Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare... Show moreCardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA. Show less
Mahdiui, M. el; Bijl, P. van der; Abou, R.; Marsan, N.A.; Delgado, V.; Bax, J.J. 2019
Background: Global left ventricular (LV) myocardial work efficiency, the ratio of constructive to wasted work in all LV segments, reflects the efficiency by which mechanical energy is expended... Show moreBackground: Global left ventricular (LV) myocardial work efficiency, the ratio of constructive to wasted work in all LV segments, reflects the efficiency by which mechanical energy is expended during the cardiac cycle. Global LV myocardial work efficiency can be derived from LV pressure-strain loop analysis incorporating both noninvasively estimated blood pressure recordings and echocardiographic strain data. The aim of this study was to characterize global LV myocardial work efficiency in healthy individuals and patients with cardiovascular (CV) risk factors or overt cardiac disease.Methods: We retrospectively included healthy individuals without structural heart disease or CV risk factors, who were selected from an ongoing database of normal individuals, and matched for age and sex with (1) individuals without structural heart disease but with CV risk factors, (2) postinfarct patients without heart failure, and (3) heart failure patients with reduced ejection fraction (HFrEF). Global LV myocardial work efficiency was estimated with a proprietary algorithm from speckle-tracking strain analyses, as well as noninvasive blood pressure measurements.Results: In total, 120 individuals (44% male, 53 +/- 13 years) were included (n = 30 per group). In healthy individuals without structural heart disease or CV risk factors, global LV myocardial work efficiency was 96.0% (interquartile range, 95.0%-96.3%). Myocardial efficiency of the LV did not differ significantly between individuals without structural heart disease and those with CV risk factors (96.0% vs 96.0%; P = .589). Global LV myocardial work efficiency, however, was significantly decreased in postinfarct patients (96.0% vs 93.0%, P < .001) and in those with HFrEF (96.0% vs 69.0%; P < .001).Conclusions: While global LV myocardial work efficiency was similar in normal individuals and in those with CV risk factors, it was decreased in postinfarct and HFrEF patients. The global LV myocardial work efficiency values presented here show distinct patterns in different cardiac pathologies. Show less
Artificial intelligence (AI) has transformed key aspects of human life. Machine learning (ML), which is a subset of AI wherein machines autonomously acquire information by extracting patterns from... Show moreArtificial intelligence (AI) has transformed key aspects of human life. Machine learning (ML), which is a subset of AI wherein machines autonomously acquire information by extracting patterns from large databases, has been increasingly used within the medical community, and specifically within the domain of cardiovascular diseases. In this review, we present a brief overview of ML methodologies that are used for the construction of inferential and predictive data-driven models. We highlight several domains of ML application such as echocardiography, electrocardiography, and recently developed non-invasive imaging modalities such as coronary artery calcium scoring and coronary computed tomography angiography. We conclude by reviewing the limitations associated with contemporary application of ML algorithms within the cardiovascular disease field. Show less
This thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis... Show moreThis thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis on statin-induced HDL-C response by the Genomic Investigation of consortium, which identified CETP as a loci of interest, and two-sample Mendelian randomization studies utilizing summary level data from the GIST and other GWAS consortia on fasted blood lipids and type 2 diabetes. We additionally examine the issue of survival bias in Mendelian randomization studies. Finally, we show that intra-individual lipid variability associates with worse neurocognitive outcomes in older individuals at high risk for vascular disease, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. Show less
Aims There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention... Show moreAims There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29 39% of individuals aged >= 40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44 51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms.Conclusion Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need. Show less
Atherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the... Show moreAtherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the vessel wall. Over time, this accumulation of lipids and immune cells induce morphological abnormalities in the vessel wall which cause the vessel lumen to narrow. This narrowing of the lumen (stenosis) causes ischemia in the downstream tissue. Prolonged ischemia causes myocardial ischemia and/or stroke. The research described in my thesis examines a well-recognized risk factor of atherosclerosis, being dyslipidemia, from an entirely new perspective. More specifically, it describes how dyslipidemia affects intrinsic metabolic processes in T cells, the conductors of the immune response characterizing atherosclerosis, and how this affects their function. My research has contributed to knowledge on the pathophysiology of atherosclerosis and might one day pave the way for the development of novel therapeutic approaches to treat cardiovascular disease. Show less
Meeuwsen, J.A.L.; Vries, J.J. de; Duijvenvoorde, A. van; Velden, S. van der; Laan, S.W. van der; Koeverden, I.D. van; ... ; Jager, S.C.A. de 2019
future AbstractMouse studies have established distinct monocyte subtypes that participate in the process of atherosclerotic lesion formation. The pro-inflammatory Ly6Chigh monocyte subtype actively... Show morefuture AbstractMouse studies have established distinct monocyte subtypes that participate in the process of atherosclerotic lesion formation. The pro-inflammatory Ly6Chigh monocyte subtype actively contributes to murineplaque progression and destabilization. Also in humans, different peripheral monocyte subtypes have been identified, of which the CD14+CD16− classical monocyte is suggested to display similar pro-atherosclerotic properties as the murine Ly6Chigh subtype. We aimed to investigate if circulating CD14+CD16− classical monocytes associate with characteristics of a vulnerable carotid atherosclerotic plaque and if they associate with the risk of secondary adverse manifestations of atherosclerotic disease.We enrolled 175 carotid endarterectomy patients of the Athero-Express biobank in our study. Just prior to surgical procedure, blood was collected and peripheral blood mononuclear cells were isolated. Characterization of monocyte subsets was performed by flow cytometry. Plaque characteristics were semi-quantitatively scored for the presence of fat, collagen, intraplaque hemorrhage and calcification. Vessel density, smooth muscle cells and macrophages were assessed quantitatively on a continuous scale. All features of a vulnerable plaque phenotype, including low amounts of collagen and smooth muscle cells, and increased fat content, vessel density, intraplaque hemorrhage and plaque macrophages were not significantly associated with differential levels of peripheral classical CD14+CD16− monocytes or other monocyte subsets. Using Cox regression models to evaluate the prognostic value of circulating monocyte subtypes, we found that total counts of peripheral monocytes, as well as CD14+CD16− classical and other monocyte subtypes were not associated with the risk of secondary cardiovascular events during 3 years follow-up.Circulating classical CD14+CD16− monocytes do not associate with specific vulnerable plaque characteristics. In addition, they do not predict secondary adverse manifestations. This suggests that in patients with established carotid artery disease, the circulating monocytes do not reflect plaque characteristics and have no value in identifying patients at risk for future cardiovascular events. Show less
