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1.  Experimental exposure to diesel exhaust increases arterial stiffness in man 
Introduction
Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness.
Methods
In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 μg/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated.
Results
Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure.
Conclusion
Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution.
doi:10.1186/1743-8977-6-7
PMCID: PMC2660278  PMID: 19284640
2.  The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia 
Objective
To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia.
Methods
This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics.
Results
Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models.
Conclusion
First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency.
doi:10.7863/ultra.32.9.1593
PMCID: PMC3929514  PMID: 23980220
ADAM12; PAPP-A; placental dysfunction; pre-eclampsia; uterine artery Doppler
3.  Structural and functional abnormalities of large arteries in the Turner syndrome 
Heart  2005;91(11):1442-1446.
Objective: To analyse the structural and functional abnormalities in the large arteries in women with the Turner syndrome.
Methods: Aortic stiffness (assessed by means of the carotid femoral pulse wave velocity), level of amplification of the carotid pressure wave (by applanation tonometry), and carotid remodelling (by high resolution ultrasound) were studied in women with the Turner syndrome. Clinical and ambulatory blood pressures were taken into account in the analysis. Thus, 24 patients with the Turner syndrome and 25 healthy female subjects matched for age were studied.
Results: Women with the Turner syndrome had a higher augmentation index than the controls (Turner, mean (SD) 0.04 (0.14) v controls, −0.14 (0.13), p < 0.001) but a lower peripheral pulse pressure (39 (8) mm Hg v 47 (11) mm Hg, p  =  0.010 in the clinic; 44 (5) mm Hg v 47 (6) mm Hg, p  =  0.036 during the 24 hour ambulatory recording). The luminal diameter of the common carotid artery and the carotid–femoral pulse wave velocity were similar in the two groups, whereas carotid intima–media thickness tended to be higher in women with the Turner syndrome (0.53 (0.06) mm v 0.50 (0.05) mm, p  =  0.06). After correction for body surface area, carotid intima–media thickness and pulse wave velocity were higher in women with the Turner syndrome.
Conclusions: Vascular abnormalities observed in the Turner syndrome are implicated in the origin of the cardiovascular complications that occur in this syndrome. These abnormalities are morphological but also functional. An increase in the augmentation index can be explained in part by the short height of these patients.
doi:10.1136/hrt.2004.048371
PMCID: PMC1769156  PMID: 15761044
Turner syndrome; large arteries; hypertension; augmentation index; arterial stiffness
4.  Triglycerides are a predictive factor for arterial stiffness: a community-based 4.8-year prospective study 
Background
Epidemiological studies have disclosed an independent effect of triglycerides on coronary heart disease despite achievement of low-density lipoprotein cholesterol goals with statin therapy. Arterial stiffness has been increasingly recognized as a strong predictor of cardiovascular disease and atherosclerotic disease. The association between triglycerides and arterial stiffness is not well characterized. We aimed to determine the relationship between triglycerides and arterial stiffness in a community-based longitudinal sample from Beijing, China.
Methods
We related levels of plasma TGs to measures of arterial stiffness (carotid–femoral pulse wave velocity [PWV] and carotid–radial PWV) in 1447 subjects (mean age, 61.3 years) from a community-based population in Beijing, China.
Results
After a median follow-up interval of 4.8 years, multiple linear regression analysis revealed that TGs were independently associated with carotid–femoral PWV (β = 0.747, P < 0.001) and carotid-radial PWV (β = 0.367, P = 0.001). In the group older than 65 years, the association between baseline TG levels and follow-up carotid–femoral PWV (β = 1.094, P = 0.001) and carotid-radial PWV (β = 0.524, P = 0.002) were strengthened. In forward stepwise multivariate logistic regression analysis, every SD increase in TGδ was associated with a 1.296-increased likelihood of the presence of carotid–femoral PWVδII (OR [per SD increase in TGδ]: 1.296; 95 % CI: 1.064 ~ 1.580; P = 0.010) in Model 2, whereas the relationship between TGδ and carotid-radial PWVδII disappeared. In addition, the relationship was strengthened between TGδ and the presence of carotid–femoral PWVδII (OR 1.526, 95 % CI: 1.088–2.141, P = 0.014) in the group older than 65 years but not carotid-radial PWVδII. No association was noted in subjects younger than 65 years.
Conclusions
Lower triglyceride levels were significantly associated with decreases in carotid–femoral PWV, indicating that achieving low TG levels may be an additional therapeutic consideration in subjects with atherosclerotic disease.
doi:10.1186/s12944-016-0266-8
PMCID: PMC4870778  PMID: 27192979
Triglycerides; Carotid–femoral pulse wave velocity; Carotid–radial pulse wave velocity
5.  The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus 
Background
Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension, contributing to cardiovascular complications. Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness, and is an important contributing factor for hypertension. Since the sodium glucose cotransport-2 (SGLT2) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus, we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity.
Methods
Blood pressure, arterial stiffness, heart rate variability (HRV) and circulating adrenergic mediators were measured during clamped euglycaemia (blood glucose 4–6 mmol/L) and hyperglycaemia (blood glucose 9–11 mmol/L) in 40 normotensive type 1 diabetes mellitus patients. Studies were repeated after 8 weeks of empagliflozin (25 mg once daily).
Results
In response to empagliflozin during clamped euglycaemia, systolic blood pressure (111 ± 9 to 109 ± 9 mmHg, p = 0.02) and augmentation indices at the radial (-52% ± 16 to -57% ± 17, p = 0.0001), carotid (+1.3 ± 1 7.0 to -5.7 ± 17.0%, p < 0.0001) and aortic positions (+0.1 ± 13.4 to -6.2 ± 14.3%, p < 0.0001) declined. Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition. Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions (p ≤ 0.0001), while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia (5.7 ± 1.1 to 5.2 ± 0.9 m/s, p = 0.0017). HRV, plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions.
Conclusions
Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects. The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition, including glucose lowering, antihypertensive and weight reduction effects.
Trial registration
Clinical trial registration: NCT01392560
doi:10.1186/1475-2840-13-28
PMCID: PMC3915232  PMID: 24475922
Diabetes mellitus; Systemic blood pressure; SGLT2 inhibition; Empagliflozin; Hyperglycaemia; Arterial stiffness; Heart rate variability
6.  Comparison of sequentially measured Aloka echo-tracking one-point pulse wave velocity with SphygmoCor carotid–femoral pulse wave velocity 
SAGE Open Medicine  2013;1:2050312113507563.
Objectives:
Recently, echo-tracking-derived measures of arterial stiffness have been introduced in clinical practice for the assessment of one-point pulse wave velocity. The purpose of this study was to find a relation between carotid–femoral pulse wave velocity and one-point carotid pulse wave velocity, and to find a value of one-point carotid pulse wave velocity that predicts carotid–femoral pulse wave velocity higher than 12 m/s.
Methods:
A total of 160 consecutive subjects (112 male/48 female, mean age = 51.5 ± 14.1 years; 96 healthy, 44 hypertensives, 13 with aortic valve disease, and 7 with left ventricular dysfunction) were studied. Carotid–femoral pulse wave velocity was measured with the SphygmoCor system and one-point carotid pulse wave velocity with high-definition echo-tracking system (ProSound Alpha10; Aloka, Tokyo, Japan).
Results:
Both carotid–femoral pulse wave velocity and one-point carotid pulse wave velocity correlated significantly with each other (r = 0.539, p < 0.001) and with age (one-point carotid pulse wave velocity r = 0.618, carotid–femoral pulse wave velocity r = 0.617, p < 0.0001 for both). Median value of carotid–femoral pulse wave velocity (7.2 m/s, 95% confidence interval = 6.2–8.9) was systematically higher than that of one-point carotid pulse wave velocity (5.8 m/s, 95% confidence interval = 5–6.6). The area under the receiver operating characteristic curve was 0.85, identifying the cutoff for one-point pulse wave velocity of 6.65 m/s as the best predictor of carotid–femoral pulse wave velocity more than 12 m/s (sensitivity = 0.818, specificity = 0.819).
Conclusions:
One-point carotid pulse wave velocity correlates with carotid–femoral pulse wave velocity, and the cutoff of 6.65 m/s was the best predictor of carotid–femoral pulse wave velocity over 12 m/s.
doi:10.1177/2050312113507563
PMCID: PMC4687782  PMID: 26770685
Arterial stiffness; arterial pulse wave velocity; local carotid stiffness; echo-tracking
7.  Pulse Wave Velocity in Korean American Men and Women 
Arterial stiffness is an important clinical marker of cardiovascular diseases. Although many studies have been conducted on different racial groups, less is known about arterial stiffness in Asian Americans. Korean Americans constitute the fifth largest subgroup in the Asian American population and reportedly have a noticeably high prevalence of hypertension. The aims of this study were to assess arterial stiffness and blood pressure and to examine the effect of age and gender on arterial stiffness and blood pressure in 102 Korean American men and women aged 21 to 60 years. The values of arterial stiffness for Korean Americans in this study were compared to published reference values for other racial and ethnic groups. Arterial stiffness was measured by carotid-femoral pulse wave velocity, which is the gold standard for determining arterial stiffness. Findings indicated that aging was an important determinant of arterial stiffness, which increased linearly with age. Although there was no gender difference observed in arterial stiffness, the effect of age on arterial stiffness was greater in women than in men. After adjusting for covariates including age, body mass index, and smoking, multiple regression models showed that arterial stiffness and gender were significant predictors of systolic and diastolic blood pressure. The comparisons of these findings to those from several other studies that used the same method to measure arterial stiffness showed that Korean Americans may have levels of arterial stiffness that are similar to or slightly higher than those of other racial groups. Considering that arterial stiffness is an independent predictor of future development of hypertension, more studies are required to examine cardiovascular risk of this understudied group.
doi:10.1097/JCN.0b013e3182376685
PMCID: PMC3553793  PMID: 22222176
arterial stiffness; hypertension; Korean Americans
8.  Dehydroepiandrosterone replacement therapy in older adults improves indices of arterial stiffness 
Aging cell  2012;11(5):876-884.
Background
Serum dehydroepiandrosterone (DHEA) concentrations decrease ~80% between ages 25 and 75 yr. Aging also results in an increase in arterial stiffness, which is an independent predictor of cardiovascular disease (CVD) risk and mortality. Therefore, it is conceivable that DHEA replacement in older adults could reduce arterial stiffness. We sought to determine if DHEA replacement therapy in older adults reduces carotid augmentation index (AI) and carotid-femoral pulse wave velocity (PWV) as indices of arterial stiffness.
Methods
A randomized, double-blind trial was conducted to study the effects of 50 mg/d DHEA replacement on AI (n=92) and PWV (n=51) in women and men aged 65–75 yr. Inflammatory cytokines and sex hormones were measured in fasting serum.
Results
AI decreased in the DHEA group but not in the placebo group (difference between groups, −6±2 AI units, p=0.002). PWV also decreased (difference between groups, −3.5±1.0 m/sec, p=0.001); however, after adjusting for baseline values, the between-group comparison became non-significant (p=0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (TNFα and IL-6, p<0.05) and correlated with increases in serum DHEAS (r = −0.31 and −0.37, respectively, p<0.05). The reductions in AI also correlated with free testosterone index (r = −0.23, p=0.03).
Conclusion
DHEA replacement in elderly men and women improves indices of arterial stiffness. Arterial stiffness increases with age and is an independent risk factor for CVD. Therefore the improvements observed in the present study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.
doi:10.1111/j.1474-9726.2012.00852.x
PMCID: PMC3444670  PMID: 22712469
vasculature; augmentation index; aging
9.  Association of glomerular filtration rate with arterial stiffness in Chinese women with normal to mildly impaired renal function 
Objective
Both decreased glomerular filtration rate (GFR) and arterial stiffness were considered as risk factors for atherosclerosis. Previous studies have suggested the association between central arterial stiffness and the degree of GFR loss. Whether decreased GFR contributes to peripheral artery stiffness remains controversial. Moreover, data analyzed from a cohort of Chinese women are rare. Our aim was to explore the relationship between GFR and regional arterial stiffness in Chinese women.
Methods
In this cross-sectional study, we randomly recruited 1131 adult women residents with GFR ≥ 60 mL/min per 1.73 m2 estimated by the Chinese Modification of Diet in Renal Disease equation from three large communities. Central and peripheral arterial stiffness were estimated simultaneously by measuring carotid-femoral pulse wave velocity (PWVcf) and carotid-radial PWV (PWVcr) using a validated automatic device. Augmentation Index at heart rate 75 beats/minutes (AIx-75) was measured by pulse wave analysis as a composite parameter reflecting both large and distal arterial properties.
Results
The mean estimated GFR (eGFR) of the study group was 100.05 ± 23.26 mL/minute per 1.73 m2. Subjects were grouped by tertiles of eGFR level. PWVcf and AIx-75 increased ongoing from the top to the bottom eGFR tertile, while the values of PWVcr were comparable. Both univariate Pearson correlations and multiple stepwise regression analyses showed that eGFR significantly correlated to PWVcf, but not to PWVcr and AIx-75.
Conclusions
In Chinese women with normal to mildly impaired renal function, decreased eGFR affected carotid-to-femoral rather than carotid-to-radial stiffening. This provides rational to conduct future prospective studies to investigate predictors of atherosclerosis in this population.
doi:10.3724/SP.J.1263.2012.03051
PMCID: PMC3418906  PMID: 22916063
Arterial stiffness; Augmentation index; Pulse wave velocity; Glomerular filtration rate; Chinese women
10.  Comprehensive multi-modality assessment of regional and global arterial structure and function in adults born preterm 
Hypertension Research  2015;39(1):39-45.
Preterm birth is associated with higher blood pressure, which could be because preterm birth alters early aortic elastin and collagen development to cause increased arterial stiffness. We measured central and conduit artery size and multiple indices of arterial stiffness to define the extent and severity of macrovascular changes in individuals born preterm. A total of 102 young adults born preterm and 102 controls who were born after an uncomplicated pregnancy underwent cardiovascular magnetic resonance on a Siemens 1.5 T scanner to measure the aortic cross-sectional area in multiple locations. Ultrasound imaging with a Philips CX50 and linear array probe was used to measure carotid and brachial artery diameters. Carotid-femoral pulse wave velocity and the augmentation index were measured by SphygmoCor, brachial-femoral pulse wave velocity by Vicorder and aortic pulse wave velocity by cardiovascular magnetic resonance. The cardio-ankle vascular index (CAVI) was used as a measurement of global stiffness, and ultrasound was used to assess peripheral vessel distensibility. Adults born preterm had 20% smaller thoracic and abdominal aortic lumens (2.19±0.44 vs. 2.69±0.60 cm2, P<0.001; 1.25±0.36 vs. 1.94±0.45 cm2, P<0.001, respectively) but similar carotid and brachial diameters to adults born at term. Pulse wave velocity was increased (5.82±0.80 vs. 5.47±0.59 m s−1, P<0.01, 9.06±1.25 vs. 8.33±1.28 m s−1, P=0.01, 5.23±1.19 vs. 4.75±0.91 m s−1, P<0.01) and carotid distensibility was decreased (4.75±1.31 vs. 5.60±1.48 mm Hg−1103, P<0.001) in this group compared with the group born at term. However, the global and peripheral arterial stiffness measured by CAVI and brachial ultrasound did not differ (5.95±0.72 vs. 5.98±0.60, P=0.80 and 1.07±0.48 vs. 1.19±0.54 mm Hg−1103, P=0.12, respectively). Adults who are born preterm have significant differences in their aortic structure from adults born at term, but they have relatively small differences in central arterial stiffness that may be partially explained by blood pressure variations.
doi:10.1038/hr.2015.102
PMCID: PMC4709461  PMID: 26399455
arterial stiffness; blood pressure; preterm birth
11.  Reproducibility of carotid-femoral pulse wave velocity in end-stage renal disease patients: methodological considerations 
Background
In end-stage renal disease (ESRD) patients, increased arterial stiffness detected by carotid-femoral pulse wave velocity (cf-PWV) is associated with fatal cardiovascular events and all-cause mortality. Since cf-PWV is an operator-dependent technique, poor reproducibility may be a source of bias in the estimation of arterial stiffness.
Objectives
We assessed the week-to-week reproducibility of cf-PWV and radial artery pulse wave analysis in healthy subjects and ESRD patients. We also determined the extent of patient eligibility, enrollment, acceptance, and comfort.
Methods
In a cohort study design, independent tonometric examinations of carotid, femoral, and radial arteries were conducted in 20 healthy subjects and 15 ESRD patients attending chronic hemodialysis treatments according to a randomized sequence by two operators on 2 days scheduled 1-week apart. cf-PWV, augmentation index (AIx@HR75) and central pulse pressure (CPP) were the outcome measures. Patients were tested at mid-week and prior to dialysis treatment. The variability on the distance measured between the suprasternal notch and femoral site using two different methods (standard vs direct) was compared. A post-examination survey assessed acceptance and comfort associated with examinations. Reproducibility was evaluated by intra-class correlations (ICCs).
Results
The mean age for healthy subjects and ESRD patients was 45 ± 12 and 63 ± 16 years, respectively. ESRD patients had higher cf-PWV (p = 0.0002), elevated AIx@HR75 (p = 0.003), and increased CPP (p = 0.001) compared to healthy subjects. The mean inter-visit differences for all stiffness indices were non-significant (p > 0.05), but the mean inter-operator differences for the cf-PWV were significant only in the healthy subject group (−0.7 m/s; p = 0.02). The ICCs between operators and visits were higher for the ESRD group compared to the healthy subjects (between operators, 0.870 vs 0.461; between visits, 0.830 vs 0.570). Distances were longer (p < 0.001), but less variable with the standard method compared to the direct method (healthy subjects, p = 0.036; ESRD, p = 0.39). There was a high rate of patient acceptance and minimal discomfort.
Conclusions
Week-to-week measurements of cf-PWV and pulse wave analysis are highly reproducible in ESRD patients prior to hemodialysis treatment. The high reproducibility and minimal test-to-test variations encourage use of cf-PWV to monitor changes in arterial stiffness and the efficacy of interventions in ESRD patients.
Trial registration
ClinicalTrials.gov, NCT02196610.
Electronic supplementary material
The online version of this article (doi:10.1186/s40697-016-0109-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s40697-016-0109-6
PMCID: PMC4818522  PMID: 27042326
Aortic stiffness; End-stage kidney disease; Inter-observer variation; Validation studies
12.  Cardiovascular biomarkers and vascular function during childhood in the offspring of mothers with hypertensive disorders of pregnancy: findings from the Avon Longitudinal Study of Parents and Children 
European Heart Journal  2011;33(3):335-345.
Aims
It is uncertain if the higher blood pressure (BP) observed in the offspring of hypertensive pregnancies is an isolated abnormality or one that is accompanied by impaired vascular function and alterations in lipid and inflammation markers that would be indicative of a more general cardiometabolic disturbance of the type observed in the mother during pre-eclampsia.
Methods and results
In a large UK cohort of maternal-offspring pairs (n = 3537–4654), assessed at age 9–12 years, we examined the associations of maternal gestational hypertension and pre-eclampsia with offspring BP, endothelial function assessed by brachial artery flow-mediated dilatation; arterial stiffness assessed by carotid to radial pulse wave velocity; brachial artery distensibility and BP (vascular outcomes); as well as markers of inflammation, lipids and apolipoproteins A1 and B. Offspring of women with pre-eclampsia or gestational hypertension had higher systolic blood pressure by 2.04 mmHg (95% CI: 1.33, 2.76) and 1.82 mmHg (95% CI: 0.03, 3.62), respectively, and higher diastolic blood pressure by 1.10 mmHg (95% CI: 0.47, 1.73) and 1.26 mmHg (95% CI: −0.32, 2.85), respectively, in analyses adjusted for maternal and offspring body mass index (BMI), offspring dietary sodium intake and other potential confounders. However, we found no associations of either hypertensive disorder of pregnancy with the other vascular outcomes or with inflammatory markers, lipids, and apolipoproteins.
Conclusion
Pre-eclampsia and gestational hypertension are associated with higher offspring BP in childhood in the absence of other vascular alterations or metabolic derangements. The findings support the existence of shared mother-offspring risk factors that are specific for higher BP, rather than the additional cardiometabolic abnormalities of hypertensive disorder of pregnancy having long-term consequences for offspring.
doi:10.1093/eurheartj/ehr300
PMCID: PMC3270043  PMID: 21862461
Hypertensive disorder of pregnancy; Endothelial function; Arterial stiffness; Blood pressure; Lipids; ALSPAC
13.  In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat 
Background
Rodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate.
Methods
We obtained PWV and EaI measurements in isoflurane anesthetized young and old SHRs, which are known to have significant differences in arterial stiffness. Doppler pulse waves were recorded from carotid and iliac arteries and the distance (D) between probe applantation sites was recorded. Simultaneously, an EKG was obtained, and the time intervals between the R-wave of the EKG to the foot of the Doppler waveforms were measured and averaged over three cardiac cycles. Pulse-transit time (T) of the carotid to iliac artery was determined, and PWV was calculated as Distance (D)/Time (T), where D = the distance from the carotid to the iliac notch and T = (R to iliac foot) - (R to carotid foot). EaI was subsequently determined from pressure volumes loops obtained via left ventricle catheterization.
Results
PWV and EaI were found to be significantly faster in the older rats (13.2 ± 2.0 vs. 8.0 ± 0.8 m/sec, p < 0.001; 120 ± 20 vs. 97 ± 16 mmHg/μl/g, p <0.05). Bland-Altman analyses of intra- and inter-observer measures demonstrate a statistically significant relationship between readings (p < 0.0001). PWV and EaI measurements were found to be significantly and positively correlated with a correlation coefficient of 0.53 (p < 0.05).
Conclusion
Our study suggests that isoflurane administration does not limit Doppler PWV or EaI measures in their ability to provide accurate, in vivo assessments of relative arterial stiffness in isoflurane anesthetised SHR rats. Furthermore, PWV data obtained in these rats correlate well with invasively determined EaI.
doi:10.1186/1476-7120-12-37
PMCID: PMC4245200  PMID: 25227282
Blood pressure; Arterial stiffness; Pulse wave velocity; Arterial elasticity index; Doppler; Ultrasound; Isoflurane; Anesthesia; SHR; Rat
14.  Circulating endothelial progenitor cells and large artery structure and function in young subjects with uncomplicated Type 1 Diabetes 
Background
Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated.
Methods
Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured.
Results
After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP.
Conclusions
Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.
doi:10.1186/1475-2840-10-88
PMCID: PMC3198903  PMID: 21981808
Type 1 diabetes; Endothelial progenitor cells; Endothelium-dependent vasodilation; Radiofrequency based ultrasound; Carotid intima-media thickness; Carotid stiffness; Aortic stiffness; Arterial wave reflection; Advanced glycation end-products; Adiponectin
15.  Long-Term Trandolapril Treatment Is Associated With Reduced Aortic Stiffness 
Hypertension  2007;49(6):1271-1277.
The Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial evaluated angiotensin-converting enzyme inhibition with trandolapril versus placebo added to conventional therapy in patients with stable coronary disease and preserved left ventricular function. The PEACE hemodynamic substudy evaluated effects of trandolapril on pulsatile hemodynamics. Hemodynamic studies were performed in 300 participants from 5 PEACE centers a median of 52 months (range, 25 to 80 months) after random assignment to trandolapril at a target dose of 4 mg per day or placebo. Central pulsatile hemodynamics and carotid–femoral pulse wave velocity were assessed by using echocardiography, tonometry of the carotid and femoral arteries, and body surface transit distances. Patients randomly assigned to trandolapril tended to be older (mean±SD: 64.2±7.9 versus 62.9±7.7 years; P=0.14), with a higher body mass index (28.5±4.0 versus 27.8±3.9 kg/m2; P=0.09) and lower ejection fraction (57.1±8.1% versus 58.7±8.4%; P<0.01). At the time of the hemodynamic substudy, the trandolapril group had lower mean arterial pressure (93.1±10.2 versus 96.3±11.3 mm Hg; P<0.01) and lower carotid-femoral pulse wave velocity (geometric mean [95% CI]: 10.4 m/s [10.0 to 10.9 m/s] versus 11.2 m/s [10.7 to 11.8 m/s]; P=0.02). The difference in carotid–femoral pulse wave velocity persisted (P<0.01) in an analysis that adjusted for baseline characteristics and follow-up mean pressure. In contrast, there was no difference in aortic compliance, characteristic impedance, augmentation index, or total arterial compliance. Angiotensin-converting enzyme inhibition with trandolapril produced a modest reduction in carotid–femoral pulse wave velocity, a measure of aortic wall stiffness, beyond what would be expected from blood pressure lowering or differences in baseline characteristics alone.
doi:10.1161/HYPERTENSIONAHA.106.085738
PMCID: PMC2553625  PMID: 17452505
angiotensin-converting enzyme; coronary artery disease; randomized clinical trial; arterial stiffness; pulse wave velocity
16.  Augmentation index and aortic stiffness in bicuspid aortic valve patients with non-dilated proximal aortas 
Background
We compared aortic stiffness, aortic impedance and pressure from wave reflections in the setting of bicuspid aortic valve (BAV) to the tricuspid aortic valve (TAV) in the absence of proximal aortic dilation. We hypothesized BAV is associated with abnormal arterial stiffness.
Methods
Ten BAV subjects (47 ± 4 years, 6 male) and 13 TAV subjects (46 ± 4 years, 10 male) without significant aortic valve disease were prospectively recruited. Characteristic impedance (Zc) was derived from echocardiographic images and pulse wave Doppler of the left ventricular outflow tract. Applanation tonometry was performed to obtain pulse wave velocity (PWV) at several sites as measures of arterial stiffness and augmentation index (AIx) as a measure of wave reflection.
Results
There were no significant differences between BAV and TAV subjects with regard to heart rate or blood pressure. Zc was similar between BAV and TAV subjects (p=0.25) as was carotid-femoral pulse wave velocity (cf-PWV) and carotid-radial PWV (cr-PWV) between BAV and TAV subjects (p=0.99). Carotid AIx was significantly higher in BAV patients compared with TAV patients (14.3 ± 4.18% versus -3.02 ± 3.96%, p=0.007).
Conclusions
Aortic stiffness and impedance is similar between subjects with BAV and TAV with normal aortic dimensions. The significantly higher carotid AIx in BAV, a proxy of increased pressure from wave reflections, may reflect abnormal vascular function distal to the aorta.
doi:10.1186/1471-2261-13-19
PMCID: PMC3602003  PMID: 23496804
Bicuspid aortic valve; Arterial stiffness; Augmentation index; Pulse wave velocity
17.  Pulse Wave Analysis in Normal Pregnancy: A Prospective Longitudinal Study 
PLoS ONE  2009;4(7):e6134.
Background
Outside pregnancy, arterial pulse wave analysis provides valuable information in hypertension and vascular disease. Studies in pregnancy using this technique show that vascular stiffness is raised in women with established pre-eclampsia. We aimed to establish normal ranges for parameters of pulse wave analysis in normal pregnancy and to compare different ethnic groups.
Methodology/Principal Findings
This prospective study was conducted at The Homerton University Hospital, London between January 2006 and March 2007. Using applanation tonometry, the radial artery pulse waveform was recorded and the aortic waveform derived. Augmentation pressure (AP) and Augmentation Index at heart rate 75/min (AIx-75), measures of arterial stiffness, were calculated.
We recruited 665 women with singleton pregnancies. Women who developed pre-eclampsia (n = 24, 3.6%) or gestational hypertension (n = 36, 5.4%) were excluded. We also excluded 47 women with other pregnancy complications or incomplete follow-up, leaving 541 healthy normotensive pregnant women for subsequent analysis. In the overall group of 541 women, there were no significant changes in AP or AIx-75 as pregnancy progressed. In 45 women followed longitudinally, AP and AIx-75 fell significantly from the first to the second trimester, then rose again in the third (P<0.001). The two main ethnic groups represented were Caucasian (n = 229) and Afrocaribbean (n = 216). There were no significant differences in AP or AIx-75 in any trimester between these two ethnic groups.
Conclusions
This study is the largest to date of pulse wave analysis in normal pregnancy, the first to report on a subset of women studied longitudinally, and the first to investigate the effect of ethnicity. These data provide the foundation for further investigation into the potential role of this technique in vascular disorders in pregnancy.
doi:10.1371/journal.pone.0006134
PMCID: PMC2700961  PMID: 19578538
18.  Association of Aortic Stiffness and Wave Reflections with Coronary Flow Reserve in Women without Obstructive Coronary Artery Disease: An Ancillary Study from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) 
American heart journal  2015;170(6):1243-1254.
Background
Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited.
Methods
CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53±11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized.
Results
Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = −0.51), pulse wave amplification (r = 0.45), augmented pressure (AP, r = −0.48), augmentation index (AIx, r = −0.44), aortic systolic pressure (r = −0.49), left ventricular wasted energy (LVEw, r = −0.47) (all P < 0.001), systolic pressure time index (r = −0.37, P < 0.008), and rate pressure product (r = −0.29, P < 0.04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < 0.008) and aortic systolic pressure (P < 0.01). No other measures contributed significant additional information.
Women with CFR ≤2.5 vs. those with CFR >2.5 had greater aPWV (894 ± 117 vs. 747 ± 93 cm/sec, P < 0.001), AP (14 ± 4.9 vs. 11 ± 4.1 mmHg, P < 0.008), AIx (32 ± 6.6 vs. 27 ± 6.6%, P < 0.003), LVEw (30 ± 12 vs. 21 ± 10 dyne-sec/cm2 × 102, P < 0.02) and reduced pulse pressure amplification (1.20 ± .07 vs. 1.26 ± .10, P < 0.008) and pressure wave travel time (133 ± 7.3 vs. 138 ± 6.9 msec, P < 0.04).
Conclusions
Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase LV afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.
doi:10.1016/j.ahj.2015.08.019
PMCID: PMC4685957  PMID: 26678647
coronary microvascular dysfunction; coronary flow reserve; aortic pressure waveform; pulse wave analysis; pulse wave velocity; wave reflections; aortic stiffness
19.  Bone Mineral Density as a Predictor of Atherosclerosis and Arterial Wall Stiffness in Obese African-American Women 
Cardiorenal Medicine  2012;2(4):328-334.
Bone demineralization is associated with higher cardiovascular event rates, possibly due to vascular calcification and accelerated atherosclerosis. African-Americans have less bone loss and less calcium content within atherosclerotic plaques. However, whether loss of bone mass is related to atherosclerosis has not been examined in African-Americans. The objective of this study was to evaluate possible associations between bone mineral density (BMD), carotid intimal-medial thickness (CIMT), and arterial stiffness. We studied 100 obese African-American women (BMI: 26.6 ± 6.2; age: 63 ± 14 years) referred for BMD estimation by dual-energy X-ray absorptiometry scan. BMD (g/cm2) was obtained at the lumbar spine (L1–L4), femoral neck, and total hip. Arterial stiffness was evaluated by the heart rate-corrected augmentation index (AI@75) and pulse wave velocity (PWV) using applanation tonometry. CIMT was measured by vascular ultrasound. Mean CIMT, AI@75, and PWV were 0.72 ± 0.14 mm, 28.8 ± 9.0%, and 8.9 ± 1.6 m/s, respectively. Mean BMD values at the lumbar spine, femoral neck, and hip were 0.96 ± 0.19, 0.80 ± 0.16, and 0.91 ± 0.17 g/cm2. Older subjects had higher CIMT (r = 0.61, p < 0.001) and AI@75 (r = 0.42, p < 0.001). There was a significant correlation between AI@75 and CIMT (r = 0.45, p < 0.001). BMD was negatively correlated with AI@75 (lumbar: r = −0.22, p = 0.03; femoral neck: r = −0.24, p = 0.01; hip: r = −0.21, p = 0.03). BMD was unrelated to CIMT (lumbar: r = −0.09, p = 0.42; femoral neck: r = −0.15, p = 0.17; hip: r = −0.13, p = 0.23). On multivariate analysis, age (p < 0.001), hypertension (p = 0.02), and lumbar BMD (p = 0.01, R2 = 0.30) were independent predictors of increased AI@75 after adjusting for age, height, and cardiovascular risk factors. These findings were unchanged upon substitution of femoral neck BMD (p = 0.05, R2 = 0.28) into the model. There was a trend with hip BMD (p = 0.06, R2 = 0.28) in the regression model. Age-matched comparison between normal BMD (n = 25) and osteoporotic patients (n = 34) demonstrated a significant difference in AI@75 (26.6 ± 8.9 vs. 31.6 ± 9.1%, p = 0.04). In summary, women with lower BMD had increased arterial stiffness. There was no relationship between BMD and atherosclerosis. In conclusion, age, hypertension, and BMD are independent predictors of higher arterial stiffness. Vascular changes are related to bone mineral loss, suggesting lower BMD may increase cardiovascular risk in African-Americans.
doi:10.1159/000345461
PMCID: PMC3551407  PMID: 23381741
Bone mineral density; Osteoporosis; Atherosclerosis; Wave reflection; Aortic stiffness
20.  Increased aortic stiffness and blood pressure in non-classic Pompe disease 
Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20 %), more Pompe patients had a history of hypertension (36 %, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly.
doi:10.1007/s10545-013-9667-2
PMCID: PMC4013448  PMID: 24407465
21.  Arterial Stiffness and Wave Reflection: Sex Differences and Relationship with Left Ventricular Diastolic Function 
Hypertension  2012;60(2):362-368.
Increased arterial stiffness and wave reflection have been reported in heart failure with normal ejection fraction (HFNEF) and in asymptomatic left ventricular (LV) diastolic dysfunction, a precursor of HFNEF. It is unclear whether women, who have higher frequency of HFNEF, are more vulnerable than men to the deleterious effects of arterial stiffness on LV diastolic function. We investigated in a large community-based cohort, whether sex differences exist in the relationship between arterial stiffness, wave reflection and LV diastolic function. Arterial stiffness and wave reflection were assessed in 983 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study using applanation tonometry. Central pulse pressure/stroke volume index (cPP/SVi), total arterial compliance, pulse pressure amplification and augmentation index were used as parameters of arterial stiffness and wave reflection. LV diastolic function was evaluated by two-dimensional echocardiography and tissue-Doppler imaging. Arterial stiffness and wave reflection were greater in women compared to men, independent of body size and heart rate (all p<0.01), and showed inverse relationships with parameters of diastolic function in both sexes. Further adjustment for cardiovascular risk factors attenuated these relationships; however, higher cPP/SVi predicted LV diastolic dysfunction in women [odds ratio (OR) 1.54, 95% confidence intervals (CI) 1.03–2.30] and men (OR: 2.09, 95% CI 1.30–3.39) independent of other risk factors. In conclusion, in our community-based cohort study, higher arterial stiffness was associated with worse LV diastolic function in men and women. Women’s higher arterial stiffness, independent of body size, may contribute to their greater susceptibility to develop HFNEF.
doi:10.1161/HYPERTENSIONAHA.112.191148
PMCID: PMC3402954  PMID: 22753223
Arterial stiffness; Wave reflection; Diastole; Sex; Echocardiography
22.  Arterial Stiffness is Associated with Increase in Blood Pressure Over Time in Treated Hypertensives 
Background
Arterial stiffness is associated with incident hypertension. We hypothesized that arterial stiffness would predict increases in systolic (SBP), mean (MAP) and pulse pressure (PP) over time in treated hypertensives.
Methods
Blood pressure (BP) was measured a mean of 8.5±0.9 years apart in 414 non-Hispanic white hypertensives (mean age 60±8 years, 55% women). The average of 3 supine right brachial BPs was recorded. Measures of arterial stiffness including carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx) and central pulse pressure (CPP) were obtained at baseline by applanation tonometry. We performed stepwise multivariable linear regression analyses adjusting for potential confounders to assess the associations of arterial stiffness parameters with BP changes over time.
Results
Systolic, mean and pulse pressure increased in 80% of participants. After adjustment for the covariates listed above, cfPWV was significantly associated with increases in SBP (β±SE: 0.71±0.31) and PP (β±SE: 1.09±0.27); AIx was associated with increases in SBP (β±SE: 0.23±0.10) and MAP (β±SE: 0.27±0.07); and CPP was associated with increases in SBP (β±SE: 0.44±0.07), MAP (β±SE: 0.24±0.05) and PP (β±SE: 0.42±0.06) over time (P≤0.02 for all).
Conclusions
Baseline arterial stiffness measures were associated with longitudinal increases in SBP, MAP and PP in treated hypertensives.
doi:10.1016/j.jash.2014.03.330
PMCID: PMC4103613  PMID: 24952654
hypertension; pulse wave velocity; pulse pressure; augmentation index
23.  Circulating Angiogenic Cell Populations, Vascular Function, and Arterial Stiffness 
Atherosclerosis  2011;220(1):145-150.
Objective
Several bone marrow-derived cell populations have been identified that may possess angiogenic activity and contribute to vascular homeostasis in experimental studies. We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness.
Methods
We studied 1,948 Framingham Heart Study participants (mean age, 66±9 years; 54% women) who were phenotyped for circulating angiogenic cells: CD34+, CD34+/KDR+, and early outgrowth colony forming units (CFU). Participants underwent non-invasive assessments of vascular function including peripheral arterial tone (PAT), arterial tonometry, and brachial reactivity testing.
Results
In unadjusted analyses, higher CD34+ and CD34+/KDR+ concentrations were modestly associated with lower PAT ratio (β=−0.052±0.011, P<0.001 and β=−0.030±0.011, P=0.008, respectively) and with higher carotid-brachial pulse wave velocity (β=0.144±0.043, P=0.001 and β=0.112±0.043, P=0.009), but not with flow-mediated dilation; higher CD34+ was also associated with lower carotid-femoral pulse wave velocity (β=−0.229±0.094, P=0.015) However, only the association of lower CD34+ concentration with higher PAT ratio persisted in multivariable analyses that adjusted for standard cardiovascular risk factors. In all analyses, CFU was not associated with measures of vascular function or arterial stiffness.
Conclusions
In our large, community-based sample of men and women, circulating angiogenic cell phenotypes largely were not associated with measures of vascular function or arterial stiffness in analyses adjusting for traditional risk factors.
doi:10.1016/j.atherosclerosis.2011.10.015
PMCID: PMC3277804  PMID: 22093724
angiogenesis; vascular function; risk factors; endothelium; epidemiology
24.  The relationship between various measures of obesity and arterial stiffness in morbidly obese patients 
Background
Obesity is associated with increased risk of cardiovascular disease. Arterial stiffness assessed by carotid femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of body composition affect arterial stiffness.
Methods
This is an analysis of cross-sectional baseline data from a controlled clinical trial addressing changes in arterial stiffness after either surgery or lifestyle intervention in a population of morbidly obese patients. High-fidelity applanation tonometry (Millar®, Sphygmocor®) was used to measure pulse wave velocity (PWV). Carotid femoral PWV is a direct measure of arterial stiffness and is considered to be the gold standard method. The Inbody 720 Body Composition Analyzer was used for bioelectrical impedance analysis (BIA). Spearman's correlation, independent samples t-test, chi-square tests, Fisher's exact test and multiple linear regression analyses were used as statistical methods.
Results
A total of 133 patients (79 women), with a mean (SD) age of 43 (11) years were included in the study. Men had a significantly higher prevalence of obesity related comorbidities and significantly higher PWV, 9.1 (2.0) m/s vs. 8.1 (1.8) m/s, p = 0.003, than women. In the female group, PWV was positively correlated with WC, WHtR, BMI and visceral fat area. In the male group, PWV was negatively correlated with BMI. Multiple linear regression analysis showed that increasing BMI, WC, WHtR, visceral fat area and fat mass were independently associated with higher PWV in women, but not in men, after adjustment for age, hypertension and type 2 diabetes.
Conclusion
Most measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients.
Trial registration
ClinicalTrials.gov Identifier NCT00626964
doi:10.1186/1471-2261-11-7
PMCID: PMC3042421  PMID: 21284837
25.  The effect of L-arginine on arterial stiffness and oxidative stress in chronic kidney disease 
Indian Journal of Nephrology  2012;22(5):340-346.
Chronic kidney disease (CKD) is a growing problem worldwide. The disproportionate increase in the burden of cardiovascular disease in patients with CKD may be significantly contributed by nontraditional risk factors. Increased arterial stiffness has been recognized as an important player in contributing to this morbidity and mortality. The aim of this study was to report the effect of L-arginine on arterial stiffness and oxidative stress in patients with CKD. Thirty patients with stage II to IV CKD were administered 9 g of L- arginine per day orally for a period of 12 weeks. The parameters evaluated at baseline, at 8 weeks, and at the end of 12 weeks were serum nitric oxide (NO), carotid.femoral pulse wave velocity (cf PWV), and radial artery pulse wave analysis which included aortic augmentation pressure (AP), aortic augmentation index (AIx), aortic augmentation index at heart rate of 75 bpm, subendocardial viability ratio, radial pressures, and central aortic pressure. Serum levels of NO and malondialdehyde (MDA) were estimated at baseline and at the end of 12 weeks. The control group was composed of age- and sex-matched healthy individuals. Twenty-five patients completed the study. Two patients were lost to follow.up; three patients developed adverse events and were excluded. Baseline NO levels were low (13.55 ± 7.49 μM/L) in all the subjects. Administration of L-arginine resulted in improvement in the carotid-radial PWV (m/s) (10.08 ± 1.72 at baseline to 8.56 ± 1.16 by 12 weeks; P < 0.001), cf PWV (m/s) (13.06 ± 2.65 at baseline to 10.62 ± 1.93 at 12 weeks; P < 0.001), Aortic Augmentation Index (%) (32 ± 10.34 at baseline to 17.84 ± 8.05 at 12 weeks; P < 0.001), aortic augmentation pressure (mm of Hg) (14.03 ± 6.53 at baseline to 7.12 ± 3.85 at 12 weeks; P < 0.001), and NO (μM/L) (13.55 ± 7.49 at baseline to 30.22 ± 9.8 at 12 weeks; P < 0.001). There was no significant change in the levels of MDA (nanomol/ml) (20.0 ± 10.14 at baseline and 19.16 ± 9.36 at 12 weeks; P = ns). In conclusion, PWV, an indicator of arterial stiffness, is greatly increased even in the early stages of CKD. Supplementation of L-arginine is a safe, well-tolerated, and effective way of improving endothelial dysfunction in patients with CKD.
doi:10.4103/0971-4065.103907
PMCID: PMC3544054  PMID: 23326043
Arterial stiffness; chronic kidney disease; L-arginine; oxidative stress; pulse wave velocity

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