Reducing cardiovascular risk: trends in risk, risk assessment, and cholesterol management.

The rate of decrease in coronary heart disease (CHD) mortality in the United States has slowed, probably in association with the aging of the population and the increasing rates of obesity, metabolic syndrome, and diabetes. Worldwide, guidelines for reducing risk of CHD and lowering lipid levels must continue to evolve to reflect disease and risk factor trends that reflect improvements in the knowledge of individual risk factors and the effects of clustered risk factors in specific patients. According to current guidelines used in the United States, Europe, and Canada for risk assessment and risk reduction, the trend is moving away from simple measurement of cholesterol and toward a more global risk assessment.

Lipid management and the elderly.

Advancing age is an independent risk factor for the development of coronary heart disease. However, the significance of hypercholesterolemia as a cardiovascular risk factor in the elderly, has been widely debated. While no large-scale, randomized clinical trial has been conducted to evaluate cholesterol lowering solely in the elderly, evidence from older subgroups in several intervention trials supports the efficacy of lowering elevated low-density lipoprotein cholesterol for reducing cardiovascular risk in the elderly.

Ezetimibe: a novel option for lowering cholesterol.

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease but lowering LDL-cholesterol to levels established in current National Cholesterol Education Program (NCEP) guidelines provides significant risk reduction. Nevertheless, many patients receiving lipid-lowering therapy, particularly those at highest coronary heart disease risk, do not reach LDL-cholesterol goals with their current medications. Ezetimibe (Zetia, Merck Schering-Plough) is the first of a new class of lipid-lowering drugs known as cholesterol absorption inhibitors.

Low-dose (0.3 mg) synthetic conjugated estrogens A is effective for managing atrophic vaginitis.

Objective: Estrogen or combined hormone (estrogen-progestin) therapy is highly efficacious for managing the signs and symptoms of urogenital atrophy. A low, effective estrogen dose may enhance patient acceptance and reduce side effects.

Methods: In this randomized, double-blind, multicenter clinical trial, 71 healthy postmenopausal women with vaginal atrophy (Vaginal Maturation Index < or =55) received either low-dose synthetic conjugated estrogens, A tablets (Cenestin) (SCE-A), 0.

Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic patient subgroups.

Background: In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C).

Hypothesis: Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients.

The safety and immunogenicity of a CETP vaccine in healthy adults.

A cholesterol ester transfer protein (CETP) vaccine (CETi-1) that induces auto-antibodies that specifically bind and inhibit activity of endogenous CETP has been demonstrated in rabbits to significantly increase HDL-C and reduce the development of atherosclerosis. In a Phase I human trial with CETi-1, one patient at the highest dose (250 mg) out of a total of 36 patients who received a single injection developed anti-CETP antibodies. In an extension study of 23 patients, 53% (8/15) who received a second injection of the active vaccine developed anti-CETP antibodies compared with 0% (0/8) in the placebo group.

Combination lipid-lowering therapy in diabetes.

Owing to the National Cholesterol Education Program Adult Treatment Panel III recommendations that patients with diabetes require a low-density lipoprotein (LDL) less than 100 mg/dL and a non-high-density lipoprotein (HDL) less than 130 mg/dL, frequently, combination lipid-lowering therapy is required. However, diabetic patients are commonly on multiple medications and have renal impairment. Therefore, the risk of myopathy with statin therapy is markedly increased.

Food products containing free tall oil-based phytosterols and oat beta-glucan lower serum total and LDL cholesterol in hypercholesterolemic adults.

This randomized, double-blind, controlled trial evaluated the influence of low fat, low saturated fat food products that contained free tall oil-based phytosterols (TOP) and oat beta-glucan (from whole oats and bran concentrate) on serum lipid concentrations in adults with mild-to-moderate hypercholesterolemia. After a 5-wk National Cholesterol Education Program Step I diet lead-in period, 112 subjects incorporated one of two treatments into their diets for 6 wk: food products (cereal, snack bar and beverage) that provided 1.8 g TOP and 2.

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia.

Objectives: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia.

Background: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals.

Combination therapy for dyslipidemia: safety and regulatory considerations.

The use of combination therapy is an effective way to manage dyslipidemia in patients with coronary artery disease (CAD). However, combination therapy is not a frequently used strategy in the treatment of CAD. Aggressive lipid-altering therapy often requires the use of combination therapy involving statins in conjunction with niacin, fibric-acid derivatives, ezetimibe, or bile acid resins.

Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil.

Background: Diacylglycerol is a natural component of edible oils that has metabolic characteristics that are distinct from those of triacylglycerol.

Objective: We assessed the efficacy of an oil containing mainly 1,3-diacylglycerol in reducing body weight and fat mass when incorporated into a reduced-energy diet.

Design: The study was a randomized, double-blind, parallel intervention trial that was conducted at an outpatient clinical research center.

A look to the future: new treatment guidelines and a perspective on statins.

New National Cholesterol Education Program treatment guidelines incorporate a global measure of coronary heart disease (CHD) that alters risk categorization in primary prevention by identifying individuals with CHD risk equivalence on the basis of estimated absolute CHD risk. Increasing recognition of the association of on-treatment non-high-density lipoprotein (HDL) cholesterol levels with risk of CHD events is also reflected in the new guidelines by incorporation of secondary non-HDL cholesterol goals. The increased complexity of the guidelines and the likelihood of more individuals being assigned to higher risk groups with lower low-density lipoprotein (LDL) cholesterol goals is of some concern, because most patients receiving lipid-lowering therapy do not achieve current guideline LDL cholesterol goals.

Management of hypercholesterolaemia in postmenopausal women.

Increased rates of coronary heart disease (CHD) occur with advancing age in both sexes, although CHD rates in women lag behind those of men by about 10 years. There is a sharp increase in CHD rate among women after approximately 50 years of age. The reasons for this are not completely understood and are undoubtedly multifactorial.

Strategies to improve Adult Treatment Panel III guideline adherence and patient compliance.

The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III report outlines the management of hypercholesterolemia through guidelines. These guidelines call for more aggressive diagnosis and treatment of hypercholesterolemia, which will substantially increase the number of individuals in the United States considered to be at risk for heart disease and will expand the number who will receive dietary and drug treatment. The new features of ATP III add complexity to the guidelines, which will impact adherence as well as add challenges to the management of hypercholesterolemia.

A multiple-dose pharmacodynamic, safety, and pharmacokinetic comparison of extended- and immediate-release formulations of lovastatin.

Background: Because lovastatin is efficiently extracted by the liver and because its administration in divided doses is associated with increased efficacy, an extended-release (ER) formulation may have the potential for a dose-sparing advantage relative to the immediate-release (IR) formulation in the treatment of hypercholesterolemia.

Objective: This study compared the short-term pharmacodynamics, safety, and pharmacokinetics of multiple doses of lovastatin ER with those of lovastatin IR in patients with fasting low-density lipoprotein cholesterol (LDL-C) levels between 130 and 250 mg/dL and fasting triglyceride levels < 350 mg/dL.

Methods: The study had a randomized, single-blind, positive-controlled, 2-way crossover design, with a 4-week diet/placebo run-in period and two 4-week active-treatment periods.

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.

Treatment of the elderly with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors: focus on drug interactions.

With the aging of the population, death from coronary heart disease (CHD) and stroke has become more prevalent. Cardiovascular disease (CVD) risk factors, such as hypertension, obesity, and diabetes mellitus increase with age as well. Recent secondary-prevention studies have established the positive effect of statins in decreasing the risk of CHD mortality through the lowering of cholesterol.

Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women.

Objective/design: The safety and tolerability of three levels of plant sterol-esters administered in reduced-fat spread and salad dressing vs. control products were evaluated in this randomized, double-blind, four-arm parallel study.

Methods: Eighty-four free-living men and women consumed reduced-fat spread and salad dressing providing 0.

Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet.

Background: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet.

Objective: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia.

Design: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.

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.

Safety profiles for the HMG-CoA reductase inhibitors: treatment and trust.

Hypercholesterolaemia is a chronic condition that often requires life-long treatment, making the safety of lipid-lowering drugs a critical issue. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') are commonly used as the pharmacotherapeutic treatment of choice for patients with hypercholesterolaemia. These agents have consistently demonstrated a positive safety and tolerability profile, and are recommended by the US National Cholesterol Education Program guidelines and by the European Joint Task Force for Prevention of Coronary Heart Disease to be used after, or in addition to, a first-line approach with diet.

Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia.

Background And Aim: Clinical data suggesting that larger decreases in low density lipoprotein cholesterol (LDL-C) result in greater reductions in coronary heart disease events have led to the establishment of aggressive LDL-C targets for the treatment of hypercholesterolemia. In view of this, the efficacy and safety of a new maximum dose of simvastatin, 80 mg, were evaluated in 9 studies involving 2819 hypercholesterolemic patients. This report focuses on the combined results from the 4 main or Pivotal studies in which a total of 1936 patients received simvastatin 40 or 80 mg for 36 to 48 weeks.