Association Between Systemic Immune Inflammation Index and Diabetes Mellitus in the NHANES 2003-2018 Population.

Objects: This study aimed to explore the association between the Systemic Immune-Inflammation Index (SII) and diabetes mellitus (DM) and to assess its influence on the prognosis of the DM and no-DM groups. Methods: The study used data from the National Health and Nutrition Examination Survey; 9643 participants were included. Logistic regression analysis was employed to evaluate connections between SII and DM. We used the Cox proportional hazards model, restricted cubic spline, and Kaplan-Meier curve to analyze the relationship between SII and mortality. Results: The logistic regression analysis indicated that a significant increase in the likelihood of developing DM with higher SII levels (odds ratio, 1.31; 95% CI, 1.09-1.57, P = .003). The Cox model showed that there is a positive association between increased SII and higher all-cause mortality. The hazard ratios for SII were 1.53 (1.31, 1.78), 1.61 (1.31, 1.98), and 1.41 (1.12, 1.78) in the total, DM and non-DM groups, respectively. We observed a linear correlation between SII and all-cause mortality in DM participants, whereas non-DM participants and the total population showed a nonlinear correlation. Conclusion: Elevated SII levels are linked to an augmented risk of DM. Those with DM and higher SII levels demonstrated an elevated risk of mortality.

Reproductive factors and risk of cardiovascular diseases and all-cause and cardiovascular mortality in American women: NHANES 2003-2018.

BACKGROUND: The evidence regarding the association of reproductive factors with cardiovascular diseases (CVDs) is limited. AIMS: To investigate the relationship of reproductive factors with the risk of CVDs, as well as all-cause and cardiovascular mortality. METHODS: This study included 16,404 adults with reproductive factors from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2019. Logistic models and restricted cubic spline models were used to assess the association of reproductive factors with CVDs. COX proportional hazards models and restricted cubic spline models, with adjustment for potential confounding, were employed to analyze the relation between reproductive factors and cardiovascular and all-cause death. RESULTS: There is a nonlinear relationship between age at menarche and CVDs. Age at menopause ≤ 11(OR 1.36, 95% CI 1.10-1.69) was associated with an increased risk of CVDs compared to ages 12-13 years. Age at Menopause ≤ 44 (OR 1.69, 95% CI 1.40-2.03) was associated with increased CVDs compared to age 35-49 years. Number of pregnancies ≥ 5(OR 1.26, 95% CI 1.02-1.55) was associated with an increased risk of CVDs compared to one pregnancy. In continuous variable COX regression models, a later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of all-cause death. A later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of cardiac death. CONCLUSIONS: Female reproductive factors are significant risk factors for CVDs American women.

Deficiency of filamin A in smooth muscle cells protects against hypoxia­mediated pulmonary hypertension in mice.

Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role of FLNA in vascular smooth muscle cells during the development of PAH. Smooth muscle cell (SMC)­specific FLNA­deficient mice were generated and the mice were then exposed to hypoxia for 28 days to build the mouse model of PAH. Human pulmonary arterial smooth muscle cells (PASMCs) were also cultured and transfected with FLNA small interfering RNA or overexpression plasmids to investigate the effects of FLNA on PASMC proliferation and migration. Notably, compared with control individuals, the expression levels of FLNA were increased in lung tissues from patients with PAH, and it was obviously expressed in the PASMCs of pulmonary arterioles. FLNA deficiency in SMCs attenuated hypoxia­induced pulmonary hypertension and pulmonary vascular remodeling. In vitro studies suggested that absence of FLNA impaired PASMC proliferation and migration, and produced lower levels of phosphorylated (p)­PAK­1 and RAC1 activity. However, FLNA overexpression promoted PASMC proliferation and migration, and increased the expression levels of p­PAK­1 and RAC1 activity. The present study highlights the role of FLNA in pulmonary vascular remodeling; therefore, it could serve as a potential target for the treatment of PAH.

Upregulation of miR-335-5p Contributes to Right Ventricular Remodeling via Calumenin in Pulmonary Arterial Hypertension.

Right ventricular (RV) failure determines the prognosis in pulmonary arterial hypertension (PAH), but the underlying mechanism is still unclear. Growing evidence has shown that microRNAs participate in RV remodeling. This study is undertaken to explore the role of miR-335-5p in regulating RV remodeling induced by PAH. Two PAH models were used in the study, including the monocrotaline rat model and hypoxia/su5416 mouse model. miRNA sequencing and RT-qPCR validation identified that miR-335-5p was elevated in the RV of PAH rats. In vitro, miR-335-5p expression was increased after angiotensin II treatment, and miR-335-5p inhibition relieved angiotensin II-induced cardiomyocyte hypertrophy. The luciferase reporter assay showed that calumenin was a target gene for miR-335-5p. Pretreatment with miR-335-5p inhibitors could rescue calumenin downregulation induced by angiotensin II in H9C2 cells. Moreover, intracellular Ca2+ concentration and apoptosis were increased after angiotensin II treatment, and miR-335-5p inhibition decreased intracellular Ca2+ accumulation and apoptosis. Finally, in vivo miR-335-5p downregulation (antagomir miR-335-5p) attenuated RV remodeling and rescued calumenin downregulation under conditions of hypoxia/su5416 exposure. Our work highlights the role of miR-335-5p and calumenin in RV remodeling and may lead to the development of novel therapeutic strategies for right heart failure.

Knockout of AKAP150 improves impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.

Vascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150-/- ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150-/- diabetic mice. Impaired Akt/GSK3ß signalling contributed to decreased BK-ß1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-ß1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-ß1 expression, and treatment with AKAP150 siRNA suppressed GSK3ß expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3ß signalling pathway in diabetes mellitus.

Percutaneous coronary intervention in patients with essential thrombocythemia: case reports and literature review.

Essential thrombocythemia (ET) can cause systemic vascular thrombosis, but the involvement of coronary arteries is rare. This study is aimed to analyze the characteristics, treatment, and prognosis during follow-up in patients with ET after percutaneous coronary intervention (PCI). A total of eight patients with ET who had coronary heart disease and treated with PCI in our hospital from 2012 to 2018 were retrospectively studied. The basic clinical information with clinical data, data of coronary intervention, application of anti-platelet and platelet reducing drugs, and the results of long-term follow-up were recorded. There were five males and three females with a median age of 67 years. Clinical presentation was unstable angina in four cases, stable angina in one case, ST-elevation myocardial infarction in two cases, and non-ST elevation myocardial infarction in one case. The average platelet count was 722 × 109/L in admission, and hydroxyurea was used in seven cases. Coronary angiography suggested that all eight cases were single-vessel lesion. All the patients received PCI treatment, and Drug-eluting stent (DES) was used in all cases. Six were treated with one stent, one was treated with two stents and one was treated with three stents. After PCI, aspirin, and clopidogrel (or ticagrelor) were used in all cases. During the follow-up, one developed stent thrombus 2 months later, two developed stent restenosis 1 year later. In conclusion, PCI is an effective method of revascularization in patients with ET; but it may be associated with a higher rate of complications including stent thrombus and restenosis.

Cardiac function modulation depends on the A-kinase anchoring protein complex.

The A-kinase anchoring proteins (AKAPs) are a group of structurally diverse proteins identified in various species and tissues. These proteins are able to anchor protein kinase and other signalling proteins to regulate cardiac function. Acting as a scaffold protein, AKAPs ensure specificity in signal transduction by enzymes close to their appropriate effectors and substrates. Over the decades, more than 70 different AKAPs have been discovered. Accumulative evidence indicates that AKAPs play crucial roles in the functional regulation of cardiac diseases, including cardiac hypertrophy, myofibre contractility dysfunction and arrhythmias. By anchoring different partner proteins (PKA, PKC, PKD and LTCCs), AKAPs take part in different regulatory pathways to function as regulators in the heart, and a damaged structure can influence the activities of these complexes. In this review, we highlight recent advances in AKAP-associated protein complexes, focusing on local signalling events that are perturbed in cardiac diseases and their roles in interacting with ion channels and their regulatory molecules. These new findings suggest that AKAPs might have potential therapeutic value in patients with cardiac diseases, particularly malignant rhythm.

Inhibition of Src activation reverses pulmonary vascular remodeling in experimental pulmonary arterial hypertension via Akt/mTOR/HIF-1 signaling pathway.

Pulmonary arterial hypertension (PAH) is a diffuse pulmonary microvascular remodeling disease accompanied by malignant proliferation of pulmonary artery smooth muscle cells (PASMCs), which causes persistent pulmonary artery pressure elevation, right ventricular hypertrophy (RVH) and death. However, current therapies targeting pulmonary vascular remodeling and RVH remain poorly effective in reversing PAH. Overactivation of the protein tyrosine kinase Src plays an important role in tumor cell growth, proliferation and invasion; we thus hypothesized that inhibitors targeting Src activation could reverse experimental PAH. We demonstrated that Src was markedly activated in hypoxia-stimulated PASMCs from donors and PASMCs isolated from PAH patients. We investigated the effects of the Src-selective inhibitor 1-(1,1-dimethylethyl)-1-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) and berberine (BBR) on PAH-PASMC proliferation and migration by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) and wound-healing assays. Our in vitro results showed that inhibition of Src (Tyr416) phosphorylation repressed PAH-PASMC proliferation and migration by inhibiting hypoxia-inducible factor-1α (HIF-1α) expression through Akt/mTOR signal pathway. In vivo, PP1 and BBR significantly alleviated distal pulmonary vascular remodeling and decreased right ventricular systolic pressure (RVSP) and RVH in Sugen (SU) 5416/hypoxia (SU-PAH) mice. These findings demonstrate that pharmacological (PP1 or BBR) inhibition of Src activation could be a novel means of treating severe pulmonary vascular remodeling and RVH in PAH patients.

Efficacy and safety of oral targeted therapies in pulmonary arterial hypertension: a meta-analysis of randomized clinical trials.

Oral targeted therapies play an important role in the treatment of pulmonary arterial hypertension (PAH). Several new oral agents have emerged for PAH in recent years. However, whether they provide a survival advantage is still not clear. This meta-analysis aimed to assess the efficacy and safety of oral targeted therapies, especially on predefined clinical worsening events. Trials were searched in the Cochrane Library, EMBASE, and PUBMED databases through June 2018. We calculated risk ratios for dichotomous data and weighted mean differences with 95% confidence intervals (CI) for continuous data. Twenty-five trials with a total of 6847 participants were included in the meta-analysis. Oral targeted therapies were associated with significant risk reduction in clinical worsening compared with placebo (relative risk [RR] 0.64; 95% CI = 0.58-0.70; P < 0.001). This reduction in risk was driven by reduction in non-fatal endpoints, including PAH-related admissions to hospital (RR = 0.66; 95% CI = 0.56-0.76; P < 0.001), treatment escalation (RR = 0.43; 95% CI = 0.28-0.66; P < 0.001), and symptomatic progression (RR = 0.55; 95% CI = 0.48-0.64; P < 0.001), but not by reduction of mortality (RR = 0.87; 95% CI = 0.68-1.12; P = 0.215). Oral targeted therapies were also associated with improvement in 6-min walk distance (26.62 m; 95% CI = 20.54-32.71; P < 0.001) and World Health Organization functional class (RR = 1.36; 95% CI = 1.20-1.54; P < 0.001). The results of this meta-analysis showed the benefits of oral treatments on clinical worsening events in PAH. However, these oral agents did not show any survival benefit in the short-term follow-up.

Glycoprotein 130 Inhibitor Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, vascular remodelling, and microthrombotic events. Inflammatory cytokine interleukin (IL-6) may be a key factor in the development of PAH, and glycoprotein 130 (Gp130) is an important signal-transducing subunit of IL-6. The aim of our study was to evaluate the effectiveness of Gp130 inhibitor in reducing inflammation and ameliorating PAH-related vascular remodelling in monocrotaline (MCT)-exposed rats. METHODS: Sprague-Dawley rats (n = 96; weight, 240-250 g) were randomly divided into 3 groups: control, MCT-exposed (MCT), and MCT-exposed plus Gp130 inhibitor (MCT-Gp) administered daily (5 mg/kg) from days 14-28. Eight rats were killed in each group at weeks 1 through 4, with the following measured variables compared across groups on day 28: hemodynamics, right ventricular hypertrophy, morphometric measurements, immunohistochemical results, levels of IL-6, phosphorylated signal transducer and activator of transcription 3, proliferating cell nuclear antigen (PCNA), bone morphogenetic protein receptor-2 (BMPR2), proangiogenic factor, vascular endothelial growth factor (VEGF), proproliferative kinase extracellular signal-regulated kinase (ERK), survivin, Bcl-2, and Bax. RESULTS: Compared with the MCT group, Gp130 inhibitor, after MCT exposure, improved hemodynamics and significantly reduced the severity of inflammation, as estimated by levels of IL-6 (P < 0.0001), and reversed pulmonary arterial remodelling, as assessed by medial wall thickness (P < 0.0001). Gp130 inhibitor upregulated BMPR2 expression in MCT-exposed lungs (P = 0.040) and decreased the expression of PCNA, VEGF, ERK, and survivin (all P < 0.05). CONCLUSIONS: Gp130 inhibitor upregulated BMPR2 expression in MCT-exposed lungs, restored the BMPR2/IL-6 balance, reduced IL-6-associated inflammation, inhibited pulmonary artery smooth muscle cell proliferation, and ameliorated pulmonary vascular remodelling in MCT-induced PH in rats.

Role of nitric oxide synthase in the development of bone cancer pain and effect of L-NMMA.

Spinal nitric oxide is involved in the mechanisms of pain generation and transmission during inflammatory and neuropathic pain. The aim of the present study was to explore the role of spinal nitric oxide in the development of bone cancer pain. 2 x 10(5) osteosarcoma cells were implanted into the intramedullary space of right femurs of C3H/HeJ mice to induce a model of ongoing bone cancer. Polymerase chain reaction and immunohistochemical analyses were performed to assess the expression of neuronal nitric oxide synthase (nNOS) and inducible (i)NOS in the spinal cord following inoculation. The results showed that inoculation of osteosarcoma cells induced progressive bone cancer, accompanied with pain-associated behavior. The levels of nNOS mRNA in the spinal cord of tumor mice began to increase at day 10 and then decreased to the level in sham mice at day 14, while iNOS mRNA markedly increased in the tumor group at days 10 and 14. Immunohistochemical analysis showed that nNOS- and iNOS-positive neurons were mainly located in the superficial dorsal horn and around the central canal of the L3-L5 spinal cord. Intrathecal injection of 50 µg NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) attenuated cancer-evoked pain behaviors at day 14. These findings indicated that an upregulation of nNOS and iNOS in the spinal cord is associated with bone cancer pain and suggests that exogenously administered L-NMMA may have beneficial effects to alleviate bone cancer pain.

Inhibition of FGFR Signaling With PD173074 Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Rescues BMPR-II Expression.

BACKGROUND: Numerous studies have demonstrated that fibroblast growth factor-2 (FGF-2) signaling may play a pivotal role in the development of pulmonary arterial hypertension (PAH). Excessive endothelial FGF-2 contributes to smooth muscle hyperplasia and disease progression. PD173074 is a potent FGF receptor 1 (FGFR-1) inhibitor that displays high activity and selectivity. The aim of this study was to investigate the effects of PD173074 on monocrotaline-induced PAH. We also evaluated whether FGFR-1 inhibition could attenuate bone morphogenetic protein type II receptor (BMPR-II) downregulation in the monocrotaline model. METHODS: PAH model was established by a single intraperitoneal injection of monocrotaline. And then a daily intraperitoneal injection of PD173074 (20 mg/kg) was administered from day 14 to day 28. Hemodynamic parameters, right ventricular hypertrophy index and morphometry were evaluated at day 28. Western blot and immunohistochemical analyses were used to determine the expression of FGF-2 and bone morphogenetic protein signaling in the lung tissue. RESULTS: The expression of FGF-2 and FGFR-1 was upregulated in lung tissue after monocrotaline injection and it was accompanied by hemodynamic changes and pulmonary vascular remodeling. PD173074 treatment ameliorated PAH and vascular remodeling. It decreased ERK1/2 activation and rescued total Akt expression, leading to a reduction in both proliferation and apoptosis in the lung. Besides, PD173074 rescued the expression of BMPR-II and p-Smad 1/5/8. CONCLUSION: These results suggest that PD173074 can alleviate monocrotaline-induced pulmonary arterial hypertension and it may be a useful option for PAH. Our data also suggest a role of FGF-2/bone morphogenetic protein signaling interaction in PAH.

High levels of serum lactate dehydrogenase correlate with the severity and mortality of idiopathic pulmonary arterial hypertension.

Liver dysfunction reflects the status of heart failure, and previous studies have demonstrated that serum lactate dehydrogenase (S-LDH) levels are increased in patients exhibiting heart failure and liver dysfunction. Right heart failure is a main characteristic of idiopathic pulmonary arterial hypertension (IPAH). The aim of the present study was to assess the prognostic significance of S-LDH levels in patients with IPAH. S-LDH levels were determined in 173 patients with IPAH, and these patients were subclassified into two groups according to a defined upper reference limit of S-LDH (250 IU/l). Right heart catheterization was performed in all patients. A total of 53 patients were found to have elevated S-LDH to ≥250 IU/l. In a mean follow-up period of 31.2±17.9 months, 57 patients succumbed. In the group with lower S-LDH levels (S-LDH <250 IU/l), 16.7% of the patients succumbed, compared with 69.8% of patients in the group with higher S-LDH levels (S-LDH ≥250 IU/l). The Kaplan-Meier survival curves demonstrated that patients with higher S-LDH levels had a significantly lower survival rate than did those with lower S-LDH levels (log-rank test, P<0.001). Cox proportional hazard analyses identified reduced body mass index, reduced cardiac index, elevated World Health Organization functional class, higher S-LDH and an absence of PAH-targeted therapy as significant predictors of adverse outcomes. In conclusion, elevated S-LDH is a risk factor for mortality in patients with IPAH.

Platelet distribution width and mean platelet volume in idiopathic pulmonary arterial hypertension.

BACKGROUND: Previous studies have demonstrated that platelet activation occurs in patients with pulmonary arterial hypertension (PAH). Mean platelet volume (MPV) and platelet distribution width (PDW) are two markers of platelet activation, and have recently been recognised as risk predictors of cardiovascular diseases. This study aimed to investigate whether MPV and PDW would be useful to reflect disease severity and predict prognosis in idiopathic PAH (IPAH). METHODS: MPV and PDW levels were measured in 82 IPAH patients without antiplatelet or anticoagulant treatment on admission and 82 healthy controls. Concurrent collected data included clinical, haemodynamic and biochemical variables. All patients were followed-up from the date of blood testing. The endpoint was all-cause mortality. RESULTS: MPV and PDW were significantly higher in patients with IPAH than in age and sex-matched control subjects (11.4±0.9fl vs. 10.3±0.9fL and 14.3±2.9% vs. 11.9±1.9%, respectively; p=0.000). Pearson's correlation analysis revealed that MPV and PDW correlated positively with right ventricular systolic pressure, mean pulmonary arterial pressure and pulmonary vascular resistance. After a mean follow-up of 14±8 months, 12 patients died of right heart failure. Receiver operating characteristic analysis showed that MPV and PDW could not predict all-cause mortality. Multivariate Cox regression analysis suggested that right/left ventricular end-diastolic diameter ratio and NT-proBNP were independent predictive parameters of all-cause mortality. CONCLUSIONS: Our results suggest that MPV and PDW were elevated in patients with IPAH. They could partly reflect disease severity, but did not predict prognosis.

Oral targeted therapies in the treatment of pulmonary arterial hypertension: a meta-analysis of clinical trials.

BACKGROUND: Oral targeted therapies have been widely used in the treatment of pulmonary arterial hypertension (PAH). Many new oral agents emerge for PAH in recent years. In this study, we performed a meta-analysis to evaluate the efficacy and safety of oral targeted therapies in PAH, focusing on overall survival improvement. METHODS: Randomized controlled trials of oral targeted therapies in patients with PAH published through September 2013 were identified by searching the Cochrane Library, EMBASE, and PUBMED databases. We calculated risk ratios for dichotomous data and weighted mean differences with 95% confidence intervals for continuous data. RESULTS: 18 trials with a total of 4363 subjects were indentified in the meta-analysis. Analysis by drug class revealed that phosphodiesterase type 5 inhibitors (PDE-5Is) were associated with a statically significant reduction in mortality (RR 0.22; 95% CI 0.07-0.71, p = 0.011), while other drugs only showed a trend toward reducing mortality. Compared with placebo, endothelin receptor antagonists (ERAs), PDE-5Is and riociguat significantly reduced clinical worsening, ameliorated WHO function class, and increased the 6-min walk distance. However, oral prostanoids only showed a mild effect on 6-min walk distance (19.88 m; 95% CI 10.12-29.64, p = 0.000), and did not have any effect on reducing mortality and clinical worsening. Moreover, oral prostanoids significantly increased the incidence of withdrawal due to adverse effects (RR 3.41; 95% CI 2.06-5.63, p = 0.000). CONCLUSIONS: This meta-analysis suggests that all oral agents confer a therapeutic benefit. Of these, only PDE-5Is has a proven survival benefit. ERAs and riociguat are efficient in reducing clinical worsening, and ameliorating exercise capacity. Oral prostanoids have the significant adverse effects and weak therapeutic effects.

Plasma soluble ST2 levels correlate with disease severity and predict clinical worsening in patients with pulmonary arterial hypertension.

BACKGROUND: Soluble suppression of tumorigenicity (sST2) has been proposed to be a marker for biomechanical strain and a possible predictor of mortality in patients with chronic heart failure. The use of sST2 in pulmonary arterial hypertension (PAH) has not been well defined. HYPOTHESIS: Plasma sST2 levels may correlate with the disease severity and predict clinical worsening in PAH. METHODS: We performed a cohort study of 40 idiopathic PAH patients with data on demographics, exercise capacity, echocardiographic parameters, laboratory tests, hemodynamics, and medications. Plasma sST2 was assessed with the high-sensitivity ST2 ELISA kit at diagnostic catheterization. All patients were followed up from the date of blood sampling. The endpoint was clinical worsening. RESULTS: sST2 was significantly elevated in patients with idiopathic PAH compared with control subjects (28.9 ± 13.9 vs 20.7 ± 7.5 ng/mL, P = 0.003). Pearson correlation analysis revealed that sST2 levels correlated with cardiac index (r = -0.534, P = 0.000) and pulmonary vascular resistance (r = 0.350, P = 0.027), and could reflect disease severity of PAH. After a mean follow-up of 14 ± 5 months, 12 patients showed clinical worsening. Receiver operating characteristic analysis suggested that sST2 levels >31.4 ng/mL discriminated clinical worsening with a sensitivity and specificity of 83.3% and 78.6%, respectively. Kaplan-Meier analysis showed that higher sST2 levels (>31.4 ng/mL) were associated with poor clinical outcomes (P = 0.008). Multivariate Cox regression analysis showed that sST2 was an independent predictor of clinical worsening (hazard ratio: 6.067, 95% confidence interval: 1.317-27.948, P = 0.021). CONCLUSIONS: sST2 correlates with disease severity and is a significant predictor of clinical worsening in patients with PAH.

Prostanoid therapy for pulmonary arterial hypertension: a meta-analysis of survival outcomes.

BACKGROUND: Prostanoids have played an important role in the treatment of pulmonary arterial hypertension (PAH). However, whether prostanoid therapy provides a survival advantage is still not clear. The aim of this meta-analysis was to evaluate the efficacy and safety of prostanoids in PAH, focusing on the improvement in overall survival. METHODS: Trials were identified from the Cochrane Library, EMBASE, and PUBMED databases. We calculated risk ratios (RR) for dichotomous data and weighted mean differences with 95 % confidence intervals (CI) for continuous data. RESULTS: Fourteen trials with a total of 2,244 adult patients (1,189 patients in the prostanoid treatment group and 1,055 patients in the placebo group) were included in the meta-analysis. All-cause mortality rate in the control group was 4.17 %. In a 13.4-week follow-up, prostanoid treatment was associated with a 44 % reduction in mortality (RR 0.56; 95 % CI 0.35-0.88; P = 0.01).Subgroup analysis suggested that only treatment with intravenous prostanoids provided a survival benefit. Compared with placebo, prostanoids significantly reduced clinical worsening (RR 0.60; 95 % CI 0.46-0.80; P = 0.0003), increased the 6-min walk distance by 27.95 m, reduced mean pulmonary arterial pressure and pulmonary vascular resistance, and increased the cardiac index and mixed venous oxygen saturation. However, patients receiving prostanoid treatment showed a much higher incidence (RR 3.25; 95 % CI 2.07-5.10; P<0.00001) of withdrawal due to its adverse effects. CONCLUSION: The results of this meta-analysis suggest that treatment with prostanoids improves the survival of patients with PAH.

Survival advantages of excess body mass index in patients with idiopathic pulmonary arterial hypertension.

OBJECTIVE: An obesity paradox, a "paradoxical" decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure. However, the impact of BMI in patients with idiopathic pulmonary arterial hypertension (IPAH) has not been studied. This study aims to find out whether BMI is a prognostic factor in IPAH. METHODS AND RESULTS: We analysed 173 patients with IPAH. The patients were subclassified into categories of BMI defined as: under-weight (< 18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight and obese (25 to 34.9 kg/m2). The three BMI groups had similar profiles in terms of haemodynamic parameters assessed by right heart catheterization and level of NT-proBNP. The overweight and obese group had higher age, and lower WHO functional class, larger left ventricular end-diastolic dimensions (LVEDDs) than the other two groups.The Kaplan-Meier survival curves for the three BMI categories demonstrated that the overweight and obese group had a significantly higher survival rate than the normal weight and underweight groups (log-rank test, P = 0.027, P = 0.000, respectively). In a stepwise forward regression, lower BMI, higher WHO functional class, lower cardiac index, smaller LVEDDs and absence of targeted medication remained independent predictors of mortality. CONCLUSIONS: Excess body mass is a protective factor for death in patients with IPAH.