Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.     

Influence of age, gender, and race on the efficacy of adding ezetimibe to atorvastatin vs. atorvastatin up-titration in patients at moderately high or high risk for coronary heart disease

Background

Age, gender, and race are factors that influence atherosclerotic coronary heart disease (CHD) risk and may conceivably affect the efficacy of lipid-altering drugs.

Methods

Post hoc analysis of two multicenter, 6-week, double-blind, randomized, parallel-group trials assessed age (< 65 and ≥ 65 years), gender, and race (white, black, and other) effects on atorvastatin plus ezetimibe versus up-titration of atorvastatin in hypercholesterolemic patients with CHD risk. High CHD risk subjects with low-density lipoprotein (LDL) cholesterol levels ≥ 70 mg/dL (~ 1.81 mmol/L) during stable atorvastatin 40 mg therapy were randomized to atorvastatin 40 mg plus ezetimibe 10 mg, or up-titrated to atorvastatin 80 mg. Moderately high CHD risk subjects with LDL cholesterol levels ≥ 100 mg/dL (~ 2.59 mmol/L) with atorvastatin 20 mg were randomized to atorvastatin 20 mg plus ezetimibe 10 mg, or atorvastatin 40 mg.

Results

Although some variability existed, age, gender, and race subgroups did not substantially differ from the entire patient population with regard to lipid-altering findings. Ezetimibe plus atorvastatin produced greater percent reductions in LDL cholesterol, total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B than up-titration of atorvastatin for all subgroups. HDL cholesterol and apolipoprotein AI changes were small and variable.

Conclusion

Treatment efficacy in age, gender, and race subgroups did not substantially differ from the entire study population. Ezetimibe combined with atorvastatin generally produced greater incremental reductions in LDL cholesterol and several other key lipid parameters compared with doubling the atorvastatin dose in hypercholesterolemic patients with high or moderately high CHD risk. These results suggest that co-administration of ezetimibe with statins is a useful therapeutic option for treatment of dyslipidemia in differing patient populations.     

Clinical trial of an educational intervention to achieve recommended cholesterol levels in patients with coronary artery disease

Background

Despite national efforts to improve cholesterol management for patients with coronary artery disease, many patients are not reaching recommended cholesterol target levels. We sought to determine whether a nurse-based educational intervention, designed to educate patients with confirmed coronary artery disease about personal low-density lipoprotein (LDL) cholesterol target levels and encourage partnership with physicians, could increase adherence with National Cholesterol Education Program target levels (LDL cholesterol level ≤100 mg/dL).

Methods

Patients hospitalized with confirmed coronary artery disease were randomized to undergo a nurse-based educational intervention (375 patients) or usual care (381 patients) for a 12-month period after hospitalization. The primary outcome was the proportion of patients at the LDL cholesterol target level 1 year after hospitalization. The secondary outcome was the proportion of patients with accurate knowledge of LDL cholesterol target levels.

Results

The groups were similar at baseline in demographic and clinical characteristics, percent at LDL cholesterol target level (43.9% and 41.1%, respectively), and percent with knowledge of LDL cholesterol target levels (both 5%). The proportion of patients at LDL cholesterol target levels at 1 year did not differ between the intervention (70.2%) and usual care group (67.4%, P = .46). At the conclusion of the trial, patient knowledge about LDL cholesterol target level was higher for the intervention group than the usual care group (19.6% and 6.7%, respectively, P = .001), but this was not associated with improved cholesterol management.

Conclusions

Our nurse-based educational intervention did not result in a significant increase in the proportion of patients who reached target LDL cholesterol levels 1 year after hospitalization. Although the intervention improved patient knowledge of LDL cholesterol target levels, overall rates of LDL cholesterol knowledge remained low, and it was not associated with improved cholesterol management.     

Effect of aggressive versus moderate lipid-lowering therapy on myocardial ischemia: the rationale, design, and baseline characteristics of the Study Assessing Goals in the Elderly (SAGE)

Background

Patients with stable CHD who experience episodes of ischemia during routine daily activities are at increased risk of coronary events. Older patients are at a particularly high risk. Few trials have specifically investigated the effects of lipid-lowering therapy with statins in older patients.

Methods

The SAGE trial is a prospective, randomized, double-blind, parallel-arm study enrolling men and women with stable CHD at 192 centers worldwide. Qualifying participants (aged 65-85 years; low-density lipoprotein cholesterol 100-250 mg/dL) have had at least 1 episode of myocardial ischemia with total ischemia duration ≥3 minutes on 48-hour ambulatory electrocardiographic (AECG) monitoring performed during routine daily activities. Participants have been randomized to either atorvastatin 80 mg/day (aggressive lipid lowering) or pravastatin 40 mg/day (moderate lipid lowering). The primary efficacy measure is the absolute change in the total duration of myocardial ischemic events on 48-hour AECG monitoring from baseline to month 12.

Results

SAGE is fully enrolled and 893 patients have been randomized. The majority of the study participants are white (97%) men (69%). The mean age of the participants is 72 years. Most participants (94%) have a history of angina. Other high-risk patient groups included in the study are patients with hypertension (65%), patients with diabetes (23%), and patients with peripheral vascular disease (12%).

Conclusions

SAGE will evaluate the effect of aggressive versus moderate lipid lowering on the total duration of myocardial ischemia in older ambulatory patients with CHD. It is likely to provide valuable data on the benefits of statins in this patient population.     

The effects of atorvastatin and rosuvastatin on oxidative stress in diabetic patients

Aim

Diabetes is associated with abnormalities in lipid profile and increased oxidative stress. Statins are preferred agents in diabetic patients due to their antioxidant and LDL-C lowering effects. This study is designed to compare the effects of atorvastatin and rosuvastatin on low density lipoprotein cholesterol (LDL-C), lipid hydroperoxide (LOOH), total oxidant status (TOS) and total antioxidant capacity (TAC) in diabetic patients with hyperlipidemia.

Materials and methods

Sixty two patients who have type 2 diabetes mellitus with serum LDL levels more than 100 mg/dL were randomly assigned to receive atorvastatin 20 mg (n = 31) or rosuvastatin 10 mg (n = 31). Blood tests were performed at the beginning of the study and after three months.

Results

There were no statistically significant differences in the pre- and after treatment levels of the LDL-C between groups. TAC values were increased in both groups and statistically significant in the former group (p = 0.007). There was no diferrence between the change percentages ((after treatment TAC − pretreatment TAC) / pretreatment level) of TAC between two treatment groups. The effects of two drugs on the other oxidative parameters were not significantly different.

Conclusion

Both atorvastatin and rosuvastatin may be helpful in reducing increased oxidative stress in diabetic patients with hyperlipidemia.     

High fasting glucose levels as a predictor of worse clinical outcome in patients with coronary artery disease: results from the Bezafibrate Infarction Prevention (BIP) study

Background

A high fasting glucose level may be a marker not only for microvascular complications, but also for macrovascular complications. We evaluated the clinical significance of a high fasting glucose level (≥110 mg/dL), detected either at baseline or during follow-up, in the Bezafibrate Infarction Prevention (BIP) study.

Methods

The BIP study was a secondary prevention prospective double-blind study comparing bezafibrate to placebo. A total of 3122 patients with documented coronary artery heart disease who were aged 45 to 74 years and had a total cholesterol level between 180 and 250 mg/dL, low-density lipoprotein cholesterol level ≤180 mg/dL, a high-density lipoprotein cholesterol level ≤45 mg/dL, a triglyceride level ≤300 mg/dL, and a fasting glucose ≤160 mg/dL were randomized to receive 400 mg of bezafibrate daily or placebo.

Results

The primary end point of the BIP study was fatal myocardial infarction, non-fatal myocardial infarction, or sudden death. Secondary end points included hospitalization for unstable angina, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting. At baseline, 330 patients (11%) had diabetes mellitus, and 293 patients (9%) had an impaired fasting blood glucose level (IFG). During 6.2 years of follow-up, diabetes mellitus developed in 186 patients (6%), IFG developed in 366 patients (12%), and 62% of patients remained with normal fasting glucose levels (NFG). Patients with diabetes mellitus and IFG both at baseline or developing during follow-up had a significantly higher rate of secondary end points than paients with NFG (P <.0001). Bezafibrate treatment reduced secondary end points only in patients with NFG (P = .04).

Conclusion

Diabetes mellitus and IFG were common in the BIP study and were predictive of a worse clinical outcome that was not attenuated with bezafibrate treatment.     

Lifetime risk for developing dyslipidemia: the Framingham Offspring Study

Background

High serum low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) cholesterol are major vascular risk factors. National surveys indicate that 40% of individuals in the United States have borderline-high LDL cholesterol, and 13-34% have low HDL. The lifetime risk of developing dyslipidemia is unknown, however.

Methods

We estimated the 10- to 30-year long-term risks of developing “borderline-high” LDL cholesterol (≥130 mg/dL [3.4 mmol/L]), “high” LDL cholesterol (≥160 mg/dL [4.1 mmol/L]) and “low” HDL cholesterol (<40 mg/dL [1.0 mmol/L]) in 4701 Framingham Offspring Study participants (53% women) who attended at least 2 examinations between 1971 and 2000. We performed sex-specific analyses (for age groups 30-34, 40-44, 50-54 years), and estimated risks conditional on surviving without the lipid abnormality up to the baseline age. We also estimated risks accounting for baseline prevalence of dyslipidemia (elevated LDL, low HDL).

Results

Over a 30-year period, approximately 6 of 10 participants developed borderline-high LDL, 4 of 10 people developed high LDL, and 2 (women) to 4 (men) of 10 individuals developed low HDL levels; estimates were generally similar for different age groups. Adjustment for baseline prevalence of dyslipidemia increased these estimates: 30-year risks exceeded 80% for borderline-high LDL, 50% for high LDL, and 25% (women) to 65% (men) for low HDL; 20-50% had or developed a low HDL along with a high LDL level. The 30-year estimates approximate the lifetime risk in 50-year-olds.

Conclusions

The long term risks of developing dyslipidemia are substantial in both sexes, and considerably exceed prevalence estimates from cross-sectional surveys.     

Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial

Background

This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease.

Methods

After a 6-week dietary lead-in period, patients with LDL-C levels ≥160 and <250 mg/dL and triglyceride levels ≤400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128).

Results

At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P < .001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P < .01], 47% [P < .001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P < .01], 59% [P < .001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-I, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P < .01). Effects of the 2 agents on triglycerides were similar.

Conclusions

Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk.     

Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS)

Background

Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins.

Methods

A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome.

Results

Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs −0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs −1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, ≥40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3× the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin).

Conclusions

Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3× the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.     

Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II

Background

National Cholestesrol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of <100 mg/dL. This target can be difficult to attain with diet and current therapy.

Methods

In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks.

Results

At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20 mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001) or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients achieved an LDL-C target of <70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P < .01). More hypertriglyceridemic patients (triglycerides ≥200 mg/dL) met LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non-HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity.

Conclusion

Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.     

Impact of physicians' beliefs and practices on cholesterol levels in patients with type 2 diabetes: a longitudinal assessment

Background

Clinical trials demonstrate significant benefit from cholesterol management for patients with type 2 diabetes. The aim of this work was to explore the correlates of lipid management in patients with type 2 diabetes, including the subjective beliefs of physicians, setting of care, and patient-related factors.

Methods

This longitudinal outcomes research study involved 2359 patients with type 2 diabetes recruited by 111 general practitioners and 214 physicians practicing in diabetes clinics. Physicians' beliefs were assessed through a questionnaire administered when the study started in 1998. Main outcome measures were total cholesterol (TC) and LDL cholesterol (LDL-C) levels over 3 years and the proportion of patients treated with lipid-lowering drugs (LLDs).

Results

Less than one-third of the physicians (27%) stated that they routinely started pharmacologic therapy for TC values ≥200 mg/dL (more aggressive), whereas 46% considered a TC level ≥240 mg/dL as the threshold for the initiation of treatment (less aggressive). During 3 years of observation, mean TC and LDL-C levels decreased from 215 ± 40 mg/dL to 203 ± 37 mg/dL and from 135 ± 36 mg/dL to 126 ± 35 mg/dL respectively, while the proportion of patients treated with LLDs increased from 13.2% to 24.6%; in particular, among individuals cared for by the more aggressive physicians, 30.0% were taking LLDs after 3 years, while only 17.7% of those followed by the less aggressive physicians and 18.1% of those followed by >1 physician were being treated with LLDs. Multilevel analysis showed that physicians' beliefs were an independent predictor of TC levels over the 3-year period. In patients treated with LLDs, TC levels decreased on average by 14%, and LDL-C levels decreased by 20%.

Conclusion

Our data show that physicians' beliefs in more aggressive management strategies will result in better mean TC values over a 3-year period.     

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS)

Background

Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy.

Methods

HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models.

Results

Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05).

Conclusion

Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.     

In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography

Background

Magnetic resonance imaging was recently reported to detect atherosclerotic plaques in thoracic and abdominal aortas.

Methods

Using magnetic resonance imaging, we investigated associations of risk factors and plasma inflammatory markers with plaques in both thoracic and abdominal aortas in 102 patients undergoing coronary angiography. Associations between coronary artery disease (CAD) and aortic plaques were also evaluated.

Results

Plaques in thoracic and abdominal aortas were detected in 61% and 90% of patients, respectively. Age and systolic blood pressure correlated with plaque extents in both the aortas. Serum LDL cholesterol level correlated with plaque extent in the thoracic aorta (r_s = 0.42). The degree of smoking correlated with plaque extent in the abdominal aorta (r_s = 0.43). In multivariate analysis, age and systolic blood pressure were associated with plaques in both the aortas. The LDL cholesterol and smoking were characteristically associated with plaques in the thoracic and abdominal aortas, respectively. Regarding inflammatory markers, fibrinogen and C-reactive protein levels correlated with total plaque extent in the aortas (r_s = 0.50 and r_s = 0.51). Compared with 24 patients without CAD, 78 with CAD more often had plaques in the thoracic (71% vs 29%) and abdominal (95% vs 75%) aortas. Although plaque extents in both the aortas correlated with the severity of CAD, only thoracic plaques were independently associated with CAD.

Conclusions

The thoracic and abdominal aortas may have different susceptibilities to risk factors. However, plasma inflammatory markers appear to reflect total extent of aortic atherosclerosis. Although aortic plaques are common in patients with CAD, only thoracic plaques are an independent factor for CAD.     

Lowering LDL cholesterol in adults: a prospective, community-based practice initiative

Purpose

The purpose of our study was to see if a clinic-wide initiative, with low-density lipoprotein cholesterol (LDL)-lowering interventions, could be an effective health maintenance strategy to decrease LDL levels to <100 mg/dL in a community-based, internal medicine outpatient setting.

Methods

There were 1375 patients screened with an initial/baseline LDL (LDL₁) measurement. Patients whose LDL₁ levels were >100 mg/dL were put on a lipid-lowering action plan and re-evaluated with a follow-up LDL (LDL₂) in 3-4 months. An additional action plan was given to patients whose LDL₂ values were still too high, and their values retested in 3-4 months for a third LDL (LDL₃). LDL₁ levels versus postintervention LDL measurement (LDL₂ or LDL₃) levels were the primary endpoints, with secondary endpoints of total cholesterol, total triglyceride, and high-density lipoprotein cholesterol (HDL) levels over the 3 measurement periods.

Results

Of 514 patients who were given action plans, 443 returned for their follow-up lipid assessment. LDL levels in this group fell from 140.7 ± 29.2 (mean ± 1 SD) mg/dL (LDL₁) to 110.9 (29.6) mg/dL (LDL₂) (P <.05). Of these 443 patients, 167 individuals had LDL₂ levels that now met National Cholesterol Education Program/Third Adult Treatment Panel III guidelines (<100 mg/dL) and 87 were now considered by their primary care provider as controlled (LDL 100-130 mg/dL). However, 158 individuals had LDL₂ levels that were either not controlled or not meeting National Cholesterol Education Program/Third Adult Treatment Panel guidelines. These 158 patients were provided with a second action plan, and of these, 50 (32%) returned to the clinic for a third lipid panel. Their LDLs, as a group, subsequently fell from an LDL₂ of 139.9 (24.4) mg/dL to 112.5 (28.2) mg/dL (LDL₃) (P <.05). Sixteen of 50 now had LDLs <100 mg/dL, and 26 of 50 were considered controlled. Initial HDL (HDL₁) levels rose from 55.4 (17.2) mg/dL to 57.3 (14.6) mg/dL (HDL₂) (n = 443). Blood levels of triglycerides and cholesterol also decreased in our returning patients over this time period (P <.05).

Conclusions

Community-based physicians can help their patients realize significant reductions in low-density lipoprotein cholesterol levels by implementing and closely monitoring lipid-lowering initiatives for their patients, resulting in potentially large positive impacts on the long-term health and well-being of their patients.     

Effects of switching statins on achievement of lipid goals: measuring effective reductions in cholesterol using rosuvastatin therapy (MERCURY I) study

Background

In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients.

Methods

Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis.

Results

Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P < .05), simvastatin 20 mg (86% vs 72%, P < .0001), and pravastatin 40 mg (88% vs 66%, P < .0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P < .01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks.

Conclusions

We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.     

Adult intensive care patients' perception of endotracheal tube-related discomforts: A prospective evaluation

Objective

This study was designed to investigate adult patients' perceptions of endotracheal tube (ETT)-related discomfort at 5 days and 2 months after discharge from the intensive care unit (ICU).

Methods

This prospective cohort study in 2 general ICUs included 250 intubated, mechanically ventilated adults admitted for more than 24 hours. Patients were interviewed 5 days and 2 months after discharge from the ICU about their ETT-related discomfort, using a modified Swedish ETT version of the ICU Stressful Experience Questionnaire that comprises 14 items.

Results

Of 116 patients describing their ETT experience during their ICU stay, 88% rated their discomfort as moderately to extremely stressful. At 2 months after discharge from the ICU, 23% (51/226) reported bothersome discomfort, vs. 46% (104/226) 5 days after discharge from the ICU, and 10 patients suffered from severe, persistent hoarseness.

Conclusion

The incidence of bothersome subjective complaints after tracheal intubation in the intensive-care setting is high, and severe ETT-related problems may persist several months after extubation.     

Diabetes Prevalence and Therapeutic Target Achievement in the United States, 1999 to 2006

Objective

Changes in the prevalence, treatment, and management of diabetes in the United States from 1999 to 2006 were studied using data from the National Health and Nutrition Examination Survey.

Methods

Data on 17,306 participants aged 20 years or more were analyzed. Glycemic, blood pressure, and cholesterol targets were glycosylated hemoglobin less than 7.0%, blood pressure less than 130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol less than 100 mg/dL, respectively.

Results

The prevalence of diagnosed diabetes was 6.5% from 1999 to 2002 and 7.8% from 2003 to 2006 (P < .05) and increased significantly in women, non-Hispanic whites, and obese people. Although there were no significant changes in the pattern of antidiabetic treatment, the age-adjusted percentage of people with diagnosed diabetes achieving glycemic and LDL targets increased from 43.1% to 57.1% (P < .05) and from 36.1% to 46.5% (P < .05), respectively. Glycosylated hemoglobin decreased from 7.62% to 7.15% during this period (P < .05). The age-adjusted percentage achieving all 3 targets increased insignificantly from 7.0% to 12.2%.

Conclusions

The prevalence of diagnosed diabetes increased significantly from 1999 to 2006. The proportion of people with diagnosed diabetes achieving glycemic and LDL targets also increased. However, there is a need to achieve glycemic, blood pressure, and LDL targets simultaneously.     

Health Insurance and Cardiovascular Disease Risk Factors

Background

Compared with those with health insurance, the uninsured receive less care for chronic conditions, such as hypertension and diabetes, and experience higher mortality.

Methods

We investigated the relations of health insurance status to the prevalence, treatment, and control of major cardiovascular disease risk factors—hypertension and elevated low-density lipoprotein (LDL) cholesterol—among Framingham Heart Study (FHS) participants in gender-specific, age-adjusted analyses. Participants who attended the seventh Offspring cohort examination cycle (1998-2001) or the first Third Generation cohort examination cycle (2002-2005) were studied.

Results

Among 6098 participants, 3.8% were uninsured at the time of the FHS clinic examination and ages ranged from 19 to 64 years. The prevalence of hypertension and elevated LDL cholesterol was similar for the insured and uninsured; however, the proportion of those who obtained treatment and achieved control of these risk factors was lower among the uninsured. Uninsured men and women were less likely to be treated for hypertension with odds ratios for treatment of 0.19 (95% confidence interval [CI], 0.07-0.56) for men and 0.31 (95% CI, 0.12-0.79) for women. Among men, the uninsured were less likely to receive treatment or achieve control of elevated LDL cholesterol than the insured, with odds ratios of 0.12 (95% CI, 0.04-0.38) for treatment and 0.17 (95% CI, 0.05-0.56) for control.

Conclusion

The treatment and control of hypertension and hypercholesterolemia are lower among uninsured adults. Increasing the proportion of insured individuals may be a means to improve the treatment and control of cardiovascular disease risk factors and to reduce health disparities.     

Change in lipid profile in celiac disease: beneficial effect of gluten-free diet

Purpose

Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults. We therefore examined the effect of a gluten-free diet on the lipid profile in patients with celiac disease.

Subjects and methods

We identified 132 patients with celiac disease who adhered to a gluten-free diet and had lipid profiles performed before and after a median of 20.5 months on the diet. The patients lacked diseases that may affect serum lipids.

Results

There were significant increases in total cholesterol and high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density lipoprotein (LDL) cholesterol (P = .06). The LDL/HDL ratio decreased by 0.36 ± 0.7 (P < .0001). Both men and women had a significant increase in total cholesterol and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases in LDL (P = .02). The greatest increase in lipid values was seen in those with the lowest initial values. The largest increase in HDL was seen in subjects with more severe disease as indicated by low albumin level and presence of total villous atrophy.

Conclusions

Diagnosis of celiac disease and its treatment with a gluten-free diet resulted in improvement in the lipoprotein profile, which included an increase in HDL and a decrease in the LDL/HDL ratio.     

Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia

Background

Epidemiologic studies have shown that serum uric acid is a risk factor of coronary artery disease. In addition to fenofibrate, there is some evidence that atorvastatin may have a hypouricemic action, but the underlying mechanisms remain speculative.

Methods

This randomized trial was conducted to investigate the effects of atorvastatin and simvastatin on uric acid homeostasis in patients treated for primary hyperlipidemia. A total of 180 patients were enrolled; patients were randomly assigned to 40 mg/d of either atorvastatin or simvastatin. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment; random urine samples were simultaneously obtained for creatinine, sodium, and uric acid determinations.

Results

Baseline serum uric acid levels correlated positively with the body mass index, serum insulin, creatinine, and triglyceride levels and inversely with serum HDL cholesterol levels. Both statins caused a favorable effect on lipids and a significant decrease in fibrinogen and high-sensitivity CRP levels. However, only atorvastatin reduced serum uric acid levels (from 5.6 ± 1.7 to 4.9 ± 1.5 mg/dL, P < .0001) by augmenting its urinary fractional excretion (from 10.4% ± 7.9% to 12.0% ± 7.4%, P < .01). In a multivariate logistic regression analysis, the reduction of uric acid levels was independently associated with baseline serum uric acid concentration but not to other variables, including lipid parameters (OR, 1.65; 95% CI, 1.14 to 2.40; P = .008).

Conclusions

Atorvastatin (but not simvastatin) significantly lowered serum uric acid levels. This result may be in favor of a preferable choice of atorvastatin for the treatment of hyperlipidemic patients presenting with hyperuricemia.