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J C M Witteman

Publications and source records attributed to J C M Witteman.

At least 19 recordsLinked to original sources
PubMed2006

Unrecognized myocardial infarction and the risk of stroke: the Rotterdam Study.

OBJECTIVE: To investigate the relationship between unrecognized myocardial infarction and the risk of stroke in a population-based cohort study. METHODS: We followed 6,439 participants from the Rotterdam Study for stroke until January 2002. Participants were free from stroke, and presence of myocardial infarction was assessed at baseline (1990-1993). We calculated hazard ratios of stroke for persons with unrecognized or recognized myocardial infarction compared with persons without myocardial infarction. Analyses were adjusted for age, sex, and cardiovascular risk factors. RESULTS: In 52,915 person-years of follow-up, 505 strokes occurred. Recognized myocardial infarction was only borderline associated with an increased risk of stroke. Unrecognized myocardial infarction increased the risk of stroke by 76% (age- and sex-adjusted hazard ratio 1.76, 95% CI 1.31 to 2.37). Stratification by sex showed that the increased risk was only found in men (hazard ratio for men 2.53, 95% CI 1.68 to 3.81; hazard ratio for women 1.27, 95% CI 0.82 to 1.96). After adjusting for cardiovascular risk factors at baseline, the risk remained significantly increased in men (hazard ratio for stroke 2.13, 95% CI 1.35 to 3.36). Subtyping of strokes revealed that unrecognized myocardial infarction was particularly associated with cortical ischemic strokes (hazard ratio for men 3.57, 95% CI 1.79 to 7.12). CONCLUSIONS: Men with unrecognized myocardial infarction have an increased risk of stroke.

Age Distribution↗
PubMed2006

Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease.

BACKGROUND: Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Higher dietary intakes of folate, vitamin B12, and vitamin B6 (cofactors in homocysteine metabolism) might decrease the risk of PD through decreasing plasma homocysteine. Moreover, vitamin B6 might influence the risk of PD through antioxidant effects unrelated to homocysteine metabolism and through its role in dopamine synthesis. METHODS: In the Rotterdam Study, a prospective, population-based cohort study of people aged 55 years and older, the authors evaluated the association between dietary intake of folate, vitamin B12, and vitamin B6 and the risk of incident PD among 5,289 participants who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination and continuous monitoring by computer linkage to medical records. Data were analyzed using Cox proportional hazards regression analysis. RESULTS: After a mean follow-up of 9.7 years, the authors identified 72 participants with incident PD. Higher dietary intake of vitamin B6 was associated with a significantly decreased risk of PD (hazard ratio per SD, 0.69 [95% CI 0.50 to 0.96]; for highest vs lowest tertile, 0.46 [0.22 to 0.96]). Stratified analyses showed that this association was restricted to smokers. No association was observed for dietary folate and vitamin B(12). CONCLUSIONS: Dietary vitamin B6 may decrease the risk of Parkinson disease, probably through mechanisms unrelated to homocysteine metabolism.

Administration, Oral↗
PubMed2006

A longitudinal population-based study of prothrombotic factors in elderly subjects with atrial fibrillation: the Rotterdam Study 1990-1999.

BACKGROUND: A prothrombotic or hypercoagulable state in atrial fibrillation may contribute to stroke and thromboembolism. Results of longitudinal population-based studies in elderly people with atrial fibrillation are not yet available. METHODS: In the Rotterdam Study, a population-based prospective cohort study, 162 participants with atrial fibrillation at baseline, aged 55 years and over, were matched for age and gender with 324 people in sinus rhythm. Associations were examined between three coagulation factors and the risk of total and cardiac mortality and stroke. Hazard rate ratios were calculated with 95% confidence intervals using Cox's proportional hazards model, adjusted for potential confounders. RESULTS: Plasma von Willebrand factor was, age- and gender-adjusted, associated with cardiac mortality in the total population (relative risk 1.16; 1.06-1.27, per 10 IU dL(-1) increase), but statistical significance was lost after additional adjustments. A strong association (1.27; 1.08-1.50, per 5-unit increase) was found between soluble P-selectin (sP-sel) and cardiac mortality in atrial fibrillation patients but not in participants in sinus rhythm. Furthermore, the expected association between fibrinogen and cardiac mortality was observed only in those in sinus rhythm (2.60; 1.69-4.01, per unit increase), and not in atrial fibrillation. No associations were found between coagulation factors and stroke. CONCLUSIONS: In this population-based study, plasma levels of sP-sel predicted clinical adverse outcomes in atrial fibrillation, suggesting a role of platelets in the prothrombotic state associated with atrial fibrillation. Fibrinogen was a risk factor of cardiac and all-cause mortality in sinus rhythm, but not in atrial fibrillation.

Aged↗
PubMed2006

ACE polymorphisms.

Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3' UTR. The potential existence of another functional polymorphism in the 5' UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.

Humans↗
PubMed2005

Heritability of the function and structure of the arterial wall: findings of the Erasmus Rucphen Family (ERF) study.

BACKGROUND AND PURPOSE: Using 930 individuals connected in a single pedigree from an isolated population, participants of the Erasmus Rucphen Family (ERF) study, we investigated the heritability of carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (IMT), and carotid plaque score. METHODS: PWV was measured between the carotid and femoral arteries as an indicator of aortic stiffness. Common carotid IMT and plaque score, quantifying alterations in arterial wall structure, were measured by ultrasonography. RESULTS: All 3 traits were significantly associated with classic cardiovascular risk factors. Age- and gender-adjusted heritability estimates were 0.36 for PWV, 0.41 for carotid IMT, and 0.28 for plaque score. After adjustment for appropriate risk factors, the heritabilities were 0.26, 0.35, and 0.21 for PWV, IMT, and plaque score, respectively. All heritability estimates were statistically significant (P<0.001). Taking into account different proportions of variance associated with covariates for each trait, genetic factors explained &12% of the total variability for each of the phenotypes. CONCLUSIONS: To our knowledge, this is the first report on the heritability of PWV. The heritability estimates of IMT and plaque score were similar to those in previous reports. We conclude that genetic factors significantly contribute to arterial structure and function in this isolated population, presenting the opportunity to locate susceptibility genes related to cardiovascular disorders.

Adult↗
PubMed2005

Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study.

BACKGROUND: Unsaturated fatty acids are important constituents of neuronal cell membranes and have neuroprotective, antioxidant, and anti-inflammatory properties. OBJECTIVE: To determine if a high intake of unsaturated fatty acids might be associated with a lower risk of Parkinson disease (PD). METHODS: In the Rotterdam Study, a prospective population-based cohort study of people ages > or =55, the association between intake of unsaturated fatty acids and the risk of incident PD was evaluated among 5,289 subjects who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination, and the cohort was continuously monitored by computer linkage to medical records. The data were analyzed using Cox proportional hazards regression models. RESULTS: After a mean follow-up of 6.0 years, 51 participants with incident PD were identified. Intakes of total fat, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were significantly associated with a lower risk of PD, with an adjusted hazard ratio per SD increase of energy-adjusted intake of 0.69 (95% CI 0.52 to 0.91) for total fat, of 0.68 (95% CI 0.50 to 0.94) for MUFAs, and 0.66 (95% CI 0.46 to 0.96) for PUFAs. No associations were found for dietary saturated fat, cholesterol, or trans-fat. CONCLUSION: These findings suggest that high intake of unsaturated fatty acids might protect against Parkinson disease.

Aged↗
PubMed2005

Ethnic differences in prenatal growth and the association with maternal and fetal characteristics.

OBJECTIVES: The objectives of this study were to determine ethnic differences in prenatal growth and to examine their association with differences in maternal and fetal characteristics such as maternal height, weight, age, parity and fetal gender. METHODS: A total of 1494 women from Rotterdam, The Netherlands, with a low-risk pregnancy who participated in a population-based cohort study, the Generation R Study, were offered three ultrasound examinations during pregnancy. Multilevel modeling was applied to determine ethnic differences in (estimated) fetal weight (including birth weight) and in the separate biometric variables that were used to calculate the estimated fetal weight (abdominal circumference, head circumference and femur length). Additionally the association of ethnic differences with maternal and fetal characteristics (i.e. maternal weight, height, age, parity and fetal gender) was studied. RESULTS: Turkish, Cape Verdian, Surinamese-Creole and Surinamese-Hindustani women had on average smaller fetuses than the native Dutch women. The differences became more pronounced towards term. In the Turkish group the differences were no longer statistically significant when adjusted for maternal weight, height, age, parity and fetal gender. In the Cape Verdian, Surinamese-Creole and Surinamese-Hindustani groups the differences decreased after adjustment (31%, 16% and 39%, respectively). CONCLUSIONS: This study shows that there are ethnic differences in fetal growth, which to a large extent may be attributed to differences in maternal weight, height, age and parity. For some ethnic groups, however, additional factors are involved, as differences remain significant after correction for fetal and maternal characteristics.

Anthropometry↗
PubMed2005

Insertion/deletion polymorphism of the ACE gene and adherence to ACE inhibitors.

AIMS: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug. METHODS: This was a cohort study among 239 subjects who started ACE inhibitor therapy. A Cox proportional hazard model was used to calculate relative risk (RR). RESULTS: During follow-up there was no significant difference between subjects with the DD, ID or II genotype (DD vs II; RR = 1.17, 95%CI: 0.78, 1.77 and ID vs II; RR = 1.06, 95%CI: 0.73, 1.55) in adherence. CONCLUSIONS: The I/D polymorphism of the ACE gene does not influence the adherence to ACE inhibitors.

Aged↗
PubMed2005

Angiotensin converting enzyme gene, smoking and mortality in a population-based study.

BACKGROUND: The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly. MATERIALS AND METHODS: Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted. RESULTS: Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1.8, 95% CI 1.1-2.9, P = 0.016). This association was significant in total and cause specific mortality only in those who smoke (P-value < 0.001 for gene-age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late. CONCLUSIONS: Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene.

Aged↗
PubMed2005

Angiotensin converting enzyme gene polymorphism and cardiovascular morbidity and mortality: the Rotterdam Study.

BACKGROUND: Findings on the association between the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene and cardiovascular morbidity and mortality have been inconsistent. Considering the possible interaction between this polymorphism and smoking, we evaluated the association between ACE I/D polymorphism and myocardial infarction (MI), mortality due to coronary heart disease (CHD), and cardiovascular disease (CVD). METHODS: The study was performed within the Rotterdam Study, a population based cohort study. The ACE I/D polymorphism was determined for 6714 participants and smoking status recorded at baseline. Fatal and non-fatal MIs and mortality events were regularly recorded. Cox proportional hazard analysis was performed separately for current smokers and non-smokers. We used age as the follow up time, presenting age specific survivals. RESULTS: During follow up, 248 MIs and 301 and 482 deaths, respectively, due to CHD and CVD occurred. There were no significant differences between the genotypes as regards MI incidence. Among smokers, there was an increased risk of CHD and CVD mortality in carriers of the DD genotype compared to the II genotype, which diminished at later ages (p<0.01 for gene-age interaction). Subgroup analysis in a younger and older group (based on the median age of 68.2 years) showed a significantly increased risk of CVD mortality in the younger group (hazard ratio = 5.19; 95% confidence interval: 1.15 to 23.42). CONCLUSIONS: This study showed that the ACE I/D polymorphism is not a strong risk factor for MI but its interaction with smoking might play a role in cardiovascular mortality especially at younger ages.

Aged↗
PubMed2004

The impact of APOE on myocardial infarction, stroke, and dementia: the Rotterdam Study.

It is unclear how the APOE genotype contributes to the incidence of vascular diseases and dementia. In a population-based sample (n = 6,852) with complete follow-up, APOE was weakly associated with myocardial infarction and not related with stroke. In the absence of epsilon4, the incidence of dementia would be 25.8% lower; in the absence of epsilon2/epsilon3, 2.8% higher. Risk estimates of dementia, specified for age, sex, and APOE, are provided for counseling. APOE is not strongly related to vascular diseases, but contributes substantially to dementia incidence.

Age Distribution↗
PubMed2004

Risk profiles and prognosis of treated and untreated hypertensive men and women in a population-based longitudinal study: the Reykjavik Study.

The aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10 062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage.

Adult↗
PubMed2004

A study of gene--environment interaction on the gene for angiotensin converting enzyme: a combined functional and population based approach.

INTRODUCTION: Studies on the role of the insertion/deletion (I/D) polymorphism of the gene coding for angiotensin converting enzyme (ACE) in atherosclerosis have been inconsistent. In a meta-analysis, we recently showed that this relationship is stronger in high risk populations. In this paper, we used a combined functional and population based approach to investigate the gene-environment interaction of the ACE I/D polymorphism in relation to carotid artery wall thickness. METHODS: The study was part of the Rotterdam Study, a prospective population based cohort study. In 5321 subjects, IMT was measured in the carotid arteries by ultrasonography and ACE genotype was determined by size analysis of polymerase chain reaction products. RESULTS: In multiple regression analysis, I/D polymorphism and smoking were the main determinants for plasma ACE activity (r(2) = 0.28). There was a positive association between the D allele of the I/D polymorphism and carotid artery thickness among current smokers (p = 0.03). Subjects carrying only one of the risk factors (smoking or the D allele) did not show significant differences in IMT compared with the non-/former smokers group carrying two II alleles, while carriers of both risk factors had significant higher IMT. The association was not present in non-/former smokers. DISCUSSION: The results provide further evidence that genetic and environmental factors interact in the formation of the arterial lesions. This study shows that large population based studies can be extremely helpful in unravelling the genetic origin of complex diseases such as atherosclerosis.

Aged↗
PubMed2003

Comparison between measures of atherosclerosis and risk of stroke: the Rotterdam Study.

BACKGROUND AND PURPOSE: Several measures of atherosclerosis predict the risk of stroke. However, a comparison between various measures of atherosclerosis is lacking, and limited information exists on the added value of individual measures of atherosclerosis to cardiovascular risk factors. We compared different measures of atherosclerosis in relation to stroke. METHODS: The study was based on the prospective cohort of the Rotterdam Study and included 6913 participants who did not suffer from previous stroke. At baseline, carotid intima-media thickness and plaques, ankle-arm index, and aortic calcifications were assessed; 3996 participants (53%) had measures of all studied markers of atherosclerosis. After a mean follow-up of 6.1 years, 378 strokes occurred. Data were analyzed with Cox proportional-hazards regression and Akaike information criteria scores. RESULTS: Carotid intima-media thickness and aortic calcifications were related most strongly to the risk of stroke (relative risk, 2.23 and 1.89; 95% confidence interval, 1.48 to 3.36 and 1.28 to 2.80 for highest versus lowest tertile, respectively). The relations between intima-media thickness, aortic calcifications, and carotid plaques and stroke remained after adjustment for cardiovascular risk factors. Intima-media thickness and aortic calcifications were related to the risk of stroke independently of each other. The relation between ankle-arm index and stroke disappeared after adjustment for cardiovascular risk factors. CONCLUSIONS: Carotid intima-media thickness and aortic calcifications are stronger predictors of incident stroke than carotid plaque or ankle-arm indexes. They have additional value to each other and to classic risk factors and may reflect different processes.

Aged↗
PubMed2003

Polymorphism in the promoter region of the insulin-like growth factor I gene is related to carotid intima-media thickness and aortic pulse wave velocity in subjects with hypertension.

BACKGROUND AND PURPOSE: Low circulating levels of insulin-like growth factor I (IGF-I) have been associated with an increased risk for atherosclerosis. Absence of the 192-bp (wild-type) allele in the promoter region of the IGF-I gene has been associated with low circulating IGF-I levels. We examined the role of this polymorphism in relation to blood pressure and 2 early markers of atherosclerosis: carotid intima-media thickness (IMT) and aortic pulse wave velocity (PWV). METHODS: A total of 5132 subjects of the Rotterdam Study, aged 55 to 75 years, were included in this study. In 3769 subjects who did not use blood pressure-lowering medication, the association between the IGF-I polymorphism and blood pressure was examined. In the total population, and in 3484 normotensive subjects, 1648 hypertensive and 462 untreated hypertensive subjects, the association between this polymorphism and IMT and PWV was examined. RESULTS: Mean systolic and diastolic blood pressure did not differ between genotypes. In hypertensive subjects IMT was significantly increased in noncarriers of the 192-bp allele (0.83 mm) compared with heterozygous or homozygous carriers (0.80 mm) (P=0.04). PWV was also significantly higher in hypertensive subjects who were noncarriers of the 192-bp allele (14.3 m/s) compared with heterozygous (14.1 m/s) or homozygous carriers (13.7 m/s) (P=0.02). Findings were more pronounced in hypertensive subjects without medication use. In normotensive subjects, no association between this polymorphism, IMT, and PWV was observed. CONCLUSIONS: Our study suggests that hypertensive subjects who have low IGF-I levels because of a genetic polymorphism in the IGF-I gene are at increased risk of developing atherosclerosis.

Aged↗
PubMed2002

Diet and risk of dementia: Does fat matter?: The Rotterdam Study.

OBJECTIVE: To examine whether high intake of total fat, saturated fatty acids (saturated fat), trans fatty acids (trans fat), and cholesterol and low intake of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-6 PUFA, and n-3 PUFA are associated with increased risk of dementia and its subtypes. METHOD: Data from the Rotterdam Study, a prospective cohort study among elderly, were used. At baseline (1990 to 1993), 5,395 subjects had normal cognition, were noninstitutionalized, and underwent complete dietary assessment by a semiquantitative food-frequency questionnaire. The cohort was continuously monitored for incident dementia, and re-examinations were performed in 1993 to 1994 and 1997 to 1999. The association between fat intake and incident dementia was examined by Cox's proportional hazards models. RESULTS: After a mean follow-up of 6.0 years, 197 subjects developed dementia (146 AD, 29 vascular dementia). High intake of total, saturated, trans fat, and cholesterol and low intake of MUFA, PUFA, n-6 PUFA, and n-3 PUFA were not associated with increased risk of dementia or its subtypes. Rate ratios of dementia per standard deviation increase in intake were for total fat 0.93 (95% CI 0.81 to 1.07), for saturated fat 0.91 (95% CI 0.79 to 1.05), for trans fat 0.90 (95% CI 0.77 to 1.06), for cholesterol 0.93 (95% CI 0.80 to 1.08), for MUFA 0.96 (95% CI 0.84 to 1.10), for PUFA 1.05 (95% CI 0.80 to 1.38), for n-6 PUFA 1.03 (95% CI 0.77 to 1.36), and for n-3 PUFA 1.07 (95% CI 0.94 to 1.22). CONCLUSION: High intake of total, saturated, and trans fat and cholesterol and low intake of MUFA, PUFA, n-6 PUFA, and n-3 PUFA were not associated with increased risk of dementia or its subtypes.

Age Factors↗
PubMed2002

Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam study.

BACKGROUND: Few studies have quantified the relation between carotid plaques and stroke in asymptomatic patients, and limited data exist on the importance of location of plaques or the association with subtypes of cerebral infarction. We investigated the relationship between carotid plaques, measured at different locations, and risk of stroke and subtypes of cerebral infarction in a population-based study. Methods and Results- The study was based on the Rotterdam Study and included 4217 neurologically asymptomatic subjects aged 55 years or older. Presence of carotid plaques at 6 locations in the carotid arteries was assessed at baseline. Severity was categorized according to the number of affected sites. After a mean follow-up of 5.2 years, 160 strokes had occurred. Data were analyzed using Cox proportional hazards regression. Plaques increased the risk of stroke and cerebral infarction approximately 1.5-fold, irrespective of plaque location. Severe carotid plaques increased the risk of nonlacunar infarction in anterior (RR 3.2 [95% CI, 1.1 to 9.7]) but not in posterior circulation (RR 0.6 [95% CI, 0.1 to 4.9]). A >10-fold increased risk of lacunar infarction was found in subjects with severe plaques (RR 10.8 [95% CI, 1.7 to 69.7]). No clear difference in risk estimates was seen between ipsilateral and contralateral infarction. CONCLUSIONS: Carotid plaques increase the risk of stroke and cerebral infarction, irrespective of their location. Plaques increase the risk of infarctions in the anterior but not in the posterior circulation. It is likely that carotid plaques in neurologically asymptomatic subjects are both markers of generalized atherosclerosis and sources of thromboemboli.

Aged↗