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Biomedical subjects

D Hunninghake

Publications and source records attributed to D Hunninghake.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of the efficacy of atorvastatin versus cerivastatin in primary hypercholesterolemia.

This 6-week Prospective, Randomized, Open-label Blinded End point (PROBE) study conducted at 12 sites in the United States compared the efficacy and safety of atorvastatin with cerivastatin. In all, 215 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.14 mmol/L]; triglycerides < or = 400 mg/dl [4.52 mmol/L]) were randomized to receive either atorvastatin 10 mg once daily (n = 108) or cerivastatin 0.3 mg once daily (n = 107). Efficacy was assessed by measuring changes from baseline in LDL cholesterol, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Atorvastatin produced significantly greater (p < 0.0001) reductions from baseline to week 6 in LDL cholesterol (37.7% vs 30.2%), total cholesterol (27.5% vs 22.2%), and apolipoprotein B (28.6% vs 21.2%), and a significantly greater (p < 0.05) increase from baseline to week 6 in high-density lipoprotein cholesterol (6.8% vs 4.3%) than cerivastatin. Atorvastatin treatment was also associated with a greater percent decrease from baseline to week 6 in triglycerides, with a trend toward statistical significance (p = 0.0982). The percentage of patients that achieved the National Cholesterol Education Program LDL cholesterol goal was greater for those receiving atorvastatin (73%) than for those receiving cerivastatin (66%). The proportion of patients experiencing drug-attributable adverse events, which were mostly mild to moderate and related to the digestive system, was significantly less (p < 0.05) with atorvastatin (5%) than with cerivastatin (14%) treatment. In conclusion, atorvastatin (10 mg/day) is more effective at lowering LDL cholesterol in hypercholesterolemic patients than cerivastatin (0.3 mg/day). Both atorvastatin and cerivastatin are well tolerated, with safety profiles similar to other members of the statin class.

Administration, Oral↗
PubMed2001

Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia.

BACKGROUND: Colesevelam hydrochloride is a novel, lipid-lowering agent that binds bile acids with high affinity. A multicenter, randomized, double-blind, placebo-controlled, parallel-design study was conducted to assess the efficacy and tolerability of combination low-dose colesevelam and lovastatin treatment in patients with primary hypercholesterolemia. HYPOTHESIS: Combination therapy with low doses of colesevelam and lovastatin decreases low density (LDL) cholesterol with minimal adverse events. METHODS: Following a 4- to 6-week dietary lead in, 135 patients were randomized into five groups for a 4-week treatment period: placebo, colesevelam 2.3 g at dinner, lovastatin 10 mg at dinner, the combination of colesevelam and lovastatin given at dinner (dosed together), and combination treatment with colesevelam given at dinner and lovastatin administered at bedtime (dosed apart). RESULTS: Combination colesevelam and lovastatin treatment decreased LDL cholesterol by 34% (60 mg/dl, p < 0.0001) and 32% (53 mg/dl, p < 0.0001) when colesevelam and lovastatin were dosed together or dosed apart, respectively. Both combination therapies were superior to either agent alone (p < 0.05). Decreases in LDL cholesterol exceeded the combined decreases observed for colesevelam alone (13 mg/dl, 7%) and lovastatin alone (39 mg/dl, 22%). Both combination treatments reduced total cholesterol by 21% (p < 0.0001) and apolipoprotein B by 24% (p < 0.0001). Neither combination treatment significantly altered high-density lipoprotein cholesterol or triglycerides. Adverse side effects were not significantly different among randomized groups. CONCLUSIONS: Combination colesevelam and lovastatin was efficacious and well tolerated, resulting in additive decreases in LDL cholesterol levels whether or not both agents were administered simultaneously.

Allylamine↗
PubMed2001

Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively.

Colesevelam hydrochloride is a novel, potent, non-absorbed lipid-lowering agent previously shown to reduce low density lipoprotein (LDL) cholesterol. To examine the efficacy and safety of coadministration of colesevelam and atorvastatin, administration of these agents alone or in combination was examined in a double-blind study of 94 hypercholesterolemic men and women (baseline LDL cholesterol > or =160 mg/dl). After 4 weeks on the American Heart Association Step I diet, patients were randomized among five groups: placebo; colesevelam 3.8 g/day; atorvastatin 10 mg/day; coadminstered colesevelam 3.8 g/day plus atorvastatin 10 mg/day; or atorvastatin 80 mg/day. Fasting lipids were measured at screening, baseline and 2 and 4 weeks of treatment. LDL cholesterol decreased by 12-53% in all active treatment groups (P<0.01). LDL cholesterol reductions with combination therapy (48%) were statistically superior to colesevelam (12%) or low-dose atorvastatin (38%) alone (P<0.01), but similar to those achieved with atorvastatin 80 mg/day (53%). Total cholesterol decreased 6-39% in all active treatment groups (P<0.05). High density lipoprotein cholesterol increased significantly for all groups including placebo (P<0.05). Triglycerides decreased in patients taking atorvastatin alone (P<0.05), but were unaffected by colesevelam alone or in combination. The frequency of side effects did not differ among groups. At recommended starting doses of each agent, coadministration of colesevelam and atorvastatin was well tolerated, efficacious and produced additive LDL cholesterol reductions comparable to those observed with the maximum atorvastatin dose.

Adult↗
PubMed2001

Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: a 24-week randomized controlled trial.

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of colesevelam hydrochloride, a new nonsystemic lipid-lowering agent. PATIENTS AND METHODS: In this double-blind, placebo-controlled trial performed in 1998, 494 patients with primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol level > or = 130 mg/dL and < or = 220 mg/dL) were randomized to receive placebo or colesevelam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum lipid profiles were measured to assess efficacy. Adverse events were monitored, and discontinuation rates and compliance rates were analyzed. The primary outcome measure was the mean absolute change of LDL cholesterol from baseline to the end of the 24-week treatment period. RESULTS: Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dose-dependent manner (P<.001), with a median LDL cholesterol reduction of 20% at 4.5 g/d. The reduction in LDL cholesterol levels was maximal after 2 weeks and sustained throughout the study. Mean total cholesterol levels decreased 4% to 10% (P<.001), while median high-density lipoprotein cholesterol levels increased 3% to 4% (P<.001). Median triglyceride levels increased by 5% to 10% in placebo and colesevelam treatment groups relative to baseline (P<.05), but none of these differences were significantly different from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an apparent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rates were between 88% and 92% for all groups. CONCLUSIONS: Colesevelam was efficacious, decreasing mean LDL cholesterol levels by up to 18%, and well tolerated without serious adverse events.

Adult↗
PubMed2000

Peripheral arterial disease in randomized trial of estrogen with progestin in women with coronary heart disease: the Heart and Estrogen/Progestin Replacement Study.

BACKGROUND: Postmenopausal estrogen use has been associated with reduced carotid atherosclerosis in observational studies, but this relationship has not been confirmed in a clinical trial. The impact of estrogen on atherosclerotic disease in other peripheral arteries is unknown. METHODS AND RESULTS: Postmenopausal women with coronary heart disease (CHD) and an intact uterus (n=2763) were randomly assigned to conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) daily or to placebo in a secondary CHD prevention trial. This analysis focuses on incident peripheral arterial procedures and deaths in the 2 treatment groups; peripheral vascular disease was a predefined secondary outcome. During a mean of 4.1 years of follow-up, 311 peripheral arterial events were reported in 213 women, an annual incidence of 2.9%. The number of women who had peripheral arterial events was 99 among those assigned to active estrogen/progestin and 114 among those assigned to placebo, a nonsignificant difference (relative hazard 0. 87, 95% CI 0.66 to 1.14). In the placebo group, hypertension and diabetes mellitus were independently associated with higher rates of peripheral arterial events, and plasma HDL cholesterol and body mass index were associated with lower rates of peripheral arterial events. In the estrogen/progestin group, current smoking and diabetes were independent predictors of peripheral arterial events. Incident peripheral arterial disease was not a significant predictor of coronary, cardiovascular, or total mortality. CONCLUSIONS: Treatment with oral conjugated estrogen plus medroxyprogesterone acetate was not associated with a significant reduction in incident peripheral arterial events in postmenopausal women with preexisting CHD.

Aged↗
PubMed2000

Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study.

BACKGROUND: Oral contraceptive use increases risk for venous thromboembolism, but data on the effect of postmenopausal hormone therapy are limited. OBJECTIVE: To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 clinical centers in the United States. PARTICIPANTS: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous venous thromboembolism and had not had a hysterectomy. INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383). MEASUREMENTS: Documented deep venous thrombosis or pulmonary embolism. RESULTS: During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess risk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 3.0 to 10.8]). Risk was decreased with aspirin (relative hazard, 0.5 [CI, 0.2 to 0.8]) or statin use (relative hazard, 0.5 [CI, 0.2 to 0.9]). CONCLUSIONS: Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart disease. This risk should be considered when the risks and benefits of therapy are being weighed.

Aged↗
PubMed2000

Sex bias and underutilization of lipid-lowering therapy in patients with coronary artery disease at academic medical centers in the United States and Canada. Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) Investigators.

BACKGROUND: The efficacy of lipid-lowering therapy (LLT) has been well established for patients with preexisting coronary artery disease (CAD). However, limited information is available assessing the extent to which these medications are prescribed in academic medical centers. METHODS: The use of LLT for patients with CAD was prospectively evaluated in 825 men and women who were recruited from 16 academic medical centers in the United States and Canada to participate in the Prospective Evaluation of the Vascular Events of Norvasc Trial (PREVENT). The assessment of LLT use during the 3-year trial was evaluated in patients receiving amlodipine therapy and placebo; levels of low-density lipoprotein cholesterol (LDL-C) were used to assess the impact of LLT. RESULTS: Despite a baseline prevalence of LLT in 42% of men (38% in 1994), half of the patients had high levels of LDL-C (>3.36 mmol [>130 mg/dL]). During the subsequent 3 years, the prevalence of elevated LDL-C levels dropped in men (29%) but remained stagnant in women (48%). These changes were associated with increased LLT in men (55%) but not in women (35%) (P = .04). In 1994, the LDL-C target goal (<2.59 mmol/L [<100 mg/dL]) was attained in 17% of men and 6% of women (P = .006). At study completion in 1997, the LDL-C target goal was achieved in 31% of men and only 12% of women (P = .001). CONCLUSIONS: This study highlights the relatively low treatment rates of hyperlipidemia among patients with CAD overall and women in particular who were participating in a clinical trial at academic medical centers in the United States and Canada. Because LLT has been proven to reduce future cardiovascular events, these results suggest that more intensive efforts should be promoted in order to maximize CAD reduction.

Academic Medical Centers↗
PubMed2000

Effect of niacin, warfarin, and antioxidant therapy on coagulation parameters in patients with peripheral arterial disease in the Arterial Disease Multiple Intervention Trial (ADMIT).

BACKGROUND: Patients with peripheral arterial disease (PAD) have high rates of cardiovascular morbidity and mortality, including that caused by associated coronary heart disease and cerebrovascular disease. Previous studies have shown that coagulation parameters are altered in PAD and that altered coagulation may play a critical role in the susceptibility to cardiovascular complications in PAD. It is therefore important to assess the effect of secondary prevention measures on coagulation in patients with PAD. The Arterial Disease Multiple Intervention Trial (ADMIT), a multicenter, randomized, placebo-controlled trial, was conducted to determine the feasibility of a combined lipid-modifying, antioxidant, and antithrombotic treatment regimen in patients with PAD. The objective of this study was to assess the effect of the ADMIT interventions on coagulation. METHODS: ADMIT participants were randomly assigned to low-dose warfarin, niacin, and antioxidant vitamin cocktail or corresponding placebos in a 2 x 2 x 2 factorial design. Specialized coagulation studies were performed in a subset of 80 ADMIT participants at baseline and after 12 months of treatment. RESULTS: Low-dose warfarin (1 to 4 mg/d) resulted in a significant decrease in factor VIIc (P <.001) and in plasma F1.2 (P =.001). Unexpectedly, niacin treatment also resulted in significant decrease in both fibrinogen (48 mg/dL; P <.001) and F1.2 (P =.04). von Willebrand factor increased after antioxidant vitamin treatment (P =.04). CONCLUSIONS: A regimen of low-dose warfarin effectively modifies coagulation in patients with PAD. Niacin also favorably modifies fibrinogen and plasma F1.2. Niacin, in addition to its lipid effects, modifies abnormal coagulation factors that accompany PAD.

Aged↗
PubMed2000

Randomized comparison of the efficacy and safety of cerivastatin and pravastatin in 1,030 hypercholesterolemic patients. The Cerivastatin Study Group.

OBJECTIVE: To determine the relative efficacy and safety of cerivastatin and pravastatin in patients with type II hypercholesterolemia. PATIENTS AND METHODS: In this prospective, double-blind, parallel-group study, hypercholesterolemic patients were randomized to treatment with cerivastatin, 0.3 mg (n=250) or 0.4 mg (n=258), or pravastatin, 20 mg (n=266) or 40 mg (n=256), for 8 weeks. RESULTS: Cerivastatin, 0.3 mg, was significantly more effective than pravastatin, 20 mg, in reducing low-density lipoprotein (LDL) cholesterol from baseline (-29.6% vs -26.8%; P=.008). Cerivastatin, 0.4 mg, was significantly more effective than pravastatin, 40 mg, in reducing LDL cholesterol (-34.2% vs -30.3%; P<.001). A larger proportion of cerivastatin-treated patients had greater than 40% reductions in LDL cholesterol than those receiving pravastatin (11.1% vs 6.0%). The percentage of patients who achieved the National Cholesterol Education Program (NCEP) target was 71.3% with cerivastatin, 0.3 mg, compared with 67.5% with pravastatin, 20 mg, and 74.0% with cerivastatin, 0.4 mg, compared with 71.1% with pravastatin, 40 mg (no significant difference). Cerivastatin, 0.3 mg, reduced total cholesterol to a greater extent than did pravastatin, 20 mg (P<.03). Both agents reduced triglycerides and increased high-density lipoprotein cholesterol to a similar degree (no significant differences). Cerivastatin and pravastatin were well tolerated. CONCLUSIONS: Cerivastatin, 0.3 mg and 0.4 mg, showed greater efficacy than pravastatin, 20 mg and 40 mg, respectively, in lowering LDL cholesterol. Cerivastatin is safe and effective for patients with hypercholesterolemia who require aggressive LDL cholesterol lowering to achieve NCEP-recommended targets.

Adolescent↗
PubMed1999

Comparison of the effects of lean red meat vs lean white meat on serum lipid levels among free-living persons with hypercholesterolemia: a long-term, randomized clinical trial.

BACKGROUND: Patients with hypercholesterolemia are often counseled to limit or eliminate intake of red meats, despite evidence that lean red meats (LRMs) are not hypercholesterolemic in comparison with lean white meats (LWMs). The objective of this study was to evaluate the long-term effects on serum lipids of incorporating LRM (beef, veal, and pork) vs LWM (poultry and fish) into a National Cholesterol Education Program (NCEP) Step I diet in free-living individuals with hypercholesterolemia. METHODS: Subjects included 191 men and women with a serum low-density lipoprotein cholesterol level of 3.37 to 4.92 mmol/L (130-190 mg/dL) and triglyceride level less than 3.96 mmol/L (350 mg/dL). After a 4-week baseline phase, subjects were counseled to follow an NCEP Step I diet including 170 g (6 oz) of lean meat per day, 5 to 7 days per week. Based on random assignment, subjects were instructed to consume at least 80% of their meat in the form of LRM or LWM. Fasting serum lipid levels were assessed 4, 12, 20, 28, and 36 weeks after randomization. RESULTS: After randomization, mean concentrations of total cholesterol (6.09 mmol/L [235.7 mg/dL] vs 6.08 mmol/L [235.2 mg/dL]) and low-density lipoprotein cholesterol (3.99 mmol/L [154.1 mg/dL] vs4.01 mmol/L [154.7 mg/dL]) were nearly identical in the LRM and LWM groups (1%-3% below baseline) during treatment. Mean triglyceride levels remained similar to baseline values and high-density lipoprotein cholesterol concentrations increased by approximately 2% in both groups. CONCLUSIONS: The NCEP Step I diets containing primarily LRM or LWM produced similar reductions in low-density lipoprotein cholesterol and elevations in high-density lipoprotein cholesterol levels, which were maintained throughout 36 weeks of treatment.

Animals↗
PubMed1999

Niacin treatment increases plasma homocyst(e)ine levels.

BACKGROUND: Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. METHODS: The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. RESULTS: During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P <.0001). At 18 weeks after randomization, there was an absolute 55% increase from baseline in mean plasma homocyst(e)ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. CONCLUSIONS: Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

Aged↗
PubMed1998

Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study)

The objective of this multicenter, randomized, open-label, parallel-group, 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40, and 80 mg compared with simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20, 40, and 80 mg, and fluvastatin 20 and 40 mg. Investigators enrolled 534 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.2 mmol/L] and triglycerides < or = 400 mg/dl [4.5 mmol/L]). The efficacy end points were mean percent change in plasma LDL cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment (week 8). Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in LDL cholesterol, -38%, -46%, and -51%, respectively, than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than (p < or = 0.02) simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20 and 40 mg, and fluvastatin 20 and 40 mg. Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in total cholesterol than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. All reductase inhibitors studied had similar tolerability. There were no incidences of persistent elevations in serum transaminases or myositis.

Adolescent↗
PubMed1998

Treating to meet NCEP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease.

BACKGROUND: Our study compared use of atorvastatin, fluvastatin, lovastatin, and simvastatin for lowering low-density lipoprotein (LDL) cholesterol concentration in patients at risk for coronary heart disease (CHD). The goal was to reach the LDL cholesterol levels recommended by the National Cholesterol Education Program (NCEP). METHODS: A combined total of 344 men and women took part in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were selected on the basis of their LDL cholesterol concentration and their risk for CHD. During treatment, doses were titrated at 12-week intervals to a maximum of 80 mg per day of atorvastatin and lovastatin, or 40 mg per day of fluvastatin and simvastatin, with colestipol added if necessary to attain the NCEP-recommended LDL cholesterol concentration. RESULTS: At the starting dose, atorvastatin decreased plasma LDL cholesterol significantly (P < .05) compared with the other reductase inhibitors, and the percentage of patients reaching target LDL cholesterol concentration at the starting dose was significantly greater in the atorvastatin group (P < .05). Overall, a significantly (P < .05) greater percentage (95%) of atorvastatin-treated patients achieved target LDL cholesterol concentration. The safety profile was similar among all reductase inhibitors tested. CONCLUSIONS: At the starting dose, a significantly (P < .05) greater percentage of atorvastatin-treated patients at risk for CHD reached the target LDL cholesterol concentration than patients with treated with other reductase inhibitors.

Adult↗
PubMed1997

Cost effectiveness of treatment to National Cholesterol Education Panel (NCEP) targets with HMG-CoA reductase inhibitors. Trial design.

HMG-CoA reductase inhibitors effectively reduce cholesterol levels, and this is associated with a lower rate of cardiovascular events. Some HMG-CoA reductase inhibitors are more effective than others in reducing low density lipoprotein (LDL) cholesterol, and such drugs should help patients achieve LDL cholesterol targets prescribed by the National Cholesterol Education Panel (NCEP). This paper describes the design of a trial comparing the clinical efficacy and cost effectiveness of four HMG-CoA reductase inhibitors in reducing LDL cholesterol to specified targets. This trial is being conducted in 30 physicians' practices in the USA. Its primary aim is to assess the resource use required to achieve and maintain NCEP targets by all patients randomised and followed up for one year.

Anticholesteremic Agents↗
PubMed1995

Estrogen replacement therapy and progression of intimal-medial thickness in the carotid arteries of postmenopausal women. ACAPS Investigators. Asymptomatic Carotid Atherosclerosis Progression Study.

The effect of estrogen replacement therapy (ERT) on 3-year changes in carotid intimal-medial thickness (IMT) was explored using serial B-mode ultrasound measurements collected during 1989-1993 as part of the Asymptomatic Carotid Atherosclerotic Progression Study (ACAPS). Eligibility included increased IMT and elevated low density lipoprotein cholesterol. Of the 186 postmenopausal ACAPS women randomly assigned to receive either placebo or lovastatin, 34% reported use of ERT. Users tended to be younger than nonusers by an average of 3 years, to have more favorable high and low density lipoprotein cholesterol levels, and to be more likely to have had hysterectomies. Baseline blood pressure, body mass index, and cross-sectional IMT were similar among ERT users and nonusers. In the placebo group, IMT tended to progress among ERT nonusers but to regress among ERT users: Mean covariate-adjusted progression rates were 0.015 +/- 0.007 mm/year versus -0.012 +/- 0.012 mm/year, respectively (p = 0.05). This difference appeared to be independent of lipoprotein concentrations. Lovastatin was associated with an approximately 25% lowering of low density lipoprotein cholesterol among both ERT users and nonusers and had a marked impact on IMT progression (p = 0.004) in these women. ERT appeared to have little additional effect on IMT in women assigned to lovastatin. ERT may reduce or halt the progression of early atherosclerosis in women not receiving active lipid-lowering medication.

Adult↗
PubMed1994

Efficacy and safety of once-daily vs twice-daily dosing with fluvastatin, a synthetic reductase inhibitor, in primary hypercholesterolemia.

BACKGROUND: Fluvastatin sodium is a new, entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that may be an effective lipid-lowering agent in patients whose hyperlipidemia does not respond to dietary therapy. We conducted a study to evaluate the effects of fluvastatin on lipoprotein levels in subjects with primary hypercholesterolemia and to compare the efficacy and safety of two fluvastatin sodium dosing regimens: 20 mg once daily vs 10 mg twice daily. DESIGN: We conducted a double-blind, placebo-controlled, multicenter trial involving 207 patients with low-density lipoprotein cholesterol levels of 4.15 mmol/L (160 mg/dL) or higher despite dietary intervention and with triglyceride levels of 3.38 mmol/L or lower. Three parallel treatment groups received 6 weeks of treatment with 20 mg of fluvastatin sodium once daily, 10 mg of fluvastatin sodium twice daily, or a placebo. RESULTS: Total cholesterol and low-density lipoprotein cholesterol levels were reduced from baseline by 16% and 22%, respectively, with 20 mg of fluvastatin sodium once daily (P < .001) and by 17% and 23%, respectively, with 10 mg of fluvastatin sodium twice daily (P < .001). Fluvastatin was well tolerated, and there were no serious clinical or biochemical adverse events ascribable to the drug. CONCLUSIONS: Fluvastatin therapy demonstrated excellent short-term safety and efficacy in reducing total and low-density lipoprotein cholesterol levels in patients with primary hypercholesterolemia. Fluvastatin sodium, the first totally synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be used in clinical trials, appears to be both effective and well tolerated at 20 mg/d, given in either a single or divided dose.

Adult↗
PubMed1993

Determination of apolipoprotein E genotypes by single-strand conformational polymorphism.

We used single-strand conformational polymorphism (SSCP) to determine apolipoprotein E (Apo E) genotypes in 47 individuals. A 295-base-pair (bp) DNA fragment coding for amino acid residues 80-178 of the Apo E protein gave distinct patterns for the three alleles. When we used SSCP to determine the Apo E polymorphism of five individuals whose phenotyping results differed from those of genotyping, the SSCP results agreed with the genotyping results obtained by the PCR-based amplification refractory mutation system (ARMS). Because most of the reported rare alleles of the Apo E gene involve mutations of amino acid residues in positions 120-160, our SSCP method is useful for determining rare as well as common alleles.

Apolipoproteins E↗