👤 Richard O Burney

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium of therapies to achieve robust and sustained reduction in LDL-C can reduce ASCVD risk. The gold standard for LDL-C assessment is ultracentrifugation but in routine clinical practice LDL-C is usually calculated and the most accurate calculation is the Martin/Hopkins equation. For primary prevention, consideration of estimated ASCVD risk frames decision making regarding use of statins and other therapies, and tools such as risk enhancing factors and coronary artery calcium enable tailoring of risk assessment and decision making. In patients with diabetes, lipid lowering therapy is recommended in most patients to reduce ASCVD risk with an opportunity to tailor therapy based on other risk factors. Patients with primary hypercholesterolemia and familial hypercholesterolemia (FH) with baseline LDL-C greater than or equal to 190 mg/dL are at elevated risk, and LDL-C lowering with high-intensity statin therapy is often combined with non-statin therapies to prevent ASCVD. Secondary prevention of ASCVD, including in patients with prior myocardial infarction or stroke, requires intensive lipid lowering therapy and lifestyle modification approaches. There is no established LDL-C level below which benefit ceases or safety concerns arise. When further LDL-C lowering is required beyond lifestyle modifications and statin therapy, additional medications include oral ezetimibe and bempedoic acid, or injectables such as PCSK9 monoclonal antibodies or siRNA therapy. A novel agent that acts independently of hepatic LDL receptors is evinacumab, which is approved for patients with homozygous FH. Other emerging agents are targeted at Lp(a) and CETP. In light of the expanding lipid treatment landscape, this manuscript reviews the importance of early, intensive, and sustained LDL-C-lowering for primary and secondary prevention of ASCVD. Show less

Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation. Show less