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

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.

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

Stroke ◽

10.1161/str.48.suppl_1.54 ◽

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.

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Evaluation of Acute Kidney Injury and Mortality After Intensive Blood Pressure Control in Patients With Intracerebral Hemorrhage

Journal of the American Heart Association ◽

10.1161/jaha.117.008439 ◽

2018 ◽

Vol 7 (8) ◽

Cited By ~ 6

Author(s):

L. Goodwin Burgess ◽

Nitin Goyal ◽

G. Morgan Jones ◽

Yasser Khorchid ◽

Ali Kerro ◽

...

Keyword(s):

Blood Pressure ◽

Acute Kidney Injury ◽

Intracerebral Hemorrhage ◽

Blood Pressure Control ◽

Kidney Injury ◽

Pressure Control ◽

Intensive Blood Pressure

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Abstract P497: Re-analysis of the Systolic Blood Pressure Intervention Trial (SPRINT): The Renal Consequences of Intensive versus Standard Blood Pressure Lowering

Hypertension ◽

10.1161/hyp.70.suppl_1.p497 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Leora Branfield Day ◽

David M Naimark

Keyword(s):

Blood Pressure ◽

Lifetime Cost ◽

Intensive Therapy ◽

Cost Savings ◽

Cost Effective ◽

Pressure Control ◽

Average Lifetime ◽

Ckd Progression ◽

Lifetime Horizon ◽

Increased Risk

Background: BP management guidelines suggest that persons with CKD should be treated to a SBP ≤ 140 mmHg. SPRINT compared this target to intensive SBP lowering (≤ 120 mmHg) in persons with and without CKD and found a reduced rate of CV events and all-cause mortality (ACM). However intensive therapy was associated with an increased risk of AKI. We extrapolated the results of SPRINT over a lifetime horizon to determine whether in the long-term, the benefit in terms of the primary outcome would be less economically attractive when the risks of more frequent AKI and subsequent CKD progression were considered. Methods: We re-configured the CKD Simulator, a Markov model of CKD progression, AKI events, fatal and non-fatal CV events, and ESRD. We recalibrated the model to be representative of the SPRINT cohort and compared intensive vs. standard blood pressure control among 10 million simulated persons with and without CKD over their lifetimes. Marginal treatment costs were calculated and hazard ratios for AKI, CV events and ACM observed in SPRINT were applied to the monthly probabilities of these events in the intensive SBP arm. Results: Lifetime average, discounted, costs per person associated with intensive vs. standard SBP lowering were predicted to be $35,811 and $30,584, respectively. Quality-adjusted, discounted average lifespans were 196.05 and 190.47 months, respectively. The cost of each quality-adjusted life-year gained by adopting intensive over standard BP lowering would be $11,220, significantly below the accepted cost-effectiveness threshold of $50,000. Intensive SBP control would reduce the lifetime incidence of at least one CV event by 5.5%, but increase the incidence of at least one AKI episode and ESRD by 1.7% and 0.7%, respectively. These differences were associated with average lifetime cost savings per person of $459 for CV events, but losses of $161 and $2,889 for AKI and ESRD. Discussion: Intensive SBP management would be cost-effective and associated with a significant lifetime reduction in CV events. However, there would be an increase in the lifetime risk of AKI and ESRD, contributing to 58% of the total increase in cost of intensive relative to usual SBP control. Intensive SBP lowering should be adopted judiciously in persons at high risk of ESRD.

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Abstract 119: Risk of Intracerebral Hemorrhage with Combined Antiplatelet and Anticoagulant Use

Stroke ◽

10.1161/str.44.suppl_1.a119 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Matthew L Flaherty ◽

Lili Ding ◽

Jessica G Woo ◽

Lisa Martin ◽

Mary Haverbusch ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Antiplatelet Agents ◽

Population Based ◽

Careful Consideration ◽

Antiplatelet Drug ◽

Treatment Groups ◽

Stroke Study ◽

Increased Risk ◽

Anticoagulant Drugs ◽

Increase Risk

Context: Intracranial bleeding is the most feared complication of antithrombotic use. Antiplatelet and anticoagulant drugs increase risk of intracerebral hemorrhage (ICH), yet in some instances, combinations of antiplatelet agents and anticoagulants are used without firm evidence of efficacy. Few studies have compared the risks of different agents and their combinations in a single population. We determined the risk of ICH associated with the most commonly used antiplatelet and anticoagulant drugs and their combinations in a population-based case-control study. Methods: This report includes data from subjects recruited from the Greater Cincinnati/Northern Kentucky area by the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study from 1997 to 2009. We compared individuals in different treatment groups to identify any differences in baseline covariates that could be associated with treatment assignment. As there were a number of statistically significant differences, we used multivariate matching to analyze risk for ICH conferred by different antithrombotic agents. Treatment effects on ICH were estimated using the matched samples while accounting for the dependence between matched individuals. Results: There were 733 subjects with ICH and 2555 controls included in this study period. Results are shown in the table. Use of aspirin, clopidogrel, or their combination was associated with a trend toward increased risk. Warfarin increased risk compared with no antithrombotic use (OR 3.98, p < 0.0001). The combination of warfarin and either aspirin or clopidogrel produced the greatest risk, compared with no antithrombic therapy (OR 4.92 p<0.001) or compared with warfarin alone (OR 3.00 p=0.009). Conclusions: The combination of warfarin and an antiplatelet drug significantly increases risk of ICH compared with no antithrombotic therapy or warfarin monotherapy. The use of combination therapy requires careful consideration in clinical practice.

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Nondipping Blood Pressure: Predictive or Reactive Failure of Renal Sodium Handling?

Physiology ◽

10.1152/physiol.00024.2020 ◽

2021 ◽

Vol 36 (1) ◽

pp. 21-34 ◽

Cited By ~ 1

Author(s):

Jessica R. Ivy ◽

Matthew A. Bailey

Keyword(s):

Blood Pressure ◽

Pressure Control ◽

Sodium Reabsorption ◽

Nocturnal Sleep ◽

Sodium Homeostasis ◽

Increased Risk ◽

Health And Disease ◽

Renal Sodium Handling ◽

Sodium Handling

Blood pressure follows a daily rhythm, dipping during nocturnal sleep in humans. Attenuation of this dip (nondipping) is associated with increased risk of cardiovascular disease. Renal control of sodium homeostasis is essential for long-term blood pressure control. Sodium reabsorption and excretion have rhythms that rely on predictive/circadian as well as reactive adaptations. We explore how these rhythms might contribute to blood pressure rhythm in health and disease.

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Blood Pressure Change from Normal to 2017 ACC/AHA Defined Stage 1 Hypertension and Cardiovascular Risk

Journal of Clinical Medicine ◽

10.3390/jcm8060820 ◽

2019 ◽

Vol 8 (6) ◽

pp. 820 ◽

Cited By ~ 4

Author(s):

Joung Sik Son ◽

Seulggie Choi ◽

Gyeongsil Lee ◽

Su-Min Jeong ◽

Sung Min Kim ◽

...

Keyword(s):

Blood Pressure ◽

Proportional Hazards ◽

Heart Association ◽

Pressure Change ◽

Cox Proportional Hazards ◽

Cvd Risk ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Stage 1 ◽

Second Period

The purpose of this study was to investigate the clinical significance of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) defined stage 1 hypertension (systolic blood pressure (SBP) 130–139 mmHg or diastolic blood pressure (DBP) 80–89 mmHg), and increase in BP from previously normal BP in Korean adults. We conducted a retrospective analysis of 60,866 participants from a nationally representative claims database. Study subjects had normal BP (SBP < 120 mmHg and DBP < 80 mmHg), no history of anti-hypertensive medication, and cardiovascular disease (CVD) in the first period (2002–2003). The BP change was defined according to the BP difference between the first and second period (2004–2005). We used time-dependent Cox proportional hazards models in order to evaluate the effect of BP elevation on mortality and CVD with a mean follow-up of 7.8 years. Compared to those who maintained normal BP during the second period, participants with BP elevation from normal BP to stage 1 hypertension had a higher risk for CVD (adjusted hazard ratio (aHR) 1.23; 95% confidence interval (CI), 1.08–1.40), and ischemic stroke (aHR 1.32; 95% CI, 1.06–1.64). BP elevation to 2017 ACC/AHA defined elevated BP (SBP 120–129 mmHg and DBP < 80 mmHg) was associated with an increased risk of CVD (aHR 1.26; 95% CI, 1.06–1.50), but stage 1 isolated diastolic hypertension (SBP < 130 and DBP 80–89 mmHg) was not significantly related with CVD risk (aHR 1.12; 95% CI, 0.95–1.31).

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Management of Presumed Acute Kidney Injury during Hypertensive Therapy: Stay Calm and Carry on?

American Journal of Nephrology ◽

10.1159/000505447 ◽

2020 ◽

Vol 51 (2) ◽

pp. 108-115

Author(s):

Teresa K. Chen ◽

Chirag R. Parikh

Keyword(s):

Blood Pressure ◽

Acute Kidney Injury ◽

Serum Creatinine ◽

Blood Pressure Control ◽

Kidney Injury ◽

Pressure Control ◽

Intensive Treatment ◽

Urinary Biomarkers ◽

Increased Risk ◽

Intensive Blood Pressure

Background: Recent studies have demonstrated that intensive blood pressure control is associated with improved cardiovascular outcomes. Acute kidney injury (AKI), however, was more common in the intensive treatment group prompting concern in the nephrology community. Summary: Clinical trials on hypertension control have traditionally defined AKI by changes in serum creatinine. However, serum creatinine has several inherent limitations as a marker of kidney injury, with various factors influencing its production, secretion, and elimination. Urinary biomarkers of kidney injury and repair have the potential to provide insight on the presence and phenotype of kidney injury. In both the Systolic Blood Pressure Intervention Trial and the Action to Control Cardiovascular Risk in Diabetes study, urinary biomarkers have suggested that the increased risk of AKI associated with intensive treatment was due to hemodynamic changes rather than structural kidney injury. As such, clinicians who encounter rises in serum creatinine during intensification of hypertension therapy should “stay calm and carry on.” Alternative explanations for serum creatinine elevation should be considered and addressed if appropriate. When the rise in serum creatinine is limited, particularly if albuminuria is stable or improving, intensive blood pressure control should be continued for its potential long-term benefits. Key Messages: Increases in serum creatinine during intensification of blood pressure control may not necessarily reflect kidney injury. Clinicians should evaluate for other contributing factors before stopping therapy. Urinary biomarkers may address limitations of serum creatinine as a marker of kidney injury.

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Significance of Quantitative Cerebral Blood Flow Measurement in the Acute Stage after Revascularization Surgery for Adult Moyamoya Disease: Implication for the Pathological Threshold of Local Cerebral Hyperperfusion

Cerebrovascular Diseases ◽

10.1159/000504835 ◽

2019 ◽

Vol 48 (3-6) ◽

pp. 217-225 ◽

Cited By ~ 4

Author(s):

Masayuki Kameyama ◽

Miki Fujimura ◽

Ryosuke Tashiro ◽

Kenichi Sato ◽

Hidenori Endo ◽

...

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Intracerebral Hemorrhage ◽

Perioperative Management ◽

Pressure Control ◽

Acute Stage ◽

Cerebral Hyperperfusion ◽

Auc Value ◽

Revascularization Surgery

Objective: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard surgical procedure for adult patients with moyamoya disease (MMD) and plays a role in preventing ischemic and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is a potential complication of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the exact threshold of the pathological increase in postoperative cerebral blood flow (CBF) is unclear. Thus, we analyzed local CBF in the acute stage after revascularization surgery for adult MMD to predict CHP syndrome under modern perioperative management. Materials and Methods: Fifty-nine consecutive adult MMD patients, aged 17–66 years old (mean 43.1), underwent STA-MCA anastomosis with indirect pial synangiosis for 65 affected hemispheres. All patients were perioperatively managed by strict blood pressure control (systolic pressure of 110–130 mm Hg) to prevent CHP syndrome. Local CBF at the site of anastomosis was quantitatively measured using the autoradiographic method by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. We defined CHP phenomenon as a local CBF increase over 150% compared to the preoperative value. Then, we investigated the correlation between local hemodynamic change and the development of CHP syndrome. Results: After 65 surgeries, 5 patients developed CHP syndrome, including 2 patients with delayed intracerebral hemorrhage (3.0%), 1 with symptomatic subarachnoid hemorrhage (1.5%), and 2 with focal neurological deterioration without hemorrhage. The CBF increase ratio was significantly higher in patients with CHP syndrome (270.7%) than in patients without CHP syndrome (135.2%, p = 0.003). Based on receiver operating characteristic analysis, the cutoff value for the pathological postoperative CBF increase ratio was 184.5% for CHP syndrome (sensitivity = 83.3%, specificity = 94.2%, area under the curve [AUC] value = 0.825) and 241.3% for hemorrhagic CHP syndrome (sensitivity = 75.0%, specificity = 97.2%, AUC value = 0.742). Conclusion: Quantitative measurement of the local CBF value in the early postoperative period provides essential information to predict CHP syndrome after STA-MCA anastomosis in patients with adult MMD. The pathological threshold of hemorrhagic CHP syndrome was as high as 241.3% by the local CBF increase ratio, but 2 patients (3.0%) developed delayed intracerebral hemorrhage in this series that were managed following the intensive perioperative management protocol. Thus, we recommend routine CBF measurement in the acute stage after direct revascularization surgery for adult MMD and satisfactory blood pressure control to avoid the deleterious effects of CHP.

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