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Biomedical subjects

C D Stehouwer

Publications and source records attributed to C D Stehouwer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus.

OBJECTIVE: Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations. METHODS: In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) <30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphism of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease. RESULTS: The T-allele of the AGT-M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.06-8.61), but only when interaction with the D-allele of the ACE-ID polymorphism was considered. A previously described positive interaction between the T-allele of the AGT-M235T polymorphism and the D-allele of the ACE-ID polymorphism could not be confirmed. The T-allele was also associated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79-8.47). The CC-genotype of the AT1-A1166C polymorphism was associated with hypertension (OR 3.58; 95% CI 1. 23-10.37). CONCLUSIONS: In a Dutch IDDM population, including 69 patients with (incipient) diabetic nephropathy, the T-allele of the AGT-M235T polymorphism is associated with an elevated UAE and diabetic retinopathy and the CC-genotype of the AT1-A1166C polymorphism is associated with hypertension. A previously described interaction between the AGT-M235T and the ACE-ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this study is small, these conclusions must be interpreted with caution.

Adult↗
PubMed2000

Change in common carotid artery diameter, distensibility and compliance in subjects with a recent history of impaired glucose tolerance: a 3-year follow-up study.

OBJECTIVE: To assess the development of common carotid artery properties (diameter, distensibility and compliance) in a cohort of 140 subjects (mean age 65.8 years, SD 7.5 years) originally diagnosed as impaired glucose tolerant in a population-based study, and to explore determinants of changes observed. DESIGN: An observational, longitudinal study over a 3-year-period. METHODS: Vessel wall movement detector system based on ultrasonography, linear generalized estimating equations. RESULTS: Carotid artery diameter rose from 6.87-7.02 mm (+ 2.2%, P<0.001). Distensibility decreased from 11.8 to 10.9 x 10-3 kPa-1 (-8.3%, P=0.009). Compliance decreased from 0.44-043 mm2 kPa-1 (P=0.17). Changes in blood pressure level were negatively associated with changes in distensibility and compliance. Baseline fasting glucose levels were positively associated with changes in diameter, while fasting insulin levels were negatively associated with changes in distensibility and compliance in men, but not in women. CONCLUSIONS: In subjects with a recent history of impaired glucose tolerance, we observed an increase in carotid artery diameter and a decrease in distensibility. Change in blood pressure level and baseline fasting glucose and HbA1c levels were positively related to the increase in diameter. In men, but not in women, baseline fasting insulin levels were associated with an acceleration of these changes.

Aged↗
PubMed2000

Birth weight relates to blood pressure and microvascular function in normal subjects.

OBJECTIVE: The relationship between low birth weight and elevated blood pressure in adult life is well established but presently unexplained. Both microvascular dysfunction and insulin resistance have been proposed as a possible explanation. We have examined the relation between birth weight and blood pressure in 30 healthy subjects exhibiting a wide range of insulin sensitivity, and assessed whether microvascular function and/or insulin resistance may underlie this relationship. METHODS: Birth weight data were obtained from birth announcements. Blood pressure was measured with an ambulatory blood pressure monitor and insulin sensitivity was assessed by the hyperinsulinaemic, euglycaemic clamp technique. Microvascular function, i.e. capillary recruitment and endothelium-dependent and -independent vasodilatation in the skin, was evaluated by videomicroscopy and iontophoresis of acetylcholine and sodium nitroprusside. RESULTS: Birth weight was significantly associated with blood pressure (r= -0.50; P< 0.05), capillary recruitment (r= +0.52; P< 0.05), acetylcholine-mediated vasodilatation (r= +0.40; P< 0.05), insulin sensitivity (r= +0.62; P< 0.01) and waist-to-hip ratio (r= -0.42; P< 0.05). Regression analysis showed a significant association of birth weight with 24 h systolic blood pressure (regression coefficient: -7.6 mmHg/kg; 95% confidence interval: -13.0 to -1.0). Adjustment for capillary recruitment and waist-to-hip ratio decreased the regression coefficient by 39 and 41%, respectively. The results were similar after adjustment for age, sex or body mass index. CONCLUSION: These results suggest that capillary recruitment and body fat distribution may partly explain the relationship between birth weight and blood pressure.

Adult↗
PubMed2000

Alterations in nitric oxide activity and sensitivity in early streptozotocin-induced diabetes depend on arteriolar size.

Changes in NO activity may play an important role in the early increase in microvascular flow that has been implicated in the pathogenesis of diabetic microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of 6 weeks' streptozotocin-diabetic rats (n = 6) and of age-matched controls (n = 8), basal inside diameters of A2-A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after N(G)-nitro-L-arginine. In diabetic rats, cholinergic vasodilatation in A2-A4 arterioles was intact. Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin-diabetic rats. The increased basal diameter in A3 arterioles was partially due to an increased contribution of NO to basal diameter. The response to nitroprusside was impaired in streptozotocin-diabetic rats in A2, but not in A3 and A4 arterioles. Thus, this study shows that NO activity and sensitivity are altered after 6 weeks of streptozotocin-induced diabetes. These streptozotocin-induced changes are anatomically specific and, for arterioles, depend on their position within the vascular tree.

Acetylcholine↗
PubMed2000

Oral, but not transdermal, administration of estrogens lowers tissue-type plasminogen activator levels in humans without affecting endothelial synthesis.

Oral estrogen administration decreases plasma levels of tissue-type plasminogen activator (tPA), which may be explained by a decrease in endothelial tPA synthesis, an increase in its hepatic clearance, or both. In the present study, we determined (1) differences between oral (ie, via the liver) ethinyl estradiol and transdermal (ie, systemic) 17beta-estradiol administration on plasma antigen levels of tPA and plasminogen activator inhibitor type-1 before and after 4 months of hormone administration and (2) effects on endothelial tPA synthesis, by measuring the local increase in plasma tPA during venous occlusion of the upper extremity. Thirty transsexual males (median age 32 years, range 20 to 44 years ) were randomly assigned to either oral ethinyl estradiol (n=15) or transdermal 17beta-estradiol (n=15); both treatments included the antiandrogen cyproterone acetate (CA). Ten males were treated with CA alone. Seventeen transsexual females (median age 27 years, range 18 to 37 years) were treated with intramuscular testosterone esters. Only oral ethinyl estradiol plus CA but neither transdermal 17beta-estradiol plus CA, nor oral CA, nor parenteral testosterone lowered plasma tPA and plasminogen activator inhibitor-1 (P<0.001 for both). tPA release during venous occlusion was not affected by oral ethinyl estradiol plus CA in males (P=0.52) or by parenteral testosterone in females (P=0.89). These data are consistent with a previous observation, in rodents, that the decrease in tPA after oral estrogen administration can be explained by an increase in hepatic tPA clearance, leaving endothelial tPA synthesis unchanged, and suggest that these mechanisms also explain the decrease in tPA in humans.

Administration, Cutaneous↗
PubMed2000

Evidence for genetic factors explaining the birth weight-blood pressure relation. Analysis in twins.

Epidemiological studies have consistently shown an inverse association between birth weight and systolic blood pressure in later life after adjustment for current size. To examine whether this association is explained by intrauterine or genetic factors, we investigated birth weight and blood pressure data in 53 dizygotic and 61 monozygotic adolescent twin pairs. Birth weight was obtained from the mothers. Blood pressure measurements were performed 6 times at rest and during mental stress. The dizygotic but not the monozygotic twins with the lowest birth weight from each pair had a systolic blood pressure measured at rest and during the reaction time experiment that was higher compared with their cotwins with the highest birth weight (dizygotic twins: blood pressure at rest, 119. 4+/-9.7 mm Hg versus 117.3+/-8.5 mm Hg, P=0.07, and during a reaction time task, 126.2+/-10.8 versus 123.6+/-9.5, P=0.09; monozygotic twins: blood pressure at rest, 117.4+/-6.4 versus 118. 4+/-9.0, P=0.4, and during a reaction time task, 122.9+/-8.4 versus 124.2+/-10.8, P=0.2). The differences in blood pressure between the cotwins with the lowest and the cotwins with the highest birth weight were different in dizygotic compared with monozygotic twin pairs (for blood pressure at rest, P=0.05; for blood pressure during reaction time, P=0.03). After adjustment for differences in current weight, intrapair differences in birth weight were negatively and significantly associated with differences in systolic blood pressure at rest and during the reaction time task in dizygotic twins (regression coefficient, -5.7 mm Hg/kg [95% confidence interval, -10.4 to -1.0] and -6.3 [-12.7 to 0], respectively) but not in monozygotic twins (-0.1 [-5.4 to 5.2] and +3.5 [-1.8 to 8.8], respectively). Interaction analysis indicated that the associations were different between dizygotic twins and monozygotic twins (P=0.1 and P<0.05, respectively). These data suggest that genetic factors may play an important role in the association between birth weight and blood pressure.

Adolescent↗
PubMed2000

Cardiovascular disease risk and hormone replacement therapy (HRT): a review based on randomised, controlled studies in postmenopausal women.

Epidemiological data suggest that the use of oestrogen replacement therapy (ERT) and combined oestrogen/progestagen replacement therapy (HRT) in healthy postmenopausal women is associated with a decreased risk of cardiovascular events. In sharp contrast, the HERS study, a secondary prevention trial in postmenopausal women with established coronary heart disease, did not show a favourable effect, with a trend towards an increased risk of cardiovascular disease in the first year of treatment. This paper provides an overview of randomised, controlled trials (RCTs) in postmenopausal women published in the literature and discusses possible explanations for the contrast between data from the epidemiological studies and the results of the HERS study. ERT and HRT are associated with: 1) an improved lipid profile; and 2) a decrease in homocysteine and endothelin levels. Data on factor VII and fibrinogen were not consistent. There were insufficient data on the effects on blood pressure, glucose metabolism, vasomotor regulation, arterial stiffness, thrombomodulin, adhesion molecules, and clotting and fibrinolysis, as well as on the effects of route of administration and the role of progestagens. Finally, endothelium-dependent vasodilatation appears to increase with ERT, but the effects of HRT are less clear This paucity of controlled data indicates that, although ERT and HRT improve surrogate measures of risk of atherothrombosis, adverse effects of ERT and HRT on biological mechanisms related to risk of atherothrombosis can by no means be excluded.

Cardiovascular Diseases↗
PubMed2000

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

Membrane-bound vascular cell adhesion molecule 1 (VCAM-1) allows the tethering and rolling of monocytes and lymphocytes as well as firm attachment and transendothelial migration of leukocytes. Soluble forms of VCAM (sVCAM-1) may serve as monitors of increased expression of membrane-bound VCAM-1 and thus may reflect progressive formation of atherosclerotic lesions. Levels of sVCAM-1 have been found to be increased among type 2 diabetic as compared with nondiabetic subjects. To study the association of plasma sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and diabetic subjects, we investigated an age-, sex-, and glucose-tolerance-stratified sample (n = 631) of a population-based cohort aged 50-75 years that was followed prospectively. Plasma levels of sVCAM-1 were determined in frozen -70 degrees C baseline samples. After 7.4 years (mean) of follow-up, 107 (17%) subjects had died (42 of cardiovascular causes). In the entire group, increased sVCAM-1 levels were significantly associated with increased risk of cardiovascular mortality (relative risks [RRs] per 100 ng/ml sVCAM-1 increase, 1.10 [1.05-1.15] after adjustment for age, sex, and glucose tolerance status). This RR was somewhat diminished by further adjustment for the presence of hypertension and cardiovascular disease; levels of total, HDL, and LDL cholesterol and homocysteine; the presence of microalbuminuria (a putative marker of endothelial dysfunction); levels of von Willebrand factor (a marker of endothelial dysfunction) and C-reactive protein (a marker of low-grade inflammation); and estimates of glomerular filtration rate. However, the RR remained statistically significant. The RR among type 2 diabetic subjects was 1.13 (1.07-1.20) per 100 ng/ml sVCAM-1 increase after adjustment for age and sex, which was somewhat higher but not significantly different from the RR in nondiabetic subjects (P value for interaction term, 0.12). Further adjustment for other risk factors gave similar results. In conclusion, levels of sVCAM-1 are independently associated with the risk of cardiovascular mortality in type 2 diabetic subjects and therefore might be useful for identifying subjects at increased cardiovascular risk. Increased plasma sVCAM-1 levels may reflect progressive formation of atherosclerotic lesions, or sVCAM-1 itself may have bioactive properties related to cardiovascular risk. Our data, however, argue against the hypotheses of sVCAM-1 levels simply being a marker of endothelial dysfunction, of low-grade inflammation, or of an impaired renal function.

Aged↗
PubMed2000

Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study.

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P<0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.

Aged↗
PubMed2000

Cardiovascular autonomic function is associated with (micro-)albuminuria in elderly Caucasian sujects with impaired glucose tolerance or type 2 diabetes: the Hoorn Study.

OBJECTIVE: To determine whether impaired cardiovascular autonomic function correlates with albuminuria in an age-, sex-, and glucose tolerance-stratified sample of an elderly (50-75 years of age) Caucasian population and to determine whether this association is independent of other determinants of albuminuria. RESEARCH DESIGN AND METHODS: We studied 536 subjects, 256 with normal glucose tolerance, 143 with impaired glucose tolerance (IGT), and 137 with type 2 diabetes. Microalbuminuria was defined as an albumin-to-creatinine ratio of > or =3.0 and < or =30 mg/mmol in an early morning urine sample. We used the deep-breathing test and the lying-to-standing test to obtain 4 measurements of cardiovascular autonomic function: 1) the heart rate (HR) variability during deep breathing, 2) the maximum HR within 15 s after standing up minus the mean HR before standing, 3) the maximum R-R interval between 15 and 30 s after standing up divided by the minimum R-R interval within 15 s after standing up, and 4) the systolic blood pressure in response to standing up. These 4 measurements were summarized in a single cardiovascular autonomic function score (CAFS). RESULTS: A total of 38 subjects with microalbuminuria and 3 subjects with macroalbuminuria (>30 mg/mmol) were grouped as having albuminuria. In bivariate analyses, albuminuria was associated with age, waist-to-hip ratio, systolic and diastolic blood pressure, calculated glomerular filtration rate, and glucose tolerance status. The mean CAFS was higher in subjects with versus without albuminuria (7.5 vs. 5.9, P<0.001). Multiple logistical regression analyses revealed that the CAFS was independently associated with albuminuria in subjects with IGT or type 2 diabetes with an odds ratio (95% CI) of 1.19 (1.02-1.39) per point increase in the CAFS. CONCLUSIONS: Impaired cardiovascular autonomic function is independently associated with (and thus a possible contributor to) the presence of albuminuria in subjects with IGT or type 2 diabetes.

Aged↗
PubMed2000

Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy.

BACKGROUND: The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment. PATIENTS AND METHODS: Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system. RESULTS: At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02). CONCLUSION: Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.

Age Factors↗
PubMed2000

Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study.

UNLABELLED: In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group). RESULTS: As compared to placebo, plasma levels of AT III were reduced only in the E2 group (approximately 28%), plasma levels of protein C decreased only in the E2+P group (approximately 4%) and plasma levels of protein S decreased in both the E2 and E2+P group (approximately 21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (approximately 10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (approximately 22%), urokinase plasminogen activator (approximately 25%) and plasminogen activator inhibitor type-1 (approximately 43%) decreased in the E2 and E2+P groups, whereas those of plasminogen increased (approximately 12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (approximately 31%), but levels of thrombin-antithrombin III complexes, and of plasmin-alpha2-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly. CONCLUSION: Short-term E2 and E2+P treatment is associated with a shift in the procoagulant-anticoagulant balance towards a procoagulant state. A substantial proportion of women do not have a net increase in fibrinolytic activity. These data may be relevant in explaining the increased risk of venous thromboembolism associated with ERT and HRT, and possibly also in explaining the negative results of the Heart and Estrogen/progestin Replacement Study.

Blood Coagulation↗
PubMed2000

Unopposed estrogen increases total plasma factor VII, but not active factor VII--a short-term placebo-controlled study in healthy postmenopausal women.

Estrogen therapy may increase the risk of arterial thromboembolism, at least in the short term. In a randomized, double-blind and placebo-controlled study in 25 healthy postmenopausal women (52.5 +/- 2.8 years), we therefore examined the short-term effect of unopposed estrogen on the fasting and fat-load-stimulated plasma levels of total factor VII versus active factor VII. Plasma total factor VII was measured by use of a chromogenic assay; plasma active FVII by a recently developed method using truncated tissue factor. As compared to placebo, 8 weeks of oral 17beta-estradiol (2 mg daily) increased the mean fasting and postprandial plasma levels of total factor VII by 17 and 21% points, respectively (both P < 0.01 ), but did not affect the fasting and/or postprandial plasma levels of active factor VII (mean change both 0.05 ng/mL; P > 0.35). Furthermore, the change in the fasting level of total factor VII after therapy was not associated with the change in the fasting level of active factor VII (r = 0.27; P = 0.21). These findings argue against the idea that elevated levels of total factor VII underlie an increased risk of arterial thromboembolism in postmenopausal women using unopposed estrogen replacement.

Double-Blind Method↗
PubMed1999

[Clinical thinking and decision-making in the practice. A patient with thrombophlebitis].

A 55-year-old man presented with deep venous thrombosis of his left leg. Laboratory evaluation disclosed macrocytic anaemia and leukocytosis. In the clinical decision process it was not verified whether all symptoms fitted in with the presumptive diagnosis of pernicious anaemia and stomach carcinoma. The ultimate diagnosis was acute lymphocytic leukaemia. A proper evaluation of a peripheral blood smear would have led to this diagnosis earlier.

Anemia, Macrocytic↗
PubMed1999

[Practice guidelines to physicians and their economic aspects; merits and drawbacks].

In drawing up policy recommendations to physicians, two crucial problems arise: to what extent can research findings be extrapolated to everyday practice? And: may or must economic arguments be considered in drawing up the policy recommendation? In the revised consensus 'Cholesterol', the proposals on secondary prevention are based on justifiable extrapolation of available data, but this is not true of those on primary prevention. Use of economic arguments in a policy recommendation to physicians is not acceptable, because it gives rise to a situation in which the treating physician constantly has to weigh economic interests against the patient's interests, so that the patient may begin to doubt if the physician is constantly any exclusively acting as the representative of his or her interests.

Coronary Disease↗
PubMed1999

[Clinical thinking and decision-making in practice. A patient with episodes of flushing].

A 74-year-old woman had an 8-year history of spells consisting of facial flushing and swelling, itching and erythema of the hands, rhinorrhoea and gastrointestinal complaints. The ultimate diagnosis was systemic mastocytosis without urticaria pigmentosa. In the clinical decision process the treating physicians used clinical axioms to try to establish a diagnosis, but these axioms were sometimes used inappropriately. In particular, spells accompanied by flushing inappropriately elicited a possible diagnosis of phenochromocytoma. Generalised mastocytosis can occur in the absence of urticaria pigmentosa and is probably an underestimated cause of spell-like complaints.

Aged↗