Apolipoprotein E polymorphisms in Mexican patients with coronary artery disease.

BACKGROUND: Apolipoprotein E polymorphisms have important effects on plasma lipid levels and in the genetic susceptibility to development of cardiovascular diseases. Thus, the purpose of this study was to investigate the association of apolipoprotein E polymorphisms with coronary artery disease and with plasma lipid levels in a group of Mexican Mestizo patients. METHODS: Apolipoprotein E polymorphisms were determined in 156 Mexican patients with coronary artery disease and 200 non-related healthy controls using the restriction fragment length polymorphism technique. The correlation of these polymorphisms with lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in the patient group was determined. RESULTS: A similar distribution of allele and genotype frequencies in coronary artery disease patients and healthy controls was found. Higher serum levels of high-density lipoprotein cholesterol and lower levels of low-density lipoprotein cholesterol, triglycerides and glucose were found in patients with the APOE*2/3 genotype when compared to patients with the APOE*3/4 and APOE*3/3 genotypes, although these differences were not significant. CONCLUSIONS: Our data suggest that genetic variation at the APOE is not a genetic factor related to the genetic susceptibility to coronary artery disease in Mexican individuals, but the role of this polymorphism in determining the lipid profile cannot be excluded.     

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. Ezetimibe has a favorable pharmacokinetic profile, which allows it to be administered once daily and to be given in conjunction with statins. In a series of randomized, controlled, multicenter studies, ezetimibe produced significant improvements in levels of LDL-cholesterol and other lipid parameters when used as monotherapy, with a safety profile comparable with that of placebo. Furthermore, coadministration of ezetimibe with a statin (simvastatin, atorvastatin, lovastatin, or pravastatin) was more effective than statin monotherapy in lowering LDL-cholesterol and improving other lipid parameters. Moreover, coadministration of ezetimibe with a statin allowed a greater percentage of patients to achieve treatment goals established in NCEP guidelines. The safety and side-effect profile of ezetimibe plus statin coadministration therapy was generally comparable with that of statin monotherapy. These studies establish ezetimibe as an effective lipid-lowering agent, which will likely be useful in the management of a broad range of patients with hypercholesterolemia. Ezetimibe can be used in conjunction with a statin at the beginning of therapy, or it can be added if patients do not achieve their LDL-cholesterol goal with statins alone.     

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. Ezetimibe has a favorable pharmacokinetic profile, which allows it to be administered once daily and to be given in conjunction with statins. In a series of randomized, controlled, multicenter studies, ezetimibe produced significant improvements in levels of LDL-cholesterol and other lipid parameters when used as monotherapy, with a safety profile comparable with that of placebo. Furthermore, coadministration of ezetimibe with a statin (simvastatin, atorvastatin, lovastatin, or pravastatin) was more effective than statin monotherapy in lowering LDL-cholesterol and improving other lipid parameters. Moreover, coadministration of ezetimibe with a statin allowed a greater percentage of patients to achieve treatment goals established in NCEP guidelines. The safety and side-effect profile of ezetimibe plus statin coadministration therapy was generally comparable with that of statin monotherapy. These studies establish ezetimibe as an effective lipid-lowering agent, which will likely be useful in the management of a broad range of patients with hypercholesterolemia. Ezetimibe can be used in conjunction with a statin at the beginning of therapy, or it can be added if patients do not achieve their LDL-cholesterol goal with statins alone.     

Achieving National Cholesterol Education Program goals for low-density lipoprotein cholesterol in cardiac patients: importance of diet, exercise, weight control, and drug therapy.

OBJECTIVE: To determine how frequently the National Cholesterol Education Program (NCEP) goal of a low-density lipoprotein (LDL) cholesterol level of 100 mg/dL or less is achieved in clinical practice in patients with coronary artery disease and what fraction of patients can achieve this goal without drug therapy. DESIGN: We examined the results of lipid management in 152 consecutive patients who had completed cardiac rehabilitation after an acute coronary event. Patients were randomized to follow-up by specially trained nurses or by preventive cardiologists, and they were not receiving lipid-lowering drugs at the start of the study. MATERIAL AND METHODS: Patients were given aggressive diet and exercise recommendations and lipid-lowering drugs in accordance with NCEP guidelines. Follow-up was continued for a mean of 526 days after the first lipid assessment subsequent to the coronary event. Multiple logistic regression analysis was used to identify independent predictors of a final LDL cholesterol level of 100 mg/dL or less. RESULTS: Of the study group, 39% achieved the NCEP goal LDL cholesterol level of 100 mg/dL or less. Characteristics of the patients with LDL cholesterol levels of 100 mg/dL or less in comparison with those with LDL cholesterol levels of more than 100 mg/dL included a greater frequency of drug therapy (65% versus 38%), more rigorous dietary compliance, longer follow-up (586 +/- 317 days versus 493 +/- 264 days), more favorable weight change (-0.3 +/- 4.9 kg versus +1.7 +/- 5.0 kg), and more extensive weekly exercise (183 +/- 118 minutes versus 127 +/- 107 minutes). CONCLUSION: The registered nurses managed the lipids of these patients as effectively as did the preventive cardiologists. Appropriate drug therapy was the most important factor in achieving an LDL cholesterol level of 100 mg/dL or less, but 35% of patients attaining this NCEP goal were not receiving drug therapy. Exercise, dietary compliance, and weight loss were also important factors.     

Type of preexisting lipid therapy predicts LDL-C response to ezetimibe

BACKGROUND: Ezetimibe as monotherapy or in combination with statins effectively lowers low-density lipoprotein cholesterol (LDL-C). However, there are few reports of ezetimibe's effect when added to ongoing non-statin lipid-lowering drugs or combination lipid-lowering therapy. OBJECTIVE: To evaluate the impact of preexisting lipid therapy on LDL-C response to ezetimibe. METHODS: We performed a retrospective review of all patients started on ezetimibe therapy at the Veterans Affairs Long Beach Healthcare System between March 1, 2003, and March 1, 2005. We calculated the ezetimibe-induced percent change in LDL-C in patients without concomitant changes in other lipid-lowering medications. We then stratified the population according to the type and number of preexisting lipid therapies and compared the LDL-C-lowering efficacy of ezetimibe among these groups. RESULTS: Overall, ezetimibe was associated with a 23.0% reduction in LDL-C. Patients with preexisting statin monotherapy had significantly greater LDL-C reduction with ezetimibe than did those with preexisting non-statin drugs (-26.1% vs -9.3%; p = 0.0138). In patients with no preexisting lipid therapy (n = 58), monotherapy (n = 115), double therapy (n = 36), or triple therapy (n = 9), ezetimibe decreased LDL-C by 17.3%, 21.4%, 33.5%, and 38.1%, respectively. This stepwise trend in increased ezetimibe efficacy was statistically significant, even with adjustments for baseline LDL-C. CONCLUSIONS: Ezetimibe's LDL-C-lowering effects are most pronounced when added to preexisting combination lipid therapy. It appears to be more effective when added to statin therapy compared with other lipid-lowering therapies.     

What future for combination therapies?

For most patients who require lipid-lowering treatment, statin monotherapy is the appropriate treatment. However, in those patients where statin monotherapy does not produce optimal lipid levels, the combination of a statin with niacin, a bile acid sequestrant, a fibric acid derivative, a cholesterol absorption inhibitor or a fish oil preparation may provide improved control. The choice of combination therapy depends upon the patient's lipid profile and tolerability of the medication. Combination of a statin with niacin, a bile acid sequestrant or ezetimibe, a cholesterol absorption inhibitor, should be considered for patients with very high low-density lipoprotein cholesterol (LDL-C) levels, while combination with either a fibric acid derivative or a fish oil should be considered for patients with high LDL-C and high triglyceride levels. A number of new lipid-lowering agents are currently in development, including cholesteryl ester transfer protein (CETP) inhibitors, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, ileal bile acid transport (IBAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors and dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonists. Introduction of these novel therapies will provide opportunities for developing different combination strategies that may help to optimise lipid profiles in patients who are currently difficult to treat. The introduction of new combinations will require careful study to ensure that the risks of drug interactions and adverse events are minimised.     

心肌梗死患者血糖控制水平对他汀类药物调脂效果的影响

目的研究心肌梗死患者血糖控制情况对调脂治疗效果的影响。方法将174例急性或陈旧性心肌梗死患者按是否合并糖尿病以及2年复查时血糖控制情况,分为糖尿病血糖控制良好组(DM+W组)、糖尿病血糖控制不佳组(DM+B组)、非糖尿病血糖控制良好组(NDM+W组)和非糖尿病血糖控制不佳组(NDM+B组),比较治疗前后及各组之间血脂水平、他汀类药物服药剂量和药物不良反应发生率。结果全部174例心肌梗死患者中合并糖尿病者51例(25.9%)。2年复查时DM+B组患者为13例(占糖尿病患者总数的25.5%),NDM+B组患者为24例(占非糖尿病患者总数的19.5%),这两组患者血浆总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-c)和低密度脂蛋白胆固醇(LDL-c)平均水平较入选时均无明显变化,LDL-c平均水平呈增高趋势。但即使DM+W组患者血浆LDL-c平均水平(2.57mmol/L)也未达到指南建议的<2.06mmol/L的标准。糖尿病与非糖尿病患者在他汀类服药方式上无明显差异,在2年复查时坚持按常规剂量服药者仅53.4%,采用较低剂量者占34.5%,未服药者占9.2%。合并糖尿病者长期服用他汀类药物未增加肝酶异常发生率。结论心肌梗死后血糖控制不佳使他汀类药物调脂治疗效果下降,合并糖尿病者他汀类药物服药剂量不足更为明显。     

Maximizing recruitment efforts in a drug lipid-lowering trial with dietary intervention to lower LDL cholesterol

A select group of screened applicants initially disqualified from a four-center, primary prevention drug lipid-lowering trial because of borderline elevated serum low-density lipoprotein cholesterol (LDL-C) levels, as defined in National Cholesterol Education Program-Adult Treatment Panel I (NCEP-ATP I) guidelines, participated in a dietary intervention protocol that was incorporated into the screening phase of the trial. Seventy-seven screened applicants for the Asymptomatic Carotid Artery Progression Study entered the dietary program, which was overseen by an experienced registered dietitian at the central operations sites who collaborated with local staff at clinical sites during program implementation. NCEP-ATP I fat-modified step I diet specifications served as the basis for the intervention. The program, consisting of five sessions conducted over an 8-week period, primarily used written and audiovisual educational materials in combination with behavioral approaches. Of the original 77 participants, 36 responded to the intervention by achieving their LDL-C goal. Twenty-nine were nonresponders and 12 were dropouts. Responders achieved an average 11.7% drop in total cholesterol at the end of the 8-week program. Mean LDL-C decline paralleled total cholesterol change. High-density lipoprotein cholesterol also decreased significantly. These results were sustained for 24 of the responders attending the final screening visit approximately a month later, when another fasting blood lipid measurement was made. Participants who dropped out were more likely to be smokers. Pre- and postintervention nutrition data assessed by semiquantitative food frequency questionnaire for 20 screenees randomized into the study indicated significant reductions in total fat, saturated fat, polyunsaturated fat, and dietary cholesterol, all known to influence blood lipid levels. Similar programs may prove useful to other drug lipid-lowering trials to maximize recruitment efforts.     

Polymorphisms in CYP-7A1, not APOE,influence the change in plasma lipids in response to population dietary change in an 8 year follow-up; results from the Czech MONICA study

OBJECTIVES: To evaluate the influence of variation in the genes for apolipoprotein E (APOE; epsilon2, epsilon3, epsilon4) and cholesterol-7alpha hydroxylase (CYP-7A1; -204A-->C) on plasma lipid level changes. DESIGN AND METHODS: 131 males for whom dietary composition markedly changed and total cholesterol decreased (from 6.21 +/- 1.31 mmol/L in 1988 - 5.43 +/- 1.06 mmol/L in 1996) over an 8 yr follow-up study. Polymorphisms were investigated using PCR. RESULTS: APOE genotype influenced plasma total and LDL cholesterol, with carriers of the epsilon4 having the highest and epsilon2 carriers the lowest levels, this reached borderline significance for cholesterol in 1988 (p = 0.06) and strongly affected the 1996 levels of LDL cholesterol (p = 0.008). However, APOE did not influence the change in these measures over time. In contrast, the CYP-7A1 -204A-->C polymorphism did not affect lipid measures per se but was strongly associated with a decrease in plasma total cholesterol [AA -0.38 (+/- 0.20) mmol/L, AC -0.65 +/- (0.08), CC -1.33 (+/- 0.3) mmol/L, p = 0.01] over the 8 yr time period. CONCLUSIONS: Variation in the CYP-7A1 gene may play an important role in an individual's sensitivity to dietary composition.     

Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice.

Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.     

The Safety of Aggressive Statin Therapy: How Much Can Low-Density Lipoprotein Cholesterol Be Lowered?

Recent clinical trials have consistently demonstrated that reducing low-density lipoprotein cholesterol to very low levels will substantially reduce cardiovascular morbidity and mortality. The lipid-lowering agents of choice are the statins, which are generally considered safe and effective. Of the various agents available, atorvastatin and rosuvastatin are the most powerful, followed by simvastatin. Serious adverse effects with statin therapy are uncommon and primarily involve effects on the liver and skeletal muscle. The risk increases with the statin dose and coadministration with other drugs metabolized by the same metabolic pathway, such as the cytochrome P-450 system. For patients who do not achieve adequate reduction in low-density lipoprotein cholesterol levels with statin therapy of moderate potency, the clinician can up-titrate the dose of the initial statin, institute combination therapy and carefully monitor for adverse effects, or switch to a lower dose of a more potent statin. The strategy chosen depends on the degree of lipid lowering required and on safety, cost, and compliance issues. This article reviews evidence concerning the benefits of reducing low-density lipoprotein cholesterol levels below currently established targets and addresses the question of whether Intensive statin therapy is likely to Increase the risk of adverse events or concomitant comorbidity.     

Pro12Ala sequence variant of the PPARG gene is associated with postprandial hypertriglyceridemia in non-E3/E3 patients with the metabolic syndrome

BACKGROUND: Postprandial hypertriglyceridemia, a component of the metabolic syndrome, has varied etiology and involves many genes related to triglyceride metabolism. Variations in these genes may affect postprandial hypertriglyceridemia in the context of the metabolic syndrome. METHODS: We orally administered 60 g of fat overload to 74 patients with the metabolic syndrome. We then measured baseline concentrations of cholesterol, triglycerides, HDL cholesterol, apolipoprotein AI, apolipoprotein B, uric acid, and uric acid excretion; we also performed homeostasis model assessments of insulin resistance and insulin sensitivity. At 3 h, we measured triglycerides, cholesterol, apolipoprotein AI, and apolipoprotein B. Patients were considered to have postprandial hypertriglyceridemia if the difference in plasma triglycerides between baseline and 3 h after the test was 1.71 mmol/L or more. We also measured anthropometrical variables and classified the patients according to their peroxisome proliferative activated receptor, gamma (PPARG) gene and apolipoprotein E (APOE) genotype. RESULTS: Postprandial hypertriglyceridemia occurred in 64.7% of patients with the Ala12 allele vs 19.9% of the Pro12Pro patients, (P = 0.00032; odds ratio, 7.6), and in 87.5% of the patients with both the Ala12 allele and the non-E3/E3 APOE genotype (odds ratio, 23.8). Logistic regression analysis showed that PPARG and APOE sequence variants were associated with the presence of postprandial hypertriglyceridemia. CONCLUSION: The Pro12Ala PPARG sequence variant together with a non-E3/E3 APOE genotype is associated with a high risk for postprandial hypertriglyceridemia in patients with the metabolic syndrome, indicating a close association between these genes and the regulation of lipoproteinase clearance.     

Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy

OBJECTIVE: To evaluate a pharmacist-conducted educational and monitoring programme, designed to promote dietary and lifestyle modification and compliance with lipid-lowering drug therapy, for patients with dyslipidaemia. METHODS: This was a prospective, randomized, controlled study. The participants were 94 adults, with 81 completing the study (intervention group: 39; control group: 42), with a cardiovascular-related diagnosis and discharged from hospital, between April and October 2001, on lipid-lowering drug therapy. Patients in the intervention group were visited at home monthly by a pharmacist, who educated the patients on the goals of lipid-lowering treatment and the importance of lifestyle issues in dyslipidaemia and compliance with therapy, assessed patients for drug-related problems, and measured total blood cholesterol levels using point-of-care testing. Patients in the control group received standard medical care. The main outcome measure was total blood cholesterol levels after 6 months, and an evaluation of patient and general practitioner satisfaction with the programme. RESULTS: There was no significant difference in baseline total blood cholesterol levels between the two groups. The reduction over the course of the study in cholesterol levels within the intervention group was statistically significant (4.9 +/- 0.7 to 4.4 +/- 0.6, P<0.005), whereas there was no change within the control group (P=0.26). At follow-up, 44% of the intervention group patients and 24% of the control group patients had cholesterol levels below 4.0 mmol/L (P=0.06). The reduction in total cholesterol in the intervention group should translate to an expected 21% reduction in cardiovascular mortality risk and a 16% reduction in total mortality risk--more than twice the risk reduction achieved in the control group. In addition, the programme was very well received by the patients and their general practitioners, by satisfaction questionnaire. CONCLUSION: A pharmacist-conducted educational and monitoring intervention improved the outcomes of lipid-lowering drug therapy.     

Pharmacogenetic study of apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase genes and simvastatin therapy in Brazilian subjects

BACKGROUND: In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response. METHODS: One hundred forty-six hypercholesterolemic patients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E*2, E*3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping. RESULTS: After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively). CONCLUSION: Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.     

The use of statins in optimising reduction of cardiovascular risk: focus on fluvastatin

Patients with widely differing degrees of cardiovascular risk can derive benefit from effective lipid-lowering therapy with statins, including patients with normal or low cholesterol levels. Clinical trials with fluvastatin have shown that it is effective in patients across a broad spectrum of cardiovascular risk. The lipid-lowering effects of fluvastatin are smaller than some statins, but major clinical outcome studies have consistently demonstrated morbidity and mortality benefits with reductions of low-density lipoprotein cholesterol of <30%. As treatment with statins is generally life-long and patients often receive multiple concomitant medications, optimal statin therapy should be well tolerated and serious consideration should be given to the avoidance of drug interactions. Although serious side-effects of statins are very rare, it is important that fluvastatin is less susceptible to drug interactions than other statins, because serious side-effects of statin therapy are generally associated with concomitant medications affecting statin metabolism. In addition, an extended-release formulation of fluvastatin has been developed to provide liver selectivity with a sustained exposure to the drug, thus improving its efficacy, and safety and tolerability profiles.     

Association between apolipoprotein E4 and rehabilitation outcome in hospitalized ischemic stroke patients

OBJECTIVE: To determine the value of apolipoprotein E4 (APOE*E4) allele in predicting discharge impairment and disability in ischemic stroke patients after acute rehabilitation. DESIGN: Prospective study comparing results of rehabilitation in patients with different APOE genotypes. SETTING: Acute neurologic rehabilitation department in Israel. PARTICIPANTS: One hundred one consecutive patients 75 years old or less with a first ischemic stroke. INTERVENTIONS: Not applicable.Main Outcome Measure: Impairment, as measured by the National Institutes of Health Stroke Scale (NIHSS), and disability, as assessed with the FIM trade mark instrument. RESULTS: On admission, there was no significant difference in the FIM or NIHSS measurements between the apo E4 group and other patients, but the prevalence of aphasia was 2.07 times more frequent in those with the APOE*E4 genotype (95% confidence interval, 0.98-4.4). A logistic regression model demonstrated that score measurements on admission were highly predictive of the NIHSS score at discharge (receiver operator curve=96.1%), whereas the presence of the APOE*E4 genotype did not add significantly to the model in predicting poorer rehabilitation treatment outcome as measured by the FIM or the NIHSS. CONCLUSIONS: The presence of the apo E4 allele did not predict a poorer outcome of rehabilitation treatment after ischemic stroke, but it was associated with an increased prevalence of aphasia. Further studies are warranted to confirm this association.     

Development of a pharmacist-managed lipid clinic

OBJECTIVE: To describe the development of a pharmacist-managed lipid clinic within a primary care medical clinic and review its results after approximately 12 months of operation. METHODS: A pharmacist-managed lipid clinic was developed at Naval Medical Center San Diego. Administrative background, treatment algorithm development, operational issues, clinical activities, and barriers to the clinic are discussed. For intermediate outcomes, data from patients who had at least 1 intervention by the pharmacist and 1 follow-up lipid panel were analyzed for medication use, changes in lipid parameters, and percent reaching the low-density-lipoprotein (LDL) target goal. Modified National Cholesterol Education Program-Adult Treatment Panel II guidelines were used to determine the LDL goal. RESULTS: Following approximately 12 months of operation, the clinic received 204 referrals and consisted of 146 active patients. A brief study was conducted to assess clinical outcomes. Of 115 patients who were seen in the clinic and met inclusion criteria, 57% were receiving treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) and 17% were receiving fibrates; 17% of the patients were not receiving lipid-lowering medications. Relative to baseline, LDL cholesterol concentrations decreased 20%, high-density-lipoprotein cholesterol increased 11%, and triglycerides decreased 19%. Overall, LDL goals were reached in 77% of the patients. LDL goals were attained by 63%, 79%, and 93% of patients with targets of <100, <130, and <160 mg/dL, respectively. Results are compared with other studies regarding lipid goal attainment. CONCLUSIONS: A pharmacist-managed lipid clinic can be developed and integrated into a primary care medical clinic. Pharmacists can effectively manage lipid-lowering therapy, helping to achieve LDL goals.     

MTP inhibitors and ACAT inhibitors. An update

Currently, statin therapy is the first-line treatment for patients with hypercholesterolemia, although their effects on plasma triglyceride(TG) levels are modest and variable. Inhibition of microsomal triglyceride transfer protein(MTP), a key protein involved in the assembly of the apoB-containing lipoproteins, is an attractive lipid-lowering strategy. In animal models, MTP inhibitors have dramatic effects not only on plasma cholesterol and LDL levels but on TG levels as well, offering the potential for greater efficacy and plasma lipid control in both hypertriglyceridemia and mixed hyperlipidemia. Inhibitors of acyl-CoA: cholesterol acyltransferase(ACAT) present another strategy in treating atherosclerosis through direct inhibition of ACAT in macrophages of the arterial wall. Recent studies in mouse models of atherosclerosis lacking ACAT1, however, may argue against the selective inhibition of macrophage ACAT1.     

Influence of elevated cardiometabolic risk factor levels on treatment changes in type 2 diabetes

Undertreatment of risk factors in patients with type 2 diabetes is common. We assessed the influence of elevated levels of blood pressure, total cholesterol, and A1C on decisions of Dutch general practitioners to change drug treatment in a cohort of 3,029 patients during a 1-year period. Respectively, 58, 71, and 21% of patients remained untreated despite poor blood pressure, lipid levels, and glycemic control. Of poorly controlled but already drug-treated patients, 52% did not receive intensification for antihypertensive medication, 81% not for lipid-lowering medication, and 43% not for glucose-lowering medication. We observed a significantly lower treatment intervention rate in moderately than in poorly controlled patients for blood pressure. This was not seen for decisions on cholesterol or A1C results. The low overall action rates observed for blood pressure and especially lipid management cannot sufficiently be explained by the use of treatment thresholds higher than those indicated by guidelines.     

Effectiveness of ezetimibe added to ongoing statin therapy in modifying lipid profiles and low-density lipoprotein cholesterol goal attainment in patients of different races and ethnicities: a substudy of the Ezetimibe add-on to statin for effectiveness trial

OBJECTIVE: To examine whether the improvements in lipid profiles and low-density lipoprotein cholesterol (LDL-C) goal attainment found in the Ezetimibe Add-On to Statin for Effectiveness trial occurred equally in the black, Hispanic, and white patient populations enrolled in the study. PATIENTS AND METHODS: In this double-blind, placebo-controlled study, patients were recruited from 299 community-based practices across the United States (January to August 2003). Patients with, hypercholesterolemia and LDL-C levels exceeding National Cholesterol Education Program Adult Treatment Panel III goals were randomized (2:1) to receive either ezetimibe (10 mg/d) or placebo in addition to their ongoing statin therapy for 6 weeks. RESULTS: A total of 5802 patients were screened at baseline for the Ezetimibe Add-On to Statin for Effectiveness study. Of these, 2772 were excluded, and the remaining 3030 eligible patients were randomized. Ezetimibe, compared with placebo, added to statin therapy significantly reduced LDL-C levels from statin-treated baseline by 23.0% (white patients), 23.0% (black patients), and 21.0% (Hispanic patients). This effect was consistent across race and ethnicity groups (P > .50 for treatment-by-race interactions). Ezetimibe added to statin therapy also statistically significantly (P < .001) increased the percentage of patients attaining their LDL-C goal for their National Cholesterol Education Program Adult Treatment Panel III risk category in black (63.0%), Hispanic (64.8%), and white (72.3%) patients compared with placebo plus statin (32.9% black patients, 19.0% Hispanic patients, and 19.7% white patients). Ezetimibe treatment improved other lipid parameters across groups, including triglyceride, high-density lipoprotein cholesterol, non-high-density ilpoprotein cholesterol, and total cholesterol levels. Finally, the addition of ezetimibe reduced high-sensitivity C-reactive protein levels overall, and no significant interaction of treatment by race occurred (P = .83), Indicating a consistent effect across races. Ezetimibe was generally well tolerated, and no detectable differences occurred in the adverse event profile by race or ethnicity. CONCLUSION: Ezetimibe added to statin therapy is effective and well tolerated for improving the lipid profile and LDL-C goal attainment of patients regardless of race or ethnicity.