Medical Management of Dyslipidemia for Secondary Stroke Prevention: Narrative Review.

Dyslipidemia is a major risk factor for stroke, following hypertension, diabetes, and smoking, and is an important risk factor for the prevention and treatment of coronary artery disease and peripheral vascular disease, including stroke. Recent guidelines recommend considering low-density lipoprotein cholesterol (LDL-C)-lowering therapies, such as statins (preferably), ezetimibe, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to prevent the occurrence or recurrence of stroke, adhering to the "lower is better" approach. In this review, we examined the evidence supporting lipid-lowering medications like statins, ezetimibe, and PCSK9 inhibitors for secondary stroke prevention and dyslipidemia management in different stroke subtypes. Stroke guidelines advocate for administering the maximum tolerable dose of statins as the primary treatment and as soon as possible despite the potential for new-onset diabetes mellitus and possible muscle and liver toxicity due to their demonstrated benefits in secondary prevention of cardiovascular diseases and mortality reduction. When statin use is insufficient for LDL lowering, ezetimibe and PCSK9 inhibitors are recommended as complementary therapies. It is essential to establish lipid-lowering therapy goals based on the stroke subtype and the presence of comorbidities.

Synergistic Effects of Sanghuang⁻Danshen Bioactives on Arterial Stiffness in a Randomized Clinical Trial of Healthy Smokers: An Integrative Approach to in silico Network Analysis.

The vascular endothelium is a favorite early target of cardiovascular risk factors, including cigarette smoking. Here, we investigated the synergistic effects of Sanghuang⁻Danshen (SD) bioactives on vascular stiffness in a controlled clinical trial of healthy chronic smokers (n = 72). Relative to placebo, 4-week SD consumption at 900 mg/day improves pulse wave velocity (p = 0.0497), reduces systolic blood pressure (peripheral, p = 0.0008; brachial, p = 0.0046; and ankle, p = 0.0066), and increases endothelial nitric oxide synthase activation (p < 0.0001). We then mapped all differential markers obtained from the clinical data, Affymetrix microarray, and ¹H NMR metabolomics, together with 12 SD bioactives, onto the network platform termed the context-oriented directed associations. The resulting vascular subnetwork demonstrates that ellagic acid, caffeic acid, protocatechuic acid, cryptotanshinone, tanshinone I, and tanshinone IIA are linked to NOS3, ARG2, and EDN1 for vascular dilation, implicated with arginine/proline metabolism. They are also linked to SUCLG1, CYP1A1, and succinate related to the mitochondrial metabolism and detoxification, implicated with various metabolic pathways. These results could explain the synergistic action mechanisms of SD bioactives in the regulation of vascular endothelial dilation and metabolism, confirming the potential of SD in improving vascular stiffness and blood pressure in healthy smokers.

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial.

Importance: In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. Objective: To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. Design, Setting, and Participants: A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. Interventions: Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. Main Outcomes and Measures: The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. Results: Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). Conclusions and Relevance: In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02042534.

Treatment Update of Chronic Migraine.

PURPOSE OF REVIEW: Although chronic migraine (CM) is a common disorder that severely impacts patient functioning and quality of life, it is usually underdiagnosed, and treatment responses often remain poor even after diagnosis. In addition, effective treatment options are limited due to the rarity of randomized controlled trials (RCTs) involving patients with CM. In the present review, we discuss updated pharmacological, non-pharmacological, and neurostimulation treatment options for CM. RECENT FINDINGS: Pharmacological treatments include both acute and preventive measures. While acute treatment options are similar between CM and episodic migraine (EM), preventive treatment with topiramate and botulinum toxin A exhibited efficacy in more than two RCTs. In addition, several studies have revealed that behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation techniques are associated with significant improvements in symptoms. Thus, these treatment options are recommended for patients with CM, especially for refractory cases. Neurostimulation procedures, such as occipital stimulation, supraorbital transcutaneous stimulation, non-invasive vagal nerve stimulation, and transcranial direct current stimulation, have shown promising results in the treatment of CM. However, current studies on neurostimulation suffer from small sample size, no replication, or negative results. Although CM is less responsive to treatment compared to EM, recent advance in pharmacological, non-pharmacological, and neurostimulation treatments may provide more chance for successful treatment of CM.

Low levels of plasma omega 3-polyunsaturated fatty acids are associated with cerebral small vessel diseases in acute ischemic stroke patients.

Cerebral small vessel diseases (SVDs) are related to stroke or cognitive dysfunction. n-3-polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) represent possible disease-modifying factors for cardiovascular disease or dementia. Our hypothesis was that a low proportion of plasma FAs would be associated with cerebral SVDs. We prospectively enrolled 220 patients with a first-episode cerebral infarction within 7 days after symptom onset. The composition of plasma FAs was analyzed by gas chromatography methods. The presence and burden of cerebral microbleeds (CMBs), high-grade white matter changes (HWCs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) were investigated. The mean proportion (± SD) was 2.0 ± 0.7 for EPA, 8.9 ± 1.5 for DHA, and 12.0 ± 2.1 for ∑ n-3-PUFAs. In total, 46 (20.9%) patients had CMBs, 64 (29.1 %) had HWCs, 57 (25.9%) had HPVSs, and 65 (29.5%) had ALIs. In univariate analyses, CMBs, HWCs, and HPVSs were each negatively correlated with the proportion of EPA, DHA, and ∑ n-3-PUFAs. In the multivariate analysis, a lower proportion of EPA, DHA and ∑ n-3-PUFAs was associated with the presence of CMBs, HWCs and HPVS, but not ALIs. Total SVDs score was inversely correlated with the proportion of EPA, DHA and ∑ n-3-PUFAs. Overall, we found an association between low proportions of plasma n-3-PUFAs and cerebral SVDs pathologies. Further studies are needed to explore the association and potential therapeutic role of FAs in cerebral SVDs.