Frank J. A. van Rooij

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.

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 × 10−8 to 7 × 10−86). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

Coronary calcium score improves classification of coronary heart disease risk in the elderly : the Rotterdam study

OBJECTIVES The purpose of this study was to examine the effect of coronary artery calcium (CAC) on the classification of 10-year hard coronary heart disease (CHD) risk and to empirically derive cut-off values of the calcium score for a general population of elderly patients. BACKGROUND Although CAC scoring has been found to improve CHD risk prediction, there are limited data on its impact in clinical practice. METHODS The study comprised 2,028 asymptomatic participants (age 69.6 ± 6.2 years) from the Rotterdam Study. During a median follow-up of 9.2 years, 135 hard coronary events occurred. Persons were classified into low (<10%), intermediate (10% to 20%), and high (>20%) 10-year coronary risk categories based on a Framingham refitted risk model. In a second step, the model was extended by CAC, and reclassification percentages were calculated. Cutoff values of CAC for persons in the intermediate-risk category were empirically derived based on 10-year hard CHD risk. RESULTS Reclassification by means of CAC scoring was most substantial in persons initially classified as intermediate risk. In this group, 52% of men and women were reclassified, all into more accurate risk categories. CAC values above 615 or below 50 Agatston units were found appropriate to reclassify persons into high or low risk, respectively. CONCLUSIONS In a general population of elderly patients at intermediate CHD risk, CAC scoring is a powerful method to reclassify persons into more appropriate risk categories. Empirically derived CAC cutoff values at which persons at intermediate risk reclassified to either high or low risk were 615 and 50 Agatston units, respectively.

Disagreement between subjective and actigraphic measures of sleep duration in a population-based study of elderly persons

Sleep duration is an important concept in epidemiological studies. It characterizes a night’s sleep or a person’s sleep pattern, and is associated with numerous health outcomes. In most large studies, sleep duration is assessed with questionnaires or sleep diaries. As an alternative, actigraphy may be used, as it objectively measures sleep parameters and is feasible in large studies. However, actigraphy and sleep diaries may not measure exactly the same phenomenon. Our study aims to determine disagreement between actigraphic and diary estimates of sleep duration, and to investigate possible determinants of this disagreement. This investigation was embedded in the population‐based Rotterdam Study. The study population consisted of 969 community‐dwelling participants aged 57–97 years. Participants wore an actigraph and kept a sleep diary for, on average, six consecutive nights. Both measures were used to determine total sleep time (TST). In 34% of the participants, the estimated TST in the sleep diaries deviated more than 1 h from actigraphically measured TST. The level of disagreement between diary and actigraphic measures decreased with subjective and actigraphic measures of sleep quality, and increased with male gender, poor cognitive function and functional disability. Actigraphically measured poor sleep was often accompanied by longer subjective estimates of TST, whereas subjectively poor sleepers tended to report shorter TST in their diaries than was measured with actigraphy. We recommend, whenever possible, to use multiple measures of sleep duration, to perform analyses with both, and to examine the consistency of the results over assessment methods.

Clinical ResearchImaging of Coronary CalciumCoronary Calcium Score Improves Classification of Coronary Heart Disease Risk in the Elderly: The Rotterdam Study

OBJECTIVES The purpose of this study was to examine the effect of coronary artery calcium (CAC) on the classification of 10-year hard coronary heart disease (CHD) risk and to empirically derive cut-off values of the calcium score for a general population of elderly patients. BACKGROUND Although CAC scoring has been found to improve CHD risk prediction, there are limited data on its impact in clinical practice. METHODS The study comprised 2,028 asymptomatic participants (age 69.6 ± 6.2 years) from the Rotterdam Study. During a median follow-up of 9.2 years, 135 hard coronary events occurred. Persons were classified into low (<10%), intermediate (10% to 20%), and high (>20%) 10-year coronary risk categories based on a Framingham refitted risk model. In a second step, the model was extended by CAC, and reclassification percentages were calculated. Cutoff values of CAC for persons in the intermediate-risk category were empirically derived based on 10-year hard CHD risk. RESULTS Reclassification by means of CAC scoring was most substantial in persons initially classified as intermediate risk. In this group, 52% of men and women were reclassified, all into more accurate risk categories. CAC values above 615 or below 50 Agatston units were found appropriate to reclassify persons into high or low risk, respectively. CONCLUSIONS In a general population of elderly patients at intermediate CHD risk, CAC scoring is a powerful method to reclassify persons into more appropriate risk categories. Empirically derived CAC cutoff values at which persons at intermediate risk reclassified to either high or low risk were 615 and 50 Agatston units, respectively.

Dietary antioxidants and long-term risk of dementia

BACKGROUND The Rotterdam Study previously found that higher dietary intakes of vitamins E and C related to lower risk of dementia and Alzheimer disease (AD) over 6 years of follow-up. OBJECTIVE To study consumption of major dietary antioxidants relative to long-term risk of dementia. DESIGN Population-based prospective cohort study. SETTING The Rotterdam Study in the Netherlands. PARTICIPANTS A total of 5395 participants, 55 years and older, who were free of dementia and provided dietary information at study baseline. MAIN OUTCOME MEASURES Incidence of dementia and AD, based on internationally accepted criteria, relative to dietary intake of vitamin E, vitamin C, beta carotene, and flavonoids. RESULTS During a mean follow-up period of 9.6 years, dementia developed in 465 participants, of whom 365 were diagnosed as having AD. In multivariate models adjusted for age, education, apolipoprotein E epsilon4 genotype, total energy intake, alcohol intake, smoking habits, body mass index, and supplement use, higher intake of vitamin E at study baseline was associated with lower long-term risk of dementia (P = .02 for trend). Compared with participants in the lowest tertile of vitamin E intake, those in the highest tertile were 25% less likely to develop dementia (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95 with adjustment for potential confounders). Dietary intake levels of vitamin C, beta carotene, and flavonoids were not associated with dementia risk after multivariate adjustment (P > .99 for trend for vitamin C and beta carotene and P = .60 for trend for flavonoids). Results were similar when risk for AD was specifically assessed. CONCLUSION Higher intake of foods rich in vitamin E may modestly reduce long-term risk of dementia and AD.

Methods of data collection and definitions of cardiac outcomes in the Rotterdam Study

The prevalence of cardiovascular diseases is rising. Therefore, adequate risk prediction and identification of its determinants is increasingly important. The Rotterdam Study is a prospective population-based cohort study ongoing since 1990 in the city of Rotterdam, The Netherlands. One of the main targets of the Rotterdam Study is to identify the determinants and prognosis of cardiovascular diseases. Case finding in epidemiological studies is strongly depending on various sources of follow-up and clear outcome definitions. The sources used for collection of data in the Rotterdam Study are diverse and the definitions of outcomes in the Rotterdam Study have changed due to the introduction of novel diagnostics and therapeutic interventions. This article gives the methods for data collection and the up-to-date definitions of the cardiac outcomes based on international guidelines, including the recently adopted cardiovascular disease mortality definitions. In all, detailed description of cardiac outcome definitions enhances the possibility to make comparisons with other studies in the field of cardiovascular research and may increase the strength of collaborations.

Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk

BACKGROUND Greater fish and omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake may reduce dementia risk; however, previous studies have reported conflicting results, which were largely based on short-term follow-up. OBJECTIVE The objective was to study the dietary consumption of fish and omega-3 PUFAs in relation to long-term dementia risk. DESIGN We studied 5395 participants aged > or =55 y in the Rotterdam Study who were free of dementia and reported dietary information at baseline. We used age- and sex-adjusted Cox proportional hazard and multivariate-adjusted models to evaluate the relative risk of dementia and Alzheimer disease (AD) across categories of typical fish intake (none, low, and high) and fish type consumed (none, lean, and fatty). We also evaluated dementia and AD risk across tertiles of omega-3 PUFA intake, specifically, total long-chain omega-3 fatty acids: eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), alpha-linolenic acid, and EPA and DHA individually. RESULTS During an average follow-up of 9.6 y, dementia developed in 465 participants (365 with a diagnosis of AD). In multivariate-adjusted models, total fish intake was unrelated to dementia risk (P for trend = 0.7). Compared with participants who typically ate no fish, those with a high fish intake had a similar dementia risk (hazard ratio: 0.95; 95% CI: 0.76, 1.19), as did those who typically ate fatty fish (hazard ratio: 0.98; 95% CI: 0.77, 1.24). Dietary intakes of omega-3 PUFAs were also not associated with dementia risk, and the results were similar when we considered AD specifically. CONCLUSION In this Dutch cohort, who had a moderate consumption of fish and omega-3 PUFAs, these dietary factors do not appear to be associated with long-term dementia risk.

Cigarette smoking and risk of atrial fibrillation: the Rotterdam Study.

BACKGROUND Cigarette smoking is an important risk factor for cardiovascular disease, but it is unknown whether it also contributes to the risk of atrial fibrillation. METHODS AND RESULTS The study is part of the Rotterdam Study, a population-based cohort study among subjects aged > or =55 years. The association between cigarette smoking and the risk of atrial fibrillation was examined in 5,668 subjects without atrial fibrillation at baseline. During a median follow-up of 7.2 years, 371 cases of atrial fibrillation were identified. Relative risks (RR) were calculated with 95% CIs using the Cox proportional hazards model, adjusted for age, gender, body mass index, hypertension, systolic blood pressure, serum cholesterol level, diabetes mellitus, left ventricular hypertrophy on the electrocardiogram, prevalent and incident myocardial infarction, prevalent heart failure, and the use of pulmonary medication. After multivariate adjustment, current smokers and former smokers had increased risks of atrial fibrillation as compared to never smokers (RR 1.51, 95% CI 1.07-2.12; and RR 1.49, 95% CI 1.14-1.97, respectively). No differences were found between men and women. CONCLUSIONS The results of this prospective, population-based study show that current and former smoking of cigarettes are associated with increased risk of atrial fibrillation.

Inverse association between dairy intake and hypertension: the Rotterdam Study

BACKGROUND Little is known about the effect of different types of dairy food products on the development of hypertension. OBJECTIVE The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. DESIGN We examined the relation between dairy intake and incident hypertension in 2245 participants of the Rotterdam Study aged > or =55 y with complete dietary and blood pressure data, who were free of hypertension at baseline (1990-1993). Blood pressure was reexamined in 1993-1995 and in 1997-1999. Hazard ratios (HRs) with 95% CIs for 2- and 6-y incidence of hypertension were obtained in quartiles of energy-adjusted dairy intake, with adjustment for age, sex, BMI, smoking, educational level, dietary factors, and intake of alcohol and total energy. RESULTS Risk of hypertension after 2 y of follow-up (664 incident cases) was inversely associated with dairy product intake. After adjustment for confounders, HRs (95% CIs) were 1.00, 0.82 (0.67, 1.02), 0.67 (0.54, 0.84), and 0.76 (0.61, 0.95) in consecutive quartiles of total dairy product intake (P for trend = 0.008). Corresponding HRs for low-fat dairy products were 1.00, 0.75 (0.60, 0.92), 0.77 (0.63, 0.96), and 0.69 (0.56, 0.86) (P for trend = 0.003). Analysis of specific types of dairy products showed an inverse association with milk and milk products (P for trend = 0.07) and no association with high-fat dairy or cheese (P > 0.6). After 6 y of follow-up (984 incident cases), the associations with hypertension were attenuated to risk reductions of approximately 20% for both total and low-fat dairy products between the extreme quartiles of intake (P for trend = 0.07 and 0.09, respectively). CONCLUSION Intake of low-fat dairy products may contribute to the prevention of hypertension at an older age.