Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction

Background and aimsLow serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients.Methods and resultsMulticenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4–41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71–12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37–0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS −0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30–9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99–14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02–18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21–10.80, p = 0.022) were associated with AEs.ConclusionLow SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.     

Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases

BackgroundThe taxonomy of cardiovascular (CV) diseases is divided into a broad spectrum of clinical entities. Many such diseases coincide in specific patient groups and suggest shared predisposition.ObjectivesThis study focused on coronary artery disease (CAD) and investigated the genetic relationship to CV and non-CV diseases with reported CAD comorbidity.MethodsThis study examined 425,196 UK Biobank participants to determine a genetic risk score (GRS) based on 300 CAD associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis.ResultsHypercholesterolemia (odds ratio [OR]: 1.27; 95% CI: 1.26 to 1.29) and hypertension (OR: 1.11; 95% CI: 1.10 to 1.12) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. However, the CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR: 1.37; 95% CI: 1.30 to 1.44). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR: 1.28; 95% CI: 1.23 to 1.32), abdominal aortic aneurysms (OR: 1.28; 95% CI: 1.20 to 1.37), and stroke (OR: 1.08; 95% CI: 1.05 to 1.10), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR: 1.25; 95% CI: 1.22 to 1.29), atrial fibrillation (OR: 1.08; 95% CI: 1.05 to 1.10), and premature death (OR: 1.04; 95% CI: 1.02 to 1.06). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. Finally, an inverse association was observed between the score and migraine headaches (OR: 0.94; 95% CI: 0.93 to 0.96).ConclusionsA wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches.     

Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD

Background and aimsSome previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD.Methods and resultsA total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77–11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30–7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3–F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype.ConclusionsSerum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.     

Triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular events in the general population: A systematic review and meta-analysis of cohort studies

AimsThe ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) has been regarded as a novel surrogate indicator of insulin resistance and the atherogenic index of plasma. This meta-analysis aimed to evaluate the association between the TG/HDL-C ratio and the incidence of cardiovascular events in the general population.Data synthesisCohort studies reporting the association between the TG/HDL-C ratio and cardiovascular events in the general population were obtained by a systematic literature search of PubMed, Embase and Web of Science databases until April 11, 2021. 13 cohort studies with a total of 207,515 participants were included in this meta-analysis. In a random-effects model, compared with those with the lowest category of the TG/HDL-C ratio, participants with the highest category were independently associated with a higher risk of cardiovascular events (pooled HR: 1.43, 95%CI: 1.26–1.62, I² = 72.9%). For the presence of publication bias detected by the Egger's test (p = 0.011), correction for publication bias using the trim-and-fill method reduced the HR to 1.26 (95%CI: 1.11–1.44). This result was consistent with the finding of the TG/HDL-C ratio analyzed as a continuous variable (pooled HR per unit increment of the TG/HDL-C ratio: 1.08, 95%CI: 1.04–1.12, I² = 67.0%). Subgroup analyses indicated that population gender, geographical region, duration of follow-up, adjustment for other lipid parameters, adjustment for diabetes and categorical number did not significantly vary the relationship.ConclusionElevated TG/HDL-C ratio may be independently associated with an increased risk of cardiovascular events in the general population. More well-designed studies are needed to confirm the current findings.Registration number in PROSPEROCRD42021244583.     

Does a high intake of green leafy vegetables protect from NAFLD? Evidence from a large population study

Background and aimsResults of in vitro and in vivo studies showed that green leafy vegetables (GLV) could attenuate liver steatosis. However, little is known regarding the association between GLV intake and nonalcoholic fatty liver disease (NAFLD) in human. We examined the association of GLV intake with NAFLD in a large-scale adult population.Methods and resultsThis cross-sectional study investigated 26,891 adults in China who participated in health examinations from 2013 to 2017. Newly diagnosed NAFLD was detected by liver ultrasonography. Dietary intake was assessed by using a validated and standardized food frequency questionnaire. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) across categories of GLV intake. After adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the OR (95% CI) for comparing the highest vs. lowest GLV intake categories (≥7 times/week vs. almost never) was 0.72 (0.59, 0.90) (P < 0.0001). In addition, a linear inverse association was demonstrated between GLV intake and NAFLD in women (P for trend = 0.04), but ORs for any intake category did not reach significance. Stratified analyses suggested a potential effect modification by obesity status; the ORs (95% CIs) for comparing the highest vs. lowest GLV intake categories was 0.72 (0.54, 0.97) in normal/overweight individuals and 1.04 (0.65, 1.65) in obese individuals (P-interaction < 0.0001).ConclusionThis large population-based study shows that high GLV intake is inversely associated with NAFLD, particularly in women and non-obese participants.     

Prevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome

ObjectiveGrowing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence.MethodsWe performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models.ResultsIn contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02–21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80–16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04–10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27–10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86–31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51–18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34–19.83, p = 0.015) in subgroup of patients older than 58.ConclusionsOS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.     

Visceral adipose tissue quality was associated with nonalcoholic fatty liver disease,independent of its quantity

Background and aimsNonalcoholic fatty liver disease (NAFLD) is a serious liver disease. Recent studies have shown that both visceral adipose tissue (VAT) quantity and density (as an indirect measure of quality) are associated with metabolic profiles. Therefore, we investigated the association between VAT quantity and quality, and the prevalence and incidence of NAFLD.Methods and resultsIn this cross-sectional, retrospective cohort study, the prevalence and incidence of NAFLD were analyzed in 627 and 360 middle-aged subjects, respectively. VAT was evaluated using an unenhanced computed tomography scan, while NAFLD was evaluated using ultrasonography. The VAT area was normalized to the square value of the subjects’ height in meters, the visceral fat area (VFA) index. The VAT density was described as the visceral fat density (VFD). The VFA index and VFD had an interaction effect on the prevalence of NAFLD (P = 0.0059). The VFA index (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.07; P = 0.0145, per 1.0 cm²/m²) and the VFD (OR, 0.90; 95% CI, 0.84–0.96; P = 0.0026, per 1.0 Hounsfield unit [HU]) were independently associated with the prevalence of NAFLD. In our cohort, 36 subjects developed NAFLD. The VFD (adjusted hazards ratio [HR], 0.84; 95% CI, 0.77–0.91; P < 0.0001, per 1.0 HU) was independently associated with the incidence of NAFLD, whereas the VFA index was not.ConclusionBoth the VFA index and VFD were independently associated with NAFLD prevalence. The VFD might be more related to the incidence of NAFLD than the VFA index.     

Association between non-alcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes—The Cooperative Health Research in South Tyrol (CHRIS)-NAFLD sub-study

Background and aimsCardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD), both with and without type 2 diabetes mellitus (T2DM). Cardiac autonomic dysfunction is a risk factor for CVD morbidity and mortality. The aim of this pilot study was to assess whether there is an association between NAFLD and impaired cardiac autonomic function.Methods and resultsAmong the first 4979 participants from the Cooperative Health Research in South Tyrol (CHRIS) study, we randomly recruited 173 individuals with T2DM and 183 age- and sex-matched nondiabetic controls. Participants underwent ultrasonography and vibration-controlled transient elastography (Fibroscan®, Echosens) to assess hepatic steatosis and liver stiffness. The low-to-high-frequency (LF/HF) power ratio and other heart rate variability (HRV) measures were calculated from a 20-min resting electrocardiogram (ECG) to derive a measure of cardiac sympathetic/parasympathetic imbalance. Among the 356 individuals recruited for the study, 117 had NAFLD and T2DM, 56 had T2DM alone, 68 had NAFLD alone, and 115 subjects had neither condition. Individuals with T2DM and NAFLD (adjusted odds ratio [OR] 4.29, 95% confidence intervals [CI] 1.90–10.6) and individuals with NAFLD alone (adjusted OR 3.41, 95% CI 1.59–7.29), but not those with T2DM alone, had a substantially increased risk of having cardiac sympathetic/parasympathetic imbalance, compared with those without NAFLD and T2DM. Logistic regression models were adjusted for age, sex, body mass index (BMI), hypertension, dyslipidemia, insulin resistance, hemoglobin A1c (HbA1c), C-reactive protein (CRP), and Fibroscan®-measured liver stiffness.ConclusionsNAFLD was associated with cardiac sympathetic/parasympathetic imbalance, regardless of the presence or absence of T2DM, liver stiffness, and other potential confounding factors.     

FFR- Versus Angiography-Guided Revascularization for Nonculprit Stenosis in STEMI and Multivessel Disease: A Network Meta-Analysis

ObjectivesThe aim of this study was to examine the efficacy and safety of fractional flow reserve (FFR)–guided versus angiography-guided approaches for nonculprit stenosis among patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel disease.BackgroundThe optimal strategy to guide revascularization of nonculprit stenosis among patients with STEMI and multivessel disease remains uncertain.MethodsElectronic databases were searched for randomized trials evaluating the outcomes of culprit-only revascularization, angiography-guided complete revascularization (CR), or FFR-guided CR. A pairwise meta-analysis comparing CR versus culprit-only revascularization and a network meta-analysis comparing the different revascularization techniques were conducted. The primary outcome was major adverse cardiac events (MACE).ResultsThe analysis included 11 trials with 8,195 patients. CR (ie, angiography-guided or FFR-guided CR) was associated with a lower incidence of MACE (odds ratio [OR]: 0.46; 95% CI: 0.35 to 0.59), cardiovascular mortality (OR: 0.63; 95% CI: 0.41 to 0.98), recurrent myocardial infarction (OR: 0.67; 95% CI: 0.48 to 0.95), and repeat ischemia-driven revascularization (OR: 0.26; 95% CI: 0.19 to 0.35). Network meta-analysis demonstrated that the incidence of MACE was lower with both angiography-guided CR (OR: 0.43; 95% CI: 0.31 to 0.58) and FFR-guided CR (OR: 0.52; 95% CI: 0.35 to 0.78) compared with a culprit-only approach, while there was no difference in risk for MACE between angiography-guided and FFR-guided CR (OR: 0.81; 95% CI: 0.51 to 1.29).ConclusionsAmong patients with STEMI and multivessel disease, CR, with angiographic or FFR guidance for nonculprit stenosis, was associated with lower incidence of adverse events compared with culprit-only revascularization. FFR-guided CR was not superior to angiography-guided CR in reducing the incidence of adverse events. Future studies investigating other tools to risk-stratify nonculprit stenoses are encouraged.     

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Background & AimsPatients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.MethodsWe performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months).ResultsBased on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02).ConclusionsIn patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.     

A systematic review and meta-analysis of the COVID-19 associated liver injury

Introduction and ObjectivesThe novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19.MethodsWe performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24^th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model.ResultsAmong 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I² = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I² = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I² = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I² = 71%) were higher subjects in critical COVID-19.ConclusionCOVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.     

Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis

Introduction and ObjectivesType 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM.Materials and MethodsThe current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events.Results6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001).ConclusionsThe identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD.     

Intake of legumes and cardiovascular disease: A systematic review and dose–response meta-analysis

AimsTo summarize the evidence on the association between the intake of legumes and the risk of cardiovascular disease (CVD) overall, coronary heart disease (CHD) and stroke, and to identify optimal intake levels for reduced disease risk through a systematic review and dose–response meta-analysis.Data synthesisWe have systematically searched PubMed, Scopus and Web of Science up to March, 2022 for the retrieval of intervention and observational studies (PROSPERO Reg. number: CRD42021247565). Pooled relative risks (RRs) comparing extreme categories of intake were computed using random-effects models. One-stage dose–response meta-analyses were also performed using random-effects models. 22 831 articles were screened resulting in 26 eligible observational studies (21 prospective cohort and 5 case–control studies). When comparing extreme categories of intake, the consumption of legumes was inversely associated with CVD (n = 25: RR = 0.94; 95%CI:0.89,0.99) and CHD (n = 16: RR = 0.90; 95%CI:0.85,0.96), but not with stroke (n = 9: RR = 1.00; 95%CI:0.93,1.08). We further found evidence for an inverse dose–response association with CHD, increasing in magnitude up to an intake of 400 g/week, after which the benefit seems to level-off.ConclusionsThe intake of legumes was associated with a reduced risk of CVD and CHD, but not with stroke, among individuals with the highest consumption levels. An intake level of 400 g/week seemed to provide the optimal cardiovascular benefit. Further research is needed to better understand the role of legumes in stroke subtypes.     

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

AimsTo evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.Data synthesisPubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.ConclusionsDrinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.Registry and registry numberThe protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).     

Contribution of metabolic risk factors and lifestyle behaviors to cardiovascular disease: A mendelian randomization study

Background and aimsEtiologic associations between some modifiable factors (metabolic risk factors and lifestyle behaviors) and cardiovascular disease (CVD) remain unclear. To identify targets for CVD prevention, we evaluated the causal associations of these factors with coronary artery disease (CAD) and ischemic stroke using a two-sample Mendelian randomization (MR) method.Methods and resultsPreviously published genome-wide association studies (GWASs) for blood pressure (BP), glucose, lipids, overweight, smoking, alcohol intake, sedentariness, and education were used to identify instruments for 15 modifiable factors. We extracted effects of the genetic variants used as instruments for the exposures on coronary artery disease (CAD) and ischemic stroke from large GWASs (N = 60 801 cases/123 504 controls for CAD and N = 40 585 cases/406 111 controls for ischemic stroke). Genetically predicted hypertension (CAD: OR, 5.19 [95% CI, 4.21–6.41]; ischemic stroke: OR, 4.92 [4.12–5.86]), systolic BP (CAD: OR, 1.03 [1.03–1.04]; ischemic stroke: OR, 1.03 [1.03–1.03]), diastolic BP (CAD: OR, 1.05 [1.05–1.06]; ischemic stroke: OR, 1.05 [1.04–1.05]), type 2 diabetes (CAD: OR, 1.11 [1.08–1.15]; ischemic stroke: OR, 1.07 [1.04-1.10]), smoking initiation (CAD: OR, 1.26 [1.18–1.35]; ischemic stroke: OR, 1.24 [1.16–1.33]), educational attainment (CAD: OR, 0.62 [0.58–0.66]; ischemic stroke: OR, 0.68 [0.63–0.72]), low-density lipoprotein cholesterol (CAD: OR, 1.55 [1.41–1.71]), high-density lipoprotein cholesterol (CAD: OR, 0.82 [0.74–0.91]), triglycerides (CAD: OR, 1.29 [1.14–1.45]), body mass index (CAD: OR, 1.25 [1.19–1.32]), and alcohol dependence (OR, 1.04 [1.03–1.06]) were causally related to CVD.ConclusionThis systematic MR study identified 11 modifiable factors as causal risk factors for CVD, indicating that these factors are important targets for preventing CVD.     

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

Lower levels of plasma NT-proBNP are associated with higher prevalence of NASH in patients with biopsy-proven NAFLD

Background and aimsEmerging evidence suggests that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are decreased in patients with imaging-defined nonalcoholic fatty liver disease (NAFLD), but no data are currently available on the association between plasma NT-proBNP levels and the histological severity of NAFLD.Methods and resultsWe enrolled 351 (73.5% men) consecutive adult patients with biopsy-proven NAFLD without a prior history of cardiovascular disease (CVD). Plasma NT-proBNP levels were measured using a commercially available immunochemical system (VITROS® 5600, Johnson, New Jersey). Fifty-three percent of these subjects had nonalcoholic steatohepatitis (NASH). After stratification of patients by plasma NT-proBNP tertiles; compared to those in the 1st tertile (NT-proBNP ≤16 pg/ml), the odds ratio for NASH was 0.52 (95% CI 0.29–0.95) in patients in the 2nd tertile (NT-proBNP of 17–33 pg/ml) and 0.49 (95% CI 0.26–0.93) in those in the 3rd tertile (NT-proBNP ≥34 pg/ml) of plasma NT-proBNP levels, even after adjustment for age, sex, body mass index, homeostasis model assessment (HOMA)-estimated insulin resistance, pre-existing diabetes, hypertension, and dyslipidemia.ConclusionIn subjects with biopsy-proven NAFLD without known CVD, this cross-sectional study shows for the first time, that lower plasma NT-proBNP levels are strongly associated with a higher prevalence of NASH.     

Advanced glycation end products via skin autofluorescence as a new biomarker for major adverse cardiovascular events: A meta-analysis of prospective studies

AimsThis meta-analysis aimed to systematically evaluate the prospective association between advanced glycation end products (AGEs) and major adverse cardiovascular events (MACE).Data synthesisProspective studies that reported the association of AGEs (measured by skin autofluorescence) with MACE were searched in PubMed and EMBASE from inception up to July 2021. Multivariable-adjusted hazard ratios (HRs) and their respective 95% confidence intervals (CIs) reflecting the risk of MACE associated with AGEs were determined using random-effects meta-analysis. Fourteen articles with sixteen items involving 79,389 participants were included. A significant association was found between AGEs and MACE (pooled HR: 1.54, 95% CI: 1.31–1.81, I² = 68%). Moreover, AGEs were associated with a significant increase in fatal cardiovascular disease (CVD) (HR: 1.88, 95% CI: 1.30–2.70) and nonfatal CVD (HR: 1.40, 95% CI: 1.12–1.74). The association between AGEs and MACE was also significant in patients with diabetes (HR: 1.88, 95% CI: 1.31–2.69) and kidney disease (HR: 1.50, 95% CI: 1.16–1.94).ConclusionsThis meta-analysis indicates that higher levels of AGEs measured by skin autofluorescence are significantly correlated with a higher pooled risk of MACE, and AGEs are closely related to both nonfatal and fatal cardiovascular events. AGEs are a valuable biomarker for predicting the occurrence of MACE.The PROSPERO registration numberCRD42021279714.     

Low levels of osteocalcin,but not CTX or P1NP,are associated with nonalcoholic hepatic steatosis and steatohepatitis

AimThe association of bone turnover with the incidence and progression of nonalcoholic fatty liver disease (NAFLD) is unclear. We aimed to evaluate serum levels of bone turnover markers in relation to NAFLD and nonalcoholic hepatic steatohepatitis (NASH).MethodsTwo cohorts were involved in our study. For the first cohort, 370 participants without NAFLD were retrospectively recruited and followed up for incident NAFLD according to ultrasound. For the second cohort, 562 subjects who underwent liver biopsy were included and grouped into non-NAFLD, non-NASH or NASH according to the NASH Clinical Research Network system. The bone turnover markers osteocalcin, C-terminal telopeptide (CTX) and N-terminal propeptide of type-1 procollagen (P1NP) were measured.ResultsBaseline osteocalcin was significantly lower in subjects who developed NAFLD (13.93 [11.03;16.39] versus 18.24 [15.45;22.47] ng/ml, P < 0.001), with a median of 26.4 months of follow-up. Low levels of osteocalcin, but not CTX or P1NP, was an independent predictor of incident NAFLD (OR 0.755 [95%CI 0.668; 0.855] P < 0.001). Moreover, the osteocalcin level was negatively associated with the degree of liver steatosis. Furthermore, subjects with NASH had significantly lower osteocalcin than non-NASH and non-NAFLD group (13.28 [10.49;16.59] versus 14.91 [12.45;18.09] versus 18.21 [15.04;22.05] ng/ml, all P < 0.001). A low osteocalcin level was an independent risk factor for NASH (OR for highest versus lowest quartile: 0.282 [0.147;0.543] P < 0.001).ConclusionLow level of osteocalcin, but not CTX or P1NP, was associated with NAFLD and NASH, indicating its potential role as an important endocrine regulator of hepatic energy metabolism.     

Impacto de las características estructurales y organizativas hospitalarias y de urgencias en el resultado evolutivo de la insuficiencia cardiaca aguda

Introduction and objectivesTo determine whether structural/organizational characteristics of hospitals and emergency departments (EDs) affect acute heart failure (AHF) outcomes.MethodsWe performed a secondary analysis of the EAHFE Registry. Six hospital/ED characteristics were collected and were related to 7 postindex events and postdischarge outcomes, adjusted by the period of patient inclusion, baseline patient characteristics, AHF episode features, and hospital and ED characteristics. The relationship between discharge directly from the ED (DDED) and outcomes was assessed, and interaction was analyzed according to the hospital/ED characteristics.ResultsWe analyzed 17 974 AHF episodes included by 40 Spanish EDs. Prolonged stays were less frequent in high-technology hospitals and those with hospitalization at home and with high-inflow EDs, and were more frequent in hospitals with a heart failure unit (HFU) and an ED observation unit. In-hospital mortality was lower in high-technology hospitals (OR, 0.78; 95%CI, 0.65-0.94). Analysis of 30-day postdischarge outcomes showed that hospitals with a short-stay unit (SSU) had higher hospitalization rates (OR, 1.19; 95%CI, 1.02-1.38), high-inflow EDs had lower mortality (OR, 0.73; 95%CI, 0.56-0.96) and fewer combined events (OR, 0.87; 95%CI, 0.76-0.99), while hospitals with HFU had fewer ED reconsultations (OR, 0.83; 95%CI, 0.76-0.91), hospitalizations (OR, 0.85; 95%CI, 0.75-0.97), and combined events (OR, 0.84; 95%CI, 0.77-0.92). The higher the percentage of DDED, the fewer the prolonged stays. Among other interactions, we found that more frequent DDED was associated with more 30-day postdischarge reconsultations, hospitalizations and combined events in hospitals without SSUs, but not in hospitals with an SSU.ConclusionsAHF outcomes were significantly affected by the structural/organizational characteristics of hospitals and EDs and their aggressiveness in ED management.Full English text available from:www.revespcardiol.org/en