Risk Factors For Pulmonary Arterial Hypertension Research Articles

PULMONARY VENO–OCCLUSIVE DISEASE ASSOCIATED WITH METHAMPHETAMINE ABUSE: A FIRST CASE DESCRIPTION

Abstract Background Recreational methamphetamine is widely used worldwide (about 35 million people), mainly as 3,4–Methylenedioxymethamphetamine (MDMA). A definite association has been established between methamphetamine and pulmonary arterial hypertension (PAH). This drug–associated form of PAH shares histological, clinical and hemodynamic characteristics, prognosis and treatment strategies with idiopathic PAH. However, the association between MDMA and a rarer and devasting form of PAH with concomitant venous involvement (pulmonary veno–occlusive disease, PVOD), has never been reported. Notably, initiation of PAH–specific treatment in PVOD may lead to catastrophic consequences. Case Description A 32–year–old man was fast–track referred to our PH Centre in December 2023, due to high echocardiographic probability of pulmonary hypertension (PH). After interrogation, he admitted the regular use of MDMA. No other risk factor for PAH was found. Right heart catheterization showed a pre–capillary PH (mean pulmonary artery pressure 35 mmHg; wedge pressure 12 mmHg; pulmonary vascular resistance 5.9 WU) with low cardiac output (2.2 L/min/m2) and no acute response to vasoreactivity testing. Exercise capacity was severely reduced (oxygen consumption 19.6 mL/Kg/min, 50% of predicted) due to absent stroke volume reserve, accompanied by augmented exercise hyperventilation (VE/VCO2 slope 60) and exercise–induced desaturation (SaO2 94 à 77%), this latter not explained by a right–to–left shunt. Diffusion capacity of the lung was severely reduced (DLCO 28%). Chest CT and perfusion scan excluded both thromboembolic etiology and parenchymal lung disease. A diagnosis of PVOD was made, based on the presence of pre–capillary PH, oxygen desaturation, extreme exercise hyperventilation and very low DLCO, even in the absence of pathognomonic CT features. Counselling for stopping MDMA abuse was offered. Cautious monotherapy with macitentan was started and was well tolerated. A genetic testing for EIF2AK4 is ongoing. Contact with transplant center has been performed. A follow–up RHC has been planned before careful therapy up–titration. Conclusions This is the first case reported of the potential association between methamphetamines and PVOD. Due to the large worldwide use of MDMA, this link should be considered because of its prognostic and therapeutic implications. The diagnosis of PVOD is a clinical one, needing a high index of suspicion especially in the absence of chest CT findings.

Diagnostic Value of Serum Galectin-3 Binding Protein Level in Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) still lacks effective biomarkers to assist in its diagnosis and prognosis. Galectin-3 binding protein (Gal-3BP) plays a role in immune and inflammatory diseases. This study aimed to evaluate Gal-3BP as a prognostic and predictive factor in patients with PAH. From January 2017 to December 2019, we enrolled 167 consecutive PAH patients and 58 healthy controls. Right heart catheterization (RHC) was used to diagnose PAH. Serum Gal-3BP levels were measured by high-sensitivity human enzyme-linked immunosorbent assay (ELISA). Serum Gal-3BP levels in the PAH group were significantly higher compared with the control group (4.87±2.09 vs 2.22±0.86 μg/mL, p<0.001). Gal-3BP level was correlated with several hemodynamic parameters obtained from RHC (p<0.001). Multivariate linear regression analysis showed that Gal-3BP was a risk factor for PAH (odds ratio (OR)=2.947, 95% CI: 1.821-4.767, p<0.001). The optimal cut-off value of serum Gal-3BP level for predicting PAH was 2.89 μg/mL (area under the curve (AUC)=0.860, 95 % CI: 0.811-0.910, p<0.001). Kaplan-Meier analysis showed that Gal-3BP levels above the median (4.87 μg/mL) were associated with an increased risk of death in patients with PAH (hazard ratio (HR)=8.868, 95 % CI: 3.631-21.65, p<0.0001). Cox multivariate risk regression analysis showed that Gal-3BP was a risk factor for death in PAH patients (HR=2.779, 95 % CI: 1.823-4.237, p<0.001). Serum Gal-3BP levels were increased in patients with PAH, and levels of Gal-3BP were associated with the severity of PAH. Gal-3BP might have predictive value for the diagnosis and prognosis of PAH.

Risk factors of pulmonary arterial hypertension in patients with systemic lupus erythematosus: A meta-analysis.

To determine the risk factors of pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) through systematic reviews and meta-analyses. We undertook electronic search strategies using Medline via PubMed, Embase, Web of Science, and Cochrane Library up to April 11, 2023. Study selection and data extraction were performed by 2 authors independently. We made risk of bias judgments based on the Newcastle-Ottawa Scale (NOS). Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to estimate the overall effect sizes of potential risk factors for PAH in SLE patients. Univariate and multivariate meta-regression models were used to assess the independent effects of each risk factor on PAH. Sensitivity analyses were also conducted to explore potential sources of heterogeneity. A total of 19 articles were included in this meta-analysis, and the results showed that gender (female) [RR = 1.04, 95% CI (1.02, 1.06), p = .0001], interstitial lung disease [RR = 4.36, 95% CI (2.42, 7.85), p = .0001], alopecia [RR = 1.39, 95% CI (1.06, 1.83), p = .017], Raynaud's phenomenon [RR = 1.83, 95% CI (1.41, 2.37), p = .0001], systemic hypertension [RR = 1.30, 95% CI (1.07, 1.58), p = .007], serositis [RR = 2.29, 95% CI (1.89, 2.77), p = .0001], pericardial effusion [RR = 3.33, 95% CI (2.20, 5.05), p = .0001], anti-RNP [RR = 1.86, 95% CI (1.19, 2.91), p = .006], anti-SSA [RR = 1.28, 95% CI (1.01, 1.62), p = .041], anti-SSB [RR = 1.38, 95% CI (1.19, 1.60), p = .0001], anti-U1RNP [RR = 1.58, 95% CI (1.07, 2.34), p = .023], thrombocytopenia [RR = 1.38, 95% CI (1.14, 1.68), p = .001], and current smokers [RR = 2.20, 95% CI (1.19, 4.06), p = .012] were all risk factors for PAH related to SLE. PAH is a serious complication of SLE. Since prognosis of SLE patients after the occurrence of PAH is poor, routine examination should be conducted for SLE patients with PAH risk factors.

Comparison of Pulmonary Arterial Hypertension and Risk Factors in End Stage Renal Disease Patients with Peritoneal Dialysis and Hemodialysis

Background: Pulmonary arterial hypertension (PAH) is associated with high mortality and frequent complications in end stage renal disease patients. Epidemiological data for this disorder across the spectrum of end stage renal disease in Thai patients is limited. Objective: To compare the prevalence and risk factors of PAH in hemodialysis and peritoneal dialysis in end stage renal disease among the Thai patients. Materials and Methods: The authors retrospectively studied in patients with end stage renal disease at Pranangklao Hospital between January 2016 and December 2021. Results: A total of 201 patients were enrolled. The average age of patients was 55.57±16.22 years (47.3% male). Most patients had hypertension. Most patients had been prescribed folic acid. The number of patients with mean pulmonary artery pressure &gt;20 mmHg was 81 (77.1%) in the hemodialysis group and 52 (54.2%) in the peritoneal dialysis group (p&lt;0.001). PAH in hemodialysis was higher than peritoneal dialysis (OR 2.86, 95% CI 1.56 to 5.24, p&lt;0.001). The following were factors associated with PAH: history of coronary artery disease (OR 2.77, 95% CI 1.29 to 5.94, p&lt;0.009), history of beta-blocker use (OR 2.09, 95% CI 1.15 to 3.79, p&lt;0.015), left ventricular ejection fraction by Simpson’s method (OR 0.95, 95% CI 0.92 to 0.98, p&lt;0.001). The variable associated with PAH (peritoneal dialysis group) in multivariate logistic regression was Hemodialysis (adjusted OR 3.16, 95% CI 1.66 to 6.03, p&lt;0.001). Conclusion: End stage renal disease in Thai patients undergoing hemodialysis carry a three-fold risk of pulmonary hypertension than peritoneal dialysis patients. Keywords: Pulmonary hypertension; Hemodialysis; Peritoneal dialysis

The Role of Anti-U1 RNP Antibody in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

Connective tissue disease (CTD) patients may suffer from pulmonary arterial hypertension (PAH), a serious complication, and anti-U1 ribonucleoprotein (RNP) antibodies can be used as a potential indicator for the development and prognosis of CTD-associated PAH (CTD-PAH). However, there are still some controversies; thus, a systematic review and meta-analysis were performed. We searched PubMed, Embase, Cochrane Library, and Scopus for eligible studies and assessed their quality using Newcastle−Ottawa scales or Agency for Healthcare Research and Quality indicators according to the type of research. Odds ratio (OR) was adopted as a measure of effect in risk factor analysis, and hazard ratio (HR) was adopted for prognostic factor analysis. Publication bias was evaluated using the Egger’s test. Thirteen studies were finally included. Anti-U1 RNP antibody was proved as a risk factor for PAH among CTD patients (OR = 5.30, 95%CI 2.96−9.48, p < 0.05) and a protective factor against mortality among CTD-PAH patients (HR = 0.55, 95%CI 0.36−0.83, p < 0.05). CTD patients with positive anti-U1 RNP antibodies are at high risk for PAH, so routine screening examinations, including echocardiography, are recommended. Additionally, anti-U1 RNP positivity has been linked to decreased mortality in patients with CTD-PAH.

Relation between endothelial nitric oxide synthase genetic polymorphisms and pulmonary arterial hypertension in newborns with congenital heart disease

ABSTRACT Objective To investigate whether endothelial nitric oxide synthase (eNOS) rs1799983, rs2070744, and rs61722009 gene polymorphisms are associated with pulmonary arterial hypertension (PAH) in South Fujian newborns with congenital heart disease (CHD). Methods Genotyping for the eNOS rs1799983, rs2070744, and rs61722009 polymorphisms was performed using Sanger sequencing in 50 newborns with PAH secondary to CHD [CHD PAH (+)], 52 newborns with CHD without PAH [CHD PAH (-)], and 60 healthy controls. Results The genotype and allele frequency distributions of eNOS rs1799983, rs2070744, and rs61722009 were similar between CHD and healthy controls (P > .05). The frequencies of the eNOS rs1799983 G/T allele were 85% and 15% in the CHD PAH (+) group and 96.15% and 3.85% in the CHD PAH (-) group, the frequency of the T allele was higher in the CHD PAH (+) group than in the CHD PAH (-) group(P< .05), and patients with the GT/TT genotypes of eNOS rs1799983 may present higher PAH (OR = 4.412, 95%CI:1.411–13.797, P= .011). Newborns with the GT/TT genotypes had decreased plasma NO production compared to newborns with the GG genotype (P< .01), and NO levels in the CHD PAH (+) group were significantly lower than those in the CHD PAH (-) group (P < .05). Conclusion The T allele could be a risk factor for PAH in newborns with CHD in South Fujian through decreased levels of nitric oxide production by the endothelium.

Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease.

The development of pulmonary hypertension (PH) is common and has adverse prognostic implications in patients with heart failure due to left heart disease (LHD), and thus far, there are no known treatments specifically for PH-LHD, also known as group 2 PH. Diagnostic thresholds for PH-LHD, and clinical classification of PH-LHD phenotypes, continue to evolve and, therefore, present a challenge for basic and translational scientists actively investigating PH-LHD in the preclinical setting. Furthermore, the pathobiology of PH-LHD is not well understood, although pulmonary vascular remodeling is thought to result from (1) increased wall stress due to increased left atrial pressures; (2) hemodynamic congestion-induced decreased shear stress in the pulmonary vascular bed; (3) comorbidity-induced endothelial dysfunction with direct injury to the pulmonary microvasculature; and (4) superimposed pulmonary arterial hypertension risk factors. To ultimately be able to modify disease, either by prevention or treatment, a better understanding of the various drivers of PH-LHD, including endothelial dysfunction, abnormalities in vascular tone, platelet aggregation, inflammation, adipocytokines, and systemic complications (including splanchnic congestion and lymphatic dysfunction) must be further investigated. Here, we review the diagnostic criteria and various hemodynamic phenotypes of PH-LHD, the potential biological mechanisms underlying this disorder, and pressing questions yet to be answered about the pathobiology of PH-LHD.

Risk factors of pulmonary arterial hypertension in patients with systemic lupus erythematosus.

Pulmonary arterial hypertension symptoms in systemic lupus erythematosus patients are non-specific and early diagnosis and intervention are challenging. It remains essential to explore risk factors for pulmonary arterial hypertension in systemic lupus erythematosus patients to identify high risk patients and allow intensive monitoring. From January 2010 to December 2018, 84 patients with systemic lupus erythematosus and pulmonary arterial hypertension and 160 patients with systemic lupus erythematosus but without pulmonary arterial hypertension were enrolled. Clinical manifestations and laboratory test results were compared between the two groups to identify predictors of pulmonary arterial hypertension. Candidate pulmonary arterial hypertension risk factors were further compared among systemic lupus erythematosus-pulmonary arterial hypertension patients with different characteristics. Among collected patient characteristics, Raynaud's phenomenon (OR 2.32, 95% CI: 1.17-4.61), digital vasculitis (OR 4.12, 95% CI: 1.48-11.49), pericardial effusion, pulmonary interstitial lesions, positive anti-u1 ribonucleoprotein antibodies, and positive anticardiolipin antibodies immunoglobulin G were associated with significantly higher risk of pulmonary arterial hypertension in systemic lupus erythematosus patients. Among these candidate risk factors, positive anti-u1 ribonucleoprotein antibody was independently associated with severe pulmonary arterial hypertension and more active disease. Digital vasculitis was independently associated with systemic lupus erythematosus alleviation, while pericardial effusion was associated with systemic lupus erythematosus deterioration. Pericardial effusion was associated with longer pulmonary arterial hypertension duration. The significant association between studied clinical and laboratory indicators and risk of pulmonary arterial hypertension, pulmonary arterial hypertension and systemic lupus erythematosus characteristics suggested that these factors can be used to identify patients at higher risk of pulmonary arterial hypertension and adverse outcomes. Close monitoring may be indicated in patients with these risk factors, especially with more than one risk factor.

Health Disparities in Pulmonary Arterial Hypertension and the Impact of the COVID-19 Pandemic

Health Disparities in Pulmonary Arterial Hypertension and the Impact of the COVID-19 Pandemic

Drug- and toxin-induced pulmonary arterial hypertension: Current state of the literature

Drug- and toxin-induced pulmonary arterial hypertension (PAH) is an increasingly important sub-group of group 1 pulmonary hypertension (PH). In the last 60 years, we have seen the rise and fall of numerous prescription and illicit agents that have caused severe and deadly outbreaks of PAH. Currently, drugs and toxins are classified into “possible” and “definite” risk factors for PAH. While the exact mechanisms and pathogenesis of drug- and toxin-induced PAH are currently unknown, novel clinical and basic science studies are beginning to unravel the biologic factors and genetic underpinnings responsible for disease development. The clinical management of affected patients can be challenging as it is often difficult to identify patients early and demonstrate causality between drugs and PAH. Given the recent trends in drug utilization and development, it is highly likely that we will continue to identify new agents capable of causing pulmonary vascular disease. We must keep a high index of suspicion in order to identify patients and new compounds deemed definite or likely risk factors for PAH. Practicing pharmacovigilance, raising awareness, and working in tandem with PH patient associations and drug regulatory agencies may ultimately be our most effective strategy in preventing the next deadly outbreak of drug- and toxin-induced PAH.

ACCELERATED DEVELOPMENT OF PULMONARY ARTERIAL HYPERTENSION IN THE SETTING OF ABATACEPT THERAPY

SESSION TITLE: Pulmonary Vascular Disease SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare and debilitating disease, commonly related to connective tissue disease (CTD), idiopathic or hereditary in nature or due to certain drugs. New medications have been acknowledged as being a risk factor for developing PAH.There are case reports of some biologic drugs as a possible risk factor. Abatacept is a chimeric protein that inhibits T-lymphocyte activation and is used as a biologic drug to treat autoimmune diseases. We present a patient with PAH and acceleration of symptoms after initiation of Abatacept for underlying autoimmune disease. CASE PRESENTATION: We present a 46-year-old woman with mixed connective tissue disease and rheumatoid arthritis for 5 years, who presented with six weeks of rapidly progressed dyspnea on exertion, orthopnea and pedal edema. She had been evaluated 2 months prior, while on Infliximab, for mild intermittent dyspnea for the past 6 months and noted to have normal pulmonary function and echocardiogram. She was subsequently switched to Abatacept due to a intolerance with Infliximab. A month after initiation of this medication her dyspnea worsen and she presented 10 weeks after with severe dyspnea. Echocardiogram revealed moderate right ventricle (RV) dilation and estimated pulmonary artery systolic pressure (PASP) of 93 mmHg and right atrial pressure (RAP) of 15 mmHg. Pulmonary embolism was ruled out. Right heart catheterization (RHC) measured a mean PAP of 50 mmHg and PVR of 20 Woods units. PAH was diagnosed with WHO functional class 3. Abatacept was discontinued as a potential risk factor that accelerated symptoms.Combination therapy was initiated with Tadalafil, Ambrisentan and Furosemide, and her WHO functional class improved to 1. Repeat echocardiogram at 6 months showed PASP: 35 mmHg, RAP: 3 mmHg with normal RV size and function and markedly improved six-minute walk distance. DISCUSSION: PAH is an uncommon debilitating disease with nonspecific symptoms, making early diagnosis challenging. This makes identification of risk factors for development and progression of PAH crucial. CTD is a well-established risk factor as are certain medications. With the growing use of biologic drugs for CTD therapy, these drugs as risk factors for PAH might grow as well. To the best of our knowledge this is the second case reported with Abatacept potentially accelerating PAH symptoms in the setting of treatment for CTD. CONCLUSIONS: In an era of increasing biologic agents use in patients with CTD, who are already at risk for PAH, physicians need to be aware of this potential association. Reference #1: Promislow, S. et al. Pulmonary arterial hypertension associated with abatacept treatment for rheumatoid arthritis: A case report. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine. 2018 Reference #2: Gibbson, E. et al Reversible pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis. Can Respir J. 2015 DISCLOSURES: No relevant relationships by Selvin Jacob, source=Web Response No relevant relationships by Ginny Marmolejos, source=Web Response No relevant relationships by Kartik Ramakrishna, source=Web Response

Stimulants and Pulmonary Arterial Hypertension: An Update.

The connection between stimulants and pulmonary arterial hypertension (PAH) was first made apparent in the 1960s during an outbreak associated with anorexigen (amphetamine-like appetite suppressants) use. Since then, a total of 16 drugs and toxins have been linked to PAH (ie, drug and toxin-associated PAH [DT-APAH]), including illicit stimulants like methamphetamine. Recently, basic science research and novel genomic studies have started to shed light on possible pathologic and genetic mechanisms implicated in disease development, namely loss of function variants in genes involved in drug detoxification. This review will discuss the history and current state of knowledge regarding stimulants and their association with PAH. It will also discuss clinical management of patients with DT-APAH. Lastly, it will highlight the importance of ongoing research efforts to identify susceptibility factors implicated in DT-APAH and the need for increased pharmacovigilance and awareness to identify new drugs that may be risk factors for PAH. Ultimately, this may be our best strategy to improve clinical outcomes and prevent deadly future outbreaks of DT-APAH.

Pulmonary Arterial Hypertension Associated With Systemic Lupus Erythematosus: Results From the French Pulmonary Hypertension Registry

Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE). We identified all patients with SLE and PAH (SLE-PAH) who were enrolled in the French Pulmonary Hypertension Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 patients with SLE without known PAH was selected from SLE expert centers participating in the Pulmonary Hypertension Registry. Survival was estimated by the Kaplan-Meier method. Hazard ratios associated with potential predictors of death were estimated using Cox proportional hazard models. Of the 69 patients with SLE-PAH identified in the French Pulmonary Hypertension Registry, 51 were included in the study. They did not differ from the control group regarding age, sex, or duration of SLE at the time of the analysis but had a higher frequency of anti-SSA and anti-SSB antibodies. The delay between SLE diagnosis and PAH diagnosis was 4.9 years (range, 2.8-12.9) years. The 3- and 5-year overall survival rates were 89.4%(95%CI, 76.2%-96.5%) and 83.9%(95%CI, 68.8%-92.1%), respectively. The survival rate was significantly better in patients with anti-U1-RNP antibodies (P= .04). Patients with SLE-PAH have an overall 5-year survival rate of 83.9%after the PAH diagnosis. Anti-SSA/SSB antibodies may be a risk factor for PAH, and the presence of anti-U1-RNP antibodies appears to be a protective factor regarding survival.

Prevalence and Risk Factor of Pulmonary Hypertension in Patients with Thalassemia Major of Ilam/ West of Iran in 2014

Pulmonary arterial hypertension (PAH) is a progressive disease with high morbidity and mortality rates. Research has shown that PAH has a prevalence rate of 10-79% in thalassemia major patients. This cross-sectional study was carried out in 2014 to determine the prevalence and risk factors of PAH in all thalassemia major patients of over 18 years of age in Ilam, Iran. A cardiologist measured systolic pulmonary artery pressure (SPAP) by using Doppler echocardiography. SPAP of higher than 25 mm Hg was defined as PAH criterion. The obtained data was analyzed using SPSS, version 17. Of the 36 studied patients, 17 (47.2%) were male and 19 (52.8%) were female. The mean age of the patients was 26.0±5.6 years. The prevalence of PAH in the thalassemia major patients was estimated to be 47.2% and the mean SPAP was determined to be 26.2±14.6 mm Hg. Among the examined PAH risk factors, only the history of pulmonary disease (0.02) and transfusion (0.03) was found to be significant.

Incidence of Pulmonary Arterial Hypertension in Patients with Psoriasis: A Retrospective Cohort Study.

Inflammatory signaling may play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). To assess the incidence of PAH in patients with mild and severe psoriasis compared with their respective controls. From January 2004 to November 2012, we performed a retrospective cohort study of patients with psoriasis in the Kaiser Permanente Southern California Health Plan. Patients with an International Classification of Diseases, Ninth Revision Clinical Modification diagnostic code for psoriasis (696.1) or psoriatic arthritis (696.0) without a prior diagnosis of primary PAH (416.0) or secondary PAH (416.8) were eligible for inclusion. Patients who had never received a diagnosis of psoriasis were frequency-matched by age, sex, and race to form the control cohorts. Incidence of PAH in patients with psoriasis compared with matched controls. There were 10,115 patients with mild psoriasis, 3821 with severe psoriasis, and 69,360 matched controls. On multivariable analysis, there was a significantly increased risk of PAH developing in the severe psoriasis cohort vs their controls (hazard ratio = 1.46, 95% confidence interval = 1.09-1.94). The systemic inflammatory process underlying psoriasis may be a cause for an increased risk of PAH, but there are numerous secondary causes of PAH, some of which were not accounted for in our study. Further prospective, randomized controlled trials are necessary to establish psoriasis as a risk factor for PAH.

Interferon-induced pulmonary hypertension: an update.

Pulmonary adverse effects of interferon (IFN) therapies are rare but can be life threatening. This article proposes to review clinical and experimental data suggesting a causal link between interferon exposure and pulmonary arterial hypertension (PAH). Interferon has recently been added to the list of possible risk factors for PAH. This was justified by the reporting of many cases of pulmonary hypertension potentially associated with IFN-α or IFN-β exposure. Some of them were reversible after cessation of interferon exposure, especially in patients without concomitant risk factors for pulmonary hypertension. In contrast, it remains a challenge to definitively confirm the causal role of IFN-α in patients treated for hepatitis C viral infection because of frequent concomitant PAH risk factors such as portal hypertension and/or HIV infection. In these patients, temporal and clinical arguments suggest that interferon may potentially act as an additional trigger for PAH. Moreover, the information obtained from clinical experience with interferon therapy has been enriched by basic science research on this topic suggesting that interferon is involved in both human and experimental pulmonary hypertension. Many clinical and experimental data corroborate the link between interferon exposure and the risk to develop PAH.

Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men.

Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men. We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men. Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease-associated PAH were compared with those from age- and body mass index-matched men without clinical cardiovascular disease. There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 control subjects. Higher E2 and E2/testosterone levels were associated with the risk of PAH (odds ratio per 1 ln[E2:testosterone], 6.0; 95% confidence interval, 2.2-16.4; P = 0.001), whereas higher levels of DHEA-S were associated with a reduced risk (odds ratio per 1 ln[DHEA-S], 0.1; 95% confidence interval, 0.0-0.3; P = 0.001). E2 and DHEA-S levels were strong predictors of case status (C statistic for both, 0.82) but testosterone was not (C statistic, 0.53). Higher levels of E2 were associated with shorter 6-minute-walk distances (P = 0.03), whereas higher levels of DHEA-S were associated with lower right atrial pressure (P = 0.02) and pulmonary vascular resistance (P = 0.01) in men with PAH. Higher levels of E2 and lower levels of DHEA-S were associated with PAH in men. Sex-based differences in sex hormone processing and signaling may contribute to unique phenotypes in pulmonary vascular disease.

Baseline Characteristics and Risk Factors of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus Patients.

Peking Union Medical College Hospital (PUMCH) has started a single-center right heart catheterization (RHC)-based pulmonary arterial hypertension (PAH) study in systemic lupus erythematosus (SLE) since 2006. The baseline characteristics of these patients were described and the risk factor for PAH in lupus was identified.The demographic, clinical, laboratory, and treatment characteristics of SLE patients with PAH when they were registered were collected as the baseline data. A case-control study was conducted by taking the admitted SLE-non-PAH patients adjusted for age and gender in a 4:1 ratio during the same period as the controls. The associated variables were examined by binary multivariate logistic regression analysis to identify possible risk factors. A total of 111 RHC-confirmed SLE-PAH patients were enrolled, with the onset age of 34.6 ± 8.6 years old and the average SLE duration of 5 years. RHC revealed mPAP as 46.4 ± 11.4 mm Hg, CI as 2.7 ± 0.8 L/min × m2, and PVR as 10.5 ± 4.8 WU. 46% of patients were WHO Fc I–II. All patients were treated with immunosuppressive agents and 65% patients had PAH-targeted therapy. The case-control study had confirmed 2 independent risk factors previously published: pericardial effusion (OR = 21.290, P < 0.001) and anti-RNP antibody (OR = 12.399, P < 0.001). Meanwhile, 6 independent variables were discovered: baseline SLE duration (OR = 1.118, P = 0.007), interstitial lung disease (OR = 17.027, P < 0.001=, without acute rash (OR = 3.258, P = 0.019), anti-SSA antibody (OR = 4.836, P = 0.004), SLEDAI≤9 (OR = 26.426, P < 0.001), ESR≤20 mm/h (OR = 12.068, P < 0.001), and uric acid > 357 μmol/L (OR = 9.666, P < 0.001) to be associated with PAH in SLE patients.The PUMCH study has shown that SLE patients complicated with PAH are usually earlier diagnosed and have less disease severity than patients without PAH. The immunosuppressive therapy rate and the PAH target therapy rate were high, which is consistent with reports from Western countries. This study has confirmed that pericardial effusion and positive anti-RNP antibody are risk factors for SLE-associated PAH. Long SLE disease duration, the presence of interstitial lung disease, without acute skin rash, positive anti-SSA antibody, low SLEDAI and ESR, and high uric acid levels are also associated with PAH in SLE patients.

Prevalence and risk factors for pulmonary arterial hypertension in end-stage renal disease patients undergoing continuous ambulatory peritoneal dialysis

Background: Pulmonary arterial hypertension (PAH) is a major complication in renal failure patients, but very little information is available on the cardiovascular parameters in these patients. The prevalence and risk factors for PAH were systematically evaluated in patients with end-stage renal diseases (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: Between January 2010 and January 2014, 177 ESRD patients (85 males and 92 females) undergoing CAPD therapy were recruited. General data, biochemical parameters and echocardiographic findings were collected and PAH risk factors studied. Results: Study participants consisted of 65 patients (36.52%) with PAH (PAH group) and 112 patients without PAH (non-PAH group). The interdialytic weight gain, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure and hypertensive nephropathy incidence in the PAH group were significantly higher than the non-PAH group (all p < 0.05). There were significant differences between PAH group and non-PAH group in C-reactive protein-positive rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), hemoglobin, prealbumin and serum albumin levels (all p < 0.05). Compared with non-PAH group, PAH group showed significant increases in right ventricular internal diameter (RVID), right ventricular outflow tract diameter (RVOTD), main pulmonary artery diameter, left atrial diameter (LAD), left ventricular end-diastolic diameter, interventricular septal thickness, left ventricular mass index, early diastolic mitral annulus velocity and valve calcification incidence (all p < 0.05), and decreased left ventricular ejection fraction (LVEF), tricuspid annulus plane systolic excursion (TAPSE) and early diastolic blood flow peak and mitral annulus velocity (E/E’) (all p < 0.05). Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E’ are major risk factors for PAH. Conclusion: We observed a high incidence of PAH in ESRD patients undergoing CAPD. Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E’ are high-risk factors for PAH in ESRD patients undergoing CAPD.

Pulmonary arterial hypertension in patients treated with interferon.

Isolated cases of pulmonary arterial hypertension (PAH) in patients treated with interferon (IFN) α or β have been reported in the literature. The aim of this study was to describe all consecutive cases of PAH patients with a history of IFN exposure identified in the French reference centre for severe pulmonary hypertension between 1998 and 2012. A total of 53 patients with PAH and a history of IFN therapy were identified. 48 patients had been treated with IFNα for chronic hepatitis C. Most of them had portal hypertension (85%) and 56% had HIV co-infection. Five additional patients had been treated with IFNβ for multiple sclerosis. The diagnosis of PAH was made within 3 years after IFN therapy in 66% of patients. Repeated haemodynamic assessment was available in 13 out of 16 patients exposed to IFN after the diagnosis of PAH. Increased pulmonary vascular resistance >20% was observed in 11 out of 13 cases (median 43% increase; IQR 32-67%). In five of these patients, IFN withdrawal resulted in spontaneous haemodynamic improvement. This retrospective analysis suggests that IFN therapy may trigger PAH. However, most of these patients had other risk factors for PAH. A prospective case-control study is necessary to definitively establish a link between IFN exposure and PAH.