Aims To estimate prevalence of atrial fibrillation (AF) in a representative sample of the Italian elderly population, projecting figures for Italy and the European Union. Methods and results A cross-sectional examination of all subjects aged 65+ years from three general practices in Northern, Central, and Southern Italy started in 2016. Participants were administered a systematic and an opportunistic screening, followed by clinical and electrocardiogram confirmation. The study sample included 6016 subjects. Excluding 235 non-eligible, among the remaining 5781 participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Prevalence of AF was 7.3% [95% confidence intervals (CI) 6.6–8.1], higher in men and with advancing age (6.6% from systematic plus 0.7% from opportunistic screening). Using prevalence figures, Italian elderly having AF in 2016 were estimated at ∼1 081 000 (95% CI 786 000–1 482 000). Considering stable prevalence, this number will increase by 75% to ∼1 892 000 in 2060 (95% CI 1 378 000–2 579 000). European Union elderly having AF in 2016 were estimated at ∼7 617 000 (95% CI 5 530 000–10 460 000), increasing by 89% to ∼14 401 000 in 2060 (95% CI 10 489 000–19 647 000). In 2016, subjects aged 80+ years represented 53.5% of cases in Italy and 51.2% in the European Union; in 2060, 69.6% and 65.2%, respectively. Conclusions Our findings indicate a high burden of AF in coming decades, especially among the oldest-old, who carry the higher AF-related risk of stroke and medical complications.

Lacunar stroke is generally considered to have a fair outcome. However 20-30% of patients with lacunar stroke worsen neurologically in hours or days after onset, reaching eventually an unexpectedly severe disability status. In the field of acute stroke, progressive lacunar stroke remains an important unresolved practice problem, because as yet no treatment does exist proven to prevent or halt progression. Pathophysiology of progression is yet incompletely understood. Hemodynamic factors, extension of thrombosis, excitotoxicity, and inflammation, have been proposed as possible mechanisms of progression. A few clinical studies also aimed at establishing presentation features that may help identifying patients at risk of deterioration. In this paper, we review hypothesized mechanisms of lacunar stroke progression and possible markers of early deterioration. Moreover, based on putative mechanisms and suggestions from reported evidence, we propose a few treatments that seem worthy to be tested by randomized clinical trials.

Eligible were patients admitted for thrombolysis in 14 Italian centers and were registered in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR), according to SITS-Monitoring Study criteria. 6 Study protocol was approved from each ethical committee, and all patients gave informed consent.Background and Purpose-Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods-We measured MMPs 1, 2, 3,7,8, 9, and Blood samples were taken before and 24 hours after tPA. Outcomes were defined as follows: (1) symptomatic intracerebral hemorrhage (SICH), using the National Institute of Neurological Disorders and Stroke criteria; 7 (2) 3-month death; (3) modified Rankin disability score, dichotomized into good (modified Rankin scale, 0-2) or poor (modified Rankin scale, 3-6) outcome. As a main explanatory variable, we used single patient's relative pre-and post-thrombolysis variation (Δ median value) of both MMPs and TIMPs levels, calculated according to the formula: (24-hour post-tPA MMP or TIMP-pre-tPA MMP or TIMP)/pre-tPA MMP or TIMP. Differences in these Δ values were analyzed in relation to demographic and clinical features and across subgroups of patients with different outcomes. Methods details are in the online-only Data Supplement. ResultsBetween October 2008 and June 2011, 534 patients were registered in the SITS-ISTR, of whom 327 (mean age, 68.9±12.1 years; 58% males) were investigated. The remaining 207 were not studied because of not fulfilling SITS-MOST criteria, not giving consent, blood samples not taken or not stored appropriately, outcomes not assessed, and other protocol violations. Except for onset-to-treatment time, the prevalence of major outcomes determinants did not differ significantly between the 2 groups (demographics and clinical characteristics of both groups are in Table I in the online-only Data Supplement).Absolute TIMPs or MMPs measures taken before thrombolysis and 24 hours after are reported in the Table II in the online-only Data Supplement.The Figure shows pre-and post-thrombolysis changes of each MMP and TIMP level measured in patients with and without SICH, in patients who died and in those who survived, and in patients scoring 3 to 6 or 0 to 2 on the 3-month modified Rankin scale. MMP9, TIMP4, and MMP2 level changes showed a tendency toward the association with SICH. Variations of MMP8, MMP9, and TIMP1 levels were significantly associated with death, whereas variations of MMP8, MMP9, and TIMP4 levels were associated with scoring 3 to 6 on the 3-month modified Rankin scale. Grading of hemorrhage severity (according to the European Cooperative Acute Stroke Study II criteria) in the 27 patients with SICH is shown in Table III in the online-only Data Supplement. The association of MMP9 level variation with he...

Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19-7.53); SAP:5.46 (1.64-18.74); Δmetalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.