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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and hypercholesterolemia frequently coexist and may require concomitant drug treatments. The efficacy and safety profile of lovastatin given in the presence of antihypertensive medication was evaluated using patient subgroups identified in the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study. The EXCEL study examined 8,245 patients with moderate hypercholesterolemia randomly assigned either to a group treated with lovastatin (20-80 mg daily) or to a group given placebo for 48 weeks. After adjustment for patient characteristics, pairwise comparisons were made between patients taking no antihypertensive agents (n = 3,772) and those taking either calcium antagonists (n = 446), selective beta 1-adrenergic receptor blockers (n = 326), nonselective beta-adrenergic receptor blockers (n = 219), potassium-sparing diuretics (n = 187), thiazide diuretics (n = 126), or angiotensin converting enzyme inhibitors (n = 171). The placebo-corrected dose-dependent effect of lovastatin on the percent change from baseline in low-density lipoprotein cholesterol was not attenuated in any subgroup and was slightly enhanced in the calcium antagonist subgroup (-29% to -44%, p = 0.06) when compared with patients taking no antihypertensive agents (-24% to -40%); this difference, however, was only of borderline significance. Patterns of lovastatin-induced increase in high-density lipoprotein cholesterol and decrease in triglycerides were not consistently different among the subgroups. Examination of mean changes in serum transaminases, mean changes in creatine kinase, and the proportion of patients discontinuing therapy for clinical adverse experiences did not indicate the presence of an interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Mar
PMID:Lovastatin and coadministered antihypertensive/cardiovascular agents. 134 57

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
Hypertension 1992 Nov
PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

This study reports the results of a 6-month, open-label multicenter study of the efficacy and tolerability of lovastatin, a 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase inhibitor, in the management of nonfamilial primary hypercholesterolemia. The study enrolled 489 patients with elevated total serum cholesterol levels, whose lipids were not controlled sufficiently by diet. There was good representation of gender (48.3% women and 51.7% men), age (mean 57, range 25 to 83) and hypertension status (55.4% normotensive and 43.6% hypertensive) in the sample. Within 1 month of lovastatin therapy, total cholesterol was reduced 19% (from a mean of 269 to 217 mg/dl, low-density lipoprotein (LDL) cholesterol was reduced 27% (191 to 140 mg/dl), high-density lipoprotein (HDL) cholesterol increased 6% (42.6 to 45.1 mg/dl), the ratio of total cholesterol to HDL was reduced 24% (6.7 to 5.1) and the ratio of LDL to HDL was reduced 30% (4.7 to 3.3). These results were consistent across age group, gender and hypertension status, and were maintained for a period of 6 months of therapy. Lovastatin was generally well tolerated. Of the 489 patients enrolled, 449 (92%) completed 6 months of therapy. Only 21 (4%) withdrew because of adverse experience regardless of cause. None of the few serious adverse experiences (e.g., myocardial infarction) could be attributed to the drug. Abnormal laboratory values during the 6 months of therapy were within expectations. Seventy-four patients had at least 1 abnormal value during 6 months of treatment. Of these, 42 had at least 1 mild to moderate creatine phosphokinase elevation during this period. Only 1 patient had an adverse change on ophthalmologic examination: a posterior subcapsular opacity in both eyes just visible on 6-month examination.
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PMID:Efficacy and tolerability of lovastatin in a six-month study: analysis by gender, age and hypertensive status. 220 30

The leukocyte glycoprotein L-selectin mediates an early step in the recruitment of leukocytes to sites of inflammation. L-Selectin surface expression is rapidly down-regulated by inflammatory signals in vitro. In a prospective study, we found L-selectin expression on umbilical cord blood granulocytes and monocytes to be significantly decreased in newborn infants with acute bacterial infection compared with controls (p < 0.01). A significantly reduced L-selectin expression of both granulocytes and monocytes was also found to be associated with an increased neutrophil immature/total ratio (p < 0.01) but not with other laboratory markers of neonatal sepsis. There was no apparent impact of prematurity, low birth weight, gestational hypertension, or gestational diabetes on L-selectin expression. Although the mode of delivery did not affect granulocyte L-selectin expression, umbilical cord blood monocytes showed an increased L-selectin expression after emergency cesarean delivery compared with samples obtained after elective cesarean or vaginal delivery (p < 0.01). We conclude that acute systemic inflammation results in down-regulation of granulocyte and monocyte L-selectin expression in vivo similar to that observed in vitro.
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PMID:L-selectin is down-regulated in umbilical cord blood granulocytes and monocytes of newborn infants with acute bacterial infection. 753 4

Previous data in rat conductance vessels indicated that cellular mevalonate contributes to vascular tone and systemic blood pressure control. Using exogenous mevalonate (M) or lovastatin, a 3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitor (L), we characterized the role of mevalonate availability in resistance artery function, both in experimental animals and humans. Rat mesenteric artery resistance vessels (MARV, n = 9) were incubated for 48 h with either L, M, L + M, or vehicle (V) and tested for reactivity to NE, serotonin, acetylcholine, atrial natriuretic peptide, and sodium nitroprusside (SNP). Lovastatin increased sensitivity to NE (P < 0.03) and serotonin (P < 0.003), and significantly impaired the response to all three vasodilators. These effects were reversed by co-incubation with mevalonate. Mevalonate alone had no effect. In separate experiments, intravascular free Ca2+ concentration (ivfCa2+) was determined in fura-2AM loaded MARV. Basal ivfCa2+ was increased after a 48-h exposure to L (52.7 +/- 4.6 nM, L, vs. 29.7 +/- 2.4 nM, V, n = 12, P < 0.003), as were ivfCa2+ levels following stimulation with low (100 nM) NE concentrations. Similar ivfCa2+ concentrations were achieved during maximum contraction with NE (10 mM) in both groups. Human resistance arteries of human adipose tissue were also studied. Lovastatin increased the sensitivity to NE (ED50 = 372 +/- 56 nM, V, and 99 +/- 33 nM, L, P < 0.001) and significantly decreased the relaxation to acetylcholine and SNP of human vessels. We conclude that mevalonate availability directly contribute to resistance vessel function and vascular signal transduction systems in both experimental animals and humans. The study calls for the identification of non-sterol, mevalonate-derived vasoactive metabolites, and suggests that disorders of the mevalonate pathway can alter vascular tone and cause hypertension.
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PMID:Mevalonate availability affects human and rat resistance vessel function. 761 93

A previously published study reported on an open-label, multicenter study of the efficacy and tolerability of lovastatin in the management of nonfamilial primary hypercholesterolemia. In the present report the results from the 213 hypercholesterolemic patients with systemic hypertension are presented. At baseline mean +/- SD of total serum cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and the ratio of total serum cholesterol to HDL cholesterol were 268 +/- 24, 189 +/- 22 and 43 +/- 10 mg/dl and 6.6 +/- 1.6, respectively. Of the 213 hypertensive patients only 24 were not receiving antihypertensive or related cardiac medication. Baseline mean systolic and diastolic blood pressures were 140 +/- 20 and 84 +/- 9 mm Hg, respectively. Within 1 month of lovastatin therapy the observed significant reductions in total serum cholesterol, low-density lipoprotein cholesterol and the ratio of total to HDL cholesterol were 19, 27 and 24%, respectively. HDL cholesterol was increased by 6%. Diastolic blood pressure did not change significantly during this 1-month period. The 1-month lipid results were maintained over the full 6 months of the study. The dosage of lovastatin was 20 mg/day for the first month of therapy and could subsequently be adjusted to response, up to a maximum of 80 mg/day. Again, without changes in diastolic blood pressure, lovastatin was generally effective in improving the serum lipids of hypercholesterolemic hypertensive patients regardless of the type of antihypertensive medications received (including diuretics and beta blockers). Lovastatin was generally well tolerated.
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PMID:Efficacy and tolerability of lovastatin in hypercholesterolemia in patients with systemic hypertension. 809 85

Single cardiovascular risk factor intervention is probably not sufficient to prevent atherosclerosis progression. There is a lack of data on concomitant use of hypocholesterolemic agents and antihypertensive drugs with respect to possible interactions and adverse experiences. We studied 293 patients (below 65 years of age) under treatment with either lisinopril (n = 144) or nifedipine (n = 149) for mild to moderate hypertension for 10 weeks, and with serum cholesterol above 6.5 mmol/L, who were randomized to either lovastatin 20 mg every day or placebo in a double-blind, double-dummy design for 6 weeks. Lovastatin effectively lowered cholesterol by 16% and 15% in the lisinopril and nifedipine group respectively (P < .01 compared to placebo for both groups) without any negative impact on the antihypertensive efficacy of either lisinopril or nifedipine. The drugs in combination were well tolerated and did not affect the well-being of the patients, and did not cause any more adverse effects than the antihypertensive agents alone. Liver enzymes increased slightly during lovastatin therapy, while no case of myopathy was reported. Combined therapy with lovastatin and antihypertensive therapy can be safely undertaken.
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PMID:Effect and tolerability of combining lovastatin with nifedipine or lisinopril. 821 32

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by high levels of cholesterol, triglycerides, or both. The basic metabolic abnormality is overproduction of apolipoprotein B-100. High atherogenicity has been attributed to all forms of FCHL. We evaluated combined bezafibrate-lovastatin therapy in 10 patients (9 men and 1 woman) with FCHL and markedly high cholesterol and triglyceride levels who were at high risk of coronary artery disease and who had not responded to diet and bezafibrate treatment alone. Eight patients had coronary artery disease, 6 had hypertension, and 3 had noninsulin-dependent diabetes mellitus. Lovastatin 20 mg/day was added to the bezafibrate 600 mg/day regimen for 6 weeks; the lovastatin dosage was then doubled to 40 mg/day for an additional 6 weeks. The addition of 20 mg of lovastatin resulted in decreases of 15%, 20%, and 13% in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, respectively. Increasing the dose of lovastatin to 40 mg resulted in further moderate decreases of 4%, 3%, and 8% in total cholesterol, LDL cholesterol, and triglycerides, respectively, compared with the 20 mg/day dosage. Although previous reports have emphasized the potential side effects of combination treatment with lovastatin and fibric acid derivatives, our patients tolerated the regimen well, with no significant subjective complaints or laboratory abnormalities. The bezafibrate-lovastatin combination is a possible therapeutic option for severe, resistant FCHL, but close medical supervision is needed because of potential side effects.
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PMID:Treatment of severe, resistant familial combined hyperlipidemia with a bezafibrate-lovastatin combination. 851 43

Insulin resistance is characterized principally by impaired insulin-mediated glucose uptake which provokes a compensatory increase in pancreatic beta-cell secretory activity. For a time this may produce well-controlled plasma glucose levels but as the insulin resistance worsens the augmented insulin production becomes inadequate to keep plasma glucose at euglycemia leading to the development of non-insulin dependent diabetes mellitus (NIDDM), accompanied by hyperinsulinemia and hyperglycemia. A number of metabolic defects are associated with NIDDM including obesity, hypercoagulability, cardiovascular disease risk factors such as hypertension and dyslipidemia and these constitute the insulin resistance syndrome. The identity of the biochemical factor that might link all these defects is not yet known. We have hypothesized that platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) may be such a link. In this study, we measured plasma acetylhydrolase (EC.1.1.48), which degrades PAF to the inactive metabolise lyso-PAF, as a surrogate for PAF activity in three groups of hypercholesterolemic subjects: lean controls (n = 9), non-diabetic obese (n = 6) and NIDDM subjects (n = 6). The ages and body mass indices of the subjects were 46 +/- 3.1 and 24.2 +/- 2.2 for the lean controls, 52 +/- 2.5 and 28.7 +/- 0.9 for the NIDDM subjects and 60 +/- 2 and 27.6 +/- 2.1 for the obese, non-diabetic subjects (mean +/- S.E.M.). The measurements were made before and after therapy with the cholesterol-lowering drug lovastatin, a 3-hydroxy 3 methylglutaryl (HMG) coenzyme. A reductase inhibitor (40 mg/day) for 3 months. Fasting plasma glucose (FPG) levels were 91 +/- 11, 96 +/- 3 and 146 +/- 11 mg/dl, for the lean, obese and NIDDM subjects, respectively, before therapy began. Lovastatin did not affect FPG in any of the three subject groups. Before treatment, the fasting plasma insulin (FPI) levels were 6.1 +/- 0.92, 10.83 +/- 2.03 and 14.68 +/- 3.64 mU/l for the lean, non-diabetic obese and NIDDM subjects, respectively. After lovastatin therapy only the obese group exhibited a significant change in FPI (15.35 +/- 2.47 mU/l) (P < 0.05). Total cholesterol levels were similar in all three groups both before and after lovastatin therapy but within each group lovastatin therapy significantly reduced the total cholesterol by 32, 29 and 34% in the lean, obese and NIDDM subject groups respectively (P < 0.0001). Lovastatin therapy reduced LDL-cholesterol levels by 40, 32 and 46% in the lean, obese and NIDDM subjects, respectively, but produced no significant effect on HDL or triglyceride levels. Before therapy, the plasma acetylyhydrolase activities were 104 +/- 7, 164 +/- 7 and 179 +/- 7 nmol/ml per min in the lean, obese and NIDDM subjects, respectively. Lovastatin therapy reduced plasma acetylhydrolase levels to 70 +/- 7, 87 +/- 6 and 86 +/- 7 nmol/ml per min in the lean, obese and NIDDM subjects, respectively. Plasma acetylhydrolase activity was predominantly (> 80%) associated with LDL cholesterol both before and after lovastatin treatment. Also, plasma acetylhydrolase activity significantly correlated with fasting plasma insulin levels before lovastatin therapy but not after. Taken together, this study clearly implicates PAF metabolism in three defects associated with the insulin resistance syndrome: hypercholesterolemia, obesity and NIDDM. Additionally, we conclude that chronic hyperinsulinemia may play a significant role in the production of plasma acetylhydrolase.
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PMID:Plasma PAF acetylhydrolase in non-insulin dependent diabetes mellitus and obesity: effect of hyperinsulinemia and lovastatin treatment. 945 36

The vascular endothelium is the inner lining of all blood vessels and serves as an important autocrine and paracrine organ, that regulates vascular wall functions. Because of its strategic location between the circulating blood and the vascular wall, the endothelium interacts with cellular and neurohumoral mediators, thus controlling vascular contractile state and cellular composition. The vascular endothelium maintains vascular homeostasis by modulating blood vessel tone, by regulating local cellular growth and extracellular matrix deposition and by controlling hemostatic as well as inflammatory responses. One of the best characterized and most important substances released from the endothelium is nitric oxide (NO). NO is a soluble gas which is continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutively expressed nitric oxide synthase. The most important stimuli represent physical factors such as shear stress and pulsatile stretching of the vessel wall as well as circulating and locally released vasoactive substances. The endothelium can be seen as a biosensor, reacting to a large variety of stimuli and therefore maintaining adequate NO release. A large number of risk factors for atherosclerosis including hypercholesterolemia, systemic hypertension, smoking and diabetes have been associated with impaired endothelial NO-mediated vasodilation. "Endothelial dysfunction" is an early marker of atherosclerosis and may be closely related to the disease process. In acute coronary syndromes dysfunctional endothelium may trigger the devastating event of plaque rupture by promoting adhesion of leukocytes, vasoconstriction, activation of platelets and thrombos formation. Atherosclerotic blood vessels are further characterized by activation through zytokines and expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (E-Selectin). After adhesion to the endothelium mononuclear cells migrate to the subendothelial space to take up oxidized LDL, thus transforming into foam cells, a hall mark of early atherosclerotic lesions. A number of conditions including infection with Chlamydia pneumoniae may cause continuous activation of the endothelium and inflammation of the vessel wall. Continuous endothelial dysfunction and activation, caused by risk factors and infection, represent the basis for atherogenesis and acute coronary syndromes.
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PMID:[Endothelial dysfunction--assessment of current status and approaches to therapy]. 1009 15


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