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Biomedical subjects

Coen D A Stehouwer

Publications and source records attributed to Coen D A Stehouwer.

At least 19 recordsLinked to original sources
PubMed2007

Homocysteine and large arteries.

High plasma concentrations of the amino acid homocysteine have been associated with atherothrombotic disease, first in individuals with inborn errors of homocysteine metabolism, who have very high plasma homocysteine concentrations, and later also in the general population. In general, the cardiovascular risk associated with hyperhomocysteinemia is significant, but modest and probably differs between populations. High homocysteine concentrations are thought to impair endothelial function, increase oxidative stress, impair methylation reactions, and alter protein structure. Although some studies have shown improvement of vascular surrogate end points, homocysteine-lowering treatment has not yet been associated with a significant reduction of cardiovascular events. Studies that have examined the relationship between plasma homocysteine and arterial stiffness parameters have shown heterogenous results.

Arteries↗
PubMed2006

Visceral and truncal subcutaneous adipose tissue are associated with impaired capillary recruitment in healthy individuals.

CONTEXT: Central adiposity is associated with cardiovascular risk independently of total adiposity. Microvascular dysfunction is thought to contribute to obesity-associated insulin resistance and hypertension and may thus link central adiposity with cardiovascular risk. OBJECTIVE: Our objective was to investigate how body fat distribution relates to microvascular function and the role of adipocytokines in these relationships. DESIGN, SETTING, AND PARTICIPANTS: We cross-sectionally studied 51 healthy adults and 29 of their prepubertal children born at the VU University Medical Center in Amsterdam. MAIN OUTCOME MEASURES: We measured visceral and abdominal sc adiposity with magnetic resonance imaging and truncal and peripheral sc adiposity with skinfold thickness. Postocclusive skin capillary recruitment was assessed with videomicroscopy. Concentrations of C-reactive protein, IL-6, and TNF-alpha were combined in an inflammation score. RESULTS: In adults, visceral adipose tissue and trunk/extremity skinfold ratio were inversely associated with capillary recruitment (partial correlation coefficients, -0.32, P = 0.03, and -0.37, P < 0.01, respectively). The inflammation score was inversely associated with capillary recruitment (r = -0.50; P < 0.01) and statistically explained 41% of the association between visceral adipose tissue and capillary recruitment. In children, trunk/extremity skinfold ratio was inversely associated with capillary recruitment (r = -0.49; P = 0.01), but other measures of adiposity were not. CONCLUSION: Our data in adults suggest a role for visceral adiposity and its associated proinflammatory state in capillary dysfunction and its possible sequelae such as hypertension and insulin resistance. Also, our findings in children and adults suggest that truncal sc adiposity is detrimental for capillary perfusion and that this process may start before puberty.

Abdominal Fat↗
PubMed2006

Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms.

Microalbuminuria is a strong and independent indicator of increased cardiovascular risk among individuals with and without diabetes. Therefore, microalbuminuria can be used for stratification of risk for cardiovascular disease. Once microalbuminuria is present, cardiovascular risk factor reduction should be more "aggressive." The nature of the link between microalbuminuria and cardiovascular risk, however, remains poorly understood. There is no strong evidence that microalbuminuria causes atherothrombosis or that atherothrombosis causes microalbuminuria. Many studies have tested the hypothesis that a common risk factor underlies the association between microalbuminuria and cardiovascular disease but, again, have found no strong evidence in favor of this contention. At present, the most likely possibility is that a common pathophysiologic process, such as endothelial dysfunction, chronic low-grade inflammation, or increased transvascular leakage of macromolecules, underlies the association between microalbuminuria and cardiovascular disease, but more and prospective studies of these hypotheses are needed.

Albuminuria↗
PubMed2006

Diet/Exercise versus pioglitazone: effects of insulin sensitization with decreasing or increasing fat mass on adipokines and inflammatory markers.

BACKGROUND: Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone. METHODS: Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone. RESULTS: Diet/exercise reduced body fat and visceral fat and improved insulin sensitivity parameters; pioglitazone improved insulin sensitivity to a similar degree but increased body fat. Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6 ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml, P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive protein decreased with diet/exercise. Adipokine concentrations were not correlated with each other at baseline or after insulin sensitization, except TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin sensitivity. Adiponectin concentrations were inversely correlated with visceral fat and with sc fat depots in men but positively correlated with sc fat in women. CONCLUSION: Plasma adipokine concentrations were not consistently interrelated, and only adiponectin displayed the expected relationship with insulin sensitivity and sensitization. These findings do not support an endocrine role for resistin, TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise or pioglitazone.

Absorptiometry, Photon↗
PubMed2006

Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study.

Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50-75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92-1.83), 1.40 (1.09-1.81) and 2.04 (1.35-3.10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21-2.92) and 1.75 (1.12-2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.

Aged↗
PubMed2006

Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study.

OBJECTIVE: The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention. METHODS AND RESULTS: In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained approximately 43% of the increase in cardiovascular mortality risk conferred by T2D. CONCLUSIONS: These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.

Aged↗
PubMed2006

Heat-shock protein 27 is a major methylglyoxal-modified protein in endothelial cells.

In endothelial cells cultured under high glucose conditions, methylglyoxal is the major intracellular precursor in the formation of advanced glycation endproducts. We found that endothelial cells incubated with 30 mM d-glucose produced approximately 2-fold higher levels of methylglyoxal but not 3-deoxyglucosone and glyoxal, as compared to 5 mM d-glucose. Under hyperglycaemic conditions, the methylglyoxal-arginine adduct argpyrimidine as detected with a specific antibody, but not N(e)-(carboxymethyl)lysine and N(e)-(carboxyethyl)lysine, was significantly elevated. The glyoxylase I inhibitor HCCG and the PPARgamma ligand troglitazone also increased argpyrimidine levels. Increased levels of argpyrimidine by glucose, HCCG and troglitazone are accompanied by a decrease in proliferation of endothelial cells. A 27 kDa protein was detected as a major argpyrimidine-modified protein. With in-gel digestion and mass spectrometric analysis, we identified this major protein as heat-shock protein 27 (Hsp27). This argpyrimidine modification of Hsp27 may contribute to changes in endothelial cell function associated to diabetes.

Cells, Cultured↗
PubMed2006

Differences in heart rate variability between depressed and non-depressed elderly.

OBJECTIVE: To determine whether older primary care patients with a Major Depressive Disorder (MDD) have lower heart rate variability (HRV) compared to non-depressed patients. HRV is a measure of cardiac autonomic functioning. METHOD: A cross-sectional comparison of 136 elderly persons with MDD and 136 non-depressed controls (matched for age and gender) recruited in family practices in the Netherlands. Depression was determined according to the DSM-IV criteria using the PRIME-MD. HRV was measured with an electrocardiogram (ECG) during a 5-minute supine rest. RESULTS: Multivariate analyses showed statistically significant decrease in HRV in MDD patients compared with controls. CONCLUSION: Older primary care patients with MDD have a reduced HRV. This may explain why depression is a risk factor for cardiovascular disease and mortality.

Aged↗
PubMed2006

Microvascular dysfunction: causative role in the association between hypertension, insulin resistance and the metabolic syndrome?

The metabolic syndrome defines a clustering of metabolic risk factors that confers an increased risk for type 2 diabetes and cardiovascular disease. The metabolic syndrome seems to have multiple etiological factors and microvascular dysfunction may be one potential factor explaining the clustering of multiple metabolic risk factors including hypertension, obesity, insulin resistance and glucose intolerance. Microvascular dysfunction may increase not only peripheral vascular resistance and blood pressure, but may also decrease insulin-mediated glucose uptake in muscle. The present article summarizes some of the data concerning the role of microvascular dysfunction in the metabolic syndrome.

Capillary Permeability↗
PubMed2006

Are retinal microvascular abnormalities associated with large artery endothelial dysfunction and intima-media thickness? The Hoorn Study.

It has been hypothesized that microvascular dysfunction affects endothelial dysfunction of the large arteries, which may explain the relationship of microvascular disease with macrovascular disease. The aim of the present study was to investigate the relationship of retinal microvascular disorders with endothelium-dependent FMD (flow-mediated vasodilatation) and carotid IMT (intima-media thickness). A total of 256 participants, aged 60-85 years, 70 with normal glucose metabolism, 69 with impaired glucose metabolism and 109 with Type II diabetes, were included in this study. All participants were ophthalmologically examined, including funduscopy and two field 45 degrees fundus photography, and were graded for retinal sclerotic vessel abnormalities and retinopathy. Retinal arteriolar and venular diameters were measured with a computer-assisted method. Brachial artery, endothelium-dependent FMD and carotid IMT were assessed ultrasonically as measurements of endothelial function and early atherosclerosis respectively. After adjustment for age, sex and glucose tolerance status, retinal vessel diameters, retinal sclerotic vessel abnormalities and retinopathy were not significantly associated with FMD. In contrast with other retinal microvascular abnormalities, retinal venular dilatation was associated with increased IMT [standardized beta value (95% confidence interval), 0.14 (0.005-0.25)]. This association was attenuated and lost statistical significance after adjustment for cardiovascular risk factors, in particular after correction for fasting insulin. In the present study, retinal microvascular disorders are not independently associated with impaired FMD. In addition, retinal venular dilatation is associated with increased IMT, although non-significantly after multivariable adjustment for cardiovascular risk factors. Therefore our data provide evidence that retinal microvascular disease is of limited value in risk stratification for future cardiovascular events.

Aged↗
PubMed2006

TNF-alpha levels are associated with skin capillary recruitment in humans: a potential explanation for the relationship between TNF-alpha and insulin resistance.

The mechanism by which TNF-alpha (tumour necrosis factor-alpha) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-alpha has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-alpha concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-alpha levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-alpha levels were associated with both capillary recruitment (r=-0.40, P=0.02) and insulin sensitivity (r=-0.33, P=0.05). In addition, capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-alpha and insulin sensitivity [-0.527 mg.kg(-1) of body weight.min(-1) per pmol/l per pg/ml TNF-alpha (95% confidence interval, -1.066 to 0.011); P=0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=-0.24, P=0.4) was significantly associated with TNF-alpha. In conclusion, in adults, but not in children, serum TNF-alpha levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-alpha and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.

Adult↗
PubMed2006

Glycaemic instability is an underestimated problem in Type II diabetes.

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA(1c) content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.

Blood Glucose↗
PubMed2006

Sagittal abdominal diameter: no advantage compared with other anthropometric measures as a correlate of components of the metabolic syndrome in elderly from the Hoorn Study.

BACKGROUND: The sagittal abdominal diameter has been proposed as a useful measure by which to estimate abdominal obesity and as being more strongly related to components of the metabolic syndrome than are other anthropometric measures. OBJECTIVE: The objective was to study which anthropometric measure (ie, sagittal abdominal diameter, waist circumference, waist-to-hip ratio, waist-to-height ratio, or body mass index) is the strongest correlate of components of the metabolic syndrome (ie, glucose and lipid concentrations and blood pressure) in the elderly. DESIGN: The Hoorn Study is a population-based cohort study in older Dutch men and women. Cross-sectional data were analyzed. Age-adjusted Pearson correlations of anthropometric measures with components of the metabolic syndrome were calculated in 826 subjects (389 men, 437 women) aged 56-83 y. Analyses were performed with adjustment for age and stratification for sex and age (<65 or >/=65 y). RESULTS: No single anthropometric measure was consistently correlated more strongly with components of the metabolic syndrome than were the other measures in either men or women. The associations were generally stronger in younger subjects than in older subjects and in women than in men. For example, the correlation between sagittal abdominal diameter and postload glucose was 0.35 (P < 0.001) in younger and 0.14 (P = 0.051) in older men, and the correlation between waist circumference and postload glucose was 0.33 (P < 0.001) in older women and 0.14 (P = 0.062) in older men. CONCLUSION: The use of sagittal abdominal diameter has no advantages over simpler and more commonly used anthropometric measures such as the waist circumference in older men and women.

Abdominal Fat↗
PubMed2006

Irbesartan treatment reduces biomarkers of inflammatory activity in patients with type 2 diabetes and microalbuminuria: an IRMA 2 substudy.

The impact of irbesartan treatment on biomarkers of low-grade inflammation, endothelial dysfunction, growth factors, and advanced glycation end products (AGEs) during the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study was evaluated. IRMA 2 was a 2-year multicenter, randomized, double-blind trial in patients comparing irbesartan (150 or 300 mg once daily) versus placebo. The primary end point was onset of overt nephropathy. A subgroup (n = 269, 68%) was analyzed for biomarkers at baseline and after 1 and 2 years. High-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, fibrinogen, adhesion molecules, transforming growth factor-beta, and AGE peptides were assessed. Irbesartan treatment yielded significant changes in hs-CRP (based on generalized estimating equation regression coefficient) with a 5.4% decrease per year versus a 10% increase per year in the placebo group (P < 0.001). Fibrinogen decreased 0.059 g/l per year from baseline versus placebo's 0.059 g/l increase per year (P = 0.027). IL-6 showed a 1.8% increase per year compared with placebo's 6.5% increase per year (P = 0.005). Changes in IL-6 were associated with changes in albumin excretion (P = 0.04). There was no treatment effect on the other biomarkers. Irbesartan (300 mg once daily) reduces low-grade inflammation in this high-risk population, and this may reduce the risk of micro- and macrovascular disease.

Aged↗
PubMed2006

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the hoorn study.

OBJECTIVE: Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS: The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS: Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively. CONCLUSIONS: A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes.

Adiponectin↗
PubMed2005

Endothelial dysfunction contributes to renal function-associated cardiovascular mortality in a population with mild renal insufficiency: the Hoorn study.

Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n = 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 +/- 12 ml/min per 1.73 m(2)) and independently associated with von Willebrand factor (standardized beta -0.09; 95% confidence interval [CI] -0.18 to -0.002; P < 0.05), soluble vascular cell adhesion molecule-1 (standardized beta -0.14; 95% CI -0.22 to -0.05; P < 0.01), and albumin-creatinine ratio (standardized beta -0.15; 95% CI -0.23 to -0.08; P < 0.001) but not with markers of inflammatory activity. Renal function was inversely associated with cardiovascular and all-cause mortality. The relative risk for cardiovascular mortality but not all-cause mortality associated with renal function decreased from 1.22 to 1.12 per 5 ml/min per 1.73 m(2) decrease of eGFR after adjustment for markers of endothelial dysfunction. In conclusion, endothelial dysfunction was related to renal function and contributed to the excess in cardiovascular mortality in this population-based cohort with mild renal insufficiency.

Aged↗