Suppression tumorigenicity 2 (ST2) turbidimetric immunoassay compared to enzyme-linked immunosorbent assay in predicting survival in heart failure patients with reduced ejection fraction.

BACKGROUND: Suppressor of tumorigenicity 2 (ST2) is a powerful marker of prognosis and treatment response in heart failure (HF), however, it is an enzyme-linked immunosorbent assay (ELISA) which may be cumbersome and costly. A turbidimetric immunoassay (TIA) that can run on common chemistry analyzers could overcome this. We studied a novel TIA for ST2, comparing it to commercial ST2 (ELISA). METHODS: Patients age ≥ 18 years meeting Framingham definition for HF were enrolled in a prospective registry (Oct 2007 - March 2015) at Henry Ford Hospital and donated blood samples. Participants with reduced ejection fraction (<50%) and available plasma samples were included and valid ST2 measurements were obtained on the same sample using both TIA and ELISA (N = 721). The primary endpoint was all cause death. Correlation between the methods was quantified. The association with survival was tested using unadjusted and adjusted (for MAGGIC score and NTproBNP) Cox models and comparing the Area Under the Curve (AUC). RESULTS: The inter-assay Spearman correlation coefficient was 0.77. Nonparametric regression showed no significant proportional difference (slope = 0.97) and a very small systematic difference (3.2 ng/mL). In univariate analyses, both TIA and ELISA ST2 were significant associates of survival with similar effect sizes (HR 4.46 and 3.50, respectively, both p < 0.001). In models adjusted for MAGGIC score, both ST2 remained significant in Cox models and incrementally improved AUC vs. MAGGIC alone (MAGGIC AUC = 0.757; TIA + MAGGIC AUC = 0.786, p = 0.025; ELISA + MAGGIC AUC = 0.793, p = 0.033). In models with both MAGGIC and NTproBNP included, both ST2 still remained significant but did not improve AUC. CONCLUSIONS: A novel TIA method for ST2 quantification correlates highly with ELISA and offers similarly powerful risk-stratification.

Substance use disorders and risk of suicide in a general US population: a case control study.

BACKGROUND: Prior research suggests that substance use disorders (SUDs) are associated with risk of suicide mortality, but most previous work has been conducted among Veterans Health Administration patients. Few studies have examined the relationship between SUDs and suicide mortality in general populations. Our study estimates the association of SUDs with suicide mortality in a general US population of men and women who receive care across eight integrated health systems. METHODS: We conducted a case-control study using electronic health records and claims data from eight integrated health systems of the Mental Health Research Network. Participants were 2674 men and women who died by suicide between 2000-2013 and 267,400 matched controls. The main outcome was suicide mortality, assessed using data from the health systems and confirmed by state death data systems. Demographic and diagnostic data on substance use disorders and other health conditions were obtained from each health system. First, we compared descriptive statistics for cases and controls, including age, gender, income, and education. Next, we compared the rate of each substance use disorder category for cases and controls. Finally, we used conditional logistic regression models to estimate unadjusted and adjusted odds of suicide associated with each substance use disorder category. RESULTS: All categories of substance use disorders were associated with increased risk of suicide mortality. Adjusted odds ratios ranged from 2.0 (CI 1.7, 2.3) for patients with tobacco use disorder only to 11.2 (CI 8.0, 15.6) for patients with multiple alcohol, drug, and tobacco use disorders. Substance use disorders were associated with increased relative risk of suicide for both women and men across all categories, but the relative risk was more pronounced in women. CONCLUSIONS: Substance use disorders are associated with significant risk of suicide mortality, especially for women, even after controlling for other important risk factors. Experiencing multiple substance use disorders is particularly risky. These findings suggest increased suicide risk screening and prevention efforts for individuals with substance use disorders are needed.

PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort.

BACKGROUND: PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. OBJECTIVE: We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. METHODS: We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. RESULTS: There was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (ß=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P<.001). In asthmatics, the risk genotype (AA/AG) was associated with a 39% increase in risk of clinically relevant airway obstruction (OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. CONCLUSIONS AND CLINICAL RELEVANCE: The decrease in the FEV1 /FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation.