Prevalence,incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.     

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.     

20‐year follow‐up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20)

Antipsychotics are effective in preventing relapses of schizophrenia, but it is generally believed that their long‐term use is harmful for patients’ physical well‐being. However, there are no long‐term studies which have verified this view. This nationwide, register‐based cohort study aimed to assess the risk of hospitalization due to physical health problems, as a marker for severe physical morbidity, and the risk of all‐cause mortality, as well as of cardiovascular and suicidal death, associated with antipsychotic use in all patients treated for schizophrenia in inpatient care between 1972 and 2014 in Finland (N=62,250), with up to 20 years of follow‐up (median: 14.1 years). The use of antipsychotic drugs (i.e., use of any antipsychotic compared with non‐use) and the use of specific antipsychotics were investigated, and outcomes were somatic and cardiovascular hospitalization, and all‐cause, cardiovascular and suicide death. Hospitalization‐based outcomes were analyzed by a within‐individual design to eliminate selection bias, comparing use and non‐use periods in the same individual by stratified Cox model. Mortality outcomes were assessed by traditional between‐individual Cox multivariate models. The adjusted hazard ratios (aHRs) for any somatic hospitalization and cardiovascular hospitalization were 1.00 (95% CI: 0.98‐1.03) and 1.00 (95% CI: 0.92‐1.07) during use of any antipsychotic compared to non‐exposure periods within the same individual. The aHRs were 0.48 (95% CI: 0.46‐0.51) for all‐cause mortality, 0.62 (95% CI: 0.57‐0.67) for cardiovascular mortality, and 0.52 (95% CI: 0.43‐0.62) for suicide mortality during use vs. non‐use of any antipsychotic. The most beneficial mortality outcome was associated with use of clozapine in terms of all‐cause (aHR=0.39, 95% CI: 0.36‐0.43), cardiovascular (aHR=0.55, 95% CI: 0.47‐0.64) and suicide mortality (aHR=0.21, 95% CI: 0.15‐0.29). The cumulative mortality rates during maximum follow‐up of 20 years were 46.2% for no antipsychotic use, 25.7% for any antipsychotic use, and 15.6% for clozapine use. These data suggest that long‐term antipsychotic use does not increase severe physical morbidity leading to hospitalization, and is associated with substantially decreased mortality, especially among patients treated with clozapine.     

Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis

Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term efficacy of antipsychotic drugs in acutely ill patients using network meta-analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded trials of at least 6-month duration on all second-generation and 18 first-generation antipsychotics. The primary outcome was change in overall symptoms of schizophrenia; secondary outcomes were all-cause discontinuation; change in positive, negative and depressive symptoms; quality of life, social functioning, weight gain, antiparkinson medication use, akathisia, serum prolactin level, QTc prolongation, and sedation. Confidence in the results was assessed by the CINeMA (Confidence in Network Meta-Analysis) framework. We included 45 studies with 11,238 participants. In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26-0.49), asenapine (SMD=0.33, 95% CI: 0.21-0.45), iloperidone (SMD=0.32, 95% CI: 0.15-0.49), paliperidone (SMD=0.28, 95% CI: 0.11-0.44), haloperidol (SMD=0.27, 95% CI: 0.14-0.39), quetiapine (SMD=0.25, 95% CI: 0.12-0.38), aripiprazole (SMD=0.16, 95% CI: 0.04-0.28) and risperidone (SMD=0.12, 95% CI: 0.03-0.21). The 95% CIs for olanzapine versus aripiprazole and risperidone included the possibility of trivial effects. The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain. These results were robust in sensitivity analyses and in line with other efficacy outcomes and all-cause discontinuation. Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from –4.58 kg (95% CI: –5.33 to –3.83) compared to ziprasidone to –2.30 kg (95% CI: –3.35 to –1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed against its side effect profile.     

Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients

Background

Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients.

Methods

A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization.

Results

During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55–3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.07–4.26, P = 0.031) and infection-related mortality (HR 3.07, 95% CI, 1.30–7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00–1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06–1.92, P = 0.028).

Conclusions

Our data demonstrate that high serum GGT levels were an independent risk factor for all-cause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients.     

Clinical Outcomes in Low Risk Coronary Artery Disease Patients Treated with Different Limus-Based Drug-Eluting Stents - A Nationwide Retrospective Cohort Study Using Insurance Claims Database

The clinical outcomes of different limus-based drug-eluting stents (DES) in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and everolimus-eluting stent (EES), using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group). Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan.     

Target Values of Cardiovascular Risk Factors Are Not Associated with All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

Background

To investigate prospectively the relationship between target values of glycated hemoglobin, blood pressure and LDL-cholesterol, as considered in a combined fashion, and all-cause mortality in patients with type 2 diabetes mellitus.

Methods

Two cohorts of patients with type 2 diabetes mellitus, the Gargano Mortality Study (n=810) and the Foggia Mortality Study (n=929), were investigated. A weighted target risk score was built as a weight linear combination of the recommended targets reached by each patient.

Results

In the Gargano Mortality Study and in the Foggia Mortality Study (mean follow up=7.4 and 5.5 years, respectively), 161 (19.9%) and 220 (23.7%) patients died, with an age and sex adjusted annual incidence rate of 2.1 and 2.8 per 100 person-years, respectively. In both study samples the weighted target risk score tended to be linearly associated with all-cause mortality (HR for one point increment=1.30, 95% CI: 1.11-1.53, p=0.001, and HR=1.08, 95% CI: 0.95-1.24, p=0.243, respectively). When the two cohorts were pooled and analyzed together, a clear association between weighted target risk score and all-cause mortality was observed (HR for one point increment=1.17, 95% CI:1.05-1.30, p=0.004). This counterintuitive association was no longer observable in a model including age, sex, body mass index, smoking habit, estimated glomerular filtration rate, albuminuria and anti-diabetic, anti-hypertensive and anti-dyslipidemic treatment as covariates (HR for one point increment=0.99, 95% CI: 0.87-1.12, p=0.852).

Conclusions

In a real life clinical set of patients with type 2 diabetes mellitus, the combination of recommended target values of established cardiovascular risk factors is not associated with all-cause mortality.     

Caveolin-1 Single Nucleotide Polymorphism in Antineutrophil Cytoplasmic Antibody Associated Vasculitis

Objective

Immunosuppression is cornerstone treatment of antineutrophil cytoplasmic antibody associated vasculitis (AAV) but is later complicated by infection, cancer, cardiovascular and chronic kidney disease. Caveolin-1 is an essential structural protein for small cell membrane invaginations known as caveolae. Its functional role has been associated with these complications. For the first time, caveolin-1 (CAV1) gene variation is studied in AAV.

Methods

CAV1 single nucleotide polymorphism rs4730751 was analysed in genomic DNA from 187 white patients with AAV from Birmingham, United Kingdom. The primary outcome measure was the composite endpoint of time to all-cause mortality or renal replacement therapy. Secondary endpoints included time to all-cause mortality, death from sepsis or vascular disease, cancer and renal replacement therapy. Validation of results was sought from 589 white AAV patients, from two European cohorts.

Results

The primary outcome occurred in 41.7% of Birmingham patients. In a multivariate model, non-CC genotype variation at the studied single nucleotide polymorphism was associated with increased risk from: the primary outcome measure [HR 1.86; 95% CI: 1.14-3.04; p=0.013], all-cause mortality [HR:1.83; 95% CI: 1.02-3.27; p=0.042], death from infection [HR:3.71; 95% CI: 1.28-10.77; p=0.016], death from vascular disease [HR:3.13; 95% CI: 1.07-9.10; p=0.037], and cancer [HR:5.55; 95% CI: 1.59-19.31; p=0.007]. In the validation cohort, the primary outcome rate was far lower (10.4%); no association between genotype and the studied endpoints was evident.

Conclusions

The presence of a CC genotype in Birmingham is associated with protection from adverse outcomes of immunosuppression treated AAV. Lack of replication in the European cohort may have resulted from low clinical event rates. These findings are worthy of further study in larger cohorts.     

All-Cause and Cause-Specific Mortality after Long-Term Sickness Absence for Psychiatric Disorders: A Prospective Cohort Study

Objective

The aim was to examine if long-term psychiatric sickness absence was associated with all-cause and diagnosis-specific (cardiovascular disease (CVD), cancer and suicide) mortality for the period 1990–2007. An additional aim was to examine these associations for psychiatric sickness absence in 1990 and 2000, with follow-up on mortality during 1991–1997 and 2001–2007, separately.

Methods

Employees within municipalities and county councils, 244,990 individuals in 1990 and 764,137 individuals in 2000, were followed up to 2007 through register linkages. Analyses were conducted with flexible parametric survival models comparing sickness absentees due to psychiatric diagnoses (>90 days) with those not receiving sick leave benefit.

Results

Long-term sickness absence for psychiatric disorders was associated with an increased risk of mortality due to all causes; CVD; cancer (smoking and non-smoking related); and suicide during the period 1990–2007. After full adjustment for socio-demographic covariates and previous inpatient care due to somatic and psychiatric diagnoses, these associations remained significant for all-cause mortality (Hazard ratios (HR) and 95% confidence interval (CI)): HR 1.56, 95% CI 1.3–1.8; CVD: HR 1.35, 95% CI 1.0–1.9, and suicide: HR 3.84, 95% CI 2.4–6.1. For both cohorts 1990 and 2000 estimates point in the same direction. For the time-period 2000–2007, we found increased risks of mortality in the fully adjusted model due to all causes: HR 1.47, 95% CI 1.2–1.7; CVD: HR 1.83, 95% CI 1.2–2.7; overall cancer: HR 1.33, 95% CI 1.0–1.7; and suicide: HR 2.15, 95% CI 1.3–3.7.

Conclusion

Long-term sickness absence for psychiatric disorders predicted premature mortality from all-causes, cardiovascular disease, cancer, and suicide.     

Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

Introduction

Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.

Methods

Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.

Results

Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.

Conclusions

In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.     

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 Erythropoietin-Stimulating Agent Responsiveness with Mortality in Hemodialysis and Peritoneal Dialysis Patients

Erythropoiesis-stimulating agent (ESA) responsiveness has been reported to be associated with increased mortality in hemodialysis (HD) patients. ESA requirement to obtain the same hemoglobin (Hb) level is different between HD and peritoneal dialysis (PD) patients. In this study, we investigated the impact of ESA responsiveness on mortality between both HD and PD patients. Prevalent HD and PD patients were selected from the Clinical Research Center registry for end-stage renal disease, a prospective cohort study in Korea. ESA responsiveness was estimated using an erythropoietin resistant index (ERI) (U/kg/week/g/dL). Patients were divided into three groups by tertiles of ERI. ESA responsiveness was also assessed based on a combination of ESA dosage and hemoglobin (Hb) levels. The primary outcome was all-cause mortality. A total of 1,594 HD and 876 PD patients were included. The median ESA dose and ERI were lower in PD patients compared with HD patients (ESA dose: 4000 U/week vs 6000 U/week, respectively. P<0.001, ERI: 7.0 vs 10.4 U/kg/week/g/dl, respectively. P<0.001). The median follow-up period was 40 months. In HD patients, the highest ERI tertile was significantly associated with higher risk for all-cause mortality (HR 1.96, 95% CI, 1.07 to 3.59, P = 0.029). HD patients with high-dose ESA and low Hb levels (ESA hypo-responsiveness) had a significantly higher risk of all-cause mortality (HR 2.24, 95% CI, 1.16 to 4.31, P = 0.016). In PD patients, there was no significant difference in all-cause mortality among the ERI groups (P = 0.247, log-rank test). ESA hypo-responsiveness was not associated with all-cause mortality (HR = 1.75, 95% CI, 0.58 to 5.28, P = 0.319). Our data showed that ESA hypo-responsiveness was associated with an increased risk of all-cause mortality in HD patients. However, in PD patients, ESA hypo-responsiveness was not related to all-cause mortality. These finding suggest the different prognostic value of ESA responsiveness between HD and PD patients.     

Upstroke Time Per Cardiac Cycle is Associated with Cardiovascular Prognosis in Type 2 Diabetes

Objective: Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes.Methods: A total of 452 patients with type 2 diabetes (age, 67.5 ± 8.6 years; male, 54%) registered in a share-care program participated in the study at an outpatient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation, and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality.Results: Increment of UTCC associations with primary and secondary outcomes were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC, 0.63 &lsqb;P = .001]; sensitivity, 67.7%; specificity, 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38 to 4.35 (P = .002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33 to 10.99 (P = .467) were calculated.Conclusion: Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes.Abbreviations: CAD = coronary artery disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; HR = hazard ratio; PAD = peripheral artery disease; UTCC = upstroke time per cardiac cycle     

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.     

Association between red blood cell distribution width and long-term mortality among patients undergoing percutaneous coronary intervention with previous history of cancer

Abstract

Background: The number of patients suffering from coronary heart disease with cancer is rising. There is scarce evidence concerning the biomarkers related to prognosis among patients undergoing percutaneous coronary intervention (PCI) with cancer. Thus, the aim of this study was to investigate the association between red blood cell distribution width (RDW) and prognosis in this population.

Methods: A total of 172 patients undergoing PCI with previous history of cancer were enrolled in this retrospective study. The endpoint was long-term all-cause mortality. According to tertiles of RDW, the patients were classified into three groups: Tertile 1 (RDW <12.8%), Tertile 2 (RDW ≥12.8% and <13.5%) and Tertile 3 (RDW ≥13.5%).

Results: During an average follow-up period of 33.3 months, 29 deaths occurred. Compared with Tertile 3, mortality of Tertile 1 and Tertile 2 was significantly lower in the Kaplan–Meier analysis. In multivariate Cox regression analysis, RDW remained an independent risk factor of mortality (HR: 1.938, 95% CI: 1.295–2.655, p?<?0.001). The all-cause mortality in Tertile 3 was significantly higher than that in Tertile 1 (HR: 5.766; 95% CI: 1.426–23.310, p?=?0.014).

Conclusions: An elevated RDW level (≥13.5%) was associated with long-term all-cause mortality among patients undergoing PCI with previous history of cancer.     

Perioperative Blood Transfusion Promotes Worse Outcomes of Bladder Cancer after Radical Cystectomy: A Systematic Review and Meta-Analysis

Background

Multiple studies have investigated the effect of perioperative blood transfusion (PBT) for patients with radical cystectomy (RC), but the results have been inconsistent. We conducted a systematic review and meta-analysis to investigate the relationship between PBT and the clinical outcomes of RC patients.

Methods

We searched MEDLINE, EMBASE, the Cochrane library and BIOSIS previews to identify relevant literature for studies that focused on the relationship of PBT and outcomes of patients undergoing RC. A fixed or random effects model was used in this meta-analysis to calculate the pooled hazard ratio (HR) with 95% confidence intervals (CIs).

Results

A total of 7080 patients in 6 studies matched the selection criteria. Aggregation of the data suggested that PBT in patients who underwent RC correlated with increased all-cause mortality, cancer-specific mortality and cancer recurrence. The combined HRs were 1.19 (n = 6 studies, 95% CI: 1.11–1.27, Z = 4.71, P<0.00001), 1.17 (n = 4 studies, 95% CI: 1.06–1.30, Z = 3.06, P = 0.002), 1.14 (n = 3 studies, 95% CI: 1.03–1.27, Z = 2.50, P = 0.01), respectively. The all-cause mortality associated with PBT did not vary by the characteristics of the study, including number of study participants, follow-up period and the median blood transfusion ratio of the study.

Conclusion

Our data showed that PBT significantly increased the risks of all-cause mortality, cancer-specific mortality and cancer recurrence in patients undergoing RC for bladder cancer.     

Is Obstructive Sleep Apnea Associated with Cardiovascular and All-Cause Mortality?

Background

Studies have reported inconsistent findings regarding the association between obstructive sleep apnea (OSA) and future risks of cardiovascular and all-cause mortality. We conducted a meta-analysis to investigate whether OSA is an independent predictor for future cardiovascular and all-cause mortality using prospective observational studies.

Methods

Electronic literature databases (Medline and Embase) were searched for prospective observational studies published prior to December 2012. Only observational studies that assessed baseline OSA and future risk of cardiovascular and all-cause mortality were selected. Pooled hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates. Subgroup analyses were based on the severity of OSA.

Results

Six studies with 11932 patients were identified and analyzed, with 239 reporting cardiovascular mortality, and 1397 all-cause mortality. Pooled HR of all-cause mortality was 1.19 (95% CI, 1.00 to 1.41) for moderate OSA and 1.90 (95% CI, 1.29 to 2.81) for severe OSA. Pooled HR of cardiovascular mortality was 1.40 (95% CI, 0.77 to 2.53) for moderate OSA and 2.65 (95% CI, 1.82 to 3.85) for severe OSA. There were no differences in cardiovascular mortality in continuous positive airway pressure (CPAP) treatment compared with healthy subjects (HR 0.82; 95% CI, 0.50 to 1.33).

Conclusions

Severe OSA is a strong independent predictor for future cardiovascular and all-cause mortality. CPAP treatment was associated with decrease cardiovascular mortality.     

Pre-procedural elevated cardiac troponin predict risk of long-term all-cause mortality after transcatheter aortic valve replacement: a meta-analysis of prospective studies

Abstract

Background: The purpose of this meta-analysis was to evaluate the relationship between elevated cardiac troponin pre-transcatheter aortic valve replacement (TAVR) and long-term all-cause mortality.

Methods: Prospective studies with the endpoint of all-cause mortality were included. We primarily used the fixed-effect model weighted by inverse variance. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics.

Results: Seven prospective studies comprising of 3049 subjects were included in our meta-analysis. Pre-procedural elevated cardiac troponin was associated with increased risk of long-term mortality post TAVR [hazard ratio (HR) 2.25, 95% CI 1.83–2.78, p?=?0.000, I² = 30.3%, p for heterogeneity 0.197]. In addition, subgroup analyses have shown that the group with an younger age (<82?y) seemed to have a higher risk of all-cause mortality than the group with older age (≥82?y) [HR 4.08 (2.41 to 6.89) VS 2.01 (1.60 to 2.53), p?=?0.016 for subgroup difference].

Conclusions: Pre-procedural elevated cardiac troponin was associated with increased long-term all-cause mortality in patients undergoing TAVR.     

Mortality Risk After Radioiodine Therapy for Hyperthyroidism: A Systematic Review and Meta-Analysis

ObjectiveRadioiodine has been increasingly used to treat hyperthyroidism for many years. Although widely regarded as an effective therapy, radioiodine treatment for hyperthyroidism has been suspected to be associated with the risk of mortality. This study aimed to quantify the mortality outcomes in patients who were treated for hyperthyroidism with radioiodine.MethodsSystematic search and meta-analysis were performed to determine the risk of mortality in patients treated with radioiodine for hyperthyroidism. Relevant studies were searched through August 2020 and selected in accordance with the inclusion criteria.ResultsA total of 13 studies were identified. The summary odds ratios (ORs) showed an increased risk of all-cause mortality in patients who were treated with radioiodine for hyperthyroidism (OR = 1.20; 95% CI = 1.07-1.35). The risk of death attributed to all forms of circulatory, respiratory, and endocrine and metabolic diseases was significantly increased, with summary ORs of 1.23 (95% CI, 1.12-1.35), 1.43 (95% CI, 1.17-1.75), and 2.38 (95% CI, 1.85-3.06), respectively. The summary ORs revealed no significant association between radioiodine treatment for hyperthyroidism and the risk of cancer mortality (OR = 1.03; 95% CI, 0.98-1.09). Radioiodine treatment for hyperthyroidism was not associated with the risk of mortality from breast, respiratory system, gastrointestinal, and genitourinary cancers.ConclusionRadioiodine treatment for hyperthyroidism is associated with the risk of all-cause mortality but not cancer mortality. Future research needs to address the causes of hyperthyroidism, effects of radioiodine therapy, and potential effects of confounding to identify causality.     

Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort – Differential effects by tumour subtype,NAT2 status,BMI and alcohol intake

BackgroundInconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking.MethodsWe used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50–74 and diagnosed with invasive tumours 2001–2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed.ResultsOverall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93–1.64, and HR 1.29, 95% CI 0.95–1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13–2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60–1.98; P_{heterogeneity} = 0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02–3.65, and HR 2.08, 95% CI 1.40–3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22–10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m²: HR 2.52, 95% CI 1.52–4.15 vs. ≥25 kg/m²: HR 0.94, 95% CI 0.38–2.36; P_{heterogeneity} = 0.04).ConclusionThe harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.