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

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

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

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

Coronary calcification detected by electron-beam computed tomography and myocardial infarction. The Rotterdam Coronary Calcification Study.

AIMS: Available data are insufficient to determine the relation between coronary calcification and coronary events in the general population. We cross-sectionally examined the association between coronary calcification and myocardial infarction in the prospective Rotterdam Coronary Calcification Study. METHODS AND RESULTS: From 1997 onwards, subjects were invited for electron-beam computed tomography scanning to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2,013 participants with a mean age of 71 years (standard deviation, 5.7 years). A history of myocardial infarction prior to scanning was present in 229 subjects. Compared to subjects in the lowest calcium score category (0-100), the age-adjusted odds ratio for myocardial infarction in subjects in the highest calcium score category (above 2,000) was 7.7 (95% confidence interval, 4.1-14.5) for men, and 6.7 (95% confidence interval, 2.4-19.1) for women. Additional adjustment for cardiovascular risk factors only slightly altered the estimates. The association was observed across all age subgroups, i.e. also in subjects of 70 years and older. CONCLUSION: A strong and graded association was found between coronary calcification and myocardial infarction. The association remained at high ages.

Bone mineral density and mortality in elderly men and women: the Rotterdam Study.

Recent studies have shown that a low bone mineral density (BMD) is associated with a higher risk of mortality. Most studies have investigated this relationship in women only and presented their risk estimates per standard deviation change in BMD. However, when using this approach, a BMD threshold might be missed when relative risks are presented in the traditional manner. Therefore, in this study our aim was to model the relation between BMD and all-cause mortality. In the Rotterdam Study, follow-up was complete for 5819 men and women aged > or =55 years for whom BMD data were available. During an average follow-up of 5.4 years, 399 men and 317 women died. We calculated BMD Z scores using measurements performed at the femoral neck. Cox proportional hazards regression was used to fit the model. An average BMD, reflected by a Z score = 0, was used as the reference. For women, no significant relationship between BMD and overall mortality was observed. For men, however, a cubic model best fitted the relationship under study, also after adjusting for age and body mass index (BMI). The risk of mortality increased when BMD was below average. Similar results were found when separate curves were made for diabetics and nondiabetics, smokers (ever or never), and tertiles of BMI. Excluding subjects who had suffered hip fractures, or adjusting for the number of drugs used and for lower limb disability, essentially did not change results. This suggests that low BMD is not mainly due to morbidity and impaired mobility in our cohort, which makes this a less likely explanation for the observed relation with mortality. The results of our study suggest that, in men, a nonlinear relationship between BMD and mortality exists, which is independent of comorbidity, whereas, in women, no significant relationship was observed.

A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study.

OBJECTIVE: To compare body mass index (BMI), waist-hip ratio (WHR) and waist circumference as predictors of all-cause mortality among the elderly. DESIGN: Population-based cohort study; mean follow-up was 5.4 y. SETTING: The Rotterdam Study. PARTICIPANTS: A total of 6296 men and women; baseline age 55-102 y. MEASUREMENTS: Sex-specific all-cause mortality was compared between quintiles of BMI, WHR and waist circumference and between predefined categories of BMI and waist circumference, stratified for smoking category. RESULTS: High quintiles of waist circumference, but not high quintiles of BMI and WHR were related to increased mortality among never smoking men, without reaching statistical significance. Only the highest category of BMI (BMI>30 kg/m2) among never smoking men was related to increased mortality, compared to normal BMI (hazard ratio 2.6 (95% confidence interval: 1.3-5.3)). Waist circumference between 94 and 102 cm and waist circumference 102 cm and larger were related to increased mortality, compared to normal waist circumference (hazard ratios 1.7 (95% confidence interval 1.1-2.8) and 1.6 (95% confidence interval 1.0-2.8), respectively). The proportion of mortality attributable to large waist circumference among never smoking men was three-fold the proportion attributable to high BMI. Among never smoking women and ex- and current smokers, categories of large body fatness did not predict increased mortality. CONCLUSION: Among never smoking elderly men waist circumference may have more potential for detecting overweight than the BMI.

Arterial stiffness as underlying mechanism of disagreement between an oscillometric blood pressure monitor and a sphygmomanometer.

Oscillometric blood pressure devices tend to overestimate systolic blood pressure and underestimate diastolic blood pressure compared with sphygmomanometers. Recent studies indicate that discrepancies in performance between these devices may differ between healthy and diabetic subjects. Arterial stiffness in diabetics could be the underlying factor explaining these differences. We studied differences between a Dinamap oscillometric blood pressure monitor and a random-zero sphygmomanometer in relation to arterial stiffness in 1808 healthy elderly subjects. The study was conducted within the Rotterdam Study, a population-based cohort study of subjects aged 55 years and older. Systolic and diastolic blood pressure differences between a Dinamap and a random-zero sphygmomanometer were related to arterial stiffness, as measured by carotid-femoral pulse wave velocity. Increased arterial stiffness was associated with higher systolic and diastolic blood pressure readings by the Dinamap compared with the random-zero sphygmomanometer, independent of age, gender, and average mean blood pressure level of both devices. The beta-coefficient (95% CI) was 0.25 (0.00 to 0.50) mm Hg/(m/s) for the systolic blood pressure difference and 0.35 (0.20 to 0.50) mm Hg/(m/s) for the diastolic blood pressure difference. The results indicate that a Dinamap oscillometric blood pressure device, in comparison to a random-zero sphygmomanometer, overestimates systolic and diastolic blood pressure readings in subjects with stiff arteries.

Blood pressure and risk of myocardial infarction in elderly men and women: the Rotterdam study.

OBJECTIVE: To study the association between blood pressure and risk of myocardial infarction in elderly subjects. DESIGN: Prospective cohort study. SETTING: The Rotterdam Study, a Dutch population-based study. PARTICIPANTS: 6004 men and women aged > or = 55 years. MAIN OUTCOME MEASURES: Fatal or non-fatal myocardial infarction (n = 190) during a 4-year follow-up. RESULTS: After excluding participants using blood pressure-lowering medication and participants with a history of myocardial infarction, increasing levels of systolic blood pressure (SBP) were associated with increasing risk of first myocardial infarction (P for trend < 0.0001). The relative risk (RR) for an SBP of 160 mmHg or higher was 5.7 (95% confidence interval (CI) 1.9-17.1) compared with an SBP below 120 mmHg. Increasing diastolic blood pressure (DBP) was also associated with increasing risk of first myocardial infarction, with the RR reaching 2.5 (95% CI 1.4-4.5) in subjects with values of 80-90 mmHg compared with values below 70 mmHg (P for trend < 0.05). Analyses in subjects aged 70 years and over showed that the positive associations between SBP and DBP and risk of first myocardial infarction remained at older age. CONCLUSION: These findings in a relatively healthy cohort of elderly subjects do not provide evidence for a J- or U-shaped relation between SBP and DBP and risk of first myocardial infarction. They suggest that the risk of first myocardial infarction increases with increasing level of systolic and diastolic blood pressure and that this relationship persists into older age.

Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands.

As part of the "IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants," a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers.