Comparative study of a microporous cholestyramine analogue (filicol) and gemfibrozil for treatment of severe primary hypercholesterolemia. Short- and long-term results

The hypolipidemic effect of gemfibrozil in severe hypercholesterolemia is not well established. Fifty patients with primary hypercholesterolemia (including 18 patients with familial hypercholesterolemia) and stable low-density lipoprotein cholesterol levels greater than 3.90 mmol/L (greater than 150 mg/dL) (6.10 +/- 1.30 [SD] mmol/L; 236 +/- 50 mg/dL) while on a hypolipidemic diet were assigned to treatment for 12 weeks with either 9 g/d of filicol, a microporous cholestyramine analogue, or 1.2 g/d of gemfibrozil in a randomized clinical trial. Tolerance was good with both drugs. Filicol and gemfibrozil caused similar decrements of total cholesterol (14% for both), low-density lipoprotein cholesterol (20% and 18%, respectively), and apolipoprotein B (16% and 21%, respectively). Close to 40% of the patients had decreases of greater than 25% in low-density lipoprotein cholesterol levels with both drugs. Gemfibrozil, but not filicol, significantly increased plasma high-density lipoprotein cholesterol (16%) and apolipoprotein A-I (17%) levels and reduced triglyceride levels (35%). No loss of efficacy was observed with either drug in subsets of patients who had a good 12-week response rate and had extended therapy for up to 12 months. This study demonstrates that gemfibrozil may have a beneficial effect on all aspects of the plasma lipid profile in patients with severe hypercholesterolemia, a clinical situation where it can be used with potential advantages over standard doses of anion-exchange resins.     

Influence of lovastatin plus gemfibrozil on plasma lipids and lipoproteins in patients with heterozygous familial hypercholesterolemia

We investigated the hypocholesterolemic effects of lovastatin alone and in combination with gemfibrozil on plasma lipids and lipoproteins in 12 adult patients with well-characterized heterozygous familial hypercholesterolemia. Plasma concentrations of low density lipoprotein (LDL) cholesterol decreased from 321 +/- 14 mg/dl on diet only to 207 +/- 8 mg/dl (-35.5%) on single-drug therapy with lovastatin at a dose of 40 mg twice daily, whereas triglyceride concentrations fell by 27.6% (from 145 +/- 20 to 105 +/- 20 mg/dl). Subsequent addition of gemfibrozil at a dose of 600 mg twice daily resulted in a nonsignificant further reduction in LDL cholesterol to 194 +/- 7 mg/dl (-39.6% change from baseline), whereas triglycerides decreased to 80 mg/dl (-44.8%, p less than 0.05 vs. single-drug therapy with lovastatin). Plasma concentrations of high density lipoprotein (HDL) increased slightly during lovastatin and combined drug therapy (from 45 +/- 4 mg/dl at baseline to 46 +/- 4 mg/dl on lovastatin to 48 +/- 4 mg/dl on lovastatin plus gemfibrozil). The response to combination drug therapy in individual patients was heterogeneous and clinically significant decreases in LDL cholesterol concentrations were noted in two of the 12 patients, whereas in three patients LDL cholesterol concentrations increased on the combined drug regimen. One patient developed an asymptomatic increase in creatine kinase on monotherapy with lovastatin and a more pronounced and symptomatic increase during combination drug therapy with lovastatin plus gemfibrozil.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipid and apolipoprotein levels in heterozygous familial hypercholesterolemic patients treated by low density lipoprotein (LDL)-apheresis

Nine heterozygous patients with familial hypercholesterolemia (FH) were treated by low density lipoprotein (LDL)-apheresis using dextran sulfate cellulose columns. After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started. Pre- and post-apheresis serum cholesterol levels were decreased significantly by CS-514, from 289 +/- 24 mg/dl (mean +/- SEM) to 247 +/- 25 mg/dl and from 118 +/- 7 mg/dl to 106 +/- 9 mg/dl, respectively. Pre- and post-apheresis apolipoprotein B levels decreased significantly on CS-514 from 160 +/- 9 mg/dl to 138 +/- 8 mg/dl and from 58 +/- 6 mg/dl to 45 +/- 6 mg/dl, respectively. No adverse effects were observed during the combination therapy. Thus, the addition of an inhibitor of HMG-CoA reductase to LDL-apheresis is a useful method for further reducing serum cholesterol and apolipoprotein B levels in FH heterozygotes.     

Plasma lipids in a rural population of Bangladesh.

BACKGROUND: Plasma lipids are associated with cardiovascular diseases. Population-based data on plasma lipids are scarce in Bangladesh. METHODS: We investigated plasma lipid levels in a rural population of Bangladesh in 2001. Fasting blood was collected in 447 adults (157 men and 290 women) aged 20-79 years (mean+/-standard deviation 40+/-11 years in men, and 39+/-10 in women). RESULTS: The mean total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and total cholesterol/HDL cholesterol ratio levels were 182+/-56, 39+/-10, 115+/-53, 139+/-72 mg/dl and 4.8+/-1.8, respectively. The prevalence of abnormal lipid levels were as follows: hypercholesterolemia (total cholesterol > or =240 mg/dl) 16.1%, high LDL cholesterol (> or =160 mg/dl) 20.4%, low HDL cholesterol (<40 mg/dl) 66.4%, hypertriglyceridemia (> or =200 mg/dl) 15.0% and total cholesterol/HDL cholesterol ratio (>5.5) 32.7%. CONCLUSIONS: The prevalence of dyslipidemias, especially in the case of low HDL cholesterol, appears to be high even in this rural population of Bangladesh.     

Efficacy of colestimide coadministered with atorvastatin in japanese patients with heterozygous familial hypercholesterolemia (FH).

BACKGROUND: Colestimide, a 2-methylimidazole-epichlorohydrin polymer, is a new bile-acid-sequestering resin, that is 4-fold as powerful at lowering low-density lipoprotein cholesterol (LDL-C) as the conventional resin (cholestyramine). Moreover, colestimide has excellent patient compliance because it is available in tablet form. METHODS AND RESULTS: The clinical efficacy of colestimide coadministered with atorvastatin on lipid and apolipoprotein concentrations was examined in 15 patients (M/F=10/5, mean+/-SE age=54+/-9 years) with heterozygous familial hypercholesterolemia (FH). After a period of wash-out of any lipid-lowering drugs, atorvastatin (20-40 mg) was administered to patients for at least 8 weeks, and then 3 g of colestimide was administered for a further 8 weeks. Total and LDL-C significantly (<0.0001) decreased by 35% from 361 to 233 mg/dl and 41% from 274 to 161 mg/dl, respectively. Addition of colestimide caused a further significant 12% and 20% reduction, respectively, from the initial values to 205 and 129 mg/dl, respectively. Colestimide was also effective in reducing serum LDL-C concentrations in heterozygous FH patients with hypertriglyceridemia (triglycerides>or=150 mg/dl). CONCLUSIONS: When monotherapy with atorvastatin is insufficient to treat severely hypercholesterolemic patients, such as those with heterozygous FH, colestimide acts to reinforce the action of statins.     

Long-term treatment with pitavastatin (NK-104), a new HMG-CoA reductase inhibitor,of patients with heterozygous familial hypercholesterolemia

The clinical efficacy and safety of pitavastatin (NK-104), a novel HMG-CoA reductase inhibitor, during long-term treatment, were examined in 25 patients (male/female=11/14, mean age=53+/-13 (mean+/-SD) years) with heterozygous familial hypercholesterolemia (FH). After a period on placebo of >4 weeks, 2 mg/day of pitavastatin was administered for 8 weeks, and the dose was increased to 4 mg/day for up to 104 weeks. Total cholesterol (TC) decreased by 31% from the initial value of 340+/-57 to 237+/-40 mg/dl (P<0.0001) at week 8. During treatment with the higher dose, TC decreased even further to 212+/-35 mg/dl at week 12; it decreased by 37% from the initial value (P<0.0001). Similarly, the baseline low-density lipoprotein (LDL)-cholesterol (LDL-C) decreased by 41% at week 8, and by 49% at week 12, from 267+/-61 mg/dl at baseline. These findings indicate a dose-dependent effect of the drug on TC and LDL-C concentrations. To examine whether the levels of circulating matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of metalloproteinases: TIMPs) are altered during lipid-lowering therapy, we also measured their plasma levels. The mean levels of MMP-2 and -3 were significantly increased. No significant alteration was found in MMP-9, TIMP-1 and -2 levels. As for the safety of pitavastatin, adverse reactions were observed in one case (4%) of subjective and objective symptoms. The effects of pitavastatin on TC and LDL-C were stable during long treatment of patients with heterozygous FH.     

Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction

Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels.     

Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus

Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were compared in-patients undergoing renal transplantation. The study included 32 cases of renal transplantation recipients who randomized to the CsA treatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism. The serum lipid levels in both groups were significantly increased at 1 month after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions. In study 2, 1 month after renal transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition, there were significant decreases in very-low-density lipoprotein cholesterol (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin levels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects.     

Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia.

Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nonselective beta-receptor blocker effect on high density lipoprotein cholesterol after chronic exercise

High density lipoprotein (HDL) cholesterol changes were followed in 45 men with coronary heart disease who underwent 12 weeks of monitored aerobic exercise. Twenty-five patients who were taking a nonselective beta-receptor blocking drug (Group 1) did not demonstrate a significant change in HDL cholesterol after exercise (mean difference 2.8 +/- 11.5 mg/dl), whereas patients who had not received a beta-blocking drug for greater than or equal to 3 months (Group 2) showed a significant increase (mean difference 8.4 +/- 5.5 mg/dl; p less than 0.05). However, for those patients in each group who had an initial HDL cholesterol level less than 35 mg/dl before exercise, there was a significant increase in HDL cholesterol levels (mean difference 8 +/- 6.9 mg/dl [p less than 0.02] and 11 +/- 3 mg/dl [p less than 0.001] for Group 1 and Group 2, respectively) and a significant decrease in the low density lipoprotein (LDL/HDL cholesterol ratio (mean difference -1.2 +/- 1.6 [p less than 0.05] and -0.9 +/- 0.57 [p less than 0.001], respectively). Patients in both groups who started exercise with an HDL cholesterol level greater than 35 mg/dl did not show a significant change after exercise. Patients in Groups 1 and 2 achieved similar levels of exercise training after 12 weeks and were closely matched in age, medications, alcohol intake and smoking. The results indicate that among high risk patients (with an abnormally low HDL cholesterol level) exercise training can induce an augmentation of HDL cholesterol in those receiving a beta-blocking drug similar to that of patients not receiving such a drug.     

Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients

Familial hypercholesterolemia (FH) is characterized by an autosomal codominant inheritance, an abnormality in low-density lipoprotein (LDL) receptor function, elevated plasma cholesterol levels and premature atherosclerosis. Sixteen patients with homozygous FH were studied to correlate the extent of their atherosclerotic disease with their lipid levels and receptor function. The age range at initial presentation was 3 to 38 years (mean 12), and at the last examination, 6 to 43 years (mean 20). The mean pretreatment total plasma cholesterol concentration for all patients was 729 +/- 58 mg/dl (+/- standard error of the mean), and the mean LDL cholesterol level was 672 +/- 58 mg/dl (normal 60 to 176). High-density lipoprotein cholesterol was 28 +/- 3 mg/dl (normal 30 to 74). In the 7 patients with FH who had symptoms of myocardial ischemia (Group I), the mean pretreatment LDL cholesterol value (817 +/- 62 mg/dl) was higher than that of the 9 asymptomatic patients (Group II) (560 +/- 74 mg/dl). In Group I, 5 of 7 patients had left or right coronary ostial narrowing and 3 had significant left ventricular outflow obstruction. Most coronary arterial narrowing occurred in the right coronary and left anterior descending arteries and the least amount in the left circumflex coronary artery. A femoral bruit was the physical finding that correlated best with the Group I population; brother:sister pairs revealed a milder clinical course for the female. Seven of the 16 patients have survived into their third decade without symptoms. Comparison of these persons with those in whom angina developed reveals a marked heterogeneity in their clinical course, which appears to be associated with receptor negative/defective status.     

Reaching recommended lipid and blood pressure targets with amlodipine/atorvastatin combination in patients with coronary heart disease

The effects of combined atorvastatin and amlodipine on blood pressure (BP) and low-density lipoprotein (LDL) cholesterol levels were investigated in 134 patients with documented coronary heart disease treated for 1 year. BP at baseline was 128 +/- 15/79 +/- 9 mm Hg and was controlled by the treating physician; no calcium channel blockers were allowed. Baseline means for plasma cholesterol were 6.4 +/- 1.1 mmol/L (147 +/- 39 mg/dl), triglycerides 2.0 +/- 0.9 mmol/L (177 +/- 88 mg/dl), LDL cholesterol 4.4 +/- 1.0 mmol/L (170 +/- 39 mg/dl), and high-density lipoprotein cholesterol 1.2 +/- 0.3 mmol/L (46 +/- 12 mg/dl). Patients were all given atorvastatin 10 mg, then increased to 80 mg if the LDL cholesterol was <2.5 mmol/L (100 mg/dl). At 3 months, patients were randomized to amlodipine 10 mg or placebo. Plasma LDL cholesterol was decreased by 50%, and the LDL cholesterol target of <2.5 mmol/L was achieved in 81% of the patients. BP targets were achieved in 69% of the atorvastatin + placebo group, versus 96% in the atorvastatin + amlodipine group (p = 0.0002). With use of combination atorvastatin + amlodipine at doses ranging from 10 to 80 mg and 5 to 10 mg, respectively, recommended therapeutic goals were reached in most select subjects with coronary artery disease who were concomitantly receiving aspirin and antihypertensive therapy.     

Comparative efficacy and tolerability of low-dose pravastatin versus lovastatin in patients with hypercholesterolemia

BACKGROUND: The HMG CoA reductase inhibitors have quickly become the most widely prescribed family of agents for the treatment of patients with elevated low-density lipoprotein (LDL) cholesterol. The incidence of side effects with these agents increases as the dose increases within the recommended dosage range. A lower dosage presumably would have a lower incidence of adverse effects. In addition, lower doses should translate into reduced drug costs. METHODS AND RESULTS: We compared the efficacy of 10 mg of pravastatin and 10 mg of lovastatin in a randomized, crossover design trial among 30 patients with hypercholesterolemia. At baseline, their total cholesterol and LDL cholesterol levels were 249.0 +/- 27.3 and 185.1 +/- 25.5 mg/dL. After 4 weeks of treatment with lovastatin, the total cholesterol and LDL cholesterol levels fell to 202.8 +/- 29.6 and 141.0 +/- 25.3 mg/dL, decreases of 19% and 24%, respectively. Four weeks of pravastatin treatment resulted in levels of 212.6 +/- 30.8 and 150.5 +/- 25.5 mg/dL, or 15% and 19%, respectively. CONCLUSIONS: There were highly significant changes in total cholesterol and LDL cholesterol levels with each agent and no differences in effect between the 2 agents. In 13 (43%) of the 30 patients, LDL levels were reduced to 相似文献   

Effects of combination cholestyramine-neomycin treatment on plasma lipoprotein concentrations in type II hyperlipoproteinemia

Recent prospective clinical trials have established that cholesterol reduction in patients with elevated (upper 90th percentile) concentrations of low-density lipoproteins (LDL) reduces the incidence of myocardial infarction and sudden death. Because the level of protection from these cardiovascular sequelae is directly related to the degree of LDL reduction, combination therapy using different hypolipidemic agents has been used in patients with type II hyperlipoproteinemia (HLP). Neomycin is as effective as cholestyramine in reducing LDL levels and combination neomycin-niacin treatment normalizes the plasma lipoproteins in 92% of patients with type II HLP. Because neomycin could theoretically ameliorate some of the gastrointestinal side effects of cholestyramine in addition to further affecting cholesterol levels, the effects of combination cholestyramine-neomycin treatment on the plasma lipoprotein were assessed in 18 patients with type II HLP in a 9-month clinical trial. Compared with diet-only treatment, cholestyramine reduced total and LDL cholesterol levels by 77 mg/dl (22%) and 78 mg/dl (31%), respectively. In addition to relieving cholestyramine-induced constipation, neomycin further reduced the total cholesterol level by 20 mg/dl (6%). However, this further reduction in total cholesterol concentration was the result of a decrease in the concentration of high-density lipoprotein cholesterol. These findings indicate that combination therapy does not have an additive LDL cholesterol-lowering effect and that neomycin and cholestyramine is not a useful drug combination. In addition, these results illustrate the importance of determining the high-density lipoprotein cholesterol concentration to fully interpret the effects of hypolipidemic treatment.     

Association of cholesterol levels and occurrence of angiographically detectable endothelial disruption during coronary angioplasty

BACKGROUND: Disruption of the atherosclerotic plaque is a common feature of both acute coronary syndromes and balloon dilatation of coronary artery stenoses. HYPOTHESIS: The study was undertaken to evaluate whether the known association of cholesterol levels and acute coronary syndromes also exists for the occurrence of angiographically detectable endothelial disruption (ED) following coronary angioplasty. METHODS: For this purpose, we examined 79 consecutive patients (men/women 58/21; mean age: 62 +/- 11 years), with a noncalcified, de novo, significant stenosis in a single native coronary artery, undergoing elective coronary intervention because of stable effort angina. Coronary angioplasty was performed using regular balloon catheters, aiming for a balloon/ artery ratio of 1, with stent implantation allowed only provisionally. Following balloon dilatation, patients were divided into two groups according to the presence or absence of angiographically detectable ED. RESULTS: Endothelial disruption occurred in 28 patients (35%). The two groups with and without ED were comparable with respect to clinical, angiographic, and procedural parameters. A history of hypercholesterolemia was significantly more frequent in patients with ED (93 vs. 2%; p < 0.001). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in the group with ED (230.1 +/- 46.5 vs. 204.4 +/- 30.2 mg/dl, p < 0.05; and 150.6 +/- 39.2 vs. 125.8 +/- 26 mg/dl, p < 0.03, respectively). A cut-off value of LDL cholesterol > or = 135 mg/dl identified patients at higher risk of developing ED. CONCLUSION: High cholesterol levels appear to favor the occurrence of ED during coronary angioplasty. Aggressive lipid-lowering therapy and a more careful procedural approach may be warranted in patients with hypercholesterolemia undergoing coronary interventions in order to decrease the occurrence of ED and the associated clinical (acute ischemia) and procedural (stent implantation) consequences.     

Mevinolin plus colestipol in therapy for severe heterozygous familial hypercholesterolemia

Twelve patients with severe heterozygous familial hypercholesterolemia, in whom other hypolipidemic drug therapy had failed to reduce serum cholesterol levels to less than 300 mg/dL, were sequentially treated with mevinolin (a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis) and colestipol. In ten patients receiving 80 mg/d of mevinolin, plasma cholesterol concentrations decreased 33%, from 487 +/- 27 (SE) mg/dL to 326 +/- 16 mg/dL. Additional therapy with colestipol resulted in a further 18% decrease, to 269 +/- 13 mg/dL. Concentrations of low density lipoprotein (LDL) cholesterol decreased in parallel (54% decrease on combined drug therapy). Plasma concentrations of high density lipoprotein cholesterol did not change significantly, but the LDL:HDL ratio decreased from 8.2 in patients on diet only to 3.8 in patients treated with mevinolin and colestipol. In seven patients treated with 40 mg/d of mevinolin, concentrations of LDL cholesterol decreased by 33%; combined therapy resulted in a further 20% decrease (46% reduction from the level achieved with diet only). No consistent side effects have been noted in up to 24 months of therapy. Combined therapy with mevinolin and colestipol promises to be effective for heterozygous familial hypercholesterolemia.     

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of 相似文献   

Design and baseline characteristics of the simvastatin and ezetimibe in aortic stenosis (SEAS) study

Aortic valve stenosis and atherosclerotic disease have several risk factors in common, in particular, hypercholesterolemia. Histologically, the diseased valves appear to have areas of inflammation much like atherosclerotic plaques. The effect of lipid-lowering therapy on the progression of aortic stenosis (AS) is unclear, and there are no randomized treatment trials evaluating cardiovascular morbidity and mortality in such patients. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study is a randomized, double-blind, placebo-controlled, multicenter study of a minimum 4 years' duration investigating the effect of lipid lowering with ezetimibe/simvastatin 10/40 mg/day in patients with asymptomatic AS with peak transvalvular jet velocity 2.5 to 4.0 m/s. Primary efficacy variables include aortic valve surgery and ischemic vascular events, including cardiovascular mortality, and second, the effect on echocardiographically evaluated progression of AS. The SEAS Study randomly assigned 1,873 patients (age 68+/-10 years, 39% women, mean transaortic maximum velocity 3.1+/-0.5 m/s) from 173 sites. Other baseline characteristics were mean blood pressure of 145+/-20/82+/-10 mm Hg (51% hypertensive); 55% were current or previous smokers; and most were overweight (mean body mass index 26.9 kg/m2). At baseline, mean total cholesterol was 5.7+/-1.0 mmol/L (222 mg/dl), low-density lipoprotein cholesterol was 3.6+/-0.9 mmol/L (139 mg/dl), high-density lipoprotein cholesterol was 1.5+/-0.4 mmol/L (58 mg/dl), and triglycerides were 1.4+/-0.7 mmol/L (126 mg/dl). The SEAS Study is the largest randomized trial to date in patients with AS and will allow determination of the prognostic value of aggressive lipid lowering in such patients.     

Cholestyramine treatment during pregnancy in the rat results in hypercholesterolemia

Timed pregnant (8 days) Sprague-Dawley rats were fed ground stock diet (CON) or ground stock diet with 4% cholestyramine (CTR) until day 20 of gestation. Animals in both groups gained weight equally well during the study period (CON (n = 7), 308 +/- 7 g; CTR (n = 6), 315 +/- 7 g, mean +/- SEM). At the end of the study period, plasma cholesterol in the CTR group was significantly greater than that in the control group (CON n = 7, 91 +/- 4 mg/dl; CTR (n = 6), 108 +/- 5 mg/dl, P less than 0.05). The fecal excretion of both neutral steroids and bile acids, studied for 3 days between days 15 and 18 of gestation, was significantly enhanced by CTR treatment. (Neutral steroids: CON, 3.9 +/- 0.3; CTR, 10.4 +/- 0.3, P less than 0.05. Bile acids: CON, 7.6 +/- 0.4; CTR, 25.8 +/- 1.7, P less than 0.05, mg/100 g body wt/day). Bile acid pool size, measured at day 20 of gestation, however, was not significantly different. Consistent with these results was the finding that hepatic cholesterol 7 alpha-hydroxylase activity (the rate-limiting enzyme of bile acid biosynthesis) measured at day 20 of gestation was significantly enhanced by CTR treatment (CON (n = 4), 14.7 +/- 1.7; CTR (n = 4), 34.8 +/- 3.3, pmoles/mg/min, P less than 0.05). The atypical finding of hypercholesterolemia, despite the CTR-induced enhanced turnover of cholesterol, may be due to changes in the homeostatic mechanisms of cholesterol and bile acid metabolism during pregnancy.