Background Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values... Show moreBackground Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. Methods From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45-65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (>= 130/80 and < 140/90 mmHg; and >= 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. Results Normal mean PWV was 6.0 m/s [95% CI 5.8-6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants >= 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants >= 55 years old in the high blood pressure subgroups. Conclusion This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population. Show less
Amier, R.P.; Marcks, N.; Hooghiemstra, A.M.; Nijveldt, R.; Buchem, M.A. van; Roos, A. de; ... ; Heart-Brain Connection Consortium 2021
OBJECTIVES This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD)... Show moreOBJECTIVES This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD) and cognitive impairment, with the aim of understanding the role of hypertension in the early stages of deteriorating brain health.BACKGROUND Preserving brain health into advanced age is one of the great challenges of modern medicine. Hypertension is thought to induce vascular brain injury through exposure of the cerebral microcirculation to increased pressure/pulsatility. Cardiovascular MRI provides markers of (subclinical) hypertensive exposure, such as aortic stiffness by puke wave velocity (PWV), left ventricular (LV) mass index (LVMi), and concentricity by mass-to-volume ratio.METHODS A total of 559 participants from the Heart-Brain Connection Study (431 patients with manifest cardiovascular disease and 128 control participants), age 67.8 +/- 8.8 years, underwent 3.0-T heart-brain MRI and extensive neuropsychological testing. Aortic PWV, LVMi, and LV mass-to-volume ratio were evaluated in relation to presence of CSVD and cognitive impairment. Effect modification by patient group was investigated by interaction terms; results are reported pooled or stratified accordingly.RESULTS Aortic PWV (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.05 to 1.30 in patient groups only), LVMi (in carotid occlusive disease, OR: 5.69; 95% CI: 1.63 to 19.87; in other groups, OR: 1.30; 95% CI: 1.05 to 1.62]) and LV mass-to-volume ratio (OR: 1.81; 95% CI: 1.46 to 2.24) were associated with CSVD. Aortic PWV (OR: 1.07; 95% CI: 1.02 to 1.13) and LV mass-to-volume ratio (OR: 1.27; 95% CI: 1.07 to 1.51) were also associated with cognitive impairment. Relations were independent of sociodemographic and cardiac index and mostly persisted after correction for systolic blood pressure or medical history of hypertension. Causal mediation analysis showed significant mediation by presence of CSVD in the relation between hypertensive exposure markers and cognitive impairment.CONCLUSIONS The extent of hypertensive exposure is associated with CSVD and cognitive impairment beyond clinical brood pressure or medical history. The mediating role of CSVD suggests that hypertension may lead to cognitive impairment through the occurrence of CSVD. (C) 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
Morelli, V.M.; Mutsert, R. de; Roos, A. de; Lamb, H.J.; Vlieg, A.V.; Bos, M.H.A.; ... ; Cannegieter, S.C. 2020
Objective:Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate... Show moreObjective:Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate the association between HTGC and coagulation factors (F)I (fibrinogen), VIII, IX, and XI while adjusting for TBF and VAT.Approach and Results:In this cross-sectional analysis of the NEO study (Netherlands Epidemiology of Obesity; n=6671), a random subset of participants underwent magnetic resonance imaging and magnetic resonance spectroscopy to assess VAT and HTGC (n=2580). We excluded participants without complete imaging and coagulation assessment, and with history of liver disease, venous thrombosis, or on anticoagulation. Mean differences in coagulation factor levels across HTGC quartiles were estimated by linear regression adjusted for age, sex, ethnicity, education, alcohol intake, physical activity, smoking, estrogen, and menopause, in addition to TBF and VAT. Among the 1946 participants included, median HTGC was 2.66% (interquartile range: 1.34%-6.27%). Coagulation factor levels increased dose-dependently across HTGC quartiles. Mean differences between the fourth and first quartiles were 14.7 mg/dL (95% CI, 2.1-27.2) for fibrinogen, 6.7 IU/dL (95% CI, 0.5-12.9) for FVIII, 26.1 IU/dL (95% CI, 22.4-29.8) for FIX, and 8.6 IU/dL (95% CI, 4.6-12.6) for FXI. With further adjustment for TBF and VAT, the dose-response association of HTGC with FIX persisted, whereas associations with other factors disappeared.Conclusions:HTGC was associated with various coagulation factors, of which FIX remained associated with HTGC after adjustment for TBF and VAT. HTGC might contribute to venous thrombosis risk beyond total body and visceral fat through FIX levels. Show less
Background It is unclear to what extent adherence to dietary guidelines may specifically affect visceral fat and liver fat. We aimed to study the association between the Dutch Healthy Diet Index ... Show moreBackground It is unclear to what extent adherence to dietary guidelines may specifically affect visceral fat and liver fat. We aimed to study the association between the Dutch Healthy Diet Index (DHD-index) and total body fat, visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) in middle-aged men and women. Design In this cross-sectional study, VAT was assessed by magnetic resonance imaging (MRI) in 2580 participants, and HTGC by proton-MR spectroscopy in 2083 participants. Habitual dietary intake and physical activity were estimated by questionnaire. Adherence to the current Dutch dietary guidelines was estimated by the 2015 DHD-index score based on the thirteen components (vegetables, fruit, wholegrain products, legumes, nuts, dairy, fish, tea, liquid fats, red meat, processed meat, sweetened beverages, and alcohol). The DHD-index ranges between 0 and 130 with a higher score indicating a healthier diet. We used linear regression to examine associations of the DHD-index with VAT and HTGC, adjusted for age, smoking, education, ethnicity, basal metabolic rate, energy restricted diet, menopausal state, physical activity, total energy intake, and total body fat. We additionally excluded the components one by one to examine individual contributions to the associations. Results Included participants (43% men) had a mean (SD) age of 56 (6) years and DHD-index score of 71 (15). A 10-point higher DHD-index score was associated with 2.3 cm(2) less visceral fat (95% CI; -3.5; -1.0 cm(2)) and less liver fat (0.94 times, 95% CI; 0.90; 0.98). Of all components, exclusion of dairy attenuated the associations with TBF and VAT. Conclusions Adherence to the dietary guidelines as estimated by the DHD-index was associated with less total body fat, and with less visceral and liver fat after adjustment for total body fat. These findings might contribute to better understanding of the mechanisms underlying associations between dietary habits and cardiometabolic diseases. Show less
Rafiq, R.; Walschot, F.; Lips, P.; Lamb, H.J.; Roos, A. de; Rosendaal, F.R.; ... ; Mutsert, R. de 2019
Background & aims: Obesity is a well-established risk factor of vitamin D deficiency. However, it is unclear which fat deposit is most strongly related to serum 25-hydroxyvitamin D (25(OH)D)... Show moreBackground & aims: Obesity is a well-established risk factor of vitamin D deficiency. However, it is unclear which fat deposit is most strongly related to serum 25-hydroxyvitamin D (25(OH)D) concentrations. Our aim was to distinguish the specific contributions of total body fat (TBF), abdominal subcutaneous adipose tissue (aSAT), visceral adipose tissue (VAT) and hepatic fat on 25(OH)D concentrations.Methods: We performed a cross-sectional analysis of the Netherlands Epidemiology of Obesity study, a population-based cohort study. We used linear regression analyses to examine associations of TBF, aSAT, VAT (n = 2441) and hepatic fat (n = 1980) with 25(OH)D concentrations. Standardized values were used to compare the different fat deposits.Results: Mean (SD) age and 25(OH)D concentrations of the study population was 56 (6) years and 70.8 (24.2) nmol/L, respectively. TBF was inversely associated with 25(OH)D concentrations in women, but not in men. One percent higher TBF was associated with 0.40 nmol/L (95%CI: -0.67 to -0.13) lower 25(OH)D. aSAT was not associated with 25(OH)D concentrations. One cm 2 higher VAT was associated with 0.05 nmol/L (-0.09 to -0.02) lower 25(OH)D in men, and 0.06 nmol/L (-0.10 to -0.01) lower 25(OH)D in women. Hepatic fat was only associated with 25(OH)D in men. A tenfold increase in hepatic fat was associated with 6.21 nmol/L (-10.70 to -1.73) lower 25(OH)D. Regressions with standardized values showed VAT was most strongly related to 25(OH)D.Conclusions: In women, TBF and VAT were inversely related to 25(OH)D concentrations. In men, VAT and hepatic fat were inversely related to 25(OH)D concentrations. In both groups, VAT was most strongly associated with 25(OH)D concentrations. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Show less
Boone, S.; Mook-Kanamori, D.; Rosendaal, F.; Heijer, M. den; Lamb, H.; Roos, A. de; ... ; Mutsert, R. de 2019
ObjectiveTo determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population.MethodsSerum... Show moreObjectiveTo determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population.MethodsSerum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion.ResultsDuring a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09-1.52]; highest vs middle quintile 1.20 [1.00-1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%-62%) and 41% (15%-74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001).ConclusionLow and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion. Show less
Elders, B.; Westenberg, J.; Boogaard, P. van den; Calkoen, E.; Blom, N.; Kroft, L.; ... ; Roest, A. 2019
OBJECTIVE. Correcting the perfusion in areas distal to coronary stenosis (risk) according to that of normal (remote) areas defines the relative myocardial perfusion index, which is similar to the... Show moreOBJECTIVE. Correcting the perfusion in areas distal to coronary stenosis (risk) according to that of normal (remote) areas defines the relative myocardial perfusion index, which is similar to the fractional flow reserve (FFR) concept. The aim of this study was to assess the value of relative myocardial perfusion by MRI in predicting lesion-specific inducible ischemia as defined by FFR.MATERIALS AND METHODS. Forty-six patients (33 men and 13 women; mean [+/- SD] age, 61 +/- 9 years) who underwent adenosine perfusion MRI and FFR measurement distal to 49 coronary artery stenoses during coronary angiography were retrospectively evaluated. Subendocardial time-enhancement maximal upslopes, normalized by the respective left ventricle cavity upslopes, were obtained in risk and remote subendocardium during adenosine and rest MRI perfusion and were correlated to the FFR values.RESULTS. The mean FFR value was 0.84 +/- 0.09 (range, 0.60-0.98) and was less than or equal to 0.80 in 31% of stenoses (n = 15). The relative subendocardial perfusion index (risk-to-remote upslopes) during hyperemia showed better correlations with the FFR value (r = 0.59) than the uncorrected risk perfusion parameters (i.e., both the upslope during hyperemia and the perfusion reserve index [stress-to-rest upslopes]; r = 0.27 and 0.29, respectively). A cutoff value of 0.84 of the relative subendocardial perfusion index had an ROC AUC of 0.88 to predict stenosis at an FFR of less than or equal to 0.80.CONCLUSION. Using adenosine perfusion MRI, the relative myocardial perfusion index enabled the best prediction of FFR-defined lesion-specific myocardial ischemia. This index could be used to noninvasively determine the need for revascularization of known coronary stenoses. Show less
Elders, B.; Westenberg, J.; Boogaard, P. van den; Calkoen, E.; Blom, N.; Kroft, L.; ... ; Roest, A. 2019
Aim: In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this... Show moreAim: In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics in the ascending aorta. Methods: In total, 30 patients after atrioventricular septal defect correction (age 27.6 +/- 12.8 years) and 28 healthy volunteers (age 24.8 +/- 13.7 years) underwent 4D flow cardiovascular magnetic resonance. Left ventricular ejection fraction and mean and peak wall shear stress calculated at ascending aortic peak systole were obtained from cardiovascular magnetic resonance. Left ventricular outflow tract data including velocity and diameter were obtained from echocardiography. Results: Patients showed a higher mean (911 +/- 173 versus 703 +/- 154 mPa, p = 0.001) and peak ascending aortic wall shear stress (1264 +/- 302 versus 1009 +/- 240 mPa, p = 0.001) compared to healthy volunteers. Increased blood flow velocities over the left ventricular outflow tract (1.49 +/- 0.30 m/s versus 1.22 +/- 0.20 m/s, p < 0.001) correlated well with mean and peak ascending aortic wall shear stress (r = 0.67, p < 0.001 and r = 0.77, p < 0.001). Conclusion: After atrioventricular septal defect correction, increased wall shear stress was observed, which correlated to velocities over the left ventricular outflow tract. These findings imply that altered outflow tract geometry contributes to changed aortic haemodynamics. Show less
Kroft, L.J.M.; Velden, L. van der; Giron, I.H.; Roelofs, J.J.H.; Roos, A. de; Geleijns, J. 2019
Purpose: The purpose of this study was to assess the clinical value of ultra-low-dose computed tomography (ULDCT) compared with chest x-ray radiography (CXR) for diagnosing chest pathology.... Show morePurpose: The purpose of this study was to assess the clinical value of ultra-low-dose computed tomography (ULDCT) compared with chest x-ray radiography (CXR) for diagnosing chest pathology. Materials and Methods: A total of 200 patients referred for CXR by outpatient clinics or general practitioners were enrolled prospectively. They underwent CXR (posteroanterior and lateral) and ULDCT (120 kV, 3 mAs) on the same day. In-room time and effective dose were recorded for each examination. Studies were categorized whether they were diagnostic or not, relevant radiologic diagnostic findings were reported, and confidence for diagnosis was recorded by a Likert scale. Differences in diagnostic confidence and effect on management decision were compared. Results: In-room time was <2 minutes for CXR and <3 minutes for ULDCT. Effective dose was 0.040 mSv for CXR and 0.071 mSv for ULDCT. CXR was considered diagnostic in 98% and ULDCT in 100%. The mean perceived confidence for diagnosis was 88 +/- 12% with CXR and 98 +/- 2% with ULDCT (P<0.0001), whereas discrepant findings between CXR and ULDCT were found in 101 of 200 patients. As compared with CXR, ULDCT had added value for management decisions in 40 of 200 patients. Conclusions: ULDCT provided added value to the radiologist by improved perceived confidence with a reduction in false-positive and false-negative CXR investigations that had management implications in 20% of patients. The effective dose of ULDCT will not be a limiting factor for introducing ULDCT of the chest on a broad scale in clinical practice. Show less
Eekelen, E. van; Beulens, J.W.J.; Geelen, A.; Schrauwen-Hinderling, V.B.; Lamb, H.; Roos, A. de; ... ; Mutsert, R. de 2019
