Orthostatic Hypotension, Cardiovascular Outcomes, and Adverse Events: Results From SPRINT.
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SUBMITTER: Juraschek SP
PROVIDER: S-EPMC7261502 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Project description:SPRINT (Systolic Blood Pressure Intervention Trial) highlighted the benefits of intensive targeted antihypertensive therapy but resulted in higher rates of treatment-related adverse events. Blood pressure (BP) variability has emerged as a significant predictor of outcomes over and above levels of BP. Using the SPRINT data set, we aimed to determine the relationship of BP variability with cardiovascular outcomes and side effects of antihypertensive therapy. The analyses included all participants randomized in SPRINT who reached the target systolic BP (SBP) for their respective groups (intensive < 120 mm Hg; standard < 140 mm Hg). Coefficients of variation (CV) for SBP, diastolic BP (DBP), and PP for each patient characterized variability. Student t test was used to compare treatment arms for each CV metric. Cox proportional hazards regression was used to identify independent predictors of the SPRINT primary outcome and adverse events. P < .15 on univariate analysis was required to enter the model and P < .05 to remain in it. A total of 8884 patients (4561 standard group; 4323 intensive group) met inclusion criteria. DBP CV differed between the groups (9.12 ± 3.20 standard group; 9.47 ± 3.49 intensive group [P < .0001]). DBP CV predicted a greater hazard for the primary outcome (hazard ratio [HR], 1.14) in the overall model as well as separate analyses by treatment arms (standard group HR, 1.15; intensive group HR, 1.19), each P < .0001. DBP CV also independently predicted a greater hazard for acute kidney injury (HR, 1.12) and hypotensive events (HR, 1.12). Visit-to-visit DBP variability independently predicted worse cardiovascular outcomes and hypoperfusion-related adverse events in SPRINT.
| S-EPMC8031192 | biostudies-literature
Project description:Purpose Hyperadrenergic orthostatic hypotension is a subtype of orthostatic hypotension associated with elevated norepinephrine levels upon standing. Our previous study found that this subtype is characterized by less severe autonomic impairment compared to orthostatic hypotension with normal or low norepinephrine levels. However, long-term outcomes have not been determined. Thus, the purpose of this study was to evaluate the all-cause mortality and phenoconversion over 7 years. Methods In this prospective observational study, 92 patients with orthostatic hypotension were recruited from the Vanderbilt Autonomic Dysfunction Center. 34 patients with upright norepinephrine levels above 600 pg/mL were included in the hyperadrenergic cohort and 58 composed the orthostatic hypotension cohort. Both cohorts were followed for 7 years while assessing all-cause mortality and phenoconversion to neurodegenerative autonomic disorders. Results Hyperadrenergic patients showed an exaggerated orthostatic increase in norepinephrine to 938 ± 305 pg/mL upon head up tilt despite presenting with impaired autonomic reflexes. The 7-year mortality rate was 35% in the hyperadrenergic cohort compared to 22% in orthostatic hypotension (p = 0.01). The hyperadrenergic cohort had a greater phenoconversion rate to multiple system atrophy (p = 0.04), whereas the orthostatic hypotension cohort had greater phenoconversion to Parkinson's disease and dementia with Lewy bodies. Conclusions Despite having less severe autonomic impairment, our data suggests that hyperadrenergic orthostatic hypotension has worse clinical outcomes than neurogenic orthostatic hypotension. Patients with hyperadrenergic orthostatic hypotension require careful monitoring, given that this condition may be associated with negative outcomes.
| S-EPMC10543399 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that orthostatic hypotension (OH) might cause cerebral hypoperfusion and injury, we examined the longitudinal relationship between OH or orthostatic symptoms and incident neurologic outcomes in a community population of older adults.MethodsCardiovascular Health Study participants (≥65 years) without dementia or stroke had blood pressure (BP) measured after lying down for 20 minutes and after standing 3 for minutes. Participants reported dizziness immediately upon standing and any dizziness in the past 2 weeks. OH was defined as a drop in standing systolic/diastolic BP ≥20/≥10 mm Hg. We determined the association between OH or dizziness with (1) MRI brain findings (ventricular size, white matter hyperintensities, brain infarcts) using linear or logistic regression, (2) cognitive function (baseline and over time) using generalized estimating equations, and (3) prospective adjudicated events (dementia, stroke, death) using Cox models. Models were adjusted for demographic characteristics and OH risk factors. We used multiple imputation to account for missing OH or dizziness (n = 534).ResultsPrior to imputation, there were 5,007 participants (mean age 72.7 ± 5.5 years, 57.6% women, 10.9% Black, 16% with OH). OH was modestly associated with death (hazard ratio [HR] 1.11; 95% confidence interval 1.02-1.20), but not MRI findings, cognition, dementia, or stroke. In contrast, dizziness upon standing was associated with lower baseline cognition (β = -1.20; -1.94 to -0.47), incident dementia (HR 1.32; 1.04-1.62), incident stroke (HR 1.22; 1.06-1.41), and death (HR 1.13; 1.06-1.21). Similarly, dizziness over the past 2 weeks was associated with higher white matter grade (β = 0.16; 0.03-0.30), brain infarcts (OR 1.31; 1.06-1.63), lower baseline cognition (β = -1.18; -2.01 to -0.34), and death (HR 1.13; 1.04-1.22).ConclusionsDizziness was more consistently associated with neurologic outcomes than OH 3 minutes after standing. Delayed OH assessments may miss pathologic information related to cerebral injury.
| S-EPMC7682840 | biostudies-literature
Project description:OBJECTIVE:To determine the effects of orthostatic hypotension (OH) measurement timing on its associations with dizziness, falls, fractures, cardiovascular disease (CVD), and mortality. METHODS:We analyzed OH measurements from the Action to Control Cardiovascular Risk in Diabetes BP trial, which evaluated two blood pressure (BP) goals (systolic BP [SBP] < 120 mm Hg vs. SBP < 140 mm Hg) and incident CVD among adults with diabetes and hypertension. Seated BP was measured after 5 minutes of rest at baseline and follow-up visits (12 months, 48 months, and exit). Standing BP was measured 3 consecutive times (M1-M3) after standing, starting at 1 minute with each measurement separated by 1 minute. Consensus OH was defined as a drop in SBP ≥ 20 mm Hg or diastolic BP (DBP) ≥ 10 mm Hg. Participants were asked about orthostatic dizziness, recent falls, and recent fractures, and underwent surveillance for CVD events and all-cause mortality. RESULTS:There were 4,268 participants with OH assessments over 8,450 visits (mean age 62.6 years [SD = 6.6]; 46.6% female; 22.3% black). Although all measures of consensus OH were significantly associated with dizziness, none were associated with falls, and only M2 (~3 minutes) was significantly associated with fractures. No measurements were associated with CVD events, but later measurements were significantly associated with mortality. BP treatment goal did not increase risk of OH regardless of timing. Associations were not consistently improved by the mean or minimum of M1-M3. CONCLUSION:In this population of adults with hypertension and diabetes, neither single time nor set of measurements were clearly superior with regard to outcomes. These findings support the use of a flexibly timed, single measurement to assess OH in clinical practice. CLINICAL TRIALS REGISTRATION:Trial Number NCT00000620.
| S-EPMC6558664 | biostudies-literature
Project description:PURPOSE OF REVIEW:This article reviews the management of orthostatic hypotension with emphasis on neurogenic orthostatic hypotension. RECENT FINDINGS:Establishing whether the cause of orthostatic hypotension is a pathologic lesion in sympathetic neurons (ie, neurogenic orthostatic hypotension) or secondary to other medical causes (ie, non-neurogenic orthostatic hypotension) can be achieved by measuring blood pressure and heart rate at the bedside. Whereas fludrocortisone has been extensively used as first-line treatment in the past, it is associated with adverse events including renal and cardiac failure and increased risk of all-cause hospitalization. Distinguishing whether neurogenic orthostatic hypotension is caused by central or peripheral dysfunction has therapeutic implications. Patients with peripheral sympathetic denervation respond better to norepinephrine agonists/precursors such as droxidopa, whereas patients with central autonomic dysfunction respond better to norepinephrine reuptake inhibitors. SUMMARY:Management of orthostatic hypotension is aimed at improving quality of life and reducing symptoms rather than at normalizing blood pressure. Nonpharmacologic measures are the key to success. Pharmacologic options include volume expansion with fludrocortisone and sympathetic enhancement with midodrine, droxidopa, and norepinephrine reuptake inhibitors. Neurogenic supine hypertension complicates management of orthostatic hypotension and is primarily ameliorated by avoiding the supine position and sleeping with the head of the bed elevated.
| S-EPMC7339914 | biostudies-literature
Project description:Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ≤92 mm Hg) or standard (mean arterial pressure, 102-107 mm Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52 864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm Hg, 95.5±14.2 mm Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15-2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09-3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80-13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21-4.30), and any CVD event (HR, 2.12; 95% CI, 1.12-3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.
| S-EPMC6214359 | biostudies-literature
Project description:Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing that can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions. OH can be caused by volume depletion, blood loss, cardiac pump failure, large varicose veins, medications, or defective activation of sympathetic nerves and reduced norepinephrine release upon standing. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and it is commonly associated with supine hypertension. Several therapeutic options are available.
| S-EPMC7029426 | biostudies-literature
Project description:ImportanceGuidelines recommend assessing orthostatic hypotension (OH) 3 minutes after rising from supine to standing positions. It is not known whether measurements performed immediately after standing predict adverse events as strongly as measurements performed closer to 3 minutes.ObjectiveTo compare early vs later OH measurements and their association with history of dizziness and longitudinal adverse outcomes.Design, setting, and participantsThis was a prospective cohort study of middle-aged (range, 44-66 years) participants in the Atherosclerosis Risk in Communities Study (1987-1989).ExposuresOrthostatic hypotension, defined as a drop in blood pressure (BP) (systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg) from the supine to standing position, was measured up to 5 times at 25-second intervals.Main outcomes and measuresWe determined the association of each of the 5 OH measurements with history of dizziness on standing (logistic regression) and risk of fall, fracture, syncope, motor vehicle crashes, and all-cause mortality (Cox regression) over a median of 23 years of follow-up (through December 31, 2013).ResultsIn 11 429 participants (mean age, 54 years; 6220 [54%] were women; 2934 [26%] were black) with at least 4 OH measurements after standing, after adjustment OH assessed at measurement 1 (mean [SD], 28 [5.4] seconds; range, 21-62 seconds) was the only measurement associated with higher odds of dizziness (odds ratio [OR], 1.49; 95% CI, 1.18-1.89). Measurement 1 was associated with the highest rates of fracture, syncope, and death at 18.9, 17.0, and 31.4 per 1000 person-years. Measurement 2 was associated with the highest rate of falls and motor vehicle crashes at 13.2 and 2.5 per 1000 person-years. Furthermore, after adjustment measurement 1 was significantly associated with risk of fall (hazard ratio [HR], 1.22; 95% CI, 1.03-1.44), fracture (HR, 1.16; 95% CI, 1.01-1.34), syncope (HR, 1.40; 95% CI, 1.20-1.63), and mortality (HR, 1.36; 95% CI, 1.23-1.51). Measurement 2 (mean [SD], 53 [7.5] seconds; range, 43-83 seconds) was associated with all long-term outcomes, including motor vehicle crashes (HR, 1.43; 95% CI, 1.04-1.96). Measurements obtained after 1 minute were not associated with dizziness and were inconsistently associated with individual long-term outcomes.Conclusions and relevanceIn contrast with prevailing recommendations, OH measurements performed within 1 minute of standing were the most strongly related to dizziness and individual adverse outcomes, suggesting that OH be assessed within 1 minute of standing.
| S-EPMC5661881 | biostudies-literature
Project description:BACKGROUND:Although orthostatic hypotension (OH) is a well-recognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease (CVD) risk is controversial. METHODS AND RESULTS:Participants with OH, defined as a decrease in blood pressure (systolic ?20 mm Hg or diastolic ?10 mm Hg) from the supine to standing position, were identified during the first visit of the ARIC (Atherosclerosis Risk in Communities) Study (1987-1989) within 2 minutes of standing. All participants were followed up for the development of myocardial infarction, heart failure, stroke, fatal coronary heart disease (CHD), any CHD (combination of silent, nonfatal, and fatal CHD or cardiac procedures), and all-cause mortality. Participants were assessed for carotid intimal thickness and plaque during the first visit. Detectable high-sensitivity troponin T (?5 ng/L) and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide; ?100 pg/mL) were determined in blood collected during the second visit (1990-1992). All associations were adjusted for known CVD risk factors. In 9139 participants (57% women; 23% black; mean age, 54±5.7 years), 3% had OH. During follow-up (median, 26 years), OH was associated with myocardial infarction (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.44-2.46), congestive heart failure (HR, 1.65; 95% CI, 1.34-2.04), stroke (HR, 1.83; 95% CI, 1.35-2.48), fatal CHD (HR, 2.77; 95% CI, 1.93-3.98), any CHD (HR, 2.00; 95% CI, 1.64-2.44), and all-cause mortality (HR, 1.68; 95% CI, 1.45-1.95). OH was also associated with carotid intimal thickness (?, 0.05 mm; 95% CI, 0.04-0.07 mm), carotid plaque (odds ratio, 1.51; 95% CI, 1.18-1.93), detectable high-sensitivity troponin T (odds ratio, 1.49; 95% CI, 1.16-1.93), and elevated NT-proBNP (odds ratio, 1.92; 95% CI, 1.48-2.49). CONCLUSIONS:OH identified in community-dwelling middle-aged adults was associated with future CVD events and subclinical CVD. Further research is necessary to establish a causal role for OH in the pathogenesis of CVD.
| S-EPMC6015335 | biostudies-literature
Project description:Orthostatic hypotension (OH) is relatively common in the early stage of Parkinson's disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.
| S-EPMC8047032 | biostudies-literature