Rosand, Jonathan M.

Background: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. Methods: This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable; 51–68 poor; 68–80.3 good; >80.3 excellent) were used to determine usability of PreventS-MD. Findings: Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. Interpretation: The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.

Abstract This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich‐club) brain regions on functional outcome post‐stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3‐months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI‐GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas‐defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non‐rich club regions. In spatial specificity analyses, we randomized the split into “rich club” and “non‐rich club” regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex‐specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female‐specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club‐combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long‐term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Background: Epsilon (e) variants in the Apolipoprotein E (APOE) gene are well-established risk factors for spontaneous intracerebral hemorrhage (s-ICH). We tested the hypothesis that APOE-e variants are also associated with warfarin-related ICH (w-ICH) and examined interactions between APOE and warfarin. Methods: Prospective multicenter 2-stage (discovery and replication) study. ICH was classified as lobar and non-lobar based on admission head CT. In the discovery stage, w-ICH cases were matched with warfarin-exposed controls (w-controls). In replication, w-ICH cases were matched with non-warfarin controls (nw-controls). APOE was directly genotyped. Association testing was performed using multivariable logistic regression. Gene-environment interaction between APOE and warfarin was formally tested using a case only approach (combining s-ICH and w-ICH cases). Results: The discovery stage included 316 w-ICHs (43% lobar and 57% non-lobar) and 355 w-controls. Results are presented in the Table: APOE-e2 was associated with lobar and non-lobar w-ICH, and APOE-e4 was associated with lobar but not with non-lobar w-ICH. In case-only analysis, 885 s-ICHs were combined with w-ICHs (total n=1201) and no evidence of interaction between APOE and warfarin was found (all p>0.20). The replication included 63 w-ICHs (44% lobar and 56% non-lobar) and 990 nw-controls. The distribution of APOE variants was similar in w-controls (discovery) and nw-controls (replication) for both e2 (p=0.81) and e4 (p=0.88). In replication, APOE-e2 and e4 were associated with lobar but not with non-lobar w-ICH. Conclusions: APOE-e variants constitute strong risk factors for lobar w-ICH. An effect may also exist between APOE-e2 and non-lobar hemorrhages, but given the lack of replication larger sample sizes are required to properly assess this association. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary.

Objectives: Genetic and environmental influences contribute to differences in ischemic stroke phenotype across race-ethnic groups. The Causative Classification System (CSS) is an ischemic stroke phenotype characterization tool developed for etiological and causative classification. The CCS phenotypes across ethnic groups were analyzed and compared. Methods: The NINDS S troke G enetics N etwork (SiGN) is a large consortium aimed at identifying subtype-specific ischemic stroke susceptibility genes. Over 12,000 subjects at 22 sites across US and Europe were enrolled, with CSS locally adjudicated. Central CCS quality control was performed on all participants. Analysis was performed on 7,674 patients with complete workups. Findings: Significant ethnic differences were found in stroke etiology across ethnic groups (p <0.0001) with large artery atherosclerosis present most commonly in Asians, cardioembolic sources among Caucasian Europeans, and lacunar strokes among African Americans. African Americans were the youngest ethnic cohort analyzed (see Table 1). Conclusion: Significant differences in stroke subtypes are present across ethnic groups. Future genetic analyses may contribute to our understanding of these differences.