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Abstract: The most common omega-3 fatty acids contain 18–22 carbons and a signature double bond at the third position from the methyl (or n, or omega) end of the molecule. These fatty acids must be obtained in the diet as they cannot be synthesized by vertebrates. They include the plant-derived α-linolenic acid (ALA, 18:3n-3), and the fish-oil-derived eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Normally, very little ALA is converted to EPA, and even less to DHA, and therefore direct intake of the latter two is optimal. EPA and DHA and their metabolites have important biologic functions, including effects on membranes, eicosanoid metabolism, and gene transcription. Studies indicate that the use of fish oil is associated with coronary heart disease risk reduction. A number of mechanisms may be responsible for such effects. These include prevention of arrhythmias as well as lowering heart rate and blood pressure, decreasing platelet aggregation, and lowering triglyceride levels. The latter is accomplished by decreasing the production of hepatic triglycerides and increasing the clearance of plasma triglycerides. Our focus is to review the potential mechanisms by which these fatty acids reduce cardiovascular disease risk. [Copyright &y& Elsevier]

Abstract: Background: Lipid management in clinical practice has been suboptimal with a significant proportion of patients not achieving recommended cholesterol levels. A reason for low goal attainment may be the limited use of upward dose titration. Objective: The aim of this study was to determine if, in routine clinical practice, a lower rate of titration is observed among rosuvastatin patients who achieved the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) target low-density lipoprotein cholesterol (LDL-C) goals as compared with patients achieving the target LDL-C goals on other statins. Methods: This retrospective database study included the patients, aged ≥18 years, of ~3000 physicians across the United States, who were newly prescribed statin treatment from August 2003 to May 2005. Patients were excluded if they started on a maximum dose of statin, were at LDL-C goal at baseline (no clinical reason for titrating), or on fluvastatin (<70 patients). Titration rate with rosuvastatin was compared with other statins. Multivariate logistic regression models adjusted for baseline LDL-C, coronary heart disease risk, treatment duration, and target LDL-C goal attainment. Results: This study assessed 12,041 patients for upward titration. Of the 5955 eligible patients (mean age, 63 years; male, 47%), 7.2% were prescribed rosuvastatin, 63.5% atorvastatin, 15.3% simvastatin, 7.2% pravastatin, and 6.9% lovastatin. Overall, 4337 patients (72.8%) attained the NCEP ATP III target LDL-C goal. Mean duration of statin treatment was 188 days for rosuvastatin compared with 238 to 260 days for the other statins (all, P < 0.05). Among patients attaining the target LDL-C goal, significantly fewer rosuvastatin patients (8.3%) had titration compared with atorvastatin (17.0%), simvastatin (20.0%), pravastatin (20.7%), and lovastatin (23.5%) (all, P < 0.05). After adjusting for baseline characteristics, patients attaining the target LDL-C goal on other statins were significantly more likely to be titrated as compared with rosuvastatin (odds ratios, 2.0-3.3; P < 0.05). Lower titration rates for rosuvastatin patients were also observed in the total population (P < 0.05). Conclusion: Our study found that rosuvastatin patients who attained the NCEP ATP III target LDL-C goal had significantly lower titration rates than patients receiving other statins. [Copyright &y& Elsevier]

We evaluated correlates of coronary atherosclerosis, measured by coronary artery calcium, in a racially diverse group of male and female subjects with type 2 diabetes. Age, systolic blood pressure, sex, and race/ethnicity were significant determinants of coronary artery calcium. Among lipoproteins, cholesterol level contained in a particle excluded from direct measures of LDL and HDL cholesterol (designated triglyceride-rich lipoprotein cholesterol) was most strongly linked to coronary artery calcium. Neither inflammatory markers nor metabolic factors correlated with coronary artery calcium in models adjusted for age and sex, but measures of adipose distribution did. Waist-to-hip ratio and the ratio of visceral to total abdominal tissue were positively associated with coronary artery calcium. In fully adjusted multivariate models, the relationship of adiposity measures to coronary artery calcium was no longer significant after inclusion of apolipoprotein B or triglyceride-rich lipoprotein cholesterol. Traditional risk factors and race/ethnicity remain important correlates of coronary artery calcium in a cohort at elevated risk of cardiovascular disease because of type 2 diabetes. Adiposity measures are significantly associated with coronary artery calcium score, but their importance may be largely explained by apolipoprotein B or triglyceride-rich lipoprotein cholesterol. Diabetes 56:849-855, 2007 [ABSTRACT FROM AUTHOR]

Context: Carotid artery intima-media thickness (CIMT) is a marker of coronary atherosclerosis and independently predicts cardiovascular events, which are increased in type 2 diabetes mellitus (DM). While studies of relatively short duration have suggested that thiazolidinediones such as pioglitazone might reduce progression of CIMT in persons with diabetes, the results of longer studies have been less clear.Objective: To evaluate the effect of pioglitazone vs glimepiride on changes in CIMT of the common carotid artery in patients with type 2 DM.Design, Setting, and Participants: Randomized, double-blind, comparator-controlled, multicenter trial in patients with type 2 DM conducted at 28 clinical sites in the multiracial/ethnic Chicago metropolitan area between October 2003 and May 2006. The treatment period was 72 weeks (1-week follow-up). CIMT images were captured by a single ultrasonographer at 1 center and read by a single treatment-blinded reader using automated edge-detection technology. Participants were 462 adults (mean age, 60 [SD, 8.1] years; mean body mass index, 32 [SD, 5.1]) with type 2 DM (mean duration, 7.7 [SD, 7.2] years; mean glycosylated hemoglobin [HbA1c] value, 7.4% [SD, 1.0%]), either newly diagnosed or currently treated with diet and exercise, sulfonylurea, metformin, insulin, or a combination thereof.Interventions: Pioglitazone hydrochloride (15-45 mg/d) or glimepiride (1-4 mg/d) as an active comparator.Main Outcome Measure: Absolute change from baseline to final visit in mean posterior-wall CIMT of the left and right common carotid arteries.Results: Mean change in CIMT was less with pioglitazone vs glimepiride at all time points (weeks 24, 48, 72). At week 72, the primary end point of progression of mean CIMT was less with pioglitazone vs glimepiride (-0.001 mm vs +0.012 mm, respectively; difference, -0.013 mm; 95% confidence interval, -0.024 to -0.002; P = .02). Pioglitazone also slowed progression of maximum CIMT compared with glimepiride (0.002 mm vs 0.026 mm, respectively, at 72 weeks; difference, -0.024 mm; 95% confidence interval, -0.042 to -0.006; P = .008). The beneficial effect of pioglitazone on mean CIMT was similar across prespecified subgroups based on age, sex, systolic blood pressure, duration of DM, body mass index, HbA(1c) value, and statin use.Conclusion: Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride.Trial Registration: clinicaltrials.gov Identifier: NCT00225264 [ABSTRACT FROM AUTHOR]

The article presents a randomized, double-blind, controlled trial comparing the effect of pioglitazone and glimepiride on carotid artery intima-media thickness in patients with type 2 diabetes mellitus. The trial was conducted at clinical sites in the Chicago, Illinois metropolitan area. The study found that over an 18-month treatment period for patients with type 2 diabetes mellitus, pioglitazone slowed the progression of carotid artery intima-media thickness to a greater degree than glimepiride.

BACKGROUND: African Americans (AA) have the highest coronary heart disease mortality rate of any ethnic group In the United States. Data from the National Cholesterol Education Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey were used to assess ethnic differences in low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS: NEPTUNE II surveyed patients with treated dyslipidemia to assess achievement of treatment goals established by the Adult Treatment Panel Ill of the National Cholesterol Education Program. United States physicians working in primary care or relevant subspecialties enrolled 10 to 20 consecutive patients (May to September 2003), and patient data were recorded in Personal Digital Assistants and uploaded to a central database via the internet. RESULTS: Among 4,885 patients receiving treatment for dyslipidemia, 79.7% were non-Hispanic white (NHW) and 8.4% were AA. Non-Hispanic white and AA patients had significantly different frequencies of treatment success, with 69.0% and 53.7%, respectively, having achieved their LDL-C goal (P<.001). African-American patients were more likely to be in the highest risk category, and less likely to be using lipid drug therapy, taking high-efficacy statins, and receiving care from a subspecialist, but the difference in goal achievement remained significant (P<.001) after adjustment for these and other predictors of treatment success. CONCLUSIONS: The frequency of treatment success in dyslipidemia management was significantly lower in AA than NHW patients. Additional research is needed to elucidate reasons for this disparity and to evaluate strategies for improving goal achievement among AA patients receiving therapy for dyslipidemia. [ABSTRACT FROM AUTHOR]

Previous studies have used standard B-mode ultrasound to quantify the aggregate mean intimal medial thickness (IMT) of the near and far wall of the common carotid artery (CCA). Many investigators have had difficulty in accurately evaluating the near wall IMT secondary to difficulty in discerning the vessel lumen and intima. The purpose of this study is to determine the effect of contrast enhanced ultrasound on IMT measurement when compared with non-enhanced images. Twenty-six patients who had standard carotid ultrasounds completed over a 6-month period were evaluated, with 24 imaged by the same sonographer. Five to six measurements of the near and far walls were obtained over a 1cm distance, beginning and ending 0.5cm and 1.5cm proximal to the carotid bifurcation. The measurements were made with and without the contrast agent OptisonTM (perflutren protein type-A microspheres), which was given as an IV bolus (0.5-0.7 cc). Of those imaged by the same sonographer, 40 carotid arteries were examined and a total of 867 measurements were obtained. A total of 10% of the carotid ultrasounds were restudied approximately 1 month after the initial interpretation to assess observer accuracy. The near wall CCA mean (SD) IMT was 0.075 (0.019)cm for left with contrast versus 0.067 (0.023)cm for left without contrast and 0.089 (0.024)cm for right with versus 0.071 (0.022)cm for right without, p 0.0001 both sides. For the far wall of the CCA, the mean (SD) IMT comparison was 0.075 (0.021)cm for left with versus 0.070 (0.016)cm for left without, p = 0.005, and 0.070 (0.023)cm for right with versus 0.070 (0.016)cm for right without, p = 0.68. In conclusion, contrast-enhanced IMT measurement showed a highly statistically significant difference in near carotid wall thickness determinations versus non-contrast values. The thicker measurement is in agreement with previously reported data showing that non-contrast images underestimated near wall common carotid IMT in histologic samples. [ABSTRACT FROM AUTHOR]

The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments. [ABSTRACT FROM AUTHOR]

Presents the findings of a survey on the awareness of respondents on the association between cholesterol level and atherosclerotic vascular disease in the U.S. Demographic profile of respondents; Profile of self-reported risk factors; Importance of personal cholesterol level; Knowledge of desirable total cholesterol level; Awareness of national guidelines for cholesterol management.

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 2.8 g beta-glucan/d and contained < or =3.0 g total fat and < or =1.0 g saturated fat (TOP/beta-glucan treatment) or similar control foods. The serum LDL cholesterol response from baseline to the end of study was significantly larger in the TOP/beta-glucan treated group than in the control group, in which there was no change (-3.7 vs. 0.4%; P = 0.013). Likewise, total cholesterol decreased in the TOP/beta-glucan treatment group and did not change significantly in the controls (-2.3 vs. 0.8%; P = 0.043). Serum HDL cholesterol and triglyceride responses did not differ between the groups. The results of this trial suggest that consumption of a group of low fat, TOP and beta-glucan- containing foods is a useful adjunct in the dietary management of hypercholesterolemia. [ABSTRACT FROM AUTHOR]

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.Methods: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups.Results: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo.Conclusions: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone. [ABSTRACT FROM AUTHOR]

This trial assessed calcium excretion, as an indicator of calcium absorption, in 50 healthy men and postmenopausal women (ages 45-75), from a beverage containing calcium, magnesium, vitamins C, D, K, zinc, phosphorous, soy isoflavones, and inulin, compared with a calcium carbonate (CaCO3) tablet. At the end of each 4-week treatment period, subjects consumed a standardized low calcium meal plus the assigned study product (time = 0 hours). Subjects had significantly higher urinary creatinine-corrected calcium concentrations after the beverage than after the CaCO3 tablet. During the beverage phase, subjects had 29% and 22% greater mean urinary creatinine-corrected calcium concentrations for 0-6 and 6-72 hours, respectively, compared with the CaCO3 phase (p < 0.01 for both). There was no difference between the CaCO3 and beverage phases in 6-hour post-meal serum calcium or magnesium concentrations. In conclusion, a specially formulated calcium-containing test beverage increased excretion of calcium, compared with a CaCO3 tablet, suggesting enhanced calcium absorption. [Copyright &y& Elsevier]

An abstract of the conference paper "Lipid sub-fractionation predicts worsening myocardial perfusion reserve in patients with low-density lipoprotein less than 100mg/dL: a regadenoson dardiac magnetic resonance study," by Amit R. Patel, and colleagues is presented.

Background: A novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia. Objective: This study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non-HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease. Methods: In this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥200 mg/ dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosa-pentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events. Results: In the 627 subjects in the intention to treat sample, non-HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (-3.9% and -6.9%, respec-tively) compared with OO (-0.9%) (both, P < 0.05), as were TG levels (-14.6% and -20.6%, respectively, vs -5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahex-aenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d. Conclusions: OM3-FFA was well tolerated and low-ered non-HDL-C and TG levels at both 2- and 4-g/d dos-ages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental im-provements compared with 2 g/d. ClinicalTrials.gov iden-tifier: NCT01408303. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes (T2D) manifest a form of dyslipidemia typified by high LDL particle concentration (PC), small LDL particle size (PS), and high triglyceride and low HDL-C levels. This diabetic dyslipidemia may contribute to the excess cardiovascular events seen in T2D. In CHICAGO, a randomized, double-blind, multicenter, 72-week study, pioglitazone (PIO) was associated with less CIMT progression compared to glimepiride (GLM) in patients with T2D (N=462). We also observed significant improvements in TG and HDL-C levels with PIO vs GLM, with no difference in LDL-C levels. Here we report the results of the lipoprotein subfraction analysis. Blood samples were obtained at baseline and weeks 24, 48, and 72 (or time of withdrawal) for determination of PC and PS of VLDL, LDL, and HDL, measured by NMR spectroscopy. At Final Visit, PIO therapy produced a significant reduction in VLDL PS due to significant decreases in large and medium VLDL PC and increases in small VLDL PC. LDL PS significantly increased due to a significant reduction in small LDL and increase in large LDL PC. HDL PS also significantly increased due to a reduction in small and an increase in large HDL PC. In aggregate, the changes in lipoprotein subfraction distribution would be predicted to produce a reduction in CVD risk with PIO vs GLM and may contribute to beneficial effects of PIO on CIMT. [ABSTRACT FROM AUTHOR]

The large administrative databases of health plans contain information on drug-related medical adverse events (AE) and constitute an increasingly powerful tool for the assessment of drug safety. We conducted a retrospective observational study using an administrative managed care claims database covering 9 million members from diverse regions of the United States. Patients aged >or=18 years who received >or=2 prescriptions for lipid-lowering drugs between July 1, 2000 and December 1, 2004 were included in the study. Hospitalizations with diagnosis codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9]) related to muscle, kidney, and liver were determined for patients exposed to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), fibrates, extended-release niacin, cholesterol absorption inhibitors, or statin combination therapy. A total of 473,343 patients contributed 490,988 person-years of monotherapy and 11,624 person-years of combination dyslipidemia therapy. Rates of hospitalization due to AEs in patients on monotherapy with currently available statins were similar, whereas the incidence of hospitalization for muscle disorders increased 6.7-fold with cerivastatin therapy. Patients who received a lipid-lowering medication with a concomitant cytochrome P450 3A4 (CYP3A4) inhibitor had a 6-fold increased rate of muscle disorders, including rhabdomyolysis. Hypertension was associated with a 5-fold increase in both muscle and renal events, whereas patients with diabetes mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of the index AEs were observed in study subjects during the 6-month period before initiation of the lipid-lowering drug. Statin monotherapy as currently prescribed is generally well tolerated and safe. [ABSTRACT FROM AUTHOR]

The large administrative databases of health plans contain information on drug-related medical adverse events (AE) and constitute an increasingly powerful tool for the assessment of drug safety. We conducted a retrospective observational study using an administrative managed care claims database covering 9 million members from diverse regions of the United States. Patients aged ≥18 years who received ≥2 prescriptions for lipid-lowering drugs between July 1, 2000 and December 1, 2004 were included in the study. Hospitalizations with diagnosis codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9]) related to muscle, kidney, and liver were determined for patients exposed to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), fibrates, extended-release niacin, cholesterol absorption inhibitors, or statin combination therapy. A total of 473,343 patients contributed 490,988 person-years of monotherapy and 11,624 person-years of combination dyslipidemia therapy. Rates of hospitalization due to AEs in patients on monotherapy with currently available statins were similar, whereas the incidence of hospitalization for muscle disorders increased 6.7-fold with cerivastatin therapy. Patients who received a lipid-lowering medication with a concomitant cytochrome P450 3A4 (CYP3A4) inhibitor had a 6-fold increased rate of muscle disorders, including rhabdomyolysis. Hypertension was associated with a 5-fold increase in both muscle and renal events, whereas patients with diabetes mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of the index AEs were observed in study subjects during the 6-month period before initiation of the lipid-lowering drug. Statin monotherapy as currently prescribed is generally well tolerated and safe. [Copyright &y& Elsevier]

Background: The enzyme acyl–coenzyme A:cholesterol acyltransferase (ACAT) esterifies cholesterol in a variety of tissues. In some animal models, ACAT inhibitors have antiatherosclerotic effects. Methods: We performed intravascular ultrasonography in 408 patients with angiographically documented coronary disease. All patients received usual care for secondary prevention, including statins, if indicated. Patients were randomly assigned to receive the ACAT inhibitor pactimibe (100 mg per day) or matching placebo. Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Results: The primary efficacy variable analyzing the progression of atherosclerosis — the change in percent atheroma volume — was similar in the pactimibe and placebo groups (0.69 percent and 0.59 percent, respectively; P=0.77). However, both secondary efficacy variables assessed by means of intravascular ultrasonography showed unfavorable effects of pactimibe treatment. As compared with baseline values, the normalized total atheroma volume showed significant regression in the placebo group (−5.6 mm3, P=0.001) but not in the pactimibe group (−1.3 mm3, P=0.39; P=0.03 for the comparison between groups). The atheroma volume in the most diseased 10-mm subsegment regressed by 3.2 mm3 in the placebo group, as compared with a decrease of 1.3 mm3 in the pactimibe group (P=0.01). The combined incidence of adverse cardiovascular outcomes was similar in the two groups (P=0.53). Conclusions: For patients with coronary disease, treatment with an ACAT inhibitor did not improve the primary efficacy variable (percent atheroma volume) and adversely affected two major secondary efficacy measures assessed by intravascular ultrasonography. ACAT inhibition is not an effective strategy for limiting atherosclerosis and may promote atherogenesis. (ClinicalTrials.gov number, NCT00268515.) N Engl J Med 2006;354:1253-63. [ABSTRACT FROM AUTHOR]

Plasma lipid and apolipoprotein ratios that include both an atherogenic and an antiatherogenic lipid component (eg, total cholesterol/high-density lipoprotein [HDL] cholesterol ratio, low-density lipoprotein [LDL] cholesterol/HDL cholesterol ratio, non-HDL cholesterol/HDL cholesterol ratio, and apolipoprotein [apo] B/apo A-I ratio) have been found to be strong predictors of coronary artery disease (CAD) risk. Three trials that compared the effects of rosuvastatin 10 mg versus atorvastatin 10 mg and 2 trials that compared the effects of rosuvastatin 10 mg versus simvastatin 20 mg and pravastatin 20 mg on lipid ratios in patients with hypercholesterolemia were prospectively designed for pooled analysis. At 12 weeks, in the 3-trial pooled analysis, rosuvastatin 10 mg (n = 389) showed significantly greater reductions in all 4 lipid ratios compared with atorvastatin 10 mg (n = 393) (p <0.001). The mean percent reduction from baseline in the LDL cholesterol/HDL cholesterol ratio was 51% in patients treated with rosuvastatin 10 mg versus 39% in patients treated with atorvastatin 10 mg. In the 2-trial pooled analysis, treatment with rosuvastatin 10 mg (n = 226) also resulted in significantly greater reductions in all 4 lipid ratios compared with both simvastatin 20 mg (n = 249) and pravastatin 20 mg (n = 252) (p <0.001). Mean percent reductions from baseline in the LDL cholesterol/HDL cholesterol ratio were 52%, 39%, and 30% for rosuvastatin 10 mg, simvastatin 20 mg, and pravastatin 20 mg, respectively, in these 2 trials. [ABSTRACT FROM AUTHOR]

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. Following key recommendations and incorporating essential elements of adherence can improve implementation of the NCEP ATP III guidelines. The use of global risk scoring aids, including the Palm Pilot cholesterol risk calculators, can improve guideline adherence and provide education and motivation to patients to maintain compliance. [ABSTRACT FROM AUTHOR]