Recent advances in prevention and acute clinical care have led to an increased survival rate of stroke. However, stroke survivors face a high risk of sustaining a second stroke and of developing disability and cognitive decline, including dementia.
While robust existing evidence indicates that hypertension is the most important contributor to this added comorbidity, only 60% of stroke survivors have their blood pressure under control.
Driven by the fact that 40% of blood pressure levels can be explained by genetic variants commonly appearing in the general population, a multidisciplinary team at the Yale/Bugher Center for Intracerebral Hemorrhage Research tested the hypothesis that stroke survivors with elevated genetic predisposition to hypertension have higher and more-difficult-to-control blood pressure. Led by Julián Acosta, MD, a former postdoctoral fellow in the Falcone Lab, the study’s findings were published on Jan. 23 in Neurology.
The study used genomic information on 732 genetic variants known to increase blood pressure to categorize 5,940 patients who survived an ischemic or hemorrhagic stroke as having very low, low, intermediate, high and very high genetic predisposition to hypertension. In each of these genetic categories, the investigators evaluated the systolic blood pressure, the proportion of patients with uncontrolled hypertension (defined as a systolic blood pressure >140 mmHg, irrespective of treatment) and resistant hypertension (defined as a systolic blood pressure >140 mmHg despite 3 or more blood pressure medications). When comparing stroke survivors with very low versus very high genetic predisposition to hypertension, the mean systolic BP was 137 versus 143 mmHg, the prevalence of uncontrolled blood pressure was 43% versus 57%, and the prevalence of resistant hypertension was 4% versus 11%. Similar results were observed when evaluating ischemic stroke and hemorrhagic stroke survivors separately. These results were replicated in an independent cohort of 1750 stroke survivors enrolled in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
These results lay the groundwork for several clinical applications of genomic data related to hypertension. First, genetic predisposition to hypertension could facilitate the identification of persons who will obtain maximum benefit from blood pressure interventions, thus influencing clinical trial design and implementation. Furthermore, the genomic information and categorization approach used in this study could help identify stroke survivors who require tailored therapies such as higher medication doses or the combination of different drugs that account for genetic resistance.
This research was supported by a grant jointly awarded by the Bugher Foundation and the American Heart Association. In addition to Acosta, the other members of the research team were Cameron P. Both; Zachariah S. Demarais; Carolyn J. Conlon; Audrey C. Leasure; Victor M. Torres-Lopez; Adam de Havenon, MD, MSCI; Nils H. Petersen, MD, PhD; Thomas M. Gill, MD; Lauren H. Sansing, MD, MS; Kevin N. Sheth, MD; and Guido J. Falcone, MD ScD.
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- Thomas M. Gill, MDHumana Foundation Professor of Medicine (Geriatrics) and Professor of Epidemiology (Chronic Diseases) and of Investigative Medicine; Director, Yale Program on Aging; Director, Claude D. Pepper Older Americans Independence Center; Director, Yale Center for Disability and Disabling Disorders; Director, Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related Research