Physical Activity and Mortality in Patients with Coronary Artery Disease.

PURPOSE OF REVIEW: Coronary artery disease (CAD) accounts for half of heart-related mortalities. Secondary prevention measures are aimed at enhancing the probability of survival in acute and chronic heart diseases. Physical activity (PA) has been shown to effectively reduce all-cause and cardiovascular (CV) mortality rates. This article reviews the relationship between PA and mortality in patients with CAD. Additionally, we discuss the process of vascular changes that contributes to survival benefits in physically active CAD patients, along with exercise dosing and guideline recommendations. RECENT FINDINGS: Recent studies have shown that physical inactivity poses a modifiable risk factor that impedes favorable vasculature remodeling, unlike active individuals. Recent meta-analyses provide strong evidence of the multifaceted advantages of PA in lowering mortality rates in patients with CAD, as opposed to physically inactive participants. In summary, substantial evidence indicates that PA is significantly associated with reduction in all-cause and CV mortality in CAD patients, with a dose-response relationship.

Temporal trends in the incidence, treatment patterns, and outcomes of coronary artery disease and peripheral artery disease in the UK, 2006-2015.

AIMS: Most reports estimating national incidence rates of coronary (CAD) and peripheral arterial disease (PAD) have focused on stable outpatients or acute or elective hospital admissions, but not on the overall burden of disease. In this study, we report the changing trends in the population-level incidence of CAD and PAD, respectively from 2006 to 2015, statin utilization for secondary prevention and survival outcomes using multiple nationally representative data sources from the UK (primary care encounters, hospital admissions, and procedure-level data). METHODS AND RESULTS: A nationally representative study of linked primary and secondary care electronic health records of 4.6 million individuals from the UK. We calculated crude and standardized annual incidence rates separately for CAD and PAD. Statin use for secondary prevention, trends in annual major vascular event rates, and mortality between 2006 and 2015, were estimated for CAD and PAD, respectively. We identified 160 376 and 70 753 patients with incident CAD and PAD, respectively. The age- and sex-standardized incidence of CAD was similar in 2006 (443 per 100 000 person-years) and 2015 [436 per 100 000 person-years; adjusted incidence rate ratio (IRR) 0.98, 95% confidence interval (CI) 0.96-1.00]. In contrast, there was a 15% decline in the standardized incidence of PAD (236 per 100 000 person-years in 2006 to 202 per 100 000 person-years in 2015; adjusted IRR 0.85, 95% CI 0.82-0.88). The proportion of incident CAD and PAD patients prescribed long-term statins, was only 66% and 55%, respectively and was less common amongst women, patients aged >70 years, with heart failure, chronic lung disease, or depression. Cardiovascular mortality declined by 43% for incident CAD (adjusted IRR 0.57, 95% CI 0.50-0.64) between 2006 and 2015 but did not decline for incident PAD (adjusted IRR 0.84, 95% CI 0.70-1.00). CONCLUSION AND RELEVANCE: In the UK, the standardized incidence of CAD appears stable but mortality rates are falling, whereas the standardized incidence of PAD is falling but mortality rates are not.

Prognostic role of circulating neutrophil extracellular traps levels for long-term mortality in new end-stage renal disease patients.

Dysregulation of innate immunity has been proposed as an important contributing factor for advanced atherosclerosis and resultant high mortality in hemodialysis (HD) patients. To evaluate the long-term prognostic role of in vivo neutrophil extracellular traps (NETs), we measured circulating serum nucleosome, myeloperoxidase (MPO), and DNase I levels in 281 incident HD patients. Circulating nucleosome level was significantly higher in HD patients compared to controls, and it was closely associated with MPO levels, suggesting increased in vivo NETs in uremia. Patients in the nucleosome Q4 group had significantly increased all-cause and adverse CV mortality compared to those in the Q1-3 group even after adjusting traditional risk factors Also, serum DNase I level was significantly higher in HD patients than controls (2.76 ±â€¯1.02 ng/ml and 1.93 ±â€¯0.85 ng/ml), but it had no correlation with NETs. Interestingly, it serves an additive biomarker for predicting poor CV outcomes. The two novel biomarkers might provide an importance independent prognostic significance in incident HD patients.

Neutrophil-to-lymphocyte ratio predicts long-term all-cause mortality in patients with chronic kidney disease stage 5.

INTRODUCTION: A high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a strong biomarker of inflammation. AIM: We sought to evaluate the impact of NLR on long-term all-cause and cardio-vascular (CV) mortality in hemodialysis (HD) patients. MATERIAL AND METHODS: total of 84 chronic kidney disease (CKD) stage 5 patients with 54 of them on HD, with a median age of 61.5 (51.3-74.8) years were enrolled. e association between NLR and clinical biomarkers was investigated. Multivariable Cox regression analysis was used to find significant predictors of all-cause and CV mortality at follow-up. RESULTS: the median NLR (interquartile range) was 3.0 (2.1-4.1). Patients with NLR ≥3.9 (the highest tertile) had higher five-year all-cause mortality then remaining patients (53.6% vs. 30.4%; p = 0.039). On the contrary, only a trend towards increased CV mortality was observed (25.0% vs. 42.9%; p = 0.10). NLR ≥3.9 was a significant predictor of all-cause mortality at five years [hazard ratio (95%CI): 2.23 (1.10-4.50); p = 0.025] in Cox regression model adjusted for age, gender, and diabetes status. Similarly, while using NLR as continuous variable a significant association between NLR and all-cause mortality was confirmed even a er adjustment for covariates [hazard ratio per 1 unit increase (95%CI): 1.26 (1.06-1.51); p = 0.009] with the area under the receiver operating characteristic (ROC) curve of 0.64. Correlations between NLR and WBC, concentration of fibrinogen, albumin were observed. CONCLUSIONS: Asymptomatic inflammation measured by NLR showed an association with long-term all-cause mortality in stage 5 CKD patients, even while white blood cell count was in the normal range.

Pulmonary Hypertension, Mortality, and Cardiovascular Disease in CKD and ESRD Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Pulmonary hypertension is common in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and may be associated with poor outcomes. The magnitude of the association between pulmonary hypertension and mortality is uncertain due to the small size and variable findings of observational studies. STUDY DESIGN: Systematic review and meta-analysis of observational studies using subgroup analyses and metaregression. SETTING & POPULATION: Patients with ESRD or earlier stages of CKD. SELECTION CRITERIA FOR STUDIES: Observational studies reporting clinical outcomes in patients with co-existing pulmonary hypertension and CKD or ESRD identified using a systematic search of PubMed and Embase. PREDICTOR: Pulmonary hypertension diagnosed by Doppler echocardiography. OUTCOMES: All-cause mortality, cardiovascular mortality, and cardiovascular events. RESULTS: 16 studies, with 7,112 patients with an overall pulmonary hypertension prevalence of 23%, were included. Pulmonary hypertension was associated with increased risk for all-cause mortality among patients with CKD (relative risk [RR], 1.44; 95% CI, 1.17-1.76), with ESRD receiving maintenance dialysis (RR, 2.32; 95% CI, 1.91-2.83), and with a functioning kidney transplant (RR, 2.08; 95% CI, 1.35-3.20). Pulmonary hypertension was associated with increased risk for cardiovascular events in patients with CKD (RR, 1.67; 95% CI, 1.07-2.60) and ESRD receiving dialysis (RR, 2.33; 95% CI, 1.76-3.08). There was an association between pulmonary hypertension and increased risk for cardiovascular mortality in patients with CKD or ESRD (RR, 2.20; 95% CI, 1.53-3.15). LIMITATIONS: Heterogeneity of included studies, possibility of residual confounding, unavailability of individual patient-level data, and possibility of outcome reporting bias. CONCLUSIONS: Pulmonary hypertension is associated with a substantially increased risk for death and cardiovascular events in patients with CKD and ESRD. Risk is higher in patients with ESRD receiving dialysis compared with patients with CKD stages 1 to 5. Understanding the effect of interventions to lower pulmonary artery pressure on the survival of these patents awaits their evaluation in randomized controlled trials.

Can Torsemide and Combination of Loop Diuretics Improve Mortality in Patients with Chronic Heart Failure After Discharge?

The aim of this study was to investigate the effect on mortality of torsemide and a combination of loop diuretics (furosemide + torsemide) in contemporary practice in patients with chronic heart failure (HF).We investigated patients with HF in the Heart Failure Center of Fuwai Hospital from 2009 to 2013 who were discharged on furosemide, torsemide, or a combination of the 2 drugs. Using inverse probability weighting (IPW) to account for nonrandom selection of diuretic strategies, we assessed the association between different diuretic strategies and mortality.Among 956 patients, 19.7% (n = 188) received furosemide, 36.6% (n = 350) torsemide, and 43.7% (n = 418) the combination therapy. The torsemide-treated and combination-treated patients had worse heart function and higher furosemide equivalent. Univariable Cox proportional hazards models showed that the combination group had worse outcomes (all-cause HR = 2.044, P = 0.008; CV HR = 1.988, P = 0.011), while torsemide was associated with an outcome (all-cause HR = 1.640, P = 0.078; CV HR = 1.509, P = 0.147) similar to that of furosemide. After IPW, torsemide was associated with a nominally lower mortality compared with furosemide (all-cause HR = 0.738, P = 0.222; CV HR = 0.667, P = 0.110), and the association between the combination treatment and increased mortality was no longer statistically significant (all-cause HR = 1.207, P = 0.470;CV HR = 1.174, P = 0.540).We found that torsemide and the combination strategy had similar outcomes when compared with furosemide. However, considering the lack of diuretic randomized clinical trials (RCTs) conducted with the aim of exploring the effect on mortality of different diuretic treatments, prospective trials are needed to investigate the effect of different diuretic strategies in chronic HF.

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: mediation analysis in SPRINT.

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. CONCLUSION: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

The benefit of intensive (<120 mmHg) blood pressure (BP) treatment, reduction in all-cause mortality (ACM), was attenuated when mediated through non-fatal major adverse cardiovascular events. This was driven by cardiovascular mortality (CVM). The harm of intensive BP treatment, increase in ACM, was amplified when mediated through serious adverse events. This was driven by non-CVM. Current reporting of treatment effects in cardiovascular trials does not allow for expansion of the lens to focus on important occurrences after the index event.

Nutritional Status According to the GLIM Criteria in Patients with Chronic Heart Failure: Association with Prognosis.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). METHODS: This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognostic power than the MNA. RESULTS: Abnormal nutritional status was identified in 19.8% of the patients with the GLIM criteria and in 25.1% with the MNA. In the multivariate analyses (age, sex, NYHA functional class, diabetes, and Barthel index), nutritional status assessed by the MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalizations during the five-year follow-up. CONCLUSIONS: Malnutrition assessed by MNA, but not by the GLIM criteria, was an independent predictor of all-cause mortality, CV mortality, and recurrent HF-related hospitalization in our cohort of outpatients with HF.

Triple Therapy in COPD: Can We Welcome the Reduction in Cardiovascular Risk and Mortality?

Chronic obstructive pulmonary disease (COPD) is a complex disease which consists in the reduction of the airflow and leads to the disruption of the pulmonary tissue due to a chronic inflammation. The progression of the disease is characterized by an exacerbation of the symptoms and the presence of life-threatening systemic complications, such as stroke and ischemic heart disease, with a progressive decline in lung function which can deeply impact the quality of life. Mortality represents the most important COPD outcome, with an increased risk in patients with cardiovascular comorbidities. The efficacy and safety of triple inhaled therapy were demonstrated by numerous controlled trials. Above all, many robust data are now available on the effectiveness of the triple therapy to reduce mortality in COPD patients.

The potential effect of cardiac function on pulmonary hypertension, other risk factors, and its impact on survival in dialysis patients.

INTRODUCTION: Pulmonary hypertension (PH) is a recently recognized as a complication of chronic kidney disease and end-stage renal disease. The pathogenesis of pulmonary hypertension in this group of patients is not fully understood, probably due to the interaction of multiple aspects of the altered cardiovascular physiology and also hormonal and metabolic disorders. The present study aimed to determine the prevalence of PH, correlation with cardiac function and other risk factors and its impact of survival in chronic hemodialysis and peritoneal dialysis patients. METHODS: We studied 125 stable hemodialysis and peritoneal patients (females 40%, mean age 52.42 ± 11.88 years) on renal replacement therapy (RRT) for more than 3 months with a follow up 2 years. Demographic information, clinical characteristics, blood test, and thoroughly echocardiographic evaluation at the optimal dry weight were collected. After conventional echocardiographic examination, tissue Doppler echocardiographic (TDE) examination was performed to evaluate global and regional myocardial systolic as well as diastolic function, and pulmonary hypertension. PH was defined as systolic pulmonary artery pressure (sPAP) ≥ 35 mmHg. To rule out secondary PH, patients with pulmonary disease, collagen vascular disease, and volume overload at the time of echocardiography were excluded. Variables were compared between two groups-subjects with PH and non-PH. Logistic regression analysis was used to evaluate the risk factor for PH and its impact on survival. RESULTS: According to the echocardiographic findings, PH was found in 28% (35 patients) of all patients. Mean PH was 33.46 ± 5.38 mmHg. The higher level of higher parathormone (PTH), C-reactive protein (CRP) and E/E' average, lower left ventricular ejection fraction (EF), peak systolic velocity at the lateral mitral annulus (MASa) and the peak systolic velocity at the lateral tricuspid annulus (TASa) were found predictor of PH. The cardiovascular mortality rate was 15.5%. Patients evaluated with PH have a significantly lower cardiovascular survival rate [Long Rank (Mantel-Cox) p = 0.0001]. In ROC analysis for CV mortality, the area under the curve (AUC) for PH and CRP was found 0.8; for LVM-I, E/E' and PP, AUC = 0.76; 0.75; 0.72 respectively while the inverse relationship was found with MASa and TASa with AUC = 0.66 and 0.95 respectively. CONCLUSION: Our study shows that PH is frequent in dialysis patients. It is influenced by inflammation, CKD-MBD biomarkers associated with diastolic and also systolic left and right ventricle dysfunction. Pulmonary hypertension, inflammation, vascular stiffness, and left ventricular hypertrophy are interrelated and all contribute to cardiovascular morbidity and mortality among dialysis patients. Easy to implement, cardiac imaging at the bedside and in outpatient clinics offers a positive perspective in early diagnosis of cardiac abnormalities and immediate approach to this condition, so is highly recommended in the dialysis population.

Comparison of three nutritional screening tools for predicting mortality in maintenance hemodialysis patients.

OBJECTIVES: The aim of this study was to compare the effect of different nutritional screening tools on predicting the risk for mortality in patients on maintenance hemodialysis (MHD). METHODS: A cohort of 1025 patients on MHD were enrolled from eight hospitals. The malnutrition-inflammation score (MIS), objective score of nutrition on dialysis (OSND), and geriatric nutritional risk index (GNRI) were measured at baseline. All-cause mortality and cardiovascular (CV) mortality were the major study outcomes. RESULTS: The median follow-up duration was 28.1 mo. The MIS (per SD increase, hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.18-1.55), the OSND (per SD decrease, HR, 1.24; 95% CI, 1.09-1.42), and the GNRI (per SD decrease, HR, 1.26; 95% CI, 1.10-1.43) were significantly associated with the risk for all-cause mortality. More importantly, the mortality predictability of the MIS appears similar to the GNRI (P = 0.182) and greater than the OSND (MIS versus OSND: P = 0.001; GNRI versus OSND: P = 0.045). Similar results were found for CV mortality. CONCLUSIONS: Each of the three nutritional screening tools was significantly associated with an increased risk for all-cause and CV mortality. The mortality predictability of the MIS was similar to the GNRI and greater than the OSND.