Purpose:Cardiac rehabilitation in older patients after hospitalization because of cardiovascular disease is recommended. However, many older patients do not receive cardiac rehabilitation in daily... Show morePurpose:Cardiac rehabilitation in older patients after hospitalization because of cardiovascular disease is recommended. However, many older patients do not receive cardiac rehabilitation in daily practice, due to lack of referral and poor adherence. This can be related to impaired clinical and functional status of these patients, who are more likely to present with frailty, frequent comorbidities, and disability. Geriatric rehabilitation might be a possible solution to reduce barriers to cardiac rehabilitation attendance. We developed and implemented an inpatient geriatric rehabilitation programme that was provided immediately after discharge from the hospital, for older patients with a significant functional decline during hospital admission because of cardiovascular disease: 'the GR-cardio programme'. The primary aim of the present study is to investigate feasibility of the GR-cardio programme.Methods:This is a retrospective real-life feasibility study describing a consecutive series of older patients receiving the GR-cardio programme, with no control group. All patients had been hospitalized because of cardiovascular disease. Data on patient characteristics, functional status, health-related quality of life (HRQoL), readmissions, and mortality were collected from the patients file on admission, at discharge and 6 months after discharge from the GR-cardio programme. Feasibility of the programme was evaluated using the following outcomes: recruitment, resulting sample characteristics, safety, and preliminary evaluation of patients' responses to the GR-cardio programme.Results:In total, 58 patients [mean age 78.8 (± 9.8) years; 43% male] were included in the study. On admission, functional status and HRQoL were severely impaired but showed clinically relevant improvements. During the programme, three patients died. Eighty-three percent of all patients were discharged back home after completing the rehabilitation programme with a mean length of 38 days. Mortality rate during follow-up was the highest in patients with heart failure (32%).Conclusions:This study indicates that geriatric rehabilitation for patients with cardiovascular disease is feasible. Furthermore, our results show that the GR-cardio programme can probably offer substantial benefits for patients in terms of improving functional status and HRQoL. Show less
Limiting the pro-inflammatory immune response is critical for the treatment of atherosclerosis. Regulatory B cells (Bregs) can modulate the immune response through interleukin-10 (IL-10). Current... Show moreLimiting the pro-inflammatory immune response is critical for the treatment of atherosclerosis. Regulatory B cells (Bregs) can modulate the immune response through interleukin-10 (IL-10). Current data regarding Bregs and atherosclerosis is scarce and conflicting.\n B cells on atherosclerosis.\n B cells on atherosclerosis.\n B cells in atherosclerosis. Show less
Worldwide, there is an strong rise of cardiometabolic disorders, which mainly comprise obesity, cardiovascular disease (CVD) and type 2 diabetes. Therefore, the development and improvement of... Show moreWorldwide, there is an strong rise of cardiometabolic disorders, which mainly comprise obesity, cardiovascular disease (CVD) and type 2 diabetes. Therefore, the development and improvement of preventive and curative strategies for cardiometabolic disease is eagerly warranted. With the studies describes in this thesis, we aimed to disentangle the interwoven physiological, environmental and genetic factors that determine cholesterol and energy metabolism to increase our understanding of their contribution to cardiometabolic disease risk. The first part of this thesis focussed on the cholesteryl ester transfer protein (CETP). The lipid transfer properties of CETP induce a proatherogenic lipoprotein profile. Therefore, CETP inhibitory molecules have been developed and tested in clinical trials for their capability to improve the lipoprotein profile and reduce CVD risk. To fully understand the role of CETP in CVD, its physiology and biological function should be fully unravelled. The focus of the second part of this thesis was on the role of energy metabolism in cardiometabolic health. Specifically, we aimed to study the association of environmental and genetic factors, which were previously described to influence brown adipose tissue (BAT) activity, with energy expenditure and disease outcomes. Show less
Metabolic disease has become pandemic in the developed world. Given our lack of understanding of its molecular pathology, we are often unable to diagnose patients before they reach an... Show moreMetabolic disease has become pandemic in the developed world. Given our lack of understanding of its molecular pathology, we are often unable to diagnose patients before they reach an irreversible state of diabetes or cardiovascular disease. Much research has been done on the role of insulin signaling in metabolic disease, as well as the resultant disturbed lipid homeostasis present in cardiovascular disease and atherosclerosis. Here we add to existing work by developing new tools and sketching out the pathology of dysregulated adipose insulin signaling. We discuss the mechanism of lipodystrophy by using adipocytes differentiated from patient-derived iPSCs. These cells mimic the clinical phenotype and hint at mechanism that reduced patients’ adipose tissue mass. In mice we find that if we knock out the adipose insulin receptor, there is disrupted adipose and liver metabolism. There is a protection from diet-induced obesity, but a dramatically reduced lifespan. We also establish a relationship between obesity and inflammation by transcriptomically assessing obese human adipocytes. We find that an immune factor is responsible for lipid droplet formation and content. Lastly, we develop a new differentiation and purification strategy for iPSC-derived hepatocytes, which we employ to in vitro model a SNP that protects against cardiovascular disease. Show less
Cardiovascular disease is the leading cause of death in the western world. Frequent or chronic reductions in heart rate variability (HRV) are a powerful predictor of cardiovascular disease.... Show moreCardiovascular disease is the leading cause of death in the western world. Frequent or chronic reductions in heart rate variability (HRV) are a powerful predictor of cardiovascular disease. Psychological stress has been suggested to be an important factor in the development of reduced HRV. Recently, Verkuil et al. (2016) introduced a laboratory-based method to measure additional HRV reduction in everyday life, and reductions in HRV related to psychological stress. In the current paper, we discuss alternative methods to detect additional HRV reductions, in real life data sets without the necessity of laboratory-based calibration, and even in existing data sets. All of these methods use a subset of 24 h' worth of HRV and movement data to do so: either the first 10 min of every hour, the full 24 h, a combination of 10 min from three consecutive hours, or a classification of level of movement. We also present a method to visualize HRV and movement data to be able to detect episodes of reduced additional HRV optically. The method that used the full 24 h' worth of data detected the largest percentage of episodes of reduced additional HRV that actually match with self-reported stress levels, making this method the most promising. Show less
Manabe, O.; Kikuchi, T.; Scholte, A.J.H.A.; Mahdiui, M. el; Nishii, R.; Zhang, M.R.; ... ; Yoshinaga, K. 2018
Cardiovascular disease (CVD) is the leading cause of death in women in the Western world. In this thesis, several studies are presented examining the association between recurrent miscarriage and... Show moreCardiovascular disease (CVD) is the leading cause of death in women in the Western world. In this thesis, several studies are presented examining the association between recurrent miscarriage and cardiovascular disease. Main aim of this thesis was to assess whether miscarriages are independently associated with an increased risk of cardiovascular disease later in life. And, if this was true, to identify cardiovascular risk factors and predict long term cardiovascular disease risk in women with a history of recurrent miscarriage. We found an increased risk of ischemic heart disease in women with a history of two (multivariate analysis HR 1.82) and three or more miscarriages (HR 3.18), irrespective whether consecutive or not (chapter 2). Women with a history of recurrent miscarriage have significantly higher 10- and 30-year cardiovascular risk scores compared to women with a history of no miscarriage. These results indicate an opportunity for the early identification of women prone to cardiovascular disease later in life. Women with a history of two or more miscarriages must be made aware of their increased cardiovascular risk and appropriate risk factor modifications will have to be offered, for example life style advises; weight management and smoking control. Show less
Atherosclerotic changes of the carotid artery are associated with elevated cardiovascular risk. Non-invasive imaging studies of the artery can provide information on the presence or absence of... Show moreAtherosclerotic changes of the carotid artery are associated with elevated cardiovascular risk. Non-invasive imaging studies of the artery can provide information on the presence or absence of abnormalities. Although the techniques are extensively used in clinical research their implementation in common practice is not widespread. In this thesis the potential benefits and challenges of carotid imaging in clinical practice are studied. Ultrasound and magnetic resonance imaging are the two modalities of interest. The findings suggest that ultrasound can be performed by the clinician in a routine outpatient setting. Clinicians are able to detect atherosclerotic plaques but not intima-media thickness. Plaques are highly prevalent in asymptomatic primary prevention patients. Magnetic resonance imaging is a new highly reproducible modality but requires further clinical validation. Its utility in individual patient risk assessment is unclear and ultrasound validity cannot be extrapolated to magnetic resonance. The use of a combination of the two imaging modalities may allow for estimation of the lamina adventitia in vivo. Finally, interpretation of the imaging parameters must be done in conjunction with all cardiovascular risk factors and treatment decision should not be based on imaging results alone. Show less
