Maggie A. Stanislawski

Nonobstructive coronary artery disease and risk of myocardial infarction.

IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.

Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program

Background— Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. Methods and Results— We analyzed retrospectively all US veterans undergoing right heart catheterization (2007–2012) in the Veterans Affairs healthcare system (n=21 727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004–1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (⩽18 mm Hg; n=4 207); (2) borderline PH (19–24 mm Hg; n=5 030); and (3) PH (≥25 mm Hg; n=12 490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12–1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96–2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01–1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09–1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. Conclusions— These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.

Adoption of Transradial Percutaneous Coronary Intervention and Outcomes According to Center Radial Volume in the Veterans Affairs Healthcare System Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program

Background—Studies examining the association between radial approach and post–percutaneous coronary intervention (PCI) bleeding and mortality have reached conflicting conclusions. There are no current data about the use and outcomes of transradial PCI (r-PCI) in the Veterans Affairs system. Methods and Results—Consecutive veterans (n=24 143 patients) undergoing PCI in the Veterans Affairs between 2007 and 2010 were examined. On the basis of propensity to undergo r-PCI, 3 cohorts matched with veterans undergoing transfemoral access were constructed among sites performing ≥1 r-PCI, ≥50 r-PCI (high volume), and <50 r-PCI (low volume). Cox proportional hazard models were used to determine the association between PCI access site, blood transfusion, and mortality. The prevalence of r-PCI increased over time (2007=2.1%; 2010=8.8%). Overall, there was no difference in procedure success between matched groups (r-PCI 97.3% versus transfemoral PCI 96.6%; P=0.182), or in the risk of postprocedure transfusion or mortality. Among matched patients treated at high r-PCI volume sites, radial access was associated with a decreased risk of post-PCI blood transfusion (hazard ratio, 0.4; 95% confidence interval, 0.3–0.7; P<0.001), and no significant difference in the risk of mortality (hazard ratio, 0.7; 95% confidence interval, 0.4–1.3; P=0.279). Conclusions—Within the Veterans Affairs, the use of r-PCI increased over time. r-PCI may be associated with a significant decreased risk of post-PCI blood transfusion among higher volume r-PCI sites. These data demonstrate that potential benefits of r-PCI in terms of reduced post-PCI blood transfusions may be more pronounced at sites that routinely use radial access.

The Microbiome in Posttraumatic Stress Disorder and Trauma-exposed Controls: An Exploratory Study

Objective Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls to identify potential differences in microbial diversity or microbial community structure. Methods The Clinician-Administered PTSD Scale for DSM-5 was used to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA gene V3/V4 amplicons were generated and sequenced. Microbial community structure, &agr;-diversity, and &bgr;-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD. Results There were no differences between PTSD and TE control groups in &agr;- or &bgr;-diversity measures (e.g., &agr;-diversity: Shannon index, t = 0.386, p = .70; &bgr;-diversity, on the basis of analysis of similarities: Bray-Curtis test statistic = –0.033, p = .70); however, random forest analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher Clinician-Administered PTSD Scale scores (r = –0.387, p = .035). Conclusions In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.

Patient Access and 1-Year Outcomes of Percutaneous Coronary Intervention Facilities With and Without On-Site Cardiothoracic Surgery Insights From the Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking (CART) Program

Background— The safety of percutaneous coronary intervention (PCI) at medical facilities without on-site cardiothoracic (CT) surgery has been established in clinical trials. However, the comparative effectiveness of this strategy in real-world practice, including impact on patient access and outcomes, is uncertain. The Veterans Affairs (VA) health care system has used this strategy, with strict quality oversight, since 2005, and can provide insight into this question. Methods and Results— Among 24 387 patients receiving PCI at VA facilities between October 2007 and September 2010, 6616 (27.1%) patients underwent PCI at facilities (n=18) without on-site CT surgery. Patient drive time (as a proxy for access), procedural complications, 1-year mortality, myocardial infarction, and rates of subsequent revascularization procedures were compared by facility. Results were stratified by procedural indication (ST–segment-elevation myocardial infarction versus non–ST–segment-elevation myocardial infarction/unstable angina versus elective) and PCI volume. With the inclusion of PCI facilities without on-site CT surgery, median drive time for patients treated at those facilities decreased by 90.8 minutes ( P <0.001). Procedural need for emergent coronary artery bypass graft and mortality rates were low and similar between facilities. Adjusted 1-year mortality and myocardial infarction rates were similar between facilities (hazard ratio in PCI facilities without relative to those with on-site CT surgery, 1.02; 95% confidence interval, 0.87–1.2), and not modified by either PCI indication or PCI volume. Subsequent revascularization rates were higher at sites without on-site CT surgery facilities (hazard ratio, 1.21; 95% confidence interval, 1.03–1.42). Conclusions— This study suggests that providing PCI facilities without on-site CT surgery in an integrated health care system with quality oversight improves patient access without compromising procedural or 1-year outcomes. # CLINICAL PERSPECTIVE {#article-title-22}Background— The safety of percutaneous coronary intervention (PCI) at medical facilities without on-site cardiothoracic (CT) surgery has been established in clinical trials. However, the comparative effectiveness of this strategy in real-world practice, including impact on patient access and outcomes, is uncertain. The Veterans Affairs (VA) health care system has used this strategy, with strict quality oversight, since 2005, and can provide insight into this question. Methods and Results— Among 24 387 patients receiving PCI at VA facilities between October 2007 and September 2010, 6616 (27.1%) patients underwent PCI at facilities (n=18) without on-site CT surgery. Patient drive time (as a proxy for access), procedural complications, 1-year mortality, myocardial infarction, and rates of subsequent revascularization procedures were compared by facility. Results were stratified by procedural indication (ST–segment-elevation myocardial infarction versus non–ST–segment-elevation myocardial infarction/unstable angina versus elective) and PCI volume. With the inclusion of PCI facilities without on-site CT surgery, median drive time for patients treated at those facilities decreased by 90.8 minutes (P<0.001). Procedural need for emergent coronary artery bypass graft and mortality rates were low and similar between facilities. Adjusted 1-year mortality and myocardial infarction rates were similar between facilities (hazard ratio in PCI facilities without relative to those with on-site CT surgery, 1.02; 95% confidence interval, 0.87–1.2), and not modified by either PCI indication or PCI volume. Subsequent revascularization rates were higher at sites without on-site CT surgery facilities (hazard ratio, 1.21; 95% confidence interval, 1.03–1.42). Conclusions— This study suggests that providing PCI facilities without on-site CT surgery in an integrated health care system with quality oversight improves patient access without compromising procedural or 1-year outcomes.

Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the VA-CART Program

Background— Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. Methods and Results— We analyzed retrospectively all US veterans undergoing right heart catheterization (2007–2012) in the Veterans Affairs healthcare system (n=21 727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004–1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (⩽18 mm Hg; n=4 207); (2) borderline PH (19–24 mm Hg; n=5 030); and (3) PH (≥25 mm Hg; n=12 490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12–1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96–2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01–1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09–1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. Conclusions— These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.

Association Between Chronic Kidney Disease and Rates of Transfusion and Progression to End‐Stage Renal Disease in Patients Undergoing Transradial Versus Transfemoral Cardiac Catheterization—An Analysis From the Veterans Affairs Clinical Assessment Reporting and Tracking (CART) Program

Background Patients with chronic kidney disease (CKD) are at increased risk for bleeding, transfusion, and dialysis after cardiac catheterization. Whether rates of these complications are increased in this high‐risk population undergoing transradial access compared with transfemoral access is unknown. Methods and Results From the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking program, we identified 229 108 patients undergoing cardiac catheterization between 2007 and 2014, of which 48 155 (21.0%) had baseline glomerular filtration rate (GFR) between 15 and 59 mL/min. We used multivariable Cox modeling to determine the independent association between transradial access and postprocedure transfusion as well as progression to new dialysis by degree of renal dysfunction. Overall, 35 979 (15.7%) of patients underwent Transradial access. Transradial patients tended to be slightly younger, but, overall, had similar rates of CKD compared to transfemoral patients (24.3% vs 27.1%). Transradial patients had longer fluoroscopy times (7.2 vs 6.0 minutes; P<0.001), but lower contrast use (85.0 vs 100.0 mL; P<0.001). The estimated rate of blood transfusion within 48 hours was lower among transradial patients (0.85% vs 1.01%) as were rates of new dialysis at 1 year (0.58% vs 0.71%). After multivariable adjustment, transradial access was associated with lower rates of progression to dialysis at 1 year overall (hazard ratio [HR], 0.83; 95% CI, 0.70–0.98), with no trend of increased risk for dialysis by degree of CKD compared with transfemoral access. Transradial access was associated with greater reduction in transfusion rates with increasing degree of CKD (P value for trend=0.04: non‐CKD: HR, 0.99; 95% CI, 0.73–1.34; GFR 45–59 mL/min: HR, 0.93; 95% CI, 0.70–1.23; GFR 30–44 mL/min: HR, 0.73; 95% CI, 0.51–1.03; GFR 15–29 mL/min: HR, 0.43; 95% CI, 0.20–0.90). Conclusions Among patients undergoing cardiac catheterization in the VA health system, transradial access was associated with lower risk for postprocedure transfusion within 48 hours among patients with more‐severe CKD, and with lower risk of progression to end‐stage renal disease at 1 year compared with transfemoral access. These data provide additional evidence that transradial access may provide significant benefit in this high‐risk population.

Invasive coronary procedure use and outcomes among veterans with posttraumatic stress disorder: Insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program

BACKGROUND Posttraumatic stress disorder (PTSD) is prevalent in the general population and US veterans in particular and is associated with an increased risk of developing coronary artery disease (CAD). We compared the patient characteristics and postprocedural outcomes of veterans with and without PTSD undergoing coronary angiography. METHODS This is a multicenter observational study of patients who underwent coronary angiography in Veterans Affairs hospitals nationally from October 2007 to September 2011. We described patient characteristics at angiography, angiographic results, and after coronary angiography, we compared risk-adjusted 1-year rates of all-cause mortality, myocardial infarction (MI), and revascularization by the presence or absence of PTSD. RESULTS Overall, of 116,488 patients undergoing angiography, 14,918 (12.8%) had PTSD. Compared with those without PTSD, patients with PTSD were younger (median age 61.9 vs 63.7; P < .001), had higher rates of cardiovascular risk factors, and were more likely to have had a prior MI (26.4% vs 24.7%; P < .001). Patients with PTSD were more likely to present for stable angina (22.4% vs 17.0%) or atypical chest pain (58.5% vs 48.6%) and less likely to have obstructive CAD identified at angiography (55.9% vs 62.2%; P < .001). After coronary angiography, PTSD was associated with lower unadjusted 1-year rates of MI (hazard ratio (HR), 0.86; 95% CI [0.75-1.00]; P = 0.04), revascularization (HR, 0.88; 95% CI [0.83-0.93]; P < .001), and all-cause mortality (HR, 0.66; 95% CI [0.60-0.71]; P < .001). After adjustment for cardiovascular risk, PTSD was no longer associated with 1-year rates of MI or revascularization but remained associated with lower 1-year all-cause mortality (HR, 0.91; 95% CI [0.84-0.99]; P = .03). Findings were similar after further adjustment for depression, anxiety, alcohol or substance use disorders, and frequency of outpatient follow-up. CONCLUSIONS Among veterans undergoing coronary angiography in the Veterans Affairs, those with PTSD were more likely to present with elective indications and less likely to have obstructive CAD. After coronary angiography, PTSD was not associated with adverse 1-year outcomes of MI, revascularization, or all-cause mortality.

Gut microbiota in adolescents and the association with fatty liver: the EPOCH study

BackgroundRecent evidence supports that the gut microbiota may be involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and may also offer avenues for treatment or prevention.MethodsWe investigated the associations among gut microbiota, diet, and hepatic fat fraction (HFF) in 107 adolescents. Magnetic resonance imaging (MRI) was used to assess HFF, and 16S rRNA gene sequencing was performed on collected fecal samples. Dietary intake was assessed using Food Frequency Questionnaires. We examined the association between gut microbiota alpha diversity and HFF, and assessed the predictive accuracy for HFF of (1) taxonomic composition, (2) dietary intake, (3) demographic and comorbid conditions, and (4) the combination of these.ResultsLower alpha diversity was associated with higher HFF (β=−0.19, 95% confidence interval (CI) −0.36, −0.02). The selected taxa explained 17.7% (95% CI: 16.0–19.4%) of the variation in HFF. The combination of two of these taxa, Bilophila and Paraprevotella, with dietary intake of monounsaturated fatty acids and BMI z-scores explained 32.0% (95% CI: 30.3–33.6%) of the variation in HFF.ConclusionThe gut microbiota is associated with HFF in adolescents and may be useful to help identify youth who would be amenable to gut microbiota-based interventions.

Gut microbiome of mothers delivering prematurely shows reduced diversity and lower relative abundance of Bifidobacterium and Streptococcus

Objective Preterm birth is the main reason for neonatal deaths worldwide. We investigate whether maternal gut microbiota may play a previously overlooked role. Methods The Norwegian Microbiota Study (NoMIC) is a case control study on preterm birth (<259 days of gestation, calculated primarily based on the last menstrual period), including two consecutively born term infants per infant born prematurely. Eligible mothers were fluent in Norwegian and recruited from the maternity ward at a county hospital in Eastern Norway in the period 2002–2005. Fecal samples were collected at day 4 postpartum, and analyzed using 16S ribosomal RNA gene sequencing. We used samples from 121 mothers giving birth vaginally. Measures of alpha diversity (Shannon, Phylogenetic Diversity and Observed Operational Taxonomic Units) and microbiome composition were combined with information from the Medical Birth Registry, pregnancy journals, and questionnaires. Results The association between maternal gut diversity and preterm delivery was examined using logistic regression. One IQR increase in Shannon diversity was significantly associated with 38% lower odds of spontaneous preterm birth, (95% confident interval (CI): 1%, 61%), and the association was stronger when adjusting for maternal age, marital status, ethnicity, parity, BMI, education, antibiotic use, pets in the household, income and smoking (48% lower odds, 95% CI: 4.2%, 72%). Mothers delivering prematurely also had lower abundance of OTUs belonging to Bifidobacterium and Streptococcus, and of the Clostridiales order. Conclusion Analysis of maternal gut microbiota using next-generation sequencing shows that low gut diversity, with a distinct microbial composition, is associated with spontaneous preterm delivery.