Abstract 54: APOE Genotype Modifies the Effect of Blood Pressure on Long-term Clinical Deterioration Following Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Alessandro Biffi ◽  
Chia-Ling Phuah ◽  
Christina Kourkoulis ◽  
Kristin Schwab ◽  
Alison M Ayres ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Apoe Genotype ◽  
Cognitive Status ◽  
Clinical Deterioration ◽  
Small Vessel ◽  
Blood Draw ◽  
Gait Impairment ◽  
Increased Risk

Introduction: Intracerebral Hemorrhage (ICH) is a severe manifestation of cerebral small vessel disease, and identifies individuals at high risk for recurrent ICH, ischemic stroke, dementia, late-life depression and gait impairment. Blood pressure (BP) following ICH is strongly associated with risk of these clinical sequelae. Hypothesis: We sought to test whether the most potent genetic risk factors for ICH recurrence, APOE ε2 / ε4, modify the effect of BP. Methods: We prospectively collected demographic and medical data for 608 consecutive ICH survivors, presenting to a single center from January 2006 to December 2013. APOE genotyping was performed on samples obtained via peripheral venous blood draw. Participants were followed longitudinally with periodic BP measurements and evaluation of recurrent ICH / ischemic stroke events. We assessed cognitive and psychiatric outcomes of interest using two validated scales: 1) Telephone Interview for Cognitive Status (TICS); 2) 4-item version of the Geriatric Depression Scale (GDS-4). We generated multivariable Cox models for each outcome, and for overall risk of clinical deterioration (i.e. developing any outcome of interest). Results: APOE ε4 and systolic BP (SBP) interacted to increase risk of ICH recurrence, small vessel ischemic stroke, dementia, and gait impairment after ICH (all p < 0.05). Among patients with average SBP 120-129 mmHg only ε4 carriers were at increased risk for clinical deterioration (Hazard Ratio = 1.67, 95% Confidence Interval 1.06-2.64, p = 0.029). ICH survivors with SBP≥130 mmHg were also at increased risk, with APOE genotype further increasing risk among those with one or more ε4 copies (Figure). Conclusions: APOE ε4 modifies the effect of BP on clinical deterioration risk following ICH, and may identify individuals most likely to benefit from aggressive BP reduction. These data raise the possibility of genetic screening informing hypertension treatment goals in ICH survivors.

Abstract 98: Blood Pressure Control and Risk of Recurrent Lobar Intracerebral Hemorrhage

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Alessandro Biffi ◽  
Christopher D Anderson ◽  
Thomas W Battey ◽  
Alison M Ayres ◽  
Kristin Schwab ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Effect Size ◽  
Apoe Genotype ◽  
Pressure Control ◽  
Recurrence Risk ◽  
Dichotomous Variable ◽  
Increased Risk ◽  
Increase Risk ◽  
Stage 1

Introduction: Elevated blood pressure (BP) is a potent risk factor for risk and recurrence of Intracerebral Hemorrhage (ICH) in non-lobar regions, but its role in lobar ICH remains unclear. Hypothesis: We tested whether: elevated BP after index lobar ICH is associated with lobar ICH recurrence and whether the role of elevated BP is influenced by APOE genotype and microbleeds on MRI. Methods: Eligible subjects were survivors of primary lobar ICH enrolled in a single-center prospective cohort study. The number of MRI-defined lobar microbleeds (MB) and APOE genotype (ε2/ε3/ε4 alleles) were determined at time of index ICH. Survivors were followed prospectively for recurrent ICH. BP measurements were captured at 3, 6, 9, 12 months, and every 6 months thereafter. BP was treated as a time-varying variable, and analyzed in two ways: 1) a dichotomous variable based on AHA/ASA ICH secondary prevention guidelines goal; 2) a categorical variable for JNC7 hypertension stages. Results: Among 505 lobar ICH survivors, there were 102 recurrences during median follow-up of 30 months. Inadequate BP control (based on AHA/ASA guidelines) was associated with increased recurrence risk (Hazard Ratio [HR] 3.53, p=0.001). Effect size correlated with JNC7 stage: pre-hypertension (HR 2.76, p=0.007), hypertension stage 1 (HR 3.90, p=0.012); hypertension stage 2 (HR 5.21, p 2 MB, interaction p = 0.037) to increase risk of lobar ICH recurrence. Conclusions: Elevated BP is associated with increased risk of recurrent lobar ICH, with effect size rising with JNC7 stage. Presence of APOE ε2 / ε4 and > 2 MB on MRI interacts with BP, further increasing risk of recurrence. Further studies are required to determine the clinical implications of these findings.

scholarly journals APOE genotype, hypertension severity and outcomes after intracerebral haemorrhage

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Alessandro Biffi ◽  
Meredith P Murphy ◽  
Patryk Kubiszewski ◽  
Christina Kourkoulis ◽  
Kristin Schwab ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Ischaemic Stroke ◽  
Intracerebral Haemorrhage ◽  
Small Vessel Disease ◽  
Apoe Genotype ◽  
Small Vessel ◽  
Gait Impairment ◽  
Vessel Disease ◽  
Recurrent Haemorrhage

Abstract Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether APOE gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained APOE genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). APOE ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all P &lt; 0.05). APOE ε4 and systolic blood pressure interacted to increase the risk of recurrent haemorrhage, ischaemic stroke, dementia and gait impairment (all interaction P &lt; 0.05). Among patients with elevated blood pressure following intracerebral haemorrhage (average systolic blood pressure 120–129 mmHg and diastolic blood pressure &lt;80 mmHg) only those with one or more APOE ε4 copies were at increased risk for one or more small vessel disease outcomes (hazard ratio = 1.97, 95% confidence interval 1.17–3.31). Among haemorrhage survivors with hypertension (stage 1 and beyond) APOE genotype also stratified risk for all small vessel disease outcomes. In conclusion, APOE genotype modifies the already strong association of hypertension with multiple small vessel disease clinical outcomes among intracerebral haemorrhage survivors. These data raise the possibility that genetic screening could inform blood pressure treatment goals in this patient population.

Blood pressure levels and the risk of intracerebral hemorrhage after ischemic stroke

Neurology ◽  
2016 ◽  
Vol 88 (2) ◽  
pp. 177-181 ◽  
Author(s):  
Nina A. Hilkens ◽  
Jacoba P. Greving ◽  
Ale Algra ◽  
Catharina J.M. Klijn
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Confidence Interval ◽  
Intracerebral Hemorrhage ◽  
Incidence Rate ◽  
Hazard Ratio ◽  
Stroke Subtype ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Ischemic Stroke Subtype

Objective:To investigate the association between blood pressure (BP) levels and risk of intracerebral hemorrhage (ICH) after ischemic stroke.Methods:We performed a post hoc analysis of data from the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a randomized clinical trial including 20,332 patients with recent noncardioembolic ischemic stroke. BP measurements were divided into predefined categories. We calculated incidence rates per BP category and performed multivariable Cox regression analysis with systolic blood pressure (SBP) and diastolic blood pressure (DBP) categories as time-dependent covariables.Results:One hundred thirty-three ICHs occurred during 50,778 person-years of follow-up, resulting in an incidence rate of 2.6 per 1,000 person-years. The incidence rate of ICH increased with increasing SBP and DBP categories. Risk of ICH was significantly higher in patients with SBP ≥160 mm Hg (hazard ratio 2.27, 95% confidence interval 1.34–3.86) compared with those with SBP of 130–<140 mm Hg and in patients with DBP ≥100 mm Hg (hazard ratio 3.08, 95% confidence interval 1.78–5.34) compared with those with DBP of 80–<90 mm Hg. The association between SBP or DBP and ICH did not differ by ischemic stroke subtype (p = 0.55 and 0.93).Conclusions:Among patients with recent noncardioembolic ischemic stroke, the risk of ICH is high. High SBP and DBP are associated with an increased risk of ICH. The association between BP and ICH is not dependent on ischemic stroke subtype.

scholarly journals Premature Ventricular Complexes on Screening Electrocardiogram and Risk of Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (5) ◽  
pp. 1365-1367 ◽  
Author(s):  
Sunil K. Agarwal ◽  
Jennifer Chao ◽  
Frederick Peace ◽  
Suzanne E. Judd ◽  
Brett Kissela ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Racial Differences ◽  
Proportional Hazards Model ◽  
Geographic Region ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Premature Ventricular Complexes ◽  
Increased Risk

Background and Purpose— Premature ventricular complexes (PVCs) detected from long-term ECG recordings have been associated with an increased risk of ischemic stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are associated with an increased risk of ischemic stroke remains unstudied. Methods— This analysis included 24 460 participants (aged, 64.5+9.3 years; 55.1% women; 40.0% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment. PVCs were ascertained from baseline ECG (2003–2007), and incident stroke cases through 2011 were confirmed by an adjudication committee. Results— A total of 1415 (5.8%) participants had at least 1 PVC at baseline, and 591 developed incident ischemic stroke during an average (SD) follow-up of 6.0 (2.0) years. In a cox proportional hazards model adjusted for age, sex, race, geographic region, education, previous heart disease, systolic blood pressure, blood pressure–lowering medications, current smoking, diabetes mellitus, left ventricular hypertrophy by ECG, and aspirin use and warfarin use, the presence of PVCs was associated with 38% increased risk of ischemic stroke (hazard ratio [95% confidence interval], 1.38 [1.05–1.81]). Conclusions— PVCs are common on routine screening ECGs and are associated with an increased risk of ischemic stroke.

scholarly journals Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)

2018 ◽  
Vol 13 (5) ◽  
pp. 454-468 ◽  
Author(s):  
Andreas Charidimou ◽  
Sara Shams ◽  
Jose R Romero ◽  
Jie Ding ◽  
Roland Veltkamp ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Intracerebral Hemorrhage ◽  
Meta Analysis ◽  
Population Based ◽  
Cerebral Microbleeds ◽  
Clinical Settings ◽  
Memory Clinic ◽  
Increased Risk ◽  
Stroke Death

Background Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. Methods Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n = 7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5 population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

Association between Apolipoprotein E Polymorphism and Clinical Outcome after Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage

2021 ◽  
pp. 1-10
Author(s):  
Wen Pan ◽  
Min Zhang ◽  
Zhenping Guo ◽  
Wenfeng Xiao ◽  
Chao You ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Subarachnoid Hemorrhage ◽  
Clinical Outcome ◽  
Intracerebral Hemorrhage ◽  
Apolipoprotein E ◽  
Functional Outcomes ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Fixed Effects Models ◽  
Increased Risk

<b><i>Backgrounds:</i></b> Previous studies reported inconsistent results regarding associations between apolipoprotein E (<i>APOE</i>) polymorphism and clinical outcomes after ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Thus, the study was designed to make a systematic review and meta-analysis regarding the association between <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH. <b><i>Methods:</i></b> To identify studies eligible for this meta-analysis, we searched for articles published before August 2021 in the databases (PubMed, Web of Science, and Google Scholar). We used STATA 12.0 software to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) regarding <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH. <b><i>Results:</i></b> Meta-analysis showed no significant association between <i>APOE</i> polymorphism and functional outcome after IS with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.00; 95% CI: 0.83–1.21, <i>I</i><sup>2</sup> = 29.4%, <i>p</i> = 0.183; ε2 carrier vs. non-ε2 carrier: HR, 0.92; 95% CI: 0.72–1.16, <i>I</i><sup>2</sup> = 15.6%, <i>p</i> = 0.307). Meta-analysis showed that ICH patients carrying ε4 allele have increased risk of poor outcome in Caucasian population with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.75; 95% CI: 1.19–2.57, <i>I</i><sup>2</sup> = 0.0%, <i>p</i> = 0.543). Meta-analysis showed no significant association between <i>APOE</i> polymorphism and functional outcomes after SAH with random effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.51; 95% CI: 0.80–2.84, <i>I</i><sup>2</sup> = 57.1%, <i>p</i> = 0.022). <b><i>Conclusions:</i></b> In conclusion, the present study demonstrated <i>APOE</i> ε4 carriers show worse functional outcomes after ICH, but not after IS or SAH. More large-scale studies were critical to explore the association between <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH.

Pregnancy and Stroke

CNS Spectrums ◽  
2005 ◽  
Vol 10 (7) ◽  
pp. 580-587 ◽  
Author(s):  
Ann K. Helms ◽  
Steven J. Kittner
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Postpartum Period ◽  
Low Dose ◽  
Paradoxical Embolism ◽  
Subsequent Pregnancy ◽  
Dose Aspirin ◽  
Increased Risk ◽  
Low Dose Aspirin ◽  
History Of

AbstractThe risks of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage are not increased in the 9 months of gestation except for a high risk in the 2 days prior and 1 day postpartum. The remaining 6 weeks postpartum also have an increased risk of ischemic stroke and intracerebral hemorrhage, though less than the peripartum period. Although there are some rare causes of stroke specific to pregnancy and the postpartum period, eclampsia, cardiomyopathy, postpartum cerebral venous thrombosis, and, possibly, paradoxical embolism warrant special consideration. The diagnostic and therapeutic approaches to stroke during pregnancy and the postpartum period are similar to the approaches in the nonpregnant woman with some minor modifications based on consideration of the welfare of the fetus. There is a theoretical risk of magnetic resonance imaging exposure during the first and second trimester but the benefit to the mother of obtaining the information may outweigh the risk. Available evidence suggests that low-dose aspirin (<150 mg/day) during the second and third trimesters is safe for both mother and fetus. Postpartum use of low-dose aspirin by breast-feeding mother is also safe for infant. While proper counseling is imperative, a history of pregnancy-related stroke should not be a contraindication for subsequent pregnancy.

scholarly journals Plasma Resistin Levels and Risk of Myocardial Infarction and Ischemic Stroke

2008 ◽  
Vol 93 (7) ◽  
pp. 2647-2653 ◽  
Author(s):  
Cornelia Weikert ◽  
Sabine Westphal ◽  
Klaus Berger ◽  
Jutta Dierkes ◽  
Matthias Möhlig ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Ischemic Stroke ◽  
Relative Risk ◽  
Confidence Interval ◽  
High Plasma ◽  
Case Control Studies ◽  
Blood Draw ◽  
Increased Risk ◽  
Aged Subjects

Abstract Context: Resistin is a hormone that has been linked to insulin resistance, inflammatory processes, and coronary heart disease in case-control studies; however, prospective data on the association between plasma resistin levels and future risk of cardiovascular disease are lacking. Objective: The objective of the study was to investigate the association between plasma resistin levels and risk of future myocardial infarction (MI) and ischemic stroke (IS) in a large prospective cohort. Methods: We investigated the association between plasma resistin levels and risk of MI and IS in a case-cohort design among 26,490 middle-aged subjects from the European Investigation into Cancer and Nutrition-Potsdam Study without history of MI or stroke at time of blood draw. Plasma resistin levels were measured in baseline blood samples of 139 individuals who developed MI, 97 who developed IS, and 817 individuals who remained free of cardiovascular events during a mean follow-up of 6 yr. Results: After multivariable adjustment for established cardiovascular risk factors including C-reactive protein, individuals in the highest compared with the lowest quartile of plasma resistin levels had a significantly increased risk of MI (relative risk 2.09; 95% confidence interval 1.01–4.31; P for trend = 0.01). In contrast, plasma resistin levels were not significantly associated with risk of IS (relative risk 0.94; 95% confidence interval 0.51–1.73; P for trend = 0.88). Conclusion: Our data suggest that high plasma resistin levels are associated with an increased risk of MI but not with risk of IS. Further studies are needed to evaluate the predictive value of plasma resistin levels for cardiovascular disease.

scholarly journals PREDIKTOR SYMPTOMATIC INTRACEREBRAL HEMORRHAGE PASCATROMBOLISIS INTRAVENA PADA STROKE ISKEMIK AKUT

2018 ◽  
Vol 35 (3) ◽  
Author(s):  
Al Rasyid ◽  
Salim Harris ◽  
Mohammad Kurniawan ◽  
Rakhmad Hidayat ◽  
Taufik Mesiano
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Intravenous Thrombolysis ◽  
Definitive Treatment ◽  
Stroke Patients ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Stroke Thrombolysis ◽  
Withholding Therapy ◽  
Diabetes Melitus

PREDICTORS OF SYMPTOMATIC INTRACEREBRAL HEMORRHAGE FOLLOWING INTRAVENOUS THROMBOLYSIS IN ACUTE ISCHEMIC STROKEABSTRACTDespite its effectiveness, the percentage of ischemic stroke patients who received definitive treatment, thrombolysis, never went above 10%, due to one of the reason is the occurrence of severe, post-therapeutic complications, such as symptomatic intracerebral hemorrhage (sICH). Several factors contribute to sICH occurrence are age, severity of stroke, early changes of ischemic sign, hyperglycemia, blood pressure, antiplatelet use and its interval. Patients with highest risk of sICH has been shown to have the greatest benefits from thrombolysis among other subgroup patients, therefore withholding therapy is not a choice. Compliance to the stroke’s guidelines could reduce the risk of complications as well as boost effectiveness of treatment.Keywords: Safety predictors, acute ischemic stroke, thrombolysis, sICH ABSTRAK Walau terbukti efektif, persentase pasien yang dapat dilakukan tindakan definitif stroke iskemik akut berupa trombolisis  tidak  pernah  mencapai  angka  10%,  salah  satunya  disebabkan  pertimbangan  terhadap  komplikasi  berat, seperti symptomatic intracerebral hemorrhage (sICH). Beberapa faktor yang berpengaruh terhadap kejadian sICH antara lain usia, derajat stroke, perubahan tanda iskemik dini, hiperglikemia dan diabetes melitus, tekanan darah, penggunaan antiplatelet, serta waktu pemberian. Pasien dengan risiko sICH tertinggi memiliki keuntungan terbesar dari trombolisis sehingga menunda tindakan bukanlah suatu opsi. Kepatuhan terhadap panduan tindakan dapat mengurangi angka kejadian komplikasi berat.Kata kunci: Prediktor keamanan, stroke iskemik akut, trombolisis, sICH

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