Reduced cardiac vagal activity in obese children and adolescents

Objective: Obese children present with various cardiovascular risk factors affecting their future health. In adults, cardiac autonomic function is a major risk factor, predicting cardiovascular morbidity and mortality. We hypothesized that obese children and adolescents had a lower cardiac vagal activity than lean subjects. We measured cardiac spontaneous baroreflex sensitivity (BRS), reflecting the dynamic regulation of cardiac vagal function, in large groups of obese and lean young individuals. Methods and results: Cardiac BRS, using the sequence approach, was assessed in 120 obese (59 girls), 43 overweight (23 girls) and 148 lean subjects (78 girls). Obese subjects showed a decreased BRS compared to both overweight and lean subjects [16 ± 7 versus 21 ± 9 (P<0·01) and 22 ± 10 ms per mmHg (P<0·0001), respectively]. The differences remained after correcting for age, gender and pubertal status. Conclusion: Children with obesity had low vagal activity at rest, and there was no gender difference.     

Abnormal vascular reactivity at rest and exercise in obese boys

Background Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild‐to‐moderate obesity and in lean controls. Materials and methods Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23·9 ± 2·6 kg m^?2)] and thirteen controls (BMI:17·4 ± 1·8 kg m^?2), matched for age (mean age: 11·6 ± 0·6 years) were recruited. We measured carotid intima‐media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow‐mediated dilation (FMD) and nitrate‐dependent dilation (NDD), lower limb blood flow during local knee‐extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. Results Compared to lean controls, obese boys had greater IMT (0·47 ± 0·06 vs. 0·42 ± 0·03 mm, P < 0·05) but lower FMD (4·6 ± 2·8 vs. 8·8 ± 3·2%, P < 0·01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min^?1·100 g^?1) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. Conclusions Mild‐to‐moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.     

Evaluation of intima-media thickness and vascular elasticity of the common carotid artery in patients with isolated systolic hypertension using ultrasound radiofrequency-data technology

Background: Radiofrequency (RF) data technology is a newly developed method to evaluate vascular disease, especially subclinical atherosclerotic change. Data regarding predictors of intima‐media thickness (IMT) and vascular elasticity of the common carotid artery (CCA) in subjects with isolated systolic hypertension (ISH) using ultrasound RF‐data technology are scarce. Aims: We evaluated the change in IMT and vascular elasticity of the CCA in patients with ISH at an early phase using US RF‐data technology. Methods: Thirty‐nine patients with ISH and 41 age‐matched control subjects were the study population. The common carotid arterial systolic diameter (Ds), diastolic diameter (Dd), IMT, carotid distensibility (CD), local pulse wave velocity (PWVβ) and stiffness (β) were compared between the two groups, as were correlations between pulse pressure (PP) and parameters of vascular stiffness. Results: Common carotid arterial Ds, Dd, IMT, PWVβ and β increased whereas CD decreased more significantly in the ISH group than in age‐matched controls. The level of PP in the ISH group had significant positive correlations with PWVβ (r = 0·298, P<0·05) and β (r = 0·291, P<0·05), whereas significant correlations with CD were not observed. Conclusions: US RF‐data technology could be used to accurately and quantitatively evaluate increased IMT and decreased arterial elasticity of the CCA in patients with ISH compared with normal subjects.     

Sex and muscle structural lipids in obese subjects – an impact on insulin action?

Background Long‐chain polyunsaturated fatty acid (LCPUFA) especially the n‐3‐FA of skeletal muscle phospholipids may facilitate insulin action, whereas saturated and trans‐FA act oppositely. Community studies show that non‐diabetic weight matched obese men and women display similar insulin resistance, despite the fact that an android fat distribution is detrimental to insulin action. The increased extramyocellular fat mass of obese women may act in a paracrine manner such that its release of free FA and cytokines may hamper in situ desaturation and elongation of FA in skeletal muscle phospholipids. Material and methods To test the hypothesis that obese women may display an inferior FA composition compared to obese men, the FA composition of skeletal muscle phospholipids was determined in vastus lateralis biopsies obtained from 12 non‐diabetic obese women with a typical gynoid fat distribution, nine non‐diabetic obese men with a typical android fat distribution and 12 (seven females) lean age matched healthy controls (body mass index 34·6 ± 1·0 kg m^?2, 36·5 ± 1·2 and 22·5 ± 0·5; age 47 ± 2 years, 51 ± 3 and 49 ± 2). Results Obese women displayed decreased LCPUFA n‐3 and ratio of n‐3/n‐6 PUFA, whereas trans‐FA and palmitic‐FA (C16 : 0) were increased compared to obese men and controls (all Ps < 0·05). Plasma high‐density lipoprotein cholesterol (HDL‐C), triglycerides and a marker of insulin sensitivity were similar between obese women and men but impaired compared to controls (Ps < 0·05). Conclusions The data support the hypothesis that insulin resistant non‐diabetic obese men display a more optimal skeletal muscle phospholipid FA composition than their female counterparts, which may be a mechanism to compensate the detrimental effect on insulin action of an android fat distribution.     

Influence of arterial wave reflection on carotid blood pressure and intima‐media thickness in older endurance trained men and women with pre‐hypertension

Increased carotid intima‐media thickness (IMT) with aging is a significant predictor of mortality. Older endurance trained (ET) individuals have lower carotid artery stiffness but similar carotid IMT when compared to sedentary (SED) age‐matched peers. The purpose of this study was to examine the contribution of arterial wave reflections to carotid hemodynamics and IMT in older ET and SED with pre‐hypertension. Subjects consisted of endurance‐trained master athletes and age‐matched sedentary controls (mean age 67 years). Carotid artery Beta‐stiffness index and IMT was assessed with ultrasonography. Carotid pressure and augmented pressure from wave reflections (obtained from pulse contour analysis) was measured with applanation tonometry. Carotid systolic blood pressure (SBP) and IMT were not different between groups (P>0·05). Carotid stiffness was significantly lower in ET versus SED (7·3 ± 0·8 versus 9·9 ± 0·6, P<0·05). Augmented pressure was significantly greater in ET versus SED (17·7 ± 1·6 versus 13·3 ± 1·5 mmHg, P<0·05). When adjusting for differences in resting heart rate, there were no group differences in augmented pressure. In conclusion, older ET persons with pre‐hypertension have reduced carotid artery stiffness, but similar carotid SBP and carotid IMT when compared to SED. The lack of change in carotid SBP and IMT in older ET may be related to the inability of chronic exercise training to reduce bradycardia‐related augmented pressure from wave reflections with aging.     

Differential effects of age on large artery stiffness and minimal vascular resistance in normotensive and mildly hypertensive individuals

Large artery stiffness and small artery structural changes are both cardiovascular risk factors. Arterial stiffness increases with age and blood pressure (BP), but it is unclear in which way large artery pulse wave velocity (PWV) and peripheral vascular resistance are related and whether age has any influence. In a cross‐sectional study, PWV and forearm minimum vascular resistance (R_min) was compared with emphasis on the impact of age. Normotensive (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24‐h BP measurements. Age ranged from 21 to 79 years with an even distribution from each age decade. PWV was assessed using tonometry. Forearm R_min was measured by venous occlusion plethysmography at maximal vasodilatation induced by 10 min of ischaemia in combination with skin heating and hand grip exercise. In both normotensive and hypertensive subjects, PWV correlated significantly with age and BP. Based on median age, both groups were assigned into two equally large subgroups. Normotensive older (66 ± 7 years) and younger (35 ± 10 years) persons had different carotid‐femoral PWV (7·9 ± 1·8 versus 5·7 ± 0·9 m/s, P<0·01), but similar R_min values (3·7 ± 0·9 versus 3·6 ± 1·2 mmHg/ml/min/100 ml). Hypertensive older (63 ± 6 years) and younger (40 ± 10 years) also had different PWV (8·0 ± 1·5 versus 6·7 ± 1·1 m/s, P<0·05), but the older had lower R_min (3·1 ± 0·8 versus 4·7 ± 2·2 mmHg/ml/min/100 ml, P<0·05). In a regression analysis adjusting for age, BP, gender and heart rate, no correlation was seen between PWV and R_min. The data suggest that age differentially affects PWV and R_min and that BP can increase in older persons without affecting R_min.     

Visfatin expression in subcutaneous adipose tissue of pre-menopausal women: relation to hormones and weight reduction

Background A novel adipokine, visfatin, was found to be related to adiposity in humans and regulated by a number of hormonal signals. The aim of this study was to investigate the relationships of visfatin expression in adipose tissue with potential regulatory factors such as insulin, testosterone and tumor necrosis factor‐α (TNF‐α) and to elucidate the effect of a diet induced weight reduction on adipose tissue mRNA expression and plasma levels of visfatin. Materials and methods Biopsies of subcutaneous abdominal adipose tissue (SCAAT) and plasma samples were obtained at the beginning of the study from 47 pre‐menopausal women (age 38·7 ± 1·7 years, body mass index (BMI) 27·9 ± 1·4 kg m^?2), consisting of 15 lean, 16 overweight and 16 obese subjects. The subgroup of 32 overweight/obese women (age 42·1 ± 1·9 years, BMI 31·2 ± 0·9 kg m^?2) underwent a 12 week hypocaloric weight reducing diet and samples were obtained at the end of the diet. Biopsy samples were analysed for visfatin and TNF‐α mRNA levels and plasma was analysed for relevant metabolites and hormones. Results In the group of 47 subjects visfatin mRNA expression in SCAAT was negatively correlated with plasma free testosterone (r = –0. 363, P < 0·05) and BMI (r = –0·558, P < 0·01) and positively associated with adipose tissue TNF‐α mRNA expression (r = 0·688, P < 0·01). The diet resulted in the reduction of body weight and in the decrease of plasma insulin, free testosterone and TNF‐α levels. In the group of overweight/obese subjects visfatin mRNA in SCAAT increased after the diet and the diet induced increase was positively correlated with the magnitude of body weight loss. Conclusion Visfatin mRNA expression in SCAAT is associated with TNF‐α expression, plasma free testosterone and BMI in pre‐menopausal women. A weight reducing hypocaloric diet results in the increase of visfatin mRNA in SCAAT.     

Retinopathy in type 2 diabetes mellitus is associated with increased intima‐media thickness and endothelial dysfunction

Background Microangioathy and macroangiopathy in type 2 diabetes mellitus (T2DM) frequently coexist. Both types of vascular complications share traditional risk factors. It is not clear whether the presence of microangiopathy, such as diabetic retinopathy (DR), constitutes a predictor of atherosclerosis in T2DM. Here we described the search for the association between DR and intima‐media thickness (IMT) in T2DM. We also compared endothelial function in subjects with and without DR. Material and methods We examined 182 consecutive patients with T2DM for at least 5 years (mean age at examination 56·3 ± 6·52 years). We assessed (i) IMT of carotid artery by ultrasound and (ii) endothelial function by flow‐mediated dilatation (FMD) method as well as by measurement of concentrations of von Willebrand factor (vWF) and s‐ICAM‐1. All patients underwent ophthalmological examination. Statistical analysis included Student's, Mann–Whitney, chi‐square, Fisher tests and multiple regression. Results DR was found in 71 (39·0%) subjects. IMT was higher in patients with DR than those without DR (0·87 mm vs. 0·79 mm, respectively, P = 0·0001). FMD was lower in the complication group than in subjects without DR (8·38% vs. 10·45%, respectively, P = 0·0023). Concentrations of s‐ICAM‐1 and vWF were not different between the groups. In multiple regression analysis, DR was among the predictors of increased IMT (P = 0·016) and decreased FMD (P = 0·002). We did not find a significant association of DR with vWF and s‐ICAM‐1 (P = 0·09 and P = 0·11, respectively). Conclusions DR is associated with increased IMT and endothelial dysfunction in T2DM. Impaired endothelial function may be a common denominator of pathogenesis of microvascular complications and atherosclerosis in T2DM.     

Conventional treatment after myocardial infarction in routine clinical practice results in regression of left common carotid intima‐media thickness

This study aimed to evaluate the effect of standard medical treatment on the progression of atherosclerosis after a myocardial infarction, in an ordinary clinical setting, by measuring the right and left common carotid intima‐media thickness (IMT). The first investigation took place 3–12 months after the index event; the second took place 3·3–8·2 years after the first. In both investigations, the right and left carotid arteries of 102 patients were examined with an ultrasound duplex scanner. Common carotid IMT and calculated cross‐sectional intima‐media area (cIMa) were measured on both sides. More than 90% of the patients were treated with aspirin, beta‐blockers and statins. In the first investigation, IMT and cIMa were significantly greater on the left side compared to the right (IMT: 0·83 ± 0·22 and 0·74 ± 0·18 mm, P<0·001; cIMa: 18·2 ± 5·2 and 16·3 ± 5·1 mm², P<0·001). In the second investigation, IMT on the left side was significantly reduced compared to the first investigation (0·79 ± 0·22 and 0·83 ± 0·22 mm, P<0·05) with a corresponding tendency towards a decrease in cIMa on the same side. In our study, conventional medical treatment after a myocardial infarction in ordinary clinical routines resulted in regression of the common carotid IMT on the left side. The significant side difference in IMT emphasizes the importance of where and how the carotid IMT is measured in studies using this surrogate end point.     

Arterial stiffness in relation to subclinical atherosclerosis

Background Increased arterial stiffness or arteriosclerosis, represents a physiological part of ageing. Atherosclerosis is a process that does not affect the arterial bed uniformly but has a variable local distribution and is frequently superimposed on stiffened vessels. We therefore addressed the question of whether any correlation exists between the general characteristics of arterial stiffness or wave reflection and subclinical atherosclerosis as assessed by carotid intima‐media thickness (IMT) in a sample of healthy subjects. Methods A total of 116 healthy subjects (mean age 55 years, 43 female) were evaluated. Arterial stiffness and wave reflection was assessed with the use of digital volume pulse analysis (DVP) and pulse wave analysis (PWA). Subclinical atherosclerosis was assessed by measurement of IMT. Results Stiffness Index (SI_DVP), the measure of general arterial stiffness correlated significantly with IMT (r = 0·37, P < 0·01). IMT correlated significantly with age (r = 0·5, P < 0·0001), waist to hip ratio (WHR) (r = 0·39, P < 0·0001) and mean blood pressure (BPmean) (r = 0·4, P < 0·0001). IMT did not correlate with measures of wave reflection. SI_DVP correlated significantly with age (r = 0·32, P < 0·005), WHR (r = 0·36, P < 0·0001), BPmean (r = 0·36, P < 0·0001) and measurements of wave reflection. However analysis of a model which included variables that significantly influenced SI_DVP and IMT, such as age, WHR and mean BP showed that arterial stiffness is not independently associated with subclinical atherosclerosis. Conclusions The indices of subclinical atherosclerosis, arterial stiffness and wave reflection, indicate different aspects of vascular status in otherwise healthy subjects     

The influence of inspiratory muscle training on diaphragmatic mobility,pulmonary function and maximum respiratory pressures in morbidly obese individuals: a pilot study

Abstract

Purpose: To investigate whether 12 week inspiratory muscle training (IMT) has any impact on pulmonary function, maximum respiratory pressures and diaphragmatic mobility (DM) in morbidly obese subjects. Method: Thirty-one morbidly obese individuals were assessed. Volunteers were randomised into two groups. The IMT group (n?=?16) followed an IMT protocol for 12 weeks, with a training load of 30% of maximal inspiratory pressure (PImax). The control group (CG) (n?=?15) followed the same protocol but without inspiratory load. Results: A total of 14 subjects performed IMT for 12 weeks. Significant increases in PImax (?86.86?±??20.70?cmH₂O versus ?106.43?±??32.97?cmH₂O, p?<?0.05) and maximal voluntary ventilation (97.84?±?37.06?L/min versus 115.17?±?34.17?L/min, p?<?0.05) were observed in the IMT group when compared to baseline. However, only FIV₁ significantly differed between the IMT group and the CG after the 12 week protocol (3.35?±?0.96?L versus 2.22?±?1.07?L, respectively; p?<?0.05). No significant differences were found in DM after the IMT protocol was performed. Conclusion: IMT improved PImax and altered the FIV₁. These results suggest that the improvements in muscular respiratory efficiency were insufficient to mobilise the diaphragm and modify ventilation mechanics. Pre-operative IMT may be a valuable approach in obese patients for preventing post-operative pulmonary complications. http://clinicaltrials.org -- NCT01449643 -- The Influence of IMT on Diaphragmatic Mobility in Morbidly Obese.

• Implications for Rehabilitation Morbid Obesity

• Morbid obesity is a disabling condition that has a serious negative impact on lung function, respiratory muscle function and quality of life.

• Inspiratory Muscle Training (IMT) is a technique which aims to improve pulmonary expansion and to prevent post surgery complications on morbid obese individuals.

• This study shows significantly increased on maximal inspiratory pressure, maximal voluntary ventilation and promoted changes on spirometric variables after IMT.

     

Correlations between Arteriograph-derived pulse wave velocity and aortic elastic properties by echocardiography

Introduction: There is an increased scientific interest on the evaluation of parameters characterizing aortic elasticity. The current study was designed to compare two characteristics of aortic distensibility: Arteriograph‐derived pulse wave velocity (PWV) and augmentation index standardized to 80 per minutes heart rate (AIx80) and aortic elastic properties by echocardiography. Methods: The study comprised 21 adult healthy volunteers. In all cases, systolic and diastolic ascending aortic diameters were recorded during transthoracic echocardiography in M‐mode at a level 3 cm above the aortic valve from a parasternal long‐axis view. Using forearm blood pressure values, the following aortic elastic properties were calculated: aortic strain, distensibility and stiffness index. All patients were examined by Arteriograph at the same time, as well. Results: The Arteriograph‐derived AIx80 and PWV correlated with aortic strain (R = ?0·495, P = 0·023 and R = ?0·527, P = 0·014, respectively) and aortic stiffness index (R = 0·454, P = 0·039 and R = 0·608, P = 0·003, respectively). Aortic distensibility did not correlated with AIx80 (R = ?0·344, P = 0·127), only with PWV (R = ?0·593, P = 0·005, respectively). Discussion: Low to moderate correlations could be demonstrated between Arteriograph‐derived PWV and aortic elastic properties by echocardiography.     

Measurement of the Intimal Thickness of the Carotid Artery: Comparison Between 40 MHz Ultrasound and Histology in Rats

Common carotid artery intimal thickness (IT) has been shown to be as useful as a measurement of the whole layer of intima-media thickness (IMT) for evaluating the early phase of atherosclerosis. The aim of this study was to elucidate the relationship between high echogenic intimal thickening (HEIT), which was measured using a 40 MHz ultrasound biomicroscope (UBM), and the histologically determined IT in rat carotid arteries. HEIT was estimated in 10 Wistar-Kyoto rats (group I), 15 spontaneous hypertensive rats (SHR) fed a standard diet (group II) and 10 SHR fed a high-fat diet (group III). IT and IMT measurements were determined in Masson trichrome-stained tissues and were compared with the HEIT and IMT evaluated using the UBM. In group I, the HEIT and the IT were 33 ± 4 μm and 12 ± 1 μm, respectively. In group II, the HEIT and the IT were 68 ± 8 μm and 16 ± 2 μm, respectively. In group III, the HEIT and the IT were 65 ± 26 μm and 33 ± 14 μm, respectively. In SHR, the HEIT and the mean IMT measured with echography were significantly correlated with the IT and the IMT that were determined by histologic measurement (r = 0.60, p = 0.003 and r = 0.53, p = 0.01, respectively). Moreover, HEIT may be associated with the intimal pathology and atherosclerotic burden. The HEIT measurement is a noninvasive method that may be used to assess atherosclerosis in humans. (E-mail:younhj@catholic.ac.kr)     

Na+/H+ antiporter activity in peripheral blood lymphocytes of obese and type 2 diabetic patients is increased only in the presence of arterial hypertension

Abstract. The aim of this work is to evaluate whether type 2 diabetes mellitus, obesity and arterial hypertension, three conditions characterized by the presence of insulin resistance, share some common genetic markers. A potential candidate is the Na⁺/H⁺ anti-porter, the increased activity of which is considered a marker of essential hypertension. This ion exchanger seems to be related to the Na⁺/Li⁺ countertransport, that is considered a marker of insulin resistance in essential hypertension and in type 1 diabetes mellitus. In this study we wished to clarify whether the activity of the Na⁺/H⁺ antiporter is increased not only in hypertensive subjects, but also in obese and type 2 diabetic patients, both in the presence and in the absence of arterial hypertension. The activity of the ion exchanger was measured in peripheral blood lymphocytes (PBL) by clamping intracellular pH (pH_i) at 5·8–6·2 and then detecting the rate of the proton efflux after sodium addition. In the absence of arterial hypertension, no significant difference in this parameter was observed in obese and type 2 diabetic patients in comparison with normal subjects. In the presence of arterial hypertension, there was a significant increase in the Na⁺-induced H⁺ efflux at the internal pH (pHi) values of 5·8 and 6·2 both in hypertensive controls and in hypertensive obese and type 2 diabetic patients (P= 0·05–0·0001 vs. normotensive subjects and patients). In particular, H⁺ efflux at pH 5·8 (mmol l^-1 min^-1) was 35·36 ± 2·48 in normotensive and 42·77 ± 1·63 in hypertensive control subjects (P= 0·045), 33·06 ± 1·88 in normotensive and 50·40 ± 5·21 in hypertensive obese patients (P= 0·009), 31·16 ± 1·84 in normotensive and 55·54 ± 5·83 in hypertensive type 2 diabetic patients (P= 0·0001). H⁺ efflux showed a significant correlation with both systolic (at pHi 5·8, r = 0·473, P= 0·001; at pHi 6·2, r = 0·357, P= 0·016) and diastolic blood pressure (at pHi 5·8, r = 0·600, P= 0·0001; at pHi 6·2, r = 0·555, P= 0·0001). Therefore, our study demonstrates that the hyperactivity of the Na⁺/H⁺ exchanger in peripheral blood lymphocytes is also a marker of arterial hypertension in obesity and in type 2 diabetes mellitus, and that the exchanger activity is not increased in these two conditions in the absence of arterial hypertension.     

Is arterial stiffening in Alström syndrome linked to the development of cardiomyopathy?

Background Alström syndrome (AS) is a rare autosomal recessive condition characterized by retinal degeneration, childhood obesity, and severe insulin resistance. Dilated cardiomyopathy of unknown aetiology is a well‐recognized and potentially lethal complication. The aim of this study was to investigate the relationship between vascular function, hyperinsulinaemia and cardiac performance in AS. Materials and methods Fifteen subjects with AS (mean age 21 years, range 10–35) were studied and compared with age‐, sex‐, and blood pressure‐matched healthy controls. Large artery stiffness and wave reflections were assessed in both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid‐femoral and carotid‐radial) and augmentation index (AIX) (Sphygmocor). In AS subjects, left ventricular function was assessed by echocardiography and metabolic parameters including fasting insulin, glucose, lipids and brain natriuretic peptide were also measured. Results Comparing AS subjects vs. controls (mean ± SD), AIX was elevated in AS subjects (18 ± 9% vs. 3 ± 11%, P < 0·0001). No significant changes in brachial PWV (8·1 ± 1·3 m s⁻¹ vs. 7·3 ± 1·1 m s⁻¹, P = 0·14) or aortic PWV (6·5 ± 1·1 m s⁻¹ vs. 6·0 ± 1·0 m s⁻¹, P = 0·26) were observed. AS subjects were hyperinsulinaemic and had disturbances in lipid profiles relative to controls. No correlations were observed between vascular, metabolic and echocardiographic parameters. Conclusions In AS there are alterations in the shape of the central arterial pressure waveform associated with augmented aortic systolic pressure and indicative of increased wave reflection. Unfavourable central arterial haemodynamics in AS may contribute to the development of cardiomyopathy but other aetiological factors are probably involved.     

Gait performance in relation to aortic pulse wave velocity,carotid artery elasticity and peripheral perfusion in healthy older adults

Arterial stiffening is a widely known physiological change that occurs with ageing, but the functional consequences of vascular ageing are unclear. The purpose of this study was to determine whether carotid–femoral pulse wave velocity (PWV), mechanical properties of the carotid and femoral arteries and/or peripheral perfusion was associated with gait performance measured using a 400‐m walk test. Twenty‐one healthy older (68 ± 5 years) adults without cardiovascular disease participated in this study. Applanation tonometry was used to measure PWV, and Doppler ultrasound was used to measure arterial wall properties of the left common carotid and common femoral artery along with femoral blood flow. The median walk distance in the first 2 min of the test was 585 ft, and the overall gait speed was 1·5 m s^?1. Gait performance was inversely correlated with PWV (distance: r = ‐0·51; speed: r = ?0·48; P<0·05) and carotid artery stiffness index β (distance: r = ?0·56; speed: r =  ? 0·51; P<0·05) after adjustment for age, body mass index, waist circumference and systolic blood pressure. No significant correlations were found between gait performance and femoral artery stiffness index β or femoral artery blood flow. These results found higher central arterial stiffness, as assessed by segmental arterial stiffness or local arterial wall properties, is associated with lower gait performance in older adults independent of other confounders.     

Factor VIII deficiency does not protect against atherosclerosis

See also Makris M, van Veen JJ. Reduced cardiovascular mortality in hemophilia despite normal atherosclerotic load. This issue, pp 20–2; Zwiers M, Lefrandt JD, Mulder DJ, Smit AJ, Gans ROB, Vliegenthart R, Brands‐Nijenhuis AVM, Kluin‐Nelemans JC, Meijer K. Coronary artery calcification score and carotid intima–media thickness in patients with hemophilia. This issue, pp 23–9. Summary. Background: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. Objectives: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. Methods: Fifty‐one obese (body mass index [BMI] ≥ 30 kg m^?2) and 47 non‐obese (BMI ≤ 25 kg m^?2) hemophilia A patients, and 42 obese and 50 matched non‐obese male controls were included. Carotid and femoral intima–media thickness [IMT] and brachial flow‐mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. Results: The overall population age was 50 ± 13 years. Carotid IMT was increased in obese subjects (0.77 ± 0.22 mm) as compared with non‐obese subjects (0.69 ± 0.16 mm) [mean difference 0.07 mm (95% confidence interval [CI] 0.02–0.13, P = 0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02 mm [95% CI ? 0.07–0.11, P = 0.67], and mean difference of 0.06 mm [95% CI ? 0.13–0.25, P = 0.55], respectively). Thirty‐five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P = 0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84% ± 3.24% and 5.32% ± 2.37%, P = 0.45). Conclusion: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary.     

Glucose turnover and intima media thickness of internal carotid artery in type 2 diabetes offspring

Background First‐degree offspring (OFF) of type 2 diabetic (T2DM) patients bear a ~40% lifetime risk of developing T2DM. They are insulin resistant and carry a risk of premature atherosclerosis, the extent of which can be estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this study examines parameters of glucose and lipid metabolism, insulin sensitivity, beta cell function (BCF) and IMT with their interrelationships in middle‐aged OFF. Materials and methods T2DM‐OFF (n = 18, 14f/4m, 45·6 ± 2·1 years, BMI: 26 ± 1 kg m^?2) were compared with 18 matching humans without a family history of diabetes (CON; 14f/4m, 44·5 ± 2·1 years, BMI: 24 ± 1 kg m^?2; each P > 0·30), all with normal glucose tolerance as tested by three‐hour (75 g) oral glucose tolerance tests (OGTT). Two‐hour hyperinsulinaemic (40 mU min^?1·m^?2)isoglycaemic clamp tests were performed with simultaneous measurement of endogenous glucose (D‐[6,6‐²H₂]glucose) production (EGP). IMT [internal (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by Adaptation Index (AI). Results Before and during OGTT, both groups were similar in plasma glucose, insulin, C‐peptide and free fatty acids (FFA), whereas OFF showed ~30% lower (P < 0·03) fasting plasma triglycerides before OGTT. During hyperinsulinaemic clamps, insulin sensitivity was ~38% lower (P < 0·03) in OFF who showed higher plasma FFA (44 ± 9 µmol L^?1) than CON (26 ± 3 µmol L^?1, P < 0·05) after 90 min. EGP was similar in both groups. OFF had 38% (P < 0·007) reduced AI. ICA‐IMT was ~18% higher in OFF (P < 0·002), but did not correlate with insulin sensitivity. Conclusion The data obtained show middle‐aged T2DM‐OFF with normal glucose tolerance displaying reduced total insulin sensitivity and impaired beta cell function, which relates to impaired insulin‐dependent suppression of plasma FFA and increased ICA‐IMT.     

Arterial tension time reflects subclinical atherosclerosis, arterial stiffness and stroke volume

Objective: To introduce and evaluate a new haemodynamic parameter known as arterial tension time (ATT) and study whether ATT is associated with traditional cardiovascular risk factors as well as with indices of arterial stiffness, cardiac pump function and subclinical atherosclerosis. Methods: Arterial tension time was measured from the whole‐body impedance cardiography (ICG) signal and defined as the time difference between the onset of arterial distension induced by stroke volume (SV) and maximal integrated arterial distension. As measures of subclinical atherosclerosis and arterial stiffness, carotid artery intima‐media thickness (IMT), Young’s elastic modulus (YEM), arterial stiffness index (ASI) and carotid artery compliance (CAC) were assessed with ultrasound in 336 Finnish adults (aged 46–76 years, 43·2% men) participating in the Health 2000 Survey. In addition, pulse wave velocity (PWV) and stroke volume index (SI), as indices of arterial stiffness and cardiac pump function, were assessed with ICG. Results: Arterial tension time was associated inversely with PWV, IMT, YEM and ASI (P<0·002 for all) and directly with SI and CAC (P<0·001 for both). Age, systolic blood pressure, diastolic blood pressure and fasting glucose were independent determinants of decreased ATT (P<0·04 for all). Moreover, accumulation of cardiovascular risk factors was associated with the decrease in ATT (P for trend <0·001). Conclusion: Decreased ATT was associated with increased arterial stiffness, increased subclinical atherosclerosis and decreased SV. Current results suggest that ATT provides simultaneous information on several aspects of cardiovascular structure and function and could possibly serve as a new integrated parameter for cardiovascular risk stratification.     

Hydration status influences the measurement of arterial stiffness

Consensus guidelines have attempted to standardize the measurement and interpretation of pulse wave velocity (PWV); however, guidelines have not addressed whether hydration status affects PWV. Moreover, multiple studies have utilized heat stress to reduce arterial stiffness which may lead to dehydration. This study utilized two experiments to investigate the effects of dehydration on PWV at rest and during passive heat stress. In experiment 1, subjects (n = 19) completed two trials, one in which they arrived euhydrated and one dehydrated (1·2[1·0]% body mass loss). In experiment 2, subjects (n = 11) began two trials euhydrated and in one trial did not receive water during heat stress, thus becoming dehydrated (1·6[0·6]% body mass loss); the other trial subjects remained euhydrated. Using Doppler ultrasound, carotid‐to‐femoral (central) and carotid‐to‐radial (peripheral) PWVs were measured. PWV was obtained at a normothermic baseline, and at a 0·5°C and 1°C elevation in rectal temperature (via passive heating). In experiment 1, baseline central PWV was significantly higher when euhydrated compared to dehydrated (628[95] versus 572[91] cm s^?1, respectively; P<0·05), but peripheral PWV was unaffected (861[117] versus 825[149] cm s^?1; P>0·05). However, starting euhydrated and becoming dehydrated during heating in experiment 2 did not affect PWV measures (P>0·05), and independent of hydration status peripheral PWV was reduced when rectal temperature was elevated 0·5°C (?74[45] cm s^?1; P<0·05) and 1·0°C (?70[48] cm s^?1; P<0·05). Overall, these data suggest that hydration status affects measurements of central PWV in normothermic, resting conditions. Therefore, future guidelines should suggest that investigators ensure adequate hydration status prior to measures of PWV.