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.     

The relationship between arterial stiffness and the lifestyle habits of female athletes after retiring from competitive sports: a prospective study

This study investigated the relationship between changes in arterial stiffness and the lifestyle habits of endurance athletes after retiring from competition. The subjects were 10 female university endurance athletes. We used formPWV/ABI^® as an index for arterial stiffness and measured brachial‐ankle pulse‐wave velocity (baPWV) directly before subjects retired (0Y) and at 2 years after retirement (2Y). Furthermore, to investigate the relationship between arterial stiffness and lifestyle habits 2 years later, Lifecorder ^® PLUS was used to measure physical activity levels, hours of sleep were surveyed using a questionnaire, and a food intake survey was conducted using Excel Eiyoukun Food Frequency Questionnaire Based on Food Group, FFQg Ver. 3.5. We found that baPWV increased significantly from 0Y to 2Y (P<0·05). Furthermore, negative correlations were observed between 2Y baPWV and step count as the physical activity index (r = ?0·653, P<0·05) and moderate physical activity (r = ?0·663, P<0·05). With regard to lifestyle habits that affected the amount of increase in baPWV from 0Y to 2Y (ΔbaPWV), negative correlations were noted between the step count (r = ?0·690, P<0·05) and total physical activity (r = ?0·657, P<0·05). However, no significant correlations were observed between 2Y baPWV and ΔbaPWV with food intake or hours of sleep. The results of this study suggested that physical activity was a lifestyle habit that inhibited an increase in arterial stiffness after retirement from competition and that having a high step count or engaging in physical activity for long periods of time in particular was useful in this regard.     

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.     

Acute resistance exercise using free weights on aortic wave reflection characteristics

Aortic wave reflection characteristics such as the augmentation index (AIx), wasted left ventricular pressure energy (ΔE_w) and aortic haemodynamics, such as aortic systolic blood pressure (ASBP), strongly predict cardiovascular events. The effects of acute resistance exercise (ARE) using free‐weight exercises on these characteristics are unknown. Therefore, we sought to determine the effects of acute free‐weight resistance exercise on aortic wave reflection characteristics and aortic haemodynamics in resistance‐trained individuals. Fifteen young, healthy resistance‐trained (9 ± 3 years) individuals performed two randomized sessions consisting of an acute bout of free‐weight resistance exercise (ARE) or a quiet control (CON). The ARE consisted of three sets of 10 repetitions at 75% one repetition maximum for squat, bench press and deadlift. In CON, the participants rested in the supine position for 30 min. Measurements were made at baseline before sessions and 10 min after sessions. A two‐way ANOVA was used to compare the effects of condition across time. There were no significant interactions for aortic or brachial blood pressures. Compared to rest, there were significant increases in augmentation pressure (rest: 5·7 ± 3·0 mmHg; recovery: 10·4 ± 5·7 mmHg, P = 0·002), AIx (rest: 116·8 ± 4·2%; recovery: 123·2 ± 8·4%, P = 0·002), AIx normalized at 75 bpm (rest: 5·2 ± 7·6%; recovery: 27·3 ± 13·2%, P<0·0001), ΔE_w (rest: 1215 ± 674 dynes s cm^?2; recovery: 2096 ± 1182 dynes s cm^?2, P = 0·008), and there was a significant decrease in transit time of the reflected wave (rest: 150·7 ± 5·8 ms; recovery 145·5 ± 5·6 ms, P<0·001) during recovery from ARE compared to CON. These data suggest that ARE using free‐weight exercises may have no effect on aortic and brachial blood pressure but may significantly alter aortic wave reflection characteristics.     

Relationship between peak cardiac pumping capability and indices of cardio-respiratory fitness in healthy individuals

Cardiac power output (CPO) is a unique and direct measure of overall cardiac function (i.e. cardiac pumping capability) that integrates both flow‐ and pressure‐generating capacities of the heart. The present study assessed the relationship between peak exercise CPO and selected indices of cardio‐respiratory fitness. Thirty‐seven healthy adults (23 men and 14 women) performed an incremental exercise test to volitional fatigue using the Bruce protocol with gas exchange and ventilatory measurements. Following a 40‐min recovery, the subjects performed a constant maximum workload exercise test at or above 95% of maximal oxygen consumption. Cardiac output was measured using the exponential CO₂ rebreathing method. The CPO, expressed in W, was calculated as the product of the mean arterial blood pressure and cardiac output. At peak exercise, CPO was well correlated with cardiac output (r = 0·92, P<0·01), stroke volume (r = 0·90, P<0·01) and peak oxygen consumption (r = 0·77, P<0·01). The coefficient of correlation was moderate between CPO and anaerobic threshold (r = 0·47, P<0·01), oxygen pulse (r = 0·57, P<0·01), minute ventilation (r = 0·53, P<0·01) and carbon dioxide production (r = 0·56, P<0·01). Small but significant relationship was found between peak CPO and peak heart rate (r = 0·23, P<0·05). These findings suggest that only peak cardiac output and stroke volume truly reflect CPO. Other indices of cardio‐respiratory fitness such as oxygen consumption, anaerobic threshold, oxygen pulse, minute ventilation, carbon dioxide production and heart rate should not be used as surrogates for overall cardiac function and pumping capability of the heart.     

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.     

Relationships between central arterial stiffness,lean body mass,and absolute and relative strength in young and older men and women

Relationships between muscular strength and arterial stiffness as well as between muscle mass and arterial stiffness have been observed suggesting a link between the neuromuscular system and vascular health. However, the relationship between central arterial stiffness and absolute and relative strength along with muscle mass has not been investigated in both sexes across a broad age range. The purpose of this study was to examine the relationship between central arterial stiffness and absolute and relative strength as well as between central arterial stiffness and lean body mass (LBM) in men and women across a broad age range. LBM, central arterial stiffness and strength were measured on 36 men and 35 women between the ages of 18 and 75 years. Strength was measured on five machine resistance exercises and summed as one measure of overall strength (absolute strength). Relative strength was calculated as total strength divided by LBM (relative strength). Central arterial stiffness was inversely related to both absolute (r = ?0·230; P = 0·029) and relative strength (r = ?0·484; P < 0·001) but not LBM (r = 0·097; P = 0·213). The relationship between central arterial stiffness and relative strength was attenuated but still present when controlling for either age, per cent body fat, LBM or mean arterial pressure. These results suggest that, across a wide age range, the expression of relative muscular strength has a stronger relationship with central arterial stiffness compared to either LBM or absolute strength. This suggests that muscle function more than muscle mass may be coupled with vascular health.     

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.     

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.     

Lipoprotein (a) and acute-phase response in patients with vestibular neuronitis

Background Vestibular neuronitis (VN) is a relatively common condition characterized by the acute onset of vertigo, nausea and vomiting, in the absence of auditory or central nervous system involvement. The exact aetiology (inflammatory, viral or vascular?) remains obscure. Lipoprotein (a) [Lp(a)] is an atherogenic particle. Its serum levels are mainly genetically determined and vary widely between individuals. Whether Lp(a) is consistently a positive acute‐phase reactant is controversial. Purpose We evaluated the alterations in lipidaemic parameters and serum biological markers (including acute‐phase reactants) in adult patients presenting acutely with VN. Subjects and methods A total of 34 consecutive VN patients (24 men and 11 women) and 37 apparently healthy controls (25 men and 12 women) were studied. Laboratory evaluation was performed during the acute episode and 6 months later (stable state). Results Serum Lp(a) concentrations were significantly lower at the time of presentation (median value 6·4 vs. 16·4 mg dL^?1 in the stable state, P < 0·001), whereas fibrinogen levels were significantly higher during the acute episode than in the stable state (median value 293·0 vs. 202·0 mg dL^?1, respectively, P < 0·0001). During the acute episode, plasma fibrinogen correlated with CRP levels (Spearman r = 0·84, P < 0·0001). By contrast, inverse correlations were noted between Lp(a) levels and CRP (Spearman r = ?0·47, P = 0·007) as well as between Lp(a) and fibrinogen levels (Spearman r = ?0·35, P = 0·05). Conclusion Vestibular neuronitis episodes are associated with evidence of an acute inflammatory response as reflected by significant elevations in plasma fibrinogen and CRP concentrations, whereas Lp(a) behaves as a negative acute‐phase reactant.     

Peripheral blood flow changes in response to postexercise cold water immersion

This study compared the effect of postexercise water immersion (WI) at different temperatures on common femoral artery blood flow (CFA), muscle (total haemoglobin; tHb) and skin perfusion (cutaneous vascular conductance; CVC), assessed by Doppler ultrasound, near‐infrared spectroscopy (NIRS) and laser Doppler flowmetry, respectively. Given that heat stress may influence the vascular response during cooling, nine men cycled for 25 min at the first ventilatory threshold followed by intermittent 30‐s cycling at 90% peak power until exhaustion at 32·8 ± 0·4°C and 32 ± 5% RH. They then received 5‐min WI at 8·6 ± 0·2°C (WI₉), 14·6 ± 0·3°C (WI₁₅), 35·0 ± 0·4°C (WI₃₅) or passive rest (CON) in a randomized, crossover manner. Heart rate (HR), mean arterial pressure (MAP), muscle (T_mu), thigh skin (T_thigh), rectal (T_re) and mean body (T_body) temperatures were assessed. At 60 min postimmersion, decreases in T_re after WI₃₅ (?0·6 ± 0·3°C) and CON (?0·6 ± 0·3°C) were different from WI₁₅ (?1·0 ± 0·3°C; P<0·05), but not from WI₉ (?1·0 ± 0·3°C; P = 0·074–0·092). WI₉ and WI₁₅ had reduced T_body, T_thigh and T_mu compared with WI₃₅ and CON (P <0·05). CFA, tHb and CVC were lower in WI₉ and WI₁₅ compared with CON (P<0·05). tHb following WI₉ remained lower than CON (P = 0·044) at 30 min postimmersion. CVC correlated with tHb during non‐cooling (WI₃₅ and CON) (r² = 0·532; P<0·001) and cooling recovery (WI₉ and WI₁₅) (r² = 0·19; P = 0·035). WI₉ resulted in prolonged reduction in muscle perfusion. This suggests that CWI below 10°C should not be used for short‐term (i.e. <60 min) recovery after exercise.     

Elevated VEGF-plasma levels in young patients with mild essential hypertension

Background Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Vascular endothelial cell growth factor (VEGF) is currently discussed as a possible mediator of inflammation. To investigate the hypothesis that VEGF plays a role as an inflammatory mediator in EH we performed the present pilot study of young patients in a very early stage of EH. Materials and methods 15 young patients with mild EH [33·8 ± 7·3 years, systolic blood pressure (SBP): 143·8 ± 10·5 mmHg, diastolic blood pressure (DBP): 88·2 ± 11·1 mmHg, mean arterial pressure (MAP) 106·6 ± 10·4 mmHg] and 15 healthy controls (31·7 ± 10·6 years) were examined. Blood was drawn from a peripheral vein and serum levels of VEGF, monocyte‐chemoattractant‐protein (MCP)‐1, high‐sensitivity C‐reactive protein (hsCRP), interleukin (IL)‐6, and tumour‐necrosis‐factor (TNF)‐α were measured via commercially available enzyme‐linked immunoassays. Results Hypertensives showed increased plasma levels of VEGF (P < 0·05) and MCP‐1 (P < 0·05). VEGF positively correlated with MAP (r = 0·46, P < 0·05) and MCP‐1 (r = 0·63, P < 0·01). Multivariate analysis demonstrated VEGF to be an independent predictor of MCP‐1 levels. Furthermore, hypertensives had higher levels of hsCRP (P < 0·01), IL‐6 (P < 0·001) and TNF‐α (P < 0·05). IL‐6 levels correlated with SBP (r = 0·59, P < 0·001), DBP (r = 0·67, P < 0·001) and MAP (r = 0·46, P < 0·001). A significant positive correlation was also found between hsCRP levels and SBP (r = 0·39, P < 0·05). Conclusions This pilot study demonstrates that in an early state of EH, inflammatory pathways have already been activated. Besides classical pro‐inflammatory cytokines, VEGF serum levels are significantly elevated. The positive correlation of VEGF with MCP‐1 is suggestive for the already described induction of MCP‐1 via VEGF.     

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R–R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R–R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r=0·76 and r=0·85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean ± SEM; 3·5 ± 0·3 versus 11·2 ± 1·4 ms mmHg^–1; P<0·01) and spontaneous sequence analysis (10·3 ± 0·8 versus 31·5 ± 2·3 ms mmHg^–1; P<0·001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7·9 ± 1·4 versus 6·7 ± 0·8 ms mmHg^–1; P=0·27) or spontaneous sequence methods (21·8 ± 2·7 versus 20·0 ± 2·1 ms mmHg^–1; P=0·24). BRG was correlated during RB and SB protocols (r=0·80; P<0·0001). ARMA and spontaneous BRG estimates were correlated (r=0·79; P<0·0001), with spontaneous sequence values being consistently larger (P<0·0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.     

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.     

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.     

Ovariectomy increases vascular calcification via the OPG/RANKL cytokine signalling pathway

Background Observational studies suggest a strong relationship between menopause and vascular calcification. Receptor activator of nuclear factor‐κΒ ligand (RANKL) and osteoprotegerin (OPG) are critical regulators of bone remodelling and modulate vascular calcification. We assessed the hypothesis that ovariectomy increases vascular calcification via the OPG/RANKL axis. Materials and methods Age‐matched sexually mature rabbits were randomized to ovariectomy (OVX, n = 12) or sham procedure (SHAM, n = 12). One month post‐procedure, atherosclerosis was induced by 15 months 0·2%‐cholesterol diet and endothelial balloon denudations (at months 1 and 3). Aortic atherosclerosis was assessed in vivo by magnetic resonance imaging (MRI) at months 9 and 15. At sacrifice, aortas were harvested for ex vivo microcomputed tomography (µCT) and molecular analysis of the vascular tissue. Results Vascular calcification density and calcific particle number were significantly greater in OVX than SHAM (8·4 ± 2·8 vs. 1·9 ± 0·6 mg cm^?3, P = 0·042, and 94 ± 26 vs. 33 ± 7 particles cm^?3, P = 0·046, respectively). Calcification morphology, as assessed by the arc angle subtended by the largest calcific particle, showed no difference between groups (OVX 33 ± 7° vs. SHAM 33 ± 5°, P = 0·99). By Western blot analysis, OVX increased the vascular OPG:RANKL ratio by 66%, P = 0·029, primarily by decreasing RANKL (P = 0·019). At month 9, MRI demonstrated no difference in atheroma volume between OVX and SHAM, and no significant change was seen by the end of the study. Conclusions In contrast to bone, vascular OPG:RANKL ratio increased in response to ovariectomy with a corresponding fourfold increase in arterial calcification. This diametrical organ‐specific response may explain the comorbid association of osteoporosis with calcifying atherosclerosis in post‐menopausal women.     

Predictors of the intima‐media thickness of carotid artery in asymptomatic newly detected severe hypercholesterolemic patients

Background: Data about predictors of intima‐media thickness (IMT) of common carotid artery (CCA) in asymptomatic subjects with newly detected severe hypercholesterolemia is scarce. Aim: This research is aimed at studying the predictors of the IMT of CCA among basic atherogenic risk biomarkers – lipid [total cholesterol (TC), triglycerides, high‐density lipoprotein cholesterol, low‐density lipoprotein (LDL) cholesterol, Apolipoprotein‐B, Apolipoprotein‐Ai, Apolipoprotein‐B/A₁ index] and non‐lipid, [asymmetric dimethylarginine (ADMA), total homocysteine, cell adhesion molecules] in asymptomatic subjects with newly detected severe hypercholesterolemia. Methods: Two hundred and fifty asymptomatic patients with severe, newly hypercholesterolemia and 200 controls were evaluated. Hypercholesterolemia was defined as TC > 7·5 mm and LDL cholesterol > 4·9 mm . The ADMA and cell adhesion molecules were determined by ELISA and total homocysteine by high‐performance liquid chromatography. Results: There was significant difference between the two groups in respect to all lipid biomarkers (P<0·001). Hypercholesterolemic patients had significantly higher level of ADMA, sVCAM‐1, sICAM‐1, IMT (P<0·001), whereas no significant difference was found between two groups with respect to total homocysteine, P‐selectin and E‐selectin (P>0·05). A strong positive correlation between IMT mean and age (r_xy = 0·714; P<0·001), Apolipoprotein‐B (r_xy = 0·706; r_xy < 0·001), Apolipoprotein‐B/A₁ (r_xy = 0·324; P<0·001), ADMA (r_xy = 0·603; P<0·001) was found. The subsequent linear and multiple regression analysis selected age and Apolipoprotein‐B as most significant factors in relation to IMT mean. Apolipoprotein‐B is a better factor for assessment of risk, as LDL cholesterol underestimates the risk in asymptomatic subjects with newly detected severe hypercholesterolemia, until more rapid and feasible methods for measurement of small and dense LDL are available.     

Interrelationships between indices of longitudinal movement of the common carotid artery wall and the conventional measures of subclinical arteriosclerosis

Our objective was to study the interrelationships between longitudinal movement of the wall of the common carotid artery and the conventional measures of arteriosclerosis in a large and well-characterized study population. Successful longitudinal movement analyses were performed on 292 subjects. The peak-to-peak and retrograde amplitudes of the longitudinal movement were directly correlated with carotid artery distensibility (r = 0·21, P<0·001 and r = 0·23, P<0·001, respectively) and inversely correlated with pulse wave velocity (r = −0·14, P<0·05 and r = −0·17, P<0·01, respectively). All longitudinal motion parameters were independent of brachial flow-mediated dilatation and intima-media thickness. Our findings indicate that arterial stiffening modulates longitudinal movement and, therefore, measurement of longitudinal movement can be of value in the assessment of vascular health.     

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects

Background To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat‐derived factor retinol‐binding protein‐4 (RBP‐4) in HIV‐infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Materials and methods Fourteen HIV‐positive, HAART‐naïve subjects were compared with 10 HIV‐negative healthy controls and reassessed after a 1‐year treatment with HAART. Plasma visfatin and RBP‐4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X‐ray absorptiometry (DXA). Homeostasis model assessment (HOMA‐IR) was assessed using insulin and glucose levels. Results Visfatin and RBP‐4 levels in HIV‐positive subjects were comparable with those of HIV‐negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6·9‐fold and 7·1‐fold increase of visfatin and RBP‐4 levels (+54·0 ± 9·7 ng mL^?1, P < 0·0001 and +95·3 ± 31·7 ng mL^?1, P < 0·01), respectively. Leptin (?2·7 ± 1·6 ng mL^?1, P = 0·054) was unchanged and adiponectin (?2·8 ± 0·7 µg mL^?1, P < 0·01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP‐4 (r = 0·78, P = 0·001), fat‐free mass (FFM, r = 0·75, P < 0·05) and change of HOMA‐IR (r = 0·64, P < 0·05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Conclusions Treatment with HAART induced a pronounced increase of plasma visfatin and RBP‐4 as well as a decrease of adiponectin in HIV‐infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.     

A methodological study of arterial wall function using ultrasound technique

We aimed to establish reference values for three important properties of the arterial wall using a conventional ultrasound scanner. We measured: (1) intima–media thickness (IMT) of the carotid arteries with the internal trace function of the ultrasound system; (2) wall stiffness by pulsatile diameter changes in the right common carotid artery assessed by M-mode; and (3) endothelial function expressed as flow-mediated dilatation (FMD) of the brachial artery. IMT and wall stiffness measurements and reproducibility were compared with those obtained by external analysing systems. All variables were obtained in healthy subjects (n = 20), 29–53 years old. IMT increased with age (P<0·01). There was no difference in IMT between men and women. The inter-operator variability for measuring IMT was 6–9%. The same order of reproducibility was obtained with an external PC-based analysing system. Regarding wall stiffness, no correlation was found with age, nor any difference between men and women. A low intra-operator variability (CV < 10%) was found for measurements of wall stiffness with both M-mode and an external wall tracking system. FMD of the brachial artery diminished with age (P<0·01). There was a relation between FMD and brachial artery size (P<0·01) and, therefore, as men have larger arterial diameters (P<0·01), smaller FMD in men. We conclude that it is possible to characterize arterial wall function non-invasively in an adequately reproducible manner using a conventional ultrasound system in healthy middle-aged men and women.