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

Abstract

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.

Keywords: hypertension; intracranial hemorrhage; secondary prevention.

Figure 1. Flow diagram of study inclusion and exclusion criteria.

BP indicates blood pressure; CT, computed tomography; EMR, electronic medical records; HK, Hong Kong University; ICH, intracerebral hemorrhage; and MGH, Massachusetts General Hospital.

Figure 2. Blood pressure variability and risk of recurrent vascular events after ICH.

Kaplan‐Meier plots of risk for all MACCE events (A), recurrent ICH (B), ischemic stroke (C), and myocardial infarction (D), based on long‐term systolic blood pressure variability during follow‐up, expressed as quintiles of variation coefficient values. HKU indicates Hong Kong University; ICH, intracerebral hemorrhage; MACCE, major adverse cardiovascular and cerebrovascular events; MGH, Massachusetts General Hospital; SBP, systolic blood pressure; and VC, variation coefficient.

Figure 3. Hypertension severity, blood pressure variability, and major adverse cardiovascular and cerebrovascular events after ICH.

Forest plot presenting the association between long‐term systolic BP variability (per quintile of variation coefficient) and MACCE (all events, recurrent ICH, ischemic stroke, and myocardial infarction) with participants’ subgroups identified by hypertension severity (based on average BP) during follow‐up. BP indicates blood pressure; ICH, intracerebral hemorrhage; MACCE, major adverse cardiovascular and cerebrovascular events; and SHR, subhazard ratio.

Figure 4. Blood pressure control and incidence of major adverse cardiovascular and cerebrovascular events after ICH.

Surface area graph presenting the yearly incidence of MACCE after ICH (Per 1000 person/years) based on combined values of average systolic BP and BP variation coefficients (by quintiles) during follow‐up. For each subgroup identified by combination of average BP and variation coefficients we report in the labels the exact MACCE yearly incidence observed in our study. Different colors identify combinations of average Bp and its variability at comparable risk for MACCE during follow‐up. BP indicates blood pressure; ICH, intracerebral hemorrhage; and MACCE, major adverse cardiovascular and cerebrovascular events.