Biomedical subjects

Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 145 records · Page 8Linked to original sources

PubMed2004

Genetic variability of von Willebrand factor and risk of coronary heart disease: the Rotterdam Study.

The von Willebrand factor (VWF) may be causally associated with coronary heart disease (CHD) or merely be a marker of endothelial damage. The G allele of the -1793 C/G promoter polymorphism in the VWF gene has been associated with higher plasma levels of VWF. To investigate whether VWF has a causal role in CHD, we designed a case-cohort study, including 352 subjects with CHD and a random cohort (n = 736), and prospectively examined the association of the -1793 C/G polymorphism with CHD in subjects with and without advanced atherosclerosis. All subjects were </=75 years of age and participating in the population-based Rotterdam Study. Atherosclerosis was assessed by the ankle-arm index. Among subjects with advanced atherosclerosis, heterozygous and homozygous carriers of the G allele had a 3.5 (1.2-10.2) and 1.5 (0.4-5.7) fold increased risk of CHD respectively, compared with C/C homozygotes. The hazard ratio was 2.6 (1.0-6.8) for carriers of at least one copy of the G allele versus non-carriers. No associations were found in the absence of advanced atherosclerosis. In conclusion, this study suggests that the G allele of the -1793 C/G polymorphism in the VWF gene is associated with an increased risk of CHD, but only in subjects with advanced atherosclerosis.

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PubMed2004

Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia.

BACKGROUND: Consumers of light-to-moderate amounts of alcohol have a lower risk of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular disease may contribute to symptoms of Alzheimer disease, reduction of cerebrovascular disease in consumers of light amounts of alcohol could account for that observation. However, a low concentration of alcohol may also have direct effects on the hippocampus, a brain structure highly affected by Alzheimer disease. OBJECTIVE: We investigated alcohol intake in relation to brain magnetic resonance imaging (MRI) findings of presumed vascular origin (ie, white matter lesions and infarcts) and findings more specifically found in early Alzheimer disease (ie, hippocampal and amygdalar atrophy). DESIGN: In a population-based sample of 1074 older persons without dementia (aged 60-90 y), we made brain MRIs from which we rated white matter lesions and brain infarcts. In a subset of 509 people, hippocampal and amygdalar volumes on MRI were measured. Alcohol intake was assessed by using a structured questionnaire. We categorized alcohol intake as lifetime abstention and very light (<1 drink/wk), light (>/=1 drink/wk to <1 drink/d), moderate (>/=1 drink/d to <4 drinks/d), and heavy (>/=4 drinks/d) intakes. RESULTS: Persons whose alcohol consumption was light to moderate had less severe white matter lesions and brain infarcts on MRI than did abstainers or heavy drinkers. Abstainers and very light drinkers had smaller hippocampal and amygdalar volumes on MRI than did light-to-moderate drinkers, but only if the former carried an apolipoprotein (APOE) epsilon4 allele. CONCLUSION: Light-to-moderate alcohol intake is associated with a lower prevalence of vascular brain findings and, in APOE epsilon4 carriers, hippocampal and amygdalar atrophy on MRI.

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PubMed2004

Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study.

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Aortic Diseases↗

PubMed2004

Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure.

BACKGROUND: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease. OBJECTIVE: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort. METHODS: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication. RESULTS: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele. CONCLUSIONS: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.

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PubMed2004

The risk of overanticoagulation in patients with cytochrome P450 CYP2C92 or CYP2C93 alleles on acenocoumarol or phenprocoumon.

Cytochrome P4502C9 (CYP2C9) is the main enzyme implicated in coumarin anticoagulant metabolism. The variant alleles CYP2C9*2 and CYP2C9*3 are associated with an increased response to warfarin. However, an effect on acenocoumarol dose requirements appears to be absent for the CYP2C9*2 allele and the consequences for the metabolism of phenprocoumon have not yet been established. We investigated CYP2C9 polymorphisms in relation to the international normalized ratio (INR) during the first 6 weeks of treatment and its effect on the maintenance dose in a cohort of 1124 patients from the Rotterdam Study who were treated with acenocoumarol or phenprocoumon. There was a statistically significant difference in first INR between patients with variant genotypes and those with the wild-type. Almost all acenocoumarol-treated patients with a variant genotype had a significantly higher mean INR and had a higher risk of an INR > or = 6.0 during the first 6 weeks of treatment. A clear genotype-dose relationship was found for acenocoumarol-treated patients. For patients on phenprocoumon, no significant differences were found between variant genotypes and the wild-type genotype. Individuals with one or more CYP2C9*2 or CYP2C9*3 allele(s) require a significantly lower dose of acenocoumarol compared to wild-type patients. Phenprocoumon appears to be a clinically useful alternative in patients carrying the CYP2C9*2 and *3 alleles.

Acenocoumarol↗

PubMed2004

Pharmacoeconomic evaluation of testing for angiotensin-converting enzyme genotype before starting beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor therapy in men.

This study aimed to assess the potential cost-effectiveness of screening men for their angiotensin-converting enzyme (ACE)-genotype before starting statin therapy. We used a combination of decision-analytic and Markov modelling techniques to evaluate the long-term incremental clinical and economic effects associated with genetic testing of men with hypercholesterolemia before starting treatment with statins. The study was performed from a health care payer perspective. We used data from the Rotterdam study, a prospective population-based cohort study in the Netherlands, which was started in 1990 and included 7983 subjects aged 55 years and older. Men treated with cholesterol-lowering drugs at baseline or with a baseline total cholesterol > or = 6.5 mmol/l were included. The ratio of difference in lifelong costs between the screening strategy and the no screening strategy to difference in life expectancy between these strategies was calculated. We also performed a cost-utility analysis. The base case was a 55-year-old man with hypercholesterolemia who was initially untreated. Several univariate sensitivity analyses were performed. All costs were discounted with an annual rate of 5%. Screening men for their ACE-genotype was the dominant strategy for the base case analysis, because the screening strategy saved money (851 Euro), but life expectancy was not changed. Screening was the dominant strategy for all age-groups in our cohort. Even in 80-year-old subjects, with the shortest life-expectancy, it was cheaper to screen than to give lifelong treatment to men with a DD genotype without success. Even if all DD subjects were treated with other (non-statin) cholesterol-lowering drugs, screening remained the cost-effective strategy. The results of the cost-utility analysis were similar. Discounting the effects with 5% per year also had no major impact on the conclusions. If other studies confirm that men with the DD genotype do not benefit from treatment with statins, screening for ACE genotype in men most likely will be a cost-effective strategy before initiating statin therapy.

Anticholesteremic Agents↗

PubMed2004

The Study on COgnition and Prognosis in the Elderly (SCOPE); outcomes in patients not receiving add-on therapy after randomization.

OBJECTIVE: To assess clinical outcomes in the Study on COgnition and Prognosis in the Elderly (SCOPE) in patients who did not receive add-on antihypertensive therapy after randomization, i.e. in patients that best reflect the original intention of a placebo-controlled trial. DESIGN: Post-hoc analysis of a prospective, randomized, controlled trial. SETTINGS AND PARTICIPANTS: Five hundred and twenty-seven centres in 15 countries participated in SCOPE. Patients aged 70-89 years, with systolic blood pressure 160-179 mmHg and/or diastolic blood pressure 90-99 mmHg, and preserved cognitive function were eligible. Out of 4937 patients in SCOPE, 2098 did not receive add-on therapy. INTERVENTION: The number of patients who received candesartan 8-16 mg once daily was 1253, and 845 received placebo. Mean follow-up was 3.7 and 3.5 years, respectively. MAIN OUTCOME MEASURES: Primary: major cardiovascular events (cardiovascular mortality, non-fatal stroke or non-fatal myocardial infarction). Secondary: total mortality, cardiovascular mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, cognitive function, and dementia. RESULTS: The treatment groups were generally well balanced for baseline characteristics. Blood pressure fell by 21.8/11.0 mmHg in the candesartan group and by 17.2/8.4 mmHg in the placebo group. There were significant relative risk reductions with candesartan in major cardiovascular events (32%, P = 0.013), cardiovascular mortality (29%, P = 0.049), and total mortality (27%, P = 0.018). There were no significant differences between the treatment groups in cognitive outcomes. Both treatments were generally well tolerated. CONCLUSIONS: Treatment of elderly patients with mild hypertension is beneficial and supports current recommendations. Candesartan appears an appropriate therapy in such patients, in view of its favourable tolerability profile and ability to reduce major cardiovascular events.

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PubMed2004

The risk of overanticoagulation in patients with heart failure on coumarin anticoagulants.

Heart failure has been identified as a risk factor for increased coumarin anticoagulant responsiveness in several small-scale experiments. Epidemiological studies quantifying the risk of overanticoagulation by heart failure in a non-selected population on coumarins are scarce. Therefore, we investigated whether patients with heart failure have an increased risk of overanticoagulation and determined the effect of incidental heart failure on coumarin dose requirements. A cohort study of all patients was performed from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon between 1 January 1990 and 1 January 2000. All cohort members were followed until the first occurrence of an international normalized ratio (INR) > or = 6.0, the last INR assessment, death, loss to follow-up, or end of the study period. Of the 1077 patients in the cohort, 396 developed an INR > or = 6.0. The risk of overanticoagulation was 1.66 [95% confidence interval (CI): 1.33-2.07] for cases of prevalent heart failure and 1.91 (95%CI: 1.31-2.79) for incidental cases. The decrease in dose requirements in patients with incidental heart failure showed a significant trend from the fifth INR measurement preceding the date of incidental heart failure to the third measurement after this date. Heart failure is an independent risk factor for overanticoagulation. Therefore, patients with heart failure should be closely monitored to prevent potential bleeding complications.

Acenocoumarol↗

PubMed2004

Growth, development and health from early fetal life until young adulthood: the Generation R Study.

In this paper the Generation R Study is presented. This study examines growth, development and health in urban children from fetal life until young adulthood. With an integrated approach of epidemiological, clinical and basic research, it focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and health care for pregnant women and children. The general aims of the study are: 1. to describe normal and abnormal growth, development and health from fetal life until young adulthood in a multiethnic population-based cohort; 2. to identify biological, social and environmental determinants of normal and abnormal growth, development and health from fetal life until adulthood; 3. to examine the utilisation and effectiveness of current strategies for prevention and early identification of groups at risk. Eventually, this study will contribute to the development of strategies for optimising health and health care for pregnant women and children. The Generation R Study is a prospective population-based cohort study in Rotterdam, the Netherlands. In this urban setting, 10 000 children will be examined from early fetal life until young adulthood. Data are collected by physical examinations, questionnaires, interviews, ultrasound and biological samples. The study entered its pilot phase to test the logistics in December 2001. Full participant recruitment and complete data collection started in 2002.

Child Development↗

PubMed2004

Blood pressure components and cardiovascular events in older adults: the Rotterdam study.

OBJECTIVES: To compare the strength of the relative risks of systolic (SBP) diastolic blood pressure (DBP) and pulse pressure (PP) as predictors of myocardial infarction and stroke in older adults. DESIGN: Prospective cohort study. SETTING: The Rotterdam Study, a Dutch population-based study. PARTICIPANTS: A total of 4,234 subjects aged 55 and older with no previous myocardial infarction (MI) or stroke at baseline. MEASUREMENTS: Blood pressure levels at baseline, first MI and stroke, all-cause mortality during follow-up. RESULTS: During follow-up, 205 subjects had an MI (average follow-up period 7 years), 137 subjects had a stroke (average follow-up period 6.1 years), and 748 subjects died. A 1-standard deviation difference in SBP, DBP, and PP was associated with relative risks of MI of 1.24 (95% confidence interval (CI)=1.06-1.46), 1.07 (0.92-1.25), and 1.25 (1.07-1.48), respectively. Corresponding relative risks for stroke were 1.59 (1.37-1.86), 1.27 (1.10-1.48), and 1.48 (1.27-1.72). For all-cause mortality the corresponding relative risks and 95% CI were 1.21 (1.11-1.31), 1.06 (0.99-1.14), and 1.20 (1.10-1.31). CONCLUSION: The results of this study suggest that, in a population of apparently healthy older adults, PP is not a better predictor of cardiovascular events and all-cause mortality than SBP.

Age Distribution↗

PubMed2004

The risk of bleeding complications in patients with cytochrome P450 CYP2C92 or CYP2C93 alleles on acenocoumarol or phenprocoumon.

The principal enzyme involved in coumarin metabolism is CYP2C9. Allelic variants of CYP2C9, CYP2C9*2 and CYP2C9*3, code for enzymes with reduced activity. Despite increasing evidence that patients with these genetic variants require lower maintenance doses of anticoagulant therapy, there is lack of agreement among studies on the risk of bleeding and CYP2C9 polymorphisms. It was, therefore, our objective to study the effect of the CYP2C9 polymorphisms on bleeding complications during initiation and maintenance phases of coumarin anticoagulant therapy. The design of the study was a population-based cohort in a sample of the Rotterdam Study, a study in 7,983 subjects. All patients who started treatment with acenocoumarol or phenprocoumon in the study period from January 1, 1991 through December 31, 1998 and for whom INR data were available were included. Patients were followed until a bleeding complication, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of a bleeding complication in relation to CYP2C9 genotype after adjustment for several potentially confounding factors such as age, gender, target INR level, INR, time between INR measurements, and aspirin use. The effect of variant genotype on bleeding risk was separately examined during the initiation phase of 90 days after starting therapy with coumarins. The 996 patients with analysable data had a mean follow-up time of 481 days (1.3 years); 311 (31.2%) had at least 1 variant CYP2C9 allele and 685 (68.8%) had the wild type genotype. For patients with the wild type genotype, the rate of minor bleeding, major bleeding and fatal bleeding was 15.9, 3.4 and 0.2 per 100 treatment-years, respectively. For patients with a variant genotype, the rate of minor, major and fatal bleeding was 14.6, 5.4 and 0.5 per 100 treatment-years. Patients with a variant genotype on acenocoumarol had a significantly increased risk for a major bleeding event (HR 1.83, 95% CI: 1.01-3.32). During the initiation phase of therapy we found no effect of variant genotype on bleeding risk. In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, having a variant allele of CYP2C9 was associated with an increased risk of major bleeding events in patients on acenocoumarol, but not in patients on phenprocoumon. Although one might consider the assessment of the CYP2C9 genotype of a patient for dose adjustment before starting treatment with acenocoumarol, a prospective randomised trial should demonstrate whether this reduces the increased risk of major bleeding events.

Acenocoumarol↗

PubMed2004

Genetic variation in Fcgamma receptor IIa protects against advanced peripheral atherosclerosis. The Rotterdam Study.

Immune processes play a substantial role in atherosclerotic disease. The role in atherosclerosis of Fcgamma receptor IIa (FcgammaRIIa), a receptor for immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet clear. Since the R/H131 polymorphism in the FcgammaRIIa gene strongly influences binding to FcgammaRIIa, we investigated the association of the R/H131 polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam Study, a population-based cohort study, we determined FcgammaRIIa genotype in 430 subjects with advanced peripheral atherosclerosis as indicated by the ankle-arm index, and 411 controls. Heterozygous and homozygous carriers of the H131 allele were protected against advanced peripheral atherosclerosis (age- and gender-adjusted odds ratio (OR) 0.77 (0.54-1.12) and 0.65 (0.44-0.98), respectively, P trend=0.04). This effect was most pronounced in subjects with modestly elevated levels of inflammation as indicated by the leukocyte count (OR 0.52 (0.29-0.93) and 0.45 (0.23-0.86), for heterozygotes and H131 homozygotes, respectively; P trend=0.02). This is the first study showing that the H131 allele of FcgammaRIIa protects against advanced peripheral atherosclerosis.

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PubMed2004

Are retinal arteriolar or venular diameters associated with markers for cardiovascular disorders? The Rotterdam Study.

PURPOSE: A lower retinal arteriolar-to-venular ratio (AVR) has been suggested to reflect generalized arteriolar narrowing and to predict the risk of cardiovascular diseases. The contribution of the separate arteriolar and venular diameters to this AVR is unknown. Thus, associations between retinal arteriolar and venular diameters, and the AVR on the one hand and blood pressure, atherosclerosis, inflammation markers, and cholesterol levels on the other were examined in the Rotterdam Study. METHODS: In this cross-sectional population-based study, for one eye of each subject (> or =55 years; n = 5674), retinal arteriolar and venular diameters (in micrometers) of the blood columns were summed on digitized images. At baseline blood pressures, cholesterol levels, and markers of atherosclerosis and inflammation were also measured. RESULTS: With increasing blood and pulse pressures, retinal arteriolar and venular diameters and the AVR decreased significantly and linearly. Lower arteriolar diameters were associated with increased carotid intima-media thickness. Larger venular diameters were associated with higher carotid plaque score, more aortic calcifications, lower ankle-arm index, higher leukocyte count, higher erythrocyte sedimentation rate, higher total serum cholesterol, lower HDL, higher waist-to-hip ratio, and smoking. A lower AVR was related to increased carotid intima-media thickness, higher carotid plaque score, higher leukocyte count, lower HDL, higher body mass index, higher waist-to-hip ratio, and smoking. CONCLUSIONS: Because larger venular diameters are associated with atherosclerosis, inflammation, and cholesterol levels, the AVR does not depend only on generalized arteriolar narrowing due to the association between smaller arteriolar diameters and higher blood pressures. These data indicate that retinal venular diameters are variable and may play their own independent role in predicting cardiovascular disorders.

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PubMed2004

Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident vertebral fractures in elderly men and women: the Rotterdam Study.

In an age-matched, case-control study, we investigated the association between endogenous sex steroid hormones and incident vertebral fractures in both elderly men and women (aged 67.7 +/- 6.8 yr). Drawn from the Rotterdam Study, participants required radiographs of the lumbar spine at both baseline and follow-up (average time of follow-up, 6.5 yr) and frozen blood samples, taken at baseline. One hundred and seventy-eight men (45 cases) and 454 women (115 cases) were thus selected. Serum estradiol, SHBG, testosterone, and insulin were measured, along with bone mineral density at both spine and hip. Women in the lowest tertile of serum estradiol (< or =15.5 pmol/liter) had a 2.1 times increased risk (95% confidence interval, 1.3-3.5) of incident vertebral fractures, independently of bone mineral density measured at either site. SHBG levels in the lowest two tertiles were associated with a 50% reduction in incident vertebral fracture risk. Women with a combination of both low estradiol and high SHBG had a 7.8 times higher risk of an incident vertebral fracture (95% confidence interval, 2.7-22.5; P < 0.001), adjusted for age and weight. This increased risk did not change when non-SHBG-bound estradiol was used instead of total estradiol. For men, no clear association was found, possibly due to insufficient power. No clear association between testosterone and incident vertebral fractures was observed in either men or women.

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PubMed2004

Height in pre- and postmenopausal women is influenced by estrogen receptor alpha gene polymorphisms.

The estrogen receptor alpha gene (ESR1) is known to be involved in metabolic pathways influencing growth. We have performed two population-based association studies using three common polymorphisms within this candidate gene to determine whether these are associated with variation in adult stature. In 607 women, aged 55-80 yr, from the Rotterdam Study, the ESR1 PvuII-XbaI haplotype 1 (px) and the L allele of the TA repeat polymorphism (<18 TA repeats) were significantly associated with an allele dose-dependent decrease in height. The per allele copy of ESR1 PvuII-XbaI haplotype 1 height was 0.9 cm shorter (P trend = 0.02) and 1.0 cm/allele copy of the TA repeat L allele (P trend = 0.003). These results were independent of age, age at menarche and menopause, and lumbar spine bone mineral density and remained significant after participants with vertebral fractures were excluded. In 483 men from the Rotterdam Study we found no association with height. In 1500 pre- and perimenopausal women from the Eindhoven Study a similar association was observed; women were 0.5 cm shorter per allele copy of the ESR1 haplotype 1 (P for trend = 0.03). In conclusion, we demonstrate a role for genetic variations in the estrogen receptor alpha gene in determining adult stature in women.

Age Factors↗

PubMed2004

Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study.

Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations.

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PubMed2003

Osteoarthritis of the knee is associated with vertebral and nonvertebral fractures in the elderly: the Rotterdam Study.

OBJECTIVE: To study the association between prevalent radiographic osteoarthritis (ROA) of the knee and incident vertebral and nonvertebral fractures. METHODS: A sample of 2,773 subjects was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. Status on knee ROA was assessed at baseline using the Kellgren score. Incident nonvertebral fractures were scored for all subjects, and for 1,466 subjects additional data on incident vertebral fractures were available. RESULTS: Although people with ROA had a higher bone mineral density (BMD), their incident fracture risk was increased as compared with those without ROA. After adjustment for potential confounding factors, including parameters of postural stability, the relative risks for incident vertebral and nonvertebral fractures in the presence of knee ROA were 2.0 (95% confidence interval [95% CI] 1.1-3.4) and 1.5 (95% CI 1.1-2.0), respectively. CONCLUSIONS: Knee ROA is associated with an increased risk of incident vertebral and nonvertebral fractures, independent of BMD and parameters of postural stability.

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PubMed2003

Coronary calcification at electron-beam CT: effect of section thickness on calcium scoring in vitro and in vivo.

PURPOSE: To compare the accuracy of electron-beam computed tomography (CT) with 3.0- and 1.5-mm section thickness for calcium quantification and the prevalence of coronary calcifications with each. MATERIALS AND METHODS: Electron-beam CT images were acquired with nonoverlapping 1.5- and 3.0-mm section thickness. Scans were obtained in an anthropomorphic thorax phantom with calcium cylinders of different sizes and densities, as well as in 1,302 study participants. A calcified lesion was defined as a minimum of 2 pixels (area, 0.52 mm2) with a minimum attenuation of 130 HU. The calcified lesions were quantified by means of a volumetric method with isotropic interpolation. From the phantom scans, mean volume scores, SDs, and measurement variations were calculated. From the participant scans, median volume scores and interquartile ranges were calculated. Participants were classified in categories based on cutoff levels for volume score quartiles for the 1.5-mm scans. An intraclass correlation coefficient (kappa value) was calculated as a measure of correlation between categories. RESULTS: In the phantom, deviations of calculated volumes from the true cylinder volumes and measurement variations were generally higher for the 3.0-mm protocol than for the 1.5-mm protocol. In the participants, the median volume score was 100 mm3 (interquartile range, 11-409 mm3) for the 3.0-mm protocol and 144 mm3 (interquartile range, 35-513 mm3) for the 1.5-mm protocol. Agreement between classifications of volume scores for the 1.5- and 3.0-mm scans was good (kappa = 0.62, P <.001). Compared with the quartile classification for the 1.5-mm scan, however, classifications for 370 (28%) participants were put in a different category with the 3.0-mm protocol. CONCLUSION: In a phantom, electron-beam CT scans with 3.0-mm section thickness yield less accurate estimates of calcified volume than do 1.5-mm scans. Electron-beam CT protocols with thinner sections considerably affect classification of individuals on the basis of the amount of coronary calcification depicted.

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