(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Hypertension

The ASCOT-LLA and ALLHAT-LLT trials provide conflicting evidence of the efficacy of statins in decreasing cardiovascular (CV) morbidity and mortality in hypertensive patients. We performed a meta-analysis to compare the overall efficacy of statins in hypertensive and nonhypertensive patients enrolled in major randomized clinical trials. We systematically reviewed PubMed publications from 1985 onward for placebo-controlled randomized trials that examined the effect of statins on cardiac morbidity and mortality. Only trials that followed >or=1,000 patients for >or=2 years were included in the meta-analysis. Outcomes included cardiac or CV death, major coronary events, or major CV events. Pooled estimates of relative risk (RR) were calculated separately for hypertensive and nonhypertensive patients. The moderating effect of the percentage of hypertensive patients at baseline was tested using meta-regression. Besides the ASCOT-LLA and ALLHAT-LLT, 12 trials enrolling 69,984 patients met inclusion criteria. Overall, in these 12 trials, statin therapy decreased cardiac death by 24% (RR 0.76, 95% confidence interval [CI] 0.71 to 0.82). There was no evidence of difference in RR estimates for hypertensive (RR 0.78, 95% CI 0.72 to 0.84) and nonhypertensive (RR 0.76, 95% CI 0.72 to 0.80) patients. Similarly, meta-regression showed that the efficacy of statins was not moderated by the percentage of hypertensive patients at baseline (Q estimate 1.51, p=0.22). In conclusion, statin therapy effectively decreases CV morbidity and mortality to the same extent in hypertensive and nonhypertensive patients.

Topics: Aged; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Male; Middle Aged; Pravastatin; Prognosis; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin; Therapeutics

To date, the published database concerning the impact of therapy on endothelial function in essential hypertension and hypercholesterolemia is small and incomplete. Chronic antihypertensive therapy had not yet been proven to restore endothelial function in patients with essential hypertension. In contrast, chronic lipid-lowering therapy is effective in restoring endothelial function of the coronary and peripheral circulation in patients with hypercholesterolemia. A beneficial effect was already documented after 3 months of therapy with fluvastatin but full restoration may last more than 1 year.

Topics: Anticholesteremic Agents; Antihypertensive Agents; Arteriosclerosis; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Indoles; Vasodilation

Atrial fibrillation (AF) is a complex cardiac arrhythmia in clinical practice with increasing incidence. However, the effects of statins on patients with AF are not quite clear.. To investigate the protective effect of calcium channel blocker (CCB) and valsartan combined fluvastatin on hypertension (HTN) patients with nonpermanent AF.. In three and a half years, 189 cases of patients diagnosed as HTN combining nonpermanent AF by eight medical centers, were recruited and randomly assigned to four groups with varied treatments: CCB group; CCB + statin group; valsartan group; and valsartan + statin group. The four groups were followed up for 24 months. The 7-day Holter ultrasound echocardiography (UCG) and biochemical indexes were completed at preset time nodes respectively.. After 24 months of follow-up, 178 patients completed the study. Compared with CCB group, the blood lipid level, inflammatory index, ultrasonic index and electrocardiographic measurement results of CCB + statin group, valsartan group and valsartan + statin group were improved in different degrees and had statistical significance (P < .05 or P < .01). Furthermore, the improvement trend of CCB + statin group and valsartan + statin group was more obvious.. The results indicated that valsartan can reduce AF load and recurrence rate, and delay the progression of nonpermanent AF to permanent AF in multiple ways, and the effect of combination of valsartan and fluvastatin is more significant. These results provide a new direction for the integrated upstream control strategy of AF.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Atrial Fibrillation; Blood Pressure; Disease Progression; Drug Therapy, Combination; Female; Fluvastatin; Heart Rate; Humans; Hypertension; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Valsartan

To investigate the upstream therapeutic effects of fluvastatin and valsartan on hypertensive patients with non-permanent atrial fibrillation (AF).. A total of 189 patients who were admitted to outpatient and inpatient department from eight medical centers in China, diagnosed as hypertension with non-permanent AF, were divided into four groups randomly: the CCBs group (group A, n = 45); CCB + fluvastatin group (group B, n = 48); valsartan group (group C, n = 46); valsartan + fluvastatin group (group D, n = 50). The four groups were followed up for 24 months. The blood routine, biochemical examination, echocardiography, high sensitive C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), the maintenance rate of sinus rhythm, and the recurrence of paroxysmal AF or persistent AF incidence were observed in these groups before and after 24 months' treatment.. After 24 months of follow-up, there were 178 cases of patients who have completed the study. (a) There was no significant difference in blood routine, liver, and renal function in each group (P > 0.05). (b) The blood lipids level in groups B and D was significantly reduced after treatment (P < 0.01). There was no significant difference of hs-CRP level in group A (P > 0.05). The left ventricular remodeling was significantly alleviated in group C and group D (P < 0.05). The NT-ProBNP level was significantly decreased in group D (P < 0.05). (c) The sinus rhythm maintenance rate of group B, group C, and group D was higher than group A (77.78%, 70.45%, 79.17% vs 43.90%), the occurrence of persistent AF was significantly lower than group A (11.11%, 14.29%, 8.33% vs 31.71%; P < 0.05).. CCB plus fluvastatin and valsartan can reduce the recurrence rate of non-permanent AF and to delay the progression from non-permanent AF to permanent AF in patients with hypertension. The combined application of valsartan and fluvastatin is more effective than valsartan or CCB alone in the upstream therapies of AF.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Anti-Arrhythmia Agents; Antihypertensive Agents; Atrial Fibrillation; Blood Pressure; China; Disease Progression; Female; Fluvastatin; Heart Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Incidence; Male; Middle Aged; Prospective Studies; Recurrence; Time Factors; Treatment Outcome; Valsartan

Previous studies regarding rhythm control in patients with atrial fibrillation (AF) could not sufficiently demonstrate the efficacy of available anti-arrhythmic drugs. 'Upstream therapy' has emerged as a potential strategy for the prevention and treatment of AF. The use of angiotensin II receptor blockers and statins has been suggested to decrease new-onset AF, but which remains inadequately explored. This study was designed to examine whether valsartan or fluvastatin can reduce the risk of non-permanent AF in patients with hypertension.. The VF-HT-AF study is a multicenter, randomized, open-label, four-arm parallel group study with comparative evaluation of valsartan and fluvastatin as upstream therapies for the treatment of non-permanent AF complicated by hypertension. The primary outcome measure is change in the development of paroxysmal AF into persistent or permanent AF, the development of persistent AF to permanent AF, and change in incidence of overall and persistent AF recurrence, as evaluated by 7-days ambulatory electrocardiograph monitoring (Holter) and patients' diaries during 2 years' follow-up. Secondary outcome measures of this study include the occurrence of: (1) fatal and nonfatal myocardial infarction; (2) heart failure (New York Heart Association stage III or IV); (3) cardiogenic shock; (4) serious bleeding necessitating hospitalization; (5) malignant ventricular arrhythmia; (6) revascularization therapy; (7) radiofrequency catheter ablation of AF; (8) changes of left atrial dimension, as measured by ultrasound echocardiography; (9) stroke; (10) cardiovascular mortality; and (11) all-cause mortality. A total of 1879 patients will be investigated from 15 medical centers throughout China to obtain the relevant information.. This is the first study in hypertensive patients complicated non-permanent AF in the Chinese population. Results of this study will inform the use of upstream therapies of AF.. chictr.org, ChiCTR-TRC-12002642.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Atrial Fibrillation; Blood Pressure; China; Clinical Protocols; Electrocardiography, Ambulatory; Fatty Acids, Monounsaturated; Fluvastatin; Heart Failure; Heart Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Myocardial Infarction; Prospective Studies; Recurrence; Research Design; Risk Assessment; Risk Factors; Shock, Cardiogenic; Time Factors; Treatment Outcome; Valsartan

The long-term event monitoring (LEM) study evaluated the lipid-lowering efficacy and safety of fluvastatin in Japanese patients with hypercholesterolemia. The present sub-analysis focused on the impact of risk factors on event prevention.. In the LEM study, patients (n=21,139) who started fluvastatin between 2000/4/1 and 2002/3/31 in Japan were prospectively registered and followed up for 3 years (secondary prevention cohort) or 5 years (primary prevention cohort).. Of the patients registered, 19,084 were included in this sub-analysis. The secondary prevention group, demonstrated 8.27- and 2.89-fold higher incidence in cardiac events and cerebral events, respectively compared with the primary prevention group (P < 0.001). Complications of cerebrovascular disease demonstrated a 2.22- and 5.29-fold higher incidence in cardiac events and cerebral events (P < 0.01 and P < 0.001, respectively). Presence of diabetes mellitus (DM) in patients without complication significantly increased the incidence in both cardiac events (2.37) and cerebral events (2.15) as compared with non-DM patients for primary prevention (P < 0.001 and P < 0.01, respectively). For the secondary prevention, DM patients with complication of cardiac disease showed a significantly higher incidence in both cardiac events (1.59) and cerebral events (3.79) compared with non-DM patients (P < 0.05 and P < 0.01, respectively). In contrast, DM patients with complications of cerebrovascular disease showed a significantly higher incidence in cerebral events (2.58, P < 0.05), but not cardiac events compared with non-DM patients. Similarly, the presence of hypertension significantly increased the incidence in both cardiac (1.64) and cerebral events (1.81) for primary prevention (P < 0.01 and P < 0.05, respectively). For secondary prevention, hypertension in patients with complication of cardiac or cerebrovascular disease did not affect incidence in both cardiac and cerebral events. In the patients without complication, high triglycerides and low high density lipoprotein cholesterol (HDL-C), but not low density lipoprotein cholesterol (LDL-C), increased cerebral events, while only LDL-C significantly increased cardiac events. For secondary prevention, high triglycerides or low HDL-C, but not LDL-C, significantly increased the relative risk of cardiac events in the patients with complication of cardiac disease.. The LEM study, a large-scale prospective study of long-term fluvastatin treatment for hypercholesterolemia in Japanese patients, demonstrated high impact of complications such as DM and hypertension as well as high triglycerides or low HDL-C on cardiac and cerebral events. After long-term statin treatment, the control of other factors rather than LDL-C alone might be important to avoid vascular events.

Topics: Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Diabetes Mellitus; Drug Monitoring; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Indoles; Japan; Male; Middle Aged; Primary Prevention; Prospective Studies; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome

Among hypertensive patients, cardiovascular disease morbidity is common, even in those who are adequately treated. New pharmacological strategies to mitigate the burden of arterial hypertension are needed. This 12-month, randomized, double-blind placebo-controlled study investigated the effect of statin (fluvastatin) treatment on ambulatory blood pressure (ABP), exercise blood pressure (EBP), myocardial structure, endothelial function and insulin resistance in 50 hypertensive patients. At baseline, the groups were comparable in terms of demographic characteristics, ABP, EBP, endothelial function and homeostasis model assessment of insulin resistance (HOMA-IR). At the end of the study, there was no difference between groups in terms of resting systolic blood pressure. However, maximum systolic EBP was lower in the treatment group than in the placebo group (175 ± 18 vs 192 ± 23 mm Hg, P<0.05), as was left ventricular mass index (LVMI; 82 ± 15 vs 100 ± 23, P<0.05), and HOMA-IR index was lower after fluvastatin treatment (2.77 ± 1.46 vs 3.33 ± 1.73, P<0.05). Changes in lipid profile were not correlated with blood pressure, endothelial function, LVMI or HOMA-IR data. In hypertensive patients, fluvastatin can improve maximum systolic EBP, myocardial remodelling and insulin resistance, independently of lipid profile variations and endothelial function.

Topics: Adult; Blood Pressure; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Insulin Resistance; Male; Middle Aged; Myocardium

Telmisartan, an angiotensin II type 1 receptor blocker (ARB), acts as a partial agonist for peroxisome proliferator-activated receptor-γ, and thus improves abnormalities of glucose metabolism and hypertriglyceridaemia in addition to its documented blood pressure-lowering effects. Recently, it has been demonstrated that telmisartan also lowers the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol levels. This study was designed to investigate the mechanism of cholesterol reduction.. We measured serum levels of cholestanol, a cholesterol absorption marker, and lathosterol, a cholesterol synthesis marker, in 20 patients with both hypercholesterolaemia and hypertension. Ten patients were treated with telmisartan and the remaining 10 with fluvastatin.. After 3 months of treatment, total and LDL cholesterol levels decreased in the telmisartan group (P<0.01 for both total and LDL cholesterol levels) and the fluvastatin group (P<0.001 for both total and LDL cholesterol levels). The change in cholestanol level after 3 months of treatment was positively correlated with the levels of total (R=0.72, P<0.05) and LDL cholesterol (R=0.81, P<0.01) in the telmisartan group. The change in lathosterol level was positively correlated with the levels of total (R=0.88, P=0.001) and LDL cholesterol (R=0.89, P=0.001) in the fluvastatin group.. Our results suggest that the cholesterol-lowering effect of telmisartan might be caused by inhibition of cholesterol absorption, whereas that of statins is by inhibition of cholesterol synthesis. If confirmed, co-treatment with the two agents may be useful for synergistically lowering cholesterol in hypertensive patients.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Anticholesteremic Agents; Benzimidazoles; Benzoates; Biomarkers; Cholestanol; Cholesterol; Cholesterol, LDL; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gastrointestinal Agents; Humans; Hypercholesterolemia; Hypertension; Indoles; Intestinal Absorption; Male; Middle Aged; PPAR gamma; Telmisartan

Patients with arterial hypertension are characterized by impaired endothelial function and increased cardiovascular risk. Statins have been proposed as a potential treatment option in hypertension, even in those with normal low-density lipoprotein (LDL)-cholesterol levels. We tested whether fluvastatin reduces oxidative stress and inflammation, and improves endothelial function in patients with arterial hypertension and normal LDL-cholesterol.. In a cross-over designed, double-blind randomized trial, 26 patients with arterial hypertension and LDL-cholesterol below 160 mg/dl were treated for 2 weeks with either placebo or fluvastatin 80 mg/day. Endothelium-dependent vasodilation (EDV) was assessed as the forearm blood flow (FBF) response to intra-arterial infusion of acetylcholine (ACH, 12 and 48 μg/min), and endothelium-independent vasodilation (EIV) as the FBF response to nitroprusside (3.2 and 12.8 μg/min). Furthermore, we measured reduced to oxidized glutathione (GSH/GSSG) ratio in red blood cells, total antioxidant capacity in plasma (TAC) and high-sensitivity C-reactive protein (hs-CRP) levels.. Fluvastatin lowered LDL-cholesterol from 118 ± 16 to 90 ± 25 mg/dl (P < 0.0001), but had no effect on blood pressure, high-density lipoprotein (HDL)-cholesterol or triglycerides. EDV and EIV were unaffected by fluvastatin treatment (e.g. increase of FBF 48 μg/min: 339 ± 285% during placebo versus 268 ± 194% during fluvastatin, n.s.). Finally, GSH/GSSG ratio, TAC and hs-CRP levels were similar between fluvastatin and placebo treatment.. Fluvastatin treatment did not improve endothelial function, oxidative stress or inflammation in patients with arterial hypertension and normal LDL-cholesterol levels. These data argue against the usefulness of statins in patients with arterial hypertension in the absence of hypercholesterolemia or other additional risk factors.

Topics: Adult; Cholesterol; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Middle Aged; Oxidative Stress; Placebos

Mixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day.. Patients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA.. The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05).. Our preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

Topics: Antihypertensive Agents; Apolipoprotein B-48; Blood Glucose; Blood Pressure; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Reducing; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glycated Hemoglobin; Humans; Hyperlipidemia, Familial Combined; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Indoles; Lipids; Male; Middle Aged

Postprandial hypertriglyceridemia is associated with a series of atherogenic abnormalities, including a prothrombotic state and inflammation. Hypertensive patients have exaggerated postprandial triglyceride response. The benefit of combined treatment of statin and angiotensin II type 1 receptor blocker (ARB) has been demonstrated in diabetic patients. The aim of this investigation was to explore the effect of a statin, fluvastatin, and the ARB valsartan, alone and in combination, on fibrinolytic activity and inflammation after a high-fat meal in patients with essential hypertension (EHP). A total of 53 EHP patients were studied. The concentrations of plasma lipid profiles, soluble P-selectin, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) antigens were measured in fasting state and at 4 hours after a single high-fat meal (800 calories; 50 g fat). Patients randomly accepted placebo, fluvastatin 40 mg/day, valsartan 80 mg/day, or both for 1 week. Then a high-fat meal and assay of plasma samples were repeated. The postprandial plasma triglyceride, soluble P-selectin, PAI-1, and t-PA antigen concentrations significantly increased after a high-fat meal. Postprandial plasma concentration of triglyceride was significantly correlated with that of soluble P-selectin and PAI-1 antigen, respectively (P<0.001). The postprandial increase in plasma P-selectin, PAI-1, and t-PA antigen levels was attenuated by 1-week fluvastatin-alone and valsartan-alone treatments; their combination is more effective on both fasting and postprandial P-selectin, plasma PAI-1, and t-PA antigen levels. The improvement of these plasma variables was not significantly related to the changes of plasma lipids and blood pressure. In conclusion, postprandial hypertriglyceridemia induces postprandial fibrinolytic dysfunction and vascular inflammation in patients with essential hypertension after a high-fat meal. Short-term combined treatment with fluvastatin and valsartan more effectively inhibits this postprandial atherogenic change in plasma than monotherapy.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Dietary Fats; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fibrinolysis; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Lipids; Male; Middle Aged; P-Selectin; Plasminogen Activator Inhibitor 1; Postprandial Period; Tetrazoles; Tissue Plasminogen Activator; Valine; Valsartan; Vasculitis

Search of new optimal treatment strategies, allowing to decrease the risk of atherosclerosis development and cardiovascular events is determined by high prevalence of hyperlipidemia in hypertensive patients.. To study the vasoprotective effects and security of Valsartan (V) or Fluvastatin extended release (XL) (F) and their combination in stage 1 and 2 essential hypertension (EH) with moderate hyperlipidemia.. 32 patients with EH after 14 days of wash-out period were randomized to receive either V (160 mg o.d.) or F (80 mg o.d.). After 8 weeks of monotherapy combination of V+F was administered to each patient for the next 8 weeks. At baseline, after 8 weeks of monotherapy, and at the end of the study sitting BP, lipids, NOs level and endothelial function were assessed. Endothelial function was measured as flow-mediated vasodilation (FMD) by high resolution ultrasound. Valsartan (Diovan) and Fluvastatin (Lescol XL) were provided by Novartis Pharma AG (Basel, Switzerland).. Combination of F (80 mg o.d) with initial therapy by V (160 mg o.d.) led to more significant decrement of BP and significant improvement of FMD.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Cholesterol; Delayed-Action Preparations; Endothelium, Vascular; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Male; Middle Aged; Prospective Studies; Tetrazoles; Valine; Valsartan

Although lowering blood pressure (BP) reduces aortic stiffness, achieving the recommended BP goal can be difficult. Recent studies have shown that short-term use of statins can reduce BP significantly. To determine the long-term effects of statins on BP and aortic stiffness, a single-blind randomized prospective study was performed on 85 hyperlipidaemic hypertensive patients whose BP was insufficiently controlled by antihypertensive therapy. Every 3 months, aortic stiffness was assessed by measuring pulse wave velocity (PWV). Patients were randomly allocated to groups treated with pravastatin, simvastatin, fluvastatin, or a nonstatin antihyperlipidaemic drug. No significant differences in patient characteristics, kinds of antihypertensive drugs, BP, ankle brachial index, PWV, or serum lipid, creatinine, or C-reactive protein levels were found between the four groups at the start of the study. During the 12-month treatment period, PWV did not change in the pravastatin group or nonstatin group, but it was transiently reduced in the simvastatin group and significantly decreased in the fluvastatin group, even though the doses of the statins used in this study were lower than the usually prescribed dose. All four antihyperlipidaemic drugs significantly decreased serum cholesterol levels without affecting BP, ankle brachial index, or serum triglyceride levels. The C-reactive protein serum levels decreased significantly in the three statin groups but not in the nonstatin group. These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP.

Topics: Anticholesteremic Agents; Arteriosclerosis; Blood Pressure; C-Reactive Protein; Cholesterol; Elasticity; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemias; Hypertension; Indoles; Male; Middle Aged; Pravastatin; Prospective Studies; Pulsatile Flow; Simvastatin; Single-Blind Method

The Hypertension High Risk Management trial (HYRIM) investigated the effect of fluvastatin treatment and lifestyle intervention on development of carotid intima-media thickness (IMT) in drug-treated hypertensive patients.. HYRIM was a placebo-controlled, 2 x 2 factorial trial in which 568 drug-treated hypertensive men aged 40-74 years with total cholesterol 4.5-8.0 mmol/L, triglycerides <4.5 mmol/L, body mass index 25-35 kg/m2, and a sedentary lifestyle were randomized to receive either fluvastatin, 40 mg daily, or placebo, and either intensive lifestyle intervention (physical activity and diet) or usual care (treatment of hypertension and other disorders by own private physician). Carotid IMT was assessed by B-mode ultrasound vasculography and left ventricular (LV) mass was calculated from ultrasound recordings of the heart. Fluvastatin alone reduced the primary study endpoint of 4-year development of IMT in the common carotid artery (CCA) compared with placebo (p=0.0297). Carotid bulb IMT progression over 4 years was also significantly (p=0.0214) reduced by fluvastatin compared with placebo. Fluvastatin significantly lowered LDL-C levels (mean net difference through 4 years, 0.6 mmol/L; p<0.0001), and reduced the 2-year development of LV mass (p=0.0144) compared with placebo. Lifestyle intervention had no significant effect on LDL-C, carotid IMT or LV mass, and did not increase the effects of fluvastatin.. In drug-treated hypertensive patients in a usual care setting, fluvastatin treatment reduces progression of carotid IMT and LV mass.

Topics: Administration, Oral; Adult; Aged; Anticholesteremic Agents; Arteriosclerosis; Cholesterol, LDL; Diet; Exercise; Fatty Acids, Monounsaturated; Fluvastatin; Heart Ventricles; Humans; Hypertension; Indoles; Life Style; Male; Middle Aged; Placebos; Tunica Intima

High serum cholesterol and LDL-cholesterol level and high blood pressure are risk factors for cardiovascular disease (CVD). CVD risk factors usually occur simultaneously, fact that enhance personal and population CVD risk. Data from interventional studies suggest that reducing CAD risk factors significantly lowered risk of CAD. Fluvastatin, a statine, has been used in hypercholesterolemic populations. We report on a clinical trial (random selection) of fluvastatin vs. placebo on hipercholesterolemic patients (total cholesterol > or = 240 mg/dl and/or low-density lipoprotein cholesterol (LDL-C) > or = 160 mg/dl) on treatment of mild to moderate high blood pressure. Forty Latin-American patients were randomized to placebo or 40 mg per day for 8 weeks of fluvastatin. Fluvastatin patients had a clinical and statistical significant reduction on total cholesterol (27.7%) and LDL-C (39.1%) Vs a non-significant reduction on the placebo group (6.9% total cholesterol and 9.1% LDL-C). One patient had elevated aspartate (AST) and alanine (ALT) aminotransferases (three times the local laboratory upper normal levels) associated with a chronic alcohol consumption, reverted 6 weeks after protocol completion. There was no important secondary effects; also there was no differences on this regard between placebo and verum group. Fluvastatin proved to be safe and well tolerated for this group of patients under a wide range of high blood pressure treatment.

Topics: Anticholesteremic Agents; Cholesterol; Combined Modality Therapy; Double-Blind Method; Exercise Therapy; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Hypertension; Indoles; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Triglycerides

62 patients with hyperlipidemia II and hypertension were 8 weeks on low fat and low cholesterol diet (acc. to EAS recommendations). If LDL-Ch > or = 4.1 mmol/l the diet was continued and 12 weeks treatment by fluvastatin (Lescol, Sandoz Pharma Ltd) started with control every 4 weeks Preliminary dosage 20 mg once daily in the evening increased to 40 mg if LDL-Ch > 3.5 mmol/l. After 12 weeks the mean level of T.Chol decreased by 21%, LDL-Ch by 29%, LDL-Ch/HDL-Ch by 31% and T.Chol/HDL-Ch by 24%. HDL-Ch increased by 8% and TG decreased by 5% but not significantly. The first goal of treatment (LDL-Ch < 4.14 mmol/l) achieved 73% and second (LDL-Ch < or = 3.5 mmol/l)-43.3% patients. In 2 patients treatment was discontinued (in one due to severe alimentary symptoms and in second-due to infection of respiratory tract with increase of SGOT and SGPT) and in next 2 the dosage was decreased to 20 mg/day (due to transitory alimentary symptoms).

Topics: Anticholesteremic Agents; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet, Fat-Restricted; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hyperlipidemias; Hypertension; Indoles; Male; Middle Aged; Triglycerides

The efficacy and safety of the HMG-CoA reductase fluvastatin was investigated in a multicenter, open label clinical therapeutic trial in the treatment of hypercholesterinaemia in hypertensive patients (WHO I-II.). 49 patients were involved, 6 patients were dropped out because of th lack of compliance, 43 patients were investigated (mean age: 57.6 +/- 9.4 years, mean blood pressure: 146 +/- 16/88+/- g mmHg (systolic/diastolic). The antihypertensive treatment was unchanged during the study. An 8 weeks low-lipid diet was started if the fasting total cholesterol (TC) level was equal or higher than 6.5 mM/L and the triglyceride level was lower than 4.6 mM/L. After the dietary period fluvastatin treatment was started (20 mg o.d.), if the level of LDL-C was higher than 4,1 mM/L. Blood pressure, heart rate, TC, HDL-C (HDL2-C, HDL3-C), apoA1, apoB, TG were measured at the 4th, 8th, 12th weeks of treatment. LDL-C was calculated with Fridewald equation. The daily dose of fluvastatin was increased to 40 mg, if LDL-C level was higher than 3.5 mM/L after 4 weeks of treatment. 36 patients completed the study (Group B). 7 patients were dropped out at the end of the dietary period, because of the significant decrease of TC and LDL-C levels (Group A). In Group B fluvastatin significantly reduced the level of TC (from 7.22 +/- 0.88 to 5.99 +/- 0.98 mM/L), of LDL-C (from 5.13 +/- 0.71 to 3.95 +/- 0.88 mM/L), and the level of ApoB (from 0.97 +/- 0.26 to 0.85 +/- 0.15 mM/L), but did not influence significantly the level of HDL-C, ApoA1 and TG. The diastolic blood pressure decreased significantly during the dietary period, while after beginning the fluvastatin treatment the decrease of the systolic blood pressure became significant. There was no change in the heart rate. Only minor side effects were observed in 3 patients (dysuria, constipation, lack of appetite). Fluvastatin proved to be an effective and well-tolerated drug in the treatment of hypercholesterinaemia in hypertensive patients.

Topics: Aged; Anticholesteremic Agents; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Hypertension; Indoles; Lipids; Male; Middle Aged; Patient Compliance

Hypertensive patients with hyperlipidemia are at high risk to develop coronary heart disease (CHD). Chemotherapeutic correction of hyperlipidemia seems most reliable modality to prevent CHD. Hypolipidemic effect and tolerance of leskol (fluvastatin) in dietotherapy-resistant hypercholesterolemia were studied in 74 patients with essential hypertension treated with hypotensive drugs. The patients were included in a multicenter trial. A 12-week course reduced total cholesterol level under 6.2 mmol/l in 59% of the patients, under 5.2 mmol/l in 29% of them. LDLP cholesterol lowered to 3.5% in 34% of the patients. Mean apo B diminished by 23%. There was a 27% decrease in the proportion of atherogenic fraction apo B to antiatherogenic fraction of transport proteins apo A-I. Leskol is well tolerated and effective against hypercholesterolemia, it is safe in relation to side effects and blood biochemistry.

Topics: Anticholesteremic Agents; Drug Tolerance; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Hypertension; Indoles; Lipids; Male; Middle Aged; Moscow; Time Factors

Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF.. This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use.. Among Africans with HF, statin treatment was associated with significant reduction in mortality.

Topics: Aged; Atorvastatin; Atrial Fibrillation; Black People; Cardiomyopathy, Dilated; Cardiovascular Diseases; Cause of Death; Comorbidity; Coronary Artery Disease; Diabetes Mellitus; Fatty Acids, Monounsaturated; Fluvastatin; Ghana; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Kaplan-Meier Estimate; Longitudinal Studies; Middle Aged; Mortality; Multivariate Analysis; Probability; Proportional Hazards Models; Renal Insufficiency, Chronic; Retrospective Studies; Rosuvastatin Calcium; Simvastatin; Treatment Outcome

Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 °C for 15 min followed by 34 °C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-β1, MMP2, p22(phox) and gp91(phox) mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin.

Topics: Animals; Blood Pressure; Capillaries; Disease Models, Animal; Echocardiography; Fatty Acids, Monounsaturated; Fibrosis; Fluvastatin; Heart Ventricles; Hot Temperature; HSP90 Heat-Shock Proteins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Myocardium; Nitric Oxide Synthase Type III; Rats; Rats, Inbred Dahl; RNA, Messenger; Sodium, Dietary; Vascular Endothelial Growth Factor A; Ventricular Function, Left; Ventricular Remodeling

Statins have been reported to prevent adverse cardiovascular events in patients with myocardial infarction (MI). However, the association of statin use and the risk of pneumonia requiring hospitalization in MI patients remains unclear.. A nested case-control study was conducted by using data from the National Health Insurance Research Database of Taiwan. Among 24,975 patients with MI, 2686 case patients with pneumonia requiring hospitalization were age- and sex-matched with 10,726 control patients using the incidence density sampling approach. Duration and dosage of statin use were obtained from pharmaceutical claims. Conditional logistic regression analyses were used to estimate the risk of hospitalization for pneumonia associated with statin use adjusted for patient's demographics, medical conditions and prescribed medications.. Statin use was associated with a 15% reduced risk of pneumonia requiring hospitalization among MI patients (adjusted odds ratio [aOR] = 0.85, 95% confidence interval [CI] = 0.77-0.95, P = 0.004). The association was more significant for MI patients unexposed to statin pretreatment (aOR = 0.76, 95% CI = 0.64-0.90, P = 0.001). Statins also exhibited favorable benefits in a time- and dose-dependent manner. The results were consistent in various subgroup analysis of the patients who were female, age ≥ 65 years, a low CHADS2 (i.e. congestive heart failure, hypertension, diabetes mellitus, previous stroke and age > 75 years old) score, and fewer comorbidities. Atorvastatin, fluvastatin and simvastatin were the most common prescribed statins and had similar effects.. Statins might be considered as an adjunctive therapy to reduce the risk of hospitalization for pneumonia for MI patients under thorough evaluation of individual comorbidities, previous statin use and optimal dosage.

Topics: Aged; Atorvastatin; Case-Control Studies; Comorbidity; Diabetes Mellitus; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Incidence; Indoles; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Pneumonia; Protective Factors; Retrospective Studies; Risk Factors; Simvastatin; Stroke; Taiwan

To elucidate the aggregation capacity of neutrophils in patients with arterial hypertension and dyslipidemia treated with fluvastatin.. 32 middle-aged patients with grade 1-2 AH and dyslipidemia (risk 3). Control group included 26 age-matched healthy subjects. We estimated lipid composition, antioxidant protection, lipid peroxidation in plasma and neutrophils and their aggregation. All patients were given 40 mg fluvastatin at bedtime. Clinical and laboratory characteristics were evaluated before and 4, 16, 52 weeks after treatment. The results were treated by the Student's t-test.. The patients showed enhanced neutrophil aggregation due to lipid imbalance in cell membranes, intense lipid peroxidation, and marked changes in carbohydrate composition of membrane glycoprotein receptors. Fluvastatin significantly improved lipid composition and peroxidation in plasma and neutrophils and caused positive dynamics in their aggregation due to optimization of glycoprotein receptors.

Topics: Cell Aggregation; Dyslipidemias; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Middle Aged; Neutrophils; Treatment Outcome

Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m(2), not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.

Topics: Albuminuria; Anticholesteremic Agents; Antihypertensive Agents; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension; Indoles; Kidney; Lipids; Male; Middle Aged; Pilot Projects; Prospective Studies; Regression Analysis; Tetrazoles; Valine; Valsartan

We examined the effects of fluvastatin treatment on the development of kidney injury in experimental deoxycorticosterone-acetate (DOCA)-salt hypertension.. Male Sprague-Dawley rats underwent unilateral nephrectomy and received subcutaneous DOCA pellets as well as 1% NaCl for drinking. Simultaneously, rats were treated with 5 mg/kg per day fluvastatin, or solvent only for 6 weeks. Mean arterial pressure was measured intraarterially. Glomerulosclerosis, interstitial fibrosis, cell proliferation, inflammation and podocyte damage were evaluated on kidney sections. Inflammatory markers were measured by real-time PCR.. Mean arterial pressure was elevated in DOCA-salt-treated rats but unaltered by fluvastatin. Serum cholesterol was markedly elevated in DOCA-salt-treated rats and tended to be lower in fluvastatin-treated animals. Fluvastatin treatment decreased the mortality of DOCA-salt-treated rats. Urinary protein excretion, glomerular proliferation and macrophage infiltration as well as glomerulosclerosis were reduced by fluvastatin. Fluvastatin alleviated podocyte damage and glomerular osteopontin protein expression, which was localized in podocytes. On the contrary, interstitial fibrosis, inflammation and interstitial cell proliferation of DOCA-salt-treated rat kidneys were not influenced by fluvastatin.. Statin treatment reduces mortality and glomerular damage independent from blood pressure in a low-renin model of hypertensive nephrosclerosis. A reduction of podocyte damage and macrophage infiltration may explain the beneficial effects of fluvastatin.

Topics: Animals; Blood Pressure; Cell Proliferation; Desoxycorticosterone; Disease Progression; Fatty Acids, Monounsaturated; Fluvastatin; Glomerulonephritis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Kidney; Male; Nephrosclerosis; Organ Size; Podocytes; Rats; Rats, Sprague-Dawley

1. The aims of the present study were, first, to determine whether, in the genetically hypertensive (GH) rat, fluvastatin would lower blood pressure and remodel mesenteric resistance arteries (MRA) and the basilar artery and, second, to see whether treatment with a combination of fluvastatin and the angiotensin receptor antagonist valsartan would have any extra beneficial effect on blood pressure and vascular remodelling. 2. Male GH rats had tail-cuff systolic blood pressure (SBP) monitored weekly from the age of 7 to 12 weeks. Groups (n = 12-14) were treated with fluvastatin (4 mg/kg per day), valsartan (5 mg/kg per day), both mixed in with chow, or a combination of fluvastatin 4 mg/kg per day + valsartan 5 mg/kg per day. Untreated GH and a group of normotensive Wistar (N) rats served as control groups. 3. At 12 weeks of age, intra-arterial (i.a.) blood pressure was measured by femoral cannulation and rats were then perfused (at the SBP of the animal) with Tyrode's solution containing heparin and papaverine followed by 2.5% glutaraldehyde in Tyrode's solution; MRA and basilar arteries were embedded in Technovit. Serial sections were cut and Giemsa stained and stereological methods used to obtain media width, lumen diameter, medial cross-sectional area (CSA) and the ratio of media width to lumen diameter. Hearts were weighed to determine left ventricular (LV) mass. 4. Fluvastatin had no effect on blood pressure or LV mass, whereas valsartan given alone or with fluvastatin significantly reduced both parameters. 5. In MRA, fluvastatin reduced medial CSA, increased lumen size and, therefore, probably decreased vascular resistance. The media/lumen ratio was reduced to a level below that seen with the combination treatment and to below that of the N group. 6. In the basilar artery, fluvastatin and valsartan showed similar outward remodelling of the lumen and reduction in the media/lumen ratio. The combination treatment group showed, in addition, a reduction in medial CSA and an even lower ratio than the GH group on fluvastatin or valsartan alone or the N group. 7. Although fluvastatin has no effect on blood pressure, it does cause significant remodelling of MRA and the basilar artery. These beneficial structural changes in a peripheral resistance artery bed and in an artery involved in regulating resistance in the brain are worthy of further study.

Topics: Animals; Basilar Artery; Blood Pressure; Fatty Acids, Monounsaturated; Fluvastatin; Hypertension; Indoles; Male; Mesenteric Arteries; Rats; Vascular Resistance

In hypercholesterolemic and hypertensive patients, an increased propensity of their low-density lipoprotein (LDL) to oxidative modification has been observed. Because oxidized LDL (ox-LDL) plays a major role in atherosclerosis, the current study analyzed the anti-oxidative effect of valsartan (an angiotensin II receptor antagonist) therapy in combination with fluvastatin therapy in these patients. Administration of 40 mg/d of fluvastatin for 2 months to seven patients resulted in significant reduction in plasma total and LDL cholesterol (by 24-28%). Valsartan administration (80 mg/d for an additional 2-month period) in combination with fluvastatin did not further affect plasma cholesterol levels. Fluvastatin therapy inhibited the susceptibility of LDL to copper ion-induced oxidation, as shown by prolongation of the lag time by 22% and by a reduction of thiobarbituric acid-reactive substances (TBARS) levels by 14%, as compared with the patient's LDL baseline oxidation. The addition of valsartan to fluvastatin resulted in a further 17% prolongation of the lag time and in an additional reduction of 21% in TBARS levels. In a parallel study, the LDL from eight patients who were first treated with 80 mg/d of valsartan for 2 months demonstrated reduced susceptibility to copper ion-induced oxidation, as observed by prolongation of lag time by 23% and reduction in TBARS levels by 19%, compared with the baseline values. The administration of 40 mg/d of fluvastatin for an additional 2 months in combination with valsartan, however, demonstrated no further inhibitory effect on LDL oxidation. The anti-oxidative properties of fluvastatin and valsartan against LDL oxidation were also demonstrated in vitro and the combination of both drugs was shown to have an additive effect. Valsartan therapy in hypercholesterolemic and hypertensive patients has an additive anti-oxidative effect to that of fluvastatin therapy. This may be related both to the anti-oxidative properties of valsartan and to the blocking of angiotensin II-induced oxidative stress.

Topics: Analysis of Variance; Antioxidants; Drug Synergism; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hypercholesterolemia; Hypertension; Indoles; Lipoproteins, LDL; Oxidation-Reduction; Tetrazoles; Valine; Valsartan

To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor, on the alterations of structure and function of resistant vessels in spontaneously hypertensive rats (SHR).. Eight-week-old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric arteries isolated from rats.. After 8 wk of treatment, histological examination showed that the wall-to-lumen area ratio was lower in SHRflu than that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P < 0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05].. Short-term treatment with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor; fluvastatin also attenuated the resistant vascular hypertrophy during the development of hypertension in SHR.

Topics: Animals; Anticholesteremic Agents; Aorta, Thoracic; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Male; Mesenteric Arteries; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoconstriction; Vasodilation

To investigate whether fluvastatin lowers cholesterol and blood pressure in hypertensives and hypercholesterolemic patients, 23 patients followed by their medical practitioner received 40 mg fluvastatin once a day for 12 weeks. Arterial blood pressure was measured by continuous ambulatory monitoring. Total mean cholesterol (mmol/l) was lowered from 7.98 +/- 1.21 to 6.25 +/- 0.88 and the atherogenic index from 7.26 +/- 2.11 to 5.49 +/- 1.35. Mean arterial systolic and diastolic blood pressure (mm Hg) was reduced from 144.8 +/- 13.7 to 138.6 +/- 18 and from 97.3 +/- 9.1 to 92 +/- 10.8. In responders (n = 12), blood pressure decreased from 142.6 +/- 11 to 126.4 +/- 11.1 and from 99.6 +/- 7.1 to 88.3 +/- 6.5. In conclusion, fluvastatin prescribed in a dose of 40 mg/day for 3 months to 23 hypertensives and hypercholesterolemic patients lowers the cholesterol level and lowers blood pressure. Lowering of blood pressure is independent of lowering of cholesterol.

Topics: Adult; Anticholesteremic Agents; Blood Pressure; Cholesterol; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Hypertension; Indoles; Male; Middle Aged; Pilot Projects

Currently available data and clinical observations which suggest that there is a pathogenetic relationship between hypertension, diabetes mellitus, and atherosclerosis have provided a concept of the X syndrome, by which hypertensive patients, mainly males, have impaired insulin tolerance along with hyperinsulinemia and concurrent atherogenic disorders of lipid metabolism. The paper discussed the specific pathogenetic mechanisms, clinical manifestations, and prospects for drug correction of the metabolic syndrome. The treatment of arterial hypertension with the calcium antagonist Lomir has indicated there are no negative changes as a control of non-insulin-dependent diabetes mellitus in the presence of effective correction of arterial hypertension and atherogenic dyslipidemias. With the monotherapy of essential hypertension concurrent with hypercholesterolemia with the alpha 1-adrenoblocker Doxazosin, in addition to the agent's high antihypertensive effects, the authors noted its favourable action on lipid spectral parameters and platelet functional activity. There is abundant evidence for the use of specific hypolipidemic agents in patients with essential hypertensive refractory to current antihypertensive drugs. The data obtained with the use of Lescol (fluvastatin) in patients with hypertensive disease and hypercholesterolemia suggest that by substantially reducing the levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and its transport protein apo B does not deteriorate the quality of correction of arterial hypertension in this group of patients.

Topics: Anticholesteremic Agents; Arteriosclerosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Doxazosin; Enzyme Inhibitors; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Indoles; Insulin Resistance; Isradipine; Lipid Metabolism; Male; Middle Aged; Syndrome

The coexistence of hypercholesterolemia and hypertension often requires concomitant drug treatments. Thus, it is interesting to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in patients receiving concomitant antihypertensive/cardiovascular drug treatments. A retrospective analysis was based on data from controlled clinical trials in which 1815 patients were treated with fluvastatin and 783 patients received placebo. The daily dose of fluvastatin was > or = 20 mg. At least one of the following drug treatments was taken by 445 of the fluvastatin-treated patients (24.5%) and 181 of those receiving placebo (23.1%): beta-adrenergic-receptor blockers (fluvastatin: n = 182; placebo: n = 84); diuretics (fluvastatin: n = 168; placebo: n = 72); calcium antagonists (fluvastatin: n = 161; placebo: n = 69); and angiotensin-converting enzyme (ACE) inhibitors (fluvastatin: n = 101; placebo: n = 30). The majority of patients received monotherapy with one of the above-mentioned antihypertensive agents (fluvastatin: 69%; placebo: 65%). The efficacy of fluvastatin in modifying low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol and triglyceride levels was not consistently different in patients taking a given antihypertensive compared with the overall group and the patients not taking the antihypertensive agent. In patients taking fluvastatin and antihypertensives, confirmed (measured at two consecutive occasions) increases more than three times the upper limit of normal in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) occurred in only two patients. One case involved the concomitant use of a beta-blocker (ASAT and ALAT) and the other a diuretic (ALAT).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Aged; Alanine Transaminase; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aspartate Aminotransferases; Calcium Channel Blockers; Clinical Trials as Topic; Creatine Kinase; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Hypertension; Indoles; Information Systems; Lipids; Lipoproteins; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies

The concurrence of hypertension and hypercholesterolemia leads to the clinical need to lower lipids in hypertensive patients. Thus, it is interesting to evaluate the efficacy and safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in such a patient population. A retrospective analysis of the clinical efficacy and safety of fluvastatin was based on the data from 1815 patients who received fluvastatin at daily doses of > or = 20 mg compared with 783 patients taking placebo. The results showed that 332 (18.3%) of the fluvastatin-treated and 124 (15.8%) of the placebo-treated patients were identified as having hypertension. The percentage change from baseline of low-density lipoprotein cholesterol (LDL-C) in hypertensive patients taking fluvastatin at doses of 20 and 40 mg/day was -20% and -26%, respectively (placebo: 1.4%), and did not differ from the response in non-hypertensive patients. Increases in high-density lipoprotein cholesterol (HDL-C) as well as decreases in triglycerides with fluvastatin were not consistently different between hypertensive and non-hypertensive patients. Irrespective of the presence or absence of hypertension, confirmed (measured on two consecutive occasions) increases > three times the upper limit of normal in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were observed in three (0.2%) and 12 (0.7%) patients, respectively. With placebo, ALAT was increased in two patients (0.2%). The incidence of notable increases more than 10 times the upper limit of normal in creatine kinase was similar with fluvastatin compared with placebo (0.3% in both).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Cholesterol, LDL; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Tolerance; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Information Systems; Lipids; Lipoproteins; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Time Factors; Triglycerides