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      Orthostatic Hypotension, Cardiovascular Outcomes, and Adverse Events : Results From SPRINT

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          Abstract

          Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either <120 or <140 mm Hg. OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mm Hg 1 minute after standing from a seated position. We used Cox models to examine the association of OH with cardiovascular disease or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1170 (5.7%) instances of OH among those assigned a standard BP goal and 1057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of cardiovascular disease events (primary outcome: hazard ratio 1.06 [95% CI, 0.78–1.44]). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (hazard ratio, 1.77 [95% CI, 1.11–2.82]) and bradycardia (hazard ratio, 1.94 [95% CI, 1.19–3.15]), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of cardiovascular disease events, and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal.

          Clinical Trial Registration—

          URL: https://www.clinicaltrials.gov . Unique identifier: NCT01206062.

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          Most cited references28

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          The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).

          High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial. To describe the design considerations of the Systolic Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of trial participants. The Systolic Blood Pressure Intervention Trial is a multicenter, randomized, controlled trial that compares two strategies for treating systolic blood pressure: one targets the standard target of <140 mm Hg, and the other targets a more intensive target of <120 mm Hg. Enrollment focused on volunteers of age ≥50 years (no upper limit) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease, chronic kidney disease, 10-year Framingham cardiovascular disease risk score ≥15%, or age ≥75 years. The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups: participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), participants with a history of cardiovascular disease, and participants 75 years of age or older. The primary outcome is first the occurrence of a myocardial infarction (MI), acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes include all-cause mortality, decline in kidney function or development of end-stage renal disease, incident dementia, decline in cognitive function, and small-vessel cerebral ischemic disease. Between 8 November 2010 and 15 March 2013, Systolic Blood Pressure Intervention Trial recruited and randomized 9361 people at 102 clinics, including 3331 women, 2648 with chronic kidney disease, 1877 with a history of cardiovascular disease, 3962 minorities, and 2636 ≥75 years of age. Although the overall recruitment target was met, the numbers recruited in the high-risk subgroups were lower than planned. The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants, including those with prior cardiovascular disease, chronic kidney disease, and those aged ≥75 years. © The Author(s) 2014.
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            Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.

            The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology.
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              Awake systolic blood pressure variability correlates with target-organ damage in hypertensive subjects.

              Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.
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                Author and article information

                Journal
                Hypertension
                Hypertension
                Ovid Technologies (Wolters Kluwer Health)
                0194-911X
                1524-4563
                January 27 2020
                January 27 2020
                Affiliations
                [1 ]From the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.P.J.)
                [2 ]Michael E. DeBakey Veterans Affairs Medical Center and Department of Medicine, Baylor College of Medicine, Houston, TX (A.A.T.)
                [3 ]Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH (J.T.W.)
                [4 ]Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC (G.W.E.)
                [5 ]The Johns Hopkins University School of Medicine, The Johns Hopkins Bloomberg School of Public Health, and The Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, MD (E.R.M., L.J.A.)
                [6 ]Larner College of Medicine at The University of Vermont, Burlington (T.B.P.)
                [7 ]Preventive Medicine Section, Memphis VA Medical Center, Memphis, TN (W.C.C.)
                [8 ]Division of General Internal Medicine and Geriatrics, Department of Internal Medicine, The Ohio State University, Columbus (T.R.G.)
                [9 ]Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL (W.E.H.)
                [10 ]Department of Medicine, University of Illinois at Chicago, College of Medicine, IL (I.M.)
                [11 ]Department of Internal Medicine; Salt Lake City VA Medical Center, UT (J.N.)
                [12 ]Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham (S.O.)
                [13 ]Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC (C.P.)
                [14 ]Institute for Medicine and Public Health, Vanderbilt University Medical Center, VA Geriatric Research Education and Clinical Center, Nashville, TN (C.L.R.)
                [15 ]Clement J. Zablocki VA Medical Center, Milwaukee, WI (J.W.)
                [16 ]Department of Primary Care, Ohio University Heritage College of Osteopathic Medicine, Cleveland (A.W.)
                [17 ]Department of Medical Physics, Mercer’s Institute for Successful Ageing, St James’s Hospital, Dublin, Ireland (C.F.)
                [18 ]Department of Medical Gerontology, Trinity College, Dublin, Ireland (C.F., R.A.K.)
                [19 ]Mercer’s Institute for Successful Ageing, St James’s Hospital, Dublin, Ireland (R.A.K.)
                [20 ]Department of Medicine, Perelman School of Medicine, University of Pennsylvania (R.R.T.).
                Article
                10.1161/HYPERTENSIONAHA.119.14309
                7261502
                31983312
                4c4911b5-102a-490b-bf18-0bf376d0a4c1
                © 2020
                History

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