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A Hofman

Publications and source records attributed to A Hofman.

At least 19 recordsLinked to original sources
PubMed2007

Polymorphisms of the renin-angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology.

BACKGROUND: The renin-angiotensin system is involved in the development of hypertension, atherosclerosis and cardiovascular disease. We studied the association between the M235T polymorphism of the angiotensinogen gene (AGT) and the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood pressure, carotid atherosclerosis and cerebrovascular disease. METHODS: We genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects from the Rotterdam Scan Study. We used logistic regression and univariate analyses, adjusting for age and sex with, for AGT, the MM and, for AT1R, the TT genotype as reference. RESULTS: We found that AGT-235T increased systolic (p for trend = 0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence of carotid plaques was increased 1.25-fold (95% CI 1.02-1.52) in AGT-TT carriers. There was a significant increase in mean volume deep subcortical white matter lesions (WML) for AGT-TT carriers (1.78 ml vs 1.09 ml in the reference group; p = 0.008). A significant interaction was found between AGT and AT1R, further increasing the effect on periventricular and subtotal WML (p for interaction = 0.02). We found a non-significant increased risk of silent brain infarction for AGT-TT carriers and AT1R-CC carriers, but no effect on stroke. CONCLUSION: We found an association between AGT and blood pressure, atherosclerosis and WML. Also, we found synergistic effects between AGT and AT1R on the development of WML. These findings raise the question of whether the renin-angiotensin system may be a therapeutic target for the prevention of cerebral white matter pathology.

Aged↗
PubMed2006

Diuretic-gene interaction and the risk of myocardial infarction and stroke.

This study investigates whether the interaction between diuretics and alpha-adducin (ADD1) G460W or G-protein beta3-subunit (GNB3) rs2301339 polymorphism modifies the risk of myocardial infarction (MI) or stroke. Data were used from the Rotterdam Study. The drug-gene interaction was determined with a Cox proportional hazard model with adjustment for each drug class as time-dependent covariates. The risk of MI in current users of low-ceiling diuretics with one or two copies of the ADD1 W-allele (hazard ration (HR)=0.92) was similar compared to the expected joint effect of the W-allele and low-ceiling diuretics on a multiplicative scale (1.04 x 0.90=0.94) (synergy index (SI):0.99; 95% confidence interval (CI): 0.43-2.27). No drug-gene interaction was found on the risk of stroke (SI:0.66; 95% CI:0.43-1.27). In addition, a trend towards an interaction was found between current use and the GNB3 rs230119 G/A polymorphism on the risk of MI (SI: 0.51; 95% CI: 0.23-1.15), whereas no interaction on the risk of stroke was found (SI: 0.84; 95% CI: 0.46-1.56).

Aged↗
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

Transforming-growth factor beta1 Leu10Pro polymorphism and breast cancer morbidity.

TGF-beta1 has a dual role in carcinogenesis. In this gene, a leucine to proline substitution in codon 10 leads to higher circulating levels of TGF-beta1. This variant has been studied in relationship to the risk for breast cancer yielding contradicting results. We aim to unravel the relationship of this polymorphism and the risk of breast cancer. Women participating in the Rotterdam Study including 143 patients with incident breast cancer were genotyped for this polymorphism. We carried out a logistic regression and a survival analysis using age as the time variable. The logistic regression analysis showed an increased risk of breast cancer for Proline carriers (OR=1.4; 95% confidence interval (CI)=1.1-2.0) versus non-carriers. The survival analysis showed that carriers of the same allele had an increased risk of breast cancer (HR=1.4, 95% CI=1.1-2.0) against non-carriers. Our data suggest that the TGF-beta1 Leu10Pro polymorphism might play a role in breast cancer risk.

Aged↗
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

Differential roles of Angiotensinogen and Angiotensin Receptor type 1 polymorphisms in breast cancer risk.

While angiotensinogen (AGT) seems to have anti proliferative properties, angiotensin II (ATII) is a potent growth factor and it mediates its actions through the angiotensin type 1 receptor (AGTR1). In the AGT gene, the M235T polymorphism has been associated with the variation in angiotensinogen levels and in the AGTR1 gene; the C573T variant is associated with different pathologies. We aimed to evaluate the relationship of these two variants and the risk of breast cancer. These polymorphisms were genotyped in 3787 women participating the Rotterdam Study. We performed a logistic regression and a disease free survival analysis by genotype. The logistic regression yielded an odds ratio of 1.4 (95% CI: 1.1-1.9) for the MM genotype carriers versus the T allele carriers. The breast cancer free survival by AGT genotype was significantly reduced in MM genotype carriers compared to non-carriers (hazard ratio (HR) = 1.5; 95% CI: 1.1-2.2). We did not find any association of the AGTR1 polymorphism and breast cancer risk or disease free survival. Our results suggest that AGT plays a role in breast cancer risk in postmenopausal women, whereas the role of AGTR1 needs further studying.

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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

Interleukin 6 G-174 C polymorphism and breast cancer risk.

Interleukin-6 (IL-6) is a growth factor involved in many processes including carcinogenesis. The C allele of the G-174 C promoter single nucleotide polymorphism (SNP) in the IL-6 gene decreases levels of IL-6 expression and it has been studied in the context of breast cancer progression yielding contradicting results. Furthermore a recent study found that carriers of the C allele were at an increased risk for this disease. We aim to evaluate the association between this variant and breast cancer risk in Caucasian postmenopausal women. Women participating in the Rotterdam Study (N=3822), including 171 patients with breast cancer were genotyped for this polymorphism. In order to assess the relationship between this SNP and breast cancer we carried out a logistic regression in relation to the incidence of breast cancer. The C allele frequency was 41.3% and the genotypes followed Hardy-Weinberg distribution (p=0.3). The logistic regression analysis showed a slight increase of risk for C allele carriers (odds ratio=1.24, 95% CI: 0.8-1.9), compared to non-carriers of this allele. This increased risk was not statistically significant. Our data suggest that the IL-6 G-174 C polymorphism does not seem to play a role in breast cancer risk, although its role as a prognostic factor remains to be studied.

Aged↗
PubMed2006

Retinal vessel diameters and risk of stroke: the Rotterdam Study.

BACKGROUND: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly predicts the risk of stroke. It is unclear if this is due to arteriolar narrowing or venular dilation. OBJECTIVE: To investigate whether smaller arteriolar or larger venular diameters are related to the risk of stroke and cerebral infarction. METHODS: This study was based on the prospective population-based Rotterdam Study and included 5,540 participants of 55 years or over, who had gradable fundus transparencies and were free of stroke at baseline (1990 to 1993). For each participant, retinal arteriolar and venular diameters were measured on digitized images of one eye. Follow-up for first-ever stroke was complete until January 1, 2002. RESULTS: After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259 had cerebral infarction. Larger venular diameters were associated with an increased risk of stroke (hazard ratio [HR] adjusted for age and sex per SD increase: 1.12 [95% CI: 1.02 to 1.24]) and cerebral infarction (HR: 1.15 [95% CI: 1.02 to 1.29]). Smaller arteriolar diameters were neither related to the risk of stroke (HR per SD decrease: 1.02 [95% CI: 0.93 to 1.13]) nor to the risk of cerebral infarction (HR: 1.02 [95% CI: 0.90 to 1.15]). After additional adjustment for other cardiovascular risk factors, the results did not change. CONCLUSIONS: Larger retinal venular diameters are associated with an increased risk of stroke and cerebral infarction. The role of venules in cerebrovascular disease warrants further exploration.

Age Factors↗
PubMed2006

MR spectroscopy of brain white matter in the prediction of dementia.

BACKGROUND: Previous 1H-MR spectroscopy (MRS) studies compared biochemical spectra of persons with dementia with those of healthy control subjects. Given the long prodromal period of Alzheimer disease (AD), the authors sought to investigate whether biochemical changes can be observed also in the preclinical period. METHODS: The authors prospectively followed 509 elderly persons (ages 60 to 90), who were free of clinical dementia at baseline, for on average 5.9 years. At baseline, 1H-MRS of the brain (1.5 T) was performed in a plane above the lateral ventricles that comprised mainly white matter voxels. Standard ratios of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were calculated. Structural MRI was administered to assess white matter lesions and hippocampal atrophy. All persons were followed for incident dementia through repeated neuropsychological testing and linkage with medical records. RESULTS: During follow-up, 37 persons developed dementia, of whom 27 fulfilled criteria for AD. Overall, biochemical ratios on 1H-MRS at baseline were not associated with the risk of incident dementia. However, people with higher Cho/Cr ratios had a higher risk to develop dementia or AD within 4 years (hazard ratio for dementia per SD increase 1.55 [95% CI 1.05 to 2.28]). This association attenuated and became nonsignificant after adjustment for white matter lesions on MRI. CONCLUSION: These data suggest that there are biochemical changes on 1H-MR spectroscopy of brains of persons with presymptomatic dementia.

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PubMed2006

Polypharmacy and falls in the middle age and elderly population.

AIM: Falls in the elderly are common and often serious. We studied the association between multiple drug use (polypharmacy) and falls in the elderly. METHODS: This was a population-based cross-sectional study, part of the Rotterdam Study. The participants were 6928 individuals aged > or = 55 years. The prevalence of falls in the previous year was assessed. Medication use was determined with an interviewer-administered questionnaire with verification of use. Polypharmacy was defined as the use of four or more drugs per day. RESULTS: The prevalence of falls strongly increased with age. Falls were more common in women than in men. Fall risk increased with increasing disability, presence of joint complaints, use of a walking aid and fracture history. The risk of falling increased significantly with the number of drugs used per day (P for trend < 0.0001). After adjustment for a large number of comorbid conditions and disability, polypharmacy remained a significant risk factor for falling. Stratification for polypharmacy with or without at least one drug which is known to increase fall risk (notably CNS drugs and diuretics) disclosed that only polypharmacy with at least one risk drug was associated with an increased risk of falling. CONCLUSIONS: Fall risk is associated with the use of polypharmacy, but only when at least one established fall risk-increasing drug was part of the daily regimen.

Accidental Falls↗
PubMed2006

Risk factors for Alzheimer's disease in Russia: a case-control study.

No reliable data on risk factors of Alzheimer's disease (AD) are available in Russia. We aimed to evaluate the relative importance of various putative environmental and medical risk factors of AD in a Russian population. We conducted a hospital-based case-control study. Two hundred and sixty consecutive AD patients and an equal number of cognitive impairment-free control subjects matched for sex, age, level of education and place of birth selected from nursing homes and other long-term healthcare facilities in the Novosibirsk region for the period from 1998 to 2002 were examined. A conditional logistic regression analysis was employed to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for various putative risk factors. Of the 260 patients with AD, 187 (72%) were females. Patients' age varied from 40 to 89 years (mean +/- SD: 69.2 +/- 7.7 years). The majority of the patients (77%) had secondary education and 12% had university education. Risk factors independently associated with AD were family history of parkinsonism among first-degree relatives (OR = 4.2; 95% CI 1.2-15.1), hypothyroidism (OR = 2.7; 95% CI 1.1-6.7), and history of head trauma with loss of consciousness (OR = 1.7; 95% CI 1.0-2.8). The most important risk factors for AD in the Russian community are family history of parkinsonism, hypothyroidism and a history of head trauma with loss of consciousness. These findings have implications for developing preventive strategies of AD.

Adult↗
PubMed2006

Insulin-like growth factor I promoter polymorphism, risk of stroke, and survival after stroke: the Rotterdam study.

BACKGROUND AND PURPOSE: Low levels of insulin-like growth factor I (IGF-I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of cardiovascular and cerebrovascular disease. A polymorphism in the promoter region of the IGF-I gene influences IGF-I levels. Non-carriers of the 192 bp allele have lower levels of IGF-I compared with 192 bp allele carriers. We studied the IGF-I polymorphism in relation to the risk of stroke and survival after stroke. METHODS: We studied 6808 subjects of the Rotterdam Study, who were followed for the occurrence of stroke and death after stroke. Subjects were grouped according to the 192 bp allele of IGF-I into non-carriers, heterozygotes, and homozygotes. The risk of stroke and survival after stroke was studied using Cox regression analysis, adjusting for age and sex, with homozygotes for the wildtype allele as the reference. RESULTS: Non-carriers had a relative risk of 0.8 (95% CI: 0.6 to 1.0) for the occurrence of any stroke and 0.7 (95% CI: 0.5 to 1.0) for ischaemic stroke. For non-carriers, the relative risk of death after any stroke was 1.5 (95% CI: 1.0 to 2.2). After an ischaemic stroke, this relative risk was 1.5 (95% CI: 0.9 to 2.6) and after a haemorrhagic stroke 5.2 (95% CI: 1.3 to 21.5). CONCLUSIONS: Our study suggests that IGF-I is a significant determinant of survival after stroke.

Aged↗
PubMed2006

An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance.

OBJECTIVE: Microalbuminuria (MA) is related to cardiovascular disease both in diabetic patients and non-diabetic subjects. DESIGN: We investigated whether a polymorphism near the promoter region of the IGF-I gene was related to the development of MA. METHODS: For this study, 1069 participants of the Rotterdam study were selected (440 participants with an abnormal glucose tolerance (AGT), 220 participants with type 2 diabetes and 254 subjects with pre-diabetes, and 595 subjects with a normal glucose tolerance (NGT). RESULTS: 787 subjects were carriers of the wild type IGF-I genotype (73.6%) and 282 subjects were variant carriers (26.4%) of this IGF-I gene polymorphism. Compared to subjects with NGT the risk for microalbuminuria was higher (Odds Ratio (OR): 3.1 (95% CI: 1.2-7.7); P = 0.02) in variant carriers with AGT than in carriers of the wild type of this IGF-I gene polymorphism (OR: 2.2 (95% CI: 1.2-4.0); P = 0.009). Compared with wild type carriers with AGT, the relative risk for MA was unadjusted and non-significantly increased in variant carriers with AGT (1.6; 95% CI: 0.8-2.9). However, after adjustment for possible confounding factors (age, gender, mean blood pressure, fasting insulin, fasting glucose and smoking) this risk became significant (OR: RR 2.1; 95% CI:1.1-4.4; P = 0.04). CONCLUSIONS: In subjects with AGT, a higher risk for MA was observed in variant carriers than in carriers of the wild type genotype of this IGF-I gene polymorphism. Since MA is primarily associated with cardiovascular disease in subjects with AGT, our study suggests that variant carriers have a higher risk for cardiovascular disease than carriers of the wild type when they develop an AGT.

Aged↗
PubMed2005

Regional variability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE).

White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions.

Aged↗
PubMed2005

C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study.

BACKGROUND: Inflammatory processes are involved in the development and consequences of atherosclerosis. Whether these processes are also involved in cerebral small-vessel disease is unknown. Cerebral white matter lesions and lacunar brain infarcts are caused by small-vessel disease and are commonly observed on MRI scans in elderly people. These lesions are associated with an increased risk of stroke and dementia. We assessed whether higher C-reactive protein (CRP) levels were related to white matter lesion and lacunar infarcts. METHODS AND RESULTS: We based our study on 1033 participants of the population-based Rotterdam Scan Study for whom complete data on CRP levels were available and who underwent brain MRI scanning. Subjects were 60 to 90 years of age and free of dementia at baseline. Six hundred thirty-six subjects had a second MRI scan on average 3.3 years later. We used multivariate regression models to assess the associations between CRP levels and markers of small-vessel disease. Higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 [95% CI 1.3 to 7.2] and 2.5 [95% CI 1.1 to 5.6] for periventricular and subcortical white matter lesion progression, respectively). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts. CONCLUSIONS: Inflammatory processes may be involved in the pathogenesis of cerebral small-vessel disease, in particular, the development of white matter lesions.

Aged↗
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↗