Biomedical subjects

Monique M B Breteler

Publications and source records attributed to Monique M B Breteler.

At least 19 recordsLinked to original sources

PubMed2024

Association analysis between an epigenetic alcohol risk score and blood pressure.

BACKGROUND: Epigenome-wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits. RESULTS: We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p < 0.0001). We examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with BP levels, i.e., a one-unit increase in ERS was associated with 0.74 mm Hg (p = 0.002) higher SBP and 0.50 mm Hg (p = 0.0006) higher DBP, but not with HTN. Longitudinal analyses in FHS (n = 3260) and five independent external cohorts (n = 4021) showed that the baseline ERS was not associated with a change in BP over time or with incident HTN. CONCLUSIONS: Our findings demonstrate that the ERS has potential clinical utility in assessing lifestyle factors related to cardiovascular risk, especially when self-reported behavioral data (e.g., alcohol consumption) are unreliable or unavailable.

Humans↗

PubMed2006

Glucocorticoid receptor variant and risk of dementia and white matter lesions.

OBJECTIVE: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities. METHODS: This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions. RESULTS: The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI. CONCLUSIONS: Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.

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PubMed2006

The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe.

CONTEXT: Thyroid function has been related to Alzheimer disease (AD) and neuroimaging markers thereof. Whether thyroid dysfunction contributes to or results from developing AD remains unclear. Variations in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes that potentially alter thyroid hormone bioactivity may help in elucidating the role of thyroid function in AD. OBJECTIVE: We investigated the association of recently identified polymorphisms in the DIO1 (D1a-C/T, D1b-A/G) and DIO2 (D2-ORFa-Gly3Asp, D2-Thr92Ala) genes with circulating thyroid parameters and early neuroimaging markers of AD. DESIGN AND PARTICIPANTS: The Rotterdam Scan Study is a population-based cohort study among 1,077 elderly individuals aged 60-90 yr. MAIN OUTCOME MEASURES: DIO1 and DIO2 polymorphisms and serum TSH, free T4, T3, and reverse T3 (rT3) levels were determined in 995 nondemented elderly, including 473 persons with assessments of hippocampal and amygdalar volume on brain magnetic resonance imaging. RESULTS: Carriers of the D1a-T allele had higher serum free T4 and rT3, lower T3, and lower T3/rT3. The D1b-G allele was associated with higher serum T3 and T3/rT3. The DIO2 variants were not associated with serum thyroid parameters. No associations were found with hippocampal or amygdalar volume. CONCLUSION: This is the first study to report an association of D1a-C/T and D1b-A/G polymorphisms with iodothyronine levels in the elderly. Polymorphisms in the DIO1 and DIO2 genes are not associated with early magnetic resonance imaging markers of AD. This suggests that the previously reported association between iodothyronine levels and brain atrophy reflects comorbidity or nonthyroidal illness rather than thyroid hormones being involved in developing AD.

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PubMed2006

Alpha-adducin polymorphism, atherosclerosis, and cardiovascular and cerebrovascular risk.

BACKGROUND AND PURPOSE: Carriers of the 460Trp allele of the alpha-adducin gene (ADD1) show higher rates of sodium reabsorption compared with homozygous carriers of the Gly460 allele and were found to have an increased risk of hypertension and cardiovascular disease. We studied the association between the Gly460Trp polymorphism and atherosclerosis, cardiovascular disease, and cerebrovascular disease. METHODS: Intima-media thickness of the common carotid artery, as well as incident stroke and myocardial infarction, were studied within 6471 subjects of the Rotterdam Study. Within 1018 subjects of the Rotterdam Scan Study, prevalent silent brain infarcts and cerebral white matter lesions were studied. Subjects were grouped into 460Trp carriers (variant carriers) and homozygous carriers of the Gly460 allele (reference). RESULTS: Intima-media thickness of the common carotid artery was 0.80 mm in variant carriers compared with 0.79 mm in the reference group (P=0.04). Variant carriers had an increased risk of any stroke (hazard ratio [HR], 1.22; 95% CI, 1.02 to 1.45), ischemic stroke (HR, 1.29; 95% CI, 1.02 to 1.63), hemorrhagic stroke (HR, 1.07; 95% CI, 0.59 to 1.92), and of myocardial infarction (HR, 1.33; 95% CI, 1.05 to 1.69). For any ischemic stroke, there was a significant interaction between the Gly460Trp polymorphism and hypertension. Variant carriers more often had a silent brain infarct (odds ratio, 1.36; 95% CI, 0.98 to 1.88) and had more subcortical white matter lesions than the reference group (1.45 vs1.24 mL; P=0.22). CONCLUSIONS: The Gly460Trp polymorphism is associated with atherosclerosis, cardiovascular disease, and cerebrovascular disease, especially in hypertensive subjects.

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PubMed2006

Clinically defined vascular depression in the general population.

BACKGROUND: Vascular depression is regarded as a subtype of depression, especially in, but not entirely restricted to, the elderly, characterized by a specific clinical presentation and an association with (cerebro)vascular risk and disease. It could have major implications for treatment if subjects at risk for such a depression could be easily identified by their clinical presentation in general practice. METHOD: We studied the symptom profile of depression in subjects with and without vascular risk factors in two large Dutch community-based studies, the Rotterdam Study and the Amsterdam Study of the Elderly (AMSTEL). RESULTS: We could not confirm the specific symptom profile in depressed subjects with vascular risk factors in either of the two cohorts. Depressed subjects with vascular risk factors showed more loss of energy and more physical disability than those without vascular risk factors. However, presumed specific symptoms of vascular depression, namely psychomotor retardation and anhedonia, were not significantly associated with any of the vascular risk indicators. Loss of energy was significantly associated with myocardial infarction and peripheral arterial disease. CONCLUSIONS: In these two large community-based studies we identified some differences between vascular and non-vascular depressed subjects but found no evidence for a specific symptom profile of vascular depression as previously defined.

Activities of Daily Living↗

PubMed2006

Plasma pterins and folate in late life depression: the Rotterdam Study.

Tetrahydrobiopterin is a cofactor in the synthesis of monoamine neurotransmitters. High neopterin levels generally signal increased immune activation. Both pterins have been investigated in several small clinical studies of depressed patients with conflicting results. Therefore, we examined the relation of plasma biopterin and neopterin with depression in a population-based study. We also studied the association of pterins with folates in depressed persons as this vitamin is required for pterin biosynthesis. We screened 3884 adults aged 60 years and over for depressive symptoms. Screen positive subjects had a psychiatric interview to diagnose DSM-IV disorder. Plasma pterins and serum folate were determined in all persons with depressive symptoms (n=238) and randomly selected non-depressed persons (n=357). We found no association between the concentration of biopterin or neopterin with depressive symptoms or depressive disorders. However, in depressed persons the relation between pterins and folates was different than in the non-depressed, i.e. neopterin concentrations increased with folate levels in persons with depressive symptoms (0.09 per log(nmol/l folate); 95% CI=0.01, 0.18, P=0.03), but not in non-depressed persons (-0.07 per log(nmol/l folate); 95% CI=-0.17, 0.03, P=0.18). The interaction between depressive symptoms, folate and neopterin was significant (P=0.03). The study suggests that the relation between folate and pterins is altered in the depressed elderly.

Age of Onset↗

PubMed2006

Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia.

CONTEXT: Recently, it was proposed that a combination of the 83,557insA polymorphism in the 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) gene and the R453Q polymorphism in the hexose-6-phosphate dehydrogenase (H6PD) gene interacts to cause cortisone reductase deficiency (CRD) when at least three alleles are affected. OBJECTIVE: The aim was to study the separate and combined effects of these polymorphisms on body composition, adrenal androgen production, blood pressure, glucose metabolism, and the incidence of dementia in the healthy elderly population. DESIGN/SETTING/PARTICIPANTS: The Rotterdam study (n = 6105) and the Frail Old Men study (n = 347) are population-based cohort studies in the elderly. MAIN OUTCOME MEASURES: Genotype distributions and influences of (combined) genotypes on body mass index, adrenal androgen production, waist to hip ratio, systolic and diastolic blood pressure, fasting glucose levels, glucose tolerance test, and incidence of dementia were measured. RESULTS: No influence of the HSD11B1 83,557insA (allele frequencies 22.0 and 21.5%) and H6PD R453Q (allele frequencies 22.9 and 20.2%) variants was found for the different outcome measures that were investigated, either separately or when at least three alleles were affected. CONCLUSIONS: Two population-based studies among Caucasian elderly showed no evidence for (combined) effects of two polymorphisms in the HSD11B1 and H6PD genes on body composition, adrenal androgen production, blood pressure, glucose metabolism, and incidence of dementia. Moreover, the high frequencies observed for these two polymorphisms do not correspond to the low incidence of CRD observed in the general population. Altogether, it is unlikely that these polymorphisms cause CRD.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2006

TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study.

BACKGROUND AND PURPOSE: Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and of cardiovascular and cerebrovascular complications. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with a central role in inflammation. Little is known of the relation of variations within the gene and risk of cardiovascular and cerebrovascular disease. We therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study. METHODS: Participants (N=6456) of the Rotterdam Study were included in the current study. Analyses of the relations of genotypes with the risk of myocardial infarction and stroke were performed according to Cox proportional-hazards methods. All analyses were adjusted for age, sex, conventional cardiovascular risk factors, and medical history. RESULTS: We found no association with the risk of myocardial infarction. A significantly increased risk of stroke was found, associated with the T allele of the -509 C/T polymorphism (relative risk, 1.26; (95% CI, 1.06 to 1.49) and the Pro variant of the codon 10 polymorphism (relative risk, 1.24; 95% CI, 1.04 to 1.48). CONCLUSIONS: No association between the TGF-beta1 polymorphisms and myocardial infarction was observed; however, the -509 C/T and codon 10 Leu/Pro polymorphisms were associated with the risk of stroke.

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PubMed2006

High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study.

BACKGROUND: Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke. METHODS AND RESULTS: The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990-1993) were > or = 55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only. CONCLUSIONS: Although CRP levels are associated with stroke risk, their use in the assessment of individual stroke risk seems limited.

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PubMed2006

Association between calcification in the coronary arteries, aortic arch and carotid arteries: the Rotterdam study.

OBJECTIVE: The present study was performed to examine the prevalence of and associations between calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT), in an elderly population. METHODS AND RESULTS: This study was part of the population-based Rotterdam study. From October 2003 until July 2004, subjects underwent a 16-slice MSCT scan. Calcification was quantified by calculating the Agatston, volume and mass score. Current analyses were performed in 600 subjects (mean age 74 years). The prevalences of calcification in the coronary and carotid arteries were higher in men compared to women. However, aortic arch calcification was more prevalent among women. In men, correlation coefficients based on the Agatston score ranged from 0.40 (between coronary and aortic arch calcification) to 0.54 (between aortic arch and carotid calcification) (p<0.001). Correlation coefficients for women ranged from 0.30 (between coronary and aortic arch calcification) to 0.40 (between coronary and carotid calcification) (p<0.001). CONCLUSIONS: While the prevalences of calcification in the coronary and the carotid arteries were higher in men compared to women, aortic arch calcification was more prevalent among women. Moderate to strong correlations between calcification in different vessel beds were found.

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PubMed2006

Serum cholesterol levels and the risk of Parkinson's disease.

Several recent findings suggest a role of lipid and cholesterol metabolism in the pathogenesis of Parkinson's disease. Therefore, the authors examined the association between serum levels of cholesterol and the risk of Parkinson's disease in the prospective, population-based Rotterdam Study among 6,465 subjects aged 55 or more years with repeated in-person examination and on average 9.4 years of follow-up (1990-2004). Higher serum levels of total cholesterol were associated with a significantly decreased risk of Parkinson's disease (age- and sex-adjusted hazard ratio per mmol/liter increase in cholesterol = 0.77, 95% confidence interval: 0.64, 0.94), with evidence for a dose-effect relation. The association was restricted to women and remained unchanged after adjustment for multiple potential confounders. These findings may indicate a role of lipids in the pathogenesis of Parkinson's disease. Alternatively, they could reflect the strong correlation-especially in women-between levels of serum cholesterol and the antioxidant coenzyme Q10. If confirmed, this would provide further support for an important role of oxidative stress in the pathogenesis of Parkinson's disease.

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PubMed2006

Polymorphisms and haplotypes in the C-reactive protein gene and risk of dementia.

OBJECTIVE: Inflammation plays a role in the pathogenesis of dementia and Alzheimer's disease (AD). Studies examining serum levels of C-reactive protein in relation to dementia yielded conflicting results. Since serum levels of C-reactive protein are partly determined by genetic factors, we examined the association between genetic variation in the C-reactive protein gene with dementia and AD. METHODS: This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly. Polymorphisms in the C-reactive protein gene (1184C>T, 2042C>T and 2911C>G) tagging the common haplotypes were genotyped and haplotypes were constructed. During follow-up (mean 9.2 years) 607 dementia cases were identified. We estimated the association between polymorphisms and haplotypes with dementia and AD with Cox' proportional hazard models. RESULTS: The T allele of the C-reactive protein 2042C>T polymorphism, related to lower serum levels of C-reactive protein, was associated with a lower risk of dementia and AD. This association was strongest in APOE epsilon4 allele carriers. CONCLUSION: These findings suggest that C-reactive protein plays a role in development of dementia.

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PubMed2006

Plasma beta amyloid and impaired CO2-induced cerebral vasomotor reactivity.

Amyloid beta (Abeta) may disturb cerebral autoregulation by damaging the wall of small cerebral blood vessels and by direct negative vasoactive properties. We assessed whether previous and concurrent plasma Abeta(1-40) and Abeta(1-42) levels were associated with an impaired CO2-induced cerebral vasomotor response. In the longitudinal population-based Rotterdam Study we measured plasma Abeta levels and cerebral vasomotor reactivity to hypercapnia with transcranial Doppler ultrasonography (TCD) in 441 people, aged 60-90 years. We performed age and sex adjusted logistic regression analysis. Plasma Abeta levels assessed on average 6.5-year before TCD were linearly associated with an impaired CO2-induced cerebral vasomotor response (odds ratio 1.48 (95%CI 1.19;1.84) per standard deviation increase in Abeta(1-40), and 1.36 (95%CI 1.09;1.70) per standard deviation increase in Abeta(1-42)). Such an association was not present for Abeta assessed concurrently with the TCD measurement. Persons whose plasma Abeta(1-40) levels had decreased in the 6.5-year period preceding TCD measurements were more likely to have an impaired CO2-induced vasomotor reactivity. Overall our observations are most compatible with plasma Abeta levels representing vascular Abeta deposits years later resulting in impaired CO2-induced vasomotor reactivity.

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PubMed2006

Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study.

BACKGROUND AND PURPOSE: The role of uric acid as a risk factor for myocardial infarction is controversial, and little is known about its role as a risk factor for stroke. Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease, for example, by inducing renal disease and hence hypertension. We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospective population-based study. METHODS: The study was based on 4385 participants of the Rotterdam Study who, at baseline (1990 to 1993), were > or =55 years of age, free from stroke and coronary heart disease, and had blood taken. Follow-up for incident stroke and myocardial infarction was complete until January 1, 2002. Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders. RESULTS: Average follow-up was 8.4 years. High serum uric acid levels were associated with risk of myocardial infarction and stroke; age- and sex-adjusted hazard ratios (95% CIs) for highest versus lowest quintile of uric acid were 1.68 (1.24 to 2.27) for cardiovascular disease (515 cases), 1.87 (1.12 to 3.13) for myocardial infarction (194 cases), 1.57 (1.11 to 2.22) for stroke (381 cases), 1.77 (1.10 to 2.83) for ischemic stroke (205 cases), and 1.68 (0.68 to 4.15) for hemorrhagic stroke (46 cases). Adjustment for other vascular risk factors only slightly attenuated these associations. Associations were stronger in persons without hypertension than in those with hypertension. CONCLUSIONS: Uric acid is a strong risk factor for myocardial infarction and stroke.

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PubMed2006

Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and risk of dementia. The Rotterdam Study.

Inflammatory mechanisms are involved in the pathogenesis of dementia. Inflammatory cytokines, including interleukin-6 (IL-6) and transforming growth factor beta1 (TGFbeta1), have been found in association with Alzheimer pathology and there is evidence for direct involvement of these cytokines in formation of amyloid plaques. Polymorphisms in genes encoding for IL-6 and TGFbeta1 are associated with plasma levels of IL-6 and TGFbeta1. Studies examining the association between polymorphisms in these genes and dementia yielded conflicting results. The purpose of this study was to examine the association between genetic variance in IL-6 and TGFbeta1 and risk of dementia. We examined this association in the Rotterdam Study, a prospective population-based cohort study in the elderly. Polymorphisms in the IL-6 (-174G>C) and TGFbeta1 gene (-800G>A, -509C>T, +10T>C, +25G>C and 263C>T) were genotyped and haplotypes of the TGFbeta1 gene were constructed. In a random subset IL-6 plasma levels were measured. During follow-up (mean 9.2 years), 743 dementia cases were identified. We estimated the association between individual polymorphisms and haplotypes with dementia with Cox' proportional hazard models. No association was found between the -174G>C polymorphism in the IL-6 gene and risk of dementia. No association was found between polymorphisms and constructed haplotypes in the TGFbeta1 gene and risk of dementia or Alzheimer's disease. No association was found between IL-6 genotype and IL-6 plasma levels in the random subset. Associations did not differ across APOE genotypes. Our findings do not suggest involvement of genetic variance in IL-6 and TGFbeta1 in the development of dementia.

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PubMed2006

Thyroid hormones, dementia, and atrophy of the medial temporal lobe.

CONTEXT: Thyroid function has been related to Alzheimer disease (AD), but it remains unclear whether thyroid dysfunction results from or contributes to developing AD. OBJECTIVE: The objective of the study was to determine the association between thyroid function and both medial temporal lobe atrophy on brain magnetic resonance imaging (MRI) as putative early sign of AD and risk of dementia. DESIGN AND PARTICIPANTS: This was a population-based cohort study among 1077 elderly subjects aged 60-90 yr and dementia free at baseline (1995-1996). MAIN OUTCOME MEASURES: Nonfasting serum levels of TSH, free T(4) (fT(4)), T(3), and rT(3) were available in 1025 subjects followed up for incident dementia until 2005. In a subset of 489 nondemented elderly, we assessed volumes of the hippocampus and amygdala on brain MRI. Subjects using thyroid medication were excluded. RESULTS: During 5657 person-years of follow-up (mean 5.5 yr), 63 subjects were diagnosed with dementia (46 with AD). TSH and thyroid hormones were not associated with risk of dementia or AD. TSH and T(3) were also not related to brain atrophy, whereas nondemented subjects with higher fT(4) levels had more hippocampal and amygdalar atrophy on MRI. Similar associations were found for rT(3). Excluding subjects with thyroid disorders or incipient AD did not change the results. CONCLUSION: In our study, TSH was related neither to risk of AD nor with early MRI markers thereof, arguing against an important role of thyroid function in the development of AD. Whether the association of higher fT(4) and rT(3) levels with brain atrophy on MRI has functional significance remains to be elucidated.

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PubMed2006

Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study.

BACKGROUND: Arterial stiffness has been associated with the risk of cardiovascular disease in selected groups of patients. We evaluated whether arterial stiffness is a predictor of coronary heart disease and stroke in a population-based study among apparently healthy subjects. METHODS AND RESULTS: The present study included 2835 subjects participating in the third examination phase of the Rotterdam Study. Arterial stiffness was measured as aortic pulse wave velocity and carotid distensibility. Cox proportional hazards regression analysis was performed to compute hazard ratios. During follow-up, 101 subjects developed coronary heart disease (mean follow-up period, 4.1 years), and 63 subjects developed a stroke (mean follow-up period, 3.2 years). The risk of cardiovascular disease increased with increasing aortic pulse wave velocity index. Hazard ratios and corresponding 95% CIs of coronary heart disease for subjects in the second and third tertiles of the aortic pulse wave velocity index compared with subjects in the reference category were 1.72 (0.91 to 3.24) and 2.45 (1.29 to 4.66), respectively, after adjustment for age, gender, mean arterial pressure, and heart rate. Corresponding estimates for stroke were 1.22 (0.55 to 2.70) and 2.28 (1.05 to 4.96). Estimates decreased only slightly after adjustment for cardiovascular risk factors, carotid intima-media thickness, the ankle-arm index, and pulse pressure. The aortic pulse wave velocity index provided additional predictive value above cardiovascular risk factors, measures of atherosclerosis, and pulse pressure. Carotid distensibility as measured in this study was not independently associated with cardiovascular disease. CONCLUSIONS: Aortic pulse wave velocity is an independent predictor of coronary heart disease and stroke in apparently healthy subjects.

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PubMed2006

Subjective complaints precede Parkinson disease: the rotterdam study.

BACKGROUND: Neuronal degeneration and dopamine loss in the preclinical phase of Parkinson disease may produce subtle complaints before clinically recognizable symptoms emerge. OBJECTIVE: To examine whether subjective complaints of stiffness, slowness, tremors, or postural imbalance in persons without clinical signs of parkinsonism are related to an increased risk of future Parkinson disease. DESIGN: Population-based cohort study. We recorded subjective complaints of stiffness, slowness of movement, tremors, falling, or a feeling of imbalance in a standardized interview of 6038 participants without dementia in whom no parkinsonian signs were found on physical examination at baseline, and we studied them prospectively for the occurrence of incident Parkinson disease. SETTING: General population. PARTICIPANTS: A total of 6038 participants who were free of dementia and parkinsonian signs. MAIN OUTCOME MEASURES: Incident Parkinson disease. Participants were examined in person both at baseline (January 1990-June 1993) and at 2 follow-up visits (September 1993-December 1994 and April 1997-December 1999), and the cohort was continuously monitored through computerized linkage of the study database to general practitioners' medical records. We analyzed the data using Cox proportional hazards regression models. RESULTS: Participants who reported stiffness, tremors, or imbalance at baseline had a significantly increased risk of developing Parkinson disease during follow-up (for stiffness, hazard ratio, 2.11; 95% confidence interval, 1.25-3.55; P = .005; for tremors, hazard ratio, 2.09; 95% confidence interval, 1.12-3.90; P = .002; and for imbalance, hazard ratio, 3.47; 95% confidence interval, 1.69-7.00; P = .001). CONCLUSIONS: Subjective complaints of stiffness, tremors, and imbalance are associated with an increased risk of future Parkinson disease and may reflect early effects of dopamine shortage, even when standard neurological testing cannot yet demonstrate any motor symptoms.

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