An in vivo study of isotropic and anisotropic wall stress in a hyperelastic holzapfel-gasser-ogden model in the human abdominal aorta: Effects of age and sex.

Background: Wall stress of the abdominal aorta (AA) appears to be an important factor in the assessment of risk for rupture based on the relationship between blood pressure and aortic diameter. We therefore investigated peak wall stress as well as isotropic and anisotropic wall stress of AA. Methods: Thirty healthy adults (male = 15) were included. Pulsatile diameter changes were determined non-invasively by an echo-tracking system, and intra-aortic pressure was measured simultaneously. A computer based mechanical model was used to compute the isotropic and anisotropic components of circumferential and longitudinal stresses. Results: Elderly males had higher total wall stress and a higher isotropic stress component in the circumferential direction and higher total longitudinal wall stress than elderly females. The isotropic component increased with age in males but not in females, whereas the anisotropic component decreased with age in both sexes. Conclusion: We found that isotropic and anisotropic properties of the abdominal aortic wall differ between young and elderly participants and between the sexes. A possible explanation could relate to chemical alterations (e.g., due to sex hormones) and changes over time in the physical distribution of fibers. Modeling of wall stress components of the human AA may contribute to a better understanding of elastin-collagen interactions during remodeling of the aortic wall.

Vascular Adaptation to Indoor Cycling Exercise in Premenopausal Women.

The early vascular adaptation to indoor cycling, a popular activity at many fitness centres, is incompletely evaluated. Forty two healthy women (21-45 years) underwent measurements of arterial wall properties and geometry as well as a maximal bicycle exercise test before and after a 3 months period during which 21 of the women joined indoor cycling classes at a gym 2-3 times per week, while 21 women served as time controls. Peak work load increased by in average 16% (p<0.001) and ascending aortic diameter by 4% (p<0.01) in the exercise group, while unchanged in control group. The exercise intervention had no significant influence on the local intima-media thickness, blood pressure or the pulse pressure wave configuration while the carotid artery distensibility (p<0.05) was higher after the intervention. There was a positive correlation between change in (Δ) peak work load and Δ-diameter of tubular ascending aorta (r=0.42, p<0.01) in the exercise group. In conclusion, after only 3 months of bicycle exercise training, signs of central arterial remodelling were seen in premenopausal women, which was associated to improvement in exercise capacity.

Visualizing and quantifying flow stasis in abdominal aortic aneurysms in men using 4D flow MRI.

PURPOSE: To examine methods for visualizing and quantifying flow stasis in abdominal aortic aneurysms (AAA) using 4D Flow MRI. METHODS: Three methods were investigated: conventional volumetric residence time (VRT), mean velocity analysis (MVA), and particle travel distance analysis (TDA). First, ideal 4D Flow MRI data was generated using numerical simulations and used as a platform to explore the effects of noise and background phase-offset errors, both of which are common 4D Flow MRI artifacts. Error-free results were compared to noise or offset affected results using linear regression. Subsequently, 4D Flow MRI data for thirteen (13) subjects with AAA was acquired and used to compare the stasis quantification methods against conventional flow visualization. RESULTS: VRT (R2 = 0.69) was more sensitive to noise than MVA (R2 = 0.98) and TDA (R2 = 0.99) at typical non-contrast signal-to-noise ratio levels (SNR = 20). VRT (R2 = 0.14) was more sensitive to background phase-offsets than MVA (R2 = 0.99) and TDA (R2 = 0.96) when considering a 95% effective background phase-offset correction. Qualitatively, TDA outperformed MVA (Wilcoxon p < 0.005, mean score improvement 1.6/5), and had good agreement (median score 4/5) with flow visualizations. CONCLUSION: Flow stasis can be quantitatively assessed using 4D Flow MRI. While conventional residence time calculations fail due to error accumulation as a result of imperfect measured velocity fields, methods that do not require lengthy particle tracking perform better. MVA and TDA are less sensitive to measurement errors, and TDA generates results most similar to those obtained using conventional flow visualization.

Longitudinal Movement of the Common Carotid Artery Wall: New Information on Cardiovascular Aging.

Putative changes in the multiphasic pattern of longitudinal movement of the common carotid artery wall in the normal aging process are unknown. The aim of this study was to explore the phases, and resulting patterns, of the longitudinal movement of the intima-media complex of the human common carotid artery with respect to age and gender. One hundred thirty-five healthy non-smoking patients of different ages were investigated using in-house-developed ultrasound methods. The patterns of longitudinal movement seen in middle-aged and older patients were markedly different from those commonly seen in young patients, including the appearance of two additional phases of motion and, thus, new complex patterns. The displacement and maximum velocity of one of the phases, occurring at the time of aortic valve closure, increased quadratically with age in both men and women.

Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain.

AIMS: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. METHODS: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25-29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. RESULTS: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. - 22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05). CONCLUSION: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons. Trial registration ClinicalTrials.gov identifier NCT 01049737.

Plasma cholesterol lowering in an AngII­infused atherosclerotic mouse model with moderate hypercholesterolemia.

Atherosclerosis is the main underlying causes of cardiovascular disease. There is a well­established association between high blood cholesterol levels and the extent of atherosclerosis. Furthermore, atherosclerosis has been proposed to augment abdominal aortic aneurysm (AAA) formation. As patients with AAA often have parallel atherosclerotic disease and are therefore often on cholesterol­lowering therapy, it is not possible to fully address the independent effects of plasma cholesterol lowering (PCL) treatment on AAA. The present study investigated the effect of angiotensin II (AngII)­infusion in modestly hypercholesterolemic Ldlr­/­Apob100/100Mttpflox/floxMx1­Cre mice with or without PCL treatment on a morphological and molecular level, in terms of atherosclerosis and AAA development. AngII infusion in the study mice resulted in an increased atherosclerotic lesion area and increased infiltration of inflammatory leukocytes, which was not observed in mice with PCL induced prior to AngII infusion. This suggested that AngII infusion in this mouse model induced atherosclerosis development, and that plasma cholesterol levels represent a controlling factor. Furthermore, AngII infusion in Ldlr­/­Apob100/100Mttpflox/floxMx1­Cre mice caused a modest aneurysmal phenotype, and no differences in AAA development were observed between the different study groups. However, the fact that modest hypercholesterolemic mice did not develop AAA in a classical aneurysmal model indicated that plasma cholesterol levels are important for disease development.

The association between circulating endostatin and a disturbed circadian blood pressure pattern in patients with type 2 diabetes.

BACKGROUND: Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure. METHODS: We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n = 593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a >10% difference between day- and night-time blood pressures. RESULTS: Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (mean ± standard deviation: 62.6 ± 1.8 µg/l vs. 58.7 ± 1.6 µg/l, respectively, p = .007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin -0.01, 95% CI, -0.02-(-0.001), p = .03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events. CONCLUSION: We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.

Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow.

Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 ± 3.0 y.o.) and 20 old normal males (70.9 ± 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3-19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 ± 1.8 mJ, old = 6.4 ± 2.4 mJ, p < 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease.

Computer-Aided Evaluation of Blood Vessel Geometry From Acoustic Images.

A method for computer-aided assessment of blood vessel geometries based on shape-fitting algorithms from metric vision was evaluated. Acoustic images of cross sections of the radial artery and cephalic vein were acquired, and medical practitioners used a computer application to measure the wall thickness and nominal diameter of these blood vessels with a caliper method and the shape-fitting method. The methods performed equally well for wall thickness measurements. The shape-fitting method was preferable for measuring the diameter, since it reduced systematic errors by up to 63% in the case of the cephalic vein because of its eccentricity.

Left Ventricular Adaptation to 12 Weeks of Indoor Cycling at the Gym in Untrained Females.

Cross-sectional studies provide evidence of larger cardiac dimensions and mass in endurance trained than in untrained females. Much less is known regarding adaptations in cardiac function following training in untrained subjects. We aimed to study left ventricular (LV) adaptation to indoor cycling in previously untrained females, in regard of LV dimensions, mass and function. 42 sedentary females were divided into 2 equally sized groups, either training indoor cycling at regular classes at a local gym for 12 weeks, in average 2.6 times per week, or maintaining their sedentary lifestyle. Echocardiography at rest and a maximal exercise test were performed before and after the intervention. Exercise capacity increased in average 16% in the exercise group (p<0.001), together with decreased heart rate at rest (p<0.05) and at 120 watts steady-state (p<0.001). There were no difference in systolic or diastolic function following the intervention and minimal increases in LV internal diameter in diastole (+1 mm, p<0.01). LV mass was unchanged with training (137±25 vs. 137±28 g, p=0.911). Our findings indicate that attending indoor cycling classes at a gym 2-to-3 times per week for 12 weeks is enough to improve exercise capacity, while a higher volume of training is required to elicit cardiac adaptations.

ADAMTS-1 in abdominal aortic aneurysm.

INTRODUCTION: Extracellular matrix degradation is a hallmark of abdominal aortic aneurysm (AAA). Among proteases that are capable of degrading extracellular matrix are a disintegrin and metalloproteases with thrombospondin motifs (ADAMTS). Pathogenesis of these proteases in AAA has not been investigated until date. METHODS AND RESULTS: Human aneurysmal and control aortas were collected and analyzed with RT-PCR measuring the ADAMTS-1, 4,5,6,8,9,10,13,17 and ADAMTSL-1. Expression of a majority of the investigated ADAMTS members on mRNA level was decreased in aneurysm compared to control aorta. ADAMTS-1 was one of the members that was reduced most. Protein analysis using immunohistochemistry and western blot for localization and expression of ADAMTS-1 revealed that ADAMTS-1 was present predominantly in areas of SMCs and macrophages in aneurysmal aorta and higher expressed in AAA compared to control aortas. The role of ADAMTS-1 in AAA disease was further examined using ADAMTS-1 transgenic/apoE-/- mice with the experimental angiotensin II induced aneurysmal model. Transgenic mice overexpressing ADAMTS-1 showed to be similar to ADAMTS-1 wild type mice pertaining collagen, elastin content and aortic diameter. CONCLUSION: Several of the ADAMTS members, and especially ADAMTS-1, are down regulated at mRNA level in AAA, due to unknown mechanisms, at the same time ADAMTS-1 protein is induced. The cleavage of its substrates, don't seem to be crucial for the pathogenesis of AAA but rather more important in the development of thoracic aortic aneurysm and atherosclerosis as shown in previous studies.

Skin microvascular endothelial dysfunction is associated with type 2 diabetes independently of microalbuminuria and arterial stiffness.

Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells × mm/s) divided into three speed regions: 0-1, 1-10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0-1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study. METHODS AND RESULTS: Human aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT. CONCLUSIONS: Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.

Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth.

BACKGROUND AND AIMS: MicroRNA (miR) are important regulators of gene expression and biological processes and have recently been suggested as possible biomarkers for abdominal aortic aneurysm (AAA) disease. The aim of the present study was to assess the role of miR as biomarkers for initiation and progression of AAA disease, through evaluation of a wide range of miRs in a large population-based cohort, with AAA patients with linked clinical data regarding risk factors, AAA size and growth, as well as controls. METHODS: The expression of the 172 most commonly expressed miRs in plasma was analyzed by real-time PCR in samples from 169 screening-detected AAA patients and 48 age-matched controls. RESULTS: For 103 miRs, there was a significant difference in expression between AAA and controls. Of these, 20 miRs were differently expressed between fast and slow growing aneurysms. These miRs target genes known to be involved in AAA disease as well as novel genes and pathways. By combining the top altered miRs together with clinical variables, strong predictive values, determining growth of AAA, were obtained (area under curve = 0.86, p < 0.001). CONCLUSIONS: This large cohort study identified several novel miRs with altered expression in AAA patients when compared to controls. Assessment of miR expression may offer an opportunity to predict disease progression and aneurysm growth.

Revisiting the cost-effectiveness of screening 65-year-old men for abdominal aortic aneurysm based on data from an implemented screening programme.

BACKGROUND: Health economic analyses based on randomized trials have shown that screening for abdominal aortic aneurysm (AAA) cost-effectively decreases AAA-related, as well as all- cause mortality. However, follow-up from implemented screening programmes now reveal substantially changed conditions in terms of prevalence, attendance rate, costs and mortality after intervention. Our aim was to evaluate whether screening for AAA among 65-year-old men is cost-effective based on contemporary data on prevalence and attendance rates from an ongoing AAA screening programme. METHODS: A decision-analytic model, previously used to analyse the cost-effectiveness of an AAA screening programme prior to implementation in clinical practice, was updated using data collected from an implemented screening programme as well as data from contemporary published data and the Swedish register for vascular surgery (Swedvasc). RESULTS: The base-case analysis showed that the cost per life-year gained and quality-adjusted life year (QALY) gained were €4832 and €6325, respectively. Based on conventional threshold values of cost-effectiveness, the probability of screening being cost-effective was high. CONCLUSION: Despite the reduction of AAA-prevalence and changes in AAA-management over time, screening 65-year-old men for AAA still appears to yield health outcomes at a cost below conventional thresholds of cost-effectiveness.

Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope.

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 ± 5.0 yr) and 15 matched controls (22.8 ± 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ∼40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis.

PURPOSE: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. METHODS: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60 × 0.60 × 0.70 mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. RESULTS: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64 ± 0.2737% versus 9.294 ± 0.1762% (mean ± standard error of the mean [SEM]; P < 0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81 ± 1.276 s-1 versus 56.94 ± 0.9095 s-1 (mean ± SEM; P < 0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2 = 0.92) as well as between cumulative R2* and IPH (R2 = 0.94). CONCLUSION: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH. Magn Reson Med 78:285-296, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men.

BACKGROUND: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. METHODS: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. RESULTS: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. CONCLUSION: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

Aortic pulse wave velocity predicts incident cardiovascular events in patients with type 2 diabetes treated in primary care.

AIMS: The aim was to evaluate the predictive value of aortic pulse wave velocity (aPWV) on incident cardiovascular events in patients with type 2 diabetes without previous cardiovascular disease who were treated in primary care, after adjustment for traditional risk factors. METHODS: We measured aPWV in 627 patients who participated in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) and who did not have previously known myocardial infarction or stroke. The outcome variable was a composite endpoint consisting of cardiovascular mortality, hospitalization for myocardial infarction and hospitalization for stroke. RESULTS: During a median follow-up time of almost eight years, the unadjusted HR per each increment of aPWV by 1m/s was 1.239 (95% CI 1.114-1.379, P<0.001) for the primary endpoint. Following adjustments for age, sex, diabetes duration, office systolic blood pressure, resting heart rate, total cholesterol, HbA1c, estimated glomerular filtration rate and smoking status, the adjusted hazard ratio was 1.142 (95% CI 1.003-1.301, P=0.044). CONCLUSIONS: In primary preventive patients with type 2 diabetes treated in primary care, aPWV predicted a composite outcome of incident cardiovascular events independently of diabetes-specific and traditional risk factors.

Slower Lower Limb Blood Pooling Increases Orthostatic Tolerance in Women with Vasovagal Syncope.

BACKGROUND AND AIM: Slower lower limb blood pooling and associated blunted sympathetic activation has been detected in healthy women prone to orthostatic syncope. Whether these findings are true also for patients with vasovagal syncope (VVS) is unknown. The aim was to investigate initial blood pooling time (poolingtime, time to 50% of total blood pooling) together with hemodynamic responses and orthostatic tolerance during lower body negative pressure (LBNP) in VVS and healthy controls. METHODS AND RESULTS: Fourteen VVS women (25.7 ± 1.3 years) and 15 healthy women (22.8 ± 0.8 years) were subjected to single-step and graded LBNP to pre-syncope. Lower limb blood pooling (ml · 100 ml(-1)), poolingtime (s), hemodynamic responses and LBNP-tolerance were evaluated. LBNP induced comparable lower limb blood pooling in both groups (controls, 3.1 ± 0.3; VVS, 2.9 ± 0.3 ml · 100 ml(-1), P = 0.70). In controls, shorter poolingtime correlated to higher LBNP-tolerance (r = -0.550, P < 0.05) as well as better maintained stroke volume (r = -0.698, P < 0.01) and cardiac output (r = -0.563, P < 0.05). In contrast, shorter poolingtime correlated to lower LBNP-tolerance in VVS (r = 0.821, P < 0.001) and larger decline in stroke volume (r = 0.611, P < 0.05). Furthermore, in controls, shorter poolingtime correlated to baroreflex-mediated hemodynamic changes during LBNP, e.g., increased vasoconstriction (P < 0.001). In VVS, poolingtime was not correlated with LBNP-induced baroreceptor unloading, but rather highly correlated to resting calf blood flow (P < 0.001). CONCLUSIONS: Shorter poolingtime seems to elicit greater sympathetic activation with a concomitant higher orthostatic tolerance in healthy women. The contrasting findings in VVS indicate a deteriorated vascular sympathetic control suggesting well-defined differences already in the initial responses during orthostatic stress.