Bruno H Ch Stricker

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (678)4153.26 Total impact

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    ABSTRACT: Purpose: Antidepressants, specifically selective serotonin reuptake-inhibiting antidepressants (SSRIs), decrease platelet activation and aggregation in in vitro experiments and could therefore decrease the risk of myocardial infarction (MI). However, prior studies addressing this hypothesis showed contradictory results. Our purpose was to investigate the association between the use of any antidepressant drug and incident MI among middle-aged and older adults. Methods: We embedded a case-control study in the prospective Rotterdam Study (1991-2011). Controls were matched to MI cases based on sex and age at the same calendar date, and confounding factors were taken into account as time-varying covariates. The relative risk of MI during current and past use of an antidepressant was analyzed with conditional logistic regression with never use of antidepressant drugs as the reference category. Results: A total of 744 out of a cohort of 9499 study participants developed MI during follow-up. After statistical adjustment for traditional cardiovascular risk factors and depression, current use of any antidepressant was associated with a lower risk of MI (odds ratio (OR), 0.71; 95 % confidence interval (CI), 0.51-0.98) compared with never use of any antidepressant. SSRI use showed the lowest relative risk (OR, 0.65; 95 % CI, 0.41-1.02), albeit marginally not statistically significant. Past use of any of the antidepressant classes was not associated with a lower risk of MI. Conclusions: Current use of antidepressants was associated with a lower risk of MI. Of the different classes, the use of SSRIs showed the lowest risk of MI, and therefore confirming the research hypothesis.
    European Journal of Clinical Pharmacology 11/2015; DOI:10.1007/s00228-015-1972-2 · 2.97 Impact Factor
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    ABSTRACT: Objective: The ATP-binding cassette B1 (ABCB1) gene encodes P-glycoprotein, a transport protein, which plays an important role in the bioavailability of digoxin. We aimed to investigate the interaction between variants within the ABCB1 gene and digoxin on the risk of sudden cardiac death (SCD). Methods: Within the Rotterdam Study, a population-based cohort study in persons 45 years of age and older, we used Cox regression to analyse the association between three polymorphisms that have been associated with digoxin bioavailability, extracted from 1000-Genomes imputed ABCB1 genotypes and the risk of SCD, stratified by digoxin use. Results: In a total study population of 10 932 persons, 419 SCDs occurred during a median follow-up of 9.8 years. In non-users of digoxin, the risk of SCD was not different across genotypes. In digoxin users, homozygous T allele carriers of C1236T (HR 1.90; 95% CI 1.09 to 3.30; allele frequency 0.43), G2677T (HR 1.89; 95% CI 1.10 to 3.24; allele frequency 0.44) and C3435T (HR 1.72; 95% CI 1.03 to 2.87; allele frequency 0.53) had a significantly increased risk of SCD in a recessive model. Interaction between the ABCB1 polymorphisms and digoxin use was significant for C1236T and G2677T in the age-adjusted and sex-adjusted model. Conclusions: In this study, we showed that in digoxin users variant alleles at each of the three loci in the ABCB1 gene were associated with an increased risk of SCD compared with digoxin users with none or one T allele. If replicated, the findings imply that the ABCB1 genotype modifies the risk of cardiac digoxin toxicity.
    Heart (British Cardiac Society) 11/2015; DOI:10.1136/heartjnl-2014-307419 · 5.60 Impact Factor

  • Value in Health 11/2015; 18(7):A431. DOI:10.1016/j.jval.2015.09.1026 · 3.28 Impact Factor
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    ABSTRACT: Background: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.
    PLoS ONE 10/2015; 10(10):e0140496. DOI:10.1371/journal.pone.0140496 · 3.23 Impact Factor
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    ABSTRACT: Rationale: Worldwide, chronic obstructive pulmonary disease (COPD) and stroke are leading causes of death. Increasing evidence suggests an association between both diseases, either caused by an increased atherosclerosis risk in patients with COPD, or as a consequence of shared risk factors between stroke and COPD. Objectives: To examine the associations between COPD and subtypes of stroke in the general population and to explore the role of cardiovascular risk factors and exacerbations on these associations. Methods: Within the prospective population-based Rotterdam Study, we followed 13115 participants without history of stroke for occurrence of stroke. Follow-up started in 1990-2008 and ended in 2012. COPD was related to stroke using a time-dependent Cox proportional hazard model. Measurements and main results: COPD was diagnosed in 1566 participants. During 126347 person-years, 1250 participants suffered a stroke, of which 701 were ischemic and 107 hemorrhagic. Adjusted for age, age2, and sex, COPD was significantly associated with all stroke (HR 1.20; 95%CI 1.00-1.43), ischemic stroke (HR 1.27; 1.02-1.59), and hemorrhagic stroke (HR 1.70; 1.01-2.84). Adjusting for cardiovascular risk factors gave similar effect sizes. In contrast, additional adjusting for smoking attenuated the effect sizes: HR 1.09 (0.91-1.31) for all stroke, HR 1.13 (0.91-1.42) for ischemic stroke, and HR 1.53 (0.91-2.59) for hemorrhagic stroke. Following an acute severe exacerbation subjects with COPD had a 6.66-fold (2.42-18.20) increased risk of stroke. Conclusion: Our cohort study demonstrated a higher risk of both ischemic and hemorrhagic stroke in subjects with COPD, and revealed the importance of smoking as a shared risk factor.
    American Journal of Respiratory and Critical Care Medicine 09/2015; DOI:10.1164/rccm.201505-0962OC · 13.00 Impact Factor
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    ABSTRACT: Importance: Atrial fibrillation (AF) has been suggested as a risk factor for dementia since it may lead to chronic cerebral hypoperfusion and stroke. However, longitudinal studies assessing the association between AF and dementia have shown inconsistent results. Objective: To determine the effect of AF on the risk of developing dementia during 20 years of follow-up. Design, setting, and participants: The association of prevalent and incident AF with incident dementia was assessed from July 6, 1989, to February 4, 2010, in 6514 dementia-free participants in the prospective population-based Rotterdam Study. Data analysis was conducted from September 18, 2014, to April 17, 2015. Cox proportional hazards regression models adjusting for age, sex, and cardiovascular risk factors; censored for stroke; and stratified by median age were used. In addition, we investigated whether the association between incident AF and dementia varied according to the duration of exposure, categorized in 6-year time bands. Exposures: Prevalent and incident AF. Main outcomes and measures: Incident dementia, determined according to the Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Results: At baseline, 318 of 6514 participants (4.9%) had prevalent AF, and during 81 483 person-years of follow-up, 994 participants (15.3%) developed incident dementia. With findings presented as adjusted hazard ratio (95% CI), prevalent AF was related to an increased risk of dementia (1.33; 1.02-1.73). Among 6196 participants without prevalent AF during 79 003 person-years of follow-up, 723 participants (11.7%) developed incident AF and 932 individuals (15.0%) developed incident dementia. Incident AF was associated with an increased risk of dementia in younger participants (<67 years: 1.81; 1.11-2.94 vs ≥67 years: 1.12; 0.85-1.46; P = .02 for interaction). The risk of dementia was strongly associated with duration of exposure to AF in the younger participants (in the highest stratum: 3.30; 1.16-9.38; P = .003 for trend) but not in the elder participants (0.25; 0.04-1.86; P = .94 for trend). Conclusions and relevance: Atrial fibrillation is associated with an increased risk of dementia, independent of clinical stroke. This association was strongest for younger participants with the longest duration of AF. Future studies should investigate whether optimal treatment of AF can prevent or postpone dementia.
    09/2015; DOI:10.1001/jamaneurol.2015.2161
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    ABSTRACT: The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over 1200 research articles and reports (see ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
    European Journal of Epidemiology 09/2015; 28(11). DOI:10.1007/s10654-015-0082-x · 5.34 Impact Factor
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    ABSTRACT: Background: Despite frailty being an important geriatric syndrome, its prevalence and associated mortality risk in older patients with chronic obstructive pulmonary disease (COPD) are unknown. Methods: We examined the relationship between COPD confirmed by spirometry, COPD severity, and frailty defined by the Fried criteria within 2,142 participants (aged 74.7±5.6 years) of the Rotterdam Study, a prospective population-based cohort study. Results: The frailty prevalence was significantly higher (p < .001) in participants with COPD (10.2%, 95% CI: 7.6%-13.5%) compared with participants without COPD (3.4%, 95% CI: 2.6%-4.4%). Adjusted for age, sex, smoking, corticosteroids, and other confounders, participants with COPD had a more than twofold increased prevalence of frailty (odds ratio 2.2, 95% CI: 1.34-3.54, p = .002). The prevalence was highest when severe airflow limitation, dyspnea, and frequent exacerbations were present. Participants with mild airflow limitation were more frequently prefrail. COPD elderly who were frail had significant worse survival. Conclusions: This population-based cohort study in elderly demonstrates that COPD is associated with frailty even after adjusting for shared risk factors. Our findings suggest that frailty-in addition to COPD severity and comorbidities-identifies those COPD participants at high risk of mortality.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2015; DOI:10.1093/gerona/glv154 · 5.42 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA1124. DOI:10.1183/13993003.congress-2015.PA1124 · 7.64 Impact Factor
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    ABSTRACT: Prolonged ventricular repolarization (measured as heart-rate corrected QT (QTc) prolongation or JT-interval prolongation) is a risk factor for ventricular arrhythmias and can be drug-induced. Drugs can be classified as having known or possible QTc-prolonging properties. Regulatory agencies recommend avoiding concomitant use of multiple QTc-prolonging drugs, but evidence is lacking to what degree ventricular repolarization is influenced by concomitant use of these drugs. Within a population-based cohort of persons aged 45 years and older, with up to five electrocardiograms recorded per participant between 1991 and 2010, we used generalised estimating equations to study the association between concomitant use of multiple QTc-prolonging drugs and repolarization duration. The study population consisted of 13 009 participants with 26 908 electrocardiograms. With the addition of a second or third QTc-prolonging drug there was no substantial increase in QTc and JT interval and no increased risk of a prolonged QTc interval, compared to use of one QTc-prolonging drug. There was a large difference between the effect of one known or one possible QTc-prolonging drugs on QTc interval: 15 ms for known, and 3 ms for possible QTc-prolonging drugs. In this study, the added prolongation in users of two or three QTc-prolonging drugs on QTc was small. There was a large difference in QTc prolongation between known and possible QTc-prolonging drugs. Further research in larger or high-risk populations is needed to establish whether it is safe to use multiple QTc-prolonging drugs concomitantly to prevent that the current advice might unnecessarily withhold beneficial drugs from patients. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 08/2015; 24(10). DOI:10.1002/pds.3853 · 2.94 Impact Factor
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    J Berkhout · JA Stone · K M Verhamme · B H Stricker · M C Sturkenboom · M Danhof · T M Post ·
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    ABSTRACT: Osteoporosis is a progressive bone disease characterized by decreased bone mass resulting in increased fracture risk. The objective of this investigation was to test whether a recently developed disease systems analysis model for osteoporosis could describe disease progression in a placebo-treated population from the Early Postmenopausal Intervention Cohort (EPIC) study. First, we qualified the model using a subset from the placebo arm of the EPIC study of 222 women who had similar demographic characteristics as the 149 women from the placebo arm of the original population. Second, we applied the model to all 470 women. Bone mineral density (BMD) dynamics were changed to an indirect response model to describe lumbar spine and total hip BMD in this second population. This updated disease systems analysis placebo model describes the dynamics of all biomarkers in the corresponding datasets to a very good approximation; a good description of an individual placebo response will be valuable for evaluating treatments for osteoporosis.
    CPT: Pharmacometrics and Systems Pharmacology 08/2015; 4(9). DOI:10.1002/psp4.12006
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    ABSTRACT: The coagulation system is known to be involved in fibrogenesis in patients with liver disease. We investigated whether common genetic prothrombotic risk factors are associated with an increased risk of fibrosis in the general population. This investigation was part of the Rotterdam Study, an ongoing, population-based cohort study. Liver stiffness (LS) was measured using transient elastography (Fibroscan®) and associated with single nucleotide polymorphisms determining blood group type and presence of the Factor V Leiden (FVL) mutation or Prothrombin G20210A gene variant. Reliable LS measurements and genetic data were obtained from 1055 Caucasian participants. LS ⩾8.0 kPa, suggestive of clinically relevant fibrosis, was observed in 101 subjects (9.6%). Presence of FVL or prothrombin G20210A was independently associated with an increased risk of LS ⩾8.0 kPa (OR 2.09, 95%CI 1.07-4.07, p=0.03). Combination of blood group type non-O and the FVL mutation or prothrombin G20210A variant resulted in an even higher risk of LS ⩾8.0 kPa (OR 3.36, 95%CI 1.50-7.56, p=0.003). Presence of the FVL mutation or prothrombin G20210A variant in participants with blood group non-O was associated with a predicted probability of 14.3% (7.7-23.8) of LS ⩾8.0 kPa. Participants carrying the FVL mutation or prothrombin G20210A variant have an increased risk of clinically relevant liver fibrosis, which is even higher in blood group type non-O carriers. The fact that genetic prothrombotic risk factors are associated with an increased risk of liver fibrosis suggests that coagulation plays an important role in fibrogenesis in the general population. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 07/2015; DOI:10.1016/j.jhep.2015.07.026 · 11.34 Impact Factor
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    ABSTRACT: Since little is known about the prevalence of and factors associated with liver fibrosis in the general population, we aimed to investigate this in a large, well-characterized cohort, by means of transient elastography (TE). This study was part of the Rotterdam Study, a population-based study among individuals ≥45 years. All participants underwent abdominal ultrasound and TE. Liver stiffness measurement (LSM) ≥8.0 kPa was used as cut-off suggesting clinically relevant fibrosis. Of 3041 participants (age 66.0±7.6 years) with reliable LSM, 169 (5.6%) participants had LSM ≥8.0 kPa. Age (OR 2.40, 95%CI 1.72-3.36,p<0.001), ALT (OR 1.24, 95%CI 1.12-1.38,p<0.001), smoking (OR 1.77, 95%CI 1.16-2.70, p=0.008), spleen size (OR 1.23, 95%CI 1.09-1.40,p=0.001), HBsAg or anti-HCV positivity (OR 5.38, 95%CI 1.60-18.0,p=0.006), and combined presence of diabetes mellitus (DM) and steatosis (OR 5.20, 95%CI 3.01-8.98, p<0.001 for combined presence) were associated with LSM ≥ 8.0 kPa in multivariable analyses. The adjusted predicted probability of LSM ≥8.0 kPa increased per age decade, with probabilities ranging from 1.4% (0.9-3.6) in participants aged 50-60 years to 9.9% (6.8-14.5) in participants >80 years. Participants with both DM and steatosis had the highest probabilities of LSM ≥8.0 kPa (overall probability 17.2% (12.5-23.4), this probability did not increase with age (p=0.8). In this large population-based study of older adults, LSM ≥8.0 kPa, suggestive of clinically relevant fibrosis, was present in 5.6% and was strongly associated with steatosis and DM. In the context of an aging population and an increased prevalence of diabetes mellitus and obesity, this study illustrates that liver fibrosis may become a more prominent public health issue in the nearby future. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 07/2015; DOI:10.1002/hep.27981 · 11.06 Impact Factor
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    ABSTRACT: Background Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. Objective To identify a proxy for ACEI-induced ADRs in prescription databases. Setting The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older. Methods All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated. Results Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %. Conclusions Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases.
    International Journal of Clinical Pharmacy 07/2015; DOI:10.1007/s11096-015-0159-3 · 1.35 Impact Factor
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    ABSTRACT: A prolonged heart-rate corrected QT (QTc) interval is a well-known risk indicator for sudden cardiac death (SCD) and a contraindication for drugs with potentially arrhythmogenic adverse effects. To study the consistency of QTc prolongation and whether a consistent prolongation correlates differently with SCD compared to an inconsistently prolonged QTc. We used a population-based cohort study of persons aged 55 years and older. We excluded participants using QTc-prolonging drugs or with a bundle branch block. QT was corrected for heart rate using Bazetts' and Fridericia's formulas. With Cox' regression we assessed the association between QTc prolongation consistency and SCD. 3,484 participants had electrocardiograms (ECG) available on two consecutive visits. In 96-98% of participants with a normal QTc on the first ECG, QTc remained normal, but only in 27-35% of those with a prolonged QTc, QTc was prolonged on the second ECG after a median of 1.8 years. A consistently prolonged QTc was associated with an increased risk of SCD compared to a consistently normal QTc interval (Bazett: HR 2.23; 95%CI 1.17;4.24, Fridericia: HR 6.67; 95%CI 2.96;15.06). A prolonged QTc preceded or followed by a normal QTc interval was not significantly associated with an increased risk of SCD. Persons with an inconsistently prolonged QTc interval did not have a higher risk of SCD than those with a consistently normal QTc. Persons with a consistently prolonged QTc did have a higher risk of SCD. Our results suggest that repeated measurements of the QTc interval could enhance risk stratification. Copyright © 2015. Published by Elsevier Inc.
    Heart rhythm: the official journal of the Heart Rhythm Society 07/2015; DOI:10.1016/j.hrthm.2015.07.011 · 5.08 Impact Factor
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    ABSTRACT: We aimed to investigate the association between antidepressants and serum lipid levels in a population-based study in older adults. We included participants from the prospective Rotterdam Study with data on lipid levels (total, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, and triglycerides). We classified antidepressants based on binding affinity to the serotonin transporter (low/intermediate- and high-affinity antidepressants). We compared lipid levels in users of these groups of antidepressants with lipid levels in non-users. Furthermore, we studied effect modification by the 102C>T polymorphism (HTR2A gene), which is associated with antidepressant drug response and metabolic outcomes. Compared with non-users (N = 6438), LDL cholesterol level was higher (2.9 versus 3.1 mmol/L, respectively; p = 0.05) in users of high-affinity antidepressants (N = 89). Similar levels of the other lipids were observed between the groups for the other lipids. The mean difference in serum LDL cholesterol level between non-users and users of high-affinity antidepressants was largest in participants with the CC genotype compared with the other genotypes (notably 0.47 mmol/L), indicative of effect modification (p-value for interaction = 0.03). Antidepressants with a high serotonin reuptake transporter affinity were associated with higher LDL cholesterol levels, which were modified by a common genetic variation in the HTR2A gene. © The Author(s) 2015.
    Journal of Psychopharmacology 07/2015; 29(10). DOI:10.1177/0269881115592340 · 3.59 Impact Factor
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    ABSTRACT: Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users. Prospective cohort study. 9,818 individuals from the general population (Rotterdam Study). PPI use and H2RA use compared to no use. Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use. Serum magnesium level was 0.022 mEq/L lower in PPI users (n=724; 95% CI, -0.032 to -0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n=36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n=270), PPI use was associated with a further increased risk of hypomagnesemia (n=5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n=250) also had a lower serum magnesium level (-0.016 [95% CI, -0.032 to -0.002] mEq/L) and increased risk of hypomagnesemia (n=12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics. Cross-sectional analysis with single serum magnesium measurement. PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 06/2015; DOI:10.1053/j.ajkd.2015.05.012 · 5.90 Impact Factor
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    ABSTRACT: A prolonged QT interval is an important risk factor for ventricular arrhythmias and sudden cardiac death. QT prolongation can be caused by drugs. There are multiple risk factors for drug-induced QT prolongation, including genetic variation. QT prolongation is one of the most common reasons for withdrawal of drugs from the market, despite the fact that these drugs may be beneficial for certain patients and not harmful in every patient. Identifying genetic variants associated with drug-induced QT prolongation might add to tailored pharmacotherapy and prevent beneficial drugs from being withdrawn unnecessarily. In this review, our objective was to provide an overview of the genetic background of drug-induced QT prolongation, distinguishing pharmacokinetic and pharmacodynamic pathways. Pharmacokinetic-mediated genetic susceptibility is mainly characterized by variation in genes encoding drug-metabolizing cytochrome P450 enzymes or drug transporters. For instance, the P-glycoprotein drug transporter plays a role in the pharmacokinetic susceptibility of drug-induced QT prolongation. The pharmacodynamic component of genetic susceptibility is mainly characterized by genes known to be associated with QT interval duration in the general population and genes in which the causal mutations of congenital long QT syndromes are located. Ethnicity influences susceptibility to drug-induced QT interval prolongation, with Caucasians being more sensitive than other ethnicities. Research on the association between pharmacogenetic interactions and clinical endpoints such as sudden cardiac death is still limited. Future studies in this area could enable us to determine the risk of arrhythmias more adequately in clinical practice.
    Drug Safety 06/2015; 38(10). DOI:10.1007/s40264-015-0316-6 · 2.82 Impact Factor
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    ABSTRACT: Pulmonary hypertension is characterized by increased pulmonary artery pressure and carries an increased mortality. Population-based studies into pulmonary hypertension are scarce and little is known about its prevalence in the general population. We aimed to describe the distribution of echocardiographically-assessed pulmonary artery systolic pressure (ePASP) in the general population, to estimate the prevalence of pulmonary hypertension, and to identify associated factors. Participants (n = 3381, mean age 76.4 years, 59% women) from the Rotterdam Study, a population-based cohort, underwent echocardiography. Echocardiographic pulmonary hypertension was defined as ePASP>40 mmHg. Mean ePASP was 26.3 mmHg (SD 7.0). Prevalence of echocardiographic pulmonary hypertension was 2.6% (95%CI: 2.0; 3.2). Prevalence was higher in older participants compared to younger ones (8.3% in those over 85 years versus 0.8% in those between 65 and 70), and in those with underlying disorders versus those without (5.9% in subjects with COPD versus 2.3%; 9.2% in those with left ventricular systolic dysfunction versus 2.3%; 23.1% in stages 3 or 4 left ventricular diastolic dysfunction versus 1.9% in normal or stage 1). Factors independently associated with higher ePASP were older age, higher BMI, left ventricular diastolic dysfunction, COPD and systemic hypertension. In this large population-based study, we show that pulmonary hypertension as measured by echocardiography has a low prevalence in the overall general population in the Netherlands, but estimates may be higher in specific subgroups, especially in those with underlying diseases. Increased pulmonary arterial pressure is likely to gain importance in the near future due to population aging and the accompanying prevalences of underlying disorders.
    PLoS ONE 06/2015; 10(6):e0130072. DOI:10.1371/journal.pone.0130072 · 3.23 Impact Factor
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    ABSTRACT: Subclinical cardiac dysfunction has been associated with increased mortality and heart failure increases the risk of sudden cardiac death (SCD). Less well-known is whether subclinical cardiac dysfunction is also a risk factor for SCD. Our objective was to assess the association between echocardiographic parameters and SCD in a community-dwelling population free of heart failure. We computed hazard ratios (HRs) for left atrium diameter, left ventricular (LV) end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD), LV mass, qualitative LV systolic function, LV fractional shortening, and diastolic function. During a median follow-up of 6.3 years in 4,686 participants, 68 participants died due to SCD. Significant associations with SCD were observed for qualitative LV systolic function and LV fractional shortening. For moderate/poor qualitative LV systolic function, the HR for SCD was 2.54 (95%CI 1.10;5.87). Each standard deviation decrease in LV fractional shortening was associated with a HR of 1.36 (95%CI 1.09;1.70). Subclinical abnormalities in left ventricular systolic function were associated with SCD risk in this general population. Although prediction of SCD remains difficult and traditional cardiovascular risk factors are of greatest importance, this knowledge might guide future directions to prevent SCD in persons with subclinical cardiac dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of cardiac failure 06/2015; DOI:10.1016/j.cardfail.2015.06.007 · 3.05 Impact Factor

Publication Stats

20k Citations
4,153.26 Total Impact Points


  • 1999-2015
    • Erasmus MC
      • Department of Epidemiology
      Rotterdam, South Holland, Netherlands
  • 1992-2015
    • Erasmus Universiteit Rotterdam
      • • Department of Epidemiology
      • • Department of Internal Medicine
      • • Department of Medical Informatics
      Rotterdam, South Holland, Netherlands
  • 2014
    • Uppsala University
      Uppsala, Uppsala, Sweden
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
  • 1986-2014
    • Leiden University Medical Centre
      • Department of Gastroenterology and Hepatology
      Leyden, South Holland, Netherlands
  • 2013
    • Catholic University of Louvain
      • Institute of Experimental and Clinical Research (IREC)
      Лувен-ла-Нев, Walloon, Belgium
  • 2009
    • National Institutes of Health
      • Branch of Epidemiology (EPI)
      Bethesda, MD, United States
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 1995-2009
    • Universiteit Utrecht
      • • Utrecht Institute for Pharmaceutical Sciences
      • • Division of Pharmacoepidemiology and Pharmacotherapy
      Utrecht, Utrecht, Netherlands
  • 2007
    • Canadian Society for Epidemiology and Biostatistics 
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1992-2006
    • University of Groningen
      • Department of Clinical Pharmacology
      Groningen, Groningen, Netherlands
  • 2002
    • The Ohio State University
      • Department of Pediatrics
      Columbus, Ohio, United States
  • 1997
    • Complutense University of Madrid
      Madrid, Madrid, Spain
  • 1996
    • Medisch Spectrum Twente
      • Hospital Medical Spectrum Twente
      Enschede, Overijssel, Netherlands
    • Diergaarde Blijdorp
      Rotterdam, South Holland, Netherlands
  • 1989
    • Georgetown University
      • Department of Medicine
      Washington, Washington, D.C., United States