Are Russians different than other Europeans in their relation of risk factors to cardiovascular disease risk.
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Cardiovascular Diseases↗
Biomedical subjects
Diederick E Grobbee
Publications and source records attributed to Diederick E Grobbee.
Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index.
OBJECTIVE: Sensitivity to glucocorticoids differs between individuals, partially due to genetic variation in the glucocorticoid receptor (GR) gene. We studied the sequence alteration of a previously described intronic BclI polymorphism of the GR gene, and investigated whether there was an association with sensitivity to glucocorticoids and anthropometric parameters in a group of healthy elderly individuals. DESIGN AND MEASUREMENTS: In study group 1, two overnight dexamethasone suppression tests (DSTs) were performed: with 1 mg dexamethasone, and 2.5 years later with 0.25 mg dexamethasone. Anthropometric parameters were measured in a larger population (study group 2), as well as in a third study group, in which we also measured body composition by dual-energy X-ray absorbtiometry (DEXA) scans. SUBJECTS: Groups 1 and 2, respectively, 191 and 1963 male and female participants of the Rotterdam study, a population-based study in Dutch elderly. Study group 3: 370 elderly males (mean age 77.8 +/- 0.2 years) from Zoetermeer, the Netherlands. RESULTS: We identified the BclI restriction site polymorphism as a C/G substitution in intron 2, 646 nucleotides downstream from exon 2. After both 1 mg and 0.25 mg DST, heterozygous (CG) and homozygous G-allele carriers (GG) had lower cortisol levels than CC-carriers (P = 0.01 and P = 0.02, respectively). In study group 2, we found a lower body mass index (BMI; P = 0.006) and waist-hip ratio (WHR; P = 0.02) in G-allele carriers. In study group 3, again we found a lower BMI (P = 0.05) in G-allele carriers. No differences were found in fat mass. However, lean mass tended to be lower in G-allele carriers (P = 0.07). CONCLUSIONS: We characterized a BclI-RFLP (restriction fragment length polymorphism) of the GR gene as a C/G polymorphism in intron 2 of which the G-allele was associated with hypersensitivity to glucocorticoids. This resulted in a lower BMI in older individuals in general, while our study in elderly males suggests that the lower BMI is probably due to a greater loss of lean mass during the ageing process.
Aged↗
Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men.
1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with four glasses of red wine, beer, spirits (Dutch gin) or sparkling mineral water (control) for 3 weeks. At the end of each 3 week period, serum NOx concentrations were measured just before and 1, 5 and 13 h after dinner. 3. Serum NOx concentrations were approximately 50% higher 1 and 5 h after dinner with any beverage compared with just before dinner (P = 0.0001). At 1 h after dinner, the serum NOx concentration was approximately 11% lower after dinner with alcoholic beverages compared with concentrations observed after dinner with water (P = 0.01). The fasted serum NOx concentration (13 h after dinner) was similar to the preprandial concentration and there were no differences in serum NOx concentrations between the alcoholic beverages. 4. Food intake acutely and transiently increased serum NOx concentrations, an effect that was slightly attenuated if combined with alcoholic beverages. Chronic moderate alcohol consumption had no effect on serum NOx concentration.
Adult↗
Diagnostic performance of various QTc interval formulas in a large family with long QT syndrome type 3: Bazett's formula not so bad after all...
BACKGROUND: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS3. The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene. METHODS: The study group consisted of 101 adult family members: 57 carriers and 44 noncarriers (mean age 44.6 +/- 14.6 and 40.3 +/- 12.8 years, respectively). In all individuals a 12-lead ECG, exercise ECG, and 24-hour Holter ECG were obtained. RESULTS: Correction for heart rate significantly improved the diagnostic performance of the QT interval. Diagnostic performance of the Bazett formula was similar to that of the newer formulas (Fridericia, Hodges, Framingham, and a logarithmic formula). At a cut-off value of 440 ms, the Bazett corrected QT interval was associated with a sensitivity and specificity of 90% and 91%, respectively. Using the 24-hour Holter ECG, a prolonged QTc at heart rates less than 60 beats/min was almost pathognomonic for genetic mutation (sensitivity and specificity both 99%), whereas the QTc calculated at the lowest heart rate using Bazett's formula provided full discrimination. CONCLUSION: In the present family, the resting ECG gave a good indication about the presence or absence of genetic mutation but a 24-hour Holter recording was mandatory to ascertain the diagnosis. In the diagnosis of this form of LQTS3, Bazett's formula was at least as good as other proposed corrections of the QT interval to heart rate.
Adult↗
Effect of a pharmacist-led intervention on diuretic compliance in heart failure patients: a randomized controlled study.
BACKGROUND: Noncompliance is a major factor in the morbidity and unnecessary hospital readmissions for patients with heart failure. Several studies have aimed to reduce rehospitalizations in heart failure patients through a comprehensive, multidisciplinary approach. Medication compliance was rarely measured in these studies or, when it was measured, the method employed was seldom valid. We aimed at determining the effect of a pharmacist-led intervention on medication compliance in patients with heart failure. METHODS: We conducted a randomized controlled trial into the effect of a pharmacist-led intervention on medication compliance in patients with heart failure (predominantly New York Heart Association [NYHA] II and III) treated with loop diuretics, presenting to a cardiology outpatient clinic or admitted to hospitals in The Netherlands. Patients in the intervention group received monthly consultations from their community pharmacist during a 6-month period. Patients in the control group received usual care. Primary endpoint was medication compliance, assessed with a medication event monitoring system, an electronic pill bottle that registers time of opening. Secondary endpoints were the number of rehospitalizations, death, and quality of life. RESULTS: A total of 152 patients were randomized: 74 patients to the intervention arm and 78 patients to the usual care arm. Over the 6-month study period, patients in the intervention group had 140/7656 days without use of loop diuretics compared with 337/6196 days in the usual care group (relative risk 0.33 [confidence interval (CI) 95% 0.24-0.38]). Two consecutive days of nondosing occurred on 18/7656 days in the intervention group compared with 46/6196 days in the usual care group (relative risk 0.32 [CI 95% 0.19-0.55]). There were no significant differences in rehospitalizations, mortality, or disease-specific quality of life between groups. CONCLUSIONS: A pharmacy-led intervention can improve medication compliance in patients with moderate to severe heart failure, even in those with relatively high compliance. Future interventions should also focus at less compliant patients.
Aged↗
Ultrasound measurements of intraabdominal fat estimate the metabolic syndrome better than do measurements of waist circumference.
BACKGROUND: We recently developed an ultrasound technique to estimate intraabdominal fat (IAF). This method is more accurate than measurement of waist and hip circumferences and is simpler and less expensive than computed tomography or magnetic resonance imaging. OBJECTIVE: We compared the associations of ultrasound and waist-circumference (WC) measurements of IAF with other components of the metabolic syndrome. DESIGN: IAF was determined in 600 consecutive participants in the Secondary Manifestations of Arterial Disease (SMART) study. The mean (+/- SD) age was 56.1 +/- 12.6 y, 30.0% of participants were women, and the mean body mass index (BMI; in kg/m2) was 26.6+/- 4.1. RESULTS: IAF increased with age (ultrasound: r = 0.28; WC: r = 0.25; P < 0.001 for both). Higher IAF, as measured by ultrasound but not by WC, was independently associated with higher metabolic risk factors. The correlation coefficients between IAF measured by ultrasound and plasma glucose, total cholesterol, HDL cholesterol, and triacylglycerol were 0.13, 0.16, -0.13, and 0.25, respectively (all P < 0.001; adjusted for age, sex, and BMI). The corresponding coefficients for IAF measured by WC were 0.17 (P < 0.001) and 0.01, -0.06, and 0.05 (all NS). CONCLUSIONS: These results confirm the findings of computed tomography and magnetic resonance imaging investigations. When IAF is measured by ultrasound, the associations are more pronounced than when WC measurements are used and are independent of BMI. This suggests that IAF can be more reliably assessed by ultrasound measurements than by WC measurements.
Abdomen↗
Subfertility reflects accelerated ovarian ageing.
BACKGROUND: The aim of the study was to explore the extent to which accelerated ovarian ageing may lead to subfertility early in reproductive life and eventually cause early menopause. METHODS: The population studied (n = 2393) never used oral contraceptives, hormone replacement therapy or an intrauterine device. Logistic regression analyses were performed using age at menopause as proxy for accelerated ovarian ageing. Measures of ovarian ageing and subfertility were menstrual cycle irregularity, ever consulted a physician for fertility problems, nulliparity, uniparity, miscarriage(s) and time interval >5 years between birth of first and second child. RESULTS: For every 5 years later menopause, the probability of reporting menstrual cycle irregularity was reduced by 26% (OR = 0.74, 95% CI: 0.63-0.86); the probability of ever consulting a physician for fertility problems was reduced by 18% (OR = 0.82, 95% CI: 0.71-0.95); the probability of staying nulliparous was reduced by 22% (OR = 0.78, 95% CI: 0.64-0.96); the probability of being uniparous was reduced by 22% (OR = 0.78, 95% CI: 0.66-0.91); the probability of having a miscarriage was reduced by 11% (OR = 0.89, 95% CI: 0.79-1.01); the probability of a large time interval between birth of first two children was reduced by 27% (OR = 0.73, 95% CI: 0.61-0.89). CONCLUSIONS: Fertility problems are frequently followed by early menopause. The findings support the view that both are an expression of accelerated ovarian ageing.
Abortion, Spontaneous↗
Adolescent blood pressure does not predict aortic stiffness in healthy young adults. The Atherosclerosis Risk in Young Adults (ARYA) study.
BACKGROUND: Increased arterial stiffness has been shown to be a good predictor of cardiovascular morbidity and mortality and to be associated with an adverse cardiovascular risk profile. OBJECTIVE: To evaluate the relationship between adolescent blood pressure and aortic stiffness in 524 healthy young adults aged 27-30 years, as a means of investigating early determinants of arterial stiffness. SETTING: General community. PARTICIPANTS: We studied 524 healthy young adults, aged 27-30 years, who attended secondary school in Utrecht, The Netherlands. MEASUREMENTS: Data on adolescent weight, height, blood pressure and stage of puberty were available from the original school health records of the Municipal Health Service. At young adulthood, a questionnaire on cardiovascular risk factors was completed and a fasting blood sample was drawn. MAIN OUTCOME MEASURE: Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV). RESULTS: Adolescent blood pressure did not predict aortic PWV at young adulthood (linear regression coefficient 0.03 m/s per 10 mmHg increase in systolic blood pressure; 95% confidence interval 0.09 to 0.14). Repeated analysis in a subgroup (n = 199) for whom two adolescent blood pressure measurements were averaged showed stronger (2-19x) associations with adult PWV, although these were not significant. CONCLUSION: Adolescent blood pressure did not predict arterial stiffness in healthy young adults. Measurement error in the baseline blood readings (regression to the mean phenomenon) may partly explain the lack of association in our study. Further studies should confirm our results in order to enable better understanding of the role of adolescent blood pressure in the aetiology of vascular damage.
Adolescent↗
Does a routinely measured blood pressure in young adolescence accurately predict hypertension and total cardiovascular risk in young adulthood?
BACKGROUND: It is insufficiently known if routine blood pressure (BP) measurement by school doctors has added predictive value for later hypertension and cardiovascular risk. OBJECTIVE: To assess whether screening of BP in adolescence has additional predictive value to already routinely collected indicators of later hypertension and cardiovascular risk. METHODS: In the Dutch city of Utrecht, routine BPs and anthropometry were collected from school health records of 750 adolescents. In The Hague, standardized repeated BP measurements and anthropometry were available for 262 adolescents. Of both cohorts, 998 now young adults were recently re-examined. Predictors of adult hypertension, systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP) > or = 90 mmHg) and 10-year cardiovascular risk were analysed by logistic regression and area under receiver operator characteristics curve (AUC). RESULTS: A total of 167 young adults had hypertension. Single adolescent SBP and DBP predicted hypertension: odds ratio (OR) 1.04 per mmHg [95% confidence interval (CI): 1.03-1.06], OR 1.02 (1.00-1.04), respectively, but with little discriminative power. Gender, adolescent body mass index (BMI) and age combined predicted hypertension: AUC 0.71 (0.67-0.75), which slightly improved by adding SBP: AUC 0.74 (0.70-0.77); difference in AUC 0.03 (0.002-0.06). SBP exclusively predicted hypertension within men: OR 1.03 (1.01-1.04), AUC: 0.59 (0.53-0.65), and within women: OR 1.08 (1.05-1.11), AUC 0.74 (0.67-0.82). However, an adolescent BP of > or = 120 mmHg did not efficiently detect hypertensive men, while it detected 57.9% of hypertensive women. Only young adult men had meaningful 10-year cardiovascular risks, which only SBP predicted: OR risk score > 95th percentile 1.04 (1.02-1.07), AUC 0.67 (0.60-0.75). CONCLUSION: A single routine BP measurement in adolescent girls efficiently predicts young adult hypertension. In adolescent boys, BP predicts young adult 10-year cardiovascular risk.
Adolescent↗
NAT2 slow acetylation and GSTM1 null genotypes may increase postmenopausal breast cancer risk in long-term smoking women.
N-acetyltransferase (NAT) 1 and 2 and glutathione S-transferase (GST) M1 and T1 are phase II enzymes that are important for activation and detoxification of carcinogenic heterocyclic and aromatic amines, as present in cigarette smoke. We studied whether genetic polymorphisms in these genes modifies the relationship between smoking and breast cancer. A nested case-control study was conducted among participants in a Dutch prospective cohort. Breast cancer cases (n=229) and controls (n=264) were frequency-matched on age, menopausal status and residence. Compared to never smoking, smoking 20 cigarettes or more per day increased breast cancer risk statistically significant only in postmenopausal women [odds ratio (OR)=2.17; 95% confidence interval (CI) 1.04-4.51]. Neither NAT1 slow genotype, or GSTT1 null genotype, alone or in combination with smoking, affected breast cancer risk. However, compared to individuals with rapid NAT2 genotype, women with the very slow acetylator genotype (NAT2*5), who smoked for 20 years showed an increased breast cancer risk (OR=2.29; 95% CI 1.06-4.95). Similarly, the presence of GSTM1 null genotype combined with high levels of cigarette smoking (OR=3.00; 95% CI 1.46-6.15) or long duration (OR=2.53; 95% CI 1.24-5.16), increased rates of breast cancer. The combined effect of GSTM1 null genotype and smoking high doses was most pronounced in postmenopausal women (OR=6.78; 95% CI 2.31-19.89). In conclusion, our results provide support for the view that women who smoke and who have a genetically determined reduced inactivation of carcinogens (GSTM1 null genotype or slow NAT2 genotype (especially very slow NAT2 genotype)) are at increased risk of breast cancer.
Acetyltransferases↗
A relation between blood pressure and stiffness of joints and skin.
BACKGROUND: Blood pressure, particularly pulse pressure, is associated with arterial wall stiffness, but little is known about its relation to stiffness of other parts of the body. We examined the extent to which blood pressure levels in young healthy children are related to stiffness of various tissues. METHODS: In November 2000, we studied 95 healthy prepubertal children (41 boys and 54 girls, within age range 8-10 years) from two primary schools in the city of Zeist, The Netherlands. Systolic and diastolic blood pressure and pulse pressure were analyzed in relation to various tissue indicators of stiffness, including active joint mobility and skin extensibility. All results were adjusted for age, sex, body height, body weight and muscle strength as possible confounders. RESULTS: Diastolic blood pressure was lower with increased active joint mobility (multivariate generalized linear regression coefficient = -4.5 mmHg per standard deviation [SD] joint mobility; 95% confidence interval [CI] = -7.8 to -1.2). Pulse pressure was lower with increased skin extensibility (-3.2 mmHg per SD skin extensibility; CI = -5.2 to -1.1), through a higher diastolic blood pressure (2.0 mmHg per SD skin extensibility; CI = 0.2-3.9) and possibly lower systolic blood pressure (-0.8 mmHg per SD skin extensibility; CI = -3.5 to 1.9). These associations were mutually independent. Additional adjustment for reported musculoskeletal problems or physical activity levels did not materially change the findings. CONCLUSIONS: Our findings support the hypothesis that constitutional stiffness of body tissues may be associated with blood pressure levels and eventually cardiovascular risk.
Blood Pressure↗
Endogenous sex hormones and cardiovascular disease in men.
Unlike women, men do not experience an abrupt reduction in endogenous sex hormone production. It has, however, become clear that an age-associated decrease in the levels of (bioactive) sex hormones does occur. Whether endogenous sex hormones have an impact on cardiovascular disease has for many years remained largely unknown, but during the last decade more attention has been drawn to the importance of testosterone, estrogens, and adrenal androgens in etiology, prevention, and treatment of male cardiovascular disease. The purpose of this article is to summarize the evidence currently available on the association between endogenous sex hormones and cardiovascular disease in males. Published studies dealing with the relationship between circulating levels of sex hormones and cardiovascular disease in males were reviewed. The studies reviewed in this article suggest that circulating endogenous sex hormones and estrogens have a neutral or beneficial effect on cardiovascular disease in men.
Cardiovascular Diseases↗
Serum insulin-like growth factor binding protein-2 levels as an indicator of functional ability in elderly men.
BACKGROUND: In a cross-sectional study in 403 healthy, independently living elderly men (mean age 78 years), we determined which are the main physiological determinants of functional ability in the elderly, and which components of the somatotropic system contribute to the maintenance of functional ability. METHODS: Functional ability was assessed by the number of problems in activities of daily living and by a measure of physical performance. Other physical characteristics included leg extensor strength, bone mineral density of total body and proximal femur, and body composition, including lean mass and fat mass. Serum insulin-like growth factor (IGF)-I and its binding proteins (IGFBP) -1, -2 and -3 concentrations were all measured by RIA. RESULTS: Muscle strength was related to a lower degree of disability. Further, it was positively related to physical performance and bone mineral density (all P<0.001). Fat mass influenced activities of daily living and physical performance negatively and bone mineral density positively (all P<0.001). Serum concentrations of IGF-I and IGFBP-3 were not related to any of the physical characteristics. High serum IGFBP-2 concentrations were related to a higher degree of disability (P<0.001), a lower physical performance (P=0.006), muscle strength (P=0.002), bone mineral density of proximal femur (P=0.007), lean mass and fat mass (both P<0.001). Serum insulin and IGFBP-1 concentrations were independently, positively related to lean mass (P=0.003) and fat mass (P<0.001). CONCLUSIONS: In independently living elderly men, functional ability appears to be determined by muscle strength (positive) and fat mass (negative). Low serum IGFBP-2 concentrations are a powerful indicator for overall good physical functional status, probably inversely reflecting the integrated sum of nutrition and the biological effects of growth hormone, IGF-I and insulin.
Activities of Daily Living↗
Endogenous sex hormones in men aged 40-80 years.
OBJECTIVE: To determine the relationship between aging, life-style factors and health-related factors and endogenous sex hormone levels. DESIGN: Cross-sectional study of 400 independently living men between 40 and 80 Years of age. METHODS: After exclusion of subjects who were not physically or mentally able to visit the study center, 400 men were randomly selected from a population-based sample. Total testosterone (TT), bioavailable testosterone (BT) (i.e. not bound to sex hormone-binding globulin (SHBG)), SHBG, estradiol (E(2)) and dehydroepiandrosterone-sulfate (DHEA-S) were investigated for their relationship with age, body mass index (BMI), waist circumference, smoking, physical activity and general health status. Multivariate models using ANCOVA analyses were used to examine the contribution of life-style factors to sex hormone variability. RESULTS: TT, BT and DHEA-S decreased with age; 0.2, 0.7 and 1.2%/Year respectively. SHBG showed an increase with age of 1.1%/Year. No changes with age were found for E(2). General health status modified the association of TT and SHBG with age (P interaction 0.10 and 0.002 respectively). Increased BMI and waist circumference were associated with decreased TT, BT, SHBG and DHEA-S and increased E(2) (all P<0.01). Current smoking, lower alcohol intake and a higher physical activity score were associated with higher TT and SHBG levels. CONCLUSION: This study showed the important determinants of sex hormones were age, BMI, waist circumference, smoking, general health status and physical activity. Furthermore, it can be concluded that general health status modified the effect between sex hormones and age. For future observational studies it should be taken into account that the above-mentioned determinants may alter the association between sex hormones and diseases and related conditions.
Adult↗
Hearing loss at school age in survivors of bacterial meningitis: assessment, incidence, and prediction.
OBJECTIVES: To establish the incidence of sensorineural hearing loss in children who survived non-Haemophilus influenzae type B (Hib) bacterial meningitis, to highlight the actual percentage whose hearing was evaluated, and to develop a prediction rule to identify those who are at risk of hearing loss. METHODS: In 1999, we compiled a cohort of 628 school-aged children who were born between January 1986 and December 1994 and had survived non-Hib bacterial meningitis between January 1990 and December 1995. Presence of sensorineural hearing loss (>25 dB) was determined, based on information from questionnaires and medical records. Potential risk factors for hearing loss were obtained from medical records; independent predictors were identified using multivariate logistic regression analysis, leading to the formulation of a prediction rule. RESULTS: The incidence of hearing loss was 7%. The hearing of 68% of the children was evaluated as part of their routine follow-up after bacterial meningitis, resulting in the detection of 75% of the cases of hearing loss. The remaining 25% were detected after this follow-up had ended. Using a prediction rule based on 5 factors-duration of symptoms before admission >2 days, absence of petechiae, cerebrospinal fluid glucose level <or=0.6 mmol/L, Streptococcus pneumoniae, and ataxia-62% of the postmeningitic children were selected as being at risk. All cases of hearing loss were in this at-risk group. CONCLUSIONS: Hearing loss can be predicted satisfactorily. When the hearing of children who are predicted to be at risk is tested as part of their routine follow-up, no children with hearing loss need be missed.
Adolescent↗
Statin treatment and progression of atherosclerotic plaque burden.
Atherosclerosis is a progressive systemic disorder that, in the initial stages, is often asymptomatic. The measurement of atherosclerotic burden using imaging techniques enables the clinical benefits of lipid-modifying therapies to be assessed in early atherosclerosis and facilitates more rapid evaluation of interventions in clinical trials compared with the measurement of clinical outcome. The effect of HMG-CoA reductase inhibitors, commonly referred to as 'statins', on disease progression has been assessed in a number of imaging studies both in patients with established coronary heart disease (CHD) and in those with subclinical atherosclerosis. Statins slow plaque progression and, in early atherosclerosis, they have been demonstrated to promote regression of atherosclerotic lesions. The benefits of statin therapy on soft atherosclerotic plaques that are still developing support the use of vascular measures to detect subclinical atherosclerosis, and the subsequent early intervention with statin therapy. Moreover, given that the effects of statins on atherosclerosis progression are evident even in normocholesterolaemic patients at increased risk of developing CHD, early intervention with statin therapy may be effective in preventing CHD, irrespective of lipid level.
Arteriosclerosis↗
No modifying effect of NAT1, GSTM1, and GSTT1 on the relation between smoking and colorectal cancer risk.
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Arylamine N-Acetyltransferase↗