Prior Statin Research Articles

A novel autoantibody recognizing 200‐kd and 100‐kd proteins is associated with an immune‐mediated necrotizing myopathy

Myofiber necrosis without prominent inflammation is a nonspecific finding in patients with dystrophies and toxic or immune-mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure, and the question of which patients would benefit from immunosuppression remains unanswered. The aim of this study was to identify novel autoantibodies in patients with necrotizing myopathy. Muscle biopsy specimens and serum samples were available for 225 patients with myopathy. Antibody specificities were determined by performing immunoprecipitations from (35)S-methionine-labeled HeLa cell lysates. Selected biopsy specimens were stained for membrane attack complex, class I major histocompatibility complex (MHC), and endothelial cell marker CD31. Muscle biopsy specimens from 38 of 225 patients showed predominantly myofiber necrosis. Twelve of these patients had a known autoantibody association with or other etiology for their myopathy. Sixteen of the remaining 26 sera immunoprecipitated 200-kd and 100-kd proteins; this specificity was observed in only 1 of 187 patients without necrotizing myopathy. Patients with the anti-200/100 autoantibody specificity had proximal weakness (100%), high creatine kinase levels (mean maximum 10,333 IU/liter), and an irritable myopathy on electromyography (88%). Sixty-three percent of these patients had been exposed to statins prior to the onset of weakness. All patients responded to immunosuppressive therapy, and many experienced a relapse of weakness when the medication was tapered. Immunohistochemical studies showed membrane attack complex on small blood vessels in 6 of 8 patients and on the surface of non-necrotic myofibers in 4 of 8 patients. Five of 8 patients had abnormal capillary morphology, and 4 of 8 patients expressed class I MHC on the surface of non-necrotic myofibers. An anti-200/100-kd specificity defines a subgroup of patients with necrotizing myopathy who previously were considered to be autoantibody negative. We propose that these patients have an immune-mediated myopathy that is frequently associated with prior statin use and should be treated with immunosuppressive therapy.

Statin Utilization in Nursing Home Patients after Cardiac Hospitalization

Coronary artery disease (CAD) is highly prevalent in nursing home residents and is associated with a substantial clinical and economic burden. Statins reduce mortality and hospitalization rates in older patients with CAD. To assess rates and predictors of statin use among high-risk patients with symptomatic coronary artery disease (CAD) admitted to nursing homes after acute cardiac hospitalization. Cohort study. Medicare beneficiaries enrolled in either a state-run drug assistance program or Medicaid in nursing homes in New Jersey from 1994 through 2005. Statin utilization within 60 days of nursing home admission was determined for patients recently hospitalized with symptomatic CAD in whom statins are indicated consisting of those with: acute coronary syndrome (ACS) without revascularization, ACS with revascularization and congestive heart failure (CHF) with revascularization. Predictors of statin use were evaluated with multivariate logistic regression models. While statin use over the 11-year period increased from 1.2% to 31.8%, overall utilization was very low. Predictors of greater statin use included prior cardiac hospitalization [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.13 to 1.57], prior statin use (OR 6.92, 95% CI 5.86 to 8.82) and receipt of a concurrent cardiac medication (range of odds ratios, 2.36-3.40). Older patients admitted for ACS with or without revascularization were less likely to receive a statin. Patients who had received anti-platelets or angiotensin-modifying agents prior to their hospitalization were less likely to receive statins after discharge. Renal disease, prior stroke, diabetes, hypertension and hyperlipidemia did not influence statin utilization. Predictors of treatment did not change when the cohort was dichotomized according to length of stay. Patients are infrequently treated with statins when discharged to nursing homes following hospitalization for a symptomatic cardiovascular event. Barriers to statin treatment in this setting require closer examination.

Carotid Atherosclerosis Progression in Familial Hypercholesterolemia Patients

Background— Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess the impact of statin treatment, before and after random assignment, on atherosclerosis progression. Methods and Results— We retrospectively evaluated cIMT change, and prior statin treatment and postbaseline LDL-C change as predictors of cIMT change, in 1513 HeFH patients who were randomly assigned to the statin arms of the early ASAP and more recent RADIANCE 1, CAPTIVATE, and ENHANCE studies. In the 3 recent studies combined, mean cIMT increased at only 33%of the rate of the simvastatin-treated patients in the ASAP study (0.014 mm/2 years [95% confidence interval, −0.0003–0.028] versus 0.041 mm/2 years [95% confidence interval, 0.020–0.061]; P <0.05). Patients whose statin therapy could be intensified, as evidenced by an LDL-C decrease after the initiation of on-trial statin therapy, showed cIMT decrease in the first 6 to 12 months and a much lower cIMT increase measured over the full 2 years. In line with this, previously statin-naive HeFH patients showed a lower overall cIMT increase. Conclusions— Over the years, intensification of statin therapy in HeFH patients has resulted in an impressive decrease in carotid atherosclerosis progression. In studies that assess other antiatherosclerotic modalities, statin therapy may still induce rapid changes in cIMT. For future cIMT studies, our analyses suggest that patient populations other than intensively pretreated HeFH patients should be selected and that the statin regimen should not be changed on study initiation.

Does a Single-Pill Antihypertensive/Lipid-Lowering Regimen Improve Adherence in US Managed Care Enrolees?

A previous study in 4703 patients suggested that a single-pill combination of amlodipine and atorvastatin is associated with greater adherence to therapy than a two-pill calcium channel antagonist (calcium channel blocker [CCB]) and HMG-CoA reductase inhibitor (statin) regimen. However, the impact of prior medication use on the potential adherence benefits of single-pill amlodipine/atorvastatin has not been studied. To compare adherence to single-pill amlodipine/atorvastatin versus two-pill CCB + statin regimens in a large managed care population, stratified according to prior CCB and statin use. This retrospective study was conducted among managed care enrolees in the US. Patients included in the analysis had to have a pharmacy claim for single-pill amlodipine/atorvastatin or claims for both a CCB and a statin within any 30-day window between April 2004 and April 2005. Adherence was measured over 6 months following the index date (the date of the first single-pill amlodipine/atorvastatin claim or of the claim for the second medication class for any two-pill CCB + statin regimen) as the proportion of days covered (PDC) by both CCB and statin therapy; patients were considered 'adherent' if PDC was > or =80%. Patients were divided into four cohorts based on pre-index CCB and statin use: (i) naive (CCB)/naive (statin); (ii) experienced (CCB)/naive (statin); (iii) naive (CCB)/experienced (statin); and (iv) experienced (CCB)/experienced (statin). Within each cohort, adherence was compared for patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin or other two-pill CCB + statin regimens (including amlodipine or atorvastatin but not both) at index. Multivariable logistic regression with propensity score weighting was used to adjust for covariates, including age, sex and co-morbidities. In total, 35,430 patients were included in the analysis. At month 6 (after adjusting for covariates), patients in the experienced (CCB)/naive (statin) cohort receiving single-pill amlodipine/atorvastatin were more than twice as likely to be adherent as those receiving two-pill amlodipine + atorvastatin (odds ratio [OR] 2.20; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.75; p < 0.0001). Similarly, patients in the naive (CCB)/experienced (statin) cohort receiving single-pill amlodipine/atorvastatin were more likely to be adherent than those receiving two-pill amlodipine + atorvastatin (OR 1.72; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.81; p < 0.0001). In contrast, in the naive (CCB)/naive (statin) cohort there was no significant difference in adherence between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.00), although patients receiving single-pill amlodipine/atorvastatin were slightly more likely to be adherent than those receiving other two-pill CCB + statin regimens (OR 1.29; p < 0.01). In the experienced (CCB)/experienced (statin) cohort there was also no significant difference between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.08), and only a slightly greater likelihood of achieving adherence to single-pill amlodipine/atorvastatin versus other two-pill CCB + statin regimens (OR 1.19; p < 0.01). This large retrospective study confirms previous observations that single-pill amlodipine/atorvastatin can help improve adherence versus two-pill CCB + statin regimens. However, greater improvements in adherence are likely to be observed in patients with prior experience of either CCB or statin therapy than in those either naive to, or experienced with, both therapies.

P273 EZETIMIBE/SIMVASTATIN 10/20 mg VERSUS ROSUVASTATIN 10 mg IN HIGH RISK HYPERCHOLESTEROLEMIC PATIENTS STRATIFIED BY PRIOR STATIN TREATMENT POTENCY

Objective: This post-hoc analysis compared the lipid-altering efficacy of Ezetimibe/Simvastatin 10/20 mg (EZ/Simva) versus Rosuvastatin 10 mg (Rosuva) in patients stratified by statin potency/dose prior to randomization. Methods: Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite prior statin treatment (n = 618) were randomized 1:1 to EZ/Simva 10/20 mg or Rosuva 10 mg for 6 weeks. Percent change from baseline in lipids and attainment of lipid targets were assessed within each subgroup (low potency n = 369, high potency n = 249). Consistency of the treatment effect across subgroups was evaluated by testing for treatment-by-subgroup interaction. No multiplicity adjustments were made. Results: Significant treatment-by-subgroup interaction occurred for LDL-C (p = 0.013), total cholesterol (p = 0.025), non-HDL-C (p = 0.032), and apolipoprotein B (p = 0.016) with greater between-treatment differences in favor of EZ/Simva observed in patients from the high potency stratum vs low potency stratum. Individual and triple target attainment was higher for Eze/Simva compared with Rosuva in both strata. Conclusions: Compared with Rosuva, switching to EZ/Simva provided greater reductions in LDL-C, total cholesterol, non-HDL-C and apolipoprotein B and higher target attainment in patients on prior statin treatment, regardless of potency, although patients treated with higher potency statins prior to randomization experienced greater between treatment differences in favor of EZ/Simva. Trial Registration: Registered at ClinicalTrials.gov: NCT00479713.

Expérience de la thrombolyse intraveineuse des infarctus cérébraux à l’hôpital d’instruction des armées Sainte-Anne de Toulon de septembre 2003 à juin 2009

Since 2003, intravenous thrombolysis with rt-PA for stroke victims has been largely developed in the military hospital of Toulon. We report the results of our practice and compare them with the literature. Wealso sought to identify predictive factors of favorable outcome after thrombolysis. All patients treated with rt-PA for a stroke in the carotid territory between September 2003 and June 2009 were prospectively included. Disability was assessed at 3 months with the modified Rankin Scale (m-RS); outcome was considered unfavorable if m-RS score was above 2. Multivariate analysis was then performed to identify parameters correlating with poor and favorable outcome at 3 months follow-up. One hundred and one patients were included in this study (mean initial National Institute of Health Stroke Scale [NIHSS]: 15.2). 53.4% had a Rankin score higher than 2 at 3 months follow-up. The absence of diabetes mellitus, low NIHSS score on admission, short time from stroke onset to treatment, and prior statin use were identified as independent predictive factors of favorable functional outcome. After 6 years of activity, our stroke unit has results that appear similar to those of the French and international trials in terms of safety and efficacy. Efficacy of rt-PA in our series is poor for strokes caused by large-vessel atherothrombotic changes and cervical artery dissection due to high incidence of internal carotid thrombosis in these cases. Our studies also suggest that prior statin use may be an independent predictive factor of favorable outcome after thrombolysis.

Ezetimibe/Simvastatin 10/20 mg Versus Rosuvastatin 10 mg in High Risk Hypercholesterolemic Patients Stratified by Previous Statin Treatment Potency

Objective: This post-hoc analysis compared the lipid-altering efficacy of Ezetimibe/Simvastatin 10/20 mg (EZ/Simva) versus Rosuvastatin 10 mg (Rosuva) in patients stratified by statin potency/dose prior to randomization. Methods: Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite prior statin treatment (n = 618) were randomized 1:1 to EZ/Simva 10/20 mg or Rosuva 10 mg for 6 weeks. Percent change from baseline in lipids and attainment of lipid targets were assessed within each subgroup (low potency n = 369, high potency n = 249). Consistency of the treatment effect across subgroups was evaluated by testing for treatment-by-subgroup interaction. No multiplicity adjustments were made. Results: Significant treatment-by-subgroup interaction occurred for LDL-C (p = 0.013), total cholesterol (p = 0.025), non-HDL-C (p = 0.032), and apolipoprotein B (p = 0.016) with greater between-treatment differences in favor of EZ/Simva observed in patients from the high potency stratum vs low potency stratum. Individual and triple target attainment was higher for Eze/Simva compared with Rosuva in both strata. Conclusions: Compared with Rosuva, switching to EZ/Simva provided greater reductions in LDL-C, total cholesterol, non-HDL-C and apolipoprotein B and higher target attainment in patients on prior statin treatment, regardless of potency, although patients treated with higher potency statins prior to randomization experienced greater between treatment differences in favor of EZ/Simva. Trial Registration: Registered at ClinicalTrials.gov: NCT00479713.

C-C4-01: Statin Use and Risk of Basal Cell Carcinoma

Maryam M Asgari, MD, MPH, Jean Tang, MD, PhD, Ervin Epstein, MD, Mary-Margaret Chren, MD, Margaret Warton, MPH, Charles P Quesenberry Jr, PhD, Alan S Go, MD and Gary D Friedman, MD, MS Maryam M Asgari, MD, MPH, Kaiser Permanente Northern California; Jean Tang, MD, PhD, Kaiser Permanente Northern California; Ervin Epstein, MD, Kaiser Permanente Northern California; Mary-Margaret Chren, MD, Kaiser Permanente Northern California; Margaret Warton, MPH, Kaiser Permanente Northern California; Charles P Quesenberry Jr, PhD, Kaiser Permanente Northern California; Alan S Go, MD, Kaiser Permanente Northern California; Gary D Friedman, MD, MS, Kaiser Permanente Northern California

Outcome of intracerebral haemorrhage patients pre‐treated with statins

Statins treatment may have potential clinical impact in vascular disease beyond cholesterol lowering. Its benefits have been documented in cerebral ischaemia and in subarachnoid haemorrhage. In intracerebral haemorrhage (ICH), experimental models in statin-treated animals have better outcome than non-treated ones, but in humans the relationship is unclear. We investigated whether patients treated with statins before the onset of intracerebral haemorrhage have a better outcome at 3 months than patients without statins pre-treatment. Retrospective review of primary intracerebral haemorrhage case series from a prospective stroke register. We recorded demographics, vascular risk factors, previous statin treatment, Glasgow coma scale (GCS) at onset, ICH scale, hematoma volume and location, ventricular extension of the hematoma, and functional outcome at 3 months. The effect of prior statin treatment on good outcome (modified Rankin scale [mRS] 0 to 2) was analysed by logistic regression analysis. We included 269 patients (age 71.9 +/- 12.4, mean +/- SD, 152 males). Thirty-four patients (12.6%) were on prior statin treatment when admitted. There were no differences in fasting serum cholesterol and triglycerides levels between the statin pre-treated groups and the group without statin pre-treatment. Multivariate regression analysis showed a significant association between age (OR: 0.95; CI 0.92-0.97), ICH volume (OR: 0.96; CI 0.94-0.98), GCS (OR: 1.55; CI 1.21-1.98), pre-treatment with statins (OR: 4.21; CI 1.47-12.17; P = 0.008), and good outcome at 3 months. Statins pre-treatment of patients with intracerebral haemorrhage may provide better functional outcome at 3 months of acute onset.

Statin Use and Functional Outcome after Tissue Plasminogen Activator Treatment in Acute Ischaemic Stroke

Background: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients prior on statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional outcome than statin-naïve patients. Methods: In a prospective observational cohort study of 476 acute ischaemic stroke patients treated with tPA we investigated the relationship between prior statin use and functional outcome at 3 months, the occurrence of symptomatic intracerebral haemorrhage (SICH) and early in-hospital mortality. Ischaemic stroke subtypes were defined according to the TOAST classification. Favourable outcome was defined as a modified Rankin Scale score ≤2. Results: Of the 476 patients included, 98 (20.6%) used a statin at stroke presentation. In the entire cohort, 45.6% of patients had a favourable outcome with no difference between patients with or without statin therapy (45.9 vs. 45.5%, p = 0.94). In the multivariable analysis, statin use was not associated with favourable outcome (OR = 1.1, 95% CI = 0.6–1.9, p = 0.87). In none of the different stroke subtype groups was statin use associated with favourable outcome. Finally, statin use was not an independent risk factor of SICH or of early in-hospital mortality. Conclusion: Prior statin therapy in patients with acute ischaemic stroke treated with tPA is not associated with a more favourable outcome, and this is independent of stroke subtype.

Impact of Prior Statin Therapy on Arrhythmic Events in Patients With Acute Coronary Syndromes (from the Global Registry of Acute Coronary Events [GRACE

Impact of Prior Statin Therapy on Arrhythmic Events in Patients With Acute Coronary Syndromes (from the Global Registry of Acute Coronary Events [GRACE

Ezetimibe/Simvastatin 10/20 mg versus Rosuvastatin 10 mg in high-risk hypercholesterolemic patients stratified by prior statin treatment potency

ObjectiveThis post-hoc analysis compared the lipid-altering efficacy of Ezetimibe/Simvastatin 10/20 mg (EZ/Simva) versus Rosuvastatin 10 mg (Rosuva) in patients stratified by statin potency/dose prior to randomization.MethodsPatients with elevated low-density lipoprotein cholesterol (LDL-C) despite prior statin treatment (n = 618) were randomized 1:1 to EZ/Simva 10/20 mg or Rosuva 10 mg for 6 weeks. Percent change from baseline in lipids and attainment of lipid targets were assessed within each subgroup (low potency n = 369, high potency n = 249). Consistency of the treatment effect across subgroups was evaluated by testing for treatment-by-subgroup interaction. No multiplicity adjustments were made.ResultsSignificant treatment-by-subgroup interaction occurred for LDL-C (p = 0.013), total cholesterol (p = 0.025), non-HDL-C (p = 0.032), and apolipoprotein B (p = 0.016) with greater between-treatment differences in favor of EZ/Simva observed in patients from the high potency stratum vs low potency stratum. Individual and triple target attainment was higher for Eze/Simva compared with Rosuva in both strata.ConclusionsCompared with Rosuva, switching to EZ/Simva provided greater reductions in LDL-C, total cholesterol, non-HDL-C and apolipoprotein B and higher target attainment in patients on prior statin treatment, regardless of potency, although patients treated with higher potency statins prior to randomization experienced greater between treatment differences in favor of EZ/Simva.Trial RegistrationRegistered at ClinicalTrials.gov: NCT00479713

Statins and clinical outcome of acute ischemic stroke: a systematic review.

BackgroundStatin therapy is considered an effective measure for the prevention of ischemic stroke. Several recent studies have indicated that treatment with statins, prior to the onset of acute ischemic stroke, may also substantially reduce the severity of stroke and the degree of patient disability. The purpose of the present review is to systematically evaluate the effectiveness of statin pretreatment on functional outcome of acute ischemic stroke and to assess potential adverse events associated with statin use.MethodsRelevant articles on the role of statins in acute ischemic stroke were identified via MEDLINE/PubMed, EMBASE, CENTRAL, and by manual searches of the references of identified papers. Clinical studies (most were prospective cohort studies) assessing statin therapy for acute ischemic stroke were selected for the review. Only two randomized controlled clinical trials met the criteria to be included in the analysis. Clinical outcome was assessed based on the degree of disability determined with the modified Rankin Scale (mRS) and Barthel index (BI). The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity. Recurrence of stroke in patients who had suffered from a previous stroke was analyzed with and without statin therapy. Incidence and severity of adverse reactions was reviewed. Because there were too many differences in study outcome measures, a quantitative analysis of data was deemed inappropriate. A qualitative summary of the data was consequently completed.ResultsThirteen reports were systematically reviewed to evaluate the efficacy and safety of statins in the pretreatment of acute ischemic stroke. Pretreatment with statins was found to reduce the recurrence of stroke and to result in more favorable outcomes for patients. The beneficial effects of prior statin therapy in acute ischemic stroke were shown to be especially profound in whites, diabetics, elderly patients with hypertension and other vascular diseases, and in patients with ideal low density lipoprotein (LDL) levels. There were few incidences of adverse reactions with statin pretreatment, most of which were not statistically significant.ConclusionsPretreatment with statins was associated with a favorable outcome in acute ischemic stroke, with few incidences of adverse reactions.

Impact of Prior Statin Therapy on Arrhythmic Events in Patients With Acute Coronary Syndromes (from the Global Registry of Acute Coronary Events [GRACE

Impact of Prior Statin Therapy on Arrhythmic Events in Patients With Acute Coronary Syndromes (from the Global Registry of Acute Coronary Events [GRACE

Impact of Prior Statin Therapy on Arrhythmic Events in Patients With Acute Coronary Syndromes (from the Global Registry of Acute Coronary Events [GRACE

Animal models of myocardial ischemia have demonstrated reduction in arrhythmias using statins. It was hypothesized that previous statin therapy before hospitalization might be associated with reductions of in-hospital arrhythmic events in patients with acute coronary syndromes. In this multinational, prospective, observational study (the Global Registry of Acute Coronary Events [GRACE]), data from 64,679 patients hospitalized for suspected acute coronary syndromes (from 1999 to 2007) were analyzed. The primary outcome of interest was in-hospital arrhythmic events in previous statin users compared with nonusers. The 2 primary end points were atrial fibrillation and the composite end point of ventricular tachycardia, ventricular fibrillation, and/or cardiac arrest. In-hospital death was also examined. Of the 64,679 patients, 17,636 (27%) had received previous statin therapy. Those taking statins had higher crude rates of histories of angina (69% vs 46%), diabetes (34% vs 22%), heart failure (15% vs 8.4%), hypertension (74% vs 58%), atrial fibrillation (9.3% vs 7.0%), and dyslipidemia (85% vs 35%). Patients previously taking statins were less likely to have in-hospital arrhythmias. In propensity-adjusted multivariable models, previous statin use was associated with a lower risk for ventricular tachycardia, ventricular fibrillation, or cardiac arrest (odds ratio 0.81, 95% confidence interval 0.72 to 0.96, p = 0.002); atrial fibrillation (odds ratio 0.81, 95% confidence interval 0.73 to 0.89, p <0.0001); and death (odds ratio 0.82, 95% confidence interval 0.70 to 0.95, p = 0.010). In conclusion, patients previously taking statins had a lower incidence of in-hospital arrhythmic events after acute coronary syndrome than those not previously taking statins. Our study suggests another possible benefit from appropriate primary and secondary prevention therapy with statins.

Hypercholesterolemia Paradox in Relation to Mortality in Acute Coronary Syndrome

Hypercholesterolemia is a risk factor for coronary artery disease, yet is associated with lower risk of adverse outcomes in patients with acute coronary syndromes (ACS). We explored this paradox in 84,429 patients with non-ST-segment elevation ACS in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines registry. We examined the association between a history of hypercholesterolemia and in-hospital mortality after adjusting for clinical covariates. After excluding patients with previously diagnosed hypercholesterolemia, we repeated the analysis, examining the association between newly diagnosed hypercholesterolemia (in-hospital low-density lipoprotein cholesterol [LDL-C] > or = 100 mg/dL) and mortality. A history of hypercholesterolemia was associated with lower in-hospital mortality (unadjusted odds ratio [OR]: 0.58; 95% confidence interval [CI]: 0.55, 0.62). This protective association persisted after adjusting for baseline characteristics (OR: 0.71; 95% CI: 0.66, 0.76) and prior statin use (OR: 0.74; 95% CI: 0.68, 0.80). Among 22,711 patients with no history of hypercholesterolemia, 12,809 had a new in-hospital diagnosis of hypercholesterolemia. Unadjusted mortality in these patients was lower than among those with normal LDL levels (OR: 0.58; 95% CI: 0.50, 0.67); however, this difference was not significant after multivariable adjustment (OR: 0.86; 95% CI: 0.73, 1.01). The association of hypercholesterolemia with better outcomes highlights a major challenge in observational analyses. Our results suggest this paradox may result from confounding due to other clinical characteristics, impact of statin treatment, and perhaps most importantly, the fact that previously diagnosed hypercholesterolemia is a marker for patients with more prior medical contact.

Prior simvastatin treatment is associated with reduced thrombin generation and platelet activation in patients with acute ST-segment elevation myocardial infarction

Background It has been reported that statin therapy produces additional effects including impaired activation of blood coagulation. It is not clear whether statins can affect hemostasis in patients with acute coronary syndrome. The aim of this study was to investigate the effect of prior statin treatment on thrombin generation and platelet activation in patients with ST-segment elevation myocardial infarction (STEMI). Methods We studied 53 consecutive STEMI patients admitted within 12 hours of pain onset, including 19 treated with simvastatin (40 mg/d) (simvastatin group) at least one month prior to STEMI, and 34 not receiving any statins (no-statin group) on admission. Thrombin-antithrombin (TAT) complexes generation and soluble CD40 ligand (sCD40L) release were determined in 60-second blood samples collected at the site of microvascular injury. Results There were no significant intergroup differences with respect to clinical and laboratory variables, including plasma TAT and sCD40L levels, except lower total cholesterol and low-density lipoprotein cholesterol in the simvastatin group. The mean maximum rate of TAT generation was 47.5% lower (p = 0.0002) and sCD40L release 33.3% lower (p = 0.0006) in the simvastatin group. Total amounts of TAT (p < 0.0001) and sCD40L (p = 0.002) collected within 5 minutes of bleeding were lower in simvastatin-pretreated patients. By multivariate regression analysis, variables describing local TAT and sCD40L profiles in the whole group were independently associated with simvastatin pretreatment (p < 0.0001), but not with cholesterol, platelet count or troponin levels. Conclusions Prior simvastatin use is associated with lower thrombin generation and platelet activation following vascular injury in the early phase of STEMI.

Admission hypoglycaemia is associated with adverse outcome in community-acquired pneumonia

The aim of our study was to investigate if hypoglycaemia correlates with outcome in community-acquired pneumonia (CAP). We performed a prospective, observational study of consecutive patients presenting with a primary diagnosis of CAP in Lothian (UK). Admission plasma glucose was measured and, on this basis, patients were divided into two groups, hypoglycaemic (<4.4 mmol x L(-1) or <79.0 mg x dL(-1)) and nonhypoglycaemic (> or = 4.4 mmol x L(-1) or > or = 79.0 mg x dL(-1)). Outcomes of interest were 30-day mortality, need for mechanical ventilation and inotropic support. Multivariable logistic regression was used to compare these outcomes in hypoglycaemic patients to nonhypoglycaemic patients, adjusting for diabetes mellitus, prior statin use and Pneumonia Severity Index. In total, 1,050 patients were included in the study with 5.4% classified as hypoglycaemic. Increased rates of 30-day mortality (28.1% versus 7.5%, p<0.0001), need for mechanical ventilation (29.8% versus 6.5%, p<0.0001) and need for inotropic support (21.1% versus 4.8%, p<0.0001) were observed in hypoglycaemic patients compared with nonhypoglycaemic patients. On multivariable analysis, hypoglycaemia was independently associated with increased 30-day mortality (OR 2.25, 95% CI 1.1-4.7; p = 0.03), need for mechanical ventilation (OR 3.8, 95% CI 1.9-7.5; p = 0.0002) and need for inotropic support (OR, 2.9, 95% CI 1.4-6.3; p = 0.0006). Admission hypoglycaemia is associated with increased 30-day mortality, need for mechanical ventilation and inotropic support in patients presenting with CAP.

The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls.

AimsPlasma levels of apolipoprotein B (apoB), the main surface protein on LDL particles, and LDL-C, the amount of cholesterol in those particles, are closely correlated and, considered separately, are positive risk factors. Plasma levels of apolipoprotein A1, the main surface protein on HDL particles, and HDL-C, the amount of cholesterol in those particles, are also closely correlated with each other and, considered separately, are negative risk factors. The interdependence of these four risk factors is unclear.Methods and resultsCase–control study among 3510 acute myocardial infarction patients (without prior vascular disease, diabetes, or statin use) in UK hospitals and 9805 controls. Relative risks (age, sex, smoking, and obesity-adjusted) were more strongly related to apoB than to LDL-C and, given apoB, more strongly negatively related to apoA1 than to HDL-C. The ratio apoB/apoA1 was uncorrelated with time since symptom onset in cases, was reproducible in samples collected a few years apart in controls (correlation 0.81), and encapsulated almost all the predictive power of these four measurements. Its effect was continuous, substantial throughout the UK normal range [relative risk, top vs. bottom decile of this ratio, 7.3 (95% CI 5.8–9.2)] and varied little with age. The ratio apoB/apoA1 was substantially more informative about risk (χ12 = 550) than were commonly used measures such as LDL-C/HDL-C, total/HDL cholesterol, non-HDL cholesterol, and total cholesterol (χ12 = 407, 334, 204, and 105, respectively). Given apoB and apoA1, the relationship with risk of LDL-C was reversed, and this reversal was strengthened by appropriate allowance for random measurement errors in two correlated variables. Given usual apoB, lower LDL-C (consistent with smaller LDL particles) was associated with higher risk (P < 0.0001). During the first 8 h after symptom onset HDL-C increased by about 10%, precluding reliable assessment of the joint relationship of apoA1 and pre-onset HDL-C with risk in such retrospective case–control studies.ConclusionApolipoprotein ratios are more informative about risk than lipid fractions are. This suggests that, among lipoprotein particles of a particular type (LDL or HDL), some smaller and larger subtypes differ in their effects on risk. Direct measurements of even more specific subtypes of lipoprotein particles may be even more informative about risk.

Statin use and risk of basal cell carcinoma

We examined the association between statin use and basal cell carcinoma (BCC) risk. We identified all members of a large integrated health care delivery system with a diagnosis of a histologically proven BCC in 1997. Subsequent BCCs were identified through 2006 from health plan electronic pathology records. Longitudinal exposure to statins and other lipid-lowering agents was determined from automated pharmacy records. We used extended Cox regression to examine the independent association between receipt of statin therapy (ever vs never, cumulative duration) and risk of subsequent BCC. To minimize confounding by indication, we conducted sensitivity analyses in the subset of individuals considered eligible for lipid-lowering therapy based on national guidelines. Among 12,123 members given a diagnosis of BCC who had no prior statin exposure, 6381 developed a subsequent BCC during follow-up. Neither "ever use of statins" (adjusted hazard ratio 1.02, 95% confidence interval: 0.92-1.12) or cumulative duration of statin (adjusted hazard ratio 1.02/year, 95% confidence interval: 0.99-1.11) was associated with subsequent BCC after adjustment for age, sex, and health care use. Risk estimates did not change appreciably when the analysis was limited to the subset of individuals who met eligibility criteria for initiating statin therapy. There was also no significant association between use of non-statin antilipemics and subsequent BCC (adjusted hazard ratio 1.10, 95% confidence interval: 0.76-1.58). No information was available for BCC risk factors, such as sun sensitivity and sun exposure. Among a large cohort of individuals with BCC, statin therapy was not significantly associated with risk of subsequent BCC.