Care Needs and Clinical Outcomes of Older People with Dementia: A Population-Based Propensity Score-Matched Cohort Study

Objective

To explore the healthcare resource utilization, psychotropic drug use and mortality of older people with dementia.

Design

A nationwide propensity score-matched cohort study.

Setting

National Health Insurance Research database.

Participants

A total of 32,649 elderly people with dementia and their propensity-score matched controls (n=32,649).

Measurements

Outpatient visits, inpatient care, psychotropic drug use, in-hospital mortality and all-cause mortality at 90 and 365 days.

Results

Compared to the non-dementia group, a higher proportion of patients with dementia used inpatient services (1 year after index date: 20.91% vs. 9.55%), and the dementia group had more outpatient visits (median [standard deviation]: 7.00 [8.87] vs. 3.00 [8.30]). Furthermore, dementia cases with acute admission had the highest psychotropic drug utilization both at baseline and at the post-index dates (difference-in-differences: all <0.001). Dementia was associated with an increased risk of all-cause mortality (90 days, Odds ratio (OR)=1.85 [95%CI 1.67-2.05], p<0.001; 365 days, OR=1.59 [1.50-1.69], p<0.001) and in-hospital mortality (90 days, OR=1.97 [1.71-2.27], p<0.001; 365 days, OR=1.82 [1.61-2.05], p<0.001) compared to matched controls.

Conclusions

When older people with dementia are admitted for acute illnesses, they may increase their use of psychotropic agents and their risk of death, particularly in-hospital mortality.     

Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART)

Background and aims

HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART.

Methods

In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.

Results

At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.

Conclusion

Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.     

Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis

Context

Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results.

Objective

To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations.

Data Source and Study Selection

MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality.

Data Extraction

Performed independently by two investigators, using a standardized data extraction sheet.

Data Synthesis

In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45).

Conclusions

Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease.     

Relationship between Body Mass Index and Mortality in HIV-Infected HAART Users in the Women's Interagency HIV Study

Background

Early HIV studies suggested protective associations of overweight against mortality, yet data are lacking for the era of potent highly active antiretroviral therapy (HAART). We evaluated associations of pre-HAART initiation body mass index (BMI) with mortality among HAART-using women.

Methods

Prospective study of time to death after HAART initiation among continuous HAART users in the Women’s Interagency HIV Study. Unadjusted Kaplan–Meier and adjusted proportional hazards survival models assessed time to AIDS and non-AIDS death by last measured pre-HAART BMI.

Results

Of 1428 continuous HAART users 39 (2.7%) were underweight, 521 (36.5%) normal weight, 441 (30.9%) overweight, and 427 (29.9%) obese at time of HAART initiation. A total of 322 deaths occurred during median follow-up of 10.4 years (IQR 5.9–14.6). Censoring at non-AIDS death, the highest rate of AIDS death was observed among underweight women (p = 0.0003 for all 4 categories). In multivariate models, women underweight prior to HAART died from AIDS more than twice as rapidly vs. normal weight women (aHR 2.04, 95% CI 1.03, 4.04); but being overweight or obese (vs. normal weight) was not independently associated with AIDS death. Cumulative incidence of non-AIDS death was similar across all pre-HAART BMI categories.

Conclusions

Among continuous HAART-using women, being overweight prior to initiation was not associated with lower risk of AIDS or non-AIDS death. Being underweight prior to HAART was associated with over double the rate of AIDS death in adjusted analyses. Although overweight and obesity may be associated with many adverse health conditions, neither was predictive of mortality among the HAART-using women.     

Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) Compared with HAART-Na?ve Patients at the Limbe Regional Hospital,Cameroon

Background

Highly active antiretroviral therapy (HAART) has greatly reduced the morbidity and mortality of HIV/AIDS patients but has also been associated with increased metabolic complications and cardiovascular diseases. Data on the association between HAART and hypertension (HTN) in Africa are scarce.

Objectives

Primarily to compare the prevalence of HTN in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to assess other socio-demographic and clinical factors associated with HTN in this population.

Methods

A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and sex to 100 HAART-naïve patients). HTN was defined as a systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg.

Results

The prevalence of HTN in patients on HAART was twice (38%; 95% CI: 28.5–48.3) that of the HAART-naïve patients (19%; 95% CI, 11.8–28.1), p = 0.003. In multivariate analyses adjusted for age, gender, smoking, family history of HTN, and BMI-defined overweight, HAART was associated with HTN, the adjusted odds ratio of the HAART-treated versus HAART-naïve group was 2.20 (95% CI: 1.07–4.52), p = 0.032. HTN was associated with older age and male gender, in the HAART group and with BMI-defined overweight in the HAART-naïve group.

Conclusion

The prevalence of hypertension in HIV/AIDS patients in Limbe stands out to be elevated, higher in patients on HAART compared to those not on treatment. Blood pressure and cardiovascular risk factors should be routinely monitored. Other factors such as diet, weight control and physical exercise should also be considered.     

Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study

Background

The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients.

Methods

NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality.

Results

We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4–11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45–10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63–6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01).

Conclusions

NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.     

Interactions between HIV infection and chronic obstructive pulmonary disease: Clinical and epidemiological aspects

Introduction

An association between HIV infection and chronic obstructive pulmonary disease (COPD) has been observed in several studies.

Objective and methods

we conducted a review of the literature linking HIV infection to COPD, focusing on clinical and epidemiological data published before and during widespread highly active antiretroviral therapy (HAART).

Results

Interactions between HIV infection and COPD appear to be influenced by multiple factors. In particular, the bronchopulmonary tract can be damaged by HIV infection, the immunodeficiency it induces, and the resulting increase in the risk of pulmonary infections. In addition, the prevalence of smoking and intravenous drug use is higher in HIV-infected populations, also increasing the risk of COPD. Before the advent of HAART, respiratory tract infections probably played a major role. Since the late 1990s and the widespread use of HAART, the frequency of opportunistic infections has fallen but new complications have emerged as life expectancy has increased.

Conclusion

given the high prevalence of smoking among HIV-infected patients, COPD may contribute significantly to morbidity and mortality in this setting.     

Scoring System for Mortality in Patients Diagnosed with and Treated Surgically for Differentiated Thyroid Carcinoma with a 20-Year Follow-Up

Background

Differentiated thyroid carcinoma (DTC) is associated with an increased mortality. Few studies have constructed predictive models of all-cause mortality with a high discriminating power for patients with this disease that would enable us to determine which patients are more likely to die.

Objective

To construct a predictive model of all-cause mortality at 5, 10, 15 and 20 years for patients diagnosed with and treated surgically for DTC for use as a mobile application.

Design

We undertook a retrospective cohort study using data from 1984 to 2013.

Setting

All patients diagnosed with and treated surgically for DTC at a general university hospital covering a population of around 200,000 inhabitants in Spain.

Participants

The study involved 201 patients diagnosed with and treated surgically for DTC (174, papillary; 27, follicular).

Exposures

Age, gender, town, family history, type of surgery, type of cancer, histological subtype, microcarcinoma, multicentricity, TNM staging system, diagnostic stage, permanent post-operative complications, local and regional tumor persistence, distant metastasis, and radioiodine therapy.

Main outcome measure

All-cause mortality.

Methods

A Cox multivariate regression model was constructed to determine which variables at diagnosis were associated with mortality. Using the model a risk table was constructed based on the sum of all points to estimate the likelihood of death. This was then incorporated into a mobile application.

Results

The mean follow-up was 8.8±6.7 years. All-cause mortality was 12.9% (95% confidence interval [CI]: 8.3–17.6%). Predictive variables: older age, local tumor persistence and distant metastasis. The area under the ROC curve was 0.81 (95% CI: 0.72–0.91, p<0.001).

Conclusion

This study provides a practical clinical tool giving a simple and rapid indication (via a mobile application) of which patients with DTC are at risk of dying in 5, 10, 15 or 20 years. Nonetheless, caution should be exercised until validation studies have corroborated our results.     

The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective

To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).

Design

Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.

Methods

Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.

Results

Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001).

Conclusion

HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.     

Testing Initiatives Increase Rates of HIV Diagnosis in Primary Care and Community Settings: An Observational Single-Centre Cohort Study

Objectives

The primary objective was to examine trends in new HIV diagnoses in a UK area of high HIV prevalence between 2000 and 2012 with respect to site of diagnosis and stage of HIV infection.

Design

Single-centre observational cohort study.

Setting

An outpatient HIV department in a secondary care UK hospital.

Participants

1359 HIV-infected adults.

Main Outcome Measures

Demographic information (age, gender, ethnicity, and sexual orientation), site of initial HIV diagnosis (Routine settings such as HIV/GUM clinics versus Non-Routine settings such as primary care and community venues), stage of HIV infection, CD4 count and seroconversion symptoms were collated for each participant.

Results

There was a significant increase in the proportion of new HIV diagnoses made in Non-Routine settings (from 27.0% in 2000 to 58.8% in 2012; p<0.001). Overall there was a decrease in the rate of late diagnosis from 50.7% to 32.9% (p=0.001). Diagnosis of recent infection increased from 23.0% to 47.1% (p=0.001). Of those with recent infection, significantly more patients were likely to report symptoms consistent with a seroconversion illness over the 13 years (17.6% to 65.0%; p<0.001).

Conclusions

This is the first study, we believe, to demonstrate significant improvements in HIV diagnosis and a shift in diagnosis of HIV from HIV/GUM settings to primary practice and community settings due to multiple initiatives.     

Angiopoietin-2 as a Prognostic Biomarker of Major Adverse Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease

Background

Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort.

Methods

A total of 621 pre-dialysis stage 3–5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality

Results

Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5±28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00–16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25–4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008).

Conclusions

Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD.     

Integrating Cervical Cancer Screening with HIV Care in Cameroon: Comparative Risk Analysis of Cervical Disease in HIV-Infected Women Receiving Antiretroviral Therapy to Women in the General Population

Background

While the effect of highly active antiretroviral therapy (HAART) on natural history of cervical lesions remains controversial, resource limited countries need to understand the relevance of their own data to their settings. We compared the risk of cervical disease in HAART-experienced women with that in women in the general population of Cameroon.

Methods

A retrospective cross sectional survey of women aged 35 years and above, attending a voluntary screening campaign for cervical cancer at the Nkongsamba Regional Hospital in Cameroon between February and May 2014. Squamous intraepithelial lesions (SIL) were determined by Pap smear. Multiple logistic regression was used to compare the odds of SIL in women on HAART to women from the community with unknown HIV status.

Results

Included were 302 women of whom 131(43.4%) were HIV-infected and receiving HAART on the site while 171 (56.6%) were women from the community. Cervical disease was observed in 51(16.9%) persons of whom 15 (11.5%) cases in the HAART group and 36 (21.1%) cases in the general group (p = 0.027). After controlling for age and other covariates, women in the HAART group had a 67% reduction in the odds of cervical lesions compared with the community group [adjusted odd ratio (aOR) = 0.33, 95%CI: 0.15–0.73, p = 0.006).

Conclusion

HIV-infected women receiving HAART have a lower risk of cancer than women in the general population. This finding may not be attributed to HAART alone but to all the health benefits derived from receiving a comprehensive HIV care.     

Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials

Background

Infection with Human Immunodeficiency virus (HIV) is an important risk factor for Tuberculosis (TB). Anti-Retroviral Therapy (ART) has improved the prognosis of HIV and reduced the risk of TB infected patients. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB.

Objective

Systematically review and synthesize effect estimates of IPT for TB prevention in adult HIV patients. Secondary objectives were to assess the effect of IPT on HIV disease progression, all-cause mortality and adverse drug reaction (ADR).

Search Strategy

Electronic databases were searched to identify relevant articles in English available by September 11^th 2015.

Selection Criteria

Research articles comparing IPT to placebo or no treatment in HIV infected adults using randomized clinical trials.

Data Analysis

A qualitative review included study-level information on randomization and treatment allocation. Effect estimates were pooled using random-effects models to account for between-study heterogeneity.

Main Results

This review assessed ten randomized clinical trials that assigned 7619 HIV patients to IPT or placebo. An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, however, larger benefit of IPT was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81. There was no statistically significant effect of IPT on TB occurrence in TST negative or unknown participants. IPT also reduced the risk of HIV disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata. All-cause mortality was not affected by IPT although participants who had 12 months of IPT tend to have a reduced risk (RR = 0.65; 95% CI(0.47, 0.90)). IPT had an elevated, yet statistically non-significant, risk of adverse drug reaction [RR = 1.20; 95% CI (1.20, 1.71)]. Only a single study assessed the effect of IPT in combination with ART in preventing TB and occurrence of multi-drug resistant tuberculosis.

Conclusions

IPT use substantially contributes in preventing TB in persons with HIV in general and in TST positive individuals in particular. More evidence is needed to explain discrepancies in the protective effect of IPT in these individuals.     

Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease

Introduction

We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality.

Methods

We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus no statin use in a nested 1:2 matched study.

Results

The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786+3,572) and idiopathic lung fibrosis (n = 261+522) was higher for statin users versus never users (log-rank: P = 7·10⁻⁹ and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all-cause mortality for statin users versus never users was 0.73 (95% confidence interval, 0.68 to 0.79) in patients with interstitial lung disease and 0.76 (0.62 to 0.93) in patients with idiopathic lung fibrosis. Results were robust in all sensitivity analyses.

Conclusion

Among patients with interstitial lung disease statin use was associated with reduced all-cause mortality.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Serum Levels of Monocyte Chemoattractant Protein-1 and All-Cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.     

Club Cell-16 and RelB as Novel Determinants of Arterial Stiffness in Exacerbating COPD Patients

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) are acute events of worsened respiratory symptoms that may increase the risk of cardiovascular disease (CVD), a leading cause of mortality amongst COPD patients. The utility of lung-specific inflammatory mediators such as club cell protein-16 (CC-16) and surfactant protein D (SPD) and that of a novel marker of CV outcomes in COPD- RelB- in predicting adverse cardiovascular events during exacerbation is not known.

Methods

Thirty-eight subjects with COPD admitted to the hospital for severe exacerbation were included in this analysis. Clinical, physiological and arterial stiffness measurements were performed within 72 hours of admission; this was followed by measurements taken every 3 days until hospital discharge, then once a week until 30 days after discharge, and then again at 90 and 180 days. Plasma concentrations of inflammatory mediators were measured from peripheral venous blood taken at admission, and at days 15, 30, 90 and 180.

Results

CC-16 and RelB concentrations were increased at day 15 of exacerbations whereas SPD concentrations were decreased. The course of change in CC-16 and RelB levels over time was inversely associated with that of carotid-femoral pulse wave velocity, the gold-standard measure of arterial stiffness. Increases in CC-16 could predict a decreased number of subsequent exacerbations during follow-up.

Conclusions

Lung-specific (CC-16) and novel (RelB) biomarkers are associated with systemic cardiovascular changes over time. CC-16 can predict subsequent exacerbations in subjects with severe COPD and may be an important biomarker of pulmonary and systemic stress in COPD.     

Association of Cytomegalovirus End-Organ Disease with Stroke in People Living with HIV/AIDS: A Nationwide Population-Based Cohort Study

Objectives

Cytomegalovirus (CMV) infection might increase the risk of cardiovascular event. However, data on the link between incident stroke and co-infections of CMV and human immunodeficiency virus (HIV) are limited and inconsistent. This nationwide population-based cohort study analyzed the association of CMV end-organ disease and stroke among people living with HIV/AIDS (PLWHA).

Methods

From January 1, 1998, this study identified adult HIV individuals with and without CMV end-organ disease in the Taiwan National Health Insurance Research Database. All patients were observed for incident stroke and were followed until December 31, 2012. Time-dependent analysis was used to evaluate associations of CMV end-organ disease with stroke.

Results

Of the 22,581 PLWHA identified (439 with CMV end-organ disease and 22,142 without CMV end-organ disease), 228 (1.01%) had all-cause stroke during a mean follow-up period of 4.85 years, including 169 (0.75%) with ischemic stroke and 59 (0.26%) with hemorrhagic stroke. After adjusting for age, sex, comorbidities, opportunistic infections after HIV diagnosis, and antiretroviral treatment, CMV end-organ disease was found to be an independent risk factor for incident all-cause stroke (adjusted hazard ratio [AHR], 3.07; 95% confidence interval [CI], 1.70 to 5.55). When stroke type was considered, CMV end-organ disease was significantly positively associated with the risk of ischemic stroke (AHR, 3.14; 95% CI, 1.49 to 6.62) but not hemorrhagic stroke (AHR, 2.52; 95% CI, 0.64 to 9.91).

Conclusions

This study suggested that CMV end-organ disease was an independent predictor of ischemic stroke among PLWHA.     

Prognostic Value of Obesity on Both Overall Mortality and Cardiovascular Disease in the General Population

Background

Obesity represents an important health problem and its association with cardiovascular risk factors is well-known. The aim of this work was to assess the correlation between obesity and mortality (both, all-cause mortality and the combined variable of all-cause mortality plus the appearance of a non-fatal first cardiovascular event) in a general population sample from the south-east of Spain.

Materials and Methods

This prospective cohort study used stratified and randomized two-stage sampling. Obesity [body mass index (BMI) ≥30 kg/m²] as a predictive variable of mortality and cardiovascular events was assessed after controlling for age, sex, cardiovascular disease history, high blood pressure, diabetes mellitus, hypercholesterolemia, high-density lipoprotein/triglycerides ratio, total cholesterol and smoking with the Cox regression model.

Results

The mean follow-up time of the 1,248 participants was 10.6 years. The incidence of all-cause mortality during this period was 97 deaths for every 10,000 person/years (95% CI: 80–113) and the incidence of all-cause mortality+cardiovascular morbidity was 143 cases for every 10,000 person/years (95% CI: 124–163). A BMI ≥35 kg/m² yielded a hazard ratio for all-cause mortality of 1.94 (95% CI: 1.11–3.42) in comparison to non-obese subjects (BMI <30 kg/m²). For the combination of cardiovascular morbidity plus all-cause mortality, a BMI ≥35 kg/m² had a hazard ratio of 1.84 (95% CI: 1.15–2.93) compared to non-obese subjects.

Conclusions

A BMI ≥35 kg/m² is an important predictor of both overall mortality and of the combination of cardiovascular morbidity plus all-cause mortality.     

Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients

Background

Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.

Methods

CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).

Results

We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.

Conclusion

HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group.