Association of peripheral arterial disease with all-cause and cardiovascular mortality in hemodialysis patients: a meta-analysis

Background

Recent studies have shown an association between peripheral arterial disease (PAD) and increased risk of mortality in hemodialysis (HD) patients; however, the estimates vary widely and are inconsistent. It is necessary to elucidate the degree of mortality risk for PAD patients in HD population.

Methods

PubMed, EMBASE, Web of Science and Cochrane Library (from inception to September 4th, 2016) were systematically searched for cohort studies assessing the association between PAD and mortality in HD patients. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CI) of all-cause and cardiovascular (CV) mortality using random effects models. Subgroup analyses were conducted to explore the source of heterogeneity.

Results

The search identified 2,973 potentially eligible records and 10 studies (n?=?32,864) were included. Our meta-analysis revealed that PAD significantly increased the risk of all-cause mortality (RR 2.15, 95 % CI 1.67–2.77, n?=?32,864) and CV mortality (RR 2.99, 95 % CI 1.66-5.38, n?=?31,794) in HD patients after multivariate adjustment. Subgroup analyses showed the study design and follow-up time might be two sources of heterogeneity.

Conclusion

PAD may be a prognostic marker of all-cause and CV mortality in HD patients. More attention should be paid to diagnosis and management of PAD in HD patients.

     

The association between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension

Previous studies had shown that an increased aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) was associated with cardiovascular disease. This study aimed to assess the relationship between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension.By March 31, 2020, a cohort of 14,220 Chinese hypertensive patients was followed up. The end point was all-cause and cardiovascular death. Hazard ratios (HRs) and 95% CIs were calculated for mortality associated with AST/ALT ratio, using Cox proportional hazards models and competing risk model.In an average of 1.7 years of follow-up, 1.39% (n = 198) of patients died, 55.5% (n = 110) of whom from cardiovascular disease. AST/ALT ratio was associated with increased risk of all-cause death (HR:1.37, 95% CI:1.15–1.63) and cardiovascular death (HR:1.32, 95% CI:1.03–1.68) after adjustment for other potential confounders. Compared with low AST/ALT ratio (Tertile 1), high AST/ALT ratio was associated with high cause mortality (Tertile 2: HR:1.35, 95% CI:0.86–2.10; Tertile 3: HR:2.10, 95% CI:1.37–3.21; P for trend <.001). Compared with low AST/ALT ratio (Tertile 1), a statistically significant increased risk of cardiovascular mortality was also observed (Tertile 2: HR:1.27, 95% CI:0.70–2.29; Tertile 3: HR:1.92, 95% CI:1.09–3.37; P for trend <.001). High AST/ALT ratio was also associated with high cardiovascular mortality (Tertile 2: HR:1.27, 95% CI:0.70–2.29; Tertile 3: HR:1.92, 95% CI:1.09–3.37; P for trend <.001).Present study indicated that increased AST/ALT ratio levels were predictive of all-cause and cardiovascular mortality among Chinese hypertensive patients.Trial registration: CHICTR, CHiCTR1800017274. Registered 20 July 2018.     

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

Aims/hypothesis  The bone-related peptide osteoprotegerin is produced by vascular cells and is involved in the process of vascular calcification. The aim of this study was to investigate the predictive value of plasma levels of osteoprotegerin in relation to mortality, cardiovascular events and deterioration in kidney function in patients with type 1 diabetes. Methods  This prospective observational follow-up study included 397 type 1 diabetic patients with overt diabetic nephropathy (243 men; age [mean±SD] 42.1 ± 10.6 years, duration of diabetes 28.3 ± 9.9 years, GFR 67 ± 28 ml min⁻¹ 1.73 m²) and a group of 176 patients with longstanding type 1 diabetes and persistent normoalbuminuria (105 men; age 42.6 ± 9.7 years, duration of diabetes 27.6 ± 8.3 years). Results  The median (range) follow-up period was 11.3 (0.0–12.9) years. Among patients with diabetic nephropathy, individuals with high osteoprotegerin levels (fourth quartile) had significantly higher all-cause mortality than patients with low levels (first quartile) (covariate-adjusted hazard ratio [HR] 3.00 [1.24–7.27]). High osteoprotegerin levels also predicted cardiovascular mortality (covariate-adjusted HR 4.88 [1.57–15.14]). Furthermore, patients with high osteoprotegerin levels had significantly higher risk of progression to end-stage renal disease than patients with low levels (covariate-adjusted HR 4.32 [1.45–12.87]). In addition, patients with high levels of plasma osteoprotegerin had an elevated rate of decline in GFR. Conclusions/interpretation  High levels of osteoprotegerin predict all-cause and cardiovascular mortality in patients with diabetic nephropathy. Furthermore, high levels of osteoprotegerin predict deterioration of kidney function towards end-stage renal disease.     

Association of physical activity with all-cause mortality and incident and prevalent cardiovascular disease among patients with type 1 diabetes: the EURODIAB Prospective Complications Study

Aims/hypothesis

The aim of this study was to examine the association of physical activity (PA) with all-cause mortality and incident and prevalent cardiovascular disease (CVD) among patients with type 1 diabetes.

Methods

The EURODIAB Prospective Complications Study is a cohort including 3,250 male and female patients with type 1 diabetes (mean age 32.7?±?10.2 years) from 16 European countries, of whom 1,880 participated in follow-up examinations. In analysis 1 (longitudinal), the association of baseline PA (based on the reported number of hours per week spent in mild, moderate and vigorous PA) with all-cause mortality and incident CVD was examined by performing survival analysis. In analysis 2 (cross-sectional), we focused on the association between PA at follow-up (data on sports, walking distance and regular bicycling) and prevalent CVD by performing logistic regression analysis. Adjustments were made for age, sex, BMI, smoking, consumption of alcohol, consumption of certain nutrients and diabetic complications.

Results

Analysis 1 (longitudinal): participation in moderate or vigorous PA once a week or more was borderline inversely associated with all-cause mortality (men and women combined) (HR 0.66, 95% CI 0.42, 1.03) and incident CVD (women only) (HR 0.66, 95% CI 0.40, 1.08). No association was found in men. Analysis 2 (cross-sectional): total PA (indexed by sports, walking, bicycling) and distance walked were inversely associated with prevalent CVD (OR_totalPA 0.66, 95% CI 0.45, 0.97; and OR_walking 0.61, 95% CI 0.42, 0.89).

Conclusions/interpretation

PA showed a borderline inverse association with both all-cause mortality (both sexes) and incident CVD (women only) in patients with type 1 diabetes. Since this is an under-researched clinical population, future longitudinal studies with objective PA measurements are needed to expand on these results.     

The association of ulceration of the foot with cardiovascular and all-cause mortality in patients with diabetes: a meta-analysis

Aims/hypothesis  

It is well established that diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. Observational studies suggest that a history of diabetic foot ulceration (DFU) may increase this risk further still. We sought to determine to what extent DFU is associated with excess risk over and above diabetes.     

Physical activity in the Japan population: association with blood lipid levels and effects in reducing cardiovascular and all-cause mortality

According to many prospective cohort studies and meta-analyses of those studies, physical inactivity and/or low levels of physical fitness are associated with an elevated risk for the development of metabolic syndrome, type 2 diabetes, hypertension, coronary artery disease (CAD), and stroke, and with an increased risk of cardiovascular disease (CVD) mortality and all-cause mortality. Most of these analyses, however, were conducted on non-Japanese populations in the West. This report summarizes prospective observational and clinical studies in Japan. The annual national nutrition survey has shown a gradual decline in the number of walking steps in both genders and in all age groups over the last 10 years. While exercise habits have been gradually increasing in the elderly, only one-fifth of young and middle-aged people undertake leisure-time physical activity. Prospective cohort studies have shown that increased physical fitness and greater physical activity in either daily life or leisure time are of benefit in preventing all-cause mortality and CVD mortality. The daily number of walking steps is positively associated with HDL cholesterol levels and negatively associated with triglyceride levels. According to a random-effects model meta-analysis of 4 randomized controlled trials comparing supervised aerobic exercise training with non-exercise control in subjects without CAD, exercise resulted in a significant increase in HDL-cholesterol (10.01 mg/dL, 95% CI 5.38 to 14.65, p< 0.0001). While this confirms the importance of physical activity in preventing CVD mortality and all-cause mortality, the levels of physical activity are on a declining trend in Japan, particularly among the young.     

Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients

Introduction. Chronic kidney disease (CKD) predisposes to a 10- to 20-fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. Methods. This is a cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23–86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient’s leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2–42) months. Results. Telomere length was shorter in CKD men, despite women being older (average ± SD 6.41 ± 1.23 vs. 6.96 ± 1.48 kb, P = 0.002). Telomere length was associated with age (rho = −0.18, P = 0.01), fetuin-A (rho = 0.26, P = 0.0004), high-sensitivity C-reactive protein (rho = −0.21, P = 0.005) and IL-6 (rho = −0.17, P = 0.02). In a multivariate logistic regression (pseudo r² = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin-A levels. Conclusion. Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin-A.     

White blood cell count predicts all-cause, cardiovascular disease-cause and infection-cause one-year mortality of maintenance hemodialysis patients

Elevated white blood cell (WBC) counts predict coronary heart disease and all-cause mortality in the general population. Chronic inflammation and malnutrition are associated with increased risk of cardiovascular death in individuals with chronic kidney disease. In this study, we investigated the association between WBC count with inflammation, malnutrition, and mortality in maintenance hemodialysis (MHD) patients. A total of 959 MHD patients were stratified into four equal sized groups based on WBC count. Demographic, hematological, nutritional and inflammatory markers, and biochemical and dialysis-related data were obtained for cross-sectional analysis. All patients were followed for one year to investigate the risks for mortality. The mean WBC count was 6.4 ± 1.8 × 10(3)/μL (range: 2.3-16.3 × 10(3)/μL). Stepwise multiple linear regression analysis indicated a positive correlation between WBC count and inflammation (high-sensitivity C-reactive protein > 3 mg/L). Forty-five patients (4.7%) died within the 1-year study period. Cox multivariate regression analysis demonstrated that total WBC count significantly predicts 1-year mortality due to all-cause (hazard ratio (HR): 1.228, 95% confidence interval (CI): 1.095-1.378; P < 0.001), due to cardiovascular disease (HR: 1.242, 95% CI: 1.046-1.475; P = 0.013) and due to infection (HR: 1.252, 95% CI: 1.066-1.470; P = 0.006). These findings suggest that total WBC count should be measured in future studies that evaluate the clinical outcome of MHD patients and that dialysis patients with elevated WBC counts require further medical attention to reduce risks of mortality.     

Elevated serum uric acid and risk of cardiovascular or all-cause mortality in maintenance hemodialysis patients: A meta-analysis

Background and aimsStudies have shown inconsistent results about the association between serum uric acid (SUA) levels and mortality in hemodialysis patients. We performed this meta-analysis to determine whether higher SUA values comprised a risk factor of cardiovascular or all-cause mortality in maintenance hemodialysis patients.Methods and resultsPubmed, Embase and the Cochrane library were searched up to August 31, 2020 for the longitudinal studies that investigated the association between the elevated SUA and cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. Pooled adjusted hazard ratios (HR) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. We included 10 studies with an overall sample of 264,571 patients with hemodialysis in this meta-analysis. Patients with the highest SUA were associated with a decreased risk of cardiovascular mortality (HR = 0.72, 95% CI 0.59–0.87) compared with patients with the lowest SUA after adjustment for potential confounders in a random effects model. Moreover, for each increase of 1 mg/dl of SUA, the overall risks of all-cause and cardiovascular mortality decreased by 6% and 9%, respectively (HR = 0.94, 95% CI 0.90–0.99; HR = 0.91, 95% CI 0.89–0.94).ConclusionElevated SUA levels are strongly and independently associated with lower risk of cardiovascular mortality in maintenance hemodialysis patients. More designed studies, especially randomized controlled trials, should be conducted to determine whether high SUA levels is an independent risk factor of all-cause mortality in hemodialysis patients.     

男性糖尿病患者踝臂指数与全因和心血管病死亡率关系的前瞻性研究

目的研究男性糖尿病患者外周动脉疾病（PDA）的危险因素及踝臂指数（ABI）与全因和心血管病（CVD）死亡率的关系。方法研究对象来自2004年7月至2005年1月北京及上海地区8所医院的有完整ABI基线资料的男性糖尿病患者815例，于2005年11月至2006年1月对其进行随访调查。结果815例男性糖尿病患者中，ABI降低的PAD组250例（30．67％），ABI正常的非PAD组565例（69．33％），年龄和吸烟史是PAD的独立危险因素，在13．6个月的随访中，有70例死亡，其中27例为CVD死亡。经Cox回归分析，PAD患者发生全因及CVD死亡的相对危险度分别为1．744（1．056—2．877）和3．677（1．588～8．509）。PAD组的生存率显著低于非PAD组。随ABI水平的降低，发生死亡及CVD死亡的危险增加。结论低ABI是男性糖尿病患者死亡和CVD死亡的独立危险因素，在男性糖尿病人群中运用无创性ABI测定对全因死亡及CVD。死亡具有预测价值。     

The combined effect of albuminuria and inflammation on all-cause and cardiovascular mortality in nondiabetic persons

Objectives and design. Recent studies have shown that albuminuria accompanied by evidence of subclinical inflammation is more strongly associated with metabolic abnormalities and the development of atherosclerosis than albuminuria alone. The aim of this population‐based prospective study was to examine the combined effect of albuminuria and inflammatory markers on all‐cause and cardiovascular‐mortality in nondiabetic individuals without macroalbuminuria. Subjects and methods. Urinary albumin and creatinine, some inflammatory markers (fibrinogen, white blood cell and monocyte count) and cardiovascular risk factors were measured in 5702 persons in Tromsø, Norway. Baseline data were collected in 1994–1995 and follow‐up was through 2005. Results. For a one standard deviation higher value of the log‐transformed ratio between albumin and creatinine (ACR), the mortality rate ratio for all‐cause mortality was 1.21 when adjusted for age, gender, established cardiovascular risk factors as well as fibrinogen and white blood cell count (P < 0.001). The corresponding mortality rate ratio for cardiovascular mortality was 1.24 (P < 0.001). Persons in the upper quartile of both ACR and either of the inflammatory markers had an age‐ and gender‐adjusted all‐cause and cardiovascular mortality rate that was four times that of subjects in the lowest quartiles (P < 0.001). Conclusion. ACR predicts all‐cause and cardiovascular mortality in persons without known diabetes and macroalbuminuria. The mortality is especially high amongst individuals with elevated levels of both ACR and inflammatory markers.