Stroke prevention: recent achievements and new challenges

Stroke remains a major health problem despite the great efforts made worldwide to fight against it. Despite therapeutic achievements to treat ischemic stroke patients in stroke units with tissue plasminogen activator (tPA), prevention remains the most powerful strategy to cure this complex disease. Stroke is a heterogeneous and multi-factorial disease caused by the combination of vascular risk factors, environment, and genetic factors. These risk factors can be subdivided into non-modifiable (age, sex, race-ethnicity, genetic variations and predispositions) and modifiable (hypertension, diabetes, dyslipidemia, atrial fibrillation, carotid artery stenosis, smoking, poor diet, physical inactivity and obesity). The metabolic syndrome, a cluster of metabolic risk factors within an individual, has been recognized as and important factor associated with an increased risk of stroke. Recently, a great emphasis has been given to the investigations of genetic factors and stroke risk, which may lead to the discovery of new biomarkers for prevention, diagnosis and to the alternative strategies for stroke treatment. In this review we sought to discuss the main risk factors for stroke and the current strategies of stroke prevention

Neurozaštita u akutnom moždanom udaru: ima li još nade?

Efficacious treatment of acute stroke is a major challenge in modern medicine. Therapeutic neuroprotection acting towards minimization of ischemic neuronal injury in penumbral tissue in the regions of reduced cerebral blood flow seems to be an appealing concept in the treatment of acute stroke and brain trauma. The ‘ischemic cascade’, a complex mechanism of metabolic events initiated by brain ischemia, offers many pathways by which the neuroprotective agents may act. Time to treatment remains a major limiting factor for many potential neuroprotective agents. Although the exact therapeutic window is not known, evidence from many animal models and clinical research suggest that neuroprotective therapy can only be efficacious if administered very early after the onset of ischemia. Various neuroprotective agents have been tested in many clinical stroke trials during the past 20 years. Large phase III clinical trials of several classes of neuroprotectants (mainly NMDA receptor antagonists, free radical scavengers, and calcium channel blockers) have recently failed to demonstrate efficacy of neuroprotection. After initial disappointment, the active research continues and some new exciting neuroprotective models emerge on the horizon.Učinkovito liječenje akutnog moždanog udara velik je izazov u suvremenoj medicini. Terapijska neurozaštita kojom bi se ishemijsko neuronsko oštećenje u tkivu penumbre u područjima smanjenog moždanog krvnog protoka svelo na najmanju moguću mjeru čini se primamljivom zamisli u liječenju akutnog moždanog udara i moždane traume. ‘Ishemijska kaskada’, odnosno složen mehanizam metaboličnih događaja što ih potiče moždana ishemija, nudi mnoštvo putanja kojima bi neurozaštitna sredstva mogla djelovati. Vrijeme proteklo do početka liječenja ostaje glavnim ograničavajućim čimbenikom za mnoga potencijalna neurozaštitna sredstva. Iako točan terapijski prozor nije poznat, rezultati dobiveni u mnogobrojnim životinjskim modelima i kliničkim istraživanjima ukazuju na to da bi neurozaštitna terapija mogla biti učinkovita samo ako se dade vrlo rano nakon nastupa ishemije. Tijekom posljednjih 20 godina različita neurozaštitna sredstva ispitivana su u moždanom udaru u mnogim kliničkim pokusima. Nedavno provedeni veliki klinički pokusi III. faze s nekoliko skupina neurozaštitnih sredstava (uglavnom antagonista NMDA receptora, čistača slobodnih radikala i blokatora kalcijevih kanala) nisu dokazali učinkovitost neurozaštite. Nakon prvotnog razočaranja djelatna se istraživanja nastavljaju, a na obzoru se naziru neki novi i uzbudljivi modeli neurozaštite

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Previous data showed that PFOs not detected by high-quality transthoracic echocardiography are smaller and associated with small right-to-left shunts (4); therefore, they are far less likely to be associated with embolic stroke features (5)

Construct Validity of Cognitive Reserve in a Multiethnic Cohort: The Northern Manhattan Study

Cognitive reserve is a hypothetical construct that has been used to inform models of cognitive aging and is presumed to be indicative of life experiences that may mitigate the effects of brain pathology. The purpose of this study was to evaluate the construct validity of cognitive reserve by examining both its convergent and its discriminant validity across three different samples of participants using structural equation modeling. The cognitive reserve variables were found to correlate highly with one another (thereby providing evidence of convergent validity), but demanding tests of discriminant validity indicated that, in two of the samples, the cognitive reserve construct was highly related to an executive functioning construct

Predicting long-term outcome after acute ischemic stroke: a simple index works in patients from controlled clinical trials

Background and Purpose—An early and reliable prognosis for recovery in stroke patients is important for initiation of individual treatment and for informing patients and relatives. We recently developed and validated models for predicting survival and functional independence within 3 months after acute stroke, based on age and the National Institutes of Health Stroke Scale score assessed within 6 hours after stroke. Herein we demonstrate the applicability of our models in an independent sample of patients from controlled clinical trials. Methods—The prognostic models were used to predict survival and functional recovery in 5419 patients from the Virtual International Stroke Trials Archive (VISTA). Furthermore, we tried to improve the accuracy by adapting intercepts and estimating new model parameters. Results—The original models were able to correctly classify 70.4% (survival) and 72.9% (functional recovery) of patients. Because the prediction was slightly pessimistic for patients in the controlled trials, adapting the intercept improved the accuracy to 74.8% (survival) and 74.0% (functional recovery). Novel estimation of parameters, however, yielded no relevant further improvement. Conclusions—For acute ischemic stroke patients included in controlled trials, our easy-to-apply prognostic models based on age and National Institutes of Health Stroke Scale score correctly predicted survival and functional recovery after 3 months. Furthermore, a simple adaptation helps to adjust for a different prognosis and is recommended if a large data set is available. (Stroke. 2008;39:000-000.

Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke.

BackgroundThe National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied.Methods and resultsWe analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]).ConclusionsThe NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.)

Rizik neželjenih događaja kod bolesnika s otvorenim foramen ovale liječenih lijekovima: pregled literature

Patent foramen ovale is associated with stroke. However, the rate of recurrent events in medically treated patients with patent foramen ovale remains undefined. Estimates differ by the studies. In order to provide a more accurate estimate of the recurrent adverse event rates in medically treated patients with patent foramen ovale, we reviewed the literature and analyzed the results from a total of 1,108 patients combining 12 studies. We found the annual rate of stroke or death to be 3.12% (95% CI, 2.32-4.11%). This estimate will provide a valuable guideline for any future study to compare the efficacy of other modalities such as percutaneous device closure of patent foramen ovale with medical treatment.Otvoreni foramen ovale (OFO) udružen je s moždanim udarom. Međutim, učestalost rekurentnih neželjenih događaja u bolesnika liječenih lijekovima s otvorenim foramen ovale nije poznata, a procjene iz različitih studija se razlikuju. Stoga smo obavili pregled literature i analizirali rezultate za ukupno 1.108 bolesnika iz 12 studija, kako bismo dobili točniju procjenu učestalosti neželjenih događaja u bolesnika s otvorenim foramen ovale liječenih lijekovima. Utvrdili smo godišnju stopu moždanog udara ili smrti od 3,12% (95% CI, 2,32-4,11%). Ova će procjena poslužiti kao vrijedna smjernica za buduća ispitivanja u kojima će se uspoređivati učinkovitost drugih načina liječenja, primjerice, zatvaranje otvorenog foramen ovale pomoću perkutanog uređaja uz medikamentno liječenje

Socioeconomic Status, Psychosocial Factors, Race and Nocturnal Blood Pressure Dipping in a Hispanic Cohort

BACKGROUND Little information is available about the relationship of socioeconomic status (SES) to blunted nocturnal ambulatory blood pressure (ABP) dipping among Hispanics and whether this relationship differs by race. We sought to characterize ABP nondipping and its determinants in a sample of Hispanics. METHODS We enrolled 180 Hispanic participants not on antihypertensive medications. SES was defined by years of educational attainment. All participants underwent 24-hour ABP monitoring. A decrease of <10% in the ratio between average awake and average asleep systolic BP was considered nondipping. RESULTS The mean age of the cohort was 67.1 ± 8.7, mean educational level was 9.4 ± 4.4 years, and 58.9% of the cohort was female. The cohort was comprised of 78.3% Caribbean Hispanics with the rest from Mexico and Central/South America; 41.4% self-identified as white Hispanic, 34.4% self-identified as black Hispanic, and 24.4% did not racially self- identify. The percentage of nondippers was 57.8%. Educational attainment (10.5 years vs. 8.6 years; P <0.01) was significantly higher among dippers than nondippers. In multivariable analyses, each 1-year increase in education was associated with a 9% reduction in the likelihood of being a nondipper (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84–0.98; P = 0.01). There were significantly greater odds of being a nondipper for black Hispanics than for white Hispanics (OR, 2.83, 95% CI, 1.29–6.23; P = 0.005). Higher SES was significantly protective of nondipping in white Hispanics but not black Hispanics. CONCLUSIONS These results document a substantial prevalence of nondipping in a cohort of predominantly normotensive Hispanics. Dipping status varied significantly by race. Lower SES is significantly associated with nondipping status, and race potentially impacts on this relation