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Clinical Autonomic Research : Official... Aug 2021To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults.
PURPOSE
To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults.
METHODS
Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis.
RESULTS
Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias.
CONCLUSION
Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020.
Topics: Adult; Blood Pressure; Caffeine; Databases, Factual; Humans; Hypotension, Orthostatic
PubMed: 34143333
DOI: 10.1007/s10286-021-00814-5 -
Journal of Clinical Hypertension... Aug 2019The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted... (Meta-Analysis)
Meta-Analysis
The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta-analysis was conducted in hopes of producing progress on this topic. A systematic database search was performed in electronic databases, including the Chinese Biomedical Database (CBM), PubMed, Web of Science, and the Cochrane Library. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by a random-effects model. Statistical heterogeneity was assessed with Cochran's Q test and the I statistic. From 1462 potentially eligible records, 15 studies met the inclusion criteria. Subjects with OH had a high risk of heart failure (HF) and atrial fibrillation (AF) (pooled HR 1.34, 95% CI 1.17-1.52, P < 0.001 and pooled HR 1.51, 95% CI 1.28-1.79, P < 0.001, respectively). This meta-analysis also showed significant associations between OH and the risks of developing coronary heart disease (CHD) (pooled HR 1.44, 95% CI 1.18-1.75, P < 0.001) and myocardial infarction (MI) (pooled HR 1.52, 95% CI 1.12-2.06, P = 0.008). Our study suggests that OH is positively associated with high risks of HF and AF. Moreover, it may be related to high risks of CHD and MI.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Diseases; Coronary Disease; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Myocardial Infarction; Prevalence; Prospective Studies; Risk Factors; Sensitivity and Specificity
PubMed: 31290595
DOI: 10.1111/jch.13613 -
Annals of Internal Medicine Jan 2021Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).
PURPOSE
To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.
DATA SOURCES
MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.
STUDY SELECTION
Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing.
DATA EXTRACTION
2 investigators independently abstracted articles and rated risk of bias.
DATA SYNTHESIS
5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH ( for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged.
LIMITATIONS
Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available.
CONCLUSION
Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension.
PRIMARY FUNDING SOURCE
National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753).
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Hypotension, Orthostatic
PubMed: 32909814
DOI: 10.7326/M20-4298 -
Heart Rhythm Jul 2020Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition increases synaptic norepinephrine reuptake, which may be able to prevent hypotension, bradycardia, and syncope.
OBJECTIVE
The objective of this systematic review was to evaluate the ability of 3 NET inhibitors-reboxetine, sibutramine, and atomoxetine-to prevent head-up tilt-induced vasovagal outcomes in healthy participants and patients with VVS.
METHODS
Relevant studies were identified from Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature without language restriction from database inception to August 2019. All randomized controlled trials comparing the benefit of a NET inhibitor vs placebo in adult populations were selected for review and meta-analysis.
RESULTS
Four studies (101 participants) met inclusion criteria. The mean study size was 25 (range 11-56) participants. NET inhibition reduced the likelihood of vasovagal reactions marked by hypotension and bradycardia in healthy participants during head-up tilt testing (relative risk 0.15; 95% confidence interval 0.04-0.52; P = .003). This relative risk reduction also occurred in patients with VVS during head-up tilt when given atomoxetine (relative risk 0.49; 95% confidence interval 0.28-0.86; P = .01). This was achieved through heart rate compensation with NET inhibition toward the end of tilt testing (106 ± 32 beats/min vs 60 ± 22 beats/min; P < .001), which in turn preserved cardiac output and mean arterial pressure (71 ± 20 mm Hg vs 43 ± 13 mm Hg; P < .001) in the absence of significantly increased systemic vascular resistance.
CONCLUSION
NET inhibition prevents severe vasovagal reactions and syncope induced by head-up tilt testing in both healthy participants and patients with VVS. Pharmacological NET inhibition is a promising potential treatment of recurrent syncope.
Topics: Adult; Cardiac Output; Heart Rate; Humans; Norepinephrine Plasma Membrane Transport Proteins; Quality of Life; Reboxetine; Syncope, Vasovagal; Young Adult
PubMed: 32151742
DOI: 10.1016/j.hrthm.2020.02.033 -
BMC Cardiovascular Disorders Dec 2019A number of published literature has reported that, physiologically, heart rate variability (HRV) in patients with postural orthostatic tachycardia syndrome (POTS) to be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A number of published literature has reported that, physiologically, heart rate variability (HRV) in patients with postural orthostatic tachycardia syndrome (POTS) to be greatly confounded by age, sex, race, physical fitness, and circadian rhythm. The purpose of this study was to compare between POTS patients versus healthy participants, in terms of heart rate (HR) and HRV after Head-Up tilt test (HUTT), by systematic review and meta-analysis of available published literature.
METHODS
MEDLINE (using PubMed interphase), EMBASE and SCOPUS were systematically searched for observational studies comparing POTS patients versus healthy patients, in terms of HR and HRV. HRV was grouped into Time and frequency domain outcome measurements. The time domain was measured as mean RR- interval and mean the square root of the mean of squares of successive R-R waves (rMSSD) in milliseconds. The frequency domain was measured as mean values of Low frequency power (LF), High frequency power (HF), LF/HF-ratio, LF-normalized units (LF(n.u)) and HF-normalized units (HF(n.u)). Demographic data, comorbidities, and mean values of HR, RR- interval, rMSSD, LF, HF, LF/HF-ratio, LF-(n.u) and H.F-n.u were extracted from each group and compared, by their mean differences as an overall outcome measure. Computer software, RevMan 5.3 was utilized, at a 95% significance level.
RESULTS
Twenty (20) eligible studies were found to report 717 POTS and 641 healthy participants. POTS group had a higher mean HR (p < 0.05), lower mean RR-Interval (p < 0.05), lower rMSSD (p < 0.05) than healthy participants. Furthermore, POTS group had lower mean HF(p > 0.05), lower mean LF(p > 0.05), and lower mean HF(n.u) (p > 0.05), higher LF/HF-Ratio (p > 0.05) and higher LF(n.u) (p > 0.05) as compared to healthy participants.
CONCLUSION
POTS patients have a higher HR than healthy patients after HUTT and lower HRV in terms of time domain measure but not in terms of frequency domain measure. HR and time domain analyses of HRV are more reliable than frequency domain analysis in differentiating POTS patients from the healthy participants. We call upon sensitivity and specificity studies.
Topics: Adolescent; Adult; Case-Control Studies; Child; Female; Heart Rate; Humans; Male; Middle Aged; Observational Studies as Topic; Postural Orthostatic Tachycardia Syndrome; Posture; Tilt-Table Test; Time Factors; Young Adult
PubMed: 31888497
DOI: 10.1186/s12872-019-01298-y -
Frontiers in Pediatrics 2019Postural tachycardia syndrome (POTS) is a severe health problem in children. Short-term β-blockers are recommended for pharmaceutical treatment. However, there have...
Postural tachycardia syndrome (POTS) is a severe health problem in children. Short-term β-blockers are recommended for pharmaceutical treatment. However, there have been contradictory data about its efficacy among pediatric patients. Eight studies comparing β-blockers to conventional treatments for children with POTS were selected, where 497 cases of pediatric POTS were included. The efficacy of β-blockers was evaluated using the effective rate, the change of symptom score, the change of heart rate difference and adverse events. The results were stated as relative ratio (RR) and mean difference (MD) with a 95% confidence interval (95% CI). A random-effects meta-analysis for the effective rate indicated that β-blockers were more effective in treating pediatric POTS than controlled treatment (79.5 vs. 57.3%, RR = 1.50, 95%CI: 1.15-1.96, < 0.05). A fixed-effects model analysis showed that β-blockers were more effective in lowering the symptom score and the heart rate increment during standing test than controlled treatment with a mean difference of 0.81 (95% CI: 0.44-1.18, < 0.05) and 3.78 (95% CI: 2.10-5.46, < 0.05), respectively. There were no reported severe adverse events in included studies. β-blockers are effective in treating POTS in children and adolescents, alleviating orthostatic intolerance, and improving hemodynamic abnormalities.
PubMed: 31788462
DOI: 10.3389/fped.2019.00460 -
Arquivos Brasileiros de Cardiologia Jul 2020Background Continuous aerobic exercise (CE) is one of the main non-pharmacological recommendations for hypertension prevention and treatment. CE is safe and effective to... (Meta-Analysis)
Meta-Analysis
Background Continuous aerobic exercise (CE) is one of the main non-pharmacological recommendations for hypertension prevention and treatment. CE is safe and effective to reduce blood pressure chronically, as well as in the first few hours after its performance, a phenomenon known as post-exercise hypotension (PEH). Interval exercise (IE) also results in PEH. Objective This systematic review and meta-analysis sought to compare the magnitude of PEH between CE and IE in adults. Methods A systematic review of studies published in journals indexed in the PubMed, Web of Knowledge, Scopus and CENTRAL databases was performed until March 2020, which compared the magnitude of PEH between CE and IE. PEH was defined as between 45-60 minutes post-exercise. The differences between groups on blood pressure were analyzed using the random effects model. Data were reported as weighted mean difference (WMD) and 95% confidence interval (CI). A p-value <0.05 was considered statistically significant. The TESTEX scale (0-15) was used to verify the methodological quality of the studies. Results The IE showed a higher magnitude of PEH on systolic blood pressure (WMD: -2.93 mmHg [95% CI: -4.96, -0.90], p = 0.005, I2 = 50%) and diastolic blood pressure (WMD: -1,73 mmHg [IC95%: 2,94, -0,51], p= 0.005, I2= 0%) when compared to CE (12 studies, 196 participants). The scores of the studies on the TEXTEX scale varied from 10 to 11 points. Conclusions The IE resulted in a higher magnitude of PEH when compared to CE between 45 and 60 minutes post-exercise. The absence of adverse event data during IE and CE in the studies prevents comparisons of the safety of these strategies. (Arq Bras Cardiol. 2020; 115(1):5-14).
Topics: Adult; Blood Pressure; Blood Pressure Determination; Exercise; Humans; Hypertension; Post-Exercise Hypotension
PubMed: 32401846
DOI: 10.36660/abc.20190107 -
Experimental Gerontology Aug 2024Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension.
METHODS
We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed.
RESULTS
Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21-0.72; I = 47 %; p < 0.01), n = 6 studies), but also after AHT discontinuation (risk ratio 0.39 (95 % CI = 0.28-0.55; I = 0 %; p < 0.01), n = 2 studies). Postural BP drop did not change after initiation or augmentation of AHT (mean difference 1.07 (95 % CI = -0.49-2.64; I = 92 %; p = 0.18), n = 11 studies). The main reason for ten studies not to be included in the meta-analyses was absence of baseline OH data. Most of these studies reported OH incidences between 0 and 2 %. Studies were heterogeneous in OH assessment methods (postural change, timing of BP measurements, and OH definition). Risk of bias was moderate to serious in twenty studies.
CONCLUSION
Results suggest that AHT initiation or augmentation decreases OH prevalence, implying that the risk of inducing OH may be overestimated in current AHT decision-making in older adults. However, the overall low level of evidence and the finding that AHT discontinuation reduces OH prevalence limit firm conclusions at present and highlight an important research gap. Future AHT trials in older adults should measure OH in a standardized protocol, adhering to consensus guidelines to overcome these limitations.
Topics: Aged; Aged, 80 and over; Humans; Antihypertensive Agents; Blood Pressure; Hypertension; Hypotension, Orthostatic; Prevalence
PubMed: 38772447
DOI: 10.1016/j.exger.2024.112461 -
Diabetes & Vascular Disease Research 2020The aim of this study was to assess the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of orthostatic hypotension (OH) in patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to assess the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of orthostatic hypotension (OH) in patients with type 2 diabetes mellitus (T2DM).
METHOD
A systematic literature retrieval was performed using PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception up to 16 October 2019. Data for study characteristics and outcomes of interest were extracted from each eligible study. Pooled risk ratios (RRs) with 95% confidence intervals (CI) for OH were calculated using a random-effects model.
RESULT
A total of 16 studies ( = 12,749) were included in our meta-analysis, with a result of 44 incident OH cases (29 in the SGLT2 inhibitor group, and 15 in the control group). The pooled RR was 1.17 (95% CI: 0.65-2.09). There was no evidence that receiving SGLT2 inhibitors increased the risk of OH, when stratified by age, duration of T2DM, or placebo-control or active-control and baseline blood pressure.
CONCLUSION
This meta-analysis suggested that, in general, SGLPT2 inhibitors did not increase the risk of OH in patients with T2DM. The possibility of OH should be, therefore, considered on an individual basis, especially in patients with a history of OH, long duration of T2DM, or comorbidities.
Topics: Adult; Aged; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 32981346
DOI: 10.1177/1479164120953625 -
Open Heart Jun 2024Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond placebo remains uncertain.
METHODS
The primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio.
RESULTS
We identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p<0.001), midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and closed-loop stimulation (CLS) pacing (RR 0.15, 95% CI 0.07 to 0.35, p<0.001). Unblinded trials reported significant benefits for all therapy categories other than beta blockers and consistently showed larger benefits than blinded trials.
CONCLUSIONS
Under blinded conditions, SSRIs, midodrine and CLS pacing significantly reduced syncope recurrence. Future trials for syncope should be blinded to avoid overestimating treatment effects.
PROSPERO REGISTRATION NUMBER
CRD42022330148.
Topics: Humans; Syncope, Vasovagal; Randomized Controlled Trials as Topic; Treatment Outcome; Recurrence
PubMed: 38890128
DOI: 10.1136/openhrt-2024-002669