Association of aortic pulse wave velocity with cardiovascular outcomes and all-cause mortality in diabetes: A systematic review and meta-analysis.

Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study

Chronic kidney disease (CKD) is a global health concern associated with an elevated risk of cardiovascular (CV) and all-cause mortality. The ankle-brachial index (ABI), a noninvasive diagnostic tool, is widely recognized for detecting peripheral arterial disease. This meta-analysis aims to assess whether abnormally low or high ABI values independently predict CV and all-cause mortality in CKD patients, including those on hemodialysis. A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using PubMed, Cochrane, and Google Scholar databases through September 2024 to identify studies on abnormal ABI and mortality outcomes in CKD patients with or without hemodialysis. Data was analyzed with random-effects models, and subgroup analyses evaluated variations by patient characteristics, region, sample size, and follow-up duration. The analysis included 10 cohort studies comprising 13,378 participants. ABI values between 0.9 and 1.3 were defined as normal. Individuals with abnormally low ABI (<0.9) demonstrated a significantly higher incidence in CV mortality [hazard ratio (HR) = 2.23; confidence interval (CI), 1.75-2.83) and all-cause mortality (HR = 1.78; CI, 1.55-2.05). Those with high ABI ≥1.3 were associated with a 2.77-fold increase in CV mortality (HR = 2.77; CI, 1.74-4.41) and a 1.49 higher risk of all-cause mortality (HR = 1.49; CI, 1.09-2.02). Overall, abnormal ABI values were linked to a 1.74 higher risk of all-cause mortality (HR = 1.74; CI, 1.54-1.96) and a 2.34-fold increase in CV mortality (HR = 2.34; CI, 1.93-2.85). Subgroup analyses revealed higher mortality risks in hemodialysis patients compared with nondialysis CKD patients and in studies conducted in Asia. Abnormal ABI values show a U-shaped relationship with mortality, serving as strong predictors of CV and all-cause mortality in CKD patients, particularly those on hemodialysis. Since CV and all-cause mortality are high in CKD patients, these findings suggest that ABI measurement is a useful screening technique to assist in prognosticating such patients. Further studies are warranted to validate these findings and to better understand the prognostic utility of ABI across different CKD stages, including both dialysis-dependent and nondialysis CKD patients.

Medullary thyroid carcinoma (MTC) is a malignancy with a high mortality rate and a wide age range. However, there are relatively few studies on the relationship between age and all-cause mortality in patients with MTC. As one of the important factors influencing cancer prognosis, the association between age and all-cause mortality in MTC patients needs to be further investigated. The aim of this study was to investigate the relationship between age and all-cause mortality in MTC patients, especially whether there is an inverse L-shaped curve relationship, in order to provide new insights for clinical management and prognostic assessment. A detailed retrospective cohort analysis of 1291 MTC patients diagnosed between 2000 and 2021 was included in this study using the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression modelling, curve fitting, Kaplan-Meier (KM) survival curves and subgroup analyses were used to assess the association between age and all-cause mortality in MTC patients. Potential confounders, including patient sex, race, Summary stage, surgery, Lymph.node.dissection, tumour size and lymph node metastasis (LNM), were rigorously controlled. The risk of all-cause mortality in MTC patients increased by 6% per 1-year increase in age (hazard ratio HR=1.06, 95% confidence interval CI: 1.05-1.06, p<0.001). Further analysis revealed a significant inverse L-shaped relationship between age and all-cause mortality in MTC patients. Specifically, before the age of 50 years, the hazard ratio increased slowly with age (HR=1.024, 95% CI: 0.991-1.059) and the difference was not statistically significant (p=0.1616). After the age of 50 years, the hazard ratio accelerated with increasing age (HR=1.066, 95% CI: 1.051-1.081) and the difference was statistically significant (p<0.001). The results of this study confirm that there is an inverse L-shaped relationship between age and all-cause mortality in MTC patients. The risk of all-cause mortality in MTC patients increased significantly with age after age >50 years. This finding provides new insights into understanding the complex relationship between age and all-cause mortality in MTC, which may help inform clinical management and prognostic assessment.

Aims The association between the triglyceride-glucose (TyG) index and cardiovascular risk in young and middle-aged individuals with Metabolic syndrome (MetS) remains unclear. This study aimed to investigate the relationship between baseline TyG index and cardiovascular events and all-cause mortality in these patients among American adults. Methods This study enrolled 4937 young and middle-aged patients with MetS from the National Health and Nutrition Examination Survey (1999–2018). Mortality outcomes were determined by linking to National Death Index records up to December 31, 2019. Multivariate Cox proportional hazards models were constructed to analyze explore the associations between baseline TyG index and cardiovascular events or all-cause mortality. Non-linear correlations were explored using restricted cubic splines, and a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results During the up to 9.3 years follow-up period, a total of 463 all-cause deaths and 143 cardiovascular events were recorded. The multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) escalate from the lowest to the highest TyG index quartile. Specifically, for cardiovascular events, the HRs range from 1.00 (reference) to 2.29 (1.22, 4.31) with a significant trend (P = 0.004). For all-cause mortality, the HRs vary from 1.00 (reference) to 1.59 (1.09, 2.32), also showing a significant trend (P = 0.003). The restricted cubic splines revealed a J-shaped association between the baseline TyG index with cardiovascular events and all-cause mortality in MetS patients. Conclusions The high TyG index was identified as an independent predictor of elevated rates of cardiovascular events among young and middle-aged patients with MetS. Additionally, a J-shaped curve pattern was observed in the association between these factors.

Aim Inconsistent investigations of the risk factors for all-cause mortality in patients undergoing peritoneal dialysis (PD) were reported. The present meta-analysis aimed to assess the impact of some clinical characteristics on the risk of mortality in PD patients. Methods PubMed and Embase were systematically searched for studies evaluating the risk factors for all-cause mortality in PD patients. Hazard ratio (HR) and 95% confidence interval (CI) were derived using a random-effect or fixed-effect model considering the heterogeneity across studies. Result A total of 26 studies were included in this meta-analysis in accordance with the inclusion and exclusion criteria. Age, primary cardiovascular diseases, diabetes mellitus, and high level of alkaline phosphatase showed significant positive associations with elevated risk of all-cause and cardiovascular mortality in PD patients, while hemoglobin acted as a benefit factor. Furthermore, early onset of peritonitis, high peritoneal transport status, elevated body mass index and high-sensitivity C-reactive protein could also considerably increase the risk of all-cause mortality. The absolute serum level of magnesium, potassium, and uric acid required to improve survival in PD patients should be verified further. Conclusions Multiple factors could affect the risk of mortality in PD patients.

Background: Available data on the effects of testosterone replacement therapy (TRT) on cardiovascular (CV) events and all-cause mortality have yielded conflicting results. There is scarcity of data from large prospective randomized controlled trials in this regard. The objective of this meta-analysis is to compare all-cause mortality and cardiovascular outcomes in patients with and without TRT. Methods: PubMed database and Google Scholars was searched through May 2024 for articles meeting the eligibility criteria. We included randomized controlled trials (RCTs) with a sample size of at least 100 patients and a follow-up of more than 12 months. The end points were all-cause mortality, CV mortality, myocardial infarction (MI), stroke, and any CV event. The Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI) was computed with Random Effects model and p&lt;0.05 was considered as a level of significance. RevMan 5.4 software was used for the analysis. Results: There were twelve studies (n=8,636) comparing CV outcomes and all-cause mortality among patients with hypogonadism treated with TRT (n=4,336) vs control groups (n=4300). There was no significant heterogeneity observed with the outcomes. There was no significant difference in MI (OR 1.11; CI 0.79-1.55), stroke (OR 1.02; CI 0.67-1.53), any CV events (OR 0.94; CI 0.62-1.43), CV mortality (OR 0.88; CI 0.0.66-1.16), and all-cause mortality (OR 0.86; CI 0.49-1.49) between TRT and control groups. Forest plots (Figure 1 and Figure 2) showed MI and any cardiovascular events, respectively. Conclusion: There was no significant difference in CV outcomes and all-cause mortality in patients treated with TRT as compared to controls. However, large RCTs with a long-term follow-up are needed to evaluate these findings.

OBJECTIVES:Geriatric nutritional risk index (GNRI) might predict the all-cause mortality in patients with heart failure (HF). We performed a meta-analysis to evaluate the correlation between GNRI and all-cause mortality in patients with HF.METHODS:We searched the PubMed, Medline, Cochrane Library, and Embase databases for clinical trials investigating the association between GNRI and all-cause mortality in patients with HF, having the primary endpoint as all-cause mortality.RESULTS:In total, nine studies involving 7,659 subjects were included in the systematic review and meta-analysis. The results indicated that major risk and moderate risk GNRI (GNRI<92) was associated with an increased risk of all-cause mortality in elderly patients with HF (hazard ratios [HR] 1.59, 95% confidence intervals [CI] 1.37-1.85). Low risk GNRI (GNRI<98) group predicted all-cause mortality in elderly HF patients (HR 1.56, 95%CI 1.12-2.18) when compared with the high GNRI value group. A subgroup analysis indicated that the relationship between GNRI and HF might differ based on the subtype of heart failure.CONCLUSIONS:GNRI is a simple and well-established nutritional assessment tool to predict all-cause mortality in patients with HF.

Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known. We analyzed prevalence, clinical phenotypes and association of LEAD - assessed by the ankle-brachial index (ABI) - and increased aortic stiffness - assessed by the aortic pulse wave velocity (PWV) - with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS. Among 270 patients admitted for ACS (mean age 67 years, 80% males), 41 (15%) had an ABI ≤0.9, with 14 of them (34%) presenting with intermittent claudication (symptomatic LEAD). Patients with symptomatic LEAD, compared with those with asymptomatic LEAD or without LEAD, had higher prevalence of cardiovascular risk factors, lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein. Patients with LEAD, either symptomatic or asymptomatic, more frequently presented with non-ST-elevation myocardial infarction and more frequently had multivessel coronary artery disease. Both symptomatic and asymptomatic LEAD were significantly associated with all-cause mortality after adjustment for confounders, including multivessel disease or carotid artery disease (hazard ratio 4.03, 95% confidence interval 1.61-10.08, P < 0.01), whereas PWV was not associated with the outcome in the univariable model. LEAD and PWV were not associated with a higher risk of MACE (myocardial infarction or unstable angina, stroke, or transient ischemic attack). LEAD, either clinical or subclinical, but not increased aortic stiffness, is an independent predictor of all-cause mortality in patients admitted for ACS.

Background Angiopoietin-2 (ANGPT2) is an important regulator of angiogenesis. Higher levels of ANGPT2 have been found to be associated with an adverse cardiovascular risk factor profile potentially reflecting maladaptive vascular remodelling including atherosclerotic plaque destabilization. Purpose To evaluate the prognostic utility of ANGPT2 added to conventional clinical risk factors for coronary heart disease, including B-type natriuretic peptide (BNP), troponin T (TnT) and C-reactive protein (CRP), in patients with suspected acute coronary syndrome (ACS). Methods 871 chest-pain patients with clinically suspected ACS from South-Western Norway and 982 patients from Northern Argentina were consecutively included in a prospective transatlantic cohort study. We measured plasma-concentrations of ANGPT2 in admission-samples from 1815 patients by enzyme immunoassay. Univariable- and multivariable Cox proportional-hazards models, applying both loge-transformed continuous values and quartiles (Q1–4), were fitted for the analysis of all-cause mortality, cardiac death and sudden cardiac death (SCD) within 24-month follow-up. Of the patients with suspected ACS, 838 patients had TnT release above the detection-limit of 0.01 ng/mL. We performed subgroup analysis for all-cause mortality in patients with and without TnT release. Results Median age in the total population was 66.0 (Q1-Q3; 55.0–76.8) years and 60.4% were males. At 24-month follow-up, 254 patients (14%) had died, of which 150 (8.3%) suffered cardiac death and 76 (4.2%) SCD. ANGPT2 levels were significantly higher in patients who died compared to long-term survivors [3.87 (2.40–7.54) ng/mL versus 2.11 (1.48–3.22) ng/mL (median, 25 and 75% percentiles), p&amp;lt;0.001]. In multivariable analysis, ANGPT2 concentrations in the highest quartile (Q4) as compared to the lowest (Q1) were significantly associated with all-cause mortality [Hazard Ratio (HR) 1.96 (95% confidence interval (CI); 1.12–3.42), p=0.018) and cardiac death [HR 2.23 (95% CI; 1.01–4.92), p=0.047] at 24-month follow-up. For SCD, ANGPT2 concentrations in both Q3 [HR 3.59 (95% CI; 1.05–12.3), p=0.041] and Q4 [HR 3.81 (95% CI; 1.12–12.9), p=0.032] as compared to Q1 were significantly related to outcome. These results were confirmed using loge-transformed continuous values of ANGPT2. ANGPT2 was also an independent predictor of all-cause mortality in both patients with and without TnT release. For patients with TnT &amp;gt;0.01 ng/mL, HR for ANGPT2 in Q4 as compared to Q1 was 2.77 (95% CI: 1.41–5.44), p=0.003. For patients with TnT ≤0.01, HR for ANGPT2-Q4 was 2.67 (95% CI: 1.08–6.62), p=0.034. Conclusion High levels of ANGPT2 were found to independently predict all-cause mortality, cardiac death and sudden cardiac death in chest-pain patients with suspected ACS, irrespective of clinical demographics, troponin-release, CRP and BNP. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Regional Health Authority

Remnant cholesterol as a risk factor for all-cause and cardiovascular mortality in incident peritoneal dialysis patients

The stress hyperglycemia ratio (SHR) is an emerging biomarker used to assess blood glucose levels under acute stress conditions and has been linked to the incidence of adverse clinical outcomes. However, the precise role of SHR in patients with diabetic kidney disease (DKD) and chronic kidney disease (CKD), particularly in relation to mortality, remains poorly understood. This study seeks to investigate the clinical value of SHR as a predictive tool for all-cause and cardiovascular mortality in these patient groups. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018, encompassing 3,507 individuals diagnosed with diabetic kidney disease (DKD) or chronic kidney disease (CKD). The primary endpoints included all-cause mortality and cardiovascular mortality, with mortality data obtained from the National Death Index (NDI) through December 31, 2019. Participants were categorized into quartiles based on the stress hyperglycemia ratio (SHR), and Cox proportional hazards regression models were employed to examine the association between SHR and mortality. Model 1 did not account for any covariates, Model 2 adjusted for age, sex, and race, while Model 3 additionally incorporated adjustments for educational attainment, marital status, body mass index, smoking behavior, hypertension, hyperlipidemia, and cardiovascular disease. The study comprised 3,507 patients with a mean age of 60.7 years, of whom 56% were female. The overall incidence of all-cause mortality was 38,000 per 100,000 person-years, while cardiovascular mortality was 11,405 per 100,000 person-years. Kaplan–Meier survival analysis revealed that the second quartile of the stress hyperglycemia ratio (SHR) (Q2) exhibited the lowest all-cause mortality (log-rank P = 0.003). Cox regression analysis indicated that the hazard ratio (HR) for all-cause mortality in Q2 was 0.76 (95% CI: 0.63, 0.92), whereas the HR for Q4 was 1.26 (95% CI: 1.04, 1.52). Restricted cubic spline (RCS) analysis revealed a J-shaped association between SHR and all-cause mortality, as well as a U-shaped association with cardiovascular mortality. The minimum risk values for SHR were 0.923 for all-cause mortality and 1.026 for cardiovascular mortality. In patients with diabetic kidney disease (DKD) and chronic kidney disease (CKD), SHR demonstrated a J-shaped relationship with all-cause mortality and a U-shaped relationship with cardiovascular mortality. Subgroup analyses indicated that the effect of spontaneous hypertension on mortality was consistent across all subgroups. This study highlights a significant association between the stress hyperglycemia ratio (SHR) and both all-cause and cardiovascular mortality in patients with diabetic kidney disease (DKD) or chronic kidney disease (CKD). SHR may serve as a critical biomarker for prognostic assessment in these populations, enabling clinicians to identify high-risk patients and tailor personalized treatment strategies that enhance patient quality of life and mitigate mortality risk.Graphical abstract

BackgroundThis study was to explore the relationship between cardiovascular health (CVH) and the risk of all-cause mortality in patients with osteoarthritis (OA).MethodsThis cohort study retrieved the data of 3642 patients with OA aged ≥ 20 years from the 2007—2018 National Health and Nutrition Examination Survey (NHANES). CVH was evaluated based on Life’s Essential 8 (LE8) includes diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The outcome of all-cause mortality was assessed using the death certificate records of participants from the National Death Index. Variables that might affect all-cause mortality were used as covariates. The weighted univariate COX proportional hazards model was used to explore the association between each covariate and all-cause mortality. The weighted univariate and multivariate COX proportional hazards models were used to explore the association between different CVH levels and all-cause mortality. A restricted cubic spline (RCS) curve was plotted to show the association between different CVH levels and all-cause mortality in OA patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated.ResultsFindings show that people with moderate CVH (HR = 0.67, 95% CI = 0.45—0.98) and high CVH (HR = 0.47, 95% CI = 0.26—0.87) were associated with reduced risk of all-cause mortality in patients with OA. The HR of all-cause mortality in patients with OA decreased by 0.12 as per 10 points increase of LE8 score (HR = 0.81, 95% CI = 0.73—0.90). The RCS curve revealed that the HR of all-cause mortality decreased with the increase in LE8 score. The survival probability of patients in the high CVH group was higher than the moderate CVH group and low CVH group (p = 0.002).ConclusionModerate-to-high CVH is associated with a decreased risk of all-cause mortality in patients with OA. These findings might provide a reference for the formulation of prognosis improvement strategies for the management of patients with OA.

Relationship of neutrophil-to-lymphocyte ratio, in addition to C-reactive protein, with cardiovascular events in patients with type 2 diabetes

Aim. To estimate outcomes and risk of all-cause mortality, cardiovascular (CV) mortality, and non-fatal CV events in patients with a history of acute cerebrovascular accident (ACVA) according to data of outpatient prospective registries.Material and methods. 986 patients with a history of ACVA (aged 70.6Ѓ}10.9 years; 56.8% women) were enrolled into the outpatient registry REGION-Ryazan, including the registry of patients with ACVA of any remoteness (ACVA-AR) – 511 (aged 70.4Ѓ}10.5 years; 58.5% women) and the registry of patients, visited outpatient clinics for the first time after ACVA (ACVA-FT) – 475 (aged 70.8Ѓ}11.3 years; 54.9% women). Outcomes, risk of all-cause and CV mortality, composite CV endpoint (CV death, nonfatal myocardial infarction and ACVA), hospitalizations due to CV diseases (CVD) were evaluated during 37 (17;52) months of follow-up period.Results. 310 (31.2%) patients died during the follow-up. The most part of fatal outcomes (56.4%) was registered during the first year of follow-up, especially during the first 3 months (33.9%). Mortality among men (35.9%) was higher than among women (28.0%), р=0.008. 147 (28.8%) and 163 (34.3%) patients died in registries ACVA-AR and ACVA-FT, respectively (70.4% and 90.2% of fatal outcomes were from CV causes, respectively; р=0.04). The higher risk of death was associated with the following factors: age – hazard ratio (HR) 1.10 for each next year of age (95% confidence interval [95%CI] 1.09-1.12); sex (men) – HR 2.01 (95%CI 1.55-2.62); atrial fibrillation (AF) – HR 1.42 (95%CI 1,09-1,86); recurrent ACVA – HR 1.64 (95%CI 1.23-2.19); history of myocardial infarction (MI) – HR 1.45 (95%CI 1.09-1.93); low blood hemoglobin level – HR 2.44 (95%CI 1.59-3.79); heart rate ≥80 beats/min – HR 1.51 (95%CI 1.13-2.03); diabetes – HR 1.56 (95%CI 1.16-2.08); chronic obstructive pulmonary disease (COPD) – HR 1.89 (95%CI 1.34-2.66); no antihypertensive therapy in arterial hypertension – HR 2.03 (95%CI 1.42-2.88). The lower risk of death was associated with the following factors: prescription of ACE inhibitors (ACEI) – HR 0.60 (95%CI 0.42-0.85); angiotensin II receptor blockers (ARB) – HR 0.26 (95%CI 0.13-0.50), beta-blockers – HR 0.71 (95%CI 0.50-0.99); statins – HR 0.59 (95%CI 0.42-0.82). Factors, listed above, had significant association not only with all-cause mortality but also with CV mortality and composite CV endpoint. The higher rate of hospitalizations due to CVD was associated with younger age (incidence rate ratio [IRR] for 1 year 1.03; 95%CI 1.02-1.05; р&lt;0.001), female sex (IRR 2.40; 95%CI 1.79-3.23; р&lt;0.001), COPD (IRR 2.44; 95%CI 1.63-3.65; р&lt;0.001) and heart rate ≥80 beats/min (IRR 1.51; 95%CI 1.12-2.04; р=0.007).Conclusions. All-cause mortality in patients with a history of ACVA, enrolled in outpatient registry REGION, was 31.2% during 3-year follow-up. The proportion of CV death among the fatal cases was higher in the ACVA-FT registry than in ACVA-AR registry. The higher mortality rate was associated with the following factors: age, sex (male), recurrent ACVA, history of MI, diagnosis of AF, COPD and diabetes, low blood hemoglobin level, heart rate ≥80 beats/min, no antihypertensive therapy in arterial hypertension. The higher incidence of hospitalizations due to CVD was associated with younger age, sex (female), COPD and heart rate ≥80 beats/min. Prescription of ACEI, ARB, beta-blockers and statins was associated with lower risk of death and composite CV endpoint.

Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19-1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79-0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053-0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12-1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed.