Projected coronary heart disease risk benefit with ezetimibe.

Low density lipoprotein (LDL) cholesterol and total cholesterol (TC) are the primary clinical parameters of interest for any cholesterol intervention. Clinicians are interested in how the reduction of these lipid parameters as well as increases in high density lipoprotein (HDL) relate to changes in coronary heart disease (CHD) risk. The objective of this analysis was to estimate the additional CHD risk reduction that could potentially be provided by co-administration of ezetimibe with statin therapy. Data from four double-blind placebo controlled clinical trials were used to predict the level of CHD risk reduction that might be achieved by co-administration of ezetimibe with statin therapy when compared to those receiving statin as monotherapy. Patients without a previous history of CHD were included in the analysis. Projected CHD risk reduction was calculated as percent change in projected CHD risk from baseline to 12 weeks based on observed lipid levels at those time points. For all the studies combined greater reductions in percent change in 5-year CHD risk were observed for patients receiving ezetimibe and statin as co-therapy, 53.4%, when compared to those receiving statin alone, 39.7%. Co-administration of ezetimibe with statin therapy provides an additional 13.7% reduction in predicted 5-year CHD risk when compared to statin monotherapy. Reductions in 5-year CHD risk for each of the statin studies ranged from 16.1% for lovastatin to 9.8% for atorvastatin. Co-administration of ezetimibe with statins could significantly reduce CHD events in patients with primary hypercholesterolemia.

Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation. RESEARCH DESIGN AND METHODS: This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8-47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis > or =50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death. RESULTS: A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or > or =50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA(1) showed no association with subsequent CAD. CONCLUSIONS: These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.

Subclinical atherosclerosis and estimated glucose disposal rate as predictors of mortality in type 1 diabetes.

PURPOSE: To investigate the usefulness of ischemic resting electrocardiogram (ECG), ankle brachial index (ABI) <0.8, ankle brachial difference (ABD) > or = 75 mm Hg (a marker of peripheral medial arterial wall calcification), and estimated glucose disposal rate (eGDR) (a marker for insulin resistance) for predicting mortality risk in the context of standard risk factors. METHODS: Data are from participants in the Pittsburgh Epidemiology of Diabetes Complications Study of 658 subjects with childhood onset Type 1 diabetes of mean age 28 years (range 8-48) and duration of diabetes 19 years (range 7-37) at baseline. Deaths were confirmed by death certificates. RESULTS: There were 68 deaths from all causes during 10 years follow-up. In univariate analysis, the mortality hazard ratios and 95% confidence intervals associated with ischemic ECG (6.7, 3.7-12.1), the lowest quintile of eGDR (i.e., the most insulin resistant) (6.7, 4.1-10.9), ABI <0.8 (2.5, 1.1-5.9), and ABD > or = 75 mm Hg (6.7) were only marginally less than those conveyed by pre-existing coronary artery disease (8.4, 4.7-15.2) or overt nephropathy (7.6, 4.5-12.9). Ischemic ECG and eGDR were independent mortality predictors, together with duration of diabetes, coronary artery disease, overt nephropathy, nonhigh density lipoprotein cholesterol, and smoking history. If serum creatinine was available, it entered, and glycosylated hemoglobin replaced eGDR. CONCLUSIONS: Estimated GDR and ECG ischemia are strong predictors of mortality in type 1 diabetes and may be useful in the identification of those at risk.

Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes.

The purpose of this study was to determine the predictors of lower extremity arterial disease (LEAD) events in a type 1 diabetes population. Data are from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes. At baseline, the study population had a mean age 28 (range, 8 to 47) years and duration 19 (range, 7 to 37) years. LEAD events, assessed by questionnaire or clinical examination, were defined as claudication (Rose questionnaire), foot ulceration, or lower extremity amputation. Estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated from glycosylated hemoglobin (HbA(1)), waist-to-hip ratio (WHR), and hypertension using an equation previously validated with hyperinsulinemic euglycemic clamp studies. There were incident LEAD events in 70 of 586 subjects during 10 years follow-up, giving an incidence density of 1.3 events/100 person-years. Incidence did not differ by gender. Major predictors of LEAD events were diabetes duration, low-density lipoprotein-cholesterol (LDL-C), heart rate, eGDR, log albumin excretion rate (AER), systolic blood pressure (SBP), hypertension, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy (each P <.001). HbA(1), low ankle brachial index (ABI) (<0.9), and a high ankle brachial difference (ABD) (SBP > or = 75 mm Hg) also predicted LEAD events. Cox modeling suggested that duration (P <.001), HbA(1) (P <.001), hypertension (P =.006), log albumin excretion rate (P =.011), and heart rate (P =.028) predicted events independently. The overall model with HbA(1) and hypertension was significantly better than with eGDR, while the alternate models in men were similar. In women, the model with eGDR showed a significantly better fit. Glycemia, insulin resistance, hypertension and renal disease are powerful predictors of symptomatic lower extremity arterial disease in type 1 diabetes.

Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy.

INTRODUCTION AND OBJECTIVE: The National Cholesterol Education Program recommends regular physician follow-up and lipid testing to promote adherence with lipid-lowering medications. The objective of this study was to determine whether lipid tests and physician visits after treatment initiation are indeed associated with adherence to statin therapy. SUBJECTS AND METHODS: A retrospective cohort study was conducted among 19 422 enrolees in a US managed care plan who initiated treatment with a statin between October 1999 and August 2001. Computerised pharmacy, medical and laboratory records were used to study the patterns and predictors of adherence with lipid-lowering therapy for up to 3 years. Adherence was assessed in 3-month intervals with patients considered 'adherent' if > or = 80% of days were covered by lipid-lowering therapy. RESULTS: In the first 3 months, 40% of patients had follow-up lipid tests and only 21% had dyslipidaemia visits (14% had both). Those receiving such care were substantially more likely to be adherent in subsequent intervals. Compared with those without follow-up, the relative odds of adherence were 1.42 and 1.27 for patients with one or more lipid test and one or more dyslipidaemia visit, respectively (95% confidence intervals [CI] 1.33, 1.50 and 1.16, 1.39). Patients who received a follow-up visit and lipid test were 45% more likely to be adherent (95% CI 1.34, 1.55). Similar associations were observed when lipid tests and dyslipidaemia visits occurred later in therapy. CONCLUSION: Early and frequent follow-up by physicians--especially lipid testing--was associated with improved adherence to lipid-lowering therapy. A randomised prospective study is needed to determine whether this relationship is causal.

Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Münster (PROCAM) study.

BACKGROUND AND AIM: Sitosterolemia, a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations, is associated with premature atherosclerosis in some individuals. This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events. METHODS AND RESULTS: A nested case-control study using stored samples from male participants in the Prospective Cardiovascular Münster (PROCAM) study was performed. Each of 159 men who suffered a myocardial infarction or sudden coronary death (major coronary event) within 10 years of follow-up in PROCAM was matched with 2 controls (N = 318) by age, smoking status, and date of investigation. Analysis was performed using conditional logistic regression. Plasma sitosterol concentrations were elevated in cases compared with controls (4.94 +/- 3.44 micromol/L versus 4.27 +/- 2.38 micromol/L; P = 0.028). The upper quartile of sitosterol (>5.25 micromol/L) was associated with a 1.8-fold increase in risk (P < 0.05) compared with the lower three quartiles. Among men with an absolute coronary risk > or = 20% in 10 years as calculated using the PROCAM algorithm, high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events (P = 0.032); a similar, significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk (P = 0.030). CONCLUSIONS: Elevations in sitosterol concentrations and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease. Further evaluations are warranted to confirm these preliminary findings.