Hypertension control after intracerebral hemorrhage among varying small vessel disease etiologies.

INTRODUCTION: Intracerebral hemorrhage (ICH) is attributable to cerebral small vessel disease (cSVD), which includes cerebral amyloid angiopathy (CAA) and hypertensive-cSVD (HTN-cSVD). HTN-cSVD includes patients with strictly deep ICH/microbleeds and mixed location ICH/microbleeds, the latter representing a more severe form of HTN-cSVD. We test the hypothesis that more severe forms of HTN-cSVD are related to worse hypertension control in long-term follow-up after ICH. METHODS: From consecutive non-traumatic ICH patients admitted to a tertiary care center, we classified the ICH as CAA, strictly deep ICH/microbleeds, and mixed-location ICH/microbleeds. CSVD burden was quantified using a validated MRI-based score (range: 0-6 points). We created a multivariable (linear mixed effects) model adjusting for age, sex, race, year of inclusion, hypertension, and antihypertensive medication usage to investigate the association of average systolic blood pressure (SBP) during follow-up with cSVD etiology/severity. RESULTS: 796 ICH survivors were followed for a median of 48.8 months (IQR 41.5-60.4). CAA-related ICH survivors (n = 373) displayed a lower median SBP (138 mmHg, IQR 133-142 mmHg) compared to those of strictly deep ICH (n = 222, 141 mmHg, IQR 136-143 mmHg, p = 0.04), and mixed location ICH/microbleeds (n = 201, 142 mmHg, IQR 135-144 mmHg, p = 0.02). In the multivariable analysis, mixed location ICH/microbleeds (effect: + 3.8 mmHg, SE: 1.3 mmHg, p = 0.01) and increasing cSVD severity (+ 1.8 mmHg per score point, SE: 0.8 mmHg, p = 0.03) were associated with higher SBP in follow-up. CONCLUSION: CSVD severity and subtype predicts long-term hypertension control in ICH patients.

Association of Depression Onset and Treatment With Blood Pressure Control After Intracerebral Hemorrhage.

BACKGROUND: Blood pressure (BP) control represents a crucial intervention to improve long-term outcomes following spontaneous intracerebral hemorrhage (ICH). However, fewer than half of ICH survivors achieve target treatment goals. ICH survivors are also at very high risk for poststroke depression, which may contribute to inadequate BP control. We, therefore, sought to determine whether depressive symptoms after ICH are associated with inadequate BP control. We also investigated whether associations between depression after ICH and BP measurements were mediated by treatment with selective serotonin reuptake inhibitors or norepinephrine-serotonin reuptake inhibitors antidepressants. METHODS: We leveraged data from a single-center longitudinal study of ICH conducted at Massachusetts General Hospital (Boston, MA) between 2006 and 2018. We collected data from semiautomated review of electronic health records, baseline and follow-up interviews, and computed tomography imaging. Information on BP measurements, depression diagnoses, antidepressants medication use, and medical visits were collected longitudinally and analyzed using mixed effects models. Primary outcomes included systolic and diastolic BP measurements during long-term follow-up after ICH. RESULTS: We included 1243 consecutive ICH patients without pre-stroke depression history. Of these, 721 (58%) were diagnosed with incident depression over a median follow-up time of 52.8 months (interquartile range, 42.1-60.5). Depression onset was associated with subsequent increase in systolic (+8.3 mm Hg, SE, 2.4 mm Hg, P=0.012) and diastolic (+4.4 mm Hg, SE, 1.2 mm Hg) BP measurements. Resolution of depressive symptoms was associated with subsequent decrease in systolic (-5.9 mm Hg, SE, 1.4 mm Hg, P=0.031) and diastolic (-3.4 mm Hg, SE, 1.1 mm Hg, P=0.041) BP measurements. We also found associations between higher systolic BP measurements and use of selective serotonin reuptake inhibitor and noradrenaline-serotonin reuptake inhibitor antidepressants, independent of whether depression symptoms were active or not (all P<0.05). CONCLUSIONS: ICH survivors displayed increasing BP values after receiving a diagnosis of depression, followed by decreasing values among those experiencing resolution of depressive symptoms. Use of selective serotonin reuptake inhibitor and noradrenaline-serotonin reuptake inhibitor antidepressants was independently associated with higher systolic BP measurements. Clinicians ought to closely monitor BP for ICH survivors being treated for depression, especially using selective serotonin reuptake inhibitor and noradrenaline-serotonin reuptake inhibitor. Future studies will also be required to investigate the mechanisms underlying these associations.

Blood Pressure Control Targets and Risk of Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP <130 mmHg and diastolic BP <80 mmHg) were at lower risk of major adverse cardiovascular and cerebrovascular events and mortality. METHODS: We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. RESULTS: During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP <120 mmHg displayed reduced risk of recurrent ICH (adjusted hazard ratio [AHR], 0.74 [95% CI, 0.59-0.94]) and major adverse cardiovascular and cerebrovascular events (AHR, 0.69 [95% CI, 0.53-0.92]). All-cause mortality (AHR, 0.76 [95% CI, 0.57-1.03]) and vascular mortality (AHR, 0.68 [95% CI, 0.45-1.01]) did not differ significantly. Among participants aged >75 years or with modified Rankin Scale score 4 to 5, systolic BP <120 mmHg was associated with increased all-cause mortality (AHR, 1.38 [95% CI, 1.02-1.85] and AHR, 1.36 [95% CI, 1.03-1.78], respectively), but not vascular mortality. We found no differences in outcome rates between survivors of ICH with diastolic BP <70 versus 70 to 79 mmHg. CONCLUSIONS: Targeting systolic BP <120 mmHg in select groups of survivors of ICH could result in decreased major adverse cardiovascular and cerebrovascular events risk without increasing mortality. Our findings warrant investigation in dedicated randomized controlled trials.

Long-Term Blood Pressure Variability and Major Adverse Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.

Background Survivors of intracranial hemorrhage (ICH) are at increased risk for major adverse cardiovascular and cerebrovascular events (MACCE), in the form of recurrent stroke and myocardial Infarction. We investigated whether long-term blood pressure (BP) variability represents a risk factor for MACCE after ICH, independent of average BP. Methods and Results We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital and the University of Hong Kong. We captured long-term (ie, visit-to-visit) BP variability, quantified as individual participants' variation coefficient. We explored determinants of systolic and diastolic BP variability and generated survival analyses models to explore their association with MACCE. Among 1828 survivors of ICH followed for a median of 46.2 months we identified 166 with recurrent ICH, 68 with ischemic strokes, and 69 with myocardial infarction. Black (coefficient +3.8, SE 1.3) and Asian (coefficient +2.2, SE 0.4) participants displayed higher BP variability. Long-term systolic BP variability was independently associated with recurrent ICH (subhazard ratio [SHR], 1.82; 95% CI, 1.19-2.79), ischemic stroke (SHR, 1.62; 95% CI, 1.06-2.47), and myocardial infarction (SHR, 1.54; 95% CI, 1.05-2.24). Average BP during follow-up did not modify the association between long-term systolic BP variability and MACCE. Conclusions Long-term BP variability is a potent risk factor for recurrent hemorrhage, ischemic stroke, and myocardial infarction after ICH, even among survivors with well-controlled hypertension. Our findings support the hypothesis that combined control of average BP and its variability after ICH is required to minimize incidence of MACCE.

Biological and Social Determinants of Hypertension Severity Before vs After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Although blood pressure (BP) control is considered the most effective measure to prevent functional decline after intracerebral hemorrhage (ICH), fewer than half of survivors achieve treatment goals. We hypothesized that long-term (i.e., prehemorrhage) hypertension severity may be a crucial factor in explaining poor BP control after ICH. We investigated changes in hypertension severity after vs before ICH using latent class analysis (LCA) and identified patient characteristics predictive of individuals' BP trajectories. METHODS: We analyzed data for ICH survivors enrolled in a study conducted at Massachusetts General Hospital (MGH) from 2002 to 2019 in Boston, a high-resource setting with near-universal medical insurance coverage. We captured BP measurements in the 12 months preceding and following the acute ICH hospitalization. Using LCA, we identified patient groups (classes) based on changes in hypertension severity over time in an unbiased manner. We then created multinomial logistic regression models to identify patient factors associated with these classes. RESULTS: Among 336 participants, the average age was 74.4 years, 166 (49%) were male, and 288 (86%) self-reported White race/ethnicity. LCA identified 3 patient classes, corresponding to minimal (n = 114, 34%), intermediate (n = 128, 38%), and substantial (n = 94, 28%) improvement in hypertension severity after vs before ICH. Survivors with undertreated (relative risk ratio [RRR] 0.05, 95% CI 0.01-0.23) or resistant (RRR 0.03, 95% CI 0.01-0.06) hypertension before ICH were less likely to experience substantial improvement afterwards. Residents of high-income neighborhoods were more likely to experience substantial improvement (RRR 1.14 per $10,000, 95% CI 1.02-1.28). Black, Hispanic, and Asian participants with uncontrolled hypertension before ICH were more likely to experience minimal improvement after hemorrhagic stroke (interaction p < 0.001). DISCUSSION: Most ICH survivors do not display consistent improvement in hypertension severity after hemorrhagic stroke. BP control after ICH is profoundly influenced by patient characteristics predating the hemorrhage, chiefly prestroke hypertension severity and socioeconomic status. Neighborhood income was associated with hypertension severity after ICH in a high-resource setting with near-universal health care coverage. These findings likely contribute to previously documented racial/ethnic disparities in BP control and clinical outcomes following ICH.

Latent profile analysis of cognitive decline and depressive symptoms after intracerebral hemorrhage.

BACKGROUND: Cognitive impairment and depressive symptoms are highly prevalent after Intracerebral Hemorrhage (ICH). We leveraged Latent Profile Analysis (LPA) to identify profiles for cognitive decline and depression onset after ICH. We also investigated differences in clinical, genetic and neuroimaging characteristics across patients' profiles. METHODS: We analyzed data from the ICH study conducted at Massachusetts General Hospital between January 1998 and December 2019. We collected information from electronical health records, follow-up interviews, CT and MRI imaging, and APOE genotype. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for cognitive decline and depression onset after ICH; 2) identify clinical, neuroimaging and genetic factors predicting individuals' likelihood to express a specific profile. RESULTS: We followed 784 ICH survivors for a median of 45.8 months. We identified four distinct profiles in cognitive and depressive symptoms after ICH: low depression and dementia risk, early-onset depression and dementia, late-onset depression and dementia, high depression with low dementia risk. Cerebral small vessel disease severity and APOE genotype were specifically associated with the late-onset profile (both p < 0.05). Acute hematoma characteristics (size, intraventricular extension) and functional disability were specifically associated with the early-onset profile (all p < 0.05). CONCLUSION: We identified four distinct profiles for cognitive and depressive symptoms after ICH, each displaying specific associations with individual patients' clinical, genetic and neuroimaging data. These associations reflect separate biological mechanisms influencing dementia and depression risk after ICH. Our findings support employing LPA in future ICH studies, and is likely applicable to stroke survivors at large.