Miranda T. Schram

Increased Central Artery Stiffness in Impaired Glucose Metabolism and Type 2 Diabetes. The Hoorn Study

Abstract—Impaired glucose metabolism (IGM) and type 2 diabetes (DM-2) are associated with high cardiovascular disease risk. Increases in peripheral and central artery stiffness may represent pathophysiologic pathways through which glucose tolerance status leads to cardiovascular disease. Peripheral artery stiffness increases with deteriorating glucose tolerance status, whereas this trend remains unclear for central artery stiffness. Therefore, we investigated the associations between glucose tolerance status and estimates of central arterial stiffness. We performed a population-based study of 619 individuals (normal glucose metabolism, n=261; IGM, n=170; and DM-2, n=188) and assessed central artery stiffness by measuring total systemic arterial compliance, aortic pressure augmentation index, and carotid-femoral transit time. After adjustment for sex, age, heart rate, height, body mass index, and mean arterial pressure, DM-2 was associated with decreased total systemic arterial compliance, increased aortic augmentation index, and decreased carotid-femoral transit time. IGM was borderline significantly associated with decreased total systemic arterial compliance. Respective regression coefficients (95% confidence intervals) for IGM and DM-2 compared with normal glucose metabolism were −0.05 (−0.11 to 0.01) and −0.13 (−0.19 to −0.07) mL/mm Hg for total systemic arterial compliance; 1.1 (−0.2 to 2.5) and 1.6 (0.2 to 3.0) percentage points for aortic augmentation index; and −0.85 (−5.20 to 3.49) and −4.95 (−9.41 to −0.48) ms for carotid-femoral transit time. IGM and DM-2 are associated with increased central artery stiffness, which is more pronounced in DM-2. Deteriorating glucose tolerance is associated with increased central and peripheral arterial stiffness, which may partly explain why both DM-2 and IGM are associated with increased cardiovascular risk.

Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes--the EURODIAB Prospective Complications Study.

Aims/hypothesisThe pathogenesis of vascular complications in type 1 diabetes is poorly understood, but may involve chronic, low-grade inflammation. We investigated the association of markers of inflammation with vascular complications in type 1 diabetes.MethodsA cross-sectional nested case-control study of the follow-up data of the EURODIAB Prospective Complications Study. This study included 543 individuals (278 men) with type 1 diabetes diagnosed at <36 years of age. Cases (n=348) had complications of diabetes, controls (n=195) had no complications.ResultsC-reactive protein, interleukin-6 and tumour necrosis factor-α levels, which were combined in an inflammatory marker Z-score, were associated with albuminuria, retinopathy and cardiovascular disease. Calculated means (95% confidence intervals) of the marker Z-score were −0.15 (−0.22 to −0.07), 0.10 (−0.05 to 0.25), and 0.28 (0.15 to 0.41), p for trend <0.0001, in individuals with normo-, micro- and macroalbuminuria; −0.23 (−0.33 to −0.13), 0.14 (0.02 to 0.25) and 0.20 (0.07 to 0.32), p for trend <0.0001, in individuals with no, non-proliferative and proliferative retinopathy; and −0.28 (−0.39 to −0.18) and 0.06 (−0.08 to 0.20), p<0.001, in individuals without and with cardiovascular disease. Per 1xa0SD increase of the inflammatory marker Z-score, GFR decreased by −4.6 (−6.6 to −2.6) ml per min per 1.73xa0m2 (p<0.001).Conclusions/interpretationWe have shown that markers of inflammation are strongly and independently associated with microvascular complications and cardiovascular disease in type 1 diabetes. These data suggest that strategies to decrease inflammatory activity may help to prevent the development of vascular complications in type 1 diabetes.

Systemic Markers of Inflammation and Cognitive Decline in Old Age

OBJECTIVES: To investigate whether higher circulating levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6), and α1‐antichymotrypsin (ACT) are associated with worse cognitive function and decline in old age.

Diabetes, pulse pressure and cardiovascular mortality: the Hoorn Study

Objective Type 2 diabetic patients have an increased arterial stiffness and a very high risk of cardiovascular death. The present study investigated the relationship between pulse pressure, an indicator of vascular stiffness, and risk of cardiovascular mortality among type 2 diabetic and non-diabetic individuals. Second, we determined the relationship between pulse pressure and its main determinant (i.e. age), and the influence of diabetes and mean arterial pressure on this relationship. Design and methods We studied a cohort of 2484 individuals including 208 type 2 diabetic patients. Mean age and median follow-up for non-diabetic and diabetic individuals, respectively, were 61 and 66 years, and 8.8 and 8.6 years. One-hundred and sixteen non-diabetic and 34 diabetic individuals died of cardiovascular causes. Relative risks of cardiovascular mortality were estimated by Cox proportional hazards regression adjusted for age, gender and mean arterial pressure. Results Pulse pressure was associated with cardiovascular mortality among the diabetic, but not among the non-diabetic individuals [adjusted relative risk (95% confidence interval) per 10 mmHg increase, 1.27 (1.00–1.61) and 0.98 (0.85–1.13), P interaction = 0.07]. Further adjustment for other risk factors gave similar results. The association, at baseline, between age and pulse pressure was dependent on the presence of diabetes (P interaction = 0.03) and on the mean arterial pressure (P interaction < 0.001) (i.e. there was a stronger association when diabetes was present and when mean arterial pressure was higher). Conclusions We conclude that, in type 2 diabetes, pulse pressure is positively associated with cardiovascular mortality. The association between age and pulse pressure is influenced by the presence of type 2 diabetes and by the height of the mean arterial pressure. These findings support the concept of accelerated vascular aging in type 2 diabetes.

Setting and registry characteristics affect the prevalence and nature of multimorbidity in the elderly

OBJECTIVEnThe aim of the study was to investigate how settings and registry characteristics affect the prevalence and nature of multimorbidity in elderly individuals.nnnSTUDY DESIGN AND SETTINGnWe used data from three population-based studies, two general practitioner registries, one hospital discharge register, and one nursing home registry to estimate the prevalence of multimorbidity. Individuals aged 55 years and over were included.nnnRESULTSnMultimorbidity was most prevalent in nursing homes (82%), followed by the general population and general practitioner registries (56%-72%) and the hospital setting (22%). There were large differences in the nature of multimorbidity between settings. Combinations of hypertension, heart disease, and osteoarthritis were dominant in the population-based setting, whereas hypertension in combination with osteoarthritis, obesity, disorders of lipid metabolism, and diabetes dominated in the general practitioner setting. In the hospital setting, combinations of heart diseases had the highest prevalence. Combinations of dementia, hypertension, and stroke were dominant within the nursing home setting.nnnCONCLUSIONnThis study shows that setting and registry characteristics have an important influence on the outcome of multimorbidity studies. We recommend provision of at least information about the setting, the (list of) conditions included, the data collection method, and the time frame used, when reporting about the size and nature of multimorbidity.

Measuring cognitive function with age: the influence of selection by health and survival.

Background: Research into the pathophysiology of age-associated cognitive function and decline requires a valid estimate of cognitive function. However, this estimation can be grossly influenced by a selective loss to follow-up. Methods: We investigated the influence of health selection on the estimated age-associated cognitive function and decline by studying the effect on this estimation of study design and of the handling of multiple and missing data. We used linear regression analyses and linear mixed models to assess cognitive function from cross-sectional and longitudinal data. Repeated measures of cognitive function (assessed with dedicated neuropsychological tests) were carried out in 2 independent population-based cohort studies: the Rotterdam Study (3719 participants; mean age 71 years) and the Leiden 85-plus Study (369 participants; age 85 years). Results: The effect of age on cognitive function was greater in cross-sectional analyses when all participants were included than when analyses were restricted to participants with repeated measurements. The decline in cognitive function over 4.6 years of follow-up was intermediate between the cross-sectional estimates from the total sample and from the restricted sample. Moreover, the estimated decline in cognitive function was larger when using a short follow-up than when using the complete follow-up over 5 years. The estimated decline using linear mixed models was similar to analyses including those with a complete follow-up over 5 years. Conclusion: Selection for health and survival results in better age-specific cognitive test scores and less cognitive decline. Statistical methods handling multiple and missing data do not fully correct for this bias.

Serum Calcium and Cognitive Function in Old Age

OBJECTIVES: To determine whether serum calcium is associated with cognitive function in elderly individuals in the general population.

Aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril as initial choice in hypertensive type II diabetic individuals: effects on albumin excretion, endothelial function and inflammation in a double-blind, randomized clinical trial.

We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals. A total of 70 hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85u2009mmHg or a decrease in systolic pressure of 10% with a diastolic pressure below 85u2009mmHg. After titration, patients were treated for 12 months. Mean blood pressures changed from 157/93, 151/94 and 149/93 at baseline to 135/80, 135/82 and 131/80u2009mmHg after titration in the hydrochlorothiazide (n=24), candesartan (n=24) and lisinopril (n=22) groups. About 70% reached target blood pressures. However, only 45% had blood pressures <130/85u2009mmHg. Urinary albumin excretion and levels of soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 decreased (GEE regression coefficients, −2.40u2009mg/24u2009h (P<0.001), −85u2009ng/ml (P=0.01) and −50u2009ng/ml (P=0.02)), but brachial artery endothelium-dependent and -independent vasodilation and levels of von Willebrand factor and C-reactive protein did not change (GEE regression coefficients, 0.21u2009mm (P=0.07), 0.04u2009mm (P=0.43), 0.04u2009IU/ml (P=0.33) and −1.15u2009mg/l (P=0.64)). No differences in outcome variables between treatment groups were observed. These data show that achievement of target blood pressures below 130/85u2009mmHg in hypertensive type II diabetes is difficult. Aggressive antihypertensive therapy can improve urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals, regardless of the type of antihypertensive therapy used.

Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension

We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on left ventricular mass (LVM) index and arterial stiffness in hypertensive type II diabetic individuals. Seventy hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85u2009mmu2009Hg or a decrease in systolic pressure of 10% with a diastolic pressure below 85u2009mmu2009Hg. After titration, patients were treated for 12 months. Mean blood pressures were 157/93, 151/94 and 149/93u2009mmu2009Hg at baseline in the hydrochlorothiazide (n=24), candesartan (n=24) and lisinopril (n=22) groups, and 135/80, 135/82 and 131/80u2009mmu2009Hg after titration. About 70% reached target blood pressures, with the median use of three antihypertensive drugs. Left ventricular mass index and all estimates of arterial stiffness showed significant improvement after 12 months: that is, LVM index (−11u2009g/m2; −8%); carotid distensibility coefficient (DC; +2.8 × 10−3u2009kPa−1; +27%), compliance coefficient (CC; +0.13u2009mm2/kPa; +21%) and elastic modulus (−0.19u2009kPa; −16%); femoral DC (+1.6 × 10−3u2009kPa−1; +50%) and CC (+0.08u2009mm2/kPa; +26%); brachial DC (+2.1 × 10−3 kPa−1; +39%) and CC (+0.03u2009mm2/kPa; +27%) and total systemic arterial compliance (+0.29u2009ml/mmu2009Hg; +16%). No differences in outcome variables between treatment groups were observed. Aggressive antihypertensive treatment, although difficult to achieve, resulted in substantial reductions of LVM index and arterial stiffness in relatively uncomplicated hypertensive type II diabetic individuals. Strategies based on renin–angiotensin system inhibitors were not clearly superior to conventional (i.e. diuretic-based) strategies.

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels.

Background:u2002 Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase‐9 (MMP‐9) levels.