Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study.

PURPOSE: Endothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals. METHODS: Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups. RESULTS: Moderate [ß (95% CI) -0.13 (-0.33; 0.07)] and high [-0.22 (-0.45; -0.003)] alcohol consumption, and red wine [-0.16 (-0.30; -0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [-0.18 (-0.33; -0.04)]. CONCLUSIONS: Alcohol and red wine consumption may favourably influence processes involved in atherothrombosis.

The epidemiology of fractures in Denmark in 2011.

UNLABELLED: In the present study, we used national health care databases to estimate fracture incidence rates (IRs) and compared these IRs based on imputed data. We showed that imputation could lead to both over- and underestimation of IRs, and future research should therefore focus on how to improve those imputations. INTRODUCTION: Osteoporosis is a major public health burden through associated (osteoporotic) fractures. In Denmark, the incidence rates (IRs) of hip fracture are widely available. However, there is limited data about other fracture sites. A recent report could only provide imputed IRs, although nationwide data is readily available in electronic healthcare databases. Therefore, our aim was to estimate fracture site-specific IRs for Denmark in 2011 and to compare those to the previously reported imputed data. METHODS: Data from the Danish National Hospital Discharge Register was used to estimate age- and gender-specific IRs for any fracture as well as for different fracture sites in the Danish population aged 20 years and older in 2011. Hip fracture IRs were stratified to sub-sites, and IRs were determined for all hip fractures which were confirmed by surgery. RESULTS: The total number of incident fractures in 2011 was 80,760 (IR 191, 95 % confidence interval (CI) 190-192 (per 10,000 person-years)), of which 35,398 (43.8 %, IR 171, 95 % CI 169-173) occurred in men and 45,362 (56.2 %, IR 211, 95 % CI 209-213) in women. The majority of the fractures occurred in the population aged 50 years and older (n = 50,470, IR 249, 95 % CI 247-251). The numbers of any hip fracture were lower than the previously imputed estimates, whereas the number of forearm fractures was higher. CONCLUSION: We showed age- and gender-specific fracture rates for any fracture as well as for different fracture sites. The IRs of most fracture sites increased with age. Estimating the number of fractures for Denmark based on imputation of data from other countries led to both over- and underestimation. Future research should therefore focus on how to improve those imputations as not all countries have nationwide registry data.

The association between glucose metabolism status, diabetes severity and a history of fractures and recent falls in participants of 50 years and older-the Maastricht Study.

In this cohort of relatively young and well-treated participants with type 2 diabetes, we found no association between diabetes status and a history of previous fractures and recent falls. Furthermore, no association between diabetes severity and previous fractures or recent falls was found. INTRODUCTION: In this study, we examined the association between glucose metabolism status and historical fractures or recent falls and the effect of diabetes severity (glucose control, insulin use, and diabetes duration) on falls and fractures in the participants with type 2 diabetes. METHODS: Cross-sectional data from 2005 participants of the Maastricht Study. Falls in the past 6 months and fractures ≥age 50 were assessed by questionnaire. Glucose metabolism status (normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes) was based on the oral glucose tolerance test and medication use. RESULTS: In the completely adjusted model, the odds for a fall were not significantly higher in those with impaired glucose metabolism status (OR (95%CI) 1.28 (0.93-1.77)) or with type 2 diabetes (OR (95%CI) 1.21 (0.80-1.81)) compared with the group with normal glucose metabolism. Within the group with type 2 diabetes, there were no significant differences with regard to reported falls between participants with HbA1c >7 % (53 mmol/mol) versus HbA1c ≤7 % (OR (95%CI) 1.05 (0.58-1.90)), insulin users versus non-insulin users (OR (95%CI) 1.51 (0.79-2.89)), and with a diabetes duration >5 versus ≤5 years (OR (95%CI) 0.52 (0.46-1.47)). Similarly, neither glucose metabolism status nor diabetes severity was associated with prior fractures. CONCLUSIONS: Glucose metabolism status was not significantly associated with previous fractures and recent falls. In addition, in this cohort of relatively young and well-treated participants with type 2 diabetes, diabetes severity was not associated with previous fractures and recent falls.

Lower verbal intelligence is associated with diabetic complications and slower walking speed in people with Type 2 diabetes: the Maastricht Study.

AIMS: To determine the association of verbal intelligence, a core constituent of health literacy, with diabetic complications and walking speed in people with Type 2 diabetes. METHODS: This study was performed in 228 people with Type 2 diabetes participating in the Maastricht Study, a population-based cohort study. We examined the cross-sectional associations of score on the vocabulary test of the Groningen Intelligence Test with: 1) determinants of diabetic complications (HbA1c , blood pressure and lipid level); 2) diabetic complications: chronic kidney disease, neuropathic pain, self-reported history of cardiovascular disease and carotid intima-media thickness; and 3) walking speed. Analyses were performed using linear regression and adjusted in separate models for potential confounders and mediators. Significant age- and sex-adjusted associations were additionally adjusted for educational level in a separate model. RESULTS: After full adjustment, lower verbal intelligence was associated with the presence of neuropathic pain [odds ratio (OR) 1.18, 95% CI 1.02;1.36], cardiovascular disease (OR 1.14, 95% CI 1.01;1.30), and slower walking speed (regression coefficient -0.011 m/s, 95% CI -0.021; -0.002 m/s). These associations were largely explained by education. Verbal intelligence was not associated with blood pressure, glycaemic control, lipid control, chronic kidney disease or carotid intima-media thickness. CONCLUSIONS: Lower verbal intelligence was associated with the presence of some diabetic complications and with a slower walking speed, a measure of physical functioning. Educational level largely explained these associations. This implies that clinicians should be aware of the educational level of people with diabetes and should provide information at a level of complexity tailored to the patient.

Endothelial dysfunction is associated with a greater depressive symptom score in a general elderly population: the Hoorn Study.

BACKGROUND: Endothelial dysfunction (ED), low-grade inflammation (LGI) and oxidative stress (OxS) may be involved in the pathobiology of depression. Previous studies on the association of these processes in depression have yielded contradictory results. We therefore investigated comprehensively, in a population-based cohort study, the association between ED, LGI and OxS on the one hand and depressive symptoms on the other. METHOD: We used data from the Hoorn Study and determined biomarkers of ED [flow-mediated dilatation (FMD), von Willebrand factor, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble thrombomodulin and soluble endothelial selectin], LGI [C-reactive protein, tumour necrosis factor-α, interleukin 6, interleukin 8, serum amyloid A, myeloperoxidase (MPO) and sICAM-1] and OxS (oxidized low density lipoprotein and MPO). Depressive symptoms were quantified by the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire (n = 493; age 68 years; 49.9% female). Regression analyses were performed with the use of biomarker Z scores. Adjustments were made for age, sex and glucose metabolism status (cohort stratification variables) and prior cardiovascular disease, hypertension, waist-to-hip ratio, cholesterol levels, education level, physical activity, dietary habits, and the use of antihypertensive and/or lipid-lowering medication and/or metformin (potential confounders). RESULTS: After adjustment for age, sex and glucose metabolism status, one standard deviation increase in the ED Z score was associated with a 1.9 [95% confidence interval (CI) 0.7-3.1] higher CES-D score. Additional adjustments did not materially change this result. LGI and OxS were not associated with the CES-D score. CONCLUSIONS: ED, as quantified by an array of circulating biomarkers and FMD, was independently associated with depressive symptoms. This study supports the hypothesis that ED plays an important role in the pathobiology of depression.

Unhealthy dietary patterns associated with inflammation and endothelial dysfunction in type 1 diabetes: the EURODIAB study.

BACKGROUND AND AIMS: A healthy diet has been inversely associated with endothelial dysfunction (ED) and low-grade inflammation (LGI). We investigated the association between nutrient consumption and biomarkers of ED and LGI in type 1 diabetes. METHODS AND RESULTS: We investigated 491 individuals. Nutrient consumption and lifestyle risk factors were measured in 1989 and 1997. Biomarkers of ED (von Willebrand factor, soluble vascular cell adhesion molecule-1 and soluble endothelial selectin) and LGI (C-reactive protein, interleukin 6 and tumour necrosis factor α) were measured in 1997 and averaged into Z-scores. The nutrient residual method was used to adjust individual nutrient intake for energy intake. Data were analysed with generalised estimation equations. We report increments/decrements in nutrient consumption, averaged over time, per +1 standard deviation (SD) of 1997 ED or LGI Z-scores, after adjustment for sex, age, duration of diabetes, investigation centre, body mass index, energy intake, smoking behaviour, alcohol consumption, and each of the other nutrients. One SD elevation in ED Z-score was associated with a diet lower in fibre [ß(95%CI);-0.09(-0.18;-0.004)], polyunsaturated fat [-0.18(-0.31;-0.05)] and vegetable protein [-0.10(-0.20;-0.001)]. For the LGI Z-score results showed associations with fibre [-0.09(-0.17;-0.01)], polyunsaturated fat [-0.14(-0.24;-0.03)] and cholesterol [0.10(0.01; 0.18)]. CONCLUSION: In type 1 diabetes, consumption of less fibre, polyunsaturated fat and vegetable protein, and more cholesterol over the study period was associated with more ED and LGI. Following dietary guidelines in type 1 diabetes may reduce cardiovascular disease risk by favourably affecting ED and LGI.

Accelerometer-derived physical activity and sedentary time and cardiac biomarkers: The Maastricht Study.

Background: Cardiac troponins and NT-proBNP are biomarkers of cardiac injury that are used clinically in the diagnosis of myocardial infarction and heart failure. It is not known whether the amount, types and patterns of physical activity (PA) and sedentary behaviour are associated with levels of cardiac biomarkers. Methods: In the population-based Maastricht Study (n = 2,370, 51.3% male, 28.3% T2D) we determined cardiac biomarkers hs-cTnI, hs-cTnT, and NT-proBNP. PA and sedentary time were measured by activPAL and divided into quartiles [quartile 1 (Q1) served as reference]. The weekly pattern of moderate-to-vigorous PA (insufficiently active; regularly actives; weekend warriors) and coefficient of variation (CV) was calculated. Linear regression analyses were conducted with adjustment for demographic, lifestyle, and cardiovascular risk factors. Results: There was no consistent pattern between physical activity (different intensities: total, light, moderate-to-vigorous and vigorous) and sedentary time on the one hand and hs-cTnI and hs-cTnT on the other. Those with the highest levels of vigorous intensity PA had significantly lower levels of NT-proBNP. With regard to PA patterns, weekend warriors and regularly actives had lower levels of NT-proBNP but not with hs-cTnI and hs-cTnT (reference:insufficiently actives). A higher weekly moderate-to-vigorous PA CV (indicating more irregular activity) was associated with lower levels of hs-cTnI and higher levels of NT-proBNP, but not with hs-cTnT. Conclusions: In general, there was no consistent association between PA and sedentary time and cardiac troponins. In contrast, vigorous and possibly moderate-to-vigorous intensity PA, especially if done regularly, were associated with lower levels of NT-proBNP.

Vitamin D in relation to myocardial structure and function after eight years of follow-up: the Hoorn study.

BACKGROUND AND AIMS: To investigate associations between baseline serum 25-hydroxyvitamin D [25(OH)D] levels and myocardial structure and function after 8 years of follow-up in older Dutch subjects. METHODS: We included 256 subjects of the Hoorn Study, a population-based cohort. They underwent a standardized 2-dimensional echocardiogram at baseline between 2000 and 2001, and again between 2007 and 2009. We studied the association of 25(OH)D quartiles with echocardiographic measures of the left ventricular mass index (LVMI), left ventricular systolic function and markers of diastolic function using linear regression analyses. RESULTS: At baseline, subjects had a mean age of 67.4 ± 5.2 years and 41.4% had prior cardiovascular disease (CVD). Low serum 25(OH)D levels were only associated with higher LVMI at 8-year follow-up in subjects without prior CVD and in subjects with low kidney function (median estimated glomerular filtration rate ≤77.5 ml/min/1.73m(2)). The associations attenuated after adjustments for parathyroid hormone (PTH), which was associated with higher LVMI (g/m(2.7)) in subjects with low kidney function (regression coefficient highest quartile 6.3, 95% CI: 0.2, 12.5). CONCLUSION: This study showed no strong associations of 25(OH)D with myocardial structure and function. However, PTH - a possible modifiable mediator in the relation between 25(OH)D and myocardial structure - was positively associated with LVMI in subjects with low kidney function.

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular, but not macrovascular, disease in individuals with and without (pre)diabetes: The Maastricht Study.

AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown. METHODS: Subjects with normal glucose metabolism (n=1796; age: 57.9±8.2 years; 43.3% men), prediabetes (n=478; age: 61.6±7.6 years; 54.0% men) and T2DM (n=669; age: 63.0±7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO. RESULTS: Fasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥30mg/24h [fasting: 1.12 (95% CI: 0.97-1.29); post-OGTT: 1.19 (1.01-1.41)], eGFR<60mL/min/1.73 m2 [fasting: 1.58 (95% CI: 1.38-1.82), post-OGTT: 1.57 (1.34-1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01-2.53), post-OGTT: 1.38 (0.77-2.48)]. No associations with prior CVD were found. CONCLUSION: Fasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.

Vitamin D deficiency and myocardial structure and function in older men and women: the Hoorn study.

BACKGROUND: Vitamin D deficiency is frequently observed in heart failure patients and it has been shown that vitamin D exerts various effects on the heart that may be relevant for the pathogenesis of myocardial diseases. AIMS: We aimed to elucidate the largely unknown association of 25-hydroxyvitamin D [25(OH)D] serum levels with echocardiographic measures of left ventricular (LV) structure and function. MATERIAL/SUBJECTS AND METHODS: We measured 25(OH)D serum levels and performed standardized LV echocardiograms in 614 persons from a population-based cohort of older men and women. Echocardiographic data were used to calculate LV mass and geometry and for classification of systolic and diastolic dysfunction. To consider the seasonal variations of 25(OH)D levels we categorized our study participants according to season-specific 25(OH)D quartiles. RESULTS: LV systolic function, mass and geometry were not significantly associated with 25(OH)D serum levels. In binary logistic regression analyses, the prevalence of LV diastolic dysfunction was significantly higher in the first season-specific 25(OH)D quartile when compared to the fourth quartile [odds ratio 2.32 (95% CI: 1.42-3.80); p=0.001] but significance was lost after adjustments for age [odds ratio 1.51 (0.89-2.57); p=0.123] and established risk factors for heart failure [odds ratio 1.47 (0.84-2.59); p=0.178]. CONCLUSIONS: Serum levels of 25(OH)D are not significantly associated with LV structure and function but a non-significant trend towards increased risk of diastolic dysfunction in persons with vitamin D deficiency warrants further studies.

Deteriorating glucose tolerance status is associated with left ventricular dysfunction--the Hoorn Study.

BACKGROUND: Type 2 diabetes (DM2) is associated with a greater risk of heart failure. The mechanisms underlying this association remain controversial and include diabetes-associated hypertension and obesity, impaired small and large artery function, and a distinct metabolic cardiomyopathy related to hyperglycaemia/ hyperinsulinaemia. The proximate causes of heart failure are left ventricular (LV) systolic dysfunction (SDF) and diastolic dysfunction (DDF). We investigated, in a population-based cohort (n=746), the association between glucose tolerance status and SDF and DDF . METHODS AND RESULTS: The study population consisted of 274 individuals with normal glucose metabolism (NGM), 174 with impaired glucose metabolism (IGM) and 298 with DM2 (mean age 68.5 years). All participants underwent an LV echocardiogram. SDF was defined as ejection fraction <55%. DDF was determined by a sum score of peak A velocity (abnormal, >or =97 cm/s), the difference between Apv and Amv duration (> or =41 ms), and left atrial volume (> or =57 ml), where cut-off values were based upon the 90th percentile in NGM. In addition, we analysed the ratio of early to late diastolic filling (E/A ratio) on a continuous scale using linear regression analyses. The age- and sex-standardised prevalences in NGM, IGM and DM2 were 13, 14 and 30% for SDF , and 26, 36 and 47% for DDF (P trend for both <0.001). After adjustment for sex, age, hypertension, body mass index, prior cardiovascular disease and (micro) albuminuria, DM2 was significantly associated with both SDF (odds ratio (95% CI) 2.04 (1.24 to 3.36)) and DDF (2.42 (1.63 to 3.60)) (90th percentile definition). This was also true for the analyses with the E/A ratio on a continuous scale (regression coefficient b (95% CI) -0.05 (-0.09 to -0.01). After adjustment for sex, age, hypertension, body mass index, prior cardiovascular disease and (micro) albuminuria IGM was not significantly associated with SDF (odds ratio (95% CI) 1.04 (0.58 to 1.88)) or DDF (1.33 (0.86 to 2.06)) using the definition based upon the 90th percentile. However, IGM was significantly associated with DDF if the E/A ratio was analysed on a continuous scale (regression coefficient beta (95% CI) -0.05 (-0.10 to -0.01). Additional adjustment for brachial artery flow-mediated vasodilation or arterial stiffness, as measures of large artery function, did not materially alter the results. Hyperglycaemia and hyperinsulinaemia together explained approximately 30% of the association of DM2 with SDF and approximately 40% of that with DDF . CONCLUSION: DM2 is independently associated with a 2.0-fold greater risk of SDF and a 2.4-fold greater risk of DDF . IGM was not associated with SDF , and the association with DDF was limited to the E/A ratio. These observations may therefore explain the increased risk of systolic and diastolic heart failure in elderly individuals with DM2.

The association between insulin use and volumetric bone mineral density, bone micro-architecture and bone strength of the distal radius in patients with type 2 diabetes - The Maastricht study.

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62±7.5years, 44% women) was used. Participants were classified as insulin user (n=13) or non-insulin user (n=37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (ß):-0.56 (95% CI:-0.89 to -0.24)), trabecular vBMD (ß:-0.58 (95% CI:-0.87 to -0.30)), trabecular thickness (ß:-0.55 (95% CI:-0.87 to -0.23)), cortical thickness (ß:-0.41 (95% CI:-0.74 to -0.08)), log cortical pore volume (ß:-0.43 (95% CI:-0.73 to -0.13)), bone stiffness (ß:-0.39 (95% CI:-0.62 to -0.17)) and failure load (ß:-0.39 (95% CI:-0.60 to -0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.

S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study.

OBJECTIVE: To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors. METHODS AND RESULTS: In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors. CONCLUSIONS: In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Plasma homocysteine and S-adenosylmethionine in erythrocytes as determinants of carotid intima-media thickness: different effects in diabetic and non-diabetic individuals. The Hoorn Study.

OBJECTIVE: Hyperhomocysteinemia is a risk factor for atherothrombosis. Through unknown mechanisms, individuals with type 2 diabetes appear particularly susceptible. We determined whether components of homocysteine metabolism are associated with intima-media thickness in individuals with and without type 2 diabetes. METHODS AND RESULTS: In a cross-sectional design, we studied 231 Caucasian individuals, 60.6% having type 2 diabetes. We measured fasting homocysteine, vitamin B6 and vitamin B12 in plasma, and folate, S-adenosylmethionine and S-adenosylhomocysteine in plasma and erythrocytes. A homocysteine concentration >12 micromol/l was associated with a greater intima-media thickness of +0.07 mm (95% CI, +0.01 to +0.13; P=0.03) among diabetic individuals and of -0.004 mm (95%CI, -0.08 to +0.07; P=0.92) among non-diabetic individuals. An erythrocyte S-adenosylmethionine concentration above >4000 nmol/l was associated with a smaller intima-media thickness of -0.04 mm (95%CI, -0.10 to +0.02; P=0.17) for diabetic individuals versus -0.12 mm (95%CI, -0.20 to -0.36; P=0.005) for non-diabetic individuals. CONCLUSIONS: With regard to carotid intima-media thickness, individuals with diabetes appear more susceptible to the detrimental effects of homocysteine than non-diabetic individuals. In addition, diabetic individuals may lack the protective effect on the vascular wall conferred by high concentrations of S-adenosylmethionine. These findings may help explain why hyperhomocysteinemia is an especially strong risk factor for atherothrombosis among individuals with type 2 diabetes.

Associations of serum n-3 and n-6 polyunsaturated fatty acids with echocardiographic measures among older adults: the Hoorn Study.

BACKGROUND/OBJECTIVES: Lower circulating polyunsaturated fatty acids (PUFAs) may induce loss of heart function. We investigated whether lower concentrations of n-3 and n-6 PUFAs were associated with less favourable echocardiographic measures and higher heart rate in older Caucasians, cross-sectionally and after 7 years of follow-up. SUBJECTS/METHODS: We used data from the Hoorn Study, a population-based cohort. Cross-sectional data were available for 621 participants and longitudinal data for 336 participants. Mean age was 68.6±6.8 years at baseline. We performed linear regression analyses using n-3 and n-6 PUFAs quartiles-assayed by gas liquid chromatography-with left ventricular ejection fraction (LVEF), left ventricular mass index, left atrial volume index and heart rate. RESULTS: In multivariable analyses (regression coefficient (95% confidence interval)), the lowest eicosapentaenoic acid and docosahexaenoic acid quartiles compared with the highest quartiles were cross-sectionally associated with lower LVEF. Lower eicosapentaenoic acid and docosahexaenoic acid concentrations were associated with higher heart rate: 3.7 b.p.m. (1.5, 6.0; P for trend <0.001) and 3.4 b.p.m. (1.2, 5.6; P for trend 0.001), respectively. Multivariate longitudinal analyses showed a significant trend across quartiles for alpha-linolenic acid in relation to LVEF. The lowest linoleic acid quartile was significantly associated with a decreased LVEF of -4.0% compared with the highest quartile. CONCLUSIONS: This study found no strong evidence of longitudinal associations of eicosapentaenoic acid and docosahexaenoic acid with echocardiographic measures, however, lower concentrations of alpha-linolenic acid and linoleic acid were associated with decreased LVEF. These results provide evidence for a potential protective role of alpha-linolenic acid and linoleic acid in relation to systolic function.

The metabolic syndrome in elderly individuals is associated with greater muscular, but not elastic arterial stiffness, independent of low-grade inflammation, endothelial dysfunction or insulin resistance--The Hoorn Study.

The metabolic syndrome (MetS) increases cardiovascular disease (CVD) risk. How MetS increases CVD risk is incompletely understood, but increasing arterial stiffness is one candidate link, which in turn could be explained by (low-grade) inflammation, endothelial dysfunction (ED) or insulin resistance (IR). However, MetS-related increases in stiffness may not be uniformly distributed over muscular and elastic arteries. Therefore, the purpose of this study was to determine: (1) the associations between the MetS, and muscular and elastic arterial stiffness, and (2) whether any such associations could be explained by inflammation, ED or IR. These questions were addressed in the Hoorn Study. MetS was defined according to the NCEP (National Cholesterol Education Program) criteria. Arterial stiffness was determined by ultrasound, tonometry and echocardiography. Inflammation, ED and IR were estimated by C-reactive protein, flow-mediated vasodilation and the homoeostatic model for the assessment of IR, respectively. The results showed that MetS was associated with both femoral and brachial arterial stiffness, significantly so for the distensibility coefficients and for the femoral compliance coefficient. In the carotid artery and aorta, no particular pattern emerged. Additional adjustment for either inflammation, ED or IR did not materially alter the results. The results therefore indicate that muscular arteries may stiffen preferentially over elastic arteries and that distensibility is affected to a greater extent than compliance, thus maintaining volume compliance over vessel wall stiffening. Additionally, the increase in stiffness was not explained by inflammation, ED or IR and suggests that stiffening of the muscular arteries in MetS may not be the consequence of these phenomena.

Relationship of adiposity with arterial stiffness as mediated by adiponectin in older men and women: the Hoorn Study.

OBJECTIVE: To investigate whether adiponectin is associated with arterial stiffness, and whether adiponectin explains the association between body composition and arterial stiffness. DESIGN: Cross-sectional cohort study. METHODS: Subjects were participants (n=456, mean age 68.9+/-6.1 years; age range 60-86 years) of the third follow-up examination of the Hoorn Study. Trunk fat, leg fat, trunk lean, and leg lean mass were measured by dual-energy X-ray absorptiometry. Ultrasound was used to measure distensibility and compliance of the carotid, femoral, and brachial arteries, and carotid Young's elastic modulus (as estimates of peripheral arterial stiffness). Results Trunk fat mass was negatively associated with (ln-transformed) adiponectin (standardized beta=-0.49, P<0.001), while leg fat mass was positively associated with adiponectin (beta=0.44, P<0.001), after adjustment for each other, age, and lean mass. After adjustment for age, sex, mean arterial pressure, and estimated glomerular filtration rate, higher adiponectin was associated with decreased peripheral arterial stiffness (beta of mean Z-scores of all three arteries=0.14, P=0.001). However, the associations of trunk fat (beta=-0.26, P<0.001) and leg fat (beta=0.16, P=0.006) with peripheral arterial stiffness were only minimally explained by adiponectin levels. CONCLUSION: Trunk fat and leg fat are oppositely associated with adiponectin. Although low adiponectin was a determinant of increased peripheral arterial stiffness, it only explained a small part of the association between body fat and peripheral arterial stiffness. This indicated that factors other than adiponectin may be more important in the pathophysiological mechanisms by which abdominal obesity leads to arterial stiffness.

Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease.

Increased arterial stiffness associated with diabetes and the metabolic syndrome may in part explain the increased cardiovascular disease risk observed in these conditions. Arterial stiffness can be estimated by quantifying pulse pressure but is better described by distensibility and compliance coefficients, pulse wave velocity and wave reflection. The most common non-invasive methodologies used to quantify these estimates of arterial stiffness (e.g. ultrasonography and applanation tonometry) are also described. We then review and summarise the current data on the associations between diabetes, the metabolic syndrome and insulin resistance on the one hand and greater arterial stiffness on the other, and identify and discuss some unresolved issues such as differential stiffening of central vs peripheral arterial segments, the impact of sex, and the pathobiology of increased arterial stiffness in diabetes and the metabolic syndrome. Finally, some considerations with regard to treatment options are presented. At present the most powerful therapy available for reducing arterial stiffness is to vigorously treat hypertension using pharmacological agents. New pharmacological strategies to reduce arterial stiffness are likely to be especially relevant to individuals with diabetes.

Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study.

OBJECTIVES: Screening for type 2 diabetes has been recommended and targeted screening might be an efficient way to screen. The aim was to investigate whether diabetic patients identified by a targeted screening procedure differ from newly diagnosed diabetic patients in general practice with regard to the prevalence of macrovascular complications. DESIGN: Cross-sectional population-based study. SETTING: Population study, primary care. SUBJECTS: Diabetic patients identified by a population-based targeted screening procedure (SDM patients), consisting of a screening questionnaire and a fasting capillary glucose measurement followed by diagnostic testing, were compared with newly diagnosed diabetic patients in general practice (GPDM patients). Ischaemic heart disease and prior myocardial infarction were assessed by ECG recording. Peripheral arterial disease was assessed by the ankle-arm index. Intima-media thickness of the right common carotid artery was measured with ultrasound. RESULTS: A total of 195 SDM patients and 60 GPDM patients participated in the medical examination. The prevalence of MI was 13.3% (95% CI 9.3-18.8%) and 3.4% (1.0-11.7%) in SDM patients and GPDM patients respectively. The prevalence of ischaemic heart disease was 39.5% (95% CI 32.9-46.5%) in SDM patients and 24.1% (15.0-36.5%) in GPDM patients. The prevalence of peripheral arterial disease was similar in both groups: 10.6% (95% CI 6.9-15.9%) and 10.2% (4.7-20.5%) respectively. Mean intima-media thickness was 0.85 mm (+/-0.17) in SDM patients and 0.90 mm (+/-0.20) in GPDM patients. The difference in intima-media thickness was not statistically significant. CONCLUSIONS: Targeted screening identified patients with a prevalence of macrovascular complications similar to that of patients detected in general practice, but with a lower degree of hyperglycaemia.

LDL oxidative modifications in well- or moderately controlled type 2 diabetes.

BACKGROUND: The aim of the study was to examine, by measurement of specific indicators of free radical-mediated oxidation of LDL, whether there is evidence of increased in vivo oxidation of LDL in type 2 diabetic patients, and to investigate their associations with carotid intima media thickness (IMT). METHODS: In native LDL, we quantified five different products of LDL oxidation reflecting various stages of LDL oxidative modification in 38 individuals with well- or moderately controlled type 2 diabetes (HbA(1c)