With ageing populations, the prevalence of age-related disorders such as dementia is on the rise. As there is currently no curable treatment for dementia, the vascular component of dementia is... Show moreWith ageing populations, the prevalence of age-related disorders such as dementia is on the rise. As there is currently no curable treatment for dementia, the vascular component of dementia is increasingly recognised as a key modifiable cause. This thesis aims to investigate biological pathways between risk factors of cardiometabolic disease and cognitive function, in a population of older adults at increased risk of cardiovascular disease (CVD). We hypothesise that changes in physiological functioning caused by (sub)clinical CVD are possible mediators within the pathway leading to cognitive dysfunction. In the first part of this thesis, we studied electrocardiogram-based intervals and serum cardiac biomarkers (such as troponin) in relation to cognitive function. In the second part of this thesis, we studied the interplay of body mass index and serum leptin, loss of body weight and body weight variability, as well as metabolomics-based health scores in relation to cognitive function. We found that various cardiometabolic risk factors are associated with worse cognitive function. The results of this thesis strongly suggest that subclinical changes in cardiometabolic health may exist before cognitive dysfunction becomes apparent. Treating these cardiometabolic risk factors may be of benefit to future cognitive health. Show less
Martens, L.G.; Hamersveld, D. van; Cessie, S. le; Dijk, K.W. van; Heemst, D. van; Noordam, R. 2023
Objectives: Low socioeconomic status (SES) is associated with cardiovascular risk factors and increased coronary artery disease (CAD) risk. We tested whether SES is an effect modifier of the... Show moreObjectives: Low socioeconomic status (SES) is associated with cardiovascular risk factors and increased coronary artery disease (CAD) risk. We tested whether SES is an effect modifier of the association between classical cardiovascular risk factors and CAD using SES-stratified Mendelian Randomization in European-ancestry participants from UK Biobank.Study Design and Setting: We calculated weighted genetic risk scores (GRS) for the risk factors body mass index (BMI), systolic blood pressure, low-density lipoprotein cholesterol, and triglycerides. Participants were stratified by Townsend deprivation index score. Lo-gistic regression models were used to investigate associations between GRSs and CAD occurrence. Additionally, stratification based on GRS-adjusted Townsend deprivation index residuals was conducted to correct for possible collider-stratification bias.Results: In a total sample size of N 5 446,485, with 52,946 cases, the risk for CAD per standard deviation increase in genetically influenced BMI was highest in the group with the lowest 25% SES (odds ratio: 1.126, 95% confidence interval: 1.106-1.145; odds ratio: 1.081, 95% confidence interval: 1.059-1.103 in high SES), remaining similar after controlling for possible collider-stratification bias. The effects of genetically influenced systolic blood pressure, low-density lipoprotein cholesterol, and triglyceride on CAD were similar between SES groups.Conclusion: CAD risk attributable to increased BMI is not homogenous and could be modified by SES. This emphasizes the need of tailor-made approaches for BMI-associated CAD risk reduction. & COPY; 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Dietz, M.F.; Prihadi, E.A.; Bijl, P. van der; Marsan, N.A.; Bax, J.J.; Delgado, V. 2021
Background: Obesity may cause right ventricular (RV) remodeling due to volume overload. However, obesity is also associated with better prognosis compared with normal weight in patients with... Show moreBackground: Obesity may cause right ventricular (RV) remodeling due to volume overload. However, obesity is also associated with better prognosis compared with normal weight in patients with various cardiac diseases. The aim of this study was to assess the impact of obesity on RV remodeling and long-term prognosis in patients with significant (moderate and severe) tricuspid regurgitation (TR).Methods: A total of 951 patients with significant TR (median age, 70 years; interquartile range, 61-77 years; 50% men) were divided into three groups according to body mass index (BMI): normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >= 30 kg/m(2)). Patients with congenital heart disease, peripheral edema, active endocarditis, and BMI < 18.5 kg/m(2) were excluded. RV size and function for each group were measured using transthoracic echocardiography and compared with reference values of healthy study populations. The primary end point was all-cause mortality. Event rates were compared across the three BMI categories.Results: Four hundred seventy-six patients (50%) with significant TR had normal weight, 356 (37%) were over-weight, and 119 (13%) were obese. RV end-diastolic and end-systolic areas were larger in overweight and obese patients compared with normal-weight patients. However, no differences in RV systolic function were observed. During a median follow-up period of 5 years, 358 patients (38%) died. Five-year survival rates were significantly better in overweight and obese patients compared with patients with normal weight (65% and 67% vs 58%, respectively, P < .001 and P = .005). In multivariate analysis, overweight and obesity were independently associated with lower rates of all-cause mortality compared with normal weight (hazard ratios, 0.628 [95% CI, 0.493-0.800] and 0.573 [95% CI, 0.387-0.848], respectively).Conclusions: In patients with significant TR, overweight and obese patients demonstrated more RV remodeling compared with patients with normal weight. Nevertheless, a higher BMI was independently associated with better long-term survival, confirming the obesity paradox in this context. Show less
Objective: To investigate the association between body mass index (BMI) and oral anticoagulant (OAC) prescription in atrial fibrillation (AF).Methods: Patients with newly diagnosed non-valvular AF ... Show moreObjective: To investigate the association between body mass index (BMI) and oral anticoagulant (OAC) prescription in atrial fibrillation (AF).Methods: Patients with newly diagnosed non-valvular AF (< 3 months) with >= 1 stroke risk factors enrolled in the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) in Asia, Europe and North America were evaluated.Results: The cohort (n = 13,793) comprised patients from all BMI categories (kg/m(2)): 1.4% were underweight (<18.5), 27.3% had a normal BMI (18.5 to <25), 37.9% were overweight (25 to <30), 19.3% were moderately obese (30 to < 35), and 12.7% were morbidly obese (>= 35). The highest proportion of Asians had a BMI of 18.5 to <25 kg/m(2), while the highest proportion of patients from Europe and North America were overweight and a substantial proportion of North Americans morbidly obese. In the multivariable analysis, the probability ratio of non-prescription of OAC, as compared to normal BMI, decreased for overweight (RR = 0.907), moderately obese (RR = 0.802) and severe very severe obese patients (RR = 0.659). Moreover, the probability ratio of non-prescription of OACs was increased in the Asia or North America regions, as compared with Europe, in patients aged <65 years or female patients, as well as in patients with prior bleeding or vascular disease.Conclusions: The distribution of BMI differed among the continents. An increased BMI was associated with a lower probability of non-prescription of OACs, as compared with a normal BMI. The probability of non-prescription of OACs was increased in the Asia or North America regions, as compared with Europe. Show less
Esch, C.C.L. van der; Kloosterboer, S.M.; Ende, J. van der; Reichart, C.G.; Kouijzer, M.E.J.; Kroon, M.M.J. de; ... ; Dierckx, B. 2020
Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term... Show moreAntipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI)zscore, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMIzscore for a follow-up of < 15 weeks, 15-52 weeks or > 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMIzscore points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMIzscore increase per week beta = 0.02, 95% CI 0.01-0.03,p = 0.002). A higher baseline BMIzscore and the absence of stimulant use were associated with a higher BMIzscore during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMIzscore. Show less
Brouwer, J.G.M.; Snellen, M.; Bisseling, T.M.; Koornstra, J.J.; Vasen, H.F.A.; Kampman, E.; Duijnhoven, F.J.B. van 2020
A cancer diagnosis is suggested to be associated with changes in dietary and lifestyle habits. Whether this applies to persons with familial cancer, such as Lynch syndrome (LS) is unknown. We... Show moreA cancer diagnosis is suggested to be associated with changes in dietary and lifestyle habits. Whether this applies to persons with familial cancer, such as Lynch syndrome (LS) is unknown. We investigated whether a colorectal neoplasm (CRN) diagnosis in persons with LS is associated with changes in dietary and lifestyle habits over time. We used data of confirmed LS mutation carriers from the GEOLynch study, a prospective cohort study. Information on dietary intake and lifestyle habits was collected with a validated semi-quantitative food frequency questionnaire and a general questionnaire administered at baseline (2006-2008) and follow-up (2012-2017). Participants' medical records were used to identify CRN diagnoses. Changes in dietary and lifestyle habits in the CRN and the no-CRN group were compared using multivariable linear regression models for continuous variables and cross-tables with percentage change at follow-up compared with baseline for categorical variables. Of the 324 included participants, 146 developed a CRN (CRN group) between baseline and follow-up, while 178 did not (no-CRN group). Smoking cessation was more often reported in the CRN than in the no-CRN group (41.4% vs. 35.0%). There were no differences in changes of energy intake, alcohol, red meat, processed meat, dairy, fruit, vegetables and dietary fiber consumption, BMI, physical activity and NSAID use. Apart from a potentially higher likelihood of smoking cessation, we found little evidence that a CRN diagnosis is associated with changes in lifestyle habits in persons with LS. Show less
Alshehri, T.; Boone, S.; Mutsert, R. de; Penninx, B.; Rosendaal, F.; Cessie, S. le; ... ; Mook-Kanamori, D. 2019
Many common disorders, including depression, dementia and obesity are for a large part heritable. Despite the fact that genome-wide association studies (GWAS) have contributed substantially to... Show moreMany common disorders, including depression, dementia and obesity are for a large part heritable. Despite the fact that genome-wide association studies (GWAS) have contributed substantially to unraveling the genetic architecture of these polygenetic disorders, a large amount of ‘missing heritability’ remains. A possible explanation is that GWAS, aside single-nucleotide polymorphisms cannot assess the contribution of other important genetic polymorphisms, especially tandem repeats. Tandem repeats constitute 3% of the human genome. Nine hereditary neurodegenerative diseases, known as polyglutamine diseases, including Huntington disease (HD), are the most prevalent disorders associated with tandem repeat variations. These diseases are caused by an elongated cytosine-adenine-guanine (CAG) repeat sequence in the respective polyglutamine disease-associated gene (PDAG). In this dissertation, we provide ample evidence that CAG repeat variations within the ‘normal’ range in PDAGs can affect various aspects of disease, including the age of onset in HD, cognitive function, depression and body mass index. Finally, we found a relatively large prevalence of intermediate and pathological PDAG alleles in the general population. Therefore, we provided support for the role of repetitive DNA polymorphisms in elucidating the ‘missing heritability’ of polygenetic disorders and emphasized the necessity to include these variations in future genetic research. Show less
Balke, E.M.; Demeester, S.; Lee, D.; Gillard, P.; Hilbrands, R.; Velde, U. van de; ... ; Gorus, F.K. 2018
