Insulin resistance and central obesity determine hepatic steatosis and explain cardiovascular risk in steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk. Methods: A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: ≥2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD. Results: Mean age was 59.4 ± 8.5 years, 51.6% were male; mean BMI was 27.0 ± 4.5 kg/m², 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference ≥102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components. Conclusion: Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients.

[The Role of the Electrocardiogram (ECG) In the Screening and Prevention of Sudden Cardiac Death in Sports]. / Die Rolle des Elektrokardiogramms (EKG) in der Prävention des plötzlichen Herztods im Sport.

The Role of the Electrocardiogram (ECG) In the Screening and Prevention of Sudden Cardiac Death in Sports Abstract: Athletes carry a higher risk for sports-related sudden cardiac death compared to the general population. The majority of these athletes suffer from an undiagnosed heart disease. Since physical activity is an essential trigger for sudden cardiac death in individuals with undiagnosed, usually hereditary, heart disease, sports can lead to sudden cardiac death in these athletes. Different heart diseases lead to sudden cardiac death at different ages during sports. The electrocardiogram (ECG) is an important screening tool to identify individuals of all ages with heart disease that are associated with sports-related sudden cardiac death. These individuals can then be treated and lives can be saved.

[The athlete's ECG : What is normal or abnormal?] / Das EKG beim Leistungssportler und Athleten : Was ist normal und was nicht?

BACKGROUND: The electrocardiogram (ECG) has become a mobile and cost-effective routine assessment tool to risk stratify leisure-time and professional athletes during preparticipation screening. A central goal is the reduction of sudden cardiac death in sports through early recognition of the most prevalent underlying cardiac pathologies, e.g., hereditary cardiomyopathies or primary arrhythmias. METHODS: Continuous evolution of the first ECG criteria for athletes, presented in 2010 by the European Society of Cardiology (ESC), has helped to improve the specificity of the criteria to both detect cardiac pathologies in early stages and differentiate from physiologic adaptation of the athlete's heart. Thus, the risk of false-positive findings and erroneous stigmatizations of athletes has been successfully reduced. CONCLUSION: This review article intends to trace back the changes of the ECG criteria in the light of a growing body of scientific evidence over the last 15 years, to present the key messages of the current International ECG criteria from 2017 and to identify some of the remaining challenges that wait to be answered by physicians in the field of sports medicine and sports cardiology.

A comparative study on the analysis of hemodynamics in the athlete's heart.

The pathophysiological mechanisms underlying the development of the athlete's heart are still poorly understood. To characterize the intracavitary blood flows in the right ventricle (RV) and right-ventricular outflow tract (RVOT) in 2 healthy probands, patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and 2 endurance athletes, we performed 4D-MRI flow measurements to assess differences in kinetic energy and shear stresses. Time evolution of velocity magnitude, mean kinetic energy (MKE), turbulent kinetic energy (TKE) and viscous shear stress (VSS) were measured both along the whole RV and in the RVOT. RVOT regions had higher kinetic energy values and higher shear stresses levels compared to the global averaging over RV among all subjects. Endurance athletes had relatively lower kinetic energy and shear stresses in the RVOT regions compared to both healthy probands and ARVC patients. The athlete's heart is characterized by lower kinetic energy and shear stresses in the RVOT, which might be explained by a higher diastolic compliance of the RV.

Helicobacter pylori and cardiovascular risk: Only a dead Helicobacter is a good Helicobacter?

OBJECTIVES: Helicobacter pylori (H. pylori) and cardiovascular (CV) disease share common symptoms and underlie many general medical complaints. Preliminary studies suggest an association between H. pylori positivity and CV risk, and gastroenterological guidelines recommend eradication of H. pylori in patients with manifest atherosclerosis. Therefore, the aim of this study was to examine the reciprocal association of H. pylori positivity and CV risk for their independence of shared risk factors. METHODS: We included 3284 asymptomatic participants of a colorectal cancer screening cohort who were offered and underwent upper gastrointestinal endoscopy. We calculated the 10-year risk for a CV event using the novel SCORE2 for each patient. We evaluated the association between H. pylori positivity and CV risk assessed by SCORE2 using both multilevel logistic and linear regression. We adjusted for age, sex and the concomitant diagnosis of metabolic syndrome. Lastly, we assessed the association between H. pylori status and mortality using proportional hazard Cox regression. RESULTS: In total, 2659 patients were H. pylori negative and 625 H. pylori positive. Helicobacter pylori positivity was associated with SCORE2 and remained so (r = .33; 95% CI 0.09-0.57; p = .006) after adjustment for age, sex, and the diagnosis of metabolic syndrome. Also, SCORE2 was associated with higher odds for H. pylori positivity (aOR 1.03 95% CI 1.01-1.05; p = .02) even after multivariable adjustment. Helicobacter pylori positivity was associated with neither CV (HR 0.60 95% CI 0.14-2.63; p = .50) nor all-cause (HR 1.20 95% CI 0.77-1.87; p = .43) mortality during a median follow-up of 9 years. CONCLUSIONS: In our study, H. pylori positivity and CV risk were independently associated. This did not translate into a dissimilar CV mortality between H. pylori positive and H. pylori negative patients. However, the overwhelming majority of our patients underwent H. pylori eradication. We, therefore, think that H. pylori eradication is at least safe from a cardiovascular perspective and warranted from gastrointestinal standpoint.

Cardiovascular Risk Assessment by SCORE2 Predicts Risk for Colorectal Neoplasia and Tumor-Related Mortality.

Objectives: The European Society of Cardiology endorsed SCORE2 to assess cardiovascular risk. The aim of this observational, retrospective study was to assess whether SCORE2 is associated with colorectal neoplasia in an asymptomatic screening population. Further, we evaluated if SCORE2 predicts tumor-related mortality. Methods: We included 3408 asymptomatic patients who underwent a screening colonoscopy. We calculated SCORE2 for each participant and stratified patients according to their predicted 10-year risk of cardiovascular disease: SCORE2 0−4.9%, SCORE2 5−9.9%, and SCORE2 ≥ 10%. We assessed the association between SCORE2 as a continuous variable, the presence of colorectal neoplasia using multilevel logistic regression, and SCORE2 and mortality using Cox regression. Results: In total, 1537 patients had a SCORE2 of 0−4.9%, 1235 a SCORE2 of 5−9.9%, and 636 a SCORE2 ≥ 10%. The respective rates of colorectal neoplasia were 20%, 37%, and 44%. SCORE2 was associated with the presence of any (OR 1.11 95%CI 1.09−1.12; p < 0.001) and advanced colorectal neoplasia (OR 1.06 95%CI 1.08−1.13; p < 0.001) in univariate analysis. After multivariable adjustment (age, sex, family history, and metabolic syndrome) a higher SCORE2 remained associated with higher odds for any (aOR 1.04 95%CI 1.02−1.06; p = 0.001) and advanced (aOR 1.06 95%CI 1.03−1.10; p < 0.001) colorectal neoplasia. SCORE2 was associated with both all-cause (HR 1.11 95%CI 1.09−1.14; p < 0.001) and tumor-related mortality (HR 1.10 95%CI 1.05−1.14; p < 0.001). Conclusions: We found that SCORE2 is associated with the presence of colorectal neoplasia. Clinicians could kill two birds with one stone calculating SCORE2. In patients with a high SCORE2, screening colonoscopy aside from cardiovascular risk mitigation could improve outcomes.

Non-alcoholic fatty liver disease is not independently associated with Helicobacter pylori in a central European screening cohort.

BACKGROUND: The association between Helicobacter pylori (Hp) infection and non-alcoholic fatty liver disease (NAFLD) is subject of a contentious debate. Data mainly stem from Asian cohorts whereas European data are scarce. We, therefore, investigated an Austrian colorectal cancer screening cohort for an association between Hp and NAFLD. METHODS: In total, 5338 consecutive participants undergoing screening colonoscopy at a single center in Austria were evaluated in this cross-sectional study. The primary risk factor was being Hp negative or positive. The primary endpoint was the presence of NAFLD defined by ultrasound (NAFLD; primary endpoint). Uni- and multivariable logistic regression models were fitted to obtain odds ratios (OR) and 95% confidence intervals (95%CI). Finally, this association was analyzed in a subgroup of 1128 patients in whom NAFLD was diagnosed by transient elastography (TE, secondary endpoint). RESULTS: NAFLD prevalence defined by ultrasound did not differ between Hp positive (48%) and negative patients (45%, P=0.097). Accordingly, in uni- (OR 1.12 95% CI 0.98-1.29; P=0.098) and multivariable analysis adjusting for different risk factors (aOR 0.96 95%CI 0.82-1.13; P=0.601) no independent association was found. On subgroup analysis, NAFLD diagnosed by TE was more prevalent in the Hp positive compared to the Hp negative group (49% vs. 38%, P=0.004) and these patients also had higher steatosis grades. However, after adjustment for risk factors, no independent association between Hp positivity and NAFLD diagnosed by TE (aOR 1.26 95%CI 0.89-1.78; P=0.194) was confirmed. CONCLUSIONS: In this Central European cohort, Hp-positivity was not associated with the diagnosis of NAFLD. Although Hp positive patients seem to be more likely to have a concomitant NAFLD diagnosis, this association might rather relate to a cardiometabolic risk phenotype than causality.

Changing Metabolic Patterns along the Colorectal Adenoma-Carcinoma Sequence.

Colorectal cancer (CRC) is a major public health burden and one of the leading causes of cancer-related deaths worldwide. Screening programs facilitate early diagnosis and can help to reduce poor outcomes. Serum metabolomics can extract vital molecular information that may increase the sensitivity and specificity of colonoscopy in combination with histopathological examination. The present study identifies serum metabolite patterns of treatment-naïve patients, diagnosed with either advanced adenoma (AA) or CRC in colonoscopy screenings, in the framework of the SAKKOPI (Salzburg Colon Cancer Prevention Initiative) program. We used a targeted flow injection analysis and liquid chromatography-tandem mass spectrometry metabolomics approach (FIA- and LC-MS/MS) to characterise the serum metabolomes of an initial screening cohort and two validation cohorts (in total 66 CRC, 76 AA and 93 controls). The lipidome was significantly perturbed, with a proportion of lipid species being downregulated in CRC patients, as compared to AA and controls. The predominant alterations observed were in the levels of lyso-lipids, glycerophosphocholines and acylcarnitines, but additionally, variations in the quantity of hydroxylated sphingolipids could be detected. Changed amino acid metabolism was restricted mainly to metabolites of the arginine/dimethylarginine/NO synthase pathway. The identified metabolic divergences observed in CRC set the foundation for mechanistic studies to characterise biochemical pathways that become deregulated during progression through the adenoma to carcinoma sequence and highlight the key importance of lipid metabolites. Biomarkers related to these pathways could improve the sensitivity and specificity of diagnosis, as well as the monitoring of therapies.

A Novel Diagnostic Score Integrating Atrial Dimensions to Differentiate between the Athlete's Heart and Arrhythmogenic Right Ventricular Cardiomyopathy.

OBJECTIVE: The 2010 Task Force Criteria (TFC) have not been tested to differentiate ARVC from the athlete's heart. Moreover, some criteria are not available (myocardial biopsy, genetic testing, morphology of ventricular tachycardia) or subject to interobserver variability (right ventricular regional wall motion abnormalities) in clinical practice. We hypothesized that atrial dimensions are useful and robust to differentiate between both entities and proposed a new diagnostic score based upon readily available parameters including echocardiographic atrial dimensions. METHODS: In this observational study, 21 patients with definite ARVC were matched for age, gender and body mass index to 42 athletes. Based on ROC analysis, the following parameters were included in the score: indexed right/left atrial volumes ratio (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX BSA-corrected), tricuspid annular motion (TAM), precordial TWI and depolarization abnormalities according to TFC. RESULTS: ARVC patients had a higher RAVI/LAVI ratio (1.76 ± 1.5 vs. 0.87 ± 0.2, p < 0.001), lower right ventricular function (fac: 29 ± 10.1 vs. 42.2 ± 5%, p < 0.001; TAM: 19.8 ± 5.4 vs. 23.8 ± 3.8 mm, p = 0.001) and higher serum NT-proBNP levels (345 ± 612 vs. 48 ± 57 ng/L, p < 0.001). Our score showed a good performance, which is comparable to the 2010 TFC using those parameters, which are available in routine clinical practice (AUC93%, p < 0.001 (95%CI 0.874-0.995) vs. AUC97%, p < 0.001 (95%CI 0.93-1.00). A score of 6/12 points yielded a specificity of 91% and an improved sensitivity of 67% for ARVC diagnosis as compared to a sensitivity of 41% for the abovementioned readily available 2010 TFC. CONCLUSIONS: ARVC patients present with significantly larger RA compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete's heart.

A sex-specific propensity-adjusted analysis of colonic adenoma detection rates in a screening cohort.

The prevalence of colorectal adenoma and advanced adenoma (AA) differs between sexes. Also, the optimal age for the first screening colonoscopy is under debate. We, therefore, performed a sex-specific and age-adjusted comparison of adenoma, AA and advanced neoplasia (AN) rates in a real-world screening cohort. In total, 2824 asymptomatic participants between 45- and 60-years undergoing screening colonoscopy at a single-centre in Austria were evaluated. 46% were females and mean age was 53 ± 4 years. A propensity score for being female was calculated, and adenoma, AA and AN detection rates evaluated using uni- and multivariable logistic regression. Sensitivity analyses for three age groups (group 1: 45 to 49 years, n = 521, 41% females, mean age 47 ± 1 years; group 2: 50 to 54 years, n = 1164, 47% females, mean age 52 ± 1 years; group 3: 55 to 60 years, n = 1139, 46% females, mean age 57 ± 2 years) were performed. The prevalence of any adenoma was lower in females (17% vs. 30%; OR 0.46, 95% CI 0.38-0.55; p < 0.001) and remained so after propensity score adjustment for baseline characteristics and lifestyle factors (aOR 0.52, 95% CI 0.41-0.66; p < 0.001). The same trend was seen for AA with a significantly lower prevalence in females (3% vs. 7%; OR 0.38, 95% CI 0.26-0.55; p < 0.001) that persisted after propensity score adjustment (aOR 0.54, 95% CI 0.34-0.86; p = 0.01). Also, all age-group sensitivity analyses showed lower adenoma, AA and AN rates in females. Similar numbers needed to screen to detect an adenoma, an AA or AN were found in female age group 3 and male age group 1. Colorectal adenoma, AA and AN were consistently lower in females even after propensity score adjustment and in all age-adjusted sensitivity analyses. Our study may add to the discussion of the optimal age for initial screening colonoscopy which may differ between the sexes.

Liver-related Mortality is Increased in Lean Subjects with Non- alcoholic Fatty Liver Disease Compared to Overweight and Obese Subjects.

BACKGROUND AND AIMS: Although non-alcoholic fatty liver disease (NAFLD) is linked to obesity, a proportion of lean subjects also have NAFLD with potentially distinct clinical features. We studied the outcome of lean NAFLD subjects. METHODS: 299 consecutive patients (215 male, 84 female, 49.5 ± 13.5years) with biopsy-proven NAFLD and a follow-up of 8.4 years (±4.1; range: 0.9-18.0) were stratified by body mass index (BMI) at the time of liver biopsy: lean (BMI ≤25.0 kg/m, n=38), overweight (BMI 25.0-29.9 kg/m2, n=165), obese (BMI ≥30.0 kg/m2, n=93). A control group of 1,013 subjects (547 male, 52.4 ± 5.8) was used for comparison. The time to the event was recorded. Multivariable Cox regression analyses were performed to assess associations with 10-year-mortality. Hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated. RESULTS: Age and gender were similar, while components of the metabolic syndrome were less frequent in lean subjects. The proportion of subjects with significant fibrosis and the number of subjects with cirrhosis was increased in lean subjects while the proportion of non-alcoholic steatohepatitis was not different. Mortality in the NAFLD groups was significantly higher than in the control group. Multivariable analysis adjusting for age, gender, and glucose confirmed lower mortality in overweight (aHR 0.21; 95% CI 0.07-0.62, p=0.005) and in obese (aHR 0.22; 95% CI 0.06-0.76, p=0.02) compared to lean subjects. Further adjustment for fibrosis weakened the difference between lean and obese (p=0.12) while the difference to overweight subjects remained intact (p=0.01). CONCLUSION: Lean subjects with NAFLD have a high risk of liver-related death. Our data support that lean NAFLD subjects deserve particular attention with regard to clinical follow-up.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-Rather a Bystander Than a Driver of Mortality.

CONTEXT: Recently, the novel metabolic dysfunction-associated fatty liver disease (MAFLD) definition has been introduced. OBJECTIVE: To assess the relevance of MAFLD for mortality. METHODS: Single-center cohort-study using colorectal cancer screening program involving 4718 subjects aged 45 to 80 who were grouped according to their body mass index (BMI) and the presence or absence of MAFLD. Mortality was compared among these groups by performing a systematic read-out of the national health insurance system, fatty liver (FL) was diagnosed using ultrasound. RESULTS: Overall prevalence of FL was 47.9%: 1200 (25.4%) patients were lean (BMI < 25 kg/m2) and did not have MAFLD, 73 (1.5%) patients were lean and had nonalcoholic fatty liver disease but did not fulfill criteria for MAFLD, and 221 (4.7%) patients were lean and fulfilled criteria for MAFLD. Additionally, 1043 (22.1%) and 925 (19.6%) subjects had MAFLD with overweight (BMI 25-30 kg/m2) and obesity (BMI ≥ 30 kg/m2), respectively, while 1041 (22.1%) and 215 (4.6%) had overweight and obesity, respectively, without FL. During a median follow-up of 7.5 (interquartile range: 4.0-9.6) years, 278 deaths (5.9%) occurred. Of these, 98 (2.1%) were cancer-related, 65 (1.4%) were cardiovascular, and 17 (0.4%) were liver-related. Overall survival was similar between patient strata (after 5 years: 93.9%-98.2%) with lean MAFLD having the numerically worst survival. Although lean and overweight patients with MAFLD had a numerically worse outcome compared to their non-MAFLD counterparts, this association was driven by age and metabolic comorbidities (predominantly diabetes) rather than the presence of MAFLD. CONCLUSION: Presence of MAFLD does not increase mortality in a cohort of individuals aged 45 to 80 years.

Nonalcoholic Fatty Liver Disease in Lean Subjects: Associations With Metabolic Dysregulation and Cardiovascular Risk-A Single-Center Cross-Sectional Study.

INTRODUCTION: Although a milder metabolic phenotype of nonalcoholic fatty liver disease (NAFLD) in lean patients (body mass index [BMI] <25 kg/m2) compared to overweight/obese patients with NAFLD is assumed, the relevance of NAFLD among lean subjects remains a matter of debate. We aimed to characterize the metabolic/cardiovascular phenotype of lean patients with NAFLD. METHODS: In total, 3,043 subjects (cohort I) and 1,048 subjects (cohort II) undergoing screening colonoscopy between 2010 and 2020 without chronic liver disease other than NAFLD were assigned to one of the following groups: lean patients without NAFLD, lean NAFLD, overweight NAFLD (BMI 25-30 kg/m2), and obese NAFLD (BMI >30 kg/m2). Diagnosis of NAFLD was established using ultrasound (cohort I) and controlled attenuation parameter (cohort II). RESULTS: The prevalence of lean patients with NAFLD was 6.7%/16.1% in the overall cohort I/II and 19.7%/40.0% in lean subjects of cohort I/II. Compared with lean subjects without NAFLD, lean patients with NAFLD had a higher prevalence of dyslipidemia, dysglycemia, and the metabolic syndrome, together with a higher median Framingham risk score in both cohorts (all P < 0.001). On multivariable analyses, NAFLD in lean subjects was associated with higher odds of metabolic syndrome (adjusted odds ratio cohort I: 4.27 [95% confidence interval (CI): 2.80-6.51], P < 0.001; cohort II: 2.97 [95% CI: 1.40-6.33], P < 0.001), and higher Framingham risk score (regression coefficient B cohort I: 1.93 [95% CI: 0.95-2.92], P < 0.003; cohort II: 1.09 [95% CI: 0.81-2.10], P = 0.034), among others. Only 69.8% of lean patients with NALFD in cohort I and 52.1% in cohort II fulfilled the novel criteria for metabolic associated fatty liver disease. DISCUSSION: NAFLD in lean patients is associated with the metabolic syndrome and increased cardiovascular risk. Novel metabolic associated fatty liver disease criteria leave a considerable proportion of patients unclassified.

NAFLD and Cardiovascular Diseases: Epidemiological, Mechanistic and Therapeutic Considerations.

Overwhelming evidence suggests an association of cardiovascular disease (CVD) with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanisms remain largely speculative. It is, however, likely that common mechanisms contribute to the development of CVD and NAFLD, with lifestyle factors such as smoking, sedentary lifestyle with poor nutrition habits and physical inactivity being major candidates. These behavioral factors, on a predisposing genetic background, trigger changes in gut microbiota, inflammation, dyslipidemia and oxidative stress, leading to metabolic syndrome, diabetes and obesity as well as atherosclerosis. Treatment options to counteract both the progression and development of CVD and NAFLD include lifestyle interventions, optimal medical therapy of comorbid conditions and, as final possibility, bariatric surgery. As no causal pharmacotherapy of NAFLD is available, further research is urgently needed to address the unmet need of a growing population with NAFLD and CVD.

Impact of malignancy on clinical outcomes in patients with acute coronary syndromes.

BACKGROUND: The impact of cancer on survival in patients with coronary artery disease has not been well defined. We designed the present study to explore the prevalence and prognostic influence of cancer in patients with acute coronary syndrome (ACS). METHODS: 2'132 patients with ACS were enrolled in the prospective, multicenter Special Program University Medicine ACS (SPUM-ACS) cohort. The primary endpoints of major cardiovascular and cerebrovascular events (MACCE) and death were independently adjudicated at 30-day and at one-year follow-up. RESULTS: Of the 2'132 ACS patients 7.74% (n = 165) had cancer. At 30-day, except for net adverse clinical events (NACE defined as MACCE plus major bleeding), outcomes did not differ significantly between the two groups. At one year, MACCE rate was higher in cancer than in non-cancer patients (21.8 vs. 12.2%, p < 0.001). Even after adjusting for covariates, one-year all-cause mortality was higher in cancer patients than in those without (30.3% vs. 11.9%; p < 0.0001) as was cardiovascular mortality (15.7% vs. 5.9%; p < 0.001) and revascularization (12.7% vs. 5.5%, p < 0.001). Net adverse clinical events were also higher in patients with cancer at one-year follow-up (33.9% vs. 19.8%, p < 0.001). A sub-analysis revealed that those with solid tumors, but not hematological malignancies were more likely to experience MACCE (p = 0.001) as well as a higher cardiovascular and all cause mortality (both p = 0.001) at one-year follow-up. CONCLUSIONS: ACS patients with cancer, specifically those with solid tumors, have a higher MACCE as well as cardiovascular and total mortality rate than non-cancer patients independent of cardiovascular risk factors. Thus, cancer is an independent risk factor for a poor outcome in ACS patients.

Nut consumption and the prevalence and severity of non-alcoholic fatty liver disease.

BACKGROUND: Nut consumption has been associated with reduced inflammation, insulin resistance, and oxidative stress. However, the influence on the prevalence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be evaluated. METHODS: 4655 subjects were included as part of a colorectal carcinoma screening program (SAKKOPI) between 07/2010 and 07/2019 and analyzed 2020. Patients were characterized using biochemical and metabolic parameters, as well as a detailed questionnaire on dietary habits. The diagnosis of NAFLD was established using abdominal ultrasound. Consumption of nuts was graded as: no consumption or <1 time/week, 1-6 times/week, 1 time/day and ≥2 times/day. RESULTS: Mean age was 58.5±9.8years with a mean BMI of 26.5±4.7kg/m2. 2058 (44.2%) patients suffered from the metabolic syndrome, 2407 (51.6%) had arterial hypertension, 2287 (49.1%) showed prediabetes/diabetes, 1854 (39.4%) had dyslipidemia and 1984 patients (43.5%) were diagnosed with NAFLD. Prevalence of metabolic syndrome (1219 [48.7%] vs. 605 [40.2%] vs. 189 [37.4%] vs. 45 [31.7%], p<0.001) and NALFD (1184 [48.1%] vs. 594 [40.7%] vs. 158 [31.7%] vs. 48 [34.0%], p<0.001). On multivariable logistic regression analysis adjusting for potential confounders and dietary patterns, nut consumption ≥1time/day was inversely associated with NAFLD in the overall cohort (adjusted Odds ratio[aOR]: 0.719 [95%CI:0.558-0.926], p = 0.011). However, following subgroup analysis, this inverse association was only confirmed in male patients (aOR: 0.589 [95%CI: 0.411-0.844], p = 0.004) but not in females (aOR: 0.886 [95%CI: 0.616-1.275], p = 0.515). Moreover, patients who consumed nuts 1-6 times/week had a significantly lower prevalence of advanced fibrosis (Fib-4 score >2.67: aOR: 0.551 [95%CI: 0.338-0.898], p = 0.017; Forns-Index >6.9: aOR: 0.585 [95%CI: 0.402-0.850], p = 0.005). CONCLUSIONS: Nut consumption might exert beneficial effects on the prevalence of NAFLD in males. The negative association with advanced fibrosis warrants further investigation.

Prognostic role of plasma galectin-3 levels in acute coronary syndrome.

AIM: Cystatin C, neutrophil gelatinase-associated lipocalin and galectin-3 have emerged as biomarker candidates to predict cardiovascular outcomes and mortality in the general population as well as in patients with coronary artery or renal disease. However, their predictive role and clinical utility in patients with acute coronary syndromes alone or in combination beyond currently used risk scores remains to be determined. METHODS AND RESULTS: Cystatin C, neutrophil gelatinase-associated lipocalin, and galectin-3 were measured in plasmas of 1832 patients at the time of presentation with acute coronary syndromes requiring percutaneous coronary intervention or coronary artery bypass grafting. The primary outcomes were major adverse cardiac and cerebrovascular events (defined as the composite of all-cause mortality, cerebrovascular events, any repeat revascularization or myocardial infarction) and all-cause mortality after 1 year and occurred in 192 (10.5%) and 78 (4.3%) of patients, respectively. All three biomarkers were increased in those with major adverse cardiac and cerebrovascular events compared with those without (p<0.001). However, only galectin-3 (all-cause mortality: hazard ratio=1.027 (95% confidence interval (1.011-1.043); p=0.001), major adverse cardiac and cerebrovascular events: hazard ratio=1.025 (95% confidence interval (1.012-1.037); p<0.001)) but not cystatin C nor neutrophil gelatinase-associated lipocalin emerged as independent predictors of both major adverse cardiac and cerebrovascular events and death. The risks were particularly high in the highest quartile of galectin-3. The integration of galectin-3 into the global registry of acute coronary events (GRACE) score improved the prediction of major adverse cardiac and cerebrovascular events and all-cause mortality significantly. The areas under the receiver operator characteristics curves increased from 0.6701 to 0.6932 for major adverse cardiac and cerebrovascular events (p=0.0474) and from 0.804 to 0.8199 for all-cause mortality (p=0.0197). Finally, we applied net reclassification improvement index using different cut-offs for major adverse cardiac and cerebrovascular events which showed negative results (for the cut-offs of 5% and 15%, net reclassification improvement index 0.028, p=0.586, for the cut-offs of 10% and 20%, net reclassification improvement index 0.072, p=0.1132 and for the cut-offs of 10% and 30% the net reclassification improvement index is 0.0843, p=0.077). CONCLUSION: In acute coronary syndromes patients, galectin-3 has moderate prognostic accuracy, provides statistically significant incremental value in some, but not all models, and that the magnitude of any improvement would seem of questionable clinical value.

Mesenchymal iron deposition is associated with adverse long-term outcome in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Approximately one-third of patients with non-alcoholic fatty liver disease (NAFLD) show signs of mild-to-moderate iron overload. The impact of histological iron deposition on the clinical course of patients with NAFLD has not been established. METHODS & RESULTS: For this retrospective study, 299 consecutive patients with biopsy-proven NAFLD and a mean follow-up of 8.4 (±4.1; range: 0.3-18.0) years were allocated to one of four groups according to presence of hepatic iron in the reticuloendothelial system (RES) and/or hepatocytes (HC): 156 subjects (52%) showed no stainable iron (NONE), 58 (19%) exclusively reticuloendothelial (xRES), 19 (6%) exclusively hepatocellular (xHC) and 66 (22%) showed a mixed (HC/RES) pattern of iron deposition. A long-term analysis for overall survival, hepatic, cardiovascular or extrahepatic-malignant events was conducted. Based on multivariate Cox proportional hazards models any reticuloendothelial iron was associated with fatal and non-fatal hepatic events. Specifically, xRES showed a cause-specific hazard ratio (csHR) of 2.4 (95%-CI, 1.0-5.8; P = .048) for hepatic as well as cardiovascular fatal and non-fatal events combined (csHR 3.2; 95%-CI, 1.2-8.2; P = .015). Furthermore, the mixed HC/RES iron pattern showed a higher rate of combined hepatic fatal and non-fatal events (csHR 3.6; 95%-CI, 1.4-9.5; P = .010), while xHC iron deposition was not associated with any defined events. CONCLUSIONS: The presence of reticuloendothelial-accentuated hepatic iron distribution patterns is associated with detrimental long-term outcomes reflected in a higher rate of both liver-related and cardiovascular fatal and non-fatal events.

Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) Is Independently Associated with Cardiovascular Risk in a Large Austrian Screening Cohort.

BACKGROUND: Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. OBJECTIVES: To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. MATERIAL AND METHODS: In total, 1965 asymptomatic subjects (59 ± 10 years, 52% females, BMI 27.2 ± 4.9 kg/m2) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (>10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. RESULTS: Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 ± 9 vs. 58 ± 10 years; p < 0.001), had higher BMI (29.6 ± 4.9 vs. 24.9 ± 3.6 kg/m2; p < 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%; p < 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 ± 6.4 vs. 5.4 ± 5.2%; p < 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02-1.07; p < 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29; p < 0.001), and FRS was highest in patients with significant fibrosis (F3-4; 11.7 ± 5.4) compared to patients with intermediate results (10.9 ± 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 ± 5.9, p < 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09-1.54; p = 0.003). CONCLUSION: The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap of advanced NAFLD and high CV risk, aggressive treatment of established CV risk factors could improve prognosis in these patients.