Association of chronic neutrophil activation with risk of mortality.

BACKGROUND: Levels of free myeloperoxidase (MPO), a cardiovascular risk marker, have been reported to decline with standard care. Whether such declines signify decreased risk of mortality remains unknown. DESIGN: Cox proportional hazard models were generated using data from a retrospective cohort study of prospectively collected measures. PARTICIPANTS: Patients (3,658) who had MPO measurements and LDL-C ≥ 90 mg/dL during 2011-2015 were selected based on a stratified random sampling on MPO risk level. Baseline MPO was either low (<470 pmol/L), moderate (470-539 pmol/L), or high (≥540 pmol/L). MAIN OUTCOMES AND MEASURES: First occurrence of MACE (myocardial infarction, stroke, coronary revascularization, or all-cause death). RESULTS: Mean age was 66.5 years, and 64.7% were women. During a mean 6.5-year follow-up, crude incidence per 1000 patient years was driven by death. The incidence and all-cause death was highest for patients with high MPO (21.2; 95% CI, 19.0-23.7), then moderate (14.6; 95% CI, 11.5-18.5) and low (2.3; 95% CI, 1.2-4.6) MPO. After adjusting for age, sex, and cardiovascular risk factors, risk of cardiovascular death did not differ significantly between patients with high and low MPO (HR, 1.57; 95% CI, 0.56-4.39), but patients with high MPO had greater risk of non-cardiovascular (HR, 6.15; 95% CI, 2.27-16.64) and all-cause (HR, 3.83; 95% CI, 1.88-7.78) death. During follow-up, a 100 pmol/L decrease in MPO correlated with a 5% reduction in mortality (HR, 0.95; 95% CI, 0.93-0.97) over 5 years. CONCLUSIONS: Free circulating MPO is a strong marker of risk of mortality. Monitoring changes in MPO levels over time may provide insight into changes in physiology that mark a patient for increased risk of mortality.

A Review of the Efficacy and Tolerability of Bempedoic Acid in the Treatment of Hypercholesterolemia.

Despite the widespread use of statins and ezetimibe to decrease low-density lipoprotein cholesterol (LDL-C) levels and associated atherosclerotic cardiovascular disease (ASCVD), many patients do not achieve adequate LDL-C lowering as per the recommended American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and demonstrate residual cardiovascular risk. The introduction of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in 2015 was a promising addition to hypercholesterolemia therapies, but their cost and subcutaneous administration has limited their use, and therefore, new affordable and patient friendly treatment strategies are crucial to help reduce ASCVD risk. Bempedoic acid, a drug currently under investigation, is a small molecule that has been shown to upregulate LDL receptors, decrease LDL-C, and reduce atherosclerotic plaque formation in hypercholesterolemic patients. Furthermore, bempedoic acid is a prodrug that becomes activated by an enzyme expressed primarily in the liver, allowing it to avoid the potential myotoxicity associated with statin therapy. The purpose of this review is to summarize the major clinical studies evaluating bempedoic acid and describe its potential addition to currently approved lipid-lowering therapies.

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Cardiovascular Disease Prevention.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Because of these associated risks, managing diabetes and CVD, including heart failure (HF), has become a joint effort to reduce the risk of adverse outcomes. Although many patients with T2DM are receiving preventive therapies for CVD, their residual risk remains high for atherosclerotic CVD (ASCVD). Recent data regarding the use of antidiabetic medications to prevent negative cardiovascular outcomes has revealed a positive association with reduced major adverse cardiovascular events (MACE). One class of medications, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, are at the forefront of the cardiovascular outcomes prevention discussion. The clinical data presented in this review indicate the potential cardiovascular benefits of SGLT-2 inhibitors in patients with CVD and its potential value as a treatment option in preventing CVD in various patient populations.

A spotlight on alirocumab in high cardiovascular risk patients with type 2 diabetes and mixed dyslipidemia: a review on the emerging data.

Diabetes is a significant and independent risk factor for atherosclerotic cardiovascular disease (ASCVD), leading to morbidity and mortality among this population. The prevention of macrovascular complications, such as CVD, peripheral arterial disease, and cerebrovascular accident, in patients with diabetes is obtained through multifactorial risk reduction, including mixed dyslipidemia management and adequate glycemic control. For patients with diabetes, it is crucial to initiate adequate dyslipidemia therapy to achieve recommended low-density lipoprotein cholesterol (LDL-C) goal of <70 mg/dL or target non-high-density lipoprotein goal of <100 mg/dL. Lipid-lowering therapies (LLTs), such as statins and ezetimibe, are the cornerstone for plasma LDL-C lowering; however, individuals with diabetes are often unable to achieve target lipid goals with these therapies alone and frequently require additional treatments. A new class of LLTs, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, provides a novel approach to lowering lipids in persons with high CV risk, such as those with diabetes. The clinical data presented in this review indicate the potential benefits of alirocumab in patients with diabetes and its value as a treatment option in patients with diabetic dyslipidemia with no significant safety concerns.