Hemostasis biomarkers and incident cognitive impairment: the REGARDS study

Essentials Cognitive disorders are increasing and vascular risk factors play a role in this. We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI). Higher baseline fibrinogen, factor VIII and D-dimer were related to incident CI over 3.5 years. Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk. SUMMARY: Background Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment. Methods We performed a nested case-control study including 1082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on two or more of three cognitive tests) and 587 controls. Results Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02-1.70) for D-dimer > 0.50 μg mL-1 , 1.83 (95% CI 1.24-2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11-2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73-1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10-2.69). Conclusion Elevated D-dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant

Scherk-Schwarz Supersymmetry Breaking for Quasi-localized Matter Fields and Supersymmetry Flavor Violation

We examine the soft supersymmetry breaking parameters induced by the Scherk-Schwarz (SS) boundary condition in 5-dimensional orbifold field theory in which the quark and lepton zero modes are quasi-localized at the orbifold fixed points to generate the hierarchical Yukawa couplings. In such theories, the radion corresponds to a flavon to generate the flavor hierarchy and at the same time plays the role of the messenger of supersymmetry breaking. As a consequence, the resulting soft scalar masses and trilinear $A$-parameters of matter zero modes at the compactification scale are highly flavor-dependent, thereby can lead to dangerous flavor violations at low energy scales. We analyze in detail the low energy flavor violations in SS-dominated supersymmetry breaking scenario under the assumption that the compactification scale is close to the grand unification scale and the 4-dimensional effective theory below the compactification scale is given by the minimal supersymmetric standard model. Our analysis can be applied to any supersymmetry breaking mechanism giving a sizable $F$-component of the radion superfield, e.g. the hidden gaugino condensation model.Comment: revtex4, 22 pages, some numerical errors are corrected in phenomenological analysis, main conclusion does not chang

Adherence to a Mediterranean diet and risk of incident cognitive impairment

Objective: We sought to determine the relationship of greater adherence to Mediterranean diet (MeD) and likelihood of incident cognitive impairment (ICI) and evaluate the interaction of race and vascular risk factors. Methods: A prospective, population-based, cohort of individuals enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 2003-2007, excluding participants with history of stroke, impaired cognitive status at baseline, and missing data on Food Frequency Questionnaires (FFQ), was evaluated. Adherence to a MeD (scored as 0-9) was computed from FFQ. Cognitive status was evaluated at baseline and annually during a mean follow-up period of 4.0 ± 1.5 years using Six-item-Screener. Results: ICI was identified in 1,248 (7%) out of 17,478 individuals fulfilling the inclusion criteria. Higher adherence to MeD was associated with lower likelihood of ICI before (odds ratio [lsqb]OR [rsqb] 0.89; 95%confidence interval [lsqb]CI[rsqb] 0.79-1.00) and after adjustment for potential confounders (OR 0.87; 95% CI 0.76-1.00) including demographic characteristics, environmental factors, vascular risk factors, depressive symptoms, and self-reported health status. There was no interaction between race (p = 0.2928) and association of adherence to MeD with cognitive status. However, we identified a strong interaction of diabetes mellitus (p = 0.0134) on the relationship of adherence to MeD with ICI; high adherence to MeD was associated with a lower likelihood of ICI in nondiabetic participants (OR 0.81; 95%CI 0.70-0.94; p = 0.0066) but not in diabetic individuals (OR 1.27; 95% CI 0.95-1.71; p = 0.1063). Conclusions: Higher adherence to MeD was associated with a lower likelihood of ICI independent of potential confounders. This association was moderated by presence of diabetes mellitus. © 2013 American Academy of Neurology

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)