Publications by authors named "Maureen J van der Vlugt"

21 Publications

  • Page 1 of 1

Low Plasma Volume and Increased Pressure Load Relate to Concentric Left Ventricular Remodeling After Preeclampsia: A Longitudinal Study.

J Am Heart Assoc 2020 10 13;9(19):e015043. Epub 2020 Sep 13.

Department of Obstetrics and Gynecology Research School GROW Maastricht University Medical Center Maastricht the Netherlands.

Background During uncomplicated pregnancy, left ventricular remodeling occurs in an eccentric way. In contrast, during preeclamptic gestation, the left ventricle hypertrophies concentrically, concurrent with loss in circulatory volume and increased blood pressure. Concentric cardiac structure persists in a substantial proportion of women and may be associated with pressure and volume load after preeclampsia. We hypothesize that low volume load, as indicated by plasma volume (PV) after preeclampsia and increased pressure load, is associated with remote concentric remodeling. Methods and Results In this longitudinal cohort study, we included 100 formerly preeclamptic women. Two visits were performed: at 0.8 years postpartum and at 4.8 years postpartum. During visit 1, we measured blood pressure and PV (I dilution technique, low PV ≤48 mL/kg lean body mass). During the second visit, we assessed cardiac geometry by cardiac ultrasound. Concentric remodeling was defined as relative wall thickness >0.42 and left ventricular mass index ≤95 g/m. We adjusted multivariable analysis for primiparity, systolic blood pressure, PV mL/kg lean body mass, and antihypertensive medication at visit 1. Low PV is associated with remote concentric remodeling (odds ratio [OR], 4.37; 95% CI, 1.06-17.40; and adjusted OR, 4.67; 95% CI, 1.02-21.42). Arterial pressure load (systolic, diastolic, and mean arterial pressure) is also associated with development of concentric remodeling (OR, 1.15 [95% CI, 0.99-1.35]; OR, 1.24 [95% CI, 0.98-1.58]; and OR, 1.20 [95% CI, 0.98-1.47], respectively). Conclusions In former preeclamptic women, development toward left ventricular concentric remodeling is associated with low volume load and increased pressure load.
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http://dx.doi.org/10.1161/JAHA.119.015043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792392PMC
October 2020

Coronary anatomy in Turner syndrome versus patients with isolated bicuspid aortic valves.

Heart 2019 05 27;105(9):701-707. Epub 2018 Oct 27.

Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.

Objective: Variations in coronary anatomy, like absent left main stem and left dominant coronary system, have been described in patients with Turner syndrome (TS) and in patients with bicuspid aortic valves (BAV). It is unknown whether coronary variations in TS are related to BAV and to specific BAV subtypes.

Aim: To compare coronary anatomy in patients with TS with/without BAV versus isolated BAV and to study BAV morphology subtypes in these groups.

Methods: Coronary anatomy and BAV morphology were studied in 86 patients with TS (20 TS-BAV, 66 TS-tricuspid aortic valve) and 86 patients with isolated BAV (37±13 years vs 42±15 years, respectively) by CT.

Results: There was no significant difference in coronary dominance between patients with TS with and without BAV (25% vs 21%, p=0.933). BAVs with fusion of right and left coronary leaflets (RL BAV) without raphe showed a high prevalence of left coronary dominance in both TS-BAV and isolated BAV (both 38%). Absent left main stem was more often seen in TS-BAV as compared with isolated BAV (10% vs 0%). All patients with TS-BAV with absent left main stem had RL BAV without raphe.

Conclusion: The equal distribution of left dominance in RL BAV without raphe in TS-BAV and isolated BAV suggests that presence of left dominance is a feature of BAVs without raphe, independent of TS. Both TS and RL BAV without raphe seem independently associated with absent left main stems. Awareness of the higher incidence of particularly absent left main stems is important to avoid complications during hypothermic perfusion.
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http://dx.doi.org/10.1136/heartjnl-2018-313724DOI Listing
May 2019

Intermodality variation of aortic dimensions: How, where and when to measure the ascending aorta.

Int J Cardiol 2019 Feb 24;276:230-235. Epub 2018 Aug 24.

Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address:

Background: No established reference-standard technique is available for ascending aortic diameter measurements. The aim of this study was to determine agreement between modalities and techniques.

Methods: In patients with aortic pathology transthoracic echocardiography, computed tomography angiography (CTA) and magnetic resonance angiography (MRA) were performed. Aortic diameters were measured at the sinus of Valsalva (SoV), sinotubular junction (STJ) and tubular ascending aorta (TAA) during mid-systole and end-diastole. In echocardiography both the inner edge-to-inner edge (I-I edge) and leading edge-to‑leading edge (L-L edge) methods were applied, and the length of the aortic annulus to the most cranial visible part of the ascending aorta was measured. In CTA and MRA the I-I method was used.

Results: Fifty patients with bicuspid aortic valve (36 ± 13 years, 26% female) and 50 Turner patients (35 ± 13 years) were included. Comparison of all aortic measurements showed a mean difference of 5.4 ± 2.7 mm for the SoV, 5.1 ± 2.0 mm for the STJ and 4.8 ± 2.1 mm for the TAA. The maximum difference was 18 mm. The best agreement was found between echocardiography L-L edge and CTA during mid-systole. CTA and MRA showed good agreement. A mean difference of 1.5 ± 1.3 mm and 1.8 ± 1.5 mm was demonstrated at the level of the STJ and TAA comparing mid-systolic with end-diastolic diameters. The visible length of the aorta increased on average 5.3 ± 5.1 mmW during mid-systole.

Conclusions: MRA and CTA showed best agreement with L-L edge method by echocardiography. In individual patients large differences in ascending aortic diameter were demonstrated, warranting measurement standardization. The use of CTA or MRA is advised at least once.
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http://dx.doi.org/10.1016/j.ijcard.2018.08.067DOI Listing
February 2019

Improving the Diagnostic Performance of F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Prosthetic Heart Valve Endocarditis.

Circulation 2018 10;138(14):1412-1427

Department of Radiology and Nuclear Medicine (L.E.S., G.P.K., R.P.J.B.), Erasmus Medical Center, Rotterdam, The Netherlands.

Background: F-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments.

Methods: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded.

Results: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of ≥2.0 was a 100% sensitive and 91% specific predictor of PVE.

Conclusions: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035032DOI Listing
October 2018

Increased Risk of Pregnancy Complications After Stroke: The FUTURE Study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation).

Stroke 2018 04 6;49(4):877-883. Epub 2018 Mar 6.

From the Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Center for Neuroscience (M.E.v.A., M.d.V., R.M.A., H.S., E.J.v.D., F.-E.d.L.) and Department of Cardiology (M.J.v.d.V.), Radboud University Nijmegen Medical Center, the Netherlands; Center for Neurology and Neurorehabilitation, State Hospital, Switzerland (N.A.M.M.M.); Department of Neurology, St. Elisabeth Hospital, the Netherlands (N.E.S.); Division of Woman and Baby, Birth Center, University Utrecht Medical Center, the Netherlands (R.d.H.); and German Center for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany (L.C.A.R.-J.).

Background And Purpose: The study goal was to investigate the prevalence of pregnancy complications and pregnancy loss in women before, during, and after young ischemic stroke/transient ischemic attack.

Methods: In the FUTURE study (Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation), a prospective young stroke study, we assessed the occurrence of pregnancy, miscarriages, and pregnancy complications in 223 women aged 18 to 50 years with a first-ever ischemic stroke/transient ischemic attack. Pregnancy complications (gestational hypertension, diabetes mellitus, preeclampsia, and hemolysis, elevated liver enzymes, low platelet count syndrome) were assessed before, during, and after stroke using standardized questionnaires. Primary outcome was occurrence of pregnancy complications and the rate of pregnancy loss compared with the Dutch population. Secondary outcome was the risk of recurrent vascular events after stroke, stratified by a history of hypertensive disorder in pregnancy.

Results: Data were available for 213 patients. Mean age at event was 39.6 years (SD=7.8) and mean follow-up 9.5 years (SD=8.5). Miscarriages occurred in 35.2% and fetal death in 6.2% versus 13.5% and 0.9% in the Dutch population, respectively (<0.05). In nulliparous women after stroke (n=22), in comparison with Dutch population, there was a high prevalence of hypertensive disorders in pregnancy (33.3 versus 12.2%; <0.05), hemolysis, elevated liver enzymes, low platelet count syndrome (9.5 versus 0.5%; <0.05), and early preterm delivery <32 weeks (9.0 versus 1.4%; <0.05). In primi/multiparous women (n=141) after stroke, 29 events occurred (20-year cumulative risk 35.2%; 95% confidence interval, 21.3-49.0), none during subsequent pregnancies, and a history of a hypertensive disorder in pregnancy did not modify this risk (log-rank =0.62).

Conclusions: When compared with the general population, women with young stroke show higher rates of pregnancy loss throughout their lives. Also, after stroke, nulliparous women more frequently experienced serious pregnancy complications.
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http://dx.doi.org/10.1161/STROKEAHA.117.019904DOI Listing
April 2018

Prothrombotic factors do not increase the risk of recurrent ischemic events after cryptogenic stroke at young age: the FUTURE study.

J Thromb Thrombolysis 2018 May;45(4):504-511

Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, RadboudUMC, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Background: The role of hypercoagulable states and preceding infections in the etiology of young stroke and their role in developing recurrent ischemic events remains unclear. Our aim is to determine the prevalence of these conditions in patients with cryptogenic stroke at young age and to assess the long-term risk of recurrent ischemic events in patients with and without a hypercoagulable state or a recent pre-stroke infection with Borrelia or Syphilis.

Patients And Methods: We prospectively included patients with a first-ever transient ischemic attack or ischemic stroke, aged 18-50, admitted to our hospital between 1995 and 2010. A retrospective analysis was conducted of prothrombotic factors and preceding infections. Outcome was recurrent ischemic events.

Results: Prevalence of prothrombotic factors did not significantly differ between patients with a cryptogenic stroke and with an identified cause (24/120 (20.0%) and 32/174 (18.4%) respectively). In patients with a cryptogenic stroke the long-term risk [mean follow-up of 8.9 years (SD 4.6)] of any recurrent ischemic event or recurrent cerebral ischemia did not significantly differ between patients with and without a hypercoagulable state or a recent infection. In patients with a cryptogenic stroke 15-years cumulative risk of any recurrent ischemic event was 24 and 23% in patients with and without any prothrombotic factor respectively.

Conclusions: The prevalence of prothrombotic factors and preceding infections did not significantly differ between stroke patients with a cryptogenic versus an identified cause of stroke and neither is significantly associated with an increased risk of recurrent ischemic events after cryptogenic stroke.
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http://dx.doi.org/10.1007/s11239-018-1631-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889776PMC
May 2018

Risk factors and mechanisms of stroke in young adults: The FUTURE study.

J Cereb Blood Flow Metab 2018 09 23;38(9):1631-1641. Epub 2017 May 23.

1 Department of Neurology, Center for Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.

Incidence of ischemic stroke and transient ischemic attack in young adults is rising. However, etiology remains unknown in 30-40% of these patients when current classification systems designed for the elderly are used. Our aim was to identify risk factors according to a pediatric approach, which might lead to both better identification of risk factors and provide a stepping stone for the understanding of disease mechanism, particularly in patients currently classified as "unknown etiology". Risk factors of 656 young stroke patients (aged 18-50) of the FUTURE study were categorized according to the "International Pediatric Stroke Study" (IPSS), with stratification on gender, age and stroke of "unknown etiology". Categorization of risk factors into ≥1 IPSS category was possible in 94% of young stroke patients. Chronic systemic conditions were more present in patients aged <35 compared to patients ≥35 (32.6% vs. 15.6%, p < 0.05). Among 226 patients classified as "stroke of unknown etiology" using TOAST, we found risk factors in 199 patients (88%) with the IPSS approach. We identified multiple risk factors linked to other mechanisms of stroke in the young than in the elderly . This can be a valuable starting point to develop an etiologic classification system specifically designed for young stroke patients.
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http://dx.doi.org/10.1177/0271678X17707138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120122PMC
September 2018

The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age: The FUTURE study.

Eur Stroke J 2016 Dec 14;1(4):337-345. Epub 2016 Oct 14.

Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, Nijmegen, The Netherlands.

Introduction: Patients who suffer a stroke at a young age, remain at a substantial risk of developing recurrent vascular events and information on very long-term prognosis and its risk factors is indispensable. Our aim is to investigate this very long-term risk and associated risk factors up to 35 years after stroke.

Patients And Methods: Prospective cohort study among 656 patients with a first-ever ischaemic stroke or transient ischaemic stroke (TIA), aged 18-50, who visited our hospital (1980-2010). Outcomes assessed at follow-up (2014-2015) included TIA or ischaemic stroke and other arterial events, whichever occurred first. Kaplan-Meier analysis quantified cumulative risks. A prediction model was constructed to assess risk factors independently associated with any ischaemic event using Cox proportional hazard analyses followed by bootstrap validation procedure to avoid overestimation.

Results: Mean follow-up was 12.4 (SD 8.2) years (8105 person-years). Twenty-five years cumulative risk was 45.4% (95%CI: 39.4-51.5) for any ischaemic event, 30.1% (95%CI: 24.8-35.4) for cerebral ischaemia and 27.0% (95%CI: 21.1-33.0) for other arterial events. Risk factors retained in the prediction model were smoking (HR 1.35, 95%CI: 1.04-1.74), poor kidney function (HR 2.10, 95%CI: 1.32-3.35), history of peripheral arterial disease (HR 2.10, 95%CI: 1.08-3.76) and cardiac disease (HR 1.84, 95%CI: 1.06-3.18) (C-statistic 0.59 (95%CI: 0.55-0.64)).

Discussion And Conclusion: Young stroke patients remain at a substantial risk for recurrent events; almost 1 of 2 develops a recurrent ischaemic event and 1 of 3 develops a recurrent stroke or TIA during 25 years of follow-up. Risk factors independently associated with recurrent events were poor kidney function, smoking, history of peripheral arterial disease and cardiac disease.
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http://dx.doi.org/10.1177/2396987316673440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301250PMC
December 2016

Kidney Dysfunction Increases Mortality and Incident Events after Young Stroke: The FUTURE Study.

Cerebrovasc Dis 2016 14;42(3-4):224-31. Epub 2016 May 14.

Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: In about 30% of young stroke patients, no cause can be identified. In elderly patients, kidney dysfunction has been suggested as a contributing risk factor for mortality as well as stroke. There are hypotheses that novel non-traditional risk factors, like chronic inflammation and oxidative stress, are involved in chronic kidney disease, affecting the cerebral microvasculature that would in turn lead to stroke. Our objective is to investigate the influence of kidney dysfunction on long-term mortality and incident vascular events after stroke in young adults aged 18 through 50 and if this relationship would be independent of other cardiovascular risk factors.

Methods: We prospectively included 460 young stroke patients with an ischemic stroke or transient ischemic attack admitted to our department between January 1, 1980 and November 1, 2010. Follow-up was done between 2014 and 2015. Estimated glomerular filtration rate (eGFR) was calculated from baseline creatinine levels and was divided in 3 subgroups: eGFR <60, 60-120 and >120 ml/min/1.73 m2. Cox proportional hazard models were used to determine the effect of kidney dysfunction on mortality and incident vascular events, adjusting for cardiovascular risk factors.

Results: An eGFR <60 (HR 4.6; 95% CI 2.6-8.2) was associated with an increased risk of death and an increased risk of incident stroke (HR 4.1; 95% CI 1.9-9.0) independent of cardiovascular risk factors, but it was not associated with other vascular events. The point estimate for the 15-year cumulative mortality was 70% (95% CI 46-94) for patients with a low eGFR, 24% (95% CI 18-30) for patients with a normal eGFR and 30% (95% CI 12-48) for patients with a high eGFR. The point estimate for the 15-year cumulative risk of incident stroke was 45% (95% CI 16-74) for patients with a low eGFR, 13% (95% CI 9-17) for patients with a normal eGFR and 8% (95% CI 0-18) for patients with a high eGFR.

Conclusions: Kidney dysfunction is related to long-term mortality and stroke recurrence, but not to incident cardiovascular disease, on average 11 years after young stroke. This warrants a more intensive follow-up of young stroke patients with signs of kidney dysfunction in the early phase. In addition, the clear association between kidney dysfunction and incident stroke seen in our young stroke population might be a first step in the recognition of kidney dysfunction as a new risk factor for the development of stroke at young age. Also, it can lead to new insights in the etiological differences between cardiovascular and cerebrovascular disease.
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http://dx.doi.org/10.1159/000444683DOI Listing
November 2017

[Choosing wisely when prescribing statins].

Ned Tijdschr Geneeskd 2015 ;159:A8695

Radboudumc, Nijmegen.

The Dutch campaign 'Verstandig kiezen', based on the American programme 'Choosing wisely', aims to improve quality in healthcare, with attention to cost control. The 'Choosing wisely'-based programme can be applied in the choice of a statin. Atorvastatin and rosuvastatin are regarded as equal choices in various guidelines regarding cardiovascular risk management. Generic atorvastatin is available, and is approximately 25 times cheaper than rosuvastatin in almost equipotent doses. Rosuvastatin provides a greater LDL reduction than atorvastatin. Patient LDL targets can usually be achieved with atorvastatin, and rosuvastatin is not needed. At group level, there are no relevant differences in adverse-events profile between both statins. Atorvastatin and rosuvastatin do have different pharmacokinetic interactions. When changing medication, good provision of information is a prerequisite for patient satisfaction and compliance. We advise use of atorvastatin instead of rosuvastatin as drug of choice when the LDL target is not reached using simvastatin. However, under specific conditions, rosuvastatin should be the treatment of choice. Efficacy and adverse effects should then be evaluated at individual patient level.
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October 2015

Observational Dutch Young Symptomatic StrokE studY (ODYSSEY): study rationale and protocol of a multicentre prospective cohort study.

BMC Neurol 2014 Mar 22;14:55. Epub 2014 Mar 22.

Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience, department of Neurology, PO Box 9101, 6500, HB Nijmegen, the Netherlands.

Background: The proportion of strokes occurring in younger adults has been rising over the past decade. Due to the far longer life expectancy in the young, stroke in this group has an even larger socio-economic impact. However, information on etiology and prognosis remains scarce.

Methods/design: ODYSSEY is a multicentre prospective cohort study on the prognosis and risk factors of patients with a first-ever TIA, ischemic stroke or intracerebral hemorrhage aged 18 to 49 years. Our aim is to include 1500 patients. Primary outcome will be all cause mortality and risk of recurrent vascular events. Secondary outcome will be the risk of post-stroke epilepsy and cognitive impairment. Patients will complete structured questionnaires on outcome measures and risk factors. Both well-documented and less well-documented risk factors and potentially acute trigger factors will be investigated. Patients will be followed every 6 months for at least 3 years. In addition, an extensive neuropsychological assessment will be administered both at baseline and 1 year after the stroke/TIA. Furthermore we will include 250 stroke-free controls, who will complete baseline assessment and one neuropsychological assessment.

Discussion: ODYSSEY is designed to prospectively determine prognosis after a young stroke and get more insight into etiology of patients with a TIA, ischemic stroke and intracerebral hemorrhage in patients aged 18 to 49 years old in a large sample size.
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http://dx.doi.org/10.1186/1471-2377-14-55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998025PMC
March 2014

High incidence of diabetes after stroke in young adults and risk of recurrent vascular events: the FUTURE study.

PLoS One 2014 23;9(1):e87171. Epub 2014 Jan 23.

Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.

Background: Diabetes diagnosed prior to stroke in young adults is strongly associated with recurrent vascular events. The relevance of impaired fasting glucose (IFG) and incidence of diabetes after young stroke is unknown. We investigated the long-term incidence of diabetes after young stroke and evaluated the association of diabetes and impaired fasting glucose with recurrent vascular events.

Methods: This study was part of the FUTURE study. All consecutive patients between January 1, 1980, and November 1, 2010 with TIA or ischemic stroke, aged 18-50, were recruited. A follow-up assessment was performed in survivors between November 1, 2009 and January 1, 2012 and included an evaluation for diabetes, fasting venous plasma glucose and recurrent vascular events. The association of diabetes and IFG with recurrent vascular events was assessed by logistic regression analysis, adjusted for age, sex and follow-up duration.

Results: 427 survivors without a medical history of diabetes were included in the present analysis (mean follow-up of 10.1 (SD 8.4) years; age 40.3 (SD 7.9) years). The incidence rate of diabetes was 7.9 per 1000 person-years and the prevalence of IFG was 21.1%. Patients with diabetes and IFG were more likely to have experienced any vascular event than those with normal fasting glucose values (OR 3.5 (95%CI 1.5-8.4) for diabetes and OR 2.5 (95%CI 1.3-4.8) for IFG).

Conclusions: Diabetes or IFG in young stroke survivors is frequent and is associated with recurrent vascular events. Regular screening for IFG and diabetes in this population, yields potential for secondary prevention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087171PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900719PMC
September 2014

Cardiovascular and thrombogenic risk of decidual vasculopathy in preeclampsia.

Am J Obstet Gynecol 2014 Jun 24;210(6):545.e1-6. Epub 2013 Dec 24.

GROW, School for Oncology and Developmental Biology, Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht, The Netherlands.

Objective: Women with a history of preeclampsia (PE) have an increased prevalence of cardiometabolic, cardiovascular, and prothrombotic risk factors. Remotely, these women are at increased risk of developing cardiovascular and thrombotic disease. Decidual vasculopathy (DV) describes vascular lesions in the maternal spiral arteries of the uterus, which are found in approximately 40-60% of women with PE. DV is thought to be related to atherosclerosis because of their morphological similarity. The aim of this study was to investigate the association of cardiovascular and thrombogenic risk factors with DV in women with a history of PE.

Study Design: We retrospectively analyzed the cardiovascular and thrombogenic risk of women with a history of PE, comparing cases with DV (n = 95) with cases without the lesions (n = 81) 7 months after the index pregnancy. Data from a cohort of patients with a history of PE were matched with records from our pathology database.

Results: The DV group showed higher diastolic blood pressure (73 vs 70 mm Hg, P = .031), lower left ventricular stroke volume (71 vs 76 mL, P = .032), higher total peripheral vascular resistance (1546 vs 1385, P = .009), and a higher percentage of low plasma volume (34% vs 19%, P = .030). DV did not relate to other cardiovascular parameters, urinary protein, body mass index, lipid or glucose metabolism parameters, or thrombophilia.

Conclusion: In this study, in women with a history of PE, cases with DV had increased cardiovascular risk, exhibiting circulatory alterations, suggesting reduced venous reserves and elevated arterial tone, without metabolic or thrombophilic disturbances.
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http://dx.doi.org/10.1016/j.ajog.2013.12.029DOI Listing
June 2014

Long-term risk of recurrent vascular events after young stroke: The FUTURE study.

Ann Neurol 2013 Oct 3;74(4):592-601. Epub 2013 Jul 3.

Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Center, Nijmegen.

Objective: Long-term data on recurrent vascular events after young stroke are limited. Our objective was to examine the long-term risk of recurrent vascular events after young stroke.

Methods: We prospectively included 724 consecutive patients with a first-ever transient ischemic attack (TIA), ischemic stroke, or intracerebral hemorrhage (ICH), aged 18 to 50 years, admitted to our hospital between January 1, 1980 and November 1, 2010. Outcomes were (1) stroke; (2) myocardial infarction or cardiac or peripheral arterial revascularization procedures; or (3) composite event of these, whichever occurred first.

Results: After a mean follow-up of 9.1 years (standard deviation = 8.2, range = 0-31.0), 142 patients (19.6%) had at least 1 recurrent vascular event. Cumulative 20-year risk of stroke was 17.3% (95% confidence interval [CI] = 9.5-25.1) after TIA, 19.4% (95% [CI] = 14.6-24.3) after ischemic stroke, and 9.8% (95% CI = 1.0-18.7) after ICH. Cumulative 20-year risk of any vascular event was 27.7% (95% CI = 18.5-37.0) after TIA and 32.8% (95% CI = 26.7-38.9) after ischemic stroke. Age and male sex were associated with other arterial events, but not with stroke. Among TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes, adjusted for age, sex, and decennium of inclusion, atherothrombotic stroke, cardioembolic stroke, and lacunar stroke were associated with recurrent stroke (hazard ratio [HR] = 2.72, 95% CI = 1.34-5.52; HR = 2.49, 95% CI = 1.23-5.07; and HR = 2.92, 95% CI = 1.45-5.88, respectively).

Interpretation: Patients with young stroke remain at substantial risk of recurrent vascular events for decades, suggesting that the underlying disease that caused stroke at a young age continues to put these patients at a high risk for vascular disease throughout their lives.
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http://dx.doi.org/10.1002/ana.23953DOI Listing
October 2013

Impaired fetal growth and low plasma volume in adult life.

Obstet Gynecol 2011 Dec;118(6):1314-1322

From the Departments of Obstetrics and Gynecology, Physiology, Nuclear Medicine, and Cardiology, Radboud University Nijmegen Medical Centre, Nijmegen, and Research School GROW, Maastricht University Medical Centre, Maastricht, The Netherlands.

Objective: To estimate whether normotensive women who were born small for gestational age have low plasma volume in adult life, which is associated with later chronic hypertension.

Methods: In 280 normotensive women with a history of hypertension in pregnancy, we recorded recalled gestational age and weight at birth and measured plasma volume (I-human serum albumin indicator dilution method). To correct for possible confounders, we recorded recent obstetric history and measured in each individual all constituents of the metabolic syndrome (World Health Organization criteria), sex hormones (progesterone and estradiol), renal function, and cardiac performance at rest (echocardiography). We estimated daily activity level with a validated questionnaire (Short Questionnaire to Assess Health-enhancing physical activity). We studied the relation between women's own birth weight centile and her adult plasma volume (mL) and adjusted for the effects of confounding variables using multiple linear regression analysis.

Results: Birth weight correlated positively with adult plasma volume (P<.001). Linear regression analysis demonstrated that each 10 centile change in birth weight is associated with an average change of 46.6 mL (95% confidence interval [CI] 30.8-62.3) in adult plasma volume. This association persisted after adjustment for confounding factors (current body surface area, mean arterial pressure, total vascular resistance, glomerular filtration rate, and a total 24 hours of sodium output). After adjustment, each 10 centile change in birth weight was associated with an average change of 32.1 mL (95% CI 19.6-44.6) in adult plasma volume. Birth centile contributes 14% to the variation in total adult plasma volume.

Conclusion: Impaired fetal growth is associated with low plasma volume in adult life.

Level Of Evidence: II.
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http://dx.doi.org/10.1097/AOG.0b013e3182383781DOI Listing
December 2011

Risk factors and prognosis of young stroke. The FUTURE study: a prospective cohort study. Study rationale and protocol.

BMC Neurol 2011 Sep 20;11:109. Epub 2011 Sep 20.

Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Background: Young stroke can have devastating consequences with respect to quality of life, the ability to work, plan or run a family, and participate in social life. Better insight into risk factors and the long-term prognosis is extremely important, especially in young stroke patients with a life expectancy of decades. To date, detailed information on risk factors and the long-term prognosis in young stroke patients, and more specific risk of mortality or recurrent vascular events, remains scarce.

Methods/design: The FUTURE study is a prospective cohort study on risk factors and prognosis of young ischemic and hemorrhagic stroke among 1006 patients, aged 18-50 years, included in our study database between 1-1-1980 and 1-11-2010. Follow-up visits at our research centre take place from the end of 2009 until the end of 2011. Control subjects will be recruited among the patients' spouses, relatives or social environment. Information on mortality and incident vascular events will be retrieved via structured questionnaires. In addition, participants are invited to the research centre to undergo an extensive sub study including MRI.

Discussion: The FUTURE study has the potential to make an important contribution to increase the knowledge on risk factors and long-term prognosis in young stroke patients. Our study differs from previous studies by having a maximal follow-up of more than 30 years, including not only TIA and ischemic stroke but also hemorrhagic stroke, the addition of healthy controls and prospectively collect data during an extensive follow-up visit. Completion of the FUTURE study may provide better information for treating physicians and patients with respect to the prognosis of young stroke.
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http://dx.doi.org/10.1186/1471-2377-11-109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185265PMC
September 2011

Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol.

BMC Neurol 2011 Feb 28;11:29. Epub 2011 Feb 28.

Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Background: Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated.

Methods/design: The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI.

Discussion: The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from "normal" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism.
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http://dx.doi.org/10.1186/1471-2377-11-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053228PMC
February 2011

Is standardized cardiac assessment of asymptomatic high-risk renal transplant candidates beneficial?

Nephrol Dial Transplant 2011 Sep 14;26(9):3006-12. Epub 2011 Feb 14.

Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Background: Perioperative cardiovascular events in renal transplantation are common and non-invasive cardiac stress tests are recommended in high-risk renal transplant candidates. In 2004, we introduced a standardized preoperative cardiac risk assessment programme with the aim of reducing perioperative cardiac events.

Methods: Since 2004, all asymptomatic high-risk renal transplant candidates had to undergo non-invasive cardiac stress testing. Patients with a positive stress test went for a coronary angiography and if indicated for revascularization. The incidence of perioperative cardiac events (≤30 days of transplantation) was analysed in all high-risk patients who received a transplantation (screening group) and compared with high-risk renal transplant recipients evaluated in the 4 years before the introduction of the cardiac assessment programme (historical control group).

Results: Since 2004, 227 of 349 asymptomatic high-risk renal transplant candidates underwent non-invasive cardiac stress testing. In 15 patients (6.6%), significant ischaemia was found. Ten of these 15 patients underwent coronary angiography (eight patients had significant coronary artery disease and in five patients, percutaneous coronary intervention was performed). One hundred and sixty of 349 renal transplant candidates have received renal transplantation so far (screening group). In the screening group, 6 perioperative cardiac events (3.8%) occurred compared to 13 perioperative events (7.6%) in the historical control group (n = 172) (P = 0.136).

Conclusions: The incidence of significant cardiac ischaemia in high-risk renal transplant patients was low and was followed by revascularization in a small percentage of patients. No significant decrease in perioperative cardiac events was observed after the introduction of the standardized cardiac assessment programme.
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http://dx.doi.org/10.1093/ndt/gfq822DOI Listing
September 2011

Cardiac diastolic dysfunction and metabolic syndrome in young women after placental syndrome.

Obstet Gynecol 2010 Jan;115(1):101-108

From the Departments of Obstetrics and Gynecology and Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Objective: To estimate whether women with a recent history of a placental syndrome and concomitant metabolic syndrome have reduced cardiac diastolic function.

Methods: In this cohort study, women with a history of a placental syndrome were included. We assessed body mass index, blood pressure, fasting serum lipids, glucose and insulin levels, and 24-hour urinary protein and albumin output after an interval of at least 6 months postpartum. Cardiac diastolic function was assessed by echocardiography.

Results: Metabolic syndrome was found in 22% of the women evaluated. Diastolic dysfunction was seen in 24% of the women with the metabolic syndrome compared with 6.3% in those without (odds ratio 4.77, 95% confidence interval 2.18-10.41; adjusted odds ratio 6.09, 95% confidence interval 2.64-14.04). Univariable analysis showed that all the constituents of the metabolic syndrome related to diastolic dysfunction.

Conclusion: In women with a history of placental syndrome complicating pregnancy, the presence of metabolic syndrome increases the risk of cardiac diastolic dysfunction fourfold.

Level Of Evidence: II.
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http://dx.doi.org/10.1097/AOG.0b013e3181c4f1e8DOI Listing
January 2010

Preoperative cardiac testing before major vascular surgery.

J Nucl Cardiol 2007 Nov-Dec;14(6):885-91

Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.nuclcard.2007.09.018DOI Listing
January 2008

Feelings of being disabled as a risk factor for mortality up to 8 years after acute myocardial infarction.

J Psychosom Res 2005 Oct;59(4):247-53

Thoraxcentre, Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.

Objective: We examined the independent prognostic value of the four subscales of the Heart Patients Psychological Questionnaire (HPPQ) on mortality in acute myocardial infarction (AMI) survivors up to 8 years after the event.

Methods: The HPPQ, which measures well-being, feelings of being disabled, despondency and social inhibition, was administered to 567 AMI patients during hospitalisation and at 3 months follow-up. The patients were followed for 8 years.

Results: During follow-up, 157 patients (28%) died. Forty-one percent of the patients had a score indicating at least mild to moderate feelings of being disabled. Patients with feelings of being disabled were at increased risk of mortality compared with those having a low score, adjusted for other cardiac risk factors [hazard ratio (HR)=1.8, 95% confidence interval (CI)=1.3-2.5]. There was no interaction between feelings of being disabled and gender. None of the other HPPQ subscales were related to mortality or recurrent myocardial infarction (MI). When the study population was stratified by low and high clinical risk (43% vs. 57%, respectively), feelings of being disabled was the most prominent predictor of mortality in the low-risk group (HR=3.5, 95% CI=1.4-8.8).

Conclusion: Feelings of being disabled measured at baseline and at 3 months was the most prominent predictor of mortality in low-risk patients 8 years post-MI. This finding adds to the existing knowledge that psychosocial variables influence morbidity and mortality in cardiac patients.
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http://dx.doi.org/10.1016/j.jpsychores.2005.03.003DOI Listing
October 2005
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