NOS activity in kidney homogenates of untreated PPARalpha WT compared with the KO mice. Clofibrate, a PPARalpha ligand, increased NOS activity in WT but not KO mice. Bezafibrate (30 mg/kg) reduced SBP in conscious rats (19+/-4%, p<0.05), increased urinary NO excretion (4.06+/-0.53-7.07+/-1.59 microM/24 h; p<0.05) and reduced plasma 8-isoprostane level (45.8+/-15 microM versus 31.4+/-8 microM), and NADP(H) oxidase activity (16+/-5%). Implantation of DOCA pellet (20mg s.c.) in uninephrectomized mice placed on 1% NaCl drinking water increased SBP by a margin that was markedly greater in KO mice (193+/-13 mmHg versus 130+/-12 mmHg). In the rat, DOCA increased SBP and NAD(P)H oxidase activity and both effects were diminished by clofibrate. In addition, clofibrate reduced ET-1 production in DOCA/salt hypertensive rats. Thus, apart from inhibition of ET-1 production, PPARalpha activation exerts protective actions in hypertension via a mechanism that involves NO production and/or inhibition of NAD(P)H oxidase activity.
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PMID:NAD(P)H oxidase/nitric oxide interactions in peroxisome proliferator activated receptor (PPAR)alpha-mediated cardiovascular effects. 1605 68


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