A Clinical Update on Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke.

PURPOSE OF REVIEW: Antiplatelet therapy remains the standard of care in secondary stroke prevention for non-cardioembolic ischemic stroke and transient ischemic attack. We aim to examine the use of antiplatelet agents in secondary prevention through highlighting relevant clinical trials and meta-analyses as well as providing commentary regarding our practice. RECENT FINDINGS: In the POINT and CHANCE trials, dual antiplatelet therapy reduced recurrent stroke compared to aspirin monotherapy. Sub-analyses of these trials suggest that genetic polymorphisms could play a role in diminishing the effectiveness of clopidogrel. Similarly, THALES demonstrated better outcomes with ticagrelor-aspirin combination therapy over aspirin monotherapy. Combination antiplatelet therapy with aspirin and the P2Y12 inhibitors, clopidogrel and ticagrelor, reduced stroke recurrence in those presenting with mild ischemic stroke or high risk TIA. Genetic polymorphisms may play a role in determining the appropriate regimen. Questions remain regarding the optimal duration of combination antiplatelet therapy for various stroke etiologies.

Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions.

BACKGROUND: Reduced microbial diversity in human intestines has been implicated in various conditions such as diabetes, colorectal cancer, and inflammatory bowel disease. The role of physical fitness in the context of human intestinal microbiota is currently not known. We used high-throughput sequencing to analyze fecal microbiota of 39 healthy participants with similar age, BMI, and diets but with varying cardiorespiratory fitness levels. Fecal short-chain fatty acids were analyzed using gas chromatography. RESULTS: We showed that peak oxygen uptake (VO2peak), the gold standard measure of cardiorespiratory fitness, can account for more than 20 % of the variation in taxonomic richness, after accounting for all other factors, including diet. While VO2peak did not explain variation in beta diversity, it did play a significant role in explaining variation in the microbiomes' predicted metagenomic functions, aligning positively with genes related to bacterial chemotaxis, motility, and fatty acid biosynthesis. These predicted functions were supported by measured increases in production of fecal butyrate, a short-chain fatty acid associated with improved gut health, amongst physically fit participants. We also identified increased abundances of key butyrate-producing taxa (Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae) amongst these individuals, which likely contributed to the observed increases in butyrate levels. CONCLUSIONS: Results from this study show that cardiorespiratory fitness is correlated with increased microbial diversity in healthy humans and that the associated changes are anchored around a set of functional cores rather than specific taxa. The microbial profiles of fit individuals favor the production of butyrate. As increased microbiota diversity and butyrate production is associated with overall host health, our findings warrant the use of exercise prescription as an adjuvant therapy in combating dysbiosis-associated diseases.

Relationship between cerebral blood flow and blood pressure in long-term heart transplant recipients.

Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted.

Influence of posture on the regulation of cerebral perfusion.

BACKGROUND: Posture has a major influence on cerebral blood flow (CBF). Unlike head-up tilt (HUT), less is known about how CBF is regulated during head-down tilt (HDT). We hypothesized that CBF would be elevated during HDT and decreased during HUT. METHODS: In 21 healthy young adults, while controlling for end-tidal Pco2, we combined concurrent measurements of middle cerebral artery velocity and posterior cerebral artery velocity (MCAv and PCAv, respectively), blood pressure (BP), and heart rate (HR). Measures were made at rest and, in a randomized order, during -90 degrees HDT and +900 HUT. Dynamic cerebral autoregulation was quantified using transfer function analysis. In a subgroup, volumetric blood flow recordings were obtained in the common carotid artery (CCA; N=11), internal and external carotid arteries (ICA; N=8 and ECA; N=6), and vertebral artery (VA; N=4). RESULTS: End-tidal Pco2, CCA, ICA, VA, MCAv(mean) and PCAv(mean) remained unchanged during -90 degrees HDT and +90 degrees HUT compared to supine. During -90 degrees HDT, mean BP (+22 mmHg) and cerebral vascular resistance (CVR) in both the MCA and PCA were elevated relative to supine, whereas HR remained unchanged. During +900 HUT, when compared to supine, HR increased (+18 bpm), and mean arterial pressure (MAP) total power and low frequency (LF) power in the MCA and PCA increased. In both the very low frequency (VLF) and LF ranges, coherence during +90 degrees HUT increased (P < 0.05 vs. supine) in both the MCA and PCA. In contrast, coherence was reduced during -90 degrees HDT. DISCUSSION: Despite marked changes in perfusion pressure with HUT or HDT, our findings indicate that cerebral perfusion is well maintained during acute severe changes in posture.