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Background: Peroxisome proliferator-activated receptor (PPAR) agonists may have favorable outcomes on non-alcoholic fatty liver disease. This study serves as proof of concept to evaluate whether dual PPAR-α/γ agonists improve non-invasive tests of liver steatosis and fibrosis., Methods: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled, multi-center trial comprising 7226 patients with type 2 diabetes mellitus and recent coronary artery disease randomized to receive aleglitazar, a PPAR-α/γ agonists, or placebo for two years. Main outcomes were change in non-invasive tests for liver steatosis and fibrosis: Liver Fat Score (LFS), Liver Accumulation Product (LAP), Fibrosis-4 (FIB-4), and NAFLD Fibrosis Score (NFS)., Results: LFS, LAP and FIB-4 decreased upon treatment, whereas scores in the placebo group remained the same or increased (P<0.001). NFS responded differently but remained consistently lower than placebo. In the treatment group more participants shifted to a lower FIB-4 and NFS category, or improved in respect to the LAP cut-off values compared to the placebo group (P<0.001 for FIB-4 and LAP, P<0.004 for NFS). LFS had a low discriminative power in this study., Conclusion: This post-hoc analysis showed improvement of non-invasive tests of liver steatosis and fibrosis after starting dual PPAR-α/γ agonist treatment, adding to the evidence that this pathway has potential in non-alcoholic fatty liver disease treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Grobbee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD). No long-term intervention trials on CVD risk factors have been published, and a debate on the efficacy of controlling traditional risk factors in RA is ongoing. We aimed to evaluate a treat-to-target approach versus usual care regarding traditional CVD risk factors in patients with RA., Methods: In this open-label, randomised controlled trial, patients with RA aged <70 years without prior CVD or diabetes mellitus were randomised 1:1 to either a treat-to-target approach or usual care of traditional CVD risk factors. The primary outcome was defined as change in carotid intima media thickness (cIMT) over 5 years, and the secondary outcome was a composite of first occurrence of fatal and non-fatal cardiovascular events., Results: A total of 320 patients (mean age 52.4 years; 69.7% female) with RA underwent randomisation and 219 patients (68.4%) completed 5 years of follow-up. The mean cIMT progression was significantly reduced in the treat-to-target group compared with usual care (0.023 [95% CI 0.011 to 0.036] mm vs 0.045 [95% CI 0.030 to 0.059] mm; p=0.028). Cardiovascular events occurred in 2 (1.3%) of the patients in the treat-to-target group vs 7 (4.7%) in those receiving usual care (p=0.048 by log-rank test)., Conclusion: This study provides evidence on the benefit of a treat-to-target approach of traditional CVD risk factors for primary prevention in patients with well-treated RA., Trial Registration Number: NTR3873., Competing Interests: Competing interests: MCC served as a consultant for Merck and received lecture honoraria from Merck., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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 treatment strategies for obesity patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Most dyslipidemic conditions have been linked to an increased risk of cardiovascular disease. Over the past few years major advances have been made regarding the genetic and metabolic basis of dyslipidemias. Detailed characterization of the genetic basis of familial lipid disorders and knowledge concerning the effects of environmental factors on the expression of dyslipidemias have increased substantially, contributing to a better diagnosis in individual patients. In addition to these developments, therapeutic options to lower cholesterol levels in clinical practice have expanded even further in patients with familial hypercholesterolemia and in subjects with cardiovascular disease. Finally, promising upcoming therapeutic lipid lowering strategies will be reviewed. All these advances will be discussed in relation to current clinical practice with special focus on common lipid disorders including familial dyslipidemias., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Obesity is related to increased cardiovascular risk. It is unknown whether increasing levels of obesity also increase levels of cardiovascular risk factors and systemic inflammation. This study describes the relationship between classic cardiovascular risk factors and inflammatory markers with BMI in a group of obese and non-obese subjects., Materials and Methods: Obese subjects (BMI ≥ 30 kg/m 2 ; n = 576; mean ± SD BMI 43.8 ± 7.58 kg/m 2 ) scheduled for bariatric surgery were included. The reference population consisted of non-obese volunteers (BMI < 30 kg/m 2 ; n = 377, BMI 25.0 ± 2.81 kg/m 2 ). The relationship between BMI quintiles and the levels of cardiovascular risk factors was analyzed. Adipose tissue volumetry was performed in 42 obese subjects using abdominal CT scans., Results: The obese group included more women and subjects with type 2 diabetes mellitus, hypertension, and current smoking behavior. In obese subjects, HDL-C and triglycerides decreased with increasing BMI. Systolic and diastolic blood pressure, total cholesterol, LDL-C, and apoB were not related to BMI in the obese group, in contrast to the non-obese group. Inflammatory markers CRP, leukocyte count, and serum complement C3 increased with increasing BMI in the obese group, while these relations were less clear in the non-obese group. The subcutaneous adipose tissue surface was positively correlated to BMI, while no correlation was observed between BMI and visceral adipose tissue., Conclusions: Markers of inflammation are strongest related to BMI in obese subjects, most likely due to increased adipose tissue mass, while cardiovascular risk factors do not seem to deteriorate above a certain BMI level. Limited expansion capacity of visceral adipose tissue may explain these findings.

Diabetes mellitus type 2 (T2DM) has been associated with an increased cardiovascular risk. Improving glycaemia or other traditional cardiovascular risk factors may reduce cardiovascular risk in patients with T2DM. However, single risk intervention in T2DM has not provided convincing evidence in the reduction of cardiovascular risk. The aim of this paper is to provide an overview of clinical trials involving reduction of cardiovascular outcomes in patients with T2DM. Trials with glucose lowering therapies have shown conflicting results. Intensive therapy to reduce glycaemia has shown some benefit on composite cardiovascular endpoints but these benefits take a longer period to emerge. Recent studies with empagliflozin and glucagon-like peptide-1 (GLP-1) agonists show promising results, but the mechanisms are most likely not mediated by improved glycaemia, given the relatively rapid effects. Both LDL-cholesterol and blood pressure reduction have been proven by large meta-analysis to reduce both cardiovascular events and mortality in all patients with T2DM. Treatment of microalbuminuria and anti-platelet therapy have only been proven in diabetic patients with increased cardiovascular risk. Classical lifestyle interventions have been disappointing with respect to cardiovascular outcome, possibly due to limited weight reduction. So far, the strongest evidence lies on bariatric surgery and a multifactorial intervention to reduce mortality and cardiovascular events in the long term., (Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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 2-14 years). The median DAS28 was 2.4 (IQR 1.6-3.2) and 114 (50.4%) of the RA patients were in remission. The presence of RA and cIMT were not associated (univariate analysis). Multivariable regression analysis showed that cIMT in RA patients was associated with age (B = 0.006, P<0.001) and systolic blood pressure (B = 0.003, P = 0.003). In controls, cIMT was associated with age (B = 0.006, P<0.001) and smoking (B = 0.097, P = 0.001)., Conclusion: cIMT values were similar between RA patients and controls. Hypertension was strongly associated with cIMT in RA patients. After adjustment, no association between cIMT and specific RA disease characteristics was found in this well treated RA cohort.

Postprandial lipemia has been associated with cardiovascular disease. The current pathophysiological concept is that postprandial remnant lipoproteins migrate into the subendothelial space and that remnants activate circulating leukocytes and endothelial cells. Activated monocytes adhere to endothelial adhesion molecules, facilitating subendothelial migration of monocytes. These cells differentiate into macrophages, with the risk of foam cell formation, due to uptake of remnants and modified lipoproteins. Evidence is emerging that specific interventions may reduce the atherogenic postprandial inflammation. Fruits rich in polyphenols, virgin olive oil, carotenoids and exercise have recently been found to reduce postprandial inflammation. Pharmaceutical interventions with fibrates or statins not only improve the overall lipid profile, but reduce postprandial inflammation as well. This review will deal with the current concept of postprandial inflammation in relation to the development of atherosclerosis and potential interventions to reduce postprandial inflammation., (Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Summary: The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high‐risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality—in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma—it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood‐ and imaging‐based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity. [ABSTRACT FROM AUTHOR]

Background Atherosclerosis is a pro-inflammatory condition, in which leucocyte activation plays an important role. The interaction between circulating leucocytes and apolipoprotein (apo) B-containing lipoproteins results in pro-inflammatory changes of these cells. We aimed to evaluate the relationship between apo B bound to circulating leucocytes and atherosclerosis. Methods Apo B on circulating leucocytes was measured by flow cytometry in subjects with and without cardiovascular disease ( CVD), expressed as mean fluorescent intensity in arbitrary units (au). Carotid intima-media thickness ( cIMT) was measured using B-mode ultrasound. Data are given as median (interquartile range). Results A total of 396 subjects were included, of whom 183 had a history of CVD. Compared to subjects without CVD, patients with CVD had lower apo B bound to neutrophils (12·7 au (9·8-16·2) and 14·2 au (10·1-17·5), respectively, P = 0·038) and to monocytes (2·5 au (1·7-3·1) and 2·7 (1·9-3·6) au, respectively, P = 0·025). No differences were found for lymphocyte-bound apo B. Neutrophil- and monocyte-bound apo B were inversely correlated with cIMT (Spearman's rho: −0·123, P = 0·017 and −0·108, P = 0·035, respectively). Both monocyte- and neutrophil-bound apo B were inversely associated with different factors related to the metabolic syndrome, such as body mass index, triglycerides and complement C3. There was a positive association between erythrocyte-bound apo B and apo B bound to each of the leucocyte classes, possibly reflecting a similar mechanism. Discontinuation of statins in 54 subjects did not influence leucocyte-bound apo B. Conclusion Unexpectedly, the presence of noninternalized apo B-containing lipoproteins on circulating neutrophil and monocyte membranes may represent a protective mechanism against atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Rheumatoid Arthritis (RA) have an increased risk for cardiovascular disease (CVD) compared to the general population. No long term intervention trials on CVD risk factors in RA have been published so far, and a debate on the efficacy of controlling traditional risk factors in RA is ongoing. Methods: In this open-label randomised controlled trial, RA patients <70 years without prior CVD or diabetes mellitus were randomized to either a treat-to-target approach (according to pre-specified treatment targets) or usual care regarding traditional CVD risk factors. The primary outcome was defined as change in carotid intima media thickness (cIMT) as a marker for subclinical atherosclerosis and the secondary outcome was a composite of cardiovascular events. Results: A total of 320 patients underwent randomization and 218 completed 5 years follow-up (115 for treat-to-target group and 103 for usual care). Mean (± SD) baseline cIMT in the treat-to-target group was 0.570 ± 0.108 vs. 0.569 ± 0.113 mm (p=0.91) for usual care. The primary outcome reached statistical significance showing decreased progression of cIMT in those allocated to the treat-to-target intervention compared to usual care (0.029 ± 0.081 vs. 0.056 ± 0.103 mm; p=0.034). There was no difference in antihypertensive treatment between groups, however more patients in the treat-to-target group received statin treatment compared to usual care (48.3% vs. 21.4%; p<0.001), resulting lower LDL-C level (2.5 ± 0.8 vs. 3.1 ± 0.6 mmol/L; p<0.001). Cardiovascular events occurred in 1.3% of the patients in the treat-to-target group vs. 4.7% in those receiving usual care (p=0.048), leading to an absolute risk reduction of 3.4%. The numbers needed to treat to prevent one single cardiovascular event over 5 years was 30, which is much lower than in most secondary prevention CVD intervention trials using anti-hypertensives or lipid lowering therapy in non-RA populations. Conclusions: Intensive treat-to-target intervention of traditional CVD risk factors for primary prevention in RA is efficient. These data underscore the urgency for cardiovascular risk management programs in RA and provide for the first time support for implementation of current guidelines targeting traditional risk factors. [ABSTRACT FROM AUTHOR]