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Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 73 records · Page 4Linked to original sources
PubMed2005

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

Generalized retinal arteriolar narrowing is an important sign of systemic hypertension, and a lower arteriolar:venular diameter ratio predicts the risk of hypertension. We investigated whether this association was based on arteriolar or venular diameters or both. This study was based on the prospective population-based Rotterdam Study (1990-1993) and included 1900 participants (> or =55 years of age) of whom 739 persons had normal blood pressure (systolic <120 mm Hg and diastolic <80 mm Hg) and 1161 prehypertension (systolic 120 to 139 mm Hg or diastolic 80 to 89 mm Hg). For each participant, retinal arteriolar and venular diameters were measured on digitized images of 1 eye. After a mean follow-up of 6.6 years, 808 persons developed hypertension, defined as either systolic blood pressure > or =140 mm Hg or diastolic blood pressure > or =90 mm Hg or use of antihypertensive medication. Adjusted for age, gender, follow-up time, body mass index, smoking, diabetes mellitus, total and high-density lipoprotein cholesterol, C-reactive protein, and intima-media thickness, arteriolar narrowing was associated with an increased risk of hypertension (odds ratio per SD: 1.38; 95% CI, 1.23 to 1.55); for venular narrowing this was less striking (OR: 1.17; 95% CI, 1.04 to 1.32). Each SD decrease in the arteriolar:venular diameter ratio significantly increased the risk of hypertension by 24%. To examine the effect of baseline blood pressure, we stratified persons into those with "normal blood pressure" or "prehypertension." Within these strata, arteriolar narrowing was still related to incident hypertension. These data show that both retinal arteriolar and venular narrowing may precede the development of systemic hypertension.

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PubMed2005

Lipoprotein-associated phospholipase A2 and measures of extracoronary atherosclerosis: the Rotterdam Study.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may be a new and independent predictor of cardiovascular events. The effect of Lp-PLA2 may be exerted through effects of the enzyme on the development of atherosclerosis. Therefore, we investigated the association between Lp-PLA2 activity and measures of extracoronary atherosclerosis. METHODS AND RESULTS: Lp-PLA2 activity was determined in a random sample of 1820 participants from the Rotterdam Study, a population-based cohort study in men and women > or =55 years. Common carotid intima-media thickness, carotid plaques, ankle-arm index, and aortic calcification were examined. Atherosclerosis status could be assigned in 1609 participants. The age-adjusted odds ratio of having atherosclerosis at any site for the highest versus the lowest tertile of Lp-PLA2 activity was 1.86 (95% CI, 1.01 to 3.43) in men and 1.60 (95% CI, 1.08 to 2.37) in women. After additional adjustment for cholesterol, these associations attenuated or even disappeared. The odds ratios of having atherosclerosis at specific sites (carotid arteries and aortic-iliac-femoral tract) followed a similar pattern. CONCLUSIONS: Although Lp-PLA2 has been found to be independently associated with cardiovascular events, the association with measures of subclinical extracoronary atherosclerosis found in this study strongly attenuated or even disappeared after adjustment for cholesterol.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study.

The direct visualization of retinal vessels provides a unique opportunity to study cerebral small vessel disease, because these vessels share many features. It was reported that persons with smaller retinal arteriolar-to-venular ratio tended to have more white matter lesions on MRI. It is unclear whether this is due to arteriolar narrowing or venular dilatation. We investigated whether smaller arteriolar or larger venular diameters or both were related to severity and progression of cerebral small vessel disease. We studied 490 persons (60-90 years) without dementia from a population-based cohort study. At baseline (1990-1993), retinal arteriolar and venular diameters were measured on digitized images of one eye of each participant. In 1995-1996, participants underwent cerebral MRI scanning. We rated the severity of periventricular white matter lesions on a 9-point scale, approximated a total subcortical white matter lesion volume (range: 0-29.5 ml) and rated the presence of lacunar infarcts. On average 3.3 years later, 279 persons had a second MRI. Changes in periventricular and subcortical white matter lesions were rated with a semi-quantitative scale, and progression was classified as no, minor and marked. An incident infarct was a new infarct on the follow-up MRI. Neither venular nor arteriolar diameters were related to the severity of cerebral small vessel disease. Larger venular diameters were, however, associated with a marked progression of cerebral small vessel disease. Age and gender adjusted odds ratios (ORs) per standard deviation increase were 1.71 [95% confidence interval (CI): 1.11-2.61] for periventricular, 1.72 (95% CI: 1.09-2.71) for subcortical white matter lesion progression and 1.59 (95% CI: 1.06-2.39) for incident lacunar infarcts. These associations were independent of other cardiovascular risk factors. Only the OR for incident lacunar infarcts was attenuated (1.24; 95% CI: 0.72-2.12). No association was observed between arteriolar diameters and progression of cerebral small vessel disease. In conclusion, retinal venular dilatation was related to progression of cerebral small vessel disease. The mechanisms underlying venular dilatation deserve more attention, as they may provide new clues into the pathophysiology of cerebral small vessel disease.

Age Factors↗
PubMed2005

Interleukin 6 -174 g/c promoter polymorphism and risk of coronary heart disease: results from the rotterdam study and a meta-analysis.

OBJECTIVE: Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Interleukin (IL) 6 has many inflammatory functions, and the IL-6 -174 G/C promoter polymorphism appears to influence IL-6 levels. Findings of previous studies on the relation between this polymorphism and risk of cardiovascular diseases are inconsistent. We investigated this polymorphism in relation to risk of coronary heart disease (CHD) in a population-based study and meta-analysis. METHODS AND RESULTS: Participants (6434) of the Rotterdam Study were genotyped. Analyses on the relation between genotype and CHD were performed using Cox proportional hazards tests, and the association between genotype and plasma levels of IL-6 and C-reactive protein was investigated. All of the analyses were adjusted for age, sex, and common cardiovascular risk factors. A meta-analysis was performed, using a random effects model. No association between genotype and risk of CHD was observed. The polymorphism was not associated with IL-6 levels, but the C-allele was associated with higher C-reactive protein levels (P<0.01). Our meta-analysis did not show a significant association between the genotype and risk of CHD. CONCLUSIONS: We conclude that the polymorphism is not a suitable genetic marker for increased risk of CHD in subjects > or =55 years of age.

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PubMed2005

Fibrinogen is associated with an increased risk of Alzheimer disease and vascular dementia.

BACKGROUND AND PURPOSE: Vascular and inflammatory factors may play an important role in the pathogenesis of dementia. Studies reported an association between plasma levels of inflammation markers and the risk of dementia. Both fibrinogen and C-reactive protein are considered inflammatory markers. Fibrinogen also has important hemostatic properties. We investigated the association of fibrinogen and C-reactive protein with dementia. METHODS: The study was based on the prospective population-based Rotterdam Study. Fibrinogen was measured in a random sample of 2835 persons. High-sensitivity C-reactive protein was measured in the total cohort of 6713 persons. We identified 395 incident dementia cases during follow-up (mean, 5.7 years). We estimated the associations of fibrinogen and C-reactive protein with dementia using Cox proportional hazard models. RESULTS: Persons with higher levels of fibrinogen had an increased risk of dementia. The hazard ratio for dementia per SD increase of fibrinogen was 1.26 (95% CI, 1.11 to 1.44), adjusted for age and gender, and 1.30 (95% CI, 1.13 to 1.50) after additional adjustment for cardiovascular factors and stroke. For Alzheimer disease, the adjusted hazard ratio was 1.25 (95% CI, 1.04 to 1.49), and for vascular dementia it was 1.76 (95% CI, 1.34 to 2.30). High levels of C-reactive protein were not associated with an increased risk of dementia. CONCLUSIONS: High fibrinogen levels were associated with an increased risk of both Alzheimer disease and vascular dementia, but levels of C-reactive protein were not. This suggests that the increased risk of dementia associated with fibrinogen is because of the hemostatic rather than the inflammatory properties of fibrinogen.

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PubMed2005

Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study.

Polymorphisms of the vitamin D receptor gene (VDR) have been shown to be associated with several complex diseases, including osteoporosis, but the mechanisms are unknown and study results have been inconsistent. We therefore determined sequence variation across the major relevant parts of VDR, including construction of linkage disequilibrium blocks and identification of haplotype alleles. We analyzed 15 haplotype-tagging SNPs in relation to 937 clinical fractures recorded in 6,148 elderly whites over a follow-up period of 7.4 years. Haplotype alleles of the 5' 1a/1e, 1b promoter region and of the 3' untranslated region (UTR) were strongly associated with increased fracture risk. For the 16% of subjects who had risk genotypes at both regions, their risk increased 48% for clinical fractures (P = .0002), independent of age, sex, height, weight, and bone mineral density. The population-attributable risk varied between 1% and 12% for each block and was 4% for the combined VDR risk genotypes. Functional analysis of the variants demonstrated 53% lower expression of a reporter construct with the 1e/1a promoter risk haplotype (P = 5 x 10(-7)) in two cell lines and 15% lower mRNA level of VDR expression constructs carrying 3'-UTR risk haplotype 1 in five cell lines (P = 2 x 10(-6)). In a further analysis, we showed 30% increased mRNA decay in an osteoblast cell line for the construct carrying the 3'-UTR risk haplotype (P = .02). This comprehensive candidate-gene analysis demonstrates that the risk allele of multiple VDR polymorphisms results in lower VDR mRNA levels. This could impact the vitamin D signaling efficiency and might contribute to the increased fracture risk we observed for these risk haplotype alleles.

3' Untranslated Regions↗
PubMed2005

A multivariate score objectively assessed health of depressed elderly.

BACKGROUND AND OBJECTIVE: The self-report health measures commonly used may be biased in depressed persons. We introduce a method to assess physical health objectively in prospective studies of elderly persons. STUDY DESIGN AND SETTING: Longitudinal and cross-sectional analyses in the Rotterdam Study, a population-based cohort. Under the assumption that good health is related to survival, all baseline variables independently associated with mortality were included in a global health index. A multivariate score function for this index was derived from a Cox proportional hazard model. RESULTS: Information on risk factors, disabilities, medical conditions, and physiologic measurements was combined into one score. This made it possible to compare the health of persons with depression to those with other diseases. Physical health of persons with depression and stroke was equally poor. Furthermore, in persons with established depression, worse health was related to more severe symptoms. Finally, we found that the association between an inflammation marker and depression is modified by health status as measured by our index. CONCLUSION: Late-life depression is strongly associated with poor health as measured by an objective global health index. The index makes it possible to quantify health and to study potential etiological risk factors for depression in health strata.

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PubMed2005

Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men.

UNLABELLED: Both LRP5 and LRP6 genes have been implicated to play a role in bone metabolism. In a large population-based study, we related common variation in both genes to bone parameters and fractures. LRP5 variation was associated to both BMD and frame size, whereas both LRP5 and 6 variations were associated with an increased fracture risk in males. INTRODUCTION: The low-density lipoprotein receptor-related protein 5 (LRP5) gene has a clear role in rare BMD traits and also in normal variation in peak BMD. We examined whether common variation in LRP5 and its close homolog, LRP6, plays a role in BMD in old age and fractures, the main clinical endpoint of osteoporosis. MATERIALS AND METHODS: We analyzed four variants of LRP5 and one amino acid variant of the LRP6 gene in a large prospective population-based cohort study of elderly subjects. RESULTS AND CONCLUSIONS: In men, the LRP5 1330-valine variant was associated with decreased BMD at the lumbar spine and the femoral neck with evidence for an allele-dose effect (p = 0.001 and 0.01, respectively). The Val allele was also associated with decreased vertebral body size and femoral neck width. Haplotype analysis of studied polymorphisms did not improve the association found and suggested that the 1330 variant was driving the association. We observed a borderline significant association of the LRP6 Ile1062Val polymorphism with height and vertebral body size in males. Male carriers of the LRP5 1330-valine variant had a 60% increased risk for fragility fractures, and the LRP6 1062-valine allele also conferred a 60% higher risk. Carriers of both the risk alleles of LRP5 and 6 had a 140% (p = 0.004) higher risk compared with noncarriers of both risk alleles and accounted for 10% of the fractures in males. The fracture risks were independent of age, height, weight, and BMD. In women, all of these associations were weaker and less consistent compared with men. The polymorphisms that were found associated were both situated in potentially important domains of the receptor and show considerable evolutionary conservation, which is evidence for functional importance of these residues.

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PubMed2005

Coronary calcification improves cardiovascular risk prediction in the elderly.

BACKGROUND: Coronary calcification detected by electron beam tomography may improve cardiovascular risk prediction. The technique is particularly promising in the elderly because the predictive power of cardiovascular risk factors weakens with age. We investigated the prognostic value of coronary calcification for cardiovascular events and mortality in a general, asymptomatic population of elderly subjects. METHODS AND RESULTS: From 1997 to 2000, electron beam tomography scanning to assess coronary calcification was performed in subjects of the population-based Rotterdam Study. Risk factors were measured by standardized procedures. Coronary calcium scores were available for 1795 asymptomatic participants (mean age, 71 years; range, 62 to 85 years). During a mean follow-up of 3.3 years, 88 cardiovascular events, including 50 coronary events, occurred. The risk of coronary heart disease increased with increasing calcium score. The multivariate-adjusted relative risk of coronary events was 3.1 (95% CI, 1.2 to 7.9) for calcium scores of 101 to 400, 4.6 (95% CI, 1.8 to 11.8) for calcium scores of 401 to 1000, and 8.3 (95% CI, 3.3 to 21.1) for calcium scores >1000 compared with calcium scores of 0 to 100. The predictive value in subjects >70 years of age was similar. Risk prediction based on the cardiovascular risk factors improved when coronary calcification was added. CONCLUSIONS: Coronary calcification is a strong and independent predictor of coronary heart disease, also in the elderly. Coronary calcification improves prediction of coronary events based on cardiovascular risk factors. Risk stratification by assessment of coronary calcification may have an important role in the primary prevention of coronary heart disease events in the elderly.

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PubMed2005

Cerebral small-vessel disease and decline in information processing speed, executive function and memory.

Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.

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PubMed2005

Common carotid intima-media thickness and risk of acute myocardial infarction: the role of lumen diameter.

BACKGROUND: It has been argued that lumen diameter of the common carotid artery should be taken into account in analyses on common carotid intima-media thickness (CIMT) and cardiovascular risk. Yet, no published report has dealt with this issue in detail. METHODS: In the Rotterdam study baseline ultrasound images of the carotid arteries were made. During follow-up of 8.2 years, 656 new acute myocardial infarctions (AMI) occurred. Regression analysis was used to study myocardial infarction relation to right (or left) common CIMT with various adjustments for right-, or left-sided lumen diameter. Lumen adjustment was made by (1) a simple adjustment in a regression equation; (2) using the CIMT-to-lumen ratio; (3) using arterial mass, calculated as ({pix[(lumen+near wall CIMT+far wall CIMT)/2]2}-[pix(lumen/2)2]). RESULTS: AMI disease risk increased per standard deviation increase in common CIMT (0.177 mm): hazard ratio (HR) 1.28 (95% CI, 1.19 to 1.37). When lumen diameter was taken into account the HR was 1.26 (95% CI, 1.18 to 1.35). The HR for the CIMT-to-lumen ratio was 1.18 (95% CI, 1.11 to 1.27) and for arterial mass 1.28 (95% CI, 1.19 to 1.37). Additional analyses indicated that the CIMT-to-lumen ratio at lower CIMT levels appears to reflect arterial remodelling rather than risk of cardiovascular disease. CONCLUSIONS: We conclude that using the CIMT-to-lumen ratio yields the weakest associations. Other approaches for adjustment for common carotid lumen diameter do not affect the magnitude or precision of the association of common CIMT to risk of AMI. When the interest is in risk relations the preference goes to either CIMT or arterial mass measurement.

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PubMed2005

Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory marker of cardiovascular disease. In the present study, we investigated whether Lp-PLA2 is an independent predictor of coronary heart disease and ischemic stroke. METHODS AND RESULTS: The Rotterdam Study is a population-based follow-up study in 7983 subjects > or =55 years of age. We performed a case-cohort study, including 308 coronary heart disease cases, 110 ischemic stroke cases, and a random sample of 1820 subjects. We used Cox proportional-hazard models with modification of the standard errors based on robust variance estimates to compute hazard ratios adjusted for age, sex, body mass index, systolic blood pressure, non-HDL cholesterol, HDL cholesterol, diabetes, smoking, alcohol consumption, cholesterol-lowering medication, white blood cell count, and C-reactive protein. Compared with the first quartile of Lp-PLA2 activity, multivariate-adjusted hazard ratios for coronary heart disease for the second, third, and fourth quartiles were 1.39 (95% CI, 0.92 to 2.10), 1.99 (95% CI, 1.32 to 3.00), and 1.97 (95% CI, 1.28 to 3.02), respectively (P for trend=0.01). Corresponding multivariate-adjusted hazard ratios for ischemic stroke were 1.08 (95% CI, 0.55 to 2.11), 1.58 (95% CI, 0.82 to 3.04), and 1.97 (95% CI, 1.03 to 3.79) (P for trend=0.03). The relation between Lp-PLA2 and coronary heart disease was present in both subjects with non-HDL cholesterol levels below the median and those with non-HDL cholesterol levels above the median. CONCLUSIONS: This study shows that Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Staphylococcus aureus nasal carriage is not associated with known polymorphism in the Vitamin D receptor gene.

The vitamin D endocrine system has been shown to influence the immune response and polymorphisms in the vitamin D receptor (VDR) gene have been associated with susceptibility to infectious diseases. We determined if the Cdx2, FokI and BsmI-ApaI-TaqI polymorphisms in the VDR gene were associated with nasal carriage of Staphylococcal aureus. We defined the S. aureus nasal carriage status (persistent, intermittent or non-carriage) for a group of more that 2000 elderly volunteers. The prevalence of persistent S. aureus nasal carriage was 18%, which was, however, not associated with any of the variant VDR genotypes. Our study into genetic determinants of S. aureus carriage patterns is the largest in the field, but still we found no association between VDR gene variation and S. aureus nasal carriage.

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PubMed2005

Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study.

BACKGROUND: Most prognostic studies on Parkinson disease have been hospital based or have applied register-based case-finding methods. Potential under-representation of mild cases may have given biased results. OBJECTIVE: To evaluate whether Parkinson disease is associated with an increased risk of dementia and death. DESIGN: Population-based cohort study. Parkinson disease and dementia were assessed through in-person examination at baseline (1990-1993) and 2 follow-up visits (1993-1994 and 1997-1999). Computerized linkage to medical and municipality records provided additional information on disease outcomes and mortality. SETTING: General population. PARTICIPANTS: A total of 6969 participants, including 99 prevalent and 67 incident cases of Parkinson disease. MAIN OUTCOME MEASURES: Incident dementia and death. Adjusted hazard ratios were calculated through Cox proportional hazards regression analysis. RESULTS: Patients with Parkinson disease had an increased risk of dementia (hazard ratio, 2.8; 95% confidence interval, 1.8-4.4), which was especially pronounced in participants carrying at least 1 apolipoprotein E gene (APOE) epsilon2 allele (13.5; 4.5-40.6). Parkinson disease was associated with an increased mortality risk (1.8; 1.5-2.3). The association consistently diminished when analyses were sequentially restricted to patients with shorter disease duration and after adjustment for the occurrence of dementia. CONCLUSIONS: Especially patients with Parkinson disease who carry an APOE epsilon2 allele have an increased risk of developing dementia. Increased mortality risk in Parkinson disease is dependent on disease duration and is only modest in the absence of dementia.

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PubMed2005

Causes of incident visual field loss in a general elderly population: the Rotterdam study.

OBJECTIVE: To determine the incidence and causes of visual field loss (VFL) in a general elderly population. METHODS: Central visual fields of both eyes were examined with suprathreshold perimetry in 3761 persons aged 55 years or older and free of VFL at baseline from the population-based Rotterdam Study. Goldmann perimetry was performed to confirm suprathreshold VFL. Causes of incident VFL (iVFL) were assessed based on all available ophthalmologic and neurological examination data and medical records. RESULTS: After a mean follow-up time of 6.3 years, 175 persons developed VFL. The overall incidence rate of iVFL was 7.4 per 1000 person-years, increasing to 21.1 per 1000 person-years in those aged 80 years and older. Glaucoma was the leading cause of iVFL in all age categories. The overall incidence of glaucomatous VFL was 2.0 per 1000 person-years. CONCLUSIONS: The incidence of all VFL increased 5-fold between 55 years and 80 years of age or older. After glaucoma, stroke was the second most common cause of iVFL in persons younger than 75 years, followed by age-related macular degeneration and retinal vascular occlusive disease.

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PubMed2005

Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study.

Cerebral blood flow (CBF) velocity is decreased in patients with Alzheimer's disease. It is being debated whether this reflects diminished demand because of advanced neurodegeneration or that cerebral hypoperfusion contributes to dementia. We examined the relation of CBF velocity as measured with transcranial Doppler with dementia and markers of incipient dementia (ie, cognitive decline and hippocampal and amygdalar atrophy on magnetic resonance imaging) in 1,730 participants of the Rotterdam Study aged 55 years and older. Cognitive decline in the 6.5 years preceding CBF velocity measurement was assessed with repeated Mini-Mental State Examinations in nondemented subjects (n = 1,716). Hippocampal and amygdalar volumes were assessed in a subset of 170 nondemented subjects. Subjects with greater CBF velocity were less likely to have dementia. Furthermore, in nondemented subjects, greater CBF velocity was related to significantly less cognitive decline over the preceding period (odds ratio per standard deviation increase in mean CBF 0.74 [95% confidence interval, 0.58-0.98]) and larger hippocampal and amygdalar volumes. A low CBF is associated with dementia, but also with markers of incipient dementia. Although we cannot exclude that this is caused by preclinical neurodegeneration leading to hypoperfusion, it does suggest that cerebral hypoperfusion precedes and possibly contributes to onset of clinical dementia.

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