Coronary Artery Calcification (CAC) and Post-Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen-Alone Trial.

BackgroundAmong women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.Methods and resultsWHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.ConclusionsAmong a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

BackgroundPreserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.MethodsData from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.ResultsThe prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter's syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative "COPD-subtype", "Restrictive-subtype", and a highly symptomatic "Metabolic-subtype".ConclusionsPRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.Trial registrationClinicaltrials.gov Identifier: NCT000608764

Cost-effectiveness of paediatric central venous catheters in the UK:A secondary publication from the CATCH clinical trial

Background: Antibiotic-impregnated central venous catheters (CVCs) reduce the risk of bloodstream infections (BSIs) in patients treated in pediatric intensive care units (PICUs). However, it is unclear if they are cost-effective from the perspective of the National Health Service (NHS) in the UK.Methods: Economic evaluation alongside the CATCH trial (ISRCTN34884569) to estimate the incremental cost effectiveness ratio (ICER) of antibiotic-impregnated (rifampicin and minocycline), heparin-bonded and standard polyurethane CVCs. The 6-month costs of CVCs and hospital admissions and visits were determined from administrative hospital data and case report forms.Results: BSIs were detected in 3.59% (18/502) of patients randomized to standard, 1.44% (7/486) to antibiotic and 3.42% (17/497) to heparin CVCs. Lengths of hospital stay did not differ between intervention groups. Total mean costs (95% confidence interval) were: £45,663 (£41,647–£50,009) for antibiotic, £42,065 (£38,322–£46,110) for heparin, and £44,503 (£40,619–£48,666) for standard CVCs. As heparin CVCs were not clinically effective at reducing BSI rate compared to standard CVCs, they were considered not to be cost-effective. The ICER for antibiotic vs. standard CVCs, of £54,057 per BSI avoided, was sensitive to the analytical time horizon.Conclusions: Substituting standard CVCs for antibiotic CVCs in PICUs will result in reduced occurrence of BSI but there is uncertainty as to whether this would be a cost-effective strategy for the NHS

Increased Risk of Hypertension Associated with Spondyloarthritis Disease Duration: Results from the ASAS-COMOSPA Study

Objective: Spondyloarthritis (SpA) is associated with a number of cardiovascular (CV) comorbidities. We examined the association of SpA disease duration and delay in diagnosis with CV-related conditions. Methods: Using data from the COMOSPA study, the associations between SpA disease duration and CV-related conditions were evaluated in univariable and multivariable logistic regression models. Each model examined 1 CV-related factor as dependent and “SpA disease duration” as a predictor, adjusted for relevant confounders. Results: Data from 3923 subjects (median SpA disease duration 5.1 yrs, interquartile range 1.3–11.8 yrs) were available for analysis. The main CV-related conditions were hypertension (HTN; 22.4%), ischemic heart disease (2.6%), stroke (1.3%), and diabetes mellitus (5.5%). HTN was associated with SpA disease duration in both univariable and multivariable analysis, with an OR of 1.129 (95% CI 1.072–1.189; p < 0.001) for each 5-year increase in SpA disease duration. Other factors associated with HTN were age, male sex, current body mass index, ever steroid therapy, and ever synthetic disease-modifying antirheumatic drug therapy, but not nonsteroidal antiinflammatory drugs (NSAID). In subgroup analysis, the strongest association of HTN and disease duration was seen in subjects with the axial-only SpA phenotype (OR 1.202, 95% CI 1.053–1.372) but not in those with peripheral-only SpA (OR 0.902, 95% CI 0.760–1.070). The other CV conditions were not associated with SpA disease duration. Conclusion: Duration of SpA disease in the ASAS-COMOSPA cohort is associated with higher odds of HTN, particularly in those with axial disease, but not with other CV-related conditions. The association with HTN does not appear to be related to NSAID exposure

Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: A report from the African American Study of Kidney Disease (AASK) Trial

Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: A report from the African American Study of Kidney Disease (AASK) Trial. African Americans have excess hypertension and end-stage renal disease presumed due to hypertension compared to Caucasians. The AASK was designed to examine the impact of antihypertensive therapies and two levels of blood pressure control on the rate of decline of GFR in African Americans with presumed hypertensive renal disease. During the pilot phase of the trial, eligible participants were requested to undergo renal biopsy to assess the underlying lesions in this population. Eighty-eight hypertensive (diastolic BP > 95mm Hg) non-diabetic African American patients between the ages of 18 to 70 years, with GFR between 25 to 70 ml/min/1.73m2 and without marked proteinuria were assessed for possible renal biopsy. Forty-three patients did not undergo renal biopsy due to refusal or contraindications. Adequate renal biopsies were obtained in 39 of the remaining 46 patients. Biopsy findings were analyzed and then compared to clinical parameters. The 39 patients studied, 29 men and 10 women, were on average 53.0 ± 11.0 years old, and had a MAP of 109 ± 15mm Hg and GFR 51.7 ± 13.6ml/min/1.73m2 (not significantly different from nonbiopsied patients). Thirty-eight of these 39 biopsies showed arteriosclerosis and/or arteriolosclerosis, severity on average 1.5 ± 0.9 and 1.5 ± 0.8, respectively on a 0 to 3+ scale. Interstitial fibrosis was moderate, 1.3 ± 0.9 (0 to 3+ scale). Segmental glomerulosclerosis was present in five biopsies, and in one patient, biopsy and clinical findings were consistent with idiopathic focal segmental glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis in one patient, basement membrane thickening suggestive of diabetic nephropathy in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis were tightly linked, and correlated with interstitial fibrosis and the reciprocal of serum creatinine. Global glomerulosclerosis was extensive, involving on average 43 ± 26% of glomeruli. The extent of this lesion did not correlate with degree of arteriolar or arterial thickening, but did correlate with systolic blood pressure (P = 0.0174), the reciprocal of serum creatinine (P = 0.0009), serum cholesterol (P = 0.0129) and interstitial fibrosis (P < 0.0001). These data underscore that renal biopsies in non-diabetic hypertensive African-Americans with mild to moderate renal insufficiency in the absence of marked proteinuria are overwhelmingly likely to show renal vascular lesions consistent with the clinical diagnosis of hypertensive nephrosclerosis

Limb interventions in patients undergoing treatment with an unsupported bifurcated aortic endograft system: A review of the Phase II EVT Trial

AbstractIntroduction: Both supported and unsupported bifurcated endograft limbs develop flow-restricting lesions, including kinks, stenoses, and occlusions, which can be identified during or after surgery. Recognition and intervention are essential to achieve long-term graft patency and a satisfactory functional result. This report represents a comprehensive retrospective review of graft limb interventions from the Phase II EVT Trial with the Endovascular Grafting System unsupported bifurcated endograft (Guidant/EVT, Menlo Park, Calif). Methods: The study population consists of 242 patients who underwent treatment with bifurcated endografts implanted during the EVT Phase II Trial. Graft limb interventions have been divided into two groups: those in whom the intervention occurred during surgery versus those in whom the intervention occurred after surgery. Parameters studied included type, incidence, and timing of graft limb intervention, indications for intervention, procedures performed, and overall patient outcome. Results: The mean follow-up period was 31 months. Primary, primary assisted, and secondary limb patency rates were 61.6%, 93.7%, and 97.1%, respectively. Technical success rate at case completion was 97.5%. In 68 of the 242 cases, limb interventions were performed during surgery to assure patency (28.1%). In 28 cases, interventions were performed after surgery (11.6%). Of these postoperative limb problems, 82% occurred during the first 6 months. Repeat limb interventions were necessitated in three patients (1.2%). Within the intraoperative intervention group, perceived indications included kinks (15%), stenosis (57%), dissection (6%), graft redundancy (12%), and instances of twists, thrombosis, and pressure gradients (10%). These findings were successfully managed with percutaneous transluminal angioplasty only (41%), percutaneous transluminal angioplasty and stent (50%), and various combined interventions. Within the postoperative intervention group, symptomatic indications included stenosis (46%) and thrombosis/occlusion (54%). These postoperative limb events were successfully managed with stent (64%), thrombolysis (32%), and femoral-femoral bypass (21%). When limb dysfunction developed in the postoperative setting, it most often occurred within the first 6 months of implantation. Only one patient in this Phase II cohort had a lower extremity amputation unrelated to a graft limb abnormality. Conclusion: The unsupported bifurcated limbs of this endograft necessitated primary adjunctive intervention in 40% of cases. Primary intervention was two times more likely to be performed at the time of the implant rather than after surgery. Repeat limb interventions were not common. Endograft limb flow problems were successfully treated with standard endovascular or surgical interventions or both. These data may support prophylactic stenting of unsupported Ancure graft limbs. A strategy that includes both intraoperative and early postoperative graft limb surveillance is essential to detect reduced limb flow. (J Vasc Surg 2002;36:118-26.

Global and regional burden of hospital admissions for pneumonia in older adults::A systematic review and meta-analysis

Pneumonia constitutes a substantial disease burden among adults overall and those who are elderly. We aimed to identify all studies investigating the disease burden among older adults (age, ≥65 years) admitted to the hospital with pneumonia. We estimated the hospital admission rate and in-hospital case-fatality ratio (CFR) of pneumonia in older adults, stratified by age and economic status (industrialized vs developing), with data from a systematic review of studies published from 1996 through 2017 and from 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burden in older adults who would have been admitted to the hospital with pneumonia that year. We estimated the number of in-hospital pneumonia deaths by combining in-hospital CFRs with hospital admission estimates from hospital-based studies. We identified 109 eligible studies; 73 used clinical pneumonia as the case definition, and 36 used radiologically confirmed pneumonia as the case definition. We estimated that, in 2015, 6.8 million episodes (uncertainty range [UR], 5.8-8.0 episodes) of clinical pneumonia resulted in hospital admissions of older adults worldwide. The hospital admission rate increased with advancing age and was higher in men. The total disease burden was likely underestimated when using the definition of radiologically confirmed pneumonia. Based on data from 52 hospital studies reporting data on pneumonia mortality, we estimated that about 1.1 million in-hospital deaths (UR, 0.9-1.4 in-hospital deaths) occurred among older adults. The burden of pneumonia requiring hospitalization among older adults is substantial. Appropriate prevention and management strategies should be developed to reduce its impact

Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction

Aims: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short‐term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH). Methods and results: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta‐analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post‐IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta‐analysis Global Group in Chronic Heart Failure score‐predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD‐treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan–Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload‐corrected exercise pulmonary capillary wedge pressure at the 6 months post‐IASD study were associated with HFH. Conclusions: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large‐scale ongoing randomized studies are required to confirm the potential benefit of this therapy

Patterns of anti-osteoporosis medication use among women at high risk of fracture: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

OBJECTIVE: To assess patterns of anti-osteoporosis medication (AOM) use over 3 years among women at high risk of major fracture. METHODS: The GLOW registry follows a cohort of more than 40,000 women aged \u3e /= 55 from 615 primary care practices in 10 countries. Self-administered surveys (baseline, 12, 24, and 36 months) collected data on patient characteristics, perception of fracture risk, and AOM use. FRAX scores were calculated from the baseline surveys and women classified as high risk if their FRAX 10-year probability of major fracture was \u3e /= 20%. RESULTS: A total of 5774 women were classified as at high risk and had complete data over 3 years. At baseline, 2271 (39%) reported receiving AOM, 739 (13%) reported prior but not current use, and 2764 (48%) said they had never used AOM. Over 3 years, 85% of baseline non-users continued as non-users and 15% initiated AOM; among baseline users, 49% continued the same medication class, 29% stopped AOM, and 12% switched. Women who stopped AOM were less likely to self-report osteoporosis (HR 0.56, 95% CI 0.42-0.75) than women who continued AOM. Compared with non-users who did not begin treatment, women initiating AOM were more likely to report a diagnosis of osteoporosis (HR 11.3, 95% CI 8.2-15.5) or osteopenia (HR 4.1, 95% CI 2.9-5.7) and be very concerned about osteoporosis (HR 1.9, 95% CI 1.3-2.8). CONCLUSIONS: Less than 40% of women at high risk of fracture reported taking AOM. Women who stopped AOM were less likely to believe they have osteoporosis. Women who initiated treatment appeared motivated primarily by a diagnosis of osteoporosis or osteopenia and concern about the condition