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Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta-Analysis.

ABSTRACT: Background Recent studies have demonstrated a continuum in clinical risk related to mean pulmonary artery pressure that begins at >19 mm Hg, which is below the traditional threshold used to define pulmonary hypertension ( PH ) of 25 mm Hg. Because of the implications on patient diagnosis and prognosis, the generalizability and validity of these data need further confirmation. Methods and Results Databases were searched from inception through January 31, 2018, to identify studies comparing all-cause mortality between patients with mildly elevated mean pulmonary artery pressure near but <25 mm Hg versus the referent group. The meta-analysis included 15 nonrandomized studies and 16 482 patients (7451 [45.2%] with measured or calculated mean pulmonary artery pressure of 19-24 mm Hg by right heart catheterization [n=6037] and echocardiography [n=1414] [mild PH ]). The mean duration of follow-up was 5.2 years. Compared with the referent group, mild PH was associated with an increased risk of mortality (risk ratio, 1.52; 95% confidence interval, 1.32-1.74; P<0.001; I2=47%). Secondary analysis using risk-adjusted time-to-event estimates showed a similar result (hazard ratio, 1.19; 95% confidence interval, 1.09-1.31; P<0.001; I2=42%). The findings were consistent between subgroups of right heart catheterization and echocardiography studies ( Pinteraction>0.05). There was evidence of publication bias; however, this did not influence the risk estimate (Duval and Tweedie's trim and fill adjusted risk ratio, 1.34; 95% confidence interval, 1.15-1.56). Conclusions The risk of mortality is increased in patients with mild PH , defined as measured or calculated mean pulmonary artery pressure >19 mm Hg. These data emphasize a need for diagnosing patients with mild PH with consideration to enrollment in PH clinical studies investigating pharmacological and nonpharmacological interventions to attenuate clinical risk and improve outcomes.

SUBMITTER: Kolte D

PROVIDER: S-EPMC6222957 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta-Analysis.

Kolte Dhaval D Lakshmanan Suvasini S Jankowich Matthew D MD Brittain Evan L EL Maron Bradley A BA Choudhary Gaurav G

Journal of the American Heart Association 20180901 18

Background Recent studies have demonstrated a continuum in clinical risk related to mean pulmonary artery pressure that begins at >19 mm Hg, which is below the traditional threshold used to define pulmonary hypertension ( PH ) of 25 mm Hg. Because of the implications on patient diagnosis and prognosis, the generalizability and validity of these data need further confirmation. Methods and Results Databases were searched from inception through January 31, 2018, to identify studies comparing all-ca ...[more]

PMID: 30371195

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Project description:ObjectivesThis meta-analysis evaluates assessment of pulmonary arterial hypertension (PAH), with a focus on clinical worsening and mortality.BackgroundCardiac magnetic resonance (CMR) has prognostic value in the assessment of patients with PAH. However, there are limited data on the prediction of clinical worsening, an important composite endpoint used in PAH therapy trials.MethodsThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science databases were searched in May 2020. All CMR studies assessing clinical worsening and the prognosis of patients with PAH were included. Pooled hazard ratios of univariate regression analyses for CMR measurements, for prediction of clinical worsening and mortality, were calculated.ResultsTwenty-two studies with 1,938 participants were included in the meta-analysis. There were 18 clinical worsening events and 8 deaths per 100 patient-years. The pooled hazard ratios show that every 1% decrease in right ventricular (RV) ejection fraction is associated with a 4.9% increase in the risk of clinical worsening over 22 months of follow-up and a 2.1% increase in the risk of death over 54 months. For every 1 ml/m2 increase in RV end-systolic volume index or RV end-diastolic volume index, the risk of clinical worsening increases by 1.3% and 1%, respectively, and the risk of mortality increases by 0.9% and 0.6%. Every 1 ml/m2 decrease in left ventricular stroke volume index or left ventricular end-diastolic volume index increased the risk of death by 2.5% and 1.8%. Left ventricular parameters were not associated with clinical worsening.ConclusionsThis review confirms CMR as a powerful prognostic marker in PAH in a large cohort of patients. In addition to confirming previous observations that RV function and RV and left ventricular volumes predict mortality, RV function and volumes also predict clinical worsening. This study provides a strong rationale for considering CMR as a clinically relevant endpoint for trials of PAH therapies.

Project description:BackgroundPrevious meta-analyses of treatments for pulmonary arterial hypertension (PAH) have not shown mortality benefit from any individual class of medication.MethodsMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through November 2009 for randomized trials that evaluated any pharmacotherapy in the treatment of PAH. Reference lists from included articles and recent review articles were also searched. Analysis included randomized placebo controlled trials of at least eight weeks duration and studies comparing intravenous medication to an unblinded control group.Results1541 unique studies were identified and twenty-four articles with 3758 patients were included in the meta-analysis. Studies were reviewed and data extracted regarding study characteristics and outcomes. Data was pooled for three classes of medication: prostanoids, endothelin-receptor antagonists (ERAs), and phosphodiesterase type 5 (PDE5) inhibitors. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for mortality, 6-minute walk distance, dyspnea scores, hemodynamic parameters, and adverse effects. Mortality in the control arms was a combined 4.2% over the mean study length of 14.9 weeks. There was significant mortality benefit with prostanoid treatment (RR 0.49, CI 0.29 to 0.82), particularly comparing intravenous agents to control (RR 0.30, CI 0.14 to 0.63). Mortality benefit was not observed for ERAs (RR 0.58, CI 0.21 to 1.60) or PDE5 inhibitors (RR 0.30, CI 0.08 to 1.08). All three classes of medication improved other clinical and hemodynamic endpoints. Adverse effects that were increased in treatment arms include jaw pain, diarrhea, peripheral edema, headache, and nausea in prostanoids; and visual disturbance, dyspepsia, flushing, headache, and limb pain in PDE5 inhibitors. No adverse events were significantly associated with ERA treatment.ConclusionsTreatment of PAH with prostanoids reduces mortality and improves multiple other clinical and hemodynamic outcomes. ERAs and PDE5 inhibitors improve clinical and hemodynamic outcomes, but have no proven effect on mortality. The long-term effects of all PAH treatment requires further study.

Project description:Despite the recent increasing worldwide attention towards pulmonary hypertension (PH), its epidemiology remains poorly described in Africa. Accordingly, we performed a systematic review and meta-analysis of PH prevalence, incidence and etiologies in Africa.We searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus. Published observational studies until September 20, 2017, including adult participants residing in Africa were considered. Two review authors independently selected studies, assessed included studies for methodological quality, and extracted data. A random-effects model was used for meta-analysis. Heterogeneity was evaluated by the ? 2 test on Cochrane's Q statistic which is quantified by I2 values. Using Newcastle-Ottawa Scale, we considered a score of 0-4, 5-7, and 8-10 as indicative of high, moderate, and low risk of bias in included studies, respectively.Of 1611 entries, 25 studies were retained. Twelve (48%), seven (28%), and six (24%) papers had respectively a low, moderate and high risk of bias. The prevalence of PH widely varied across different populations: 9.8% (95% confidence interval: 3.2-19.3; I2?=?99.4%; 6 studies) in 11,163 people presenting with cardiac complaints; 10.6% (4.3-19.1; I2?=?90.3%; 4 studies) in 937 HIV-infected people; 32.9% (17.6-50.4; I2?=?97.2%; 3 studies) in 2077 patients with heart failure; 23.2% (15.2-32.2; I2?=?59.4%; 3 studies) in 248 patients on hemodialysis; 12.9% (11.8-14.0; I2?=?79.7%; 2 studies) in 3750 patients with rheumatic heart disease; 36.9% (29.7-44.3; I2?=?79.7; 2 studies) in 79 patients with sickle cell disease; 62.7% (49.0-74.7; 1 study) in 51 patients with chronic obstructive pulmonary disease; 25.4% (16.3-37.3; 1 study) in 63 patients with systemic lupus erythematous; 68.7% (62.8-74.1; 1 study) in 259 patients with cardiac surgery; and 7.4% (4.6-11.9; 1 study) in 202 patients with systemic sclerosis. No study reported PH incidence. From one international study (n?=?209), PH etiologies were: left heart disease (68.9%), pulmonary arterial hypertension (15.8%), lung disease and/or hypoxia (12.0%), chronic thromboembolic PH (1.9%) and unclear/multifactorial PH (15.8%).The prevalence of PH is relatively high in some populations in Africa, perhaps mainly driven by left heart diseases, highlighting the need for context-specific interventions.

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Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta-Analysis.

Publications

Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta-Analysis.

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