HDL cholesterol efflux capacity and phospholipid content are associated with the severity of acute ischemic stroke and predict its outcome.

BACKGROUND/AIMS: Impaired high-density lipoprotein (HDL) function and composition are more strongly related to cardiovascular morbidity than HDL concentration. However, it is unclear whether HDL function and composition predict ischemic stroke severity and outcome. We aimed to evaluate these associations. METHODS: We prospectively studied 199 consecutive patients who were admitted with acute ischemic stroke. The severity of stroke was evaluated at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS ≥ 5. The outcome was assessed with dependency at discharge (modified Rankin scale 2-5) and in-hospital mortality. Cholesterol efflux capacity (CEC), phospholipid levels, lecithin:cholesterol acyl transferase (LCAT)-phospholipase activity, paraoxonase-1 (PON1)-arylesterase activity and serum amyloid A1 (SAA1) content of HDL were measured. RESULTS: CEC, phospholipid levels and LCAT-phospholipase activity of HDL were lower and SAA1 content of HDL was higher in patients with severe stroke. Patients who were dependent at discharge had lower CEC, PON1-arylesterase activity, phospholipid content and LCAT-phospholipase activity of HDL and higher HDL-SAA1 content. Independent predictors of dependency at discharge were the NIHSS at admission (RR 2.60, 95% CI 1.39-4.87), lipid-lowering treatment (RR 0.17, 95% CI 0.01-0.75), HDL-CEC (RR 0.21, 95% CI 0.05-0.87) and HDL-associated PON1-arylesterase activity (RR 0.95, 95% CI 0.91-0.99). In patients who died during hospitalization, phospholipids, LCAT-phospholipase and PON1-arylesterase activities of HDL were lower. CONCLUSIONS: Changes in CEC and composition of HDL appear to be associated with the severity and outcome of acute ischemic stroke and could represent biomarkers that may inform risk stratification and management strategies in these patients.

The Role of Angiotensin Receptor Blockers in the Personalized Management of Diabetic Neuropathy.

Neuropathy is a frequent complication of diabetes mellitus (DM) and is associated with the increased risk ofamputation and vascular events. Tight glycemic control is an important component inthe prevention of diabetic neuropathy. However, accumulating data suggest that angiotensin receptor blockers (ARBs) might also be useful in this setting. We discuss the findings of both experimental and clinical studies that evaluated the effects of ARBs on indices of diabetic neuropathy. We also review the implicated mechanisms of the neuroprotective actions of these agents. Overall, it appears that ARBs might be a helpful tool for preventing and delaying the progression of diabetic neuropathy, but more data are needed to clarify their role in the management of this overlooked complication of DM.

Experimental therapies targeting apolipoprotein C-III for the treatment of hyperlipidemia - spotlight on volanesorsen.

INTRODUCTION: Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides (TG). Apolipoprotein C3 (APOC3) is a key regulator of TG metabolism and its targeting may reduce TG levels and cardiovascular risk. AREAS COVERED: We discuss APOC3-targeted experimental treatments for dyslipidemia. There is an emphasis on volanesorsen because it the agent in the most advanced stage of development. M580, a retinoic acid receptor-α specific agonist, an agent in early-stage development is briefly covered. Preclinical data suggest that this agent decreases APOC3 mRNA levels and reduces total cholesterol, TG levels and hepatic lipid accumulation. EXPERT OPINION: The effects of this novel therapeutic approach on cardiovascular morbidity and mortality should be determined in randomized controlled trials. The cost of volanesorsen, the unfavorable safety profile and the need for subcutaneous administration present barriers to long-term use. AM580 may hold promise in the management of hypertriglyceridemia but further investigations are necessary to evaluate safety and efficacy.

Incretin-Based Antihyperglycemic Agents for the Management of Acute Ischemic Stroke in Patients with Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is a major risk factor for ischemic stroke. Moreover, patients with DM suffer more severe strokes and have worse functional outcome following an acute stroke than patients without DM. In this context, data from animal studies and emerging evidence from clinical studies suggest that incretin-based antihyperglycemic agents might exert beneficial effects in patients with DM who suffer ischemic stroke. It appears that these agents exert neuroprotective actions that might both reduce infarct size and promote recovery. The present review summarizes the evidence on the potential role of incretin-based antihyperglycemic agents in the management of acute ischemic stroke.

Sodium-glucose Cotransporter 2 Inhibitors and Ischemic Stroke.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with substantially increased risk for cardiovascular events, including ischemic stroke. In turn, ischemic stroke represents a leading cause of mortality and long-term disability worldwide. The recent class of glucose-lowering agents is sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which act through inhibition of glucose reabsorption in the kidney, resulting in glucose excretion without stimulating insulin release. Accumulating data suggests that these agents improve multiple risk factors for ischemic stroke except their glucose-lowering effect. OBJECTIVE: In the present review, the pleiotropic actions of SGLT-2 inhibitors are summarized and their potential implications on ischemic stroke prevention are discussed. METHODS: We performed a comprehensive search of the literature in terms of SGLT-2 inhibitors efficacy on ischemic stroke and traditional risk factors of cerebrovascular disease. RESULTS: Several studies consistently showed that SGLT-2 inhibitors reduce blood pressure, induce weight loss, increase high-density lipoprotein cholesterol levels and reduce triglyceride levels. In addition, they improve several emerging cardiovascular risk factors, most notably arterial stiffness, albuminuria and oxidative stress. However, in the only trial that evaluated the effects of these agents on the incidence of ischemic stroke, empagliflozin did not reduce the risk of first or recurrent stroke despite a significant reduction in cardiovascular and all-cause mortality. CONCLUSION: Despite the multiple pleiotropic effects of SGLT-2 inhibitors, these agents do not appear to affect stroke risk. Ongoing large trials with longer follow-up will evaluate whether the pleiotropic effects of this class will translate into benefits in ischemic stroke prevention.