Effect of Fenofibrate on Adiponectin and Inflammatory Biomarkers in Metabolic Syndrome Patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93679/1/oby.2008.530.pd

Cerebral artery signal intensity gradient from Time-of-Flight Magnetic Resonance Angiography and clinical outcome in lenticulostriate infarction: a retrospective cohort study

PurposeLenticulostriate infarction requires further research of arterial hemodynamic factors, as the disease is diagnosed in the absence of major arterial stenosis or cardioembolism.MethodsIn this multicenter retrospective cohort study, we included patients who were hospitalized for lenticulostriate infarction from January 2015 to March 2021 at three stroke centers in South Korea. We obtained hemodynamic information on cerebral arteries using signal intensity gradient (SIG), an in-vivo approximated wall shear stress (WSS) derived from Time-of-Flight Magnetic Resonance Angiography (TOF-MRA). A favorable outcome was defined as a modified Rankin Scale of 0 to 2 at hospital discharge.ResultsA total of 294 patients were included, of whom 146 (49.7%) had an unfavorable outcome. The unfavorable outcome group showed significantly lower SIG in both middle cerebral arteries (MCAs) than the favorable group (5.2 ± 1.2 SI/mm vs. 5.9 ± 1.2, p < 0.001), and similar findings were observed in other cerebral arteries. The SIGs in both MCAs were independently associated with favorable outcome, with an odds ratio of 1.42 (95% confidence interval, 1.11–1.80; p = 0.005) for the right MCA and 1.49 (95% CI, 1.15–1.93; p = 0.003) for the left MCA, after adjusting for potential confounders. Similar findings were observed in other cerebral artery SIGs.ConclusionCerebral artery SIG from TOF-MRA was significantly associated with short-term functional outcomes in patients with lenticulostriate infarction. Further studies are needed to investigate the temporal relationships of SIG in patients with cerebral infarction

Efficacy and tolerability of evolocumab vs. ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial

Importance: Muscle-related statin intolerance is reported by 5% to 20% of patients. Objective: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. Design, Setting, and Participants: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. Interventions: Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Main Outcome and Measures: Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. Results: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, −16.7% (95% CI, −20.5% to −12.9%), absolute change, −31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, −54.5% (95% CI, −57.2% to −51.8%); absolute change, −106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, −16.7% (95% CI, −20.8% to −12.5%); absolute change, −31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, −52.8% (95% CI, −55.8% to −49.8%); absolute change, −102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was −37.8%; absolute difference, −75.8 mg/dL. For week 24, between-group difference in LDL-C was −36.1%; absolute difference, –71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). Conclusions and Relevance: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety