Carotid Artery Distensibility Coefficient Research Articles

Comparison between Carotid Distensibility-Based Vascular Age and Risk-Based Vascular Age in Middle-Aged Population Free of Cardiovascular Disease.

The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.

Association of Vascular Properties With the Brain White Matter Hyperintensity in Middle-Aged Population.

BackgroundThe periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation.Methods and ResultsA total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold.ConclusionsWe show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.

Prenatal Exercise and Cardiovascular Health (PEACH) Study: Impact on the Vascular System.

Healthy pregnancy is typically associated with favorable vascular adaptations to both structure and function of the peripheral arteries. Exercise is independently associated with improvements in peripheral vascular health; however, the impact of exercise on prenatal adaptations is unclear. Therefore, we hypothesized that a structured aerobic exercise intervention between the second and third trimesters (TM2 and TM3, respectively) of pregnancy would augment the already-positive changes in vascular outcomes. We recruited 59 inactive pregnant women (<20 wk of gestation) and randomized them into control (standard care; n = 28) or exercise (moderate-intensity aerobic exercise, 3-4 d·wk-1, 25-40 min, 14 ± 1 wk; n = 31) conditions. Before and after the intervention, all women completed the comprehensive peripheral vascular assessment, which included blood markers of vascular health, carotid distensibility metrics, measures of arterial stiffness (pulse wave velocity), and [superficial] femoral artery reactivity during cold pressor test. Carotid artery diameter increased from 6.5 to 6.9 mm (P < 0.001), and strain (%) decreased from 9.9% to 8.4% (P < 0.001). Carotid artery blood flow, compliance and distensibility coefficients, stiffness (β), distensibility (1/β), and elastic modulus were not different across gestation. Pulse wave velocity was not different across gestation. Superficial femoral artery diameter was increased from 5.4 to 5.6 mm (P = 0.004), whereas blood flow, conductance, and resistance at rest and during the cold pressor test were not different across gestation. None of our measures of vascular health were impacted by exercise. We did not observe an impact of aerobic exercise on altering the changes across pregnancy in blood vessel health. However, the present study was conducted in women who were overall at low risk for developing gestational hypertension and should be interpreted with caution. Future work in high-risk women is needed.

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Arterial stiffness as a risk factor for cardiovascular events and all-cause mortality in people with Type 2 diabetes.

AimTo quantify the risk of different non‐invasive arterial stiffness measurements with macrovascular disease and all‐cause mortality in high‐risk people with Type 2 diabetes.MethodsWe conducted a prospective cohort study of 1910 people with Type 2 diabetes included in the Second Manifestations of ARTerial disease (SMART) study. Arterial stiffness was assessed by brachial artery pulse pressure, normal range (≥0.9) ankle–brachial index and carotid artery distension. Cox regression was used to evaluate the effects of arterial stiffness on risk of cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all‐cause mortality.ResultsA total of 380 new cardiovascular events and 436 deaths occurred during a median (interquartile range) follow‐up of 7.5 (4.1–11.0) years. A 10‐mmHg higher brachial pulse pressure was related to higher hazard of cardiovascular events (hazard ratio 1.09, 95% CI 1.02 to 1.16) and all‐cause mortality (hazard ratio 1.10, 95% CI 1.03 to 1.16). A 0.1‐point lower ankle–brachial index within the normal range was related to a higher hazard of cardiovascular events (hazard ratio 1.13, 95% CI 1.01 to 1.27) and all‐cause mortality (hazard ratio 1.17, 95% CI 1.04 to 1.31). A one‐unit (10−3×kPa−1) lower carotid artery distensibility coefficient was related to a higher hazard of vascular mortality (hazard ratio 1.04, 95% CI 1.00 to 1.09) and all‐cause mortality (hazard ratio 1.04, 95% CI 1.00 to 1.07).ConclusionIncreased arterial stiffness, as measured by either increased pulse pressure, normal‐range ankle–brachial index or carotid artery distensibility coefficient, is related to increased hazard of cardiovascular events and all‐cause mortality in people with Type 2 diabetes.

Distensibility coefficient of the common carotid artery in acute cerebral infarct by M-mode ultrasound: A cross-sectional study

Introduction: Distensibility coefficient (DC) is abnormal in most cases of acute cerebral infarct patients. Intima-media thickness (IMT) is measured by B (brightness)-mode and distensibility by M (motion)-mode ultrasound. DC is not routinely measured in clinical practice even though it is the earliest functional change to occur in common carotid arteries. IMT represents structural change and DC represents functional changes that occur in common carotid.Aim: DC is a valid independent indicator for risk assessment of acute cerebral infarcts. The present study is aimed at knowing the association of abnormal DC with acute cerebral infarct patients.Materials and Methods: Cross sectional study was undertaken over a period of 9 months with 210 cases of acute cerebral infarct. Distensibility of common carotid artery was measured by M-mode ultrasound. Cramer's V value ranged from 0.0 to 1.0 and P < 0.05 was considered statistically significant.Results: DC was reduced in 62.8% of the total 210 cases of acute cerebral infarct. Maximum cases (38%) were in the age groups of 61–70 years. Cramer's V value ranged from <15 to <24 × 10−3 kPa (P < 0.001). There was a good association between reduced DC and acute cerebral infarct in the present study.Conclusion: DC is a valid independent risk factor for acute cerebral infarct. DC represents functional vessel wall property and decreases with age. M-mode-derived measurements for DC are valid, and abnormal DC value is associated well with acute cerebral infarct.

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease

Objectives: Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS.Materials and methods: We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery.Results: Integrated BRS was reduced in patients [7.00 (5.80–9.25) vs. 11.1 (8.50–14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54 ± 1.20 vs. 4.48 ± 1.43 ms/10−3). FMD was higher in patients (9.81 ± 3.77 vs. 5.59 ± 1.36%). FMD and neural BRS were directly related in controls (r = 0.62), but inversely related in patients (r = –0.49).Conclusions: Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.

Carotid Artery Structure during and after Long‐Duration Space Flight

Space flight missions may expose astronauts to increased risk of oxidative stress and inflammatory damage induced by a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Given that evidence exists that these factors can accelerate the development of atherosclerosis, the purpose of this investigation is to determine whether long‐duration space flight (&gt;4 months) on the International Space Station results in structural changes in the carotid artery.METHODSCarotid artery intima‐media thickness (cIMT) and diameter during systole (Ds) and diastole (Dd) were measured using standard ultrasound (VividQ, GE Healthcare) in 10 astronauts (9 M, 1 F) approximately 180 and 60 days before launch, at approximately 15 (FD15) and 60 days of flight (FD60), within two weeks before landing (R‐14), and within one week after landing. Pre‐ and post‐flight measures were obtained after the subjects had been supine for at least 20 min. Inflight measures were acquired by trained astronauts while being guided by an expert sonographer on the ground using telemedicine techniques. Carotid artery distensibility coefficient was calculated (cDC = (Ds2−Dd2)/(PP·Dd2); Gepner et al., Stroke 45: 48–53, 2014). Pre‐flight data were averaged to represent baseline. Results were analyzed using one‐way repeated measures ANOVA.RESULTSCarotid artery diameters during systole (Ds FD15: 7.6 ± 0.4; FD60: 7.6 ± 0.4; R‐14: 7.7 ± 0.4 mm; mean ± SD) and diastole (Dd FD15: 7.2± 0.3; FD60: 7.3 ± 0.4; R‐14: 7.3 ± 0.5 mm) were significantly greater during space flight than pre‐ (Ds: 7.3 ± 0.4; Dd: 6.9 ± 0.4 mm) and post‐flight (Ds: 7.4 ± 0.4; Dd: 7.1 ± 0.5 mm). There was a main effect of time on cIMT, but post‐hoc analyses did not reveal significant difference from pre‐flight (Pre: 0.58 ± 0.09 mm) at any time point (FD15: 0.58 ± 0.14; FD60: 0.54 ± 0.09; R‐14: 0.54 ± 0.09; Post: 0.62 ± 0.10 mm). Although pre‐flight cDC (0.0028 ± 0.0011/mmHg) was not different than in‐flight (FD15: 0.0023 ± 0.0011; FD60: 0.0020 ± 0.0008; R‐14: 0.0023 ± 0.0012/mmHg), post‐flight cDC (0.0019 ± 0.0010/mmHg) was significantly less than pre‐flight.CONCLUSIONSAlthough the carotid artery was distended chronically during space flight and cDC was decreased in the week after landing, in these astronauts pathological remodeling of this vessel was not evident.Support or Funding InformationSupported by the NASA Human Research Program

Progression of Carotid Arterial Stiffness With Treatment of Hypertension Over 10 Years: The Multi-Ethnic Study of Atherosclerosis.

Associations with antihypertensive medication classes and progression of arterial stiffness have not been studied in a prospective multiethnic cohort. All participants had hypertension at baseline, defined as blood pressure ≥140/90 mm Hg or use of antihypertensive medications. Medication use and blood pressure were assessed at 5 time points. Young's elastic modulus and distensibility coefficient of the right common carotid artery were obtained by ultrasound at baseline and after a mean (SD) follow-up period of 9.4 (0.5) years. Associations with changes in Young's elastic modulus and distensibility coefficient, baseline antihypertensive medication use, number of visits each medication class was reported, and blood pressure control (<140/90 mm Hg) were assessed using multiple linear regression models. At baseline, mean age of participants (n=1206) was 63.2 (9.0) years (55% female; 35% African American, 19% Hispanic, 12% Chinese). Mean systolic blood pressure was 136.5 (20.6) mm Hg. Greater progression of arterial stiffness was associated with older age, African American ethnicity, and baseline calcium channel blocker use. There were no other associations between changes in Young's elastic modulus or distensibility coefficient and use of other medication classes (all P>0.4). Achieving blood pressure control (<140/90 mm Hg) at all visits was associated with slower progression of arterial stiffness (Young's elastic modulus: β=-790.1 mm Hg, P=0.01; distensibility coefficient: β=7.34×10-4 mm Hg-1, P=0.001). Blood pressure control, rather than use of any particular antihypertensive medication class, was associated most strongly with slowing arterial stiffness progression. Over nearly a decade of follow-up, no consistent associations between any specific antihypertensive medication class and progressive carotid arterial stiffening were identified.

Influence of blood flow velocity on arterial distensibility of carotid artery in healthy men.

Decreased distensibility of carotid artery is independently associated with the incidence of cardiovascular and cerebrovascular events. Arterial distensibility is determined by vascular tone. Since shear stress is an important driving force of vasodilatory substances production form endothelial cells, we hypothesized that local basal (i.e., resting) arterial blood flow velocity is associated with regional arterial distensibility. To test this hypothesis, we determined the influence of local blood flow velocity on carotid arterial distensibility in cross-sectional study design. In a total of 73 apparent healthy men (18-64years), carotid arterial properties, including measures of carotid arterial distensibility and BFV at rest, were evaluated via B-mode and Doppler ultrasound imaging and applanation tonometry system. Carotid arterial peak BFV and the absolute and normalized pulsatile BFV significantly correlated with age (r=-0.453 to -0.600, p<0.0001), whereas mean and minimum BFV were not influenced by age. Distensibility coefficient of carotid artery correlated with peak BFV (r=0.305, p<0.01) and more strongly with pulsatile (i.e., systolic minus end-diastolic) BFV (r=0.406, p<0.0001) and the normalized pulsatile BFV by time-averaged velocity (r=0.591, p<0.0001). Multi-regression analysis revealed that age (β=-0.57, p<0.0001) was the primary independent determinant for distensibility coefficient. In addition with this, carotid lumen diameter (β=-0.202, p<0.01) and the normalized pulsatile BFV (β=0.237, p<0.05) were significant independent determinants of distensibility coefficient. Qualitatively similar results (although inverse in direction) were obtained by use of β-stiffness index. These results suggest that greater gradient of blood flow velocity during a cardiac cycle are favorably associated with distensibility of carotid artery.

Reference values for local arterial stiffness. Part A: carotid artery.

Non-invasive measures of common carotid artery properties, such as diameter and distension, and pulse pressure, have been widely used to determine carotid artery distensibility coefficient - a measure of carotid stiffness (stiffness ∼1/distensibility coefficient). Carotid stiffness has been associated with incident cardiovascular disease (CVD) and may therefore be a useful intermediate marker for CVD. We aimed to establish age and sex-specific reference intervals of carotid stiffness. We combined data on 22 708 individuals (age range 15-99 years, 54% men) from 24 research centres worldwide. Individuals without CVD and established cardiovascular risk factors constituted a healthy sub-population (n = 3601, 48% men) and were used to establish sex-specific equations for percentiles of carotid distensibility coefficient across age. In the sub-population without CVD and treatment (n = 12 906, 52% men), carotid distensibility coefficient Z-scores based on these percentile equations were independently and negatively associated, in men and women, respectively, with diabetes {-0.28 [95% confidence interval (CI) -0.41; -0.15] and -0.27 (-0.43; -0.12)}, mean arterial pressure [-0.26 (-0.29; -0.24) and -0.32 (-0.35; -0.29)], total-to-high-density lipoprotein cholesterol ratio [-0.05 (-0.09; -0.02) and -0.05 (-0.11; 0.01)] and BMI [-0.06 (-0.09; -0.04) and -0.05 (-0.08; -0.02)], whereas these were positively associated with smoking [0.30 (0.24; 0.36) and 0.24 (0.18; 0.31)]. We estimated age and sex-specific percentiles of carotid stiffness in a healthy population and assessed the association between cardiovascular risk factors and carotid distensibility coefficient Z-scores, which enables comparison of carotid stiffness values between (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures.

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs. In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted. Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.

Vitamin D, carotid intima-media thickness and bone structure in patients with type 2 diabetes.

Despite aggressive treatment of cardiovascular disease (CVD) risk factors individuals with type 2 diabetes (T2D) still have increased risk of cardiovascular morbidity and mortality. The primary aim of this study was to examine the cross-sectional association between total (25-hydroxy vitamin D (25(OH)D)) and risk of CVD in patients with T2D. Secondary objective was to examine the association between 25(OH)D and bone health. A Danish cohort of patients with T2D participating in a randomised clinical trial were analysed. In total 415 patients (68% men, age 60±9 years (mean±s.d.), duration of diabetes 12±6 years), including 294 patients (71%) treated with insulin. Carotid intima–media thickness (IMT) and arterial stiffness (carotid artery distensibility coefficient (DC) and Young's elastic modulus (YEM)) were measured by ultrasound scan as indicators of CVD. Bone health was assessed by bone mineral density and trabecular bone score measured by dual energy X-ray absorptiometry. In this cohort, 214 patients (52%) were vitamin D deficient (25(OH)D <50 nmol/l). Carotid IMT was 0.793±0.137 mm, DC was 0.0030±0.001 mmHg, YEM was 2354±1038 mmHg and 13 (3%) of the patients were diagnosed with osteoporosis. A 25(OH)D level was not associated with carotid IMT or arterial stiffness (P>0.3) or bone health (P>0.6) after adjustment for CVD risk factors. In conclusion, 25(OH)D status was not associated with carotid IMT, arterial stiffness or bone health in this cohort of patients with T2D. To explore these associations and the association with other biomarkers further, multicentre studies with large numbers of patients are required.

Abstract MP90: Carotid Arterial Stiffness is Associated with An Increased Risk of Incident Cerebral Microbleeds in Older People: the Age, Gene/Environment Susceptibility-Reykjavik Study

Introduction: Cerebral microbleeds (CMBs) resulting from cerebral amyloid angiopathy are predominantly located in lobar regions, whereas those from hypertension are in deep and infratentorial regions. Although age and high blood pressure are major risk factors for CMBs, the underlying mechanisms remain unclear; arterial stiffness may be important. Hypothesis: We hypothesized that carotid arterial stiffness, would be associated with incident CMBs. Given the spatial distributions of the underlying arteriopathies in which hypertensive arteriopathy typically affects the small perforating end-arteries of the deep structures, we further hypothesized that the associations would be more robust for deep CMBs attributed to hypertensive arteriopathy. Methods: In the prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study, 2,512 participants aged 66-97 years underwent a baseline brain MRI examination and carotid ultrasound in 2002-2006, and returned for a repeat brain MRI in 2007-2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain (CAS), distensibility coefficient (DC) and Young’s elastic modulus (YEM). Log-binomial regression was applied to relate carotid arterial stiffness parameters to CMBs incidence. Results: During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex and brain MRI interval, all arterial stiffness parameters were each significantly associated with incident CMBs (Risk ratio [RR] per SD decrease in CAS, 1.11 [95%CI, 1.02-1.21]; RR per SD decrease in natural log-transformed DC, 1.14[1.05-1.23]; RR per SD decrease in natural log-transformed YEM, 1.13[1.04-1.22]) and deep CMBs (RR, 1.17[1.00-1.36]; 1.24[1.07-1.43]; 1.22[1.06-1.41] respectively) but not with lobar CMBs. When further adjusted for baseline vascular risk factors including blood pressure and use of blood pressure lowering drugs, the presence of carotid plaque, prevalent CMBs, subcortical infarcts and white matter hyperintensities, the associations persisted. Conclusion: Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially those occuring in a deep location.

SERUM 25-HYDROXYVITAMIN D AND PARATHYROID HORMONE LEVELS DO NOT PREDICT CHANGES IN CAROTID ARTERIAL STIFFNESS AFTER 10 YEARS: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS

To evaluate the impacts of vitamin D and parathyroid hormone (PTH) on longitudinal changes in arterial stiffness. Distensibility coefficient (DC) and Young's elastic modulus (YEM) of the right common carotid artery were evaluated at baseline and after a mean (standard deviation) of 9.4 (0.5) years

Effect of Golimumab on Carotid Atherosclerotic Disease Measures and Cardiovascular Events in Inflammatory Arthritides

The objective of this study was to assess the effect of golimumab on carotid ultrasound measures and cardiovascular serious adverse events (SAEs) in patients with inflammatory arthritides. An exploratory carotid artery ultrasound substudy was performed in the GO-BEFORE study of methotrexate (MTX)-naive rheumatoid arthritis patients, with ultrasounds performed at weeks 0, 24, and 52 to measure common carotid artery intima-media thickness, distensibility coefficient, interadventitial diameter, and plaque count. Cardiovascular SAEs reported over 2 years of follow-up were assessed in 5 golimumab phase 3 clinical trials of patients with rheumatoid arthritis (GO-BEFORE, GO-FORWARD, and GO-AFTER), psoriatic arthritis (GO-REVEAL), and ankylosing spondylitis (GO-RAISE). In GO-BEFORE and GO-FORWARD, patients received placebo + MTX, golimumab 50 mg + MTX, or golimumab 100 mg +/- MTX at baseline and every 4 weeks; in the other 3 trials, patients received placebo or golimumab 50 or 100 mg. The carotid ultrasound substudy showed inconsistent changes in common carotid artery intima-media thickness in the golimumab + MTX groups over time, and there was large variability in the measurements. Increases in interadventitial diameter were observed in the golimumab 100 mg + placebo group, but not in the golimumab + MTX groups. There were no significant differences in the distensibility coefficient and plaque count between the golimumab and placebo groups. Very few patients overall experienced a cardiovascular SAE, and the incidence of cardiovascular SAEs was not statistically different between the golimumab and placebo groups. The results of the carotid ultrasound substudy were inconclusive, and no increase or decrease in cardiovascular SAEs was observed following 2 years of treatment with golimumab with or without MTX.

Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy

Radiotherapy has been associated with an increased risk for cardiovascular disease (CVD) in Hodgkin lymphoma survivors (HLS). Identifying subjects most likely to develop these complications is challenging. Arterial stiffness has been frequently used as an early marker of CVD, but has never previously been investigated in patients treated with radiotherapy. The carotid–femoral pulse wave velocity (PWV) and the distensibility coefficient (DC) of the common carotid artery were used as markers of arterial stiffness. Eighty-two HLS and 40 age- and gender-matched control subjects were studied. The aorta and the carotid arteries were situated within the radiation field in 50 and 39 patients. Mean PWV was not significantly different in HLS treated with radiotherapy on the mediastinum when compared to HLS treated without mediastinal radiotherapy and to controls. If HLS were 40 years or older at radiotherapy their PWV was significantly higher (8.54 m/s) than patients irradiated at a younger age (7.14 m/s, p = 0.004) and controls (6.91 m/s, p < 0.001), after adjusting for current age and other CVD risk factors. Mean DC was lower, indicative of stiffer arteries, in HLS treated with radiotherapy on the common carotid artery (2.79) than in HLS without radiotherapy (3.35, p = 0.029) and versus controls (3.60, p = 0.001). DC was lowest in HLS treated at 35 years of age or later (2.05), compared to HLS irradiated at a younger age (2.98, p = 0.046). In HLS, radiotherapy is associated with increased arterial stiffness. The effect of radiotherapy seems most evident when radiotherapy is administered at ages above 35–40 years.

Influence of Erythropoietin on Arterial Stiffness and Endothelial Function in Renal Transplant Recipients

Background/Aims: Recent retrospective studies suggest an association of therapy with erythropoiesis-stimulating agents (ESAs) and increased mortality in renal transplant recipients (RTR). Large artery structure and function are significantly impaired in RTR which contributes to their high cardiovascular morbidity and could be altered by erythropoietin. We aimed to examine the influence of ESA therapy on large artery stiffness and endothelial function in RTR. Methods: 63 RTR with chronic allograft dysfunction and renal anemia were randomized to a group receiving darbepoetin alfa (Dar) and a control group (Co). At baseline and after 8 months of treatment (cumulative Dar dose 11.1 µg/kg b.w.) brachial and common carotid artery distensibility coefficients, aortic pulse wave velocity, brachial artery flow-mediated and nitroglycerin-mediated vasodilation were measured as well as the following biomarkers of vascular function: vWF, sVCAM, sICAM, E-selectin, t-PA and PAI-1. Results: 23 patients in the Dar group and 17 patients in the Co group were available for per-protocol analysis. Hemoglobin increased significantly from 10.9 to 12.6 g/dl after 8 months in the Dar group, whereas it remained stable at 11.3 g/dl in the Co group. Effects on large artery stiffness, endothelial function and biomarkers of vascular function did not differ significantly between the two groups. Conclusion: Therapy with Dar during 8 months did not significantly impact parameters of large artery stiffness and endothelial function in RTR. These data suggest that therapy with erythropoietin does not deteriorate arterial stiffness and endothelial function in RTR.

Serum hsCRP and visfatin are elevated and correlate to carotid arterial stiffness in spinal cord-injured subjects

Cross-sectional comparison, control group. To investigate the relationship between carotid arterial stiffness and circulating markers for cardiovascular disease (CVD) in spinal cord-injured (SCI) subjects compared with able-bodied (AB) individuals. University Research Laboratory, University of Louisville. SCI (n=14) and AB (n=13) subjects between 20-52 years of age were recruited to participate in the study. B-mode Doppler ultrasound was used to obtain carotid artery diameter measurements. Arterial stiffness was assessed via the stiffness index and distensibility coefficient. Markers of CVD risk were obtained by fasting blood draw. Carotid arterial stiffness index (P=0.061) and distensibility coefficient (P=0.370) were not different between the SCI and AB groups. The SCI group had higher high-sensitivity C-reactive protein (hsCRP) (P=0.046), triglycerides (P=0.017), leptin (P=0.040) and visfatin (P<0.001) compared with the control group. Visfatin (r=0.559, P=0.047), hsCRP (r=0.633, P=0.037), insulin (r=0.637, P=0.019) and HOMA (r=0.614, P=0.026) significantly correlated with carotid arterial stiffness index in the SCI group. This study demonstrated that SCI subjects are at a high cardiovascular risk as indicated by elevated hsCRP levels. Elevations in hsCRP and visfatin may contribute to accelerated atherogenic processes in the SCI population.

Relationship of Carotid Distensibility and Thoracic Aorta Calcification

Stiffening of the central elastic arteries is one of the earliest detectable manifestations of adverse change within the vessel wall. Although an association between carotid artery stiffness and adverse events has been demonstrated, little is known about the relationship between stiffness and atherosclerosis. Even less is known about the impact of age, sex, and race on this association. To elucidate this question, we used baseline data from the Multi-Ethnic Study of Atherosclerosis (2000-2002). Carotid artery distensibility coefficient was calculated after visualization of the instantaneous waveform of the common carotid diameter using a high-resolution B-mode ultrasound. Thoracic aorta calcification was identified using noncontrast cardiac computed tomography. We found a strong association between decreasing distensibility coefficient (increasing carotid stiffness) and increasing thoracic aorta calcification, as well as a graded increase in the thoracic aorta calcification score (P<0.001). After controlling for age, sex, race, and traditional and emerging cardiovascular risk factors, individuals in the stiffest quartile had a prevalence ratio of 1.52 (95% CI: 1.15 to 2.00) for thoracic aorta calcification compared with the least stiff quartile. In exploratory analysis, carotid stiffness was more highly correlated with calcification of the aorta than calcification of the coronary arteries (rho=0.32 versus 0.22; P<0.001 for comparison). In conclusion, there is a strong independent association between carotid stiffness and thoracic aorta calcification. Carotid stiffness is more highly correlated with calcification of the aorta, a central elastic artery, than calcification of the coronary arteries. The prognostic significance of these findings requires longitudinal follow-up of the Multi-Ethnic Study of Atherosclerosis cohort.