Showing papers by "Diederick E. Grobbee published in 1998"

Peripheral Arterial Disease in the Elderly The Rotterdam Study

Abstract: To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC.

Genetic association of apolipoprotein E with age-related macular degeneration

Abstract: Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic-association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam Study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2. 82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.

QTc Dispersion Predicts Cardiac Mortality in the Elderly The Rotterdam Study

Abstract: Background—Increased QTc dispersion has been associated with an increased risk for ventricular arrhythmias and cardiac death in selected patient populations. We examined the association between computerized QTc-dispersion measurements and mortality in a prospective analysis of the population-based Rotterdam Study among men and women aged ≥55 years. Methods and Results—QTc dispersion was computed with the use of the Modular ECG Analysis System as the difference between the maximum and minimum QTc intervals in 12 and 8 leads (ie, the 6 precordial leads, the shortest extremity lead, and the median of the 5 other extremity leads). After exclusion of those without a digitally stored ECG, the population consisted of 2358 men and 3454 women. During the 3 to 6.5 years (mean, 4 years) of follow-up, 568 subjects (9.8%) died. The degree of QTc dispersion was categorized into tertiles. Data were analyzed using the Cox proportional hazards model, with adjustment for age. For QTc dispersion in 8 leads, those in the hig...

Fish Oil and Glycemic Control in Diabetes: A meta-analysis

Abstract: OBJECTIVE Hypertriglyceridemia is associated with cardiovascular disease in diabetes. Fibrates effectively lower, but do not always normalize, serum triglyceride levels. Fish oil supplements may then be added to lower serum triglyceride levels. Doubt remains whether the net effect of fish oil intake on glycemic control is beneficial in diabetes. We therefore performed a meta-analysis from published clinical trials. RESEARCH DESIGN AND METHODS Data sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents, review articles, and published reference lists. Publications of 26 trials were selected, and all trials included more than five diabetes (IDDM and NIDDM) patients and addressed the effects offish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F, M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies were classified according to design. RESULTS All studies combined showed a decrease in mean triglyceride concentrations in association with fish oil: −0.60 mmol/1 (95% CI, −0.84 to −0.33, P P = 0.01), with both findings most prominent in NIDDM. No significant changes in HbA 1c percentages occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels were increased with borderline significance in NIDDM subjects (0.43 mmol/1 [95% CI, 0.00–0.87], P = 0.06) and were significantly lower in IDDM subjects (−1.86 mmol/1 [95% CI, −3.1 to −0.61], P 1c and triglycerides and of DHA (g/day) on fasting blood glucose levels, HbA 1c , and triglycerides were demonstrated only in NIDDM subjects. CONCLUSIONS The use of fish oil has no adverse affects on HbA 1c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

Serum Total IGF-I, Free IGF-I, and IGFBP-1 Levels in an Elderly Population Relation to Cardiovascular Risk Factors and Disease

Abstract: Recently, a method to measure free insulin-like growth factor-I (IGF-I) levels has been developed. Free IGF-I levels may have greater physiological and clinical relevance than total (bound and free) IGF-I. The associations between the circulating IGF-I/IGF binding protein (IGFBP) system and cardiovascular disorders was studied. In a cross-sectional study of 218 healthy persons (103 men, 115 women) aged 55 to 80 years, fasting serum (total and free) IGF-I and IGFBP-1 levels, lipid profile, insulin, and glucose were measured. In addition, blood pressure, body mass index (BMI), and waist-hip ratio (WHR) were measured. Ultrasonography of both carotid arteries was performed to investigate the presence of atherosclerotic lesions. A history of angina pectoris, the presence of a possible or definite myocardial infarction on the ECG, and plaques in the carotid arteries were used as indicators of presence of cardiovascular signs and symptoms. Free IGF-I was inversely related to serum triglycerides (P=.04, adjusted for age and sex). Mean free IGF-I levels in subjects without signs or symptoms of cardiovascular diseases were significantly higher than in those with at least one cardiovascular symptom or sign (P=.002, adjusted for age and sex). Free IGF-I levels were also higher in subjects who had no atherosclerotic plaques in the carotid arteries (P=.02, adjusted for age and sex) and who had never smoked (P=.02, adjusted for age and sex). IGFBP-1 showed an inverse relation with insulin, BMI, and WHR and a positive relation with HDL cholesterol. The associations between IGFBP-1 levels and HDL cholesterol, WHR, and BMI remained significant after adjustment for fasting insulin levels. High fasting serum free IGF-I levels are associated with a decreased presence of atherosclerotic plaques and coronary artery disease and lower serum triglycerides, whereas high fasting IGFBP-1 levels are associated with a more favorable cardiovascular risk profile. The findings suggest that the IGF-I/IGFBP system is related to cardiovascular risk factors and atherosclerosis.

Associations of radiological osteoarthritis of the hip and knee with locomotor disability in the Rotterdam Study

Abstract: OBJECTIVE—To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function. METHODS—During a home interview 1156 men and 1739 women, randomly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam (the Rotterdam Study) were asked about locomotor disability by six questions of the Health Assessment Questionnaire (HAQ) and about pain in the hips and knees in the past month. Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis. RESULTS—The prevalence of locomotor disability, defined as at least some difficulty with three or more out of six lower limb functions, was 20.2% for men and 31.9% for women; hip pain was present in 8.3% of the men and 16.6% of the women; knee pain in 12.6% of the men and 22.3% of the women. The prevalence of radiological osteoarthritis grade 2+ of the hip was 14.1% for men and 15.9% for women, and of the knee 16.3% and 29.1% respectively. The odds ratio (OR) (95% confidence intervals) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men: 1.4 (0.9, 2.1) and for women: 2.2 (1.6, 2.9). The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 (0.9, 2.1) and 1.4 (1.1, 1.8) respectively. Severe radiological osteoarthritis (grade 3+) was stronger associated. The ORs of pain in the hips or knees and morning stiffness were much higher (between 2.7 and 5.5 for men and between 2.1 and 5.1 for women). CONCLUSIONS—Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women, and not at all independently associated with locomotor disability in men. Age, pain of the hips and knees, and morning stiffness seem to be the most important independent determinants of locomotor disability. Keywords: osteoarthritis; hip; knee; locomotor disability

Breast-cancer incidence in relation to height, weight and body-fat distribution in the Dutch "DOM" cohort.

Abstract: In a cohort of 11,663 participants in a breast-cancer screening program, height, weight, waist circumference and hip circumference were measured, and information about menstrual and reproductive history was obtained by questionnaire. After exclusion of 83 women with unclear menopausal status, the subjects were divided into 3 sub-cohorts: 5,891 women who were pre-menopausal at the time of data collection, 3,521 women who had entered the study after natural menopause, and 2068 women who had been hysterectomized and/or ovariectomized. After a median follow-up of 10.6 years, 147, 76 and 52 incident cases of breast cancer were detected in the 3 respective sub-cohorts. No statistically significant association was found in any of the sub-cohorts between breast-cancer risk and height, weight, body-mass index (BMI) or hip circumference. In the sub-cohort of women with natural menopause, however, risk of breast cancer was positively and significantly associated with the ratio of waist-to-hip circumferences (WHR) (RR = 2.63 for upper vs. lower quartile), and this association did not change after adjustment for variations in disease risk related to body height and weight. Although similar to observations in other cohort studies showing positive associations between obesity and breast-cancer risk in post-menopausal women, our results are different, in that WHR and not BMI appears to be the more specific indicator of breast-cancer risk.

Evaluation of the angiotensinogen locus in human essential hypertension: A European study

Abstract: Different family and case-control studies support genetic linkage and association at the human angiotensinogen (AGT) locus with essential hypertension. To extend these previous observations, a European collaborative study of nine centers was set up to create a large resource of affected sibling pairs. The AGT locus was studied using a highly polymorphic dinucleotide repeat in the 3'-flanking region of the gene in 350 European families, comprising 630 affected sibling pairs. Statistical analyses using two different methods did not show any evidence for linkage either in the whole panel or in family subsets selected for severity or early onset of disease. Although several arguments from association studies suggest a role of the AGT gene in essential hypertension, this large family study did not replicate the initial linkage reported in smaller studies. Our results highlight the difficulty of identifying susceptibility genes by linkage analysis in complex diseases.

Methodological aspects of physical activity assessment in epidemiological studies

Abstract: A range of epidemiological studies conducted over the past decades has produced strong support for the view that lack of physical activity is associated with increased risks of several chronic diseases, such as cardiovascular disease, diabetes mellitus, cancer, etc. Much is still unknown about the type and degree of activity that is required to influence the risk of specific diseases. Furthermore, physical activity can act as a confounder in relationships between other exposure variables (e.g. diet) and disease. Thus, the measurement of physical activity in epidemiological studies is of great importance. The questionnaire is the most frequently used method in epidemiological research. Before using a questionnaire on a large scale, validity and reproducibility should be assessed in a representative population. Some practical and methodological aspects of physical activity validation studies are described, together with the possible implications of the results.

LDL Oxidation and Extent of Coronary Atherosclerosis

Abstract: Accumulated evidence indicates that oxidative modification of LDL plays an important role in the atherogenic process. Therefore, we investigated the relation between coronary atherosclerosis and susceptibility of LDL to oxidation in a case-control study in men between 45 and 80 years of age. Case subjects and hospital control subjects were selected from subjects undergoing a first coronary angiography. Subjects with severe coronary stenosis (≤85% stenosis in one and ≤50% stenosis in a second major coronary vessel) were classified as case subjects (n=91). Hospital control subjects with no or minor stenosis (≤50% stenosis in no more than two of the three major coronary vessels, n=94) and population control subjects flee of plaques in the carotid artery (n=85) were pooled for the statistical analysis into one control category. Enrollment procedures allowed for similar distributions in age and smoking habits. Case subjects had higher levels of total and LDL cholesterol and triglycerides and lower levels of HDL cholesterol. Resistance time, maximum rate of oxidation, and maximum diene production were measured ex vivo using copper-induced LDL oxidation. A borderline significant inverse trend was observed for coronary atherosclerosis risk at increasing resistance time. Odds ratios (95% confidence interval) for the successive quartiles were 1.0 (reference), 0.77 (0.39 to 1.53), 0.67 (0.33 to 1.34), and 0.55 (0.27 to 1.15) (P(trend)=0.07). No relation with maximum rate of oxidation was found, and higher maximum diene levels were found in control subjects (P<.01). The main determinant of oxidation was the fatty acid composition of LDL. No effect of smoking or use of medication was observed. We conclude that although LDL resistance to oxidation may be a factor in atherogenesis, the ex vivo measure is not a strong predictor of severity of coronary atherosclerosis.

Prevention of relapse in patients with congestive heart failure: the role of precipitating factors

Abstract: Relapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only limited data on the role of precipitating factors that trigger relapse of CHF. Knowledge of potential precipitating factors may help to optimise treatment and provide guidance for patients with CHF. The literature was reviewed to identify factors that may influence haemodynamic homeostasis in CHF. Precipitating factors that may offer opportunities for preventing relapse of CHF were selected. Potential precipitating factors are discussed in relation to the pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment compliance, and inappropriate medical treatment. Poor treatment compliance in particular is frequently encountered in patients with CHF. Furthermore, studies of medical treatment under everyday circumstances indicate that some aspects of the management of CHF can be improved. In conclusion, the identification of precipitating factors for relapse of CHF may strongly contribute to optimal treatment. Improvement of treatment compliance and optimalisation of medical treatment may offer important possibilities to clinicians to reduce the number of relapses in patients with CHF.

Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension

Abstract: Objective To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension, Design A double-blind randomized, placebo-controlled trial. Setting General practitioners referred patients to the trial physician. Patients The study population comprised 121 patients with non-insulin-dependent diabetes mellitus, inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure less than or equal to 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. Intervention Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41), The treatment period was 48 weeks. Main outcome measures The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment, The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. Results Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m(2), 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m(2), 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m(2), 95% confidence interval 2-16), Conclusion These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo. (C) 1998 Lippincott-Raven Publishers.

Dutch case-control study of anaesthesia-related morbidity and mortality. Rationale and methods

Abstract: To date, anaesthesia-related mortality, morbidity and risk factors have almost exclusively been studied qualitatively rather than quantitatively. Therefore, knowledge of the relative risk associated with many anaesthesia-related factors is still lacking. Recently, a quantitative study of the determinants and prevention of morbidity and mortality in anaesthesia was started in the Netherlands. Its objective is to study severe peri-operative morbidity and mortality as a function of anaesthesia-related risk factors. The study is designed as a case-control study within a prospectively defined cohort. The cohort comprises all patients undergoing an anaesthetic procedure, either general, regional or a combination, in one of 61 hospitals between 1 January 1995 and 1 January 1997. A 'case' is a patient who dies within 24 h of undergoing an anaesthetic procedure or who remains comatose 24 h after an anaesthetic procedure. A 'control' patient is a randomly chosen patient who has undergone anaesthesia and is matched for gender and age. The present report discusses the study protocol.

Exercise testing in patients with chest pain to sumatriptan

Abstract: Objectives: In order to assess whether chest pain attributed to sumatriptan is associated with abnormalities on cardiac exercise testing, we performed a case-control study. Subjects: Cases were selected as consumers of sumatriptan who reported sumatriptan associated chest pain. A reference group was selected randomly from consumers of sumatriptan with the same GP as the case, who reported no chest pain after use of sumatriptan. If possible, controls were matched for age (within 5-year groups) and gender. Outcomes: In a total of 74 cases and 55 controls symptom-limited exercise tests were performed. Besides a small difference in age, there were no differences in basic characteristics between cases and controls. Three cases had ST-depression on ECG during exercise. However, none of the variables measured during exercise testing differed significantly between cases and controls. Conclusions: The prevalence of abnormal exercise tests in patients with sumatriptan-induced chest pain is low, and not statistically different from patients without chest pain after intake of sumatriptan. Routine performance of exercise testing in patients with sumatriptan-associated chest pain is not recommended.

Likelihood of underreporting of outlet strut fracture from examination of the Dutch Björk-Shiley CC cohort

Abstract: The Dutch Bjork-Shiley convexo-concave (BScc) cohort serves as a reference population on the risk of outlet strut fracture and is being used to formulate guidelines for prophylactic replacement. Fractures, however, may be undetected at death. The aim of this study was to quantify the degree of underestimation of strut fracture in the Dutch BScc cohort. Multivariate Cox regression analysis was used to assess the relative and absolute risk of death from different causes within 14 years. The unexplained “excess” mortality among 70° BScc valve recipients was attributed to unreported fatal strut fractures and used to estimate its extent in this group, which then was extrapolated to the 60° BScc valve recipients. For 70° BScc valve recipients, the adjusted hazard ratio for death from all causes except strut fracture was 1.2 (95% confidence interval [CI] 1.0 to 1.5). The 14-year absolute risks for 70° and 60° BScc valve recipients were 44% and 37%, respectively. Among 70° and 60° BScc valve recipients, underreporting of fracture was estimated to be 25% (95% CI 0 to 49) and 26% (95% CI 0 to 52), respectively. Estimates based on sudden death and fatal congestive heart failure yielded essentially the same results. Thus, underreporting of fatal strut fracture in the Dutch BScc cohort is estimated to be approximately 25%. Hence, the risk and lethality of fracture of BScc valves are underestimated and indications for prophylactic replacement should be adjusted accordingly. For example, the advantage of valve replacement in a 40-year-old patient with a 29-mm 60° BScc mitral valve would almost double to 0.82 years.

Lessons from a heart valve prosthesis controversy

Abstract: Two lessons are to be learnt from the Bjork-Shiley heart valve prosthesis tragedy. In the first place pharmacoepidemiologic studies are seriously hampered by recent privacy legislation. Individual patients carrying such a prosthesis cannot be traced and advised as to their health risks any more, because their legal autonomy has to be respected. This is clearly not to their advantage. In the second place the atmosphere of marketing and litigation and the increasing dependency of researchers on money from sources with conflicting interests is not conducive to a well-informed and balanced judgement of the epidemiological evidence of safety and efficacy of medical treatments.