Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

Objective

To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI).

Research Design and Methods

Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE.

Results

Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points.

Conclusion

Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention.     

Major Adverse Cardiovascular Events in Treated Periodontitis: A Population-Based Follow-Up Study from Taiwan

Background

The aim of the present study was to identify the long-term major adverse cardiovascular events (MACE) in treated periodontitis patients in Taiwan.

Methods

From the National Health Insurance Research Database (2001-2010), adult patients (≥ 18 years) with treated periodontitis were identified. Comparison was made between patients with mild form and severe form of treated periodontitis after propensity score matching. The primary end point was the incidence of MACE.

Results

A total of 32,504 adult patients with treated periodontitis were identified between 2001 and 2010. After propensity score matching, 27,146 patients were preserved for comparison, including 13,573 patients with mild form and 13,573 patients with severe form of treated periodontitis. During follow-up, 728 individuals in mild treated periodontitis group and 1,206 individuals in severe treated periodontitis group had at least 1 MACE event. After adjustment for gender, hyperlipidemia, hypertension and diabetes mellitus, severe treated periodontitis was associated with a mildly but significantly increased risk of MACE among older patients > 60 years of age (incidence rate ratio, 1.26; 95% confidence interval, 1.08–1.46). No association was found among younger patients ≤ 60 years of age.

Conclusions

Severe form of treated periodontitis was associated with an increased risk of MACE among older Taiwanese patients, but not among younger Taiwanese patients. We should put more efforts on the improvement of periodontal health to prevent further MACE.     

Hyponatremia Predicts New-Onset Cardiovascular Events in Peritoneal Dialysis Patients

Background and Aim

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear.

Methods

To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients.

Results

During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83–0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event.

Conclusions

These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.     

Effects of Body Mass Index on Risks for Ischemic Stroke,Thromboembolism, and Mortality in Chinese Atrial Fibrillation Patients: A Single-Center Experience

Background

Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial.

Objective

This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients.

Methods

Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality).

Results

A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5–2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m²) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m²), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m²), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05).

Conclusions

Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.     

Associations between Retinal Markers of Microvascular Disease and Cognitive Impairment in Newly Diagnosed Type 2 Diabetes Mellitus: A Case Control Study

Objective

To investigate associations between retinal microvascular changes and cognitive impairment in newly diagnosed type 2 diabetes mellitus.

Design

Case control study.

Setting

A primary care cohort with newly diagnosed type 2 diabetes mellitus.

Methods

For this analysis, we compared 69 cases with lowest decile scores (for the cohort) on the Modified Telephone Interview for Cognitive Status and 68 controls randomly selected from the remainder of the cohort. Retinal images were rated and the following measures compared between cases and controls: retinal vessel calibre, arterio-venous ratio, retinal fractal dimension, and simple and curvature retinal vessel tortuosity.

Results

Total and venular (but not arteriolar) simple retinal vessel tortuosity levels were significantly higher in cases than controls (t = 2.45, p = 0.015; t = 2.53, p = 0.013 respectively). The associations persisted after adjustment for demographic factors, retinopathy, neuropathy, obesity and blood pressure. There were no other significant differences between cases and controls in retinal measures.

Conclusions

A novel association was found between higher venular tortuosity and cognitive impairment in newly diagnosed type 2 diabetes mellitus. This might be accounted for by factors such as hypoxia, thrombus formation, increased vasoendothelial growth factor release and inflammation affecting both the visible retinal and the unobserved cerebral microvasculature.     

Gastroesophageal Reflux Disease and Atrial Fibrillation: A Nationwide Population-Based Study

Objectives

Precise mechanisms of atrial fibrillation (AF) are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD), the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF.

Methods and Results

Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62%) patients in the GERD cohort and 167 (0.56%) in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024). After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06–1.61, p = 0.013).

Conclusion

GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort.     

Newly Developed Sarcopenia as a Prognostic Factor for Survival in Patients who Underwent Liver Transplantation

Introduction

The relationship between a perioperative change in sarcopenic status and clinical outcome of liver transplantation (LT) is unknown. We investigated whether post-LT sarcopenia and changes in sarcopenic status were associated with the survival of patients.

Method

This retrospective study was based on a cohort of 145 patients from a single transplant center who during a mean of 1 year after LT underwent computed tomography imaging evaluation. The cross-sectional area of the psoas muscle of LT patients was compared with that of age- and sex-matched healthy individuals. The Cox proportional hazards regression model was used to determine whether post-LT sarcopenia and changes in sarcopenic status affect post-LT survival.

Results

The mean age at LT of the 116 male and 29 female patients was 50.2 ± 7.9 years; the mean follow-up duration was 51.6 ± 32.9 months. All pre-LT patients with sarcopenia still had sarcopenia 1 year after LT; 14 (15%) patients had newly developed sarcopenia. The mean survival duration was 91.8 ± 4.2 months for non-sarcopenic patients and 80.0 ± 5.2 months for sarcopenic patients (log-rank test, p = 0.069). In subgroup analysis, newly developed sarcopenia was an independent negative predictor for post-LT survival (hazard ratio: 10.53, 95% confidence interval: 1.37–80.93, p = 0.024).

Conclusion

Sarcopenia in LT recipients did not improve in any of the previously sarcopenic patients and newly developed within 1 year in others. Newly developed sarcopenia was associated with increased mortality. Newly developed sarcopenia can be used to stratify patients with regard to the risk of post-LT mortality.     

Renal Function Interferes with Copeptin in Prediction of Major Adverse Cardiac Events in Patients Undergoing Vascular Surgery

Objective

Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient’s perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease.

Methods

477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE).

Results

41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages.

Conclusion

Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery.     

The Use of Alendronate Is Associated with a Decreased Incidence of Type 2 Diabetes Mellitus—A Population-Based Cohort Study in Taiwan

Purpose

Bone remodeling has been linked to glucose metabolism in animal studies, but the results of human trials were inconclusive. Bisphosphonates may play a role in glucose metabolism through their impacts on bone remodeling enzymes. In this study, we aimed to examine the influence of alendronate usage on the incidence of type 2 diabetes mellitus (DM) among osteoporotic patients.

Methods

A retrospective cohort study was designed to include osteoporotic patients without DM from a population-based cohort containing 1,000,000 subjects. Patients treated with alendronate (exposed group, N=1,011) were compared with those who received no treatment (age and gender matched non-exposed group, N=3,033). Newly diagnosed DM was identified from medical records by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) code. The incidence of DM in both groups was calculated for comparison.

Results

The non-exposed group had a significantly higher incidence of DM (Odds ratio 1.21, 95% confidence interval 1.03~1.41) when compared with the exposed group. In subgroup analysis, the DM risk reduction in exposed group was only significant among those younger than 65 years and those without hypertension or dyslipidemia. Patients who were prescribed alendronate more than or equal to 3 times had demonstrated a significant reduction in DM risk.

Conclusions

Our study showed alendronate might yield a protective effect for incident DM. This effect became insignificant in patients with older age, dyslipidemia or hypertension. The underlying mechanism needs further exploration with prospective data for confirmation of the observed findings.     

Diastolic Dysfunction Is an Independent Predictor of Cardiovascular Events in Incident Dialysis Patients with Preserved Systolic Function

Background

Diastolic heart failure (HF), the prevalence of which is gradually increasing, is associated with cardiovascular (CV) morbidity and mortality in the general population and, more specifically, in patients with end-stage renal disease (ESRD). However, the impact of diastolic dysfunction on CV outcomes has not been studied in incident dialysis patients with preserved systolic function.

Methods

This prospective observational cohort study investigates the clinical consequence of diastolic dysfunction and the predictive power of diastolic echocardiographic parameters for CV events in 194 incident ESRD patients with normal or near normal systolic function, who started dialysis between July 2008 and August 2012.

Results

During a mean follow-up duration of 27.2 months, 57 patients (29.4%) experienced CV events. Compared to the CV event-free group, patients with CV events had a significantly higher left ventricular (LV) mass index, ratio of early mitral flow velocity (E) to early mitral annulus velocity (E’) (E/E’), LA volume index (LAVI), deceleration time, and right ventricular systolic pressure, and a significantly lower LV ejection fraction and E’. In multivariate Cox proportional hazard analysis, E/E’>15 and LAVI>32 mL/m² significantly predicted CV events (E/E’>15: hazard ratio [HR] = 5.40, 95% confidence interval [CI] = 2.73–10.70, P< .001; LAVI>32 mL/m²: HR = 5.56, 95% CI = 2.28–13.59, P< .001]. Kaplan-Meier analysis revealed that patients with both E/E’>15 and LAVI>32mL/m² had the worst CV outcomes.

Conclusion

An increase in E/E’ or LAVI is a significant risk factor for CV events in incident dialysis patients with preserved LV systolic function.     

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.     

Atrial Fibrillation and Colonic Neoplasia in African Americans

Background

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American.

Methods

We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression.

Results

The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9–2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7–1.6, P = 0.7) were not significantly associated AF compared to control group.

Conclusions

AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.     

Mucosal Healing and the Risk of Ischemic Heart Disease or Atrial Fibrillation in Patients with Celiac Disease; A Population-Based Study

Background

Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF.

Methods

We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF.

Results

Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were ≥60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73–1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73–1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74–1.30).

Conclusions

In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.     

Circulating Progenitor Cell Count for Cardiovascular Risk Stratification: A Pooled Analysis

Background

Circulating progenitor cells (CPC) contribute to the homeostasis of the vessel wall, and a reduced CPC count predicts cardiovascular morbidity and mortality. We tested the hypothesis that CPC count improves cardiovascular risk stratification and that this is modulated by low-grade inflammation.

Methodology/Principal Findings

We pooled data from 4 longitudinal studies, including a total of 1,057 patients having CPC determined and major adverse cardiovascular events (MACE) collected. We recorded cardiovascular risk factors and high-sensitive C-reactive protein (hsCRP) level. Risk estimates were derived from Cox proportional hazard analyses. CPC count and/or hsCRP level were added to a reference model including age, sex, cardiovascular risk factors, prevalent CVD, chronic renal failure (CRF) and medications. The sample was composed of high-risk individuals, as 76.3% had prevalent CVD and 31.6% had CRF. There were 331 (31.3%) incident MACE during an average 1.7±1.1 year follow-up time. CPC count was independently associated with incident MACE even after correction for hsCRP. According to C-statistics, models including CPC yielded a non-significant improvement in accuracy of MACE prediction. However, the integrated discrimination improvement index (IDI) showed better performance of models including CPC compared to the reference model and models including hsCRP in identifying MACE. CPC count also yielded significant net reclassification improvements (NRI) for CV death, non-fatal AMI and other CV events. The effect of CPC was independent of hsCRP, but there was a significant more-than-additive interaction between low CPC count and raised hsCRP level in predicting incident MACE.

Conclusions/Significance

In high risk individuals, a reduced CPC count helps identifying more patients at higher risk of MACE over the short term, especially in combination with a raised hsCRP level.     

Multi Drug and Other Forms of Drug Resistant Tuberculosis Are Uncommon among Treatment Na?ve Tuberculosis Patients in Tanzania

Background

Surveillance and effective management of drug resistance is important to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance rates to first line anti tuberculosis drugs and to describe factors associated with the resistance to any of the first line anti tuberculosis drugs in Dar es Salaam Tanzania.

Materials

Newly diagnosed, TB patients with neither history of tuberculosis treatment nor isoniazid prophylaxis were included into the study. Sputum specimens were cultured on either mycobacteria growth indicator tube 960 (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin, streptomycin and ethambutol was determined by either Lowenstein–Jensen (LJ) medium or mycobacteria growth indicator tube 960 (MGIT 960).

Results

A total of 933 newly diagnosed TB patients, were included into the study. Multi drug resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to any of the four tested drugs was detected among 54 (5.8%) patients. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3 (0.3%), 13 (1.4%), 9 (1.0%) respectively.

Conclusion

Primary resistance to first line anti tuberculosis drugs is still low in this setting. Continued vigilance including periodic national surveillance of anti-tuberculosis resistance is recommended.     

Plasma B-type Natriuretic Peptide as a Predictor of Cardiovascular Events in Subjects with Atrial Fibrillation: A Community-Based Study

Objectives

Atrial fibrillation (AF) is a significant public health issue due to its high prevalence in the general population, and is associated with an increased risk of cardiovascular (CV) events including systemic thrombo-embolism, heart failure, and coronary artery disease. The relationship between plasma B-type natriuretic peptide (BNP) and CV risk in real world AF subjects remains unknown.

Methods

The subject of the study (n = 228; mean age = 69 years) was unselected individuals with AF in a community-based population (n = 15,394; AF prevalence rate = 1.5%). The CV event free rate within each BNP tertile was estimated, and Cox regression analysis was performed to examine the relative risk of the onset of CV events among the tertiles. The prognostic ability of BNP was compared to an established risk score for embolic events (CHADS2 score). In addition, to determine the usefulness of BNP as a predictor in addition to CHADS2 score, we calculated Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) indices.

Results

During the follow-up period 58 subjects experienced CV events (52 per 1,000 person-years). The event-free ratio was significantly lower in the highest tertile (p < 0.02). After adjustment for established CV risk factors, the hazard ratio (HR) of the highest tertile was significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02). The predictive abilities of plasma BNP in terms of sensitivity and specificity for general CV events were comparable to those of CHADS2 score. Adding BNP to the CHADS2 score only model improved the NRI (0.319; p < 0.05) and the IDI (0.046; p < 0.05).

Conclusion

Plasma BNP is a valuable biomarker both singly or in combination with an established scoring system for assessing general CV risk including stroke, heart failure and acute coronary syndrome in real-world AF subjects.     

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.     

Prediction of Perioperative Cardiac Events through Preoperative NT-pro-BNP and cTnI after Emergent Non-Cardiac Surgery in Elderly Patients

Objectives

Clinical risk stratification has an important function in preoperative evaluation of patients at risk for cardiac events prior to non-cardiac surgery. The aim of this study was to determine whether the combined measurement of pre-operative N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac troponin I (cTnI) could provide useful prognostic information about postoperative major adverse cardiac events (MACE) within 30 days in patients aged over 60 years undergoing emergent non-cardiac surgery.

Methods

The study group comprised 2519 patients aged over 60 years that were undergoing emergent non-cardiac surgery between December 2007 and December 2013. NT-pro-BNP and cTnI were measured during hospital admission. The patients were monitored for MACE (cardiac death, non-fatal myocardial infarction, or cardiac arrest) during the 30-day postoperative follow-up period.

Results

MACE occurred in 251 patients (10.0%). Preoperative NT-pro-BNP and cTNI level were significantly higher in the individuals that experienced MACE than in those who did not (P < 0.001). The confounding factors of age, sex, co-morbidities and preoperative medications were adjusted in a multivariate logistic regression analysis. This analysis showed that preoperative NT-proBNP level > 917 pg/mL (OR 4.81, 95% CI 3.446–6.722, P < 0.001) and cTnI ≥ 0.07 ng/mL (OR 8.74, 95% CI 5.881–12.987, P < 0.001) remained significantly and independently associated with MACE after the adjustment of the confounding factors. Kaplan-Meier event-free survival curves demonstrated that patients with preoperative simultaneous NT-proBNP level > 917 pg/mL and cTnT ≥0.07 ng/mL had worse event-free survival than individual assessments of either biomarker.

Conclusion

Preoperative plasma NT-proBNP and cTnI are both independently associated with an increased risk of MACE in elderly patients after emergent non-cardiac surgery. The combination of these biomarkers provides better prognostic information than using either biomarker separately.     

Body Mass Index,Mortality, and Gender Difference in Advanced Chronic Kidney Disease

Background and Aim

A higher body mass index (BMI) appears to be reversely associated with mortality in dialysis patients. Moreover, although women have better survival in chronic kidney disease (CKD), this survival advantage is cancelled in dialysis. The association between BMI and mortality and the gender difference remain controversial in advanced CKD.

Methods

This study enrolled 3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD stages 3–5 with a BMI of 15.0–35.0 kg/m².

Results

During a median 2.9-year follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%) cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause mortality and 224 (16.2%) CV events and death in female patients. Compared with the reference BMI of 27.6–30.0 kg/m² in an adjusted Cox model, lower-BMI groups in men, BMI 15.0–20.0 kg/m² and 20.1–22.5 kg/m², were associated with higher risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval [CI], 1.97–5.18) and 2.01 (95% CI, 1.29–3.14), respectively. Higher-BMI group in men, BMI 30.1–35.0 kg/m², was associated with a higher risk of all-cause mortality: HR 1.72 (95% CI, 1.02–2.96). Likewise, lower- and higher-BMI groups in men were associated with a higher risk of CV events and death. In women, these associations between BMI and poor outcomes were not observed.

Conclusions

In advanced CKD, there was a reverse J-shaped association between BMI and all-cause mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral associations between BMI and poor outcomes were detected in women. Gender could modify the effect of BMI on mortality in patients with CKD.     

Association of serum bilirubin with contrast-induced nephropathy and future cardiovascular events in patients undergoing coronary intervention

Objectives

Enhanced reactive oxygen species formation within the kidney following the administration of contrast media may play a key role in the development of contrast-induced nephropathy (CIN). Bilirubin has emerged as an important endogenous antioxidant molecule. This study was undertaken to determine whether bilirubin is associated with CIN and future cardiovascular events in patients undergoing coronary intervention.

Methods

Totally, 544 consecutive patients received coronary intervention were enrolled. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary endpoint was CIN, defined as a rise in serum creatinine (SCr) of 0.5 mg/dl or a 25% increase from the baseline value within 48 hours after the procedure. The secondary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including death, nonfatal myocardial infarction, and ischemic stroke.

Results

Overall, CIN occurred in 85 (15.6%) patients. All patients were stratified into 3 groups (low/normal/high) according to the serum bilirubin levels. In a multivariate logistic analysis, the odds ratio for CIN with low-bilirubin levels relative to high-bilirubin levels was 11.82 (95% CI, 3.25–43.03). By Cox regression analysis, serum bilirubin levels was an independent predictor of MACE in patients undergoing coronary intervention (low vs. high hazard ratio 2.26; 95% CI, 1.05–4.90).

Conclusions

CIN is a serious complication of coronary intervention. Higher serum bilirubin concentrations were associated with lower risk of CIN and fewer cardiovascular events. The development of interventions that promote bilirubin levels may be a potential target to reduce CIN and future MACE in patients undergoing coronary intervention.