Calcium intake and blood pressure: an update.
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Adult↗
Biomedical subjects
D E Grobbee
Publications and source records attributed to D E Grobbee.
Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men.
In the present cross-sectional study of 403 independently living elderly men, we tested the hypothesis that the decreases in bone mass, body composition, and muscle strength with age are related to the fall in circulating endogenous testosterone (T) and estrogen concentrations. We compared various measures of the level of bioactive androgen and estrogen to which tissues are exposed. After exclusion of subjects with severe mobility problems and signs of dementia, 403 healthy men (age, 73-94 yr) were randomly selected from a population-based sample. Total T (TT), free T (FT), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were determined by RIA. Levels of non-SHBG-bound T (non-SHBG-T), FT (calc-FT), the TT/SHBG ratio, non-SHBG-bound E2, and free E2 were calculated. Physical characteristics of aging included muscle strength measured using dynamometry, total body bone mineral density (BMD), hip BMD, and body composition, including lean mass and fat mass, measured by dual-energy x-ray absorptiometry. In this population of healthy elderly men, calc-FT, non-SHBG-T, E1, and E2 (total, free, and non-SHBG bound) decreased significantly with age. T (total and non-SHBG-T) was positively related with muscle strength and total body BMD (for non-SHBG-T, respectively, beta = 1.93 +/- 0.52, P < 0.001 and beta = 0.011 +/- 0.002, P < 0.001). An inverse association existed between T and fat mass (beta = -0.53 +/- 0.15, P < 0.001). Non-SHBG-T and calc-FT were more strongly related to muscle strength, BMD, and fat mass than TT and were also significantly related to hip BMD. E1 and E2 were both positively, independently associated with BMD (for E2, beta = 0.21 +/- 0.08, P < 0.01). Non-SHBG-bound E2 was slightly strongly related to BMD than total E2. The positive relation between T and BMD was independent of E2. E1 and E2 were not related with muscle strength or body composition. In summary, bioavailable T, E1, total E2, and bioavailable E2 all decrease with age in healthy old men. In this cross-sectional study in healthy elderly men, non-SHBG-bound T seems to be the best parameter for serum levels of bioactive T, which seems to play a direct role in the various physiological changes that occur during aging. A positive relation with muscle strength and BMD and a negative relation with fat mass was found. In addition, both serum E1 and E2 seem to play a role in the age-related bone loss in elderly men, although the cross-sectional nature of the study precludes a definitive conclusion. Non-SHBG-bound E2 seems to be the best parameter of serum bioactive E2 in describing its positive relation with BMD.
Absorptiometry, Photon↗
Osteoporosis and salt intake.
AIM: Recently, it has been hypothesized that salt intake may be related to the risk of osteoporosis. The aim of this review was to summarize the evidence for such relationship and to discuss possible mechanisms. DATA SYNTHESIS: We performed a review of the scientific literature on osteoporosis, particularly its etiology, and then focussed on studies addressing the relation between salt intake on the one hand, and calcium balance, bone resorption, bone mineral density and fractures on the other. Although a relation between high salt intake and increased bone loss is biologically plausible, the most pertinent studies relating salt intake to bone mineral density are only suggestive of high salt consumption as a risk factor for osteoporosis. Unfortunately, studies on fracture risk and salt intake are lacking. CONCLUSION: The relationship between salt intake and osteoporosis is still controversial. A possible relation between salt intake and fracture risk should be addressed in future studies.
Bone Density↗
Phyto-oestrogens and cardiovascular disease risk.
AIM: To present the currently available evidence on the cardiovascular benefits and risks associated with phyto-oestrogens. DATA-SYNTHESIS: Medline search from 1966-1999 updated with cross-check of references of papers with keywords such as phyto-oestrogens, isoflavones, lignans, genistein, daidzein, enterolactone, enterodiol, cardiovascular disease, cardiovascular disease risk factors. CONCLUSIONS: Phyto-oestrogens are plant chemicals divided into three main classes: isoflavones, coumestans, and lignans that display oestrogen-like activity due to their ability to bind to the oestrogen receptor. They are found in grains, beans, green vegetables, fruits, nuts, and grasses. Isoflavones are primarily found in soybeans and soy foods. For epidemiological studies of the relation between phyto-oestrogen intake and disease parameters, intake is estimated with several measures, such as biomarkers (concentrations in urine or blood) or dietary questionnaires, though the optimal method is not yet clear. Phyto-oestrogens are considered to act as selective oestrogen receptor modulators (SERM), exerting both oestrogen agonist and antagonist action. Supplementation with isolated soy protein containing the isoflavones genistein and daidzein reduces serum total and LDL-cholesterol and triglycerides in animals and in humans. Vascular reactivity might be improved by supplementation with isolated soy protein or isoflavones isolated from red clover. Studies on atherosclerosis in animals indicate a potential for risk reduction. Evidence in humans is still scanty. The little we know of the effects of regular dietary phyto-oestrogen intake comes from studies in which phyto-oestrogens were added to the usual diet. Most supplementation studies have been conducted with soy isoflavones, whereas the importance of lignans has not been determined, though they could be more important sources than isoflavones in Western populations. Research has been focused on risk factors. Studies of clinically manifest endpoints are urgently needed.
Animals↗
Endogenous clotting factor activity and long-term outcome in patients with moderate haemophilia.
In order to address the question of the optimum target level for prophylactic treatment of severe haemophilia patients, the association between endogenous clotting factor activity and outcome was studied in a cohort of 46 patients with moderate haemophilia. Data on treatment and outcome were collected annually. Median follow-up was 8.0 years (range 1-26). Median joint bleed frequency was 1 per year and median radiological score according to Pettersson was 1 point (max. 78) at the age of 25 years. One percent increase in clotting factor level was associated with a 4 months later onset of joint bleeds (95% Confidence Interval (CI): 2-6 months) and a 16% lower Pettersson score (95% CI: 3-27%). No statistically significant effect of clotting factor activity on joint bleed frequency could be demonstrated. These findings confirm that patients with moderate haemophilia experience only mild arthropathy, and provide evidence for a protective effect of higher clotting factor levels on joint damage.
Adolescent↗
Both decreased and increased heart rate variability on the standard 10-second electrocardiogram predict cardiac mortality in the elderly: the Rotterdam Study.
Decreased heart rate variability has been associated with an adverse prognosis in patients after myocardial infarction. Studies carried out in the population at large show contradictory results. The authors examined the association between heart rate variability on a standard 10-second electrocardiogram and cardiac and all-cause mortality in the Rotterdam Study, a population-based cohort study of men and women aged > or =55 years, using data collected between 1990 and 1996 (mean follow-up = 4 years). Heart rate variability, taken as the standard deviation of normal R-R intervals (SDNN), was computed by means of the Modular ECG Analysis System. After exclusion of subjects with arrhythmia and those with fewer than six normal R-R intervals, the study population consisted of 2,088 men and 3,184 women. Cox's proportional hazards model was used to examine the age- and sex-adjusted risk for cardiac, noncardiac, and total mortality in relation to quartiles of SDNN, using the third quartile of SDNN as the reference category. Subjects in the lowest quartile of SDNN relative to those in the third quartile had an 80 percent age- and sex-adjusted increased risk for cardiac mortality (hazard ratio = 1.8; 95% confidence interval: 1.0, 3.2). Interestingly, for subjects in the highest quartile of SDNN, an even more pronounced risk for cardiac mortality was present (hazard ratio = 2.3; 95% confidence interval: 1.3, 4.0). Additional adjustment for possible confounders did not materially change the risk estimates. The authors conclude that heart rate variability measured on the standard 10-second electrocardiogram can be used to identify older men and women with an increased risk for cardiac mortality. In the elderly, increased heart rate variability is an even stronger indicator of cardiac mortality than decreased heart rate variability. Further studies are needed to confirm these findings and to elucidate their physiologic meaning.
Aged↗
Common carotid intima-media thickness and arterial stiffness: indicators of cardiovascular risk in high-risk patients. The SMART Study (Second Manifestations of ARTerial disease).
BACKGROUND: Common carotid intima-media thickness (IMT) and distensibility are markers of structural and functional vessel wall properties. Both parameters have been found in population-based studies to be associated with cardiovascular risk factors and prevalent cardiovascular disease. We investigated cross-sectionally whether IMT and distensibility are associated with cardiovascular risk in patients who already have vascular disease or atherosclerotic risk factors and evaluated the diagnostic ability of IMT and distensibility to discriminate between low- and high-risk patients. METHODS AND RESULTS: IMT and distensibility (change of diameter) of the left and right common carotid arteries were measured in the first 570 patients (537 for distensibility) enrolled in the Second Manifestations of ARTerial disease (SMART) study, a cohort study among patients with a manifestation of vascular disease or cardiovascular risk factors. Three risk scores were used to classify each patient's vascular risk. Areas under the curve (AUCs) of receiver-operating characteristic curves were calculated for IMT and distensibility after the patients were dichotomized on the median of the risk scores as the outcome. Risk scores increased nearly linearly with increasing IMT and decreasing distensibility. The AUCs for IMT predicting high-risk patients were 0.77, 0.73, and 0.77 based on the 3 risk scores. The AUCs for distensibility were 0. 65, 0.62, and 0.66. CONCLUSIONS: Common carotid IMT and distensibility are clear markers of cardiovascular risk in patients who already have vascular disease or atherosclerotic risk factors. IMT appears to discriminate between low- and high-risk patients better than distensibility.
Adult↗
Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness.
OBJECTIVES: To assess the 2-year effects of a combined regimen of oral 17beta-estradiol and desogestrel (17betaE-D) and a sequential combination of conjugated equine estrogens and norgestrel (CEE-N) on common carotid intima-media thickness and end-diastolic lumen diameter in comparison to placebo in perimenopausal women. METHODS: The study was a single center, randomized, group-comparative, double-blind study with respect to the 17betaE-D and placebo groups and open with respect to CEE-N. After cycle 6, the blind was broken and the trial was continued as an open trial for another 18 months for the active study arms. The study included 121 perimenopausal women recruited from the general population. Common carotid intima-media thickness and end-diastolic lumen diameter were measured at baseline and cycle 24 with B-mode ultrasonography. RESULTS: At cycle 24 small changes in intima-media thickness and lumen diameter were observed. Relative to placebo, changes in intima-media thickness were -0.009 mm [95% CI -0.045; 0.027] for 17betaE-D and -0.016 mm [95% CI -0.055; 0.024] for CEE-N. For end-diastolic lumen diameter the changes were -0.091 mm [95% CI -0.236; 0.055] and -0.125 mm [95% CI -0.820; 0.032] for 17betaE-D and CEE-N, respectively. CONCLUSIONS: In this study among perimenopausal women a significant effect of 17betaE-D and CEE-N on common carotid intima-media thickness and lumen diameter could not be demonstrated. Although the sample size of the present trial is too limited to provide definite conclusions, the direction of the effect is in agreement with evidence from earlier studies on the effects of hormone replacement therapy in postmenopausal women.
Adult↗
Insulin resistance syndrome and left ventricular mass in an elderly population (The Rotterdam Study).
In a study of elderly men and women, age, body mass index, and systolic blood pressure (and in men, also glucose) were significant predictors of left ventricular mass. Postload insulin was not independently associated with left ventricular mass.
Age Factors↗
Socioeconomic status and aortic atherosclerosis in Dutch elderly people: the Rotterdam Study.
An inverse association has been reported between socioeconomic status (SES) and cardiovascular morbidity and mortality. Studies on subclinical manifestations of atherosclerotic disease are limited and have not been carried out among elderly persons. The authors investigated the relation between SES and aortic atherosclerosis among elderly people. As part of the Rotterdam Study, data on SES and atherosclerosis were collected for 4,451 persons aged 55-94 years. Atherosclerosis was estimated by radiographic assessment of calcified deposits in the abdominal aorta. Aortic atherosclerosis was more common among women in the lower educational and occupational strata. The lowest educational group and the lowest occupational group had increased risks of aortic atherosclerosis compared with the highest groups (odds ratios were 1.3 (95% confidence interval (CI) 1.0-1.6) and 1.3 (95% CI 1.0-1.8), respectively). The odds ratios for severe atherosclerosis among women in the lowest socioeconomic stratum compared with those in the highest stratum were 1.6 (95% CI 1.0-2.7) for education, 2.8 (95% CI 1.1-7.5) for occupation, and 1.7 (95% CI 0.9-3.3) for income. After exclusion of persons with a history of cardiovascular disease, the same trends still emerged. No relations were observed among men. These findings show that SES is related to aortic atherosclerosis in women. This suggests that SES affects the incidence of cardiovascular disease before its clinical manifestation.
Age Factors↗
Trends in the prevalence of hypertension, antihypertensive therapy, and left ventricular hypertrophy from 1950 to 1989.
BACKGROUND: Men and women with hypertension are at increased risk for cardiovascular disease, especially when left ventricular hypertrophy is present. We examined temporal trends in the use of antihypertensive medications and studied the relation between their use, the prevalence of high blood pressure, and the presence of electrocardiographic evidence of left ventricular hypertrophy. METHODS: A total of 10,333 participants in the Framingham Heart Study who were 45 to 74 years of age underwent a total of 51,756 examinations from 1950 to 1989. Data were obtained on blood pressure and the use of antihypertensive medications, and electrocardiograms were assessed for left ventricular hypertrophy. The generalized-estimating-equation method was used to test for trends over time. RESULTS: From 1950 to 1989, the rate of use of antihypertensive medications increased from 2.3 percent to 24.6 percent among men and from 5.7 percent to 27.7 percent among women. The age-adjusted prevalence of systolic blood pressure of at least 160 mm Hg or diastolic blood pressure of at least 100 mm Hg declined from 18.5 percent to 9.2 percent among men and from 28.0 percent to 7.7 percent among women. This decline was accompanied by age-adjusted reductions in the prevalence of electrocardiographic evidence of left ventricular hypertrophy, from 4.5 percent to 2.5 percent among men and from 3.6 percent to 1.1 percent among women. CONCLUSIONS: Our findings support the notion that the increasing use of antihypertensive medication has resulted in a reduced prevalence of high blood pressure and a concomitant decline in left ventricular hypertrophy in the general population. Our observations may in part explain the considerable decline in mortality from cardiovascular disease observed since the late 1960s.
Age Factors↗
Factor V Arg506Gln mutation is not associated with cardiovascular mortality in older women.
Factor V Arg506Gln is the most common genetic risk factor for venous thrombosis and is associated with myocardial infarction in young women, especially among smokers. The authors studied the relation of factor V Arg506Gln to cardiovascular mortality in older women in a prospective cohort study of 12,239 women, living in the city of Utrecht, who were initially aged between 52 and 67 years. Women were followed on vital status between 1976 and 1995 (168,513 years). The factor V Arg506Gln mutation was determined in urine samples of 524 women who died of cardiovascular disease and in a reference group of 517 women who did not. Data were analyzed using a nested case-referent analysis. Factor V Arg506Gln heterozygosity was not associated with the risk of mortality by myocardial infarction, cerebrovascular disease, and other cardiovascular disease, with respective rate ratios and 95% confidence intervals being 1.1 (0.5-2.3), 1.2 (0.5-3.1), and 0.6 (0.2-1.7). No evidence of association was found in subgroups of smokers and age. Factor V Arg506Gln is not a risk factor for cardiovascular mortality in older women. Discrepancies with other studies may be explained by different study populations, as age and sex may modify both the frequency of cardiovascular disease and the effect of its risk factors.
Aged↗
Dietary iron and risk of myocardial infarction in the Rotterdam Study.
Free iron has been implicated in lipid peroxidation and ischemic myocardial damage, and it has been suggested that iron is an independent risk factor for myocardial infarction. The authors investigated whether dietary iron is associated with an increased risk of fatal and nonfatal myocardial infarction in the Rotterdam Study, a community-based prospective cohort study of 7,983 elderly subjects in Rotterdam, the Netherlands. The study sample consisted of 4,802 participants who at baseline had no known history of myocardial infarction and for whom dietary data were available. From 1990 to 1996, 124 subjects had a myocardial infarction. No association was observed between total iron intake and risk of myocardial infarction after adjustment for age and sex (relative risk for the highest vs. the lowest tertile of intake = 0.89, 95% confidence interval (CI) 0.55-1.45, p for trend = 0.640). Heme iron intake was positively associated with risk of myocardial infarction (relative risk for the highest vs. the lowest tertile of intake = 1.83, 95% CI 1.16-2.91, p for trend = 0.008) after adjustment for age and sex, and this association persisted after multivariate adjustment (relative risk = 1.86, 95% CI 1.14-3.09, p for trend = 0.010). A distinction between fatal and nonfatal cases of myocardial infarction indicated that the association of heme iron with myocardial infarction was more pronounced in fatal cases. The results suggest that a high dietary heme iron intake is related to an increased risk of myocardial infarction and that it may specifically affect the rate of fatality from myocardial infarction.
Diet↗
Physical activity in elderly subjects with impaired glucose tolerance and newly diagnosed diabetes mellitus.
The authors carried out a study to investigate the association between different indicators of physical activity and the prevalence of impaired glucose tolerance (IGT) and newly diagnosed diabetes (nDM) in a population-based cohort of elderly men and women in the Netherlands. A sample of participants of the Rotterdam Study (n = 1,016) aged 55-75 years who were not known to have diabetes mellitus underwent an oral glucose tolerance test. Physical activity was assessed by means of a self-administered questionnaire and expressed as time spent on activities per week. Associations with the prevalence of IGT and nDM were assessed by logistic regression analysis after adjustment for age, body mass index, waist-hip ratio, family history of diabetes, and smoking. A total of 745 subjects had normal glucose tolerance, 153 IGT, and 118 nDM. The total amount of time spent on physical activity decreased with increasing glucose intolerance. Adjusted for main confounders, vigorous activities such as bicycling (men: odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.14-0.49; women: OR = 0.37, 95% CI 0.18-0.78) and sports (men: OR = 0.28, 95% CI 0.11-0.74) showed an inverse association with the presence of nDM. For IGT, the associations pointed in the same direction but did not reach statistical significance. These results indicate that physical inactivity and glucose intolerance are associated among older adults similar to the way they are associated among middle-aged adults.
Activities of Daily Living↗
Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study.
BACKGROUND: Elevated homocysteine level increases vascular disease risk. Most data are based on subjects younger than 60 years; data for the elderly are more limited. We examined the relationship of homocysteine level to incident myocardial infarction and stroke among older subjects in a nested case-control study. METHODS: Subjects were participants in the Rotterdam Study, a cohort study among 7983 subjects residing in the Ommoord district of Rotterdam, the Netherlands. Baseline examinations were performed from March 1, 1990, to July 31, 1993. The analysis is restricted to myocardial infarction and stroke that occurred before December 31, 1994. One hundred four patients with a myocardial infarction and 120 with a stroke were identified with complete data. Control subjects consisted of a sample of 533 subjects drawn from the study base, free of myocardial infarction and stroke. Nonfasting total homocysteine levels were measured. RESULTS: Results were adjusted for age and sex. The risk of stroke and myocardial infarction increased directly with total homocysteine. The linear coefficient suggested a risk increase by 6% to 7% for every 1-micromol/L increase in total homocysteine. The risk by quintiles of total homocysteine level was significantly increased only in the group with levels above 18.6 micromol/L (upper quintile): odds ratios were 2.43 (95% confidence interval, 1.11-5.35) for myocardial infarction and 2.53 (95% confidence interval, 1.19-5.35) for stroke. Associations were more pronounced among those with hypertension. CONCLUSIONS: The present study, based on a relatively short follow-up period, provides evidence that among elderly subjects an elevated homocysteine level is associated with an increased risk of cardiovascular disease.
Aged↗
Variants in the sulphonylurea receptor gene: association of the exon 16-3t variant with Type II diabetes mellitus in Dutch Caucasians.
AIMS/HYPOTHESIS: We have analysed to what extent two previously reported single nucleotide polymorphisms in the sulphonylurea receptor gene (SUR1) are associated with Type II (non-insulin-dependent) diabetes mellitus in The Netherlands. Furthermore, we estimated haplotype frequencies in control and diabetic populations, including data extracted from three other studies. METHODS: Subjects with Type II diabetes (n = 388) and normoglycaemic subjects (n = 336) were randomly selected from two population-based studies, the Hoorn and Rotterdam studies. DNA was typed for variants in exon 16 (-3c-->t variant in the splice acceptor site) and exon 18 (Thr759Thr, ACC-->ACT). RESULTS: The genotype frequencies in both populations were similar. We observed an association of the exon 16-3t variant with Type II diabetes (allele frequencies 0.41 % vs 0.48 % in NGT and Type II diabetes, respectively, p = 0.01). There was no association between Type II diabetes and the variant in exon 18 or the combination of both variants (p > 0.5). A strong linkage disequilibrium between the exon 16 and exon 18 variants was observed in the diabetic groups but not, or less pronounced, in the control groups from the different studies. Haplotype estimation shows that several different risk haplotypes exist in different Caucasian populations. CONCLUSION/INTERPRETATION: The exon 16-3t allele of the SUR1 gene is associated with Type II diabetes in the Netherlands. Based on estimated haplotype frequencies in different Caucasian populations we conclude that multiple haplotypes on the SUR1 gene seem to confer a risk for developing Type II diabetes in Caucasians.
ATP-Binding Cassette Transporters↗
Continuous ST-segment monitoring associated with infarct size and left ventricular function in the GUSTO-I trial.
BACKGROUND: The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. METHODS AND RESULTS: The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of alpha-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. CONCLUSIONS: These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy.
Aged↗
Common carotid intima-media thickness in patients with peripheral arterial disease or abdominal aortic aneurysm: the SMART study. Second Manifestations of ARTerial disease.
Evidence is emerging that the contribution of atherosclerosis to the development of abdominal aortic aneurysm may differ from that of other manifestations of arterial disease. B-mode ultrasound may be helpful in understanding the characteristics and factors that contribute to the development of different manifestations of arterial disease. We examined whether there is a difference in common carotid intima-media thickness (IMT), an indicator of generalized atherosclerosis, in patients with peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA). IMT of the left and right common carotid artery was measured in the first 172 patients (123 PAD and 49 AAA) enrolled in the Second Manifestations of ARTerial disease (SMART) study, a cohort study among patients with a manifestation of atherosclerotic vascular disease or risk factors for atherosclerosis. Mean IMT was 0.98 +/- 0.34 mm in patients with PAD and 0.91 +/- 0.20 mm in patients with AAA, with an age and sex adjusted mean difference of 0.18 mm (95% CI 0.08; 0.28). After additional adjustments for cardiovascular risk factors, the difference remained 0.11 mm (95% Cl 0.01; 0.21). Common carotid IMT in patients with AAA is on average smaller than in patients with PAD, independent of other determinants of IMT. These findings support the view that the development of AAA cannot completely be explained by atherosclerosis and is in part due to other pathophysiological mechanisms.
Aged↗