Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease

Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ ²=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease.     

Frailty for predicting all-cause mortality in elderly acute coronary syndrome patients: A meta-analysis

BackgroundFrailty has been identified as a risk factor for mortality in patients with acute coronary syndrome (ACS). This meta-analysis aimed to evaluate the association between frailty and all-cause mortality outcome in patients with ACS.MethodsPubmed and Embase databases were searched up to September 26, 2018 for the observational studies evaluating the association between frailty and all-cause mortality in elderly ACS patients. Outcome measures were in-hospital death, short-term all-cause mortality (≤6 months),and long-term all-cause mortality (≥12 months).The impact of frailty on all-cause mortality was summarized as hazard ratios (HR) with 95% confidence intervals (CI) for the frail versus nonfrail patients.ResultsA total of 9 cohort studies involving 2475 elderly ACS patients were included. Meta-analysis showed that ACS patients with frailty had an increased risk of in-hospital death (HR 5.49; 95% CI 2.19–13.77), short-term all-cause mortality (HR 3.56; 95% CI 1.96–6.48), and long-term all-cause mortality (HR 2.44; 95% CI 1.92–3.12) after adjustment for confounding factors. In addition, prefrailty was also associated with an increased all-cause mortality (HR 1.65; 95% CI 1.01–2.69).ConclusionsThis meta-analysis demonstrates that frailty independently predicts all-cause mortality in elderly ACS patients. Elderly ACS patients should be assessed the frailty status for improving risk stratification.     

Clinical Characteristics and Impact of Diabetes Mellitus on Outcomes in Patients with Nonvalvular Atrial Fibrillation

Purpose

Studies have shown that diabetes mellitus (DM) is a risk factor for cardiovascular disease, including atrial fibrillation (AF); however, the clinical characteristics and prognostic impact of DM in patients with nonvalvular AF have not been well understood in China.

Materials and Methods

Included were 1644 consecutive patients with nonvalvular AF. Endpoints included all-cause mortality, cardiovascular mortality, stroke, major bleeding, and combined endpoint events (CEE) during a 1-year follow-up.

Results

The prevalence of DM was 16.8% in nonvalvular AF patients. Compared with non-diabetic AF patients, diabetic AF patients were older and tended to coexist with other cardiovascular diseases. Most patients with DM (93.5%) were eligible for anticoagulation, as determined by CHADS₂ scores. However, only 11.2% of patients received anticoagulation. During a 1-year follow-up, the all-cause mortality and CEE rate in the DM group were significantly higher than those of the non-DM group, while the incidence of stroke was comparable. After multivariate adjustments, DM was still an independent risk factor for 1-year all-cause mortality [hazard ratio (HR)=1.558; 95% confidence interval (CI) 1.126-2.156; p=0.007], cardiovascular mortality (HR=1.615; 95% CI 1.052-2.479; p=0.028), and CEE (HR=1.523; 95% CI 1.098-2.112; p=0.012), yet not for stroke (HR=1.119; 95% CI 0.724-1.728; p=0.614).

Conclusion

DM is a common morbidity coexisting with nonvalvular AF and is associated with an increased risk of 1-year all-cause mortality, cardiovascular mortality, and CEE. However, no increased risk of stroke was found during a 1-year follow-up in patients with AF and DM.     

Plasma CTGF is independently related to an increased risk of cardiovascular events and mortality in patients with atherosclerotic disease: the SMART study

Aims: Connective tissue growth factor (CTGF) plays a key role in tissue fibrogenesis and growing evidence indicates a pathogenic role in cardiovascular disease. Aim of this study is to investigate the association of connective tissue growth factor (CTGF/CCN2) with cardiovascular risk and mortality in patients with manifest vascular disease. Methods and results: Plasma CTGF was measured by ELISA in a prospective cohort study of 1227 patients with manifest vascular disease (mean age 59.0?±?9.9 years). Linear regression analysis was performed to quantify the association between CTGF and cardiovascular risk factors. Results are expressed as beta (β) regression coefficients with 95% confidence intervals (CI). The relation between CTGF and the occurrence of new cardiovascular events and mortality was assessed with Cox proportional hazard analysis. Adjustments were made for potential confounding factors. Plasma CTGF was positively related to total cholesterol (β 0.040;95%CI 0.013–0.067) and LDL cholesterol (β 0.031;95%CI 0.000–0.062) and inversely to glomerular filtration rate (β ?0.004;95%CI ?0.005 to ?0.002). CTGF was significantly lower in patients with cerebrovascular disease. During a median follow-up of 6.5 years (IQR 5.3–7.4) 131 subjects died, 92 experienced an ischemic cardiac complication and 45 an ischemic stroke. CTGF was associated with an increased risk of new vascular events (HR 1.21;95%CI 1.04–1.42), ischemic cardiac events (HR 1.41;95%CI 1.18–1.67) and all-cause mortality (HR 1.18;95%CI 1.00–1.38) for every 1?nmol/L increase in CTGF. No relation was observed between CTGF and the occurrence of ischemic stroke. Conclusions: In patients with manifest vascular disease, elevated plasma CTGF confers an increased risk of new cardiovascular events and all-cause mortality.     

Compliance Index,a Marker of Peripheral Arterial Stiffness,may Predict Renal Function Decline in Patients with Chronic Kidney Disease

Background: Compliance index derived from digital volume pulse (CI-DVP), measuring the relationship between volume and pressure changes in fingertip, is a surrogate marker of peripheral arterial stiffness. This study investigated if CI-DVP can predict renal function deterioration, cardiovascular events and mortality in patients with chronic kidney disease (CKD).Methods: In this prospective observational study, 149 CKD patients were included for final analysis. CI-DVP and brachial-ankle pulse wave velocity (baPWV) were measured, decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope. Composite renal and cardiovascular outcomes were evaluated, including ≥50% eGFR decline, start of renal replacement therapy, and major adverse events.Results: Patients in CKD stages 3b to 5 had higher baPWV and lower CI-DVP values than those in patients with CKD stages 1 to 3a. Stepwise multivariate linear regression analysis showed that lower CI-DVP (p =0.0001) and greater proteinuria (p =0.0023) were independent determinants of higher eGFR decline rate. Multivariate Cox regression analysis revealed that CI-DVP (HR 0.68, 95% CI 0.46-1.00), baseline eGFR (HR 0.96, 95% CI 0.94-0.98) and serum albumin (HR 0.17, 95% CI 0.07-0.42) were independent predictors for composite renal and cardiovascular outcomes.Conclusions: Compliance index, CI-DVP, was significantly associated with renal function decline in patients with CKD. A higher CI-DVP may have independent prognostic value in slower renal function decline and better composite renal and cardiovascular outcomes in CKD patients.     

Clinical characteristics,management and in-hospital mortality of patients with coronavirus disease 2019 in Genoa,Italy

ObjectivesTo describe clinical characteristics, management and outcome of individuals with coronavirus disease 2019 (COVID-19); and to evaluate risk factors for all-cause in-hospital mortality.MethodsThis retrospective study from a University tertiary care hospital in northern Italy, included hospitalized adult patients with a diagnosis of COVID-19 between 25 February 2020 and 25 March 2020.ResultsOverall, 317 individuals were enrolled. Their median age was 71 years and 67.2% were male (213/317). The most common underlying diseases were hypertension (149/317; 47.0%), cardiovascular disease (63/317; 19.9%) and diabetes (49/317; 15.5%). Common symptoms at the time of COVID-19 diagnosis included fever (285/317; 89.9%), shortness of breath (167/317; 52.7%) and dry cough (156/317; 49.2%). An ‘atypical’ presentation including at least one among mental confusion, diarrhoea or nausea and vomiting was observed in 53/317 patients (16.7%). Hypokalaemia occurred in 25.8% (78/302) and 18.5% (56/303) had acute kidney injury. During hospitalization, 111/317 patients (35.0%) received non-invasive respiratory support, 65/317 (20.5%) were admitted to the intensive care unit (ICU) and 60/317 (18.5%) required invasive mechanical ventilation. All-cause in-hospital mortality, assessed in 275 patients, was 43.6% (120/275). On multivariable analysis, age (per-year increase OR 1.07; 95% CI 1.04–1.10; p < 0.001), cardiovascular disease (OR 2.58; 95% CI 1.07–6.25; p 0.03), and C-reactive protein levels (per-point increase OR 1.009; 95% CI 1.004–1.014; p 0.001) were independent risk factors for all-cause in-hospital mortality.ConclusionsCOVID-19 mainly affected elderly patients with predisposing conditions and caused severe illness, frequently requiring non-invasive respiratory support or ICU admission. Despite supportive care, COVID-19 remains associated with a substantial risk of all-cause in-hospital mortality.     

Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort

BACKGROUND: Sleep-disordered breathing (SDB) is a treatable but markedly under-diagnosed condition of frequent breathing pauses during sleep. SDB is linked to incident cardiovascular disease, stroke, and other morbidity. However, the risk of mortality with untreated SDB, determined by polysomnography screening, in the general population has not been established. METHODS: An 18-year mortality follow-up was conducted on the population-based Wisconsin Sleep Cohort sample (n = 1522), assessed at baseline for SDB with polysomnography, the clinical diagnostic standard. SDB was described by the number of apnea and hypopnea episodes/hour of sleep; cutpoints at 5, 15 and 30 identified mild, moderate, and severe SDB, respectively. Cox proportional hazards regression was used to estimate all-cause and cardiovascular mortality risks, adjusted for potential confounding factors, associated with SDB severity levels. RESULTS: All-cause mortality risk, adjusted for age, sex, BMI, and other factors was significantly increased with SDB severity. The adjusted hazard ratio (HR, 95% CI) for all-cause mortality with severe versus no SDB was 3.0 (1.4,6.3). After excluding persons who had used CPAP treatment (n = 126), the adjusted HR (95% CI) for all-cause mortality with severe versus no SDB was 3.8 (1.6,9.0); the adjusted HR (95% CI) for cardiovascular mortality was 5.2 (1.4,19.2). Results were unchanged after accounting for daytime sleepiness. CONCLUSIONS: Our findings of a significant, high mortality risk with untreated SDB, independent of age, sex, and BMI underscore the need for heightened clinical recognition and treatment of SDB, indicated by frequent episodes of apnea and hypopnea, irrespective of symptoms of sleepiness.     

Impact of frailty on all-cause mortality or major amputation in patients with lower extremity peripheral artery disease: A meta-analysis

BackgroundFrailty has been increasingly identified as a risk factor of adverse outcomes in vascular disease. However, its impact on the survival and amputation in patients with lower extremity peripheral artery disease (PAD) remains controversial. This meta-analysis aimed to examine the value of frailty in predicting all-cause mortality or major amputation in patients with lower extremity PAD.MethodsPubMed, Embase, Web of Sciences, and Scopus databases (up to April 7, 2022) were comprehensively searched to identify relevant studies that investigated the association between frailty and all-cause mortality or major amputation in patients with lower extremity PAD. The impact of frailty on adverse outcomes was summarized by pooling the fully adjusted hazard ratio (HR) with 95% confidence intervals (CI) using a random effect (DerSimonian-Laird) model.ResultsSeven studies reporting on eight articles that involved 122,892 patients were included. The prevalence of frailty ranged from 42% to 80% based on the frailty tool used. Meta-analysis showed that frailty was associated with an increased risk of 30-day all-cause mortality (HR 2.11; 95% CI 1.41–3.15; I² =47.6%, p = 0.148, Tau-squared=0.058) and long-term all-cause mortality (HR 1.86; 95% CI 1.25–2.76; I² =76.1%, p = 0.002, Tau-squared=0.118). However, no clear association was observed between frailty and major amputation (HR 1.07; 95% CI 0.83–1.36; I² =23.0%, p = 0.273, Tau-squared=0.019).ConclusionFrailty independently predicts short and long-term all-cause mortality but not major amputation in patients with lower extremity PAD. Frailty status may play an important role in risk stratification of lower extremity PAD.     

Cardiac troponins in chronic kidney disease patients with special emphasis on their importance in acute coronary syndrome

Troponin measurement is one of crucial assessments facilitating diagnosis of acute coronary syndrome. Patients with chronic kidney disease are decimated by cardiovascular disease. Unfortunately, elevated concentration of serum troponin is commonly faced in clinical practice creating a challenge to rule out acute cardiac ischaemia in this vulnerable population. This review presents current knowlegde on analytical differences in troponin T and I measurements, their prognostic significance and their application in diagnosing acute coronary syndrome in chronic kidney disease patients. It also points out poorly known aspects and suggests directions for future research.     

Comparison of Clinical and Imaging Characteristics and Outcomes between Provoked and Unprovoked Acute Pulmonary Embolism in Koreans

This study was performed to compare clinical and imaging parameters and prognosis of unprovoked pulmonary embolism (PE), provoked PE with reversible risk factors (provoked-rRF), and provoked PE with irreversible risk factors (provoked-iRF) in Koreans. Three hundred consecutive patients (mean age, 63.6 ± 15.0 yr; 42.8% male) diagnosed with acute PE were included. The patients were classified into 3 groups; unprovoked PE, provoked-rRF, and provoked-iRF; 43.7%, 14.7%, and 41.7%, respectively. We followed up the patients for 25.4 ± 33.7 months. Composite endpoint was all-cause mortality and recurrent PE. The provoked-iRF group had significantly higher all-cause mortality, mortality from PE and recurrent PE than the unprovoked and provoked-rRF groups (P < 0.001, P < 0.001, and P = 0.034, respectively). Prognostic factors of composite endpoint in the unprovoked group were high creatinine (> 1.2 mg/dL; P < 0.001; hazard ratio [HR], 4.735; 95% confidence interval [CI], 1.845-12.152), C-reactive protein (CRP; > 5 mg/L; P = 0.002; HR, 5.308; 95% CI, 1.824-15.447) and computed tomography (CT) obstruction index (P = 0.034; HR, 1.090; 95% CI, 1.006-1.181). In conclusion, provoked-iRF has a poorer prognosis than unprovoked PE and provoked-rRF. Renal insufficiency, high CRP, and CT obstruction index are poor prognostic factors in unprovoked PE.     

Clinical implications of elevated serum soluble CD137 levels in patients with acute coronary syndrome

OBJECTIVES:

Atherosclerosis is a chronic inflammatory disease. Research has focused on identifying specific serum biomarkers to detect vulnerable plaques. These markers serve as diagnostic tools for acute coronary syndrome and assist in identifying high-risk patients. However, the existing data are limited and conflicting. This study tested the hypothesis that CD137 levels identify patients with acute coronary syndrome who are at a heightened risk for recurrent cardiac events.

METHODS:

The levels of soluble CD137 (sCD137) were measured using ELISA in 180 patients with acute coronary syndrome and 120 patients with acute chest pain. Platelet activation was assessed by flow cytometry. Receiver operating characteristic curve analysis was performed to evaluate the prognostic characteristics of sCD137.

RESULTS:

The levels of sCD137 were elevated in 75 patients with acute coronary syndromes and 20 patients with acute chest pain (>35.0 ng/ml). In patients with acute coronary syndrome, elevated sCD137 levels (>35.0 ng/ml) indicated an increased risk for major adverse cardiovascular events (OR = 1.93, 95% CI: 1.39-2.54). Elevated serum levels of sCD137 and cTnT were correlated with a significantly increased risk of major adverse cardiovascular events in both groups after 30 days, six months and nine months of follow-up. The increased sCD137 levels were significantly correlated with the levels of troponin I (r = 0.4799, p<0.001). Importantly, 26 patients with normal cTnI levels had acute coronary syndrome. However, elevated sCD137 levels identified these patients as a being high-risk subgroup (OR = 2.14, 95% CI: 1.25-4.13).

CONCLUSIONS:

Elevated sCD137 levels indicate an increased risk of cardiovascular events in patients with acute coronary syndrome. Soluble CD137 may be a useful prognostic marker or indicator for adverse events in patients with acute coronary syndrome.     

High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality

YKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40 production in human in vivo studies. High serum YKL-40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We studied whether serum YKL-40 was associated with systemic low-level inflammation, an immune risk phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40, IL-6 and tumour necrosis factor (TNF)-alpha were measured by enzyme-linked immunosorbent assays (ELISAs) in octogenarians (n = 151) and serum YKL-40 in 18-30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year follow-up. Serum YKL-40 in octogenarians was higher compared to the level in young people (median 116 versus 31 microg/l, P < 0.0005). Serum YKL-40 correlated with serum IL-6 in elderly women (Spearman's rho = 0.30, P = 0.009) and men (rho = 0.25, P = 0.003), but only with serum TNF-alpha (rho = 0.23, P = 0.05) and C-reactive protein (CRP) (rho = 0.57, P < 0.0005) among the elderly women. In addition, high serum level of YKL-40 was associated with a low CD4 : CD8 cell ratio. Univariate analysis of serum YKL-40 (logarithmically transformed and divided by tertiles) showed significant association with all-cause mortality [tertile 3: hazard ratio (HR) = 2.38, 95% confidence interval (CI): 1.19-4.78, P = 0.02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass index, chronic disease and anti-inflammatory medicine). These results suggest that serum YKL-40 is a prognostic and sensitive biomarker of all-cause mortality in octogenarians.     

Prognostic Role of C-Reactive Protein in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background: C-reactive protein (CRP) which used to be a prototypical inflammatory cytokine has been identified involving in the progression of tumor-promoting inflammation. Several studies have indicated that CRP is a predictor for hepatocellular carcinoma (HCC), but the results are controversial. Methods: We conducted a systematic review of ten studies (1885 patients) to examine the association of high serum CRP expression with overall survival (OS) and recurrence-free survival (RFS) in HCC patients by meta-analysis. Moreover, the correlation between high serum CRP and tumor clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Results: Our pooled results showed that high expression level of serum CRP (≥10 mg/L) was associated with poor OS (HR: 2.15, 95% CI: 1.76-2.63) and RFS (HR: 2.66, 95% CI: 1.54-4.58) in HCC. Serum CRP overexpression (≥10 mg/L) was also significantly associated with the presence of tumor vascular invasion (OR: 3.05, 95% CI: 1.79-5.23), multiple tumor (OR: 2.36, 95% CI: 1.36-4.10), larger tumor size (OR: 3.41, 95% CI: 1.04-11.18), and advanced TNM stage (OR: 3.23, 95% CI: 2.29-4.57). In addition, serum CRP overexpression (≥10 mg/L) tended to be correlated with poor differentiation (OR: 1.58, 95% CI: 0.74-3.39), though not significantly. Conclusion: The present systematic review and meta-analysis demonstrate that high serum level of CRP (≥10 mg/L) denotes a poor prognosis of patients with HCC.     

Vascular calcifications as a footprint of increased calcium load and chronic inflammation in uremic patients: a need for a neutral calcium balance during hemodialysis?

Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Hyperphosphatemia and an increased calcium-phosphate ion product have also been associated with an increased risk of death. Cardiovascular calcifications secondary to increases in phosphate and calcium load in dialysis patients might exert an important contribution to the excess cardiovascular mortality and morbidity in dialysis patients. Elevated serum levels of plasma C-reactive protein (CRP) are associated with the extent and severity of the atherosclerotic processes as well as with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. In patients affected by pre-dialytic renal failure increased levels of CRP and IL-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation--even in the predialytic phase of renal failure--of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could be at least in part due to the dialytic technique. We have shown that the increase of CRP in stable dialysis patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants. During conventional dialysis, a positive calcium balance and a concomitant inflammatory state may act as cofactors in the development of cardiovascular calcifications. We suggest that this hypothesis should be verified by clinical studies. A reevaluation of the ideal calcium levels in the dialysate is warranted: a neutral intradialytic calcium balance is probably more appropriate, although not easily attainable.     

Predictors and clinical impact of inappropriate implantable cardioverter-defibrillator shocks in Korean patients

Limited data are available on inappropriate shocks in Korean patients implanted with an implantable cardioverter-defibrillator (ICD). We investigated the impact of inappropriate shocks on clinical outcomes. This retrospective, single-center study included 148 patients treated between October 1999 and June 2011. The primary outcome was a composite event of all-cause mortality or hospitalization for any cardiac reason. The median follow-up duration was 29 months (interquartile range: 8 to 53). One or more inappropriate shocks occurred in 34 (23.0%) patients. A history of atrial fibrillation was the only independent predictor of inappropriate shock (hazard ratio [HR]: 4.16, 95% confidence interval [CI]: 1.89-9.15, P < 0.001). Atrial fibrillation was the most common cause of inappropriate shock (67.7%), followed by supraventricular tachycardia (23.5%), and abnormal sensing (8.8%). A composite event of all-cause mortality or hospitalizations for any cardiac reason during follow-up was not significantly different between patients with or without inappropriate shock (inappropriate shock vs no inappropriate shock: 35.3% vs 35.4%, adjusted HR: 1.06, 95% CI: 0.49-2.29, P = 0.877). Inappropriate shocks do not affect clinical outcomes in patients implanted with an ICD, although the incidence of inappropriate shocks is high.     

Elevation of pro-inflammatory cytokines, C-reactive protein and cardiac troponin T in chronic renal failure patients on dialysis

Chronic renal failure (CRF) patients suffer from a chronic inflammation. They are at increased risk of cardiovascular disease. In order to investigate this inflammatory process and cardiovascular risk factors associated with haemodialysis (HD) and peritoneal dialysis (PD), we compared serum/plasma pro-inflammatory cytokines, C-reactive protein (CRP), and cardiac troponin T (cTnT) of 146 CRF patients treated or not treated with PD or HD. Serum cytokines and CRP as well as plasma cTnT were measured by enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and electrochemiluminescence immunoassay, respectively. Results indicated that serum interleukin (IL)-18 concentrations were significantly higher in PD and low creatinine clearance pre-dialysis CRF (LCC) patients than HD patients (both p < 0.05). IL-6 and tumour necrosis factor (TNF)-alpha concentrations were significantly higher in PD patients than LCC patients (both p < 0.01). Serum hsCRP and plasma cTnT in HD were significantly higher than LCC (both p < 0.01). The elevation of pro-inflammatory cytokines should play an important role in the chronic inflammation and increased cardiovascular risk of CRF patients on dialysis. We are evaluating further the diagnostic and prognostic applications of pro-inflammatory cytokines and biochemical inflammatory markers for these patients.     

Elevated iron status strongly predicts mortality in West African adults with HIV infection

OBJECTIVE: To comprehensively assess iron status and determine whether elevated iron status, like anemia, predicts mortality. METHODS: We followed 1362 Gambian adults (53% female) in an HIV-seroprevalent clinic-based cohort over 11.5 years to ascertain all-cause mortality. Baseline iron status (iron, soluble transferrin receptor [sTfR], transferrin, ferritin, transferrin saturation, log [transferrin receptor: ferritin]), age, gender, ethnicity, hemoglobin, body mass index, HIV type, absolute CD4 count, malaria status, and [alpha]-(1)-antichymotrypsin were measured. RESULTS: The mortality rate was 25.9/100 person-years. Elevated iron universally predicted greater mortality compared to normal iron status for all iron status indices, with the exception of sTfR in unadjusted models. In fully adjusted models, transferrin (elevated vs. normal, hazard ratio [HR]: 1.77; 95% confidence interval [CI]: 1.30 to 2.42; P < 0.001), ferritin (elevated vs. normal, HR: 1.40; 95% CI: 1.07 to 1.83; P = 0.014), and the combined iron status index (highly elevated vs. normal, HR: 2.20; 95% CI: 1.16 to 4.18; P = 0.016) remained significant predictors. As expected, hemoglobin (Hb) concentration and absolute CD4 counts were each inversely associated with mortality. CONCLUSIONS: Elevated iron status predicts mortality in HIV infection, even after adjustment for immunosuppression and other confounders. This finding has implications in the clinical monitoring of disease progression and for iron-supplementation practices in areas of high HIV prevalence.     

Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis

Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (−3.7 g/L, 95% CI, −5.3 to −2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.     

Relationships between myocardial injury, all-cause mortality, vitamin D, PTH, and biochemical bone turnover markers in older patients with hip fractures

This study examined the relationships between myocardial injury as indicated by serum cardiac troponin I (cTnI) elevation, 25 hydroxyvitamin D [25(OH)D], and PTH status and biochemical markers of bone metabolism in older patients with hip fracture (HF). In 238 consecutive patients (mean age 81.9 +/- 7.8 yr; 72% women) with low trauma HF, serum concentrations of cTnI, 25(OH)D, PTH, calcium, phosphorus, magnesium, osteocalcin, bone-specific alkaline phosphatase (BAP), and urine excretion of free deoxypyridinoline (DPD) and N-terminal cross-linked teleopeptide of type I collagen (NTx) were measured and clinical data were collected prospectively. Myocardial injury (cTnI >0.06 microg/L) presented in 29%, 25(OH)D deficiency (<50 nmol/L) in 81.6%, elevated PTH (>6.5 pmol/L) in 53%, and excessive bone resorption (increased DPD and/or NTx excretion) in 93.7%. Multivariate logistic regression showed that elevated serum PTH level is a major predictor of peri-operative myocardial injury (OR = 2.13; 95% CI 1.01-4.51; p = 0.049) and in-hospital all-cause mortality (OR = 18.5; 95% CI 2.0-72.3; p = 0.010), independent of age, sex, 25(OH)D status, and comorbidities. The degree of hyperparathyroidism was associated with the risk of cTnI elevation and the mortality rate. In cTnI positive patients, PTH levels correlated with cTnI concentrations (r = 0.28; p = 0.026) and urine DPD exretion (r = 0.37; p = 0.004). These results suggest for the first time that in older patients with HF, elevated PTH level is associated with peri-operative myocardial injury and in-hospital all-cause mortality, and that elevated PTH level contributes to both disturbed bone metabolism and poor outcomes.     

Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease

BACKGROUND: In patients with unstable coronary artery disease, there is a relation between the short-term risk of death and blood levels of troponin T (a marker of myocardial damage) and C-reactive protein and fibrinogen (markers of inflammation). Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial, we evaluated the usefulness of troponin T, C-reactive protein, and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes. METHODS: Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease. The patients were followed for a mean of 37.0 months (range, 1.6 to 50.6). RESULTS: During follow-up, 1.2 percent of the 173 patients with maximal blood troponin T levels of less than 0.06 microg per liter died of cardiac causes, as compared with 8.7 percent of the 367 patients with levels of 0.06 to 0.59 microg per liter and 15.4 percent of the 377 patients with levels of at least 0.60 microg per liter (P=0.007 and P=0.001, respectively). The rates of death from cardiac causes were 5.7 percent among the 314 patients with blood C-reactive protein levels of less than 2 mg per liter, 7.8 percent among the 294 with levels of 2 to 10 mg per liter, and 16.5 percent among the 309 with levels of more than 10 mg per liter (P=0.29 and P=0.001, respectively). The rates of death from cardiac causes were 5.4 percent among the 314 patients with blood fibrinogen levels of less than 3.4 g per liter, 12.0 percent among the 300 with levels of 3.4 to 3.9 g per liter, and 12.9 percent among the 303 with levels of at least 4.0 g per liter (P=0.004 and P=0.69, respectively). In a multivariate analysis, levels of troponin T and C-reactive protein were independent predictors of the risk of death from cardiac causes. CONCLUSIONS: In unstable coronary artery disease, elevated levels of troponin T and C-reactive protein are strongly related to the long-term risk of death from cardiac causes. These markers are independent risk factors, and their effects are additive with respect to each other and other clinical indicators of risk.