Carotid Stiffness Research Articles

Subclinical vasculopathy and skeletal muscle metrics in the singapore longitudinal ageing study.

Frailty is associated with future cardiovascular events in older adults. This cross-sectional study examined the relationship between subclinical vasculopathy with measures of skeletal muscle mass and function. Asymptomatic community-dwelling Asians ≥55 years underwent assessments for subclinical vasculopathy (carotid intima-media thickness (cIMT), aortic and carotid stiffness, and endothelial function), muscle mass (calf circumference adjusted for body mass index) and function (knee extension strength, 6-meter fast gait speed). Multivariable regression analyses for associates of muscle mass/function controlled for demographics and cardiometabolic risk factors. Among 336 participants (median age 62 years, 55.1% male, 3.6% sarcopenia), cIMT, aortic and carotid stiffness inversely correlated with muscle mass, strength and gait speed; cIMT remained independently associated with gait speed (β=-0.26) in multivariable analyses. Age and sex significantly modified the relationship between subclinical vasculopathy and muscle mass/function. Associations, only found in those aged ≥70, included cIMT with gait speed (β=-0.48) and knee strength (β=-9.33), and aortic augmentation index and aortic stiffness composite z-score with gait speed (β=-0.11 and β=-0.19 respectively). Among males, cIMT correlated with gait speed (β=-0.31). The association of subclinical vasculopathy with skeletal muscle mass and function in asymptomatic adults ≥55 years is best reflected by cIMT. The roles of mediating pathways deserve further evaluation.

Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure-independent mechanisms in patients with or at risk of type 2 diabetes mellitus.

To test if 6months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/doxazosin, to control for blood pressure (BP). A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate-containing beetroot juice or placebo nitrate-depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima-media thickness (CIMT, mm) was performed at baseline, 3- and 6-months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed-model effect, adjusted for confounders. In total, 93 subjects had a baseline evaluation and 86% had follow-up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate-containing vs. placebo juice significantly lowered CIMT (-0.06 [95% confidence interval -0.12, -0.01],P = .034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (-0.34 [-0.62, -0.06]) however, no difference was detected vs. spironolactone (-0.15 [-0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD. Our results show that 6months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP-independent effect on carotid structure and function.

Impact of acute changes in blood pressure and arterial stiffness on cerebral pulsatile haemodynamics in young and middle-aged adults.

What is the central question of this study? Does cerebrovascular pulsatility respond differently to acute increases in arterial stiffness in middle-aged compared with young adults? What is the main finding and its importance? Compared with young adults, middle-aged adults exhibited similar changes in cerebral pulsatile damping despite attenuated changes in carotid diameter and cerebrovascular pulsatility during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness. Acute manipulation of arterial stiffness through interventions that increase sympathetic activity might provoke cerebral pulsatility and damping and reveal whether cerebrovascular haemodynamics respond differently to transient elevations in arterial stiffness in middle-aged compared with young adults. We compared cerebral pulsatility and damping in middle-aged versus young adults during two different sympathetic interventions [cold pressor test (CP) and lower-body negative pressure (LBNP)] that increase arterial stiffness acutely. Cerebrovascular haemodynamics were assessed in 15 middle-aged (54 ± 7years old; 11 female) and 15 sex-matched young adults (25 ± 4years old) at rest and during the CP test (4min, 6.4 ± 0.8°C) and LBNP (6min, -20mmHg). Mean blood pressure was measured continuously via finger photoplethysmography. Carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness were measured via tonometry and ultrasound. Blood velocity pulsatility index (PI) was measured at the middle cerebral (MCA) and common carotid artery (CCA) using Doppler, with pulsatile damping calculated as CCA PI divided by MCA PI. Increases in cfPWV were driven by changes in mean pressure during CP but not during LBNP in both groups (P<0.05). Pulsatile damping decreased in both groups (P<0.05) despite reductions in MCA PI and greater carotid dilatation during CP in young compared with middle-aged adults (P<0.05). Pressure-independent increases in cfPWV during LBNP did not alter pulsatile damping but decreased MCA PI in both young and middle-aged adults (P<0.05). These data suggest that changes in carotid diameter and cerebrovascular pulsatility differ between young and middle-aged adults despite similar changes in cerebral pulsatile damping during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness.

Carotid stiffness, intima-media thickness and aortic augmentation index among adults with SARS-CoV-2.

New Findings What is the central question of this study? We sought to investigate whether carotid stiffness, carotid intima–media thickness and the aortic augmentation index are altered in young adults 3–4 weeks after contraction of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) compared with young healthy adults. What is the main finding and its importance? We found that carotid stiffness, Young's modulus and the aortic augmentation index were greater in young adults who tested positive for SARS‐CoV‐2 compared with healthy young adults. These findings provide additional evidence for detrimental effects of SARS‐CoV‐2 on young adult vasculature, which might have implications for cardiovascular health. Contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been observed to cause decrements in vascular function of young adults. However, less is known about the impact of SARS‐CoV‐2 on arterial stiffness and structure, which might have additional implications for cardiovascular health. The purpose of this study was to assess the carotid artery stiffness and structure using ultrasound and the aortic augmentation index (AIx) using applanation tonometry in young adults after they tested positive for SARS‐CoV‐2. We hypothesized that carotid artery stiffness, carotid intima–media thickness (cIMT) and aortic AIx would be elevated in young adults with SARS‐CoV‐2 compared with healthy young adults. We evaluated 15 young adults (six male and nine female; 20 ± 1 years of age; body mass index, 24 ± 3 kg m−2) 3–4 weeks after a positive SARS‐CoV‐2 test result compared with young healthy adults (five male and 10 female; 23 ± 1 years of age; body mass index, 22 ± 2 kg m−2) who were evaluated before the coronavirus 2019 pandemic. Carotid stiffness, Young's modulus and cIMT were assessed using ultrasound, whereas aortic AIx and aortic AIx standardized to 75 beats min−1 (AIx@HR75) were assessed from carotid pulse wave analysis using SphygmoCor. Group differences were observed for carotid stiffness (control, 5 ± 1 m s−1; SARS‐CoV‐2, 6 ± 1 m s−1), Young's modulus (control, 396 ± 120 kPa; SARS‐CoV‐2, 576 ± 224 kPa), aortic AIx (control, 3 ± 13%; SARS‐CoV‐2, 13 ± 9%) and aortic AIx@HR75 (control, −3 ± 16%; SARS‐CoV‐2, 10 ± 7%; P < 0.05). However, cIMT was similar between groups (control, 0.42 ± 0.06 mm; SARS‐CoV‐2, 0.44 ± 0.08 mm; P > 0.05). This cross‐sectional analysis revealed higher carotid artery stiffness and aortic stiffness among young adults with SARS‐CoV‐2. These results provide further evidence of cardiovascular impairments among young adults recovering from SARS‐CoV‐2 infection, which should be considered for cardiovascular complications associated with SARS‐CoV‐2.

Associations of markers of arterial stiffness and remodeling with new-onset type 2 diabetes mellitus

Abstract Funding Acknowledgements Type of funding sources: None. Background. Arterial stiffness/remodeling results in impaired blood flow and, eventually, decreased glucose disposal in peripheral tissues and increased blood glucose. Besides, increased arterial stiffness/remodeling may lead to hypertension, as a potential reciprocal risk factor for type 2 diabetes mellitus (T2D). We, therefore, hypothesized that increased arterial stiffness/remodeling is associated with an increased risk of T2D. Purpose. To study the associations between arterial stiffness/remodeling and incident T2D. Methods. We used the prospective population-based Rotterdam Study. Common carotid arterial properties were ultrasonically determined in plaque-free areas. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (cf_PWV), carotid stiffness was estimated by the carotid distensibility coefficient (carDC). Arterial remodeling was estimated by carotid artery lumen diameter (carDi), carotid intima-media thickness (cIMT), mean circumferential wall stress (CWSmean), and pulsatile circumferential wall stress (CWSpuls). Cox proportional hazard regression analysis was used to estimate the associations between arterial stiffness/remodeling and the risk of incident T2D, adjusted for age, sex, cohort, mean arterial pressure (MAP), antihypertensive medications, heart rate, non- high-density lipoprotein (HDL)-cholesterol, lipid-lowering medications, and smoking. We included interaction terms in the fully adjusted models to study whether any significant associations were modified by sex, age, blood glucose, or MAP. Spearman correlation analyses were applied to examine the correlations between measurements of arterial stiffness/remodeling and glycemic traits. Results. We included 3,055 individuals free of T2D at baseline (mean (SD) age, 67.2 (7.9) years). During a median follow-up of 14.0 years, 395 (12.9%) T2D occurred. After adjustments, higher cf_PWV (hazard ratio (HR),1.18; 95%CI:1.04-1.35), carDi (1.17; 1.04-1.32), cIMT (1.15; 1.01-1.32), and CWSpuls (1.28; 1.12-1.47) were associated with increased risk of incident T2D. After further adjustment for the baseline glucose, the associations attenuated but remained statistically significant. Sex, age, blood glucose, or MAP did not modify the associations between measurements of arterial stiffness/remodeling, and incident T2D. Among the population with prediabetes at baseline (n = 513) compared to the general population, larger cIMT was associated with a greater increase in the risk of T2D. Most measurements of arterial stiffness/remodeling significantly but weakly correlated with baseline glycemic traits, particularly with blood glucose. Conclusions. Our study suggests that greater arterial stiffness/remodeling is independently associated with an increased risk of T2D development. Blood glucose and hypertension do not seem to play significant roles in these associations. Further studies should disentangle the underlying mechanism that links arterial stiffness/remodeling and T2D.

Carotid stiffness is associated with retinal microvascular dysfunction-The Maastricht study.

ObjectiveThis study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy.Research design and methodsThis study used cross‐sectional data from the Maastricht Study, a type 2 diabetes‐enriched population‐based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid‐femoral pulse wave velocity with retinal microvascular diameters and flicker light‐induced dilation and adjusted for cardiovascular and lifestyle risk factors.ResultsThe retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light‐induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non‐significantly, but directionally similarly, associated with greater retinal venular flicker light‐induced dilation (0.04 [−0.02; 0.10]). Carotid‐femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light‐induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light‐induced dilation were two‐ to threefold stronger in individuals with type 2 diabetes than in those without.ConclusionIn this population‐based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light‐induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction.

Longitudinal Tracking of Arterial Stiffness Among Young Adults with SARS‐CoV‐2

IntroductionSystemic vascular alterations have been implicated as a result of contracting SARS‐CoV‐2. While our group has recently observed acute decrements in vascular function and arterial stiffness, the long‐term implications of SARS‐CoV‐2 on arterial stiffness and vascular architecture in subsequent months is unknown.Purpose: The purpose of this study was to determine the prolonged implications of SARS‐CoV‐2 on carotid stiffness, carotid‐femoral pulse wave velocity (PWV), and pulse wave analysis (PWA) three months after infection. We hypothesized PWVcf, carotid stiffness, and PWA measures would decrease three months after contracting SARS‐CoV‐2.Methods: We assessed 7 young adults (4M/3F) at baseline (3‐4 weeks after testing positive for SARS‐CoV‐2) and at 1‐month and 2‐month follow‐up visits. Doppler ultrasound was used to assess carotid distensibility, stiffness, carotid intima media thickness, and PWVcf. Sphygmocor was utilized to determine carotid distensibility and aortic augmentation (AIx), as well as brachial and aortic arterial pressures.Results: Mean arterial pressure (MAP) decreased following infection (BL: 98.7±4.8 mmHg; 1‐month follow‐up: 92.7±10.4mmHg; 2‐month follow‐up: 88.6±5.0mmHg; p<0.05). There was a tendency for brachial systolic blood pressure (BL: 129.7±8.5mmHg; 1‐month follow‐up: 124.9±12.3mmHg; 2‐month follow‐up: 121.4±8.4mmHg; p=0.073), brachial diastolic blood pressure (BL: 74.0±6.7mmHg; 1‐month follow‐up: 73.6±10.6mmHg; 2‐month follow‐up: 67.0±8.9; p=0.066), and aortic systolic pressure (BL: 123.9±7.3mmHg; 1‐month follow‐up: 119.7±11.9mmHg; 2‐month follow‐up: 114.1±7.1mmHg; p=0.089) and aortic diastolic pressure (BL: 74.00±6.6mmHg; 1‐month follow‐up: 73.4±10.7mmHg; 2‐month follow‐up: 67.3±9.4mmHg; p=0.068) to decrease (p<0.1). Carotid stiffness, PWVcf, PWA measures were unaltered months following SARS‐CoV‐2 infection.Conclusion: Preliminary results indicate a lack of improvement in arterial stiffness in young adults three months following contraction of SARS‐CoV‐2. The tendency for a decrease in arterial pressures, however, indicates a possible improvement of overall cardiovascular health.

The Vobarno Study.

The Vobarno Study represents the first observational study aimed to assess in a general population sample the relationship between parameters of cardiac and vascular structure (and function) and blood pressure values, measured in the clinic and during the 24 hours. In the frame of The Vobarno Study blood samples for hematochemistry and DNA extraction, clinic and 24-hour blood pressure measurements, cardiac and carotid ultrasound, and aortic stiffness were measured in all subjects, living in a small town (Vobarno) between Brescia and the Garda Lake (Italy), and randomly selected from electoral roles. In this sample of a general population an extensive evaluation of organ damage, including left ventricular (LV) mass and hypertrophy, LV systolic function, left atrial dimensions and aortic root diameters, carotid intima media thickness (IMT) and carotid plaques, carotid and aortic stiffness were performed. In this study subjects were included in a long follow-up, lasting 25 years, and cardiovascular morbility and mortality were assessed up to 2019. This will allow to update the information related to cardiovascular morbidity and mortality in the study cohort. The present paper will report the results of some analyses performed, exploring epidemiological and clinical aspects of target organ damage.

Lipid Profile and Vascular Remodelling in Young Dyslipidemic Subjects Treated with Nutraceuticals Derived from Red Yeast Rice.

Background and Aims A relevant role is emerging for functional foods in cardiovascular prevention. The aim of this study was to assess the effect of a nutraceutical multitargeted approach on lipid profile and inflammatory markers along with vascular remodelling in a cohort of dyslipidemic subjects without history of cardiovascular (CV) disease. Methods and Results We enrolled 25 subjects (mean age 48.2 years) with low to moderate CV risk profile and total cholesterol (TC) levels between 150 and 250 mg/dl. The patients were assigned to receive for one year a tablet/die of a nutraceutical combination containing red yeast rice (RYR) extract (Monacolin 3 mg/tablet) and coenzyme Q10 (30 mg/tablet). Treatment with the nutraceutical compounds led to a significant reduction of TC (from 227 to 201 mg/dl, p < 0.001), LDL-c (from 150 to 130 mg/dl, p = 0.001), triglycerides (from 121 to 109 mg/dl, p = 0.013), non-HDL-cholesterol (from 168 to 141 mg/dl, p < 0.001), hs-CRP (from 1.74 to 1.20 mg/l, p = 0.015), and osteoprotegerin (from 1488 to 1328 pg/ml, p = 0.045). Levels of HDL-c, Lp(a), glucose, liver enzyme, CPK, or creatinine did not change over time. An ultrasound study was performed to assess changes in mean carotid intima-media thickness (IMT) and maximum IMT (M-MAX) as well as modification in local carotid stiffness by means of determining the carotid compliance coefficient (CC) and distensibility coefficient (DC). At the end of the treatment, we observed small but significant reductions in both mean-IMT (from 0.62 to 0.57 mm, p = 0.022) and M-MAX (from 0.79 to 0.73 mm, p = 0.002), and an improvement in carotid elasticity (DC from 22.4 to 24.3 × 10−3/kPa, p = 0.006 and CC from 0.77 to 0.85 mm2/kPa, p = 0.019). Conclusions A long-term treatment with a combination of RYR and coenzyme Q10 showed lipid-lowering activity along with a reduction of inflammatory mediators and an improvement of vascular properties in young subjects with a low-to-moderate CV risk profile.

Association of Carotid Intima-Media Thickness and Other Carotid Ultrasound Features With Incident Dementia in the ARIC-NCS.

BackgroundIncreased carotid intima‐media thickness, interadventitial diameter, presence of carotid plaque, and lower distensibility are predictors for cardiovascular disease. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer disease–related dementia. Therefore, we assessed the relationship of carotid measurements and arterial stiffness with incident dementia in the ARIC (Atherosclerosis Risk in Communities) study.Methods and ResultsA total of 12 459 ARIC participants with carotid arterial ultrasounds in 1990 to 1992 were followed through 2017 for dementia. Dementia cases were identified using in‐person and phone cognitive status assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident dementia. Participants were aged 57±6 at baseline, 57% were women, and 23% were Black individuals. Over a median follow‐up time of 24 years, 2224 dementia events were ascertained. After multivariable adjustments, the highest quintile of carotid intima‐media thickness and interadventitial diameter in midlife was associated with increased risk of dementia (HR [95% CIs], 1.25 [1.08–1.45]; and 1.22 [1.04–1.43], respectively) compared with its respective lowest quintile. Presence of carotid plaque did not have a significant association with dementia (HR [95% CI], 1.06 [0.97–1.15]). Higher distensibility was associated with lower risk of dementia (HR [95% CI] highest versus lowest quintile, 0.76 [0.63–0.91]).ConclusionsGreater carotid intima‐media thickness, interadventitial diameter, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.

Do individuals with autoimmune disease have increased risk of subclinical carotid atherosclerosis and stiffness?

To explore the role of chronic inflammation inherent to autoimmune diseases in the development of subclinical atherosclerosis and arterial stiffness, this study recruited two population-based samples of individuals with and without autoimmune disease (ratio 1:5) matched by age, sex, and education level and with a longstanding (≥6 years) diagnosis of autoimmune disease. Common carotid intima-media thickness (IMT) and arterial distensibility and compliance were assessed with carotid ultrasound. Multivariable linear and logistic regression models were adjusted for 10-year cardiovascular risk. In total, 546 individuals with and without autoimmune diseases (91 and 455, respectively) were included. The mean age was 66 years (standard deviation 12), and 240 (43.9%) were women. Arterial stiffness did not differ according to the presence of autoimmune diseases. In men, the diagnosis of autoimmune diseases significantly increased common carotid IMT [beta-coefficient (95% confidence interval): 0.058 (0.009; 0.108); p value = 0.022] and the percentage with IMT ≥ 75th percentile [1.012 (0.145; 1.880); p value = 0.022]. Women without autoimmune disease were more likely to have IMT ≥ the 75th percentile [-2.181 (-4.214; -0.149); p value = 0.035], but the analysis of IMT as a continuous variable did not yield significant results. In conclusion, subclinical carotid atherosclerosis, but not arterial stiffness, was more common in men with autoimmune diseases. Women did not show significant differences in any of these carotid features. Sex was an effect modifier in the association between common carotid IMT values and the diagnosis of autoimmune diseases.

PULSE PRESSURE SIGNIFICANTLY AND INDEPENDENTLY CORRELATES WITH CAROTID PULSE WAVE VELOCITY AND BETA-STIFFNESS INDEX IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objective: Introduction: Pulse wave velocity (PWV) and beta-stiffness index (BSI) are the most popular echo-tracking parameters indicating increased carotid stiffness. Pulse pressure (PP) values turns out to be higher in patients with increased indices of arterial stiffness and is an independent predictor of cardiovascular disease and mortality. This is of greater importance for patients with type 2 Diabetes Mellitus (T2DM). Aim: To find out correlation between the pulse pressure and carotid stiffness indices. Design and method: 100 patients with T2DM without overt cardio-vascular diseases and 30 healthy age and sex matched controls were included in the study. All participants underwent carotid examination of PWV and BSI, by echo-tracking method with Aloka Hitachi Prosound alfa-7. Patients with uncontrolled blood pressure and history of CV diseases were excluded from the study. Results: Pulse pressure significantly correlated with left carotid artery PWV (r = 0.43; p = 0.0001) and BSI (r = 0.44; p = 0.001) and right carotid artery PWV (r = 0.38; p = 0.001), BSI (r = 0.39; p = 0.001). Multivariate regression analysis with independent variable PWV, revealed that PP remained a significant and independent determinant (B = 5.78; p &lt; 0.0001), similar to systolic blood pressure (B = 2.97; p = 0.003). Conclusions: PP is among the most important independent determinants associated with increased carotid stiffness in patients with T2DM without cardiovascular complications and with well controlled blood pressure. PP may serve as an early marker of increased cardiovascular risk in patients with T2DM.

CHANGES IN CAROTID LOCAL STIFFNESS DURING A SIX-YEARS FOLLOW UP IN A GENERAL POPULATION: THE VOBARNO STUDY

Objective: Local carotid stiffness (Carotid PWV) is an independent predictor of cardiovascular events but few data are available on the progression of Carotid stiffness over time. The aim of the present longitudinal study was to analyze the progression of local carotid stiffness over a 6-year period in a general population in Northern Italy (Vobarno Study). Design and method: 123 subjects, age 55 ± 4 years (42% males, hypertension in 43% at baseline visit), underwent a baseline (BL) and a follow up (FU) visit, 6.2 ± 0.5 years apart. In all subjects laboratory examinations, measurements of blood pressure (BP) and of Carotid PWV (using an echotracking approach) were performed at BL and at FU. Progression rate of Carotid PWV (δCarotid_PWV/Year) was defined as (Carotid PWV at FU-Carotid PWV at BL)/years of FU. Results: In the overall population, Carotid PWV increased from 6.39 ± 1.41 at BL to 6.79 ± 1.18 m/s at FU (p &lt; 0.05). δCarotid_PWV/Year was inversely related to BP (mean BP: r = -0.193, p &lt; 0.05; pulse pressure: r = -0.1.81, p &lt; 0.05) and to Carotid PWV at BL (r = -0.669, p &lt; 0.001). No other correlation was observed between δCarotid_PWV/Year and demographic or laboratory parameters at BL. δCarotid_PWV/Year was also related to changes over time in BP values (δSystolicBP: r = 0.291, p &lt; 0.01; δDiastolicBP: r = 0.266, p &lt; 0.01; δMeanBP: r = 0.310, p &lt; 0.0001). At multivariate analysis the variables independently related to the annual progression rate of Carotid PWV were Carotid PWV and mean BP at BL (beta -0.68, p &lt; 0.0001, and beta 0.20, p &lt; 0.05, respectively) and changes in mean BP during follow-up (beta 0.18, p &lt; 0.05). Conclusions: In a general population sample in Northern Italy the main determinants of the increase in local carotid stiffness during a 6 years FU were local carotid stiffness and mean BP at BL and change in mean BP over time.

CHANGE IN HEMODYNAMIC PARAMETERS AND CAROTID STIFFNESS INDICES AFTER VITAMIN K2 SUPPLEMENTATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objective: Vitamin K2 is a cofactor of gamma-carboxylase activating group of vitamin K-dependent proteins involved in vascular calcification and arterial stiffness. Data on the protective effects of vitamin K2 supplementation in the progression of vascular damage in patients with type 2 diabetes mellitus (T2DM) are scarce. Aim: to investigate the change in systolic (SAP), diastolic (DAP), pulse (PP), mean (MAP) blood pressure, central systolic aortic pressure (CASP), pulse wave velocity (PWV) and beta-stiffness index (BSI) in patients with T2DM after vitamin K2 supplementation. Design and method: We included 18 patients with T2DM (mean age 59.09 ± 8.5 men 38.8%) who received Vitamin K2 (Menaquinone-7) 75 μg once daily for a period of 4 weeks. Patients with overt cardio-vascular diseases, uncontrolled blood pressure and vitamin K-antagonists intake were excluded from the study. Hemodynamic parameters were measured using an A-pulse CASP-AL device. Carotid stiffness indices were measured by one-point echo-tracking method with Aloka Hitachi Prosound on the both common carotid arteries (CA). Results: All hemodynamic parameters showed increased values compared to the baseline: SAP (+5 mmHg) (p = 0.1), DAP (+2.9mmHg) (p = 0.19), PP (+1.4mmHg) (p = 1.4), MAP (+3.4 mmHg) (p = 0.08). CASP increased from 119.8 ± 12.1mmHg to 126.8 ± 11.4 mmHg (+5 mmHg), and this change was significant (p = 0.02). PWV on the right CA did not change significantly before (7.0 ± 1.48 m/s) and after (7.19 ± 1.28 m/s) supplementation (p = 0.47), similar to BSI 10.08 ± 3.41 and respectively 10.51 ± 3.99 (p = 0.61). PWV on the left CA before supplementation is 7.01 ± 1.22 m/c, respectively after 7.19 ± 1.56 m/c (p = 0.49). BSI on the left CA is 9.97 ± 2.79, resp. 10.69 ± 5.07 (p = 0.43). Conclusions: Vitamin K2 supplementation for four weeks showed significant increase in CASP in our cohort of patients with T2DM. The other hemodynamic parameters as well as the indicators of carotid stiffness do not change significantly. A limitation of our study is the small number of patients included and the short period of intake of vitamin K2, which may not lead to morphological changes in the vessel wall. More extensive research is needed in the field.

LONG-TERM EFFECT OF ANTIHYPERTENSIVE AGENTS ON THE NEURAL BAROREFLEX SENSITIVITY-A SUBSTUDY OF THE PARIS PROSPECTIVE STUDY III

Objective: The baroreflex is a crucial mechanism regulating moment-to-moment blood pressure (BP) to ensure appropriate flow and pressure to the brain and other organs. All antihypertensive treatments, because of their BP lowering effect, interact with the autonomic nervous system by stimulating the sympathetic response. In addition, specific drugs may further interact with the BRS because of their specific mode of action. Whether antihypertensive agents have remnant effect is still unknown. Design and method: In the Paris Prospective Study III, spontaneous baroreflex, carotid stiffness and pharmacological drugs intake were available in 7967 adults (mean age of 60 ± 6 years, 62% men). The neural component of the baroreflex sensitivity (nBRS) was obtained with a cross-spectral analysis of variations in carotid distention rate and R-R intervals. Individuals with a BP lowering medication (BP-treated) were paired to non-BP treated individuals (controls) with similar cardiovascular comorbidities using a propensity score matching procedure (n = 1182 pairs). Results: Sympathetic activity was higher in the BP-treated group compared to their matched-controls, as shown by the increased spectral power of distention rate in the low frequency band (log LF distrate: 4.106 ± 0.530 vs 4.055 ± 0.514, p = 0.018). Amongst pharmacological classes of BP lowering agents, only agents acting on the angiotensin system (ACEi-ARB) were associated with nBRS. Compared to their matched controls (n = 331 pairs), ACEi-ARB users had lower nBRS (2.79 ± 0.66 (ln) vs. 2.90 ± 0.62 (ln), p = 0.03). After adjustment for carotid stiffness (stdbeta = 0.25, p &lt; 0.001) and systolic pressure (stdbeta = -0.20, p &lt; 0.001), ACEi-ARB remained significantly associated with nBRS (stdbeta = -0.09, p = 0.025). Conclusions: In this community-based population study, antihypertensive treatments induced activation of the autonomic nervous system independently of cardiovascular comorbidities. Taken as a whole, BP treatments did not have any effect on the neural component of the baroreflex loop, with the exception of ACEi-ARB which were negatively associated with nBRS. This effect was independent of BP and stiffness, which may suggest an inhibition of sympathetic activity by ACEi-ARB.

AORTIC AND CAROTID STIFFNESS IN CHILDREN AND ADOLESCENTS: RELATIONSHIP AND DETERMINANTS

Abstract Objective: Arterial stiffness is an established surrogate measure of preclinical target-organ damage by elevated blood pressure (BP). This study assessed regional (aortic) and local (carotid) arterial stiffness measured by different noninvasive methods in children and adolescents and their relationship with BP levels. Design and method: Apparently healthy children and adolescents (age 6–18 years) referred for elevated BP were evaluated with: (i) office BP (OBP) measurement (3 visits, triplicate readings/visit), (ii) 24 h ambulatory BP (ABP) monitoring, (iii) home BP (HBP) monitoring during daytime and nighttime, (iv) M- and B-mode ultrasonography for the assessment of carotid distensibility coefficient (cCD) and carotid intima-media thickness (cIMT), (v) determination of carotid-femoral pulse wave velocity (cfPWV; Complior). Results: 93 subjects were analyzed (mean age 13.1 ± 2.9 years, 55 males, BMI 24.7 ± 5.2 kg/m2, 18 with 24 h ABP &gt; = 95th percentile). There was an inverse association between cfPWV and cCD (r = -0.42, p &lt; 0.01). Hypertensive subjects had higher PWV than normotensives (6.3 ± 1.0 vs. 5.3 ± 0.9 m/sec respectively, p &lt; 0.01 after adjustment for age and gender), but similar cCD (57.1 ± 47.6 vs. 57.8 ± 18.4 kPa-1/103, p = NS). cfPWV compared to cCD tended to be more strongly correlated with age (r = 0.65 vs. -0.28, p &lt; 0.01 for comparison), systolic OBP (0.60 vs. -0.31, p &lt; 0.01), systolic ABP (24 h/day/nighttime 0.60/0.57/0.49 vs. -0.39/-0.38/-0.31, p = 0.02/0.04/0.07), systolic HBP (day/nighttime 0.48/0.55 vs. -0.33/-0.26, p = 0.13/ &lt; 0.01), cIMT (0.24 vs. -0.08, p = NS), and similarly to BMI (0.28 vs. -0.26, p = NS for comparison). Conclusions: In young individuals aortic PWV as an index of regional stiffness appears to be more closely associated with age and BP levels than local carotid stiffness.

Augmentation index predicts mortality in patients with aortic stenosis: an echo-tracking study.

Aortic valve stenosis (AS) shares similarities with the atherosclerotic process but little is known about the effect of the mechanical properties of large arteries on outcome in patients with AS. The aims of this study were (1) to determine the relationship between indexes of carotid stiffness/compliance and the severity of AS and (2) to identify whether local arterial stiffness is independently associated with mortality. 133 patients with moderate to severe isolated AS and preserved LV ejection fraction (LVEF) were included. All underwent transthoracic echocardiography and local carotid stiffness evaluation by means of high-definition echo-tracking ultrasound with the calculation of stiffness/compliance parameters included augmentation index (AIx). None of the carotid stiffness parameters were significantly associated with AS severity parameters. During a mean follow-up of 51.6 ± 39.4 months, 70 patients received aortic valve replacement, 45 died and 18 were alive with no surgery. Who died were older (79.2 ± 6.9 vs. 73 ± 8.8 years, p < 0.0001), had higher carotid AIx (21.3 ± 14 vs. 16 ± 12%, p = 0.028). In multivariate Cox regression analysis AIx was independently associated with mortality (HR 1.048, 95% CI 1.01-1.07, p = 0.001), also after inclusion of age and creatinine. There was a significant association between the level of AIx and mortality in those patients who did not have surgery (p = 0.016). In severe AS and a normal LVEF, carotid AIx measured by echo-tracking system was independently associated with death. No relationship between AS severity and local carotid stiffness was found. These data emphasize the importance of arterial stiffness has a hallmark of long-term atherosclerotic burden and impaired prognosis.

Physical activity is associated with lower pulsatile stress but not carotid stiffness in children.

The cardiovascular disease (CVD) process may begin early in life when accompanied by atherosclerotic risk factors. CVD risk factors in children are associated with stiffening of the large elastic arteries, a reflection of subclinical atherosclerosis. Physical activity is a preventative lifestyle strategy that may benefit arterial stiffness by attenuating the hemodynamic stress on the artery wall. This study examined the relations between physical activity, carotid pulsatile stress, and carotid stiffness in children. One hundred and forty children (9-11 yrs; 50.0% male, 57.9% African American, 42.10% Caucasian, body mass index (BMI) 20.1±4.7 kg/m2) participated in this study. Physical activity counts were measured using a wrist-worn accelerometer and averaged over 7 days. Carotid artery β-stiffness and pulse pressure (calibrated to brachial mean and diastolic pressure) were assessed as via ultrasound and tonometry, respectively. Pulsatile stress was calculated as the product of carotid pulse pressure and heart rate. Physical activity counts were correlated with pulsatile stress (r= -0.27), and BMI (r= -0.23), but were unrelated to carotid stiffness. In multivariate models, associations between physical activity counts and pulsatile stress remained (B= -1.3 [95%CI, -2.4, -0.2], β= -0.20, p<0.05) after covariate adjustment for age, race, sex, pubertal stage and BMI. Carotid pulsatile stress was related to regional carotid stiffness (r=0.45, p<0.05). These data suggest that higher levels of physical activity at young age are associated with lower hemodynamic stress in the carotid artery. Findings are discussed in the context of an inverse relationship between hemodynamic pulsatile stress and carotid stiffness in children.

An Accelerometric Sensor System With Integrated Hydrostatic Pressure Correction to Assess Carotid Arterial Stiffness

Non-invasive evaluation of vascular stiffness has established utility in cardiovascular risk and stroke prediction. This work presents an accelerometric sensor-based system with an integrated hydrostatic pressure correction unit for arterial luminal diameter measurement and local vascular stiffness assessment. A custom-designed accelerometric patch for continuous monitoring of percutaneous acceleration plethysmogram (APG) from the common carotid artery, which could estimate the arterial wall displacement, was developed. A calibration model was established to estimate the true carotid luminal diameter waveform from the accelerometer-based arterial wall displacement signals. The system’s accuracy for carotid stiffness measurement was validated by multiple in-vivo human subject studies and compared against a clinical-grade B-mode ultrasound imaging system. Accelerometric-derived carotid diameter waveform morphologically replicated the anachrotic, and dicrotic limb of the true carotid diameter recorded using reference devices. The group-average baseline value of measured carotid end-diastolic diameter and distension was 5.81 ± 0.53 mm and 0.51 ± 0.15 mm with a maximum observed beat-by-beat variation of 6.5% and 9%, respectively. Accelerometer-based vascular stiffness measures showed a significant correlation (R2 > 0.88, P < 0.0001), and clinically acceptable agreement with a reference standard imaging system. APG derived carotid stiffness indices demonstrated the capability to detect expected age-associated changes in stiffness. The study revealed that the accelerometric sensor system offers a reliable, cost-effective method for long-term non-invasive monitoring of location-specific vascular stiffness measures with potential applications in ambulatory healthcare monitors.

Is Stiffness Parameter β Useful for the Evaluation of Atherosclerosis?~ Its Clinical Implications, Limitations, and Future Perspectives ~.

Atherosclerosis comprises two components, atherosis and sclerosis, characterized by morphological wall thickening and functional stiffening, respectively, of the arterial wall. In recent years, much interest has been directed to the role of functional changes in large arteries, i.e., increased stiffness or decreased elasticity, on the development of cardiovascular diseases. In fact, the clinical evaluation of arterial stiffness is increasingly performed in patients with cardiovascular risk factors. Local arterial stiffness is measured using an ultrasound technique implemented with an echo-tracking system at the common carotid and femoral arteries. Several indices of local arterial stiffness are obtained by ultrasound, among which stiffness parameter β is unique because it is the least affected by blood pressure at the time of measurement. Evidence from cross-sectional studies indicates that increased stiffness parameter β is associated with a number of cardiovascular risk factors, such as older age, smoking, insufficient physical activity, hypertension, obesity, metabolic syndrome, insulin resistance, type 2 diabetes, chronic kidney disease, and comorbid cardiovascular disease. Results from several prospective observational studies also suggest that carotid stiffness parameter β is a useful surrogate marker of cardiovascular events and/or mortality, although the results differ depending on the characteristics of the study subjects. Furthermore, several interventional studies have shown that carotid stiffness parameter β improved after lifestyle modification or drug treatment. In this review, we summarize the current evidence of stiffness parameter β of the carotid artery and discuss its clinical implications as a marker of vascular health or as a predictor of cardiovascular outcomes.