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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 -
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 -
Journal of Neurology, Neurosurgery, and... Nov 2020Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.
METHODS
Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.
RESULTS
A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).
INTERPRETATION
Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
Topics: Alzheimer Disease; Antihypertensive Agents; Cognition; Craniocerebral Trauma; Depression; Diabetes Mellitus; Education; Evidence-Based Medicine; Exercise; Humans; Hyperhomocysteinemia; Hypertension; Hypotension, Orthostatic; Life Style; Obesity; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Stress, Psychological
PubMed: 32690803
DOI: 10.1136/jnnp-2019-321913 -
The American Journal of Medicine Dec 2020Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes.
METHODS
We conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate.
RESULTS
A total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (<60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by -3.97 beats per minute (95% CI, -4.08 to -3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses.
CONCLUSIONS
Our meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes.
Topics: Adult; Humans; Middle Aged; Orthostatic Intolerance; Sodium Chloride, Dietary; Young Adult
PubMed: 32603788
DOI: 10.1016/j.amjmed.2020.05.028 -
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 -
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 -
Journal of Clinical Medicine Jan 2020Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and... (Review)
Review
Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case-control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing-remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.
PubMed: 31991711
DOI: 10.3390/jcm9020335 -
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 -
Indian Heart Journal 2019Orthostatic hypotension (OH) is common among elderly patients. Its presence may herald severe underlying comorbidities and be associated with a higher risk of mortality.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Orthostatic hypotension (OH) is common among elderly patients. Its presence may herald severe underlying comorbidities and be associated with a higher risk of mortality. Interestingly, recent studies suggest that OH is associated with new-onset atrial fibrillation (AF). However, a systematic review and meta-analysis of the literature has not been performed. We assessed the association between AF and OH through a systematic review of the literature and a meta-analysis.
METHODS
We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2018. Published prospective or retrospective cohort studies that compared new-onset AF between male patients with and without OH were included. Data from each study were combined using the random-effects, generic inverse-variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.
RESULTS
Four studies from October 2010 to March 2018 were included in the meta-analysis involving 76,963 subjects (of which 3318 were diagnosed with OH). The presence of OH was associated with new-onset AF (pooled risk ratio 1.48; 95% confidence interval [1.21, 1.81], p?< 0.001; I2 = 69.4%). In hypertensive patients, analysis revealed an association between OH and the occurrence of new-onset AF (OR 1.46; 95% CI [1.27, 1.68], p < 0.001 with I2 = 0).
CONCLUSIONS
OH was associated with new-onset AF up to 1.5-fold compared with those subjects without OH. The interplay between OH and AF is likely bidirectional.
Topics: Aged; Atrial Fibrillation; Humans; Hypotension, Orthostatic; Risk Factors
PubMed: 31779860
DOI: 10.1016/j.ihj.2019.07.009