Abstract
Only few follow-up studies have studied in detail the role of most important risk factors, but no reports were found on critical values (cut-offs) for such factors in prospectively predicting cerebrovascular events (CVE) in patients with minor ischaemic stroke (MIS). Estimates of predictive importance of such cut-offs may better inform and contribute to optimize treatment. This was a post-hoc modelling study with unique data from Bulgaria on 54 consecutive patients with MIS, aged ł 40, followed for 12 months for nonfatal or fatal CV events. A set of routine clinical demographic and known risk factors (SBP, DBP, HDL cholesterol, etc.) were explored using univariate statistics and multivariate regression models to identify the most important independent predictors of secondary CVE. An artificial neural network (ANN) model, irrespective of usual statistical constraints, also confirmed the specific role and importance of identified predictors. A receiver operating characteristics (ROC) curve and stratified survival analyses were used to define the best cut-off of most important predictors and validate the final model. During follow-up period of 11.1±2.4 months, 8 secondary CV events (14.8%) were observed only in males with MIS at the 5.8±2.7 months mark. No difference in age of patients with CV event (61.1±12.6 years) vs. those without (62.1±9.6 years) was found (p>0.05). The one-year risk for CVE was.15% (95%CI 7.1, 27.7%). The two most important risk factors in patients with versus without CV events were acute MIS onset (62.5 vs. 13.0%) and mean DBP at day 30 post-MIS (101.3±9.9 vs. 92.3±10.8 mmHg), with a relative importance by ANN of 20.92 versus 15.9 points, respectively. At multivariate logistic analysis only MIS onset and DBP were independently associated with the risk for secondary CVE (79.6% model accuracy, p model=0.0015). An increase of DBP with 1 mmHg was associated with 8% higher risk of CVE [adjusted OR=1.08 (95%Cl 1.004, 1.158)]. With this method, a novel cut-off predictive DBP value of 95 mmHg (ROCAUC=0.79, 95%Cl 0.60, 0.99, p=0.009) for CV events in patients with MIS has been found. In conclusions the new DBP cut-off (sensitivity >87%, specificity >69%) clearly discriminated between absence and presence of secondary CVE as also confirmed by stratified survival analysis (7 vs. 1 events, plog-rank =0.0103). This cut-off may be applied to better precisely evaluate and define, as earlier as possible, MIS patients at increased risk of secondary CV events.
[1] De Reuck J., De Groote L., Van Maele G., Delayed transient worsening of neurological deficits after ischaemic stroke, Cerebrovasc. Dis., 2006, 22, 27–32 http://dx.doi.org/10.1159/00009233410.1159/000092334Search in Google Scholar PubMed
[2] Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), JAMA, 2001, 285, 2486–97 10.1001/jama.285.19.2486Search in Google Scholar PubMed
[3] Grundy S.M., Cleeman J.I., Merz C.N., Brewer H.B.Jr., Clark L.T., Hunninghake D.B., et al., Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines, Circulation 2004, 110, 227–239 http://dx.doi.org/10.1161/01.CIR.0000133317.49796.0E10.1161/01.CIR.0000133317.49796.0ESearch in Google Scholar PubMed
[4] Ross G.W., Petrovitch H., White L.R., Masaki K.H., Li C.Y., Curb J.D., et al., Characterization of risk factors for vascular dementia: the Honolulu-Asia Aging Study, Neurology, 1999, 53, 337–343 10.1212/WNL.53.2.337Search in Google Scholar PubMed
[5] Tatemichi T.K., Desmond D.W., Paik M., Figueroa M., Gropen T.I., Stern Y., et al., Clinical determinants of dementia related to stroke, Ann. Neurol., 1993, 33, 568–575 http://dx.doi.org/10.1002/ana.41033060310.1002/ana.410330603Search in Google Scholar PubMed
[6] Albers G.W., Choice of endpoints in antiplatelet trials: which outcomes are most relevant to stroke patients? Neurology, 2000, 54, 1022–1028 10.1212/WNL.54.5.1022Search in Google Scholar
[7] Atanassova P.A., Chalakova N.T., Dimitrov B.D., Major vascular events after transient ischaemic attack and minor ischaemic stroke: post-hoc modelling of incidence dynamics. Cerebrovasc Dis, 2008, 25, 225–233 http://dx.doi.org/10.1159/00011386010.1159/000113860Search in Google Scholar PubMed
[8] Atanasova P., Vukov M., Probability for arising of a repeated vascular incident after the primary brain infarction, with a complete clinical repair. Social Medicine 1998, 1, 19–20 Search in Google Scholar
[9] Atanassova P., Voukov M., Tchalakova N., Prediction models for probable subsequent cerebral events in patients with reversible ischaemic neurological deficit, Cerebrovasc. Dis., 2002, 2, 10–15 Search in Google Scholar
[10] Atanassova P., Clinical and Electrophysiological Study of Patients with Minor Stroke, D.M. Thesis, MU-Plovdiv, Bulgaria, 1998 Search in Google Scholar
[11] Atanassova P.A., Angelova E., Tzvetanov P., Semerdjieva M., Dimitrov B.D., Modelling of increased homocysteine in ischaemic stroke, Arq. Neuropsiquiatr., 2007, 65, 24–31 10.1590/S0004-282X2007000100007Search in Google Scholar
[12] Bamford J., Sandercock P., Dennis M., Burn J., Warlow C., A prospective study of acute cerebrovascular disease in the community: The Oxfordshire Community Stroke Project 1981–1986. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoidal haemorrhage, J. Neurol. Neurosurg. Psychiatry, 1990, 53, 16–22 10.1136/jnnp.53.1.16Search in Google Scholar PubMed PubMed Central
[13] Dimitrov B.D., Assessment of the dynamics in the spread of some malignant neoplasms in Bulgaria: nonlinear prognostic models, D.M. Thesis, MU-Plovdiv, Bulgaria, 2006 Search in Google Scholar
[14] Sarle W.S. (ed), Neural Network FAQ, part 1 of 7. Introduction, periodic posting to the Usenet newsgroup comp.ai.neural-nets URL: ftp://ftp.sas.com/pub/neural/FAQ.html, 1997 Search in Google Scholar
[15] Velcheva I., Tzoneva-Pencheva T., Yancheva S., Hadjiev D., Risk factors in cerebrovascular disease in Bulgaria. In: Cerebral stroke. Ways for prophylactics in Bulgaria. Working Meeting 2/94, Sofia, 1994, 45–64. Search in Google Scholar
[16] Lechner H., Hadjiev D., Epidemiology of cerebrovascular risk factors in South-East Europe. In: Book of Abstracts. 11th Thessaloniki Conference, Thessaloniki, Greece, 25–28 September 1996 Search in Google Scholar
[17] Calandre L., Bermejo F., Balseiro J., Long-term outcome of TIAs, RINDs and infarctions with minimum residium. A prospective study in Madrid, Acta Neurol. Scand., 1990, 82, 104–108 http://dx.doi.org/10.1111/j.1600-0447.1990.tb05299.x10.1111/j.1600-0447.1990.tb05299.xSearch in Google Scholar PubMed
[18] Wiebers D.O., Whisnant J.P., O’Fallon W.M., Reversible ischemic neurologic deficit (RIND) in a community: Rochester, Minnesota, 1955–1974, Neurology, 1982, 32, 459–465 10.1212/WNL.32.5.459Search in Google Scholar
[19] Bamford J., Sandercock P., Jones L., Warlow C.P., The natural history of lacunar infarction: The Oxfordshire Community Stroke Project, Stroke, 1987, 18, 545–551 10.1161/01.STR.18.3.545Search in Google Scholar
[20] Hier D.B., Foulkes M.A., Swiontoniowski M., Sacco R.L., Gorelick P.B., Mohr J.P., Stroke recurrence within 2 years after ischemic infarction, Stroke, 1991, 22, 155–161 10.1161/01.STR.22.2.155Search in Google Scholar
[21] Boiten J., Lodder J., Prognosis for survival, handicap and recurrence of stroke in lacunar and superficial infarction, Cerebrovasc. Dis., 1993, 3, 221–226 http://dx.doi.org/10.1159/00010870410.1159/000108704Search in Google Scholar
[22] Miyao A., Teramoto J., Takahashi A., Leikoaraiosis in relation to prognosis for patients with lacunar infarction, Stroke 1992, 23, 1434–1438 10.1161/01.STR.23.10.1434Search in Google Scholar
[23] PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack, Lancet, 2001, 358, 1033–1041 http://dx.doi.org/10.1016/S0140-6736(01)06178-510.1016/S0140-6736(01)06178-5Search in Google Scholar
[24] Diener H.C., Cunha L., Forbes C., Sivenius J., Smets P., Lowenthal A., European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke, J. Neurol. Sci., 1996, 143, 1–13 http://dx.doi.org/10.1016/S0022-510X(96)00308-510.1016/S0022-510X(96)00308-5Search in Google Scholar
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