Adequacy of preadmission oral anticoagulation with vitamin K antagonists and ischemic stroke severity and outcome in patients with atrial fibrillation.

It is unclear whether vitamin K antagonists affect stroke severity and outcome in patients with atrial fibrillation (AF). We aimed to evaluate this association. We prospectively studied 539 consecutive patients admitted with acute ischemic stroke (41.2 % males, age 78.9 ± 6.6 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). The outcome was assessed with dependency rates at discharge (modified Rankin scale 2-5) and with in-hospital mortality. 177 patients had a history of AF. The median NIHSS at admission did not differ between patients on acenocoumarol with INR 2.0-3.0, on acenocoumarol with INR < 2.0, on single antiplatelet treatment, on dual antiplatelet treatment, or on no treatment [4 (range 0-26), 13 (0-39), 8 (0-33), 3 (2-23) and 7 (0-33), respectively; p = 0.433]. Dependency rates were lower in patients on acenocoumarol with INR 2.0-3.0 or on dual antiplatelet treatment than in those on acenocoumarol with INR < 2.0, single antiplatelet treatment, or no treatment (20.0, 22.2, 61.5, 58.7 and 68.0 %, respectively; p = 0.024). Independent predictors of dependency were age, NIHSS at admission and history of ischemic stroke. In-hospital mortality did not differ between patients on acenocoumarol with INR 2.0-3.0, on acenocoumarol with INR < 2.0, on single antiplatelet treatment, on dual antiplatelet treatment, or on no treatment (7.7, 18.2, 16.1, 16.7 and 22.2 %, respectively; p = 0.822). In conclusion, optimally anticoagulated patients with AF have more favorable functional outcome after stroke and a trend for less severe stroke whereas patients with subtherapeutic anticoagulation have similar stroke severity and outcome with those on no treatment.

Cardiovascular Risk Prediction Models and Scores in the Era of Personalized Medicine.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Management of cardiovascular risk factors, particularly hypertension and dyslipidemia, has been shown to reduce cardiovascular morbidity and mortality. However, current guidelines recommend adjusting the intensity of blood pressure- and lipid-lowering treatment according to the cardiovascular risk of the patient. Therefore, cardiovascular risk prediction is a sine qua non for optimizing cardiovascular prevention strategies, particularly in patients without established CVD or type 2 diabetes mellitus (T2DM). As a result, several cardiovascular risk prediction equations have been developed. Nevertheless, it is still unclear which is the optimal prediction risk equation. In the present review, we summarize the current knowledge regarding the accuracy of the most widely used cardiovascular risk prediction equations. Notably, most of these risk scores have not been validated in external cohorts or were shown to over- or underestimate risk in populations other than those in which they derive. Accordingly, country-specific risk scores, where available, should be preferred for cardiovascular risk stratification.

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.

Using Serum Biomarkers for Identifying Unstable Carotid Plaque: Update of Current Evidence.

Carotid atherosclerosis is responsible for a great proportion of ischemic strokes. Early identification of unstable or vulnerable carotid plaques, and therefore, of patients at high risk for stroke, is of significant medical and socioeconomical value. We reviewed the current literature and discussed the potential role of the most important serum biomarkers in identifying patients with carotid atherosclerosis who are at high risk for atheroembolic stroke.

Oral Semaglutide, A New Option in the Management of Type 2 Diabetes Mellitus: A Narrative Review.

According to current guidelines, glucagon-like peptide-1 (GLP-1) receptor agonists are the antidiabetic agent of choice in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) and are also the preferable antidiabetic agent in patients with T2DM without CVD but with indicators of high cardiovascular risk. A limitation in the use of GLP-1 receptor agonists is that they are delivered by subcutaneous injections. In this context, the development of an orally administered formulation of semaglutide offers an additional option in the management of patients with T2DM. In the present review, we discuss the findings of the main trials that evaluated the safety and efficacy of oral semaglutide. Oral semaglutide appears to be more effective in reducing HbA1c levels and body weight than other antidiabetic agents and similarly effective to other GLP-1 receptor agonists. The safety profile of oral semaglutide is also comparable with other members of its class. Even though oral semaglutide did not reduce the incidence of the composite primary endpoint in a randomized controlled trial, a reduction in cardiovascular and all-cause mortality was observed. Therefore, oral semaglutide appears to represent a useful tool in the management of patients with TD2M, particularly those with established CVD or high cardiovascular risk and unwilling to receive injectable GLP-1 receptor agonists.

Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update.

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver disease worldwide. NAFLD progresses in some cases to non-alcoholic steatohepatitis (NASH), which is characterized, in addition to liver fat deposition, by hepatocyte ballooning, inflammation and liver fibrosis, and in some cases may lead to hepatocellular carcinoma. NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus (T2DM). Currently, lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used in the management of T2DM and do not have major side effects like hypoglycemia. In patients with NAFLD, the GLP-1 receptor production is down-regulated. Recently, several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation, alleviating the inflammatory environment and preventing NAFLD progression to NASH. In this review, we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH. Finally, as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD, we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.

Impaired antioxidative activity of high-density lipoprotein is associated with more severe acute ischemic stroke.

BACKGROUND/AIMS: High-density lipoprotein (HDL) has important anti-atherogenic functions, including antioxidant effects. However, it is unclear whether the antioxidative activity of HDL is associated with the severity and outcome of acute ischemic stroke. We aimed to evaluate this association. METHODS: We prospectively studied 199 consecutive patients admitted with acute ischemic stroke and followed them up until discharge. We measured HDL antioxidant capacity, HDL-associated paraoxonase-1 (PON1) activity and HDL-associated myeloperoxidase (MPO) levels. Severe stroke was defined as National Institutes of Health Stroke Scale (NIHSS) at admission ≥5. Dependency was defined as modified Rankin scale at discharge between 2 and 5. RESULTS: Patients with severe stroke had lower HDL antioxidant capacity, higher MPO levels and higher MPO/PON1 ratio. Independent risk factors for severe stroke were female gender (RR 2.80, 95% CI 1.37-5.70, p = 0.005), glucose levels (RR 1.01, 95% CI 1.0-1.02, p < 0.01) and HDL antioxidant capacity (RR 1.03, 95% CI 1.01-1.06, p < 0.05). Patients who were dependent at discharge had lower HDL antioxidant capacity, higher MPO levels and higher MPO/PON1 ratio. Independent predictors of dependency at discharge were lack of lipid-lowering treatment (RR 6.86, 95% CI 1.83-25.67, p < 0.005) and NIHSS (RR 1.56, 95% CI 1.29-1.88, p < 0.0001). The HDL antioxidant capacity did not differ between patients who died during hospitalization and those who were discharged. The only independent predictor of in-hospital mortality was NIHSS (RR 1.16, 95% CI 1.06-1.27, p < 0.005). CONCLUSIONS: Impaired antioxidative activity of HDL is associated with more severe acute ischemic stroke and might also predict a worse functional outcome in these patients.

Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease.

In the last decades, the role of inflammation in the pathogenesis of atherosclerosis has been the topic of intense research. Several markers of inflammation have shown predictive value for first and recurrent coronary events in patients without and with established Coronary Heart Disease (CHD). Among these markers, lipoprotein- associated phospholipase A2 (Lp-PLA2) has recently received considerable attention. In the present review, the potential role of Lp-PLA2 as a marker of CHD risk and as a therapeutic target is discussed. Elevated Lp- PLA2 mass and activity appears to be associated with increased risk for CHD, both in the general population and in patients with established CHD. However, it is unclear whether the measurement of Lp-PLA2 improves risk discrimination when incorporated in models that include traditional cardiovascular risk factors. Moreover, the lack of effect on CHD events of darapladib, a potent, selective Lp-PLA2 inhibitor, in two large, randomized, placebo-controlled trials and the mostly negative findings of genetic association studies suggest that Lp-PLA2 is unlikely to represent a causal factor in atherogenesis. Therefore, it is doubtful whether Lp-PLA2 will constitute a therapeutic target for the prevention of CHD.

Left ventricular hypertrophy assessed by electrocardiogram is associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke.

BACKGROUND AND AIMS: Left ventricular hypertrophy (LVH), assessed by electrocardiogram (ECG), is associated with increased risk for stroke. However, few studies that evaluated whether ECG-detected LVH predicts ischemic stroke severity and outcome. We aimed to evaluate these associations. METHODS: We prospectively studied 922 patients consecutively admitted with acute ischemic stroke (age 79.6 ±â€¯6.9 years). Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS≥5. LVH was evaluated with the Sokolow-Lyon index and the Cornell voltage-duration product criteria in an ECG obtained at admission. The outcome was assessed with dependency at discharge (modified Rankin scale 2-5) and in-hospital mortality. RESULTS: Independent predictors of severe stroke were age (relative risk (RR) per year 1.07, 95% confidence interval (CI) 1.03-1.11, p<0.001), female gender (RR 0.36, 95% CI 0.17-0.76, p<0.01), atrial fibrillation (RR 2.07, 95% CI 1.30-3.29, p<0.005), chronic kidney disease (RR 2.38, 95% CI 1.04-5.44, p<0.05), heart rate (RR per 1/min 1.02, 95% CI 1.01-1.04, p<0.005), glucose levels (RR 1.012, 95% CI 1.006-1.018, p<0.001), high-density lipoprotein cholesterol levels (RR 0.976, 95% CI 0.960-0.993, p<0.005) and LVH defined according to the Cornell voltage-duration product criteria (RR 2.08, 95% CI 1.12-3.86, p<0.05). Independent predictors of dependency at discharge were age (RR per year 1.08, 95% CI 1.03-1.13, p<0.001), past smoking (RR versus no smoking 0.42, 95% 0.19-0.89, p<0.05), history of ischemic stroke (RR 2.13, 95% CI 1.23-3.71, p<0.01) and NIHSS at admission (RR 1.48, 95% CI 1.35-1.63, p<0.001). Independent predictors of in-hospital mortality were glucose levels (RR 1.014, 95% CI 1.003-1.025, p<0.05), NIHSS at admission (RR 1.29, 95% CI 1.19-1.41, p<0.001) and LVH according to the Cornell voltage-duration product criteria (RR 4.95, 95% CI 1.09-22.37, p<0.05). CONCLUSIONS: LVH according to the Cornell voltage-duration product criteria appears to be associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke.

Is There a Role for Continuous Positive Airway Pressure Treatment in the Management of Obstructive Sleep Apnea-related Hypertension?

BACKGROUND: Obstructive sleep apnea (OSA) is a major cause of secondary hypertension. Moreover, a considerable proportion of patients with essential hypertension have OSA. OSA also appears to increase the risk for cardiovascular disease and all-cause mortality. Continuous positive airway pressure (CPAP) treatment substantially reduces daytime somnolence and improves quality of life in patients with OSA. However, the effects of CPAP treatment on blood pressure (BP) are questionable. The aim of the present review is to summarize the evidence regarding the association between OSA with hypertension and the effects of CPAP treatment on BP in patients with OSA. The severity of OSA directly correlates with the increase in BP. Moreover, patients with OSA are at increased risk for developing hypertension. However, CPAP treatment does not result in substantial reductions in BP in unselected patients with OSA with moderate adherence to this treatment. Nevertheless, these effects are more pronounced in patients with more severe hypertension, more severe OSA and more importantly, in those who adhere to CPAP treatment. CONCLUSION: Therefore, it is essential to improve the adherence to CPAP treatment in order to optimally manage this important cause of hypertension.

Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis (NASH). Since NASH progresses to cirrhosis more frequently and increases liver-related and cardiovascular disease risk substantially more than simple steatosis, there is a great need to differentiate the two entities. Liver biopsy is the gold standard for the diagnosis of NAFLD but its disadvantages, including the risk of complications and sampling bias, stress the need for developing alternative diagnostic methods. Accordingly, several non-invasive markers have been evaluated for the diagnosis of simple steatosis and NASH, including both serological indices and imaging methods. The present review summarizes the current knowledge on the role of these markers in the diagnosis of NAFLD. Current data suggest that ultrasound and the fibrosis-4 score are probably the most appealing methods for detecting steatosis and for distinguishing NASH from simple steatosis, respectively, because of their low cost and relatively high accuracy. However, currently available methods, both serologic and imaging, cannot obviate the need for liver biopsy for diagnosing NASH due to their substantial false positive and false negative rates. Therefore, the current role of these methods is probably limited in patients who are unwilling or have contraindications for undergoing biopsy.