Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study

Background: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. Methods: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. Results: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). Conclusions: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke.publishedVersio

O Treinamento deve ser um Processo Vivo: uma entrevista com Torgeir Wethal

O Treinamento deve ser um Processo Vivo: uma entrevista com Torgeir Wetha

O Treinamento deve ser um Processo Vivo: uma entrevista com Torgeir Wethal

O Treinamento deve ser um Processo Vivo: uma entrevista com Torgeir Wetha

L’Entraînement doit Rester un Processus Vivant: un entretien avec Torgeir Wethal

Entretien.L’Entraînement doit Rester un Processus Vivant: un entretien avec Torgeir Wetha

Accelerometer-measured physical activity at 3 months as a predictor of symptoms of depression and anxiety 1 year after stroke: a multicentre prospective cohort study in central Norway

Objectives: To study sedentary behaviour and physical activity at 3 months as predictors for symptoms of depression and anxiety at 1-year post-stroke. Design: A prospective cohort study. Patients: Patients with first-ever ischaemic stroke. Methods: Mood was assessed 3- and 12-months post-stroke using the Hospital Anxiety and Depression Scale. Sedentary behaviour and physical activity were measured using accelerometry 3 months post-stroke. Results: A total of 292 participants (116 (39.7%) females; mean age 71.7 (standard deviation 11.3) years) were included. At 12 months, 16.7% experienced depression and 19.5% anxiety, respectively. Adjusting for age and sex, regression analysis showed that comorbidity burden (β 0.26; 95% confidence interval (95% CI) 0.02, 0.51; p = 0.038), stroke severity (β 0.22; 95% CI 0.10, 0.35; p = 0.001), functional disability (β 0.89, 95% CI 0.49, 1.30; p = 0.000), and global cognition (β–0.15; 95% CI –0.25, –0.05; p = 0.004) predicted depression. Multi-adjusted analysis showed sedentary behaviour and physical activity did not significantly predict depression or anxiety (p > 0.05). Conclusion: Sedentary behaviour and physical activity did not significantly predict mood after stroke. Comorbidity burden, stroke severity, functional disability, and global cognition were identified as possible predictors of depression. More research is needed to determine the impact of physical activity on depression and anxiety symptoms

ABCD3-I and ABCD2 Scores in a TIA Population with Low Stroke Risk

Objectives. We aimed to evaluate the ABCD3-I score and compare it with the ABCD2 score in short- (1 week) and long-term (3 months; 1 year) stroke risk prediction in our post-TIA stroke risk study, MIDNOR TIA. Materials and Methods. We performed a prospective, multicenter study in Central Norway from 2012 to 2015, enrolling 577 patients with TIA. In a subset of patients with complete data for both scores (), we calculated the AUC statistics of the ABCD3-I score and compared this with the ABCD2 score. A telephone follow-up and registry data were used for assessing stroke occurrence. Results. Within 1 week, 3 months, and 1 year, 1.0% (), 3.3% (), and 5.2% () experienced a stroke, respectively. The AUCs for the ABCD3-I score were 0.72 (95% CI, 0.54 to 0.89) at 1 week, 0.66 (95% CI, 0.53 to 0.80) at 3 months, and 0.68 (0.95% CI, 0.56 to 0.79) at 1 year. The corresponding AUCs for the ABCD2 score were 0.55 (95% CI, 0.24 to 0.86), 0.55 (95% CI, 0.42 to 0.68), and 0.63 (95% CI, 0.50 to 0.76). Conclusions. The ABCD3-I score had limited value in a short-term prediction of subsequent stroke after TIA and did not reliably discriminate between low- and high-risk patients in a long-term follow-up. The ABCD2 score did not predict subsequent stroke accurately at any time point. Since there is a generally lower stroke risk after TIA during the last years, the benefit of these clinical risk scores and their role in TIA management seems limited. Clinical Trial Registration. This trial is registered with NCT02038725 (retrospectively registered, January 16, 2014)

ABCD3-I and ABCD2 Scores in a TIA Population with Low Stroke Risk

Objectives. We aimed to evaluate the ABCD3-I score and compare it with the ABCD2 score in short- (1 week) and long-term (3 months; 1 year) stroke risk prediction in our post-TIA stroke risk study, MIDNOR TIA. Materials and Methods. We performed a prospective, multicenter study in Central Norway from 2012 to 2015, enrolling 577 patients with TIA. In a subset of patients with complete data for both scores (n=305), we calculated the AUC statistics of the ABCD3-I score and compared this with the ABCD2 score. A telephone follow-up and registry data were used for assessing stroke occurrence. Results. Within 1 week, 3 months, and 1 year, 1.0% (n=3), 3.3% (n=10), and 5.2% (n=16) experienced a stroke, respectively. The AUCs for the ABCD3-I score were 0.72 (95% CI, 0.54 to 0.89) at 1 week, 0.66 (95% CI, 0.53 to 0.80) at 3 months, and 0.68 (0.95% CI, 0.56 to 0.79) at 1 year. The corresponding AUCs for the ABCD2 score were 0.55 (95% CI, 0.24 to 0.86), 0.55 (95% CI, 0.42 to 0.68), and 0.63 (95% CI, 0.50 to 0.76). Conclusions. The ABCD3-I score had limited value in a short-term prediction of subsequent stroke after TIA and did not reliably discriminate between low- and high-risk patients in a long-term follow-up. The ABCD2 score did not predict subsequent stroke accurately at any time point. Since there is a generally lower stroke risk after TIA during the last years, the benefit of these clinical risk scores and their role in TIA management seems limited. Clinical Trial Registration. This trial is registered with NCT02038725 (retrospectively registered, January 16, 2014)

Risk Stratification in Patients with Ischemic Stroke and Residual Cardiovascular Risk with Current Secondary Prevention

Purpose: Suboptimal secondary prevention in patients with stroke causes a remaining cardiovascular risk desirable to reduce. We have validated a prognostic model for secondary preventive settings and estimated future cardiovascular risk and theoretical benefit of reaching guideline recommended risk factor targets. Patients and Methods: The SMART-REACH (Secondary Manifestations of Arterial Disease-Reduction of Atherothrombosis for Continued Health) model for 10-year and lifetime risk of cardiovascular events was applied to 465 patients in the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, a multicenter observational study with twoyear follow-up by linkage to national registries for cardiovascular disease and mortality. The residual risk when reaching recommended targets for blood pressure, low-density lipoprotein cholesterol, smoking cessation and antithrombotics was estimated. Results: In total, 11.2% had a new event. Calibration plots showed adequate agreement between estimated and observed 2-year prognosis (C-statistics 0.63, 95% confidence interval 0.55–0.71). Median estimated 10-year risk of recurrent cardiovascular events was 42% (Interquartile range (IQR) 32–54%) and could be reduced to 32% by optimal guidelinebased therapy. The corresponding numbers for lifetime risk were 70% (IQR 63–76%) and 61%. We estimated an overall median gain of 1.4 (IQR 0.2–3.4) event-free life years if guideline targets were met. Conclusion: Secondary prevention was suboptimal and residual risk remains elevated even after optimization according to current guidelines. Considerable interindividual variation in risk exists, with a corresponding variation in benefit from intensification of treatment. The SMART-REACH model can be used to identify patients with the largest benefit from more intensive treatment and follow-up

Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial

Background Recent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt in potentially life-saving adjuvant cancer therapy. Early initiated neurohormonal blockade may prevent or attenuate the cardiotoxicity-induced reduction in cardiac function, but prior studies have been inconclusive. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to be superior to traditional treatment in heart failure with reduced ejection fraction, but its cardioprotective effects in the cardio-oncology setting remains to be tested. Objective To assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. Methods PRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations. Results The study is ongoing. Results will be published when the study is completed. Conclusion PRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy. Trial registration The trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588). Registered 30 November 2018