Statin-Associated Muscle Adverse Events : Update for clinicians

Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statinassociated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event. Recent guidelines and guideline updates on SaMAEs and statin intolerance have included revised definitions of SaMAEs, incorporating new evidence on their pathogenesis and management. As SaMAEs emerge as a therapeutic challenge, it is important for physicians to be aware of updates on management strategies to ensure better patient outcomes. The majority of patients who are considered statin-intolerant can nevertheless tolerate some forms of statin therapy and successfully achieve optimal LDL-C levels. This review article discusses the recent classification of SaMAEs with emphasis on pathogenesis and management strategies.

Controlling complexity: the clinical relevance of mouse complex genetics.

Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches

Clinical usefulness of lipid ratios to identify men and women with metabolic syndrome: a cross-sectional study

Background: Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components. Methods Men and women (N = 797) of Aboriginal, Chinese, European, and South Asian origin (35–60 years), recruited across ranges of body mass index (BMI), with no diagnosed cardiovascular disease (CVD) or on medications to treat CVD risk factors were assessed for anthropometrics, family history of CVD, MetSy components (waist circumference, blood pressure, glucose, triglycerides (TG), high-density-lipoprotein-cholesterol (HDL-C)), low-density-lipoprotein-cholesterol (LDL-C), nonHDL-C, and health-related behaviours. Results Mean levels of lipid ratios significantly increased with increasing number of MetSy components in men and women (p < 0.05). After adjustment for age, ethnicity, smoking, alcohol consumption, physical activity, family history of CVD and BMI, (and menopausal status in women), all lipid ratios were associated with the number of MetSy components in men and women (Poisson regression, p < 0.001). Compared to the rest of the lipid ratios (ROC curve analysis), TG/HDL-C was best able to discriminate between individuals with and without MetSy (AUC = 0.869 (95% CI: 0.830, 0.908) men; AUC = 0.872 (95% CI: 0.832, 0.912) women). The discriminatory power of TC/HDL-C and nonHDL-C/HDL-C to identify individuals with MetSY was the same (for both ratios, AUC = 0.793 (95% CI: 0.744, 0.842) men; 0.818 (95% CI: 0.772, 0.864) women). Additionally, LDL-C/HDL-C was a good marker for women (AUC = 0.759 (95% CI: 0.706, 0.812)), but not for men (AUC = 0.689 (95% CI: 0.631, 0.748)). Based on a multiethnic sample, we identified TG/HDL-C cut-off values of 1.62 in men and 1.18 in women that were best able to discriminate between men and women with and without MetSY. Conclusions Our results indicate that TG/HDL-C is a superior marker to identify men and women with MetSy compared to TC/HDL-C, LDL-C/HDL-C, and nonHDL-C/HDL-C.Medicine, Department ofMedicine, Faculty ofPathology and Laboratory Medicine, Department ofNon UBCReviewedFacult

Coronary artery calcium findings in asymptomatic subjects with family history of premature coronary artery disease

Background: To evaluate the frequency of positive coronary arteries calcium (CAC) scores in a unique population of asymptomatic first degree relatives (FDRs) of patients with angiographically confirmed early onset of coronary artery disease (CAD) and to assess their association with carotid ultrasound findings and other cardiovascular risk factors. Method and results We scanned, using 64-slice multi-detector computed tomography, 57 asymptomatic FDRs (47 ± 9 years old; 44% male, 56% female), out of the 111 FDRs previously phenotyped for cardiovascular (CV) risk factors. The controls were 616 individuals (57 ± 10 years old; 76% male, 24% female) with no family history of cardiovascular disease, chest pain or diabetes selected out of the 3500 subjects scanned between 2002 and 2007. FDRs had higher risk of abnormal CAC scores compared to controls; odds ratio (OR) for the 75th percentile was 1.96 (95% CI 1.04 – 3.67, p < 0.05). Conclusion The frequency of abnormal CAC scores is two-fold higher in asymptomatic FDRs than in controls. CAC scan provides additional information on CV risk assessment in asymptomatic FDRs, particularly for those in the intermediate risk category. Clinical trial registration NCT00387595Medicine, Department ofMedicine, Faculty ofPathology and Laboratory Medicine, Department ofRadiology, Department ofNon UBCReviewedFacult