Jan Heeringa - Academia.edu (original) (raw)
Papers by Jan Heeringa
Nederlands tijdschrift voor geneeskunde, 2010
The revised practice guideline 'Atrial fibrillation' from the Dutch College of General Pr... more The revised practice guideline 'Atrial fibrillation' from the Dutch College of General Practitioners provides the general practitioner with guidelines for diagnosis and management of patients with atrial fibrillation. To find patients with atrial fibrillation, it is advised to check cardiac rhythm at every blood pressure measurement. In patients over 65 years old, acceptance of atrial fibrillation with control of ventricular rate is preferred to sinus rhythm normalisation. In therapy with beta-blockers, slow release metoprolol is the drug of choice. An important goal of treatment is the prevention of thrombo-embolic complications. The choice between anticoagulants such as aspirin and coumarin derivatives is based on the CHADS2 score and determined by age (above 75 years) and comorbidity including cardiac failure, diabetes, hypertension, and previous transient ischaemic attack (TIA) or cardiovascular accident (CVA). The adequacy of antithrombotic treatment should be reassesse...
European Heart Journal, 2008
Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significa... more Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significant morbidity and mortality. A recent genome wide association study identified a haplotype block on Chromosome 4q25 associated with AF.
PLOS ONE, 2015
Atrial fibrillation (AF) is the most common chronic arrhythmia and it increases the risk of cardi... more Atrial fibrillation (AF) is the most common chronic arrhythmia and it increases the risk of cardiovascular morbidity and mortality. Still there is not a complete understanding of its etiology and underlying pathways. Vitamin D might regulate renin-angiotensin-aldosterone system and might be involved in inflammation, both implicated in the pathophysiology of AF. The objective of this work was to investigate the association between vitamin D status with the risk of AF in the elderly. This study was conducted within the Rotterdam Study, a community-based cohort of middle-aged and elderly participants in Rotterdam, The Netherlands. We had 3,395 participants who were free of AF diagnosis at the start of our study and who had vitamin D data available. We analyzed the association between serum 25-hydroxivitamin D (25(OH)D) and incidence of AF using Cox regression models. Vitamin D deficiency was defined as serum 25(OH)D concentrations <50nmol/l, insufficiency between 50nmol/l and 75nmol/l, while serum 25(OH)D concentrations equal to and above 75nmol/l were considered as adequate. After mean follow-up of 12.0 years 263 (7.7%) participants were diagnosed with incident AF. Vitamin D status was not associated with AF in any of the 3 multivariate models tested (model adjusted for socio-demographic factors and life-style factors: HR per 10 unit increment in serum 25(OH)D 0.96, 95% CI: 0.91-1.02; HR for insufficiency: 0.82, 95%CI: 0.60-1.11,and HR for adequate status: 0.76, 95%CI: 0.52-1.12 compared to deficiency). This prospective cohort study does not support the hypothesis that vitamin D status is associated with AF.
Persons with a clinically recognized myocardial infarction are at increased risk for atrial fibri... more Persons with a clinically recognized myocardial infarction are at increased risk for atrial fibrillation. However a large proportion of all myocardial infarctions remain clinically unrecognized. Whether subjects with electrocardiographic signs of an unrecognized myocardial infarction are also at an increased risk of developing atrial fibrillation is unknown. The objective of this study was to investigate whether unrecognized myocardial infarction was associated with an increased risk of atrial fibrillation in a prospective population-based cohort study. The study is set within the prospective population-based Rotterdam Study. The study population comprised 2505 men and 3670 women without atrial fibrillation at baseline. Participants were classified based on electrocardiography, interview, and clinical data into those with recognized myocardial infarction, those with ECG based unrecognized myocardial infarction and those without myocardial infarction. Atrial fibrillation was ascertained from ECG assessments as well as medical records. During a mean follow-up of 11.7 years (SD 5.0), 329 men and 398 women developed atrial fibrillation. Unrecognized myocardial infarction was associated with a two-fold risk of developing atrial fibrillation in men (HR: 2.21, 95%CI:1.51 to 3.23) compared to men without a history of myocardial infarction, independent of age, and cardiovascular risk factors. In women, unrecognized myocardial infarction was not associated with atrial fibrillation (HR: 0.92, 95%CI:0.59 to 1.44). The presence of an unrecognized myocardial infarction is associated with a twofold increased risk of atrial fibrillation in men, independent of known cardiovascular risk factors.
Heart rhythm : the official journal of the Heart Rhythm Society, 2015
Although sudden cardiac death (SCD) is relatively common, contemporary data on its incidence are ... more Although sudden cardiac death (SCD) is relatively common, contemporary data on its incidence are lacking. The purpose of this study was to investigate the current incidence of SCD and its trend over the past 2 decades in a general middle-aged and elderly population. This study was performed within the Rotterdam Study, a prospective population-based cohort study of persons aged 45 years and older. Age-standardized incidence rates of SCD were calculated. To study trends in incidence, we compared 2 subcohorts within the total study population, 1 followed from 1990-2000 and the other from 2001-2010. From 1990-2010, 5512 of 14,628 participants died, of whom 583 (4.0%) were classified as SCD. The overall incidence was 4.2 per 1000 person-years. The incidence was higher in men (5.2 per 1000 person-years) than in women (3.6 per 1000 person-years). Age-adjusted hazard ratio (HR) 1.84 (95% confidence [CI] 1.56-2.17) and risk of SCD increased with age (HR 1.10 per year; 95% CI 1.09-1.11). The ...
BMJ (Clinical research ed.), 2014
To evaluate differences in first manifestations of cardiovascular disease between men and women i... more To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Prospective population based cohort study. People living in the community in Rotterdam, the Netherlands. 8419 participants (60.9% women) aged ≥ 55 and free from cardiovascular disease at baseline. First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetim...
Preventive Medicine, 2004
In identifying opportunities to improve the quality of stroke prevention in general practice, ins... more In identifying opportunities to improve the quality of stroke prevention in general practice, insight in areas of suboptimal care is essential. This study investigated the quality of care in stroke prevention in general practice and its relation to the occurrence of stroke. Retrospective case-based audit with guideline-based review criteria and final judgment of suboptimal care by an expert panel. A total of 292 stroke patients were identified through stroke registers of two main referral hospitals for stroke in Rotterdam. The general practitioners (GPs) (n = 95) of these patients were approached. The overall response rate from GPs was 81%, and a total of 193 patients from 77 GPs were included in the study. Data on the process of care at patient level were collected by chart review and by structured interviews with GPs during site visits. All cases were presented to a six-member panel of GPs and neurologists. In 44% of the cases, suboptimal care was identified (31% judged as possibly or likely failing to prevent stroke). Of the total number of identified shortcomings, 52% was related to inadequate hypertension control, particularly lack of follow-up after established hypertension. Another 17% of identified shortcomings concerned inadequate cardiovascular risk assessment. A substantial number of shortcomings in care, particularly in the domain of hypertension control and the assessment of patient's risk profiles for cardiovascular disease (CVD), were identified. This study suggests that improving preventive care delivery in general practice could reduce the occurrence of stroke.
PLoS medicine, 2012
Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy ... more Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y...
Journal of the American College of Cardiology, 2004
Journal of the American College of Cardiology, 2006
This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interv... more This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND In developed countries, sudden cardiac death is a major cause of cardiovascular mortality.
Journal of Clinical Epidemiology, 2008
Objective: The aim of the study was to investigate how settings and registry characteristics affe... more Objective: The aim of the study was to investigate how settings and registry characteristics affect the prevalence and nature of multimorbidity in elderly individuals.
Nature genetics, 2009
We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in par... more We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)).
European Journal of Human Genetics, 2003
The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elde... more The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elderly, these mutations might be associated with increased morbidity because of the lifelong accumulation of iron. In a population-based sample of the elderly, we determined the value of genotyping for HFE mutations to screen for subclinical hemochromatosis. HFE genotype frequencies were determined in a random group of 2095 subjects (55 years and over). In this random group, we selected within the six genotype groups a total of 342 individuals and measured their serum transferrin saturation, iron and ferritin levels. We also estimated the heritability and parameters needed to evaluate screening, including the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of HFE genotypes. Iron parameters were significantly increased in subjects homozygous, heterozygous or compound heterozygous. The effect of the mutations was more pronounced in men than in women. For the H63D mutation, an allele dose effect was observed. The HFE gene explained about 5% of the variability in serum iron indices. The PPV for hemochromatosis for the C282Y homozygous was 100% in men and 67% in women. The NPV of the wild-type allele was 97% for both men and women. The sensitivity of both mutations was 70% for men and 52% for women and the specificity was 62% for men and 64% for women. Our study shows that the HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. However, when screening based on these two mutations, some individuals with subclinical hemochromatosis will be missed.
European Heart Journal, 2005
Aims We aimed to investigate the prevalence and incidence of atrial fibrillation (AF) in a large ... more Aims We aimed to investigate the prevalence and incidence of atrial fibrillation (AF) in a large European population-based study.
European Heart Journal, 2008
Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significa... more Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significant morbidity and mortality. A recent genome wide association study identified a haplotype block on Chromosome 4q25 associated with AF.
British Journal of Clinical Pharmacology, 2008
Round 1 -source population: 7983 participants 771 died before round 2 794 refused participation i... more Round 1 -source population: 7983 participants 771 died before round 2 794 refused participation in round 2 106 lost to follow-up Round 2 -baseline population: 6312 participants -with 948 chronic users, who were excluded Study population: 5364 participants at risk of new-onset chronic benzodiazepine use Figure 1
BMJ, 2008
Objective To determine the efficacy of statin treatment on risk of coronary heart disease in pati... more Objective To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia.
Archives of Internal Medicine, 2007
Background: Myocardial infarction is an important risk factor for atrial fibrillation, but the ro... more Background: Myocardial infarction is an important risk factor for atrial fibrillation, but the role of subclinical atherosclerosis is unknown. This longitudinal study evaluates whether atherosclerosis affects the risk of atrial fibrillation in persons without overt coronary disease.
Archives of Internal Medicine, 2006
High-dose (pulse) corticosteroid therapy has been associated with the development of atrial fibri... more High-dose (pulse) corticosteroid therapy has been associated with the development of atrial fibrillation. This association, however, is mainly based on case reports. To test the hypothesis that high-dose corticosteroid exposure increases the risk of new-onset atrial fibrillation, we performed a nested case-control study within the Rotterdam Study, a population-based cohort study among 7983 older adults. Cases were defined as persons with incident atrial fibrillation between July 1, 1991, and January 1, 2000. Their date of diagnosis was defined as the index date. All noncases within the Rotterdam Study who were alive and eligible on this index date were used as controls. Subsequently, we compared the proportion of cases and controls that received a corticosteroid prescription within 1 month preceding the index date. Corticosteroid exposure was categorized into high-dose exposure (oral or parenteral steroid at a daily dose &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =7.5 mg of prednisone equivalents) and low-intermediate-dose exposure (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5 mg of prednisone equivalents or inhaled corticosteroids). There were 385 eligible cases of new-onset atrial fibrillation during the study period. The risk of new-onset atrial fibrillation was significantly higher for persons who received a corticosteroid prescription within 1 month before the index date than for those without (odds ratio [OR], 3.75; 95% confidence interval [CI], 2.38-5.87). However, only high-dose corticosteroid use was associated with an increased risk (OR, 6.07; 95% CI, 3.90-9.42), whereas low-intermediate-dose use was not (OR, 1.42; 95% CI, 0.72-2.82). The association of atrial fibrillation with high-dose corticosteroid use was largely independent of the indication for corticosteroid therapy, since the risk of new-onset atrial fibrillation was not only increased in patients with asthma or chronic obstructive pulmonary disease (OR, 4.02; 95% CI, 2.07-7.81) but also in patients with rheumatic, allergic, or malignant hematologic diseases (OR, 7.90; 95% CI, 4.47-13.98). Our findings strongly suggest that patients receiving high-dose corticosteroid therapy are at increased risk of developing atrial fibrillation.
Archives of Internal Medicine, 2008
Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fib... more Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fibrillation. We aimed to investigate the association of high-normal thyroid function with the development of atrial fibrillation in a prospective population-based study in the elderly. The association between thyroid-stimulating hormone (TSH) levels and atrial fibrillation was examined in 1426 subjects with TSH levels in the normal range (0.4-4.0 mU/L) and without atrial fibrillation at baseline. In 1177 of the 1426 persons in this group, we also examined the association between free thyroxine levels within the normal range (0.86-1.94 ng/dL [to convert to picomoles per liter, multiply by 12.871]) and atrial fibrillation. During a median follow-up of 8 years, 105 new cases of atrial fibrillation were identified. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs) using Cox proportional hazards models after adjustment for age, sex, current smoking, former smoking, body mass index, systolic blood pressure, hypertension, history of myocardial infarction, presence of heart failure, left ventricular hypertrophy on the electrocardiogram, diabetes mellitus, total cholesterol level, and time of the drawing of blood samples. The risk of atrial fibrillation was associated with the TSH level. The multivariate adjusted HR was 1.94 (95% CI, 1.13-3.34, lowest vs highest quartile; P for trend, .02). The multivariate adjusted level of free thyroxine showed a graded association with risk of atrial fibrillation (HR, 1.62; 95% CI, 0.84-3.14, highest vs lowest quartile; P for trend, .06). Within the normal range of thyroid parameters, persons with high-normal thyroid function are at an increased risk of atrial fibrillation.
Nederlands tijdschrift voor geneeskunde, 2010
The revised practice guideline 'Atrial fibrillation' from the Dutch College of General Pr... more The revised practice guideline 'Atrial fibrillation' from the Dutch College of General Practitioners provides the general practitioner with guidelines for diagnosis and management of patients with atrial fibrillation. To find patients with atrial fibrillation, it is advised to check cardiac rhythm at every blood pressure measurement. In patients over 65 years old, acceptance of atrial fibrillation with control of ventricular rate is preferred to sinus rhythm normalisation. In therapy with beta-blockers, slow release metoprolol is the drug of choice. An important goal of treatment is the prevention of thrombo-embolic complications. The choice between anticoagulants such as aspirin and coumarin derivatives is based on the CHADS2 score and determined by age (above 75 years) and comorbidity including cardiac failure, diabetes, hypertension, and previous transient ischaemic attack (TIA) or cardiovascular accident (CVA). The adequacy of antithrombotic treatment should be reassesse...
European Heart Journal, 2008
Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significa... more Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significant morbidity and mortality. A recent genome wide association study identified a haplotype block on Chromosome 4q25 associated with AF.
PLOS ONE, 2015
Atrial fibrillation (AF) is the most common chronic arrhythmia and it increases the risk of cardi... more Atrial fibrillation (AF) is the most common chronic arrhythmia and it increases the risk of cardiovascular morbidity and mortality. Still there is not a complete understanding of its etiology and underlying pathways. Vitamin D might regulate renin-angiotensin-aldosterone system and might be involved in inflammation, both implicated in the pathophysiology of AF. The objective of this work was to investigate the association between vitamin D status with the risk of AF in the elderly. This study was conducted within the Rotterdam Study, a community-based cohort of middle-aged and elderly participants in Rotterdam, The Netherlands. We had 3,395 participants who were free of AF diagnosis at the start of our study and who had vitamin D data available. We analyzed the association between serum 25-hydroxivitamin D (25(OH)D) and incidence of AF using Cox regression models. Vitamin D deficiency was defined as serum 25(OH)D concentrations &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50nmol/l, insufficiency between 50nmol/l and 75nmol/l, while serum 25(OH)D concentrations equal to and above 75nmol/l were considered as adequate. After mean follow-up of 12.0 years 263 (7.7%) participants were diagnosed with incident AF. Vitamin D status was not associated with AF in any of the 3 multivariate models tested (model adjusted for socio-demographic factors and life-style factors: HR per 10 unit increment in serum 25(OH)D 0.96, 95% CI: 0.91-1.02; HR for insufficiency: 0.82, 95%CI: 0.60-1.11,and HR for adequate status: 0.76, 95%CI: 0.52-1.12 compared to deficiency). This prospective cohort study does not support the hypothesis that vitamin D status is associated with AF.
Persons with a clinically recognized myocardial infarction are at increased risk for atrial fibri... more Persons with a clinically recognized myocardial infarction are at increased risk for atrial fibrillation. However a large proportion of all myocardial infarctions remain clinically unrecognized. Whether subjects with electrocardiographic signs of an unrecognized myocardial infarction are also at an increased risk of developing atrial fibrillation is unknown. The objective of this study was to investigate whether unrecognized myocardial infarction was associated with an increased risk of atrial fibrillation in a prospective population-based cohort study. The study is set within the prospective population-based Rotterdam Study. The study population comprised 2505 men and 3670 women without atrial fibrillation at baseline. Participants were classified based on electrocardiography, interview, and clinical data into those with recognized myocardial infarction, those with ECG based unrecognized myocardial infarction and those without myocardial infarction. Atrial fibrillation was ascertained from ECG assessments as well as medical records. During a mean follow-up of 11.7 years (SD 5.0), 329 men and 398 women developed atrial fibrillation. Unrecognized myocardial infarction was associated with a two-fold risk of developing atrial fibrillation in men (HR: 2.21, 95%CI:1.51 to 3.23) compared to men without a history of myocardial infarction, independent of age, and cardiovascular risk factors. In women, unrecognized myocardial infarction was not associated with atrial fibrillation (HR: 0.92, 95%CI:0.59 to 1.44). The presence of an unrecognized myocardial infarction is associated with a twofold increased risk of atrial fibrillation in men, independent of known cardiovascular risk factors.
Heart rhythm : the official journal of the Heart Rhythm Society, 2015
Although sudden cardiac death (SCD) is relatively common, contemporary data on its incidence are ... more Although sudden cardiac death (SCD) is relatively common, contemporary data on its incidence are lacking. The purpose of this study was to investigate the current incidence of SCD and its trend over the past 2 decades in a general middle-aged and elderly population. This study was performed within the Rotterdam Study, a prospective population-based cohort study of persons aged 45 years and older. Age-standardized incidence rates of SCD were calculated. To study trends in incidence, we compared 2 subcohorts within the total study population, 1 followed from 1990-2000 and the other from 2001-2010. From 1990-2010, 5512 of 14,628 participants died, of whom 583 (4.0%) were classified as SCD. The overall incidence was 4.2 per 1000 person-years. The incidence was higher in men (5.2 per 1000 person-years) than in women (3.6 per 1000 person-years). Age-adjusted hazard ratio (HR) 1.84 (95% confidence [CI] 1.56-2.17) and risk of SCD increased with age (HR 1.10 per year; 95% CI 1.09-1.11). The ...
BMJ (Clinical research ed.), 2014
To evaluate differences in first manifestations of cardiovascular disease between men and women i... more To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Prospective population based cohort study. People living in the community in Rotterdam, the Netherlands. 8419 participants (60.9% women) aged ≥ 55 and free from cardiovascular disease at baseline. First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetim...
Preventive Medicine, 2004
In identifying opportunities to improve the quality of stroke prevention in general practice, ins... more In identifying opportunities to improve the quality of stroke prevention in general practice, insight in areas of suboptimal care is essential. This study investigated the quality of care in stroke prevention in general practice and its relation to the occurrence of stroke. Retrospective case-based audit with guideline-based review criteria and final judgment of suboptimal care by an expert panel. A total of 292 stroke patients were identified through stroke registers of two main referral hospitals for stroke in Rotterdam. The general practitioners (GPs) (n = 95) of these patients were approached. The overall response rate from GPs was 81%, and a total of 193 patients from 77 GPs were included in the study. Data on the process of care at patient level were collected by chart review and by structured interviews with GPs during site visits. All cases were presented to a six-member panel of GPs and neurologists. In 44% of the cases, suboptimal care was identified (31% judged as possibly or likely failing to prevent stroke). Of the total number of identified shortcomings, 52% was related to inadequate hypertension control, particularly lack of follow-up after established hypertension. Another 17% of identified shortcomings concerned inadequate cardiovascular risk assessment. A substantial number of shortcomings in care, particularly in the domain of hypertension control and the assessment of patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s risk profiles for cardiovascular disease (CVD), were identified. This study suggests that improving preventive care delivery in general practice could reduce the occurrence of stroke.
PLoS medicine, 2012
Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy ... more Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y...
Journal of the American College of Cardiology, 2004
Journal of the American College of Cardiology, 2006
This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interv... more This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND In developed countries, sudden cardiac death is a major cause of cardiovascular mortality.
Journal of Clinical Epidemiology, 2008
Objective: The aim of the study was to investigate how settings and registry characteristics affe... more Objective: The aim of the study was to investigate how settings and registry characteristics affect the prevalence and nature of multimorbidity in elderly individuals.
Nature genetics, 2009
We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in par... more We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)).
European Journal of Human Genetics, 2003
The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elde... more The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elderly, these mutations might be associated with increased morbidity because of the lifelong accumulation of iron. In a population-based sample of the elderly, we determined the value of genotyping for HFE mutations to screen for subclinical hemochromatosis. HFE genotype frequencies were determined in a random group of 2095 subjects (55 years and over). In this random group, we selected within the six genotype groups a total of 342 individuals and measured their serum transferrin saturation, iron and ferritin levels. We also estimated the heritability and parameters needed to evaluate screening, including the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of HFE genotypes. Iron parameters were significantly increased in subjects homozygous, heterozygous or compound heterozygous. The effect of the mutations was more pronounced in men than in women. For the H63D mutation, an allele dose effect was observed. The HFE gene explained about 5% of the variability in serum iron indices. The PPV for hemochromatosis for the C282Y homozygous was 100% in men and 67% in women. The NPV of the wild-type allele was 97% for both men and women. The sensitivity of both mutations was 70% for men and 52% for women and the specificity was 62% for men and 64% for women. Our study shows that the HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. However, when screening based on these two mutations, some individuals with subclinical hemochromatosis will be missed.
European Heart Journal, 2005
Aims We aimed to investigate the prevalence and incidence of atrial fibrillation (AF) in a large ... more Aims We aimed to investigate the prevalence and incidence of atrial fibrillation (AF) in a large European population-based study.
European Heart Journal, 2008
Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significa... more Context Atrial fibrillation (AF) is the most common sustained arrhythmia and results in significant morbidity and mortality. A recent genome wide association study identified a haplotype block on Chromosome 4q25 associated with AF.
British Journal of Clinical Pharmacology, 2008
Round 1 -source population: 7983 participants 771 died before round 2 794 refused participation i... more Round 1 -source population: 7983 participants 771 died before round 2 794 refused participation in round 2 106 lost to follow-up Round 2 -baseline population: 6312 participants -with 948 chronic users, who were excluded Study population: 5364 participants at risk of new-onset chronic benzodiazepine use Figure 1
BMJ, 2008
Objective To determine the efficacy of statin treatment on risk of coronary heart disease in pati... more Objective To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia.
Archives of Internal Medicine, 2007
Background: Myocardial infarction is an important risk factor for atrial fibrillation, but the ro... more Background: Myocardial infarction is an important risk factor for atrial fibrillation, but the role of subclinical atherosclerosis is unknown. This longitudinal study evaluates whether atherosclerosis affects the risk of atrial fibrillation in persons without overt coronary disease.
Archives of Internal Medicine, 2006
High-dose (pulse) corticosteroid therapy has been associated with the development of atrial fibri... more High-dose (pulse) corticosteroid therapy has been associated with the development of atrial fibrillation. This association, however, is mainly based on case reports. To test the hypothesis that high-dose corticosteroid exposure increases the risk of new-onset atrial fibrillation, we performed a nested case-control study within the Rotterdam Study, a population-based cohort study among 7983 older adults. Cases were defined as persons with incident atrial fibrillation between July 1, 1991, and January 1, 2000. Their date of diagnosis was defined as the index date. All noncases within the Rotterdam Study who were alive and eligible on this index date were used as controls. Subsequently, we compared the proportion of cases and controls that received a corticosteroid prescription within 1 month preceding the index date. Corticosteroid exposure was categorized into high-dose exposure (oral or parenteral steroid at a daily dose &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =7.5 mg of prednisone equivalents) and low-intermediate-dose exposure (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.5 mg of prednisone equivalents or inhaled corticosteroids). There were 385 eligible cases of new-onset atrial fibrillation during the study period. The risk of new-onset atrial fibrillation was significantly higher for persons who received a corticosteroid prescription within 1 month before the index date than for those without (odds ratio [OR], 3.75; 95% confidence interval [CI], 2.38-5.87). However, only high-dose corticosteroid use was associated with an increased risk (OR, 6.07; 95% CI, 3.90-9.42), whereas low-intermediate-dose use was not (OR, 1.42; 95% CI, 0.72-2.82). The association of atrial fibrillation with high-dose corticosteroid use was largely independent of the indication for corticosteroid therapy, since the risk of new-onset atrial fibrillation was not only increased in patients with asthma or chronic obstructive pulmonary disease (OR, 4.02; 95% CI, 2.07-7.81) but also in patients with rheumatic, allergic, or malignant hematologic diseases (OR, 7.90; 95% CI, 4.47-13.98). Our findings strongly suggest that patients receiving high-dose corticosteroid therapy are at increased risk of developing atrial fibrillation.
Archives of Internal Medicine, 2008
Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fib... more Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fibrillation. We aimed to investigate the association of high-normal thyroid function with the development of atrial fibrillation in a prospective population-based study in the elderly. The association between thyroid-stimulating hormone (TSH) levels and atrial fibrillation was examined in 1426 subjects with TSH levels in the normal range (0.4-4.0 mU/L) and without atrial fibrillation at baseline. In 1177 of the 1426 persons in this group, we also examined the association between free thyroxine levels within the normal range (0.86-1.94 ng/dL [to convert to picomoles per liter, multiply by 12.871]) and atrial fibrillation. During a median follow-up of 8 years, 105 new cases of atrial fibrillation were identified. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs) using Cox proportional hazards models after adjustment for age, sex, current smoking, former smoking, body mass index, systolic blood pressure, hypertension, history of myocardial infarction, presence of heart failure, left ventricular hypertrophy on the electrocardiogram, diabetes mellitus, total cholesterol level, and time of the drawing of blood samples. The risk of atrial fibrillation was associated with the TSH level. The multivariate adjusted HR was 1.94 (95% CI, 1.13-3.34, lowest vs highest quartile; P for trend, .02). The multivariate adjusted level of free thyroxine showed a graded association with risk of atrial fibrillation (HR, 1.62; 95% CI, 0.84-3.14, highest vs lowest quartile; P for trend, .06). Within the normal range of thyroid parameters, persons with high-normal thyroid function are at an increased risk of atrial fibrillation.