Publications (35)261.64 Total impact
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Article: Blood Pressure Parameters and Carotid Intraplaque Hemorrhage as Measured by Magnetic Resonance Imaging: The Rotterdam Study.
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ABSTRACT: Intraplaque hemorrhage (IPH) is a characteristic of the vulnerable atherosclerotic plaque that has been associated with ischemic stroke. Not much is known about determinants of IPH. We studied whether blood pressure parameters are associated with presence of IPH. Within the framework of a prospective population-based cohort study, The Rotterdam Study, the carotid arteries of 1006 healthy participants ≥45 years and with intima-media thickening (≥2.5 mm) on ultrasound were imaged with a 1.5-T magnetic resonance imaging scanner. IPH was defined as a hyperintense signal on a 3D-T1w-GRE magnetic resonance sequence. Generalized estimation equation analysis, adjusted for age, sex, carotid wall thickness, and cardiovascular risk factors, was used to assess the association between blood pressure parameters and IPH. Magnetic resonance imaging of the carotid arteries revealed presence of IPH in 444 of 1860 plaques (24%). Systolic blood pressure and pulse pressure (PP) were significantly associated with IPH after adjustment for age and sex. In multivariate analysis, PP yielded the strongest association, with an odds ratio per SD increase in PP of 1.22 (95% CI, 1.07-1.40). The odds ratio per SD for systolic blood pressure was 1.13 (0.99-1.28). Only PP remained significant after additional adjustment for other blood pressure components. The combination of smoking and isolated systolic hypertension was associated with 2.5 times increased risk of IPH (1.2-5.2). In conclusion, PP was the strongest determinant of IPH independent of cardiovascular risk factors and other blood pressure components. The association between pulsatile flow and IPH may provide novel insights in the development of the vulnerable plaque.Hypertension 12/2012; · 6.21 Impact Factor -
Article: Arterial stiffness and cerebral small vessel disease: the rotterdam scan study.
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ABSTRACT: Aging and vascular risk factors contribute to arterial stiffening. Increased arterial stiffness exposes the small vessels in the brain to abnormal flow pulsations and, as such, may contribute to the pathogenesis of cerebral small vessel disease. In a population-based study, we investigated the association between arterial stiffness, as measured by aortic pulse wave velocity (aPWV), and small vessel disease. Overall, 1460 participants (mean age, 58.2 years) underwent aPWV measurement and brain MRI scanning. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI analysis, we obtained white matter lesion volumes. Infarcts and microbleeds were rated visually. We used linear and logistic regression models to associate aPWV with small vessel disease, adjusting for age, sex, mean arterial pressure, and heart rate and additionally for cardiovascular risk factors. Subsequently, we explored associations in strata of hypertension. In the study group, higher aPWV was associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.07; 95% CI, 0.02-0.12) but not with lacunar infarcts or microbleeds. In persons with uncontrolled hypertension, higher aPWV was significantly associated with larger white matter lesion volume (difference in volume per SD increase in aPWV 0.09; 95% CI, 0.00-0.18), deep or infratentorial microbleeds (OR, 2.13; 95% CI, 1.16-3.91), and to a lesser extent also with lacunar infarcts (OR, 1.63; 95% CI, 0.98-2.70). No such associations were present in persons with controlled hypertension or without hypertension. In our study, increased arterial stiffness is associated with a larger volume of white matter lesions.Stroke 08/2012; 43(10):2637-42. · 5.73 Impact Factor -
Article: Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study.
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ABSTRACT: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear. To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions. Prospective population-based study. The Rotterdam Study, Rotterdam, the Netherlands. 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]). Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity). Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal. The findings may not be generalizable to younger or nonwhite populations. Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems. Primary Funding Source: Netherlands Organization for Health Research and Development (ZonMw).Annals of internal medicine 03/2012; 156(6):438-44. · 16.73 Impact Factor -
Article: Methods of data collection and definitions of cardiac outcomes in the Rotterdam Study.
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ABSTRACT: The prevalence of cardiovascular diseases is rising. Therefore, adequate risk prediction and identification of its determinants is increasingly important. The Rotterdam Study is a prospective population-based cohort study ongoing since 1990 in the city of Rotterdam, The Netherlands. One of the main targets of the Rotterdam Study is to identify the determinants and prognosis of cardiovascular diseases. Case finding in epidemiological studies is strongly depending on various sources of follow-up and clear outcome definitions. The sources used for collection of data in the Rotterdam Study are diverse and the definitions of outcomes in the Rotterdam Study have changed due to the introduction of novel diagnostics and therapeutic interventions. This article gives the methods for data collection and the up-to-date definitions of the cardiac outcomes based on international guidelines, including the recently adopted cardiovascular disease mortality definitions. In all, detailed description of cardiac outcome definitions enhances the possibility to make comparisons with other studies in the field of cardiovascular research and may increase the strength of collaborations.European Journal of Epidemiology 03/2012; 27(3):173-85. · 4.71 Impact Factor -
Article: Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity.
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ABSTRACT: Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.Journal of hypertension 03/2012; 30(3):445-8. · 4.02 Impact Factor -
Article: Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity
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ABSTRACT: Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.Journal of Hypertension 02/2012; 30(3):445–448. · 4.02 Impact Factor -
Article: Visuomotor impairment in early-stage Alzheimer's disease: changes in relative timing of eye and hand movements.
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ABSTRACT: Although memory complaints are one of the first clinical symptoms in patients with Alzheimer's disease (AD), damage to the parietal lobe, a key structure in the visuomotor coordination network, was recently identified in early-stage AD. The aim of this study was to quantify visuomotor coordination in patients with probable AD and to compare their visuomotor performance with controls using five eye-hand coordination tasks of variable complexity. Eye and hand movements were measured in 16 AD patients and 18 controls. The measurement setup consisted of a touch screen, an eye-tracking device, and a motion capturing system. We investigated eye-hand coordination by quantifying absolute and relative latencies of eye and hand movements and by analyzing eye and hand kinematics. We found that AD patients need significantly more time to initiate and execute goal-directed hand movements. AD patients are also unable to suppress reflexive eye and, to a lesser extent, hand movements. Furthermore, AD patients use a stepwise approach of eye and hand movements to touch a sequence of stimuli, whereas controls more often show an anticipatory approach. The impairments in reflex suppression of eye and hand movements, and changes in relative timing of eye-hand coordination, in AD patients support the notion that cortical networks involving the posterior parietal cortex are affected at an early disease-stage. It also suggests that the problems of AD patients to perform daily activities that require eye-hand coordination are not only caused by cognitive decline, but also by degeneration of neural networks involved in visuomotor coordination.Journal of Alzheimer's disease: JAD 02/2012; 30(1):131-43. · 3.74 Impact Factor -
Article: Aortic augmentation index and pulse wave velocity in response to head-up tilting: effect of autonomic failure.
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ABSTRACT: Aortic augmentation index (AIx) but not carotid-femoral pulse wave velocity (cfPWV) has reported to decrease in response to vasodilators, which has been related to changes in the timing and/or intensity of wave reflection. Yet, recent evidence indicates that arterial reservoir pressure rather than wave reflection is the most important determinant of AIx. Using radial artery applanation tonometry and a general transfer function AIx, aortic pulse wave reflection time and cfPWV (foot-to-foot method) were determined in 10 patients with severe autonomic failure and in 14 healthy individuals during supine rest and graded head-up tilting. During supine rest, mean blood pressure (BP) (127.6 ± 21.5 and 97.5 ± 9.4 mmHg), AIx (32.4 ± 13.0 and 23.1 ± 8.7%) and cfPWV (12.1 ± 3.6 and 8.9 ± 1.6 m/s) were higher in patients than in controls. In patients, BP decreased by 18.7 ± 9.8 and 39.6 ± 11.7%, AIx by 39.2 ± 27.5 and 100.9 ± 78.1% and cfPWV by 12.0 ± 10.5 and 27.7 ± 13.5% in response to 30 and 60° head-up tilting. Decreases in AIx and cfPWV correlated with the BP fall (r = 0.67, P = 0.001 and r = 0.75, P < 0.001), but changes in AIx and cfPWV were unrelated. In controls, AIx during head-up tilting decreased despite increases in vascular tone and cfPWV. Aortic reflection time in patients and controls during tilting did not change. Stepwise regression analysis revealed that 68% of the variation in AIx could be explained by the BP fall and reflection time and 76% of the variation in cfPWV by the BP fall and sex. In a clinical model of autonomic failure, both AIx and cfPWV largely depend on instantaneous BP, but these two variables are unrelated, supporting the contention that aortic reservoir pressure rather than wave reflection is the main determinant of AIx.Journal of hypertension 12/2011; 30(2):307-14. · 4.02 Impact Factor -
Article: Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.
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ABSTRACT: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, β=-0.075±0.012 SD/allele, P=2.8×10(-10); replication β=-0.086±0.020 SD/allele, P=1.4×10(-6)). Combined results for rs7152623 from 11 cohorts gave β=-0.076±0.010 SD/allele, P=3.1×10(-15). The association persisted when adjusted for mean arterial pressure (β=-0.060±0.009 SD/allele, P=1.0×10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, β=-0.081±0.014 SD/allele, P=2.3×10(-9)) and older (9 cohorts, n=12 026, β=-0.061±0.014 SD/allele, P=9.4×10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004). Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.Circulation Cardiovascular Genetics 11/2011; 5(1):81-90. · 6.11 Impact Factor -
Article: Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
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ABSTRACT: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.Nature Genetics 09/2011; 43(10):1005-11. · 35.53 Impact Factor -
Article: Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
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ABSTRACT: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.Nature 09/2011; 478(7367):103-9. · 36.28 Impact Factor -
Article: Arterial stiffness as determinant of increased amino terminal pro-B-type natriuretic peptide levels in individuals with and without cardiovascular disease--the Rotterdam Study.
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ABSTRACT: Large artery stiffening has adverse effects on cardiac structure and function and, therefore, may be associated with elevated circulating levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP). In a large community-dwelling older population (n = 6211, mean age 69.2 years), serum NT-proBNP, brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (cfPWV) were measured. In individuals without cardiovascular disease (CVD), median NT-proBNP was 6.7 pmol/l in men (n = 2073) and 10.1 pmol/l in women (n = 3085) (P < 0.001). In these individuals, indices of arterial stiffness correlated with NT-proBNP with beta-coefficients for brachial PP and cfPWV of 0.315 and 0.255 in men and 0.233 and 0.232 in women (all P < 0.001). After multivariable adjustment (age, weight, height, mean arterial pressure, heart rate, smoking, diabetes, estimated glomerular filtration rate, total and high-density lipoprotein-cholesterol and use of lipid-lowering and antihypertensive medication), these associations remained significant for brachial PP and cfPWV in men and for brachial PP in women. In multivariable-adjusted models, brachial PP explained 20.3% and cfPWV 10.7% of the variation of NT-proBNP in men and, respectively, 10.8 and 9.4% in women. In patients with prevalent CVD, indices of arterial stiffness and NT-proBNP were unrelated in multivariable-adjusted models. Our findings show that arterial stiffness is independently associated with elevated NT-proBNP levels in individuals without prevalent CVD. The association between vascular stiffness and NT-proBNP is stronger in men than in women and absent in individuals with prevalent CVD.Journal of hypertension 10/2010; 28(10):2061-7. · 4.02 Impact Factor -
Article: Primary arachnoid cyst mimicking depressive symptoms in an elderly woman.
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ABSTRACT: We describe an 81-year old female patient who was seen at our outpatient clinic with a history of falls. The clinical diagnosis was concurrent with depressive symptoms, but an arachnoid cyst turned out to be the cause of her problems. The patient recovered completely after surgery.International Psychogeriatrics 05/2010; 22(5):832-3. · 2.24 Impact Factor -
Article: Amino-terminal pro-B-type natriuretic peptide improves cardiovascular and cerebrovascular risk prediction in the population: the Rotterdam study.
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ABSTRACT: Increased circulating amino-terminal pro-B-type natriuretic (NT-proBNP) levels are a marker of cardiac dysfunction but also associate with coronary heart disease and stroke. We aimed to investigate whether increased circulating NT-proBNP levels have additive prognostic value for first cardiovascular and cerebrovascular events beyond classic risk factors. In a community-based cohort of 5063 participants free of cardiovascular disease, aged > or =55 years, circulating NT-proBNP levels and cardiovascular risk factors were measured. Participants were followed for the occurrence of first major fatal or nonfatal cardiovascular event. A total of 420 participants developed a first cardiovascular event (108 fatal). After adjustment for classic risk factors, the hazard ratio for cardiovascular events was 2.32 (95% CI: 1.55 to 2.70) in men and 3.08 (95% CI: 1.91 to 3.74) in women for participants with NT-proBNP in the upper compared with the lowest tertile. Corresponding hazard ratios for coronary heart disease, heart failure, and ischemic stroke were 2.01 (95% CI: 1.14 to 2.59), 2.90 (95% CI: 1.33 to 4.34), and 2.06 (95% CI: 0.91 to 3.18) for men and 2.95 (95% CI: 1.30 to 4.55), 5.93 (95% CI: 2.04 to 11.2), and 2.07 (95% CI: 1.00 to 2.97) for women. Incorporation of NT-proBNP in the classic risk model significantly improved the C-statistic both in men and women and resulted in a net reclassification improvement of 9.2% (95% CI: 3.5% to 14.9%; P=0.001) in men and 13.3% (95% CI: 5.9% to 20.8%; P<0.001) in women. We conclude that, in an asymptomatic older population, NT-proBNP improves risk prediction not only of heart failure but also of cardiovascular disease in general beyond classic risk factors, resulting in a substantial reclassification of participants to a lower or higher risk category.Hypertension 03/2010; 55(3):785-91. · 6.21 Impact Factor -
Article: Comparison of Candesartan versus Metoprolol for treatment of systemic hypertension after repaired aortic coarctation.
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ABSTRACT: Even after successful repair, hypertension is one of the main determinants of cardiovascular morbidity and mortality in patients with aortic coarctation (CoA). We compared the effect of candesartan (angiotensin II receptor blockade) and metoprolol (beta-adrenergic receptor blockade) on blood pressure, large artery stiffness, and neurohormonal status in hypertensive patients after repair of CoA. In the present open-label, crossover study, hypertensive patients after CoA repair were first randomly assigned to treatment with candesartan 8 mg or metoprolol 100 mg once per day. After 8 weeks of treatment with one of the drugs, the other treatment was given for 8 weeks. The treatment effects were assessed with 24-hour ambulatory blood pressure monitoring, measurement of large artery stiffness, and neurohormonal plasma levels at baseline and after 8 weeks of either treatment. Sixteen patients (mean age 37 +/- 12 years, 26 +/- 15 years after repair, 63% men) completed the study. The 24-hour mean arterial pressure at baseline was 97.7 +/- 6.2 mm Hg. Metoprolol (mean dose 163 +/- 50 mg/day) decreased the mean arterial pressure (7.0 +/- 4.2 and 4.1 +/- 3.6 mm Hg, respectively) more than did candesartan (mean dose 13 +/- 4 mg/day; p = 0.018, 95% confidence interval 0.6 to 5.5). Large artery stiffness did not change with either treatment. With metoprolol, plasma B-type natriuretic peptide increased and plasma renin decreased. With candesartan, the plasma renin and noradrenaline levels increased and aldosterone levels decreased. In conclusion, in adult hypertensive patients after CoA repair, metoprolol had more of an antihypertensive effect than did candesartan. Moreover, the neurohormonal outcome did not support a significant role for the renin-angiotensin system in the causative mechanism of hypertension after CoA.The American journal of cardiology 01/2010; 105(2):217-22. · 3.58 Impact Factor -
Article: High systolic and pulse pressure levels are associated with better cognitive performance in patients with probable Alzheimer's disease: a cross-sectional observational study in a geriatric outpatient population.
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ABSTRACT: The prevalence of cardiovascular disease and Alzheimer's disease (AD) increases with age. A number of studies have demonstrated an association between AD and cardiovascular risk factors and disease. However, data are inconsistent. Cross-sectional observational study in a geriatric outpatient population. Analysis of data from 327 patients diagnosed with probable AD in a geriatric outpatient clinic. Comparison of blood pressure levels, cardiovascular diagnoses, and Mini-Mental State Examination (MMSE) score between the patients. MMSE score decreased with age (beta = -0.25; 95% CI: -0.35 to 0.15), and a positive correlation was found with systolic blood pressure (beta = 0.03; 95% CI: 0.003-0.06), pulse pressure (beta = 0.05; 95% CI: 0.01-0.08) and hypertension (beta = 1.56; 95% CI: 0.05-3.07). An increase in cardiovascular disease load had a negative effect on cognitive performance. After adjustment for duration of dementia (data present for 216 patients), results were slightly changed. Higher systolic blood pressure and pulse pressure were associated with a better cognitive test performance. Patients with probable AD and 2 or more cardiovascular diagnoses had lower MMSE scores.Dementia and Geriatric Cognitive Disorders 10/2009; 28(4):320-4. · 2.14 Impact Factor -
Article: Large artery stiffness and microalbuminuria: a causal relationship?
Journal of hypertension 08/2009; 27(7):1355-7. · 4.02 Impact Factor -
Article: Genetic variation in the renin-angiotensin system and arterial stiffness. The Rotterdam Study.
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ABSTRACT: We studied the associations of three renin-angiotensin system polymorphisms, angiotensin-converting enzyme (ACE) I/D, angiotensinogen 235 M/T, and angiotensin II receptor type I 573 C/T, with arterial stiffness. The study was embedded in the Rotterdam Study, a population-based study older adults. The association of the polymorphisms with pulse wave velocity, the carotid distensibility, and pulse pressure was investigated in 3706 subjects. We found no association of the ACE I/D polymorphism with pulse wave velocity, but the D-allele was associated with a lower distensibility coefficient (p = 0.05) and higher pulse pressure (p = 0.01). For the angiotensinogen 235 M/T polymorphism, no significant associations with either pulse wave velocity (p = 0.71), the distensibility coefficient (p = 0.16) or pulse pressure (p = 0.34) were found. Also, we found no significant associations of pulse wave velocity (PWV) (p = 0.32), the distensibility coefficient (p = 0.08), and pulse pressure (p = 0.09) with the angiotensin II receptor type 1 573 C/T polymorphism. No epistatic effects were observed between the three renin-angiotensin system (RAS) genes with arterial stiffness. Our findings suggest that genetic variation in the renin-angiotensin system may play a role in determining carotid distensibility and pulse pressure.Clinical and Experimental Hypertension 07/2009; 31(5):389-99. · 1.07 Impact Factor -
Article: Genome-wide association study of blood pressure and hypertension.
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ABSTRACT: Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7). The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10(-8)) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.Nature Genetics 05/2009; 41(6):677-87. · 35.53 Impact Factor -
Article: Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study.
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ABSTRACT: To determine the prognostic role of orthostatic hypotension for cardiovascular disease (CVD) and all-cause mortality in elderly people. Prospective study. Community based. Five thousand sixty-four subjects from the Rotterdam study aged 55 and older. Orthostatic hypotension was measured using a Dinamap automatic blood pressure recorder. Orthostatic hypotension is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to standing position at any of three measurements taken 1, 2, and 3 minutes after standing. At baseline, 901 subjects had orthostatic hypotension. During follow-up, 668 subjects had coronary heart disease (CHD) (mean follow-up 6.0 +/- 3.5 years), and 1,835 subjects died (mean follow-up period 7.8 +/- 3.8 years). Orthostatic hypotension increased the risk of CHD (hazard ratio (HR)=1.31, 95% confidence interval (CI)=1.08-1.57) and all-cause mortality (HR=1.22, 95% CI=1.09-1.36), in models adjusted for age and sex. The risk was slightly lower after additional adjustment for cardiovascular risk factors. In analyses stratified for age, the HRs for all-cause mortality were 1.80 (95% CI 1.25-2.60), 1.13 (0.89-1.42), and 1.27 (95% CI=1.11-1.44), in the first, second, and third tertile of age, respectively. Orthostatic hypotension increases the risk of CHD and all-cause mortality in elderly people. The risk of CVD and mortality is strongest in younger and very old subjects.Journal of the American Geriatrics Society 10/2008; 56(10):1816-20. · 3.74 Impact Factor
Top co-authors
Top Journals
Institutions
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2006–2012
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Erasmus Universiteit Rotterdam
- • Department of Internal Medicine
- • Department of Epidemiology
Rotterdam, South Holland, Netherlands
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2004–2010
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Erasmus MC
- Department of Internal Medicine
Rotterdam, South Holland, Netherlands
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