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01 september 2023, Contains fulltext : 296518.pdf (Publisher’s version ) (Open Access), BACKGROUND: The estimated global prevalence and burden of non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), is increasing. Yet, NAFLD remains largely underdiagnosed. In addition to hepatic morbidity and mortality, NAFLD is associated with increased cardiovascular complications, warranting a multidisciplinary approach. Despite its rapidly increasing prevalence, knowledge of NAFLD among healthcare workers is limited, especially with specialists outside the field of hepatology and gastroenterology. OBJECTIVES: To investigate knowledge, practice and opinions/attitudes of healthcare workers towards diagnosis and management of NAFLD/NASH. METHODS: The survey was designed in collaboration with a multidisciplinary scientific committee established especially for this study. The survey was disseminated to healthcare workers from seven different disciplines through four collaborating societies, social media and at a cardiology-themed conference from February to June 2022. Median and interquartile range were mentioned for numeric responses and proportions for categorical responses or responses on a Likert scale. Likert scale responses were treated as ordinal data and analysed with the appropriate tests. RESULTS: The full dataset included 613 respondents from 88 different countries (including 488 physicians). 64% of the surveyed physicians underestimated the prevalence of NAFLD. General practitioners and cardiologists underestimated the prevalence most often (74% and 77%, respectively). Compared to the other disciplines, cardiologists were least familiar with the symptoms and diagnostic criteria and felt least confident in diagnosing and managing NAFLD. Overall, 65% of physicians reported regularly using evidence-based guidelines for managing NAFLD, yet 72% reported challenges in providing lifestyle recommendations. A lack of awareness was the most common reported reason for the lack of screening for NAFLD (68% respectively).

Background Several characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19. Methods A prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity - assessed by an increased waist-hip ratio - and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses. Results In total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014). Conclusion This study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference.

Introduction: Tibial nerve entrapment is highly prevalent in diabetic subjects, resulting in significantly more neuropathic complaints and concomitant sensory disturbances. The study aim was to assess the impact of tarsal tunnel syndrome (TTS) and sensory loss at baseline on incident diabetic foot ulceration (DFU) in diabetic patients, since decompressing the tibial nerve might change the natural history of the disease. Methods: In this study, 113 subjects with TTS (69 bilateral, 23 left-sided and 21 right-sided) participating in the prospective Rotterdam Diabetic Foot Study were compared to 303 diabetic controls without TTS, regarding incident DFU. Kaplan–Meier analysis and Cox’s regression analysis were used to determine the independent hazard of baseline variables for new DFU. Results: The median observation period was 836.5 days (IQR, 459–1077.8). In bilateral TTS, 17.4% (95% CI: 8.4–26.3%) of subjects experienced DFU versus 8.3% (95% CI: 5.1–11.6%) in controls (left or right) during follow-up (p = 0.0036). In left-sided TTS, no subjects versus 6.2% (95% CI: 3.4–9.0%) in controls had DFUs (p = 0.243). Incident ulceration was seen in 14.3% (95% CI: −0.7% to −29.3%) of right-sided TTS subjects versus 4.1% (95% CI: 1.5–6.3%) in controls (p = 0.034). Besides HbA1c, diminished sensation at the hallux independently increased the risk of ulceration, in patients with (HR: 4.692, p = 0.003) and without (HR: 2.307, p = 0.002) prior DFU. Discussion: Elevated sensory thresholds in TTS render diabetic patients at a higher risk for DFU. With effective surgery, TTS is likely to be an amenable factor to potentially prevent diabetic foot disease and thereby reduce amputation risk. Level of evidence: II.

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. Material and Methods: Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change −24.7%; P = 0.018) and fasting apoB48 serum levels (−35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (−26.4%; P = 0.006) and apoB48 AUC (−55.7%; P = 0.046), as well as plasma TG incremental AUC (−21.4%; P = 0.04) and apoB48 incremental AUC (−26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions: In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants.

Aims: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. Methods and results: The CARDIOBESE study is a cross-sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2] without known cardiovascular disease and 50 age-matched and gender-matched non-obese controls (BMI ≤ 30 kg/m2). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty-nine obesity patients [48 (42–50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non-obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. Conclusions: There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C-reactive protein, increased BNP, increased high-sensitivity troponin I, or increased left ventricular mass.

Aims: Sensory loss and impaired balance are considered risk factors of incident falls. The aim of this study was to assess the relationship between degree of foot sensation and balance, risk of falls, incidence of fall-related injuries and costs in a cohort of patients with diabetes. Methods: (Non)-neuropathic subjects participating in the Rotterdam Diabetic Foot Study were followed prospectively. Subjects underwent sensory testing of the feet (39 item Rotterdam Diabetic Foot Study Test Battery (RDF-39)); balance was assessed at the second follow-up (Brief-BESTest) as were data on incident falls. Medical records and financial data were abstracted to estimate fall-related morbidity and in-hospital costs. Results: A higher RDF-39 score, cerebral artery disease, type 2 diabetes, height and age were predictors of the Brief-BESTest total score. 41/296 patients (13.9%) reported two or more falls during follow-up. Predictors for recurrent falls were a higher RDF-39 score (aOR: 1.124, p < 0.0005), male gender (aOR: 0.319, p = 0.016), age (aOR: 0.938, p = 0.003) and type 2 diabetes (aOR: 3.157, p = 0.100). Thirty-one patients used medical resources (median US$ 440.45 (IQR: 179–1162). Conclusions: Degree of sensory loss correlates significantly with an increased imbalance and risk of falls. The RDF-39 may be used as stratification tool in medical decision-making and patient information.

Background: Women are relatively protected from cardiovascular disease compared with men. Since morbid obesity is an independent risk factor for cardiovascular disease, the current study investigated whether the association between sex and cardiovascular risk factors and outcomes can be demonstrated in subjects suffering from morbid obesity. Materials and methods: Two hundred subjects enrolled in a study on cardiovascular risk factors in morbid obesity underwent extensive laboratory screening, carotid intima‐media thickness (cIMT) and pulse wave velocity (PWV) measurements. Gender differences were analysed using univariate and multivariable linear regression models. In addition, the effect of menopause on cIMT and PWV was analysed. Results of these models were reported as B coefficients with 95% confidence intervals. Results: The group consisted of 52 men and 148 women, with a mean age of 41 (±11.8) years and a mean body mass index (BMI) of 42.7 (±5.2) kg/m2 . Both, cIMT and PWV were significantly higher in men than in women, although the difference in cIMT disappeared after adjustment for covariables such as waist circumference, age, high‐density lipoprotein cholesterol and mean arterial pressure. PWV was associated with sex after adjustments for covariables in morbidly obese patients. Postmenopausal women had significantly increased cIMT and PWV when compared with premenopausal women. Conclusion: Sex differences in PWV persist in subjects suffering from morbid obesity. However, no difference was found in cIMT between morbidly obese men and women after adjustment for classic cardiovascular risk factors. Premenopausal morbidly obese women are protected for cardiovascular disease when compared with postmenopausal morbidly obese women.

Introduction: Loss of sensation due to diabetes-related neuropathy often leads to diabetic foot ulceration. Several test instruments are used to assess sensation, such as static and moving 2-point discrimination (S2PD, M2PD), monofilaments, and tuning forks. Methods: Mokken scale analysis was applied to the Rotterdam Diabetic Foot Study data to select hierarchies of tests to construct measurement scales. Results: We developed 39-item and 31-item scales to measure loss of sensation for research purposes and a 13-item scale for clinical practice. All instruments were strongly scalable and reliable. The 39 items can be classified into 5 hierarchically ordered core clusters: S2PD, M2PD, vibration sense, monofilaments, and prior ulcer or amputation. Discussion: Guided by the presented scales, clinicians may better classify the grade of sensory loss in diabetic patients’ feet. Thus, a more personalized approach concerning individual recommendations, intervention strategies, and patient information may be applied.

Introduction In view of the increasing occurrence of both obesity and heart failure, a growing overlap of these two clinical entities in the near future is expected. Significant advances in our understanding of the pathophysiological consequences of obesity for the cardiovascular system have been made over the past two decades. However, to optimise management and treatment of obesity patients, further research is required to improve early identification of cardiac dysfunction in obesity and to gain insight in the underlying pathophysiology. The CARdiac Dysfunction In OBesity - Early Signs Evaluation (CARDIOBESE) study has been designed to address these issues. Methods and analysis CARDIOBESE is a cross-sectional multicentre study of 100 obesity patients scheduled for bariatric surgery (body mass index (BMI) ≥35 kg/m 2) without known cardiovascular disease, and 50 age-matched and gender-matched non-obese controls (BMI <30 kg/m 2). Echocardiography, blood and urine biomarkers and Holter monitoring will be used to identify parameters that are able to show cardiac dysfunction at a very early stage in obesity patients (primary objective). Furthermore, a prospective follow-up study of obesity patients before and 1 year after bariatric surgery will be done to gain insight in the pathophysiology of obesity causing cardiac dysfunction (secondary objective). Ethics and dissemination The study was approved by the Medical Ethics Committee Toetsingscommissie Wetenschappelijk Onderzoek Rotterdam e.o. (TWOR). Inclusion of patients and controls is almost complete. Analyses of the investigations are currently being performed, and dissemination through peer-reviewed publications and conference presentations is expected from the first quarter of 2019. By identifying early markers of cardiac dysfunction in obesity, and by understanding the underlying pathophysiology of the abnormalities of these markers, the CARDIOBESE study may provide guidance for risk stratification, monitoring and

Introduction: Type 2 diabetes mellitus (T2DM) and obesity are both related to increased risk of cardiovascular disease and mortality. Early atherosclerotic vascular changes can be detected by non-invasive tests like carotid artery intima-media thickness (cIMT) and pulse wave velocity (PWV). Both cIMT and PWV are significantly impaired in T2DM patients and in obese patients, but the additional effect of T2DM on these vascular measurements in obese subjects has not been evaluated. Methods: Two hundred morbidly obese patients with or without T2DM were enrolled in a prospective cohort study and underwent extensive laboratory testing, including cIMT and PWV measurements. The cohort was divided into a group with and a group without T2DM. Results: Within this cohort, 43 patients (21.5%) were diagnosed with T2DM. These patients were older and had more often (a history of) hypertension as compared to patients without T2DM. HbA1c levels were significantly increased, while LDL cholesterol was significantly lower and the use of statins higher than in non-diabetic participants. cIMT and PWV were significantly increased in subjects suffering from T2DM. The variability in cIMT and PWV was related to differences in age and systolic blood pressure, but not to the presence of T2DM. Conclusion: While T2DM negatively affects the vasculature in morbid obesity, hypertension and age seem to be the major risk factors, independent from the presence of T2DM. Clinical Trial Registration: Dutch Trial Register NTR5172.

Objectives Rheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA. Methods Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound. Results In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQR

__Abstract__ __Background__: Obesity and asthma are associated. There is a relationship between lung function impairment and the metabolic syndrome. Whether this relationship also exists in the morbidly obese patients is still unknown. Hypothesis. Low-grade systemic inflammation associated with the metabolic syndrome causes inflammation in the lungs and, hence, lung function impairment. __Methods__: This is cross-sectional study of morbidly obese patients undergoing preoperative screening for bariatric surgery.Metabolic syndrome was assessed according to the revised NCEP-ATP III criteria. Results. A total of 452 patients were included. Patients with the metabolic syndrome ( = 293) had significantly higher blood monocyte (mean 5.3 versus 4.9, = 0.044) and eosinophil percentages (median 1.0 versus 0.8, = 0.002), while the total leukocyte count did not differ between the groups.The FEV1/FVC ratio was significantly lower in patients with the metabolic syndrome (76.7% versus 78.2%, = 0.032). Blood eosinophils were associated with FEV1/FVC ratio (adj. B −0.113, = 0.018). Conclusion. Although the difference in FEV1/FVC ratio between the groups is relatively small, in this cross-sectional study, and its clinical relevancemay be limited, these data indicate that the presence of the metabolic syndrome may influence lung function impairment, through the induction of relative eosinophilia.

Introduction:Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB) are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms.Methods:Subjects with and without CVD were included (N = 398). Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT) was determined as a measure of (subclinical) atherosclerosis.Results:Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80±0.09 mm, N = 140) compared to subjects with a normal CIMT (0.57±0.08 mm, N = 258) (P = 0.007, adjusted P<0.001). CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021). A total of 55 subjects (13.6%) were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82). Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56±0.94 a.u.) when compared to subjects with blood group A (0.89±1.15 a.u), blood group B (0.73±0.1.12 a.u.) or blood group AB (0.69±0.69 a.u.) (P-ANOVA = 0.002).Conclusion:Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant.

__Abstract__ Fasting and postprandial triglyceride concentrations largely depend on dietary and lifestyle factors. Alcohol intake is associated with triglycerides, but the effect of alcohol on diurnal triglyceridemia in a free living situation is unknown. During three days, 139 men (range: 18-80 years) measured their own capillary triglyceride (cTG) concentrations daily on six fixed time-points before and after meals, and the total daily alcohol intake was recorded. The impact of daily alcohol intake (none; low, <10 g/day; moderate, 10-30 g/day; high, >30 g/day) on diurnal triglyceridemia was analyzed by the incremental area under the cTG curve (∆cTG-AUC) reflecting the mean of the six different time-points. Fasting cTG were similar between the alcohol groups, but a trend of increased cTG was observed in men with moderate and high alcohol intake after dinner and at bedtime (p for trend <0.001) which persisted after adjustment for age, smoking and body mass index. The ∆cTG-AUC was significantly lower in males with low alcohol intake (3.0 ± 1.9 mmol·h/L) (n = 27) compared to males with no (7.0 ± 1.8 mmol·h/L) (n = 34), moderate (6.5 ± 1.8 mmol·h/L) (n = 54) or high alcohol intake (7.2 ± 2.2 mmol·h/L) (n = 24), when adjusted for age, smoking and body mass index (adjusted p value < 0.05). In males, low alcohol intake was associated with decreased diurnal triglyceridemia, whereas moderate and high alcohol intake was associated with increased triglycerides after dinner and at bed time.

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia.