Measure Of Large Artery Stiffness Research Articles

The relationship between large artery stiffness, wave reflection and pulsatility in the micro-circulation: new insights into the management of both hypertension and diabetes

Objective: Increased arterial stiffness is associated with a reduced buffering capacity of the large arteries, therefore predisposing the microcirculation to increased flow and pressure pulsatility. However, increased wave reflection may be protective, by reducing the amount of pulsatility transmitted to the microcirculation. The aim of this study was to examine this hypothesis by exploring the relationship between large artery stiffness, wave reflections and pulsatility in the microvasculature. Design and Method: 67 volunteers, aged 64 ± 10 years, not taking any sympathomimetic compounds and free from any acute ocular symptoms participated. Aortic pulse wave velocity (aPWV) and augmentation index (AIx) were recorded using the SphygmoCor system as measures of large artery stiffness and wave reflection, respectively. Retinal artery resistance index (RI), a measure of early retinal organ damage and pulsatility ratio (PR), a measure of retinal artery pulsatility were recorded using doppler ultrasound (Aloca). Results: aPWV was significantly associated with RI (R = 0.43,P = 0.001) and PR (R = 0.54,P = < 0.001) whereas AIx was significantly and inversely related to RI (R = -0.26,P = 0.047) and PR (R = -0.33, P = 0.011, respectively). Stratifying individuals according to tertile of aPWV and AIx revealed that RI and PR were significantly higher in those individuals with high aPWV but low AIx, compared with individuals with low aPWV and high AIx (0.51 ± 0.13 vs 0.37 ± 0.06, P = 0.004,RI; and 2.2 ± 0.61vs1.6 ± 0.20; P = 0.008, PR). Conclusions: Increased large artery stiffness is implicated in microcirculatory damage. However, increased wave reflections may exert a protective effect. Future mechanistic studies linking the macro and micro-circulations may provide important insights into the management of conditions such as hypertension and diabetes.

Dissociation of Aortic Pulse Wave Velocity With Risk Factors for Cardiovascular Disease Other Than Hypertension

Carotid-femoral pulse wave velocity (cfPWV), a measure of large artery stiffness, is an important predictor of cardiovascular events. This has been attributed to it being an integrative measure of the impact of cardiovascular risk factors on the arterial wall. Pulse wave velocity is strongly associated with age and blood pressure. However, findings with regard to its relation with other risk factors have been inconsistent. We performed a systematic review of cross-sectional published literature reporting independent associations of cfPWV in multivariable regression models. Articles were selected from a PubMed search using a prespecified search strategy. Studies were included if they did the following: (1) measured cfPWV; (2) reported on associations with cfPWV from regression models; and (3) considered age and blood pressure in the model. From 637 retrieved articles, 65 met our inclusion criteria, and 12 studies were included from reference searches. Age and blood pressure were consistently independently associated with cfPWV (91% and 90% of studies, respectively). Diabetes mellitus was associated with cfPWV in 52% studies, but the strength of the association was low. The majority of studies found no independent association between cfPWV and sex, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, or body mass index. The contribution of risk factors other than age and blood pressure to cfPWV is, thus, small or insignificant. The prognostic value of cfPWV may relate to a process of arterial ageing unrelated to classic risk factors other than hypertension.

Effects of cardiovascular angiotensin II type 1 receptor blockade on nitric oxide synthase inhibition in patients with insulin resistance syndrome

Background. There is evidence that in the early stages of type II diabetes, the cardiovascular system compensates by increasing endothelial nitric oxide synthase (e-NOS) expression. In the advanced stages of disease, e-NOS is diminished, and is associated with endothelial dysfunction. Angiotensin II, acting via the angiotensin II type 1 (AT1) receptor, is central to the development of endothelial dysfunction. The effect of AT1 receptor blockade on NOS expression and activity in humans with early insulin resistance syndrome (INSR) has not been previously investigated. Eight subjects with INSR participated in a randomized, double-blind, placebo-controlled, crossover study. Subjects were randomized to receive telmisartan or placebo (1 month of each) in a two-period crossover study with a 1-week washout period in between. The arterial stiffness and haemodynamic response to intravenous L-nitro-monomethyl arginine (L-NMMA 3mg/kg) was assessed at baseline and at the end of each treatment phase. SI (Stiffness index, a measure of large artery stiffness) and RI (Reflection index, small- to medium-sized arterial stiffness) were measured using digital photoplethysmography. Haemodynamic parameters [Heart rate (HR), Systolic blood pressure (SBP), Diastolic BP (DBP) and systemic vascular resistance index (SVRI)] were measured non-invasively using trans-thoracic bioimpedance. Results. Telmisartan significantly reduced baseline SI, SBP, DBP and SVRI. Infusion of L-NMMA produced a significant increase in RI and a significant reduction in HR during placebo therapy. Telmisartan therapy attenuated these responses. Conclusion. Telmisartan therapy reduced NOS activity and/or expression in these subjects, possibly because of improved vascular function arising from AT1 receptor blockade.

Long-Term Effects of Fenofibrate on Carotid Intima-Media Thickness and Augmentation Index in Subjects With Type 2 Diabetes Mellitus

The aim of this substudy was to ascertain whether long-term treatment with fenofibrate reduces surrogate measures of atherosclerosis, biomarkers of inflammation, and endothelial activation in patients with type 2 diabetes. Some fibrates may decrease cardiovascular events, improve endothelial function, and reduce levels of acute-phase proteins. In the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study, fenofibrate failed to decrease the primary end point of coronary events in patients with type 2 diabetes. A total of 170 patients with type 2 diabetes of the FIELD Helsinki cohort were randomly assigned to micronized fenofibrate 200 mg/day or placebo in a double-blind design. Carotid intima-media thickness (IMT) and the augmentation index (a measure of large artery stiffness) were measured at baseline and at second- and fifth-year visits. Plasma levels of interleukin (IL)-6, C-reactive protein (CRP), serum amyloid A (SAA), secretory phospholipase A2 IIA (SPLA2), E-selectin, vascular cellular adhesion molecule (VCAM)-1, and intercellular adhesion molecule (CAM)-1 were determined by commercial enzyme-linked immunosorbent assay kits at the same visits. IMT and the augmentation index increased similarly in both treatment groups during the study. Plasma levels of CRP, IL-6, SPLA2, SAA, VCAM-1, ICAM-1, and E-selectin remained unchanged in both groups. Fenofibrate treatment was not associated with beneficial changes in IMT, augmentation index, or biomarkers of inflammation and endothelial function. (Fenofibrate Intervention and Event Lowering in Diabetes; NCT00132886).

Effect of dietary supplementation with βcasein A1 or A2 on markers of disease development in individuals at high risk of cardiovascular disease

The present study is the first to examine the hypothesis that dietary supplementation with beta-casein A1 promotes an increased risk relative to supplementation with beta-casein A2 in patients traditionally at high risk of developing CVD. The study was conducted in fifteen asymptomatic participants (six male; nine female) at high risk of developing CVD. A double-blind cross-over study design was used with a total duration of 24 weeks. Dietary intervention was a daily supplementation (25 g) of either casein A1 or A2 (for 12 weeks each). Surrogate measures of cardioprotection studied included the examination of vascular (endothelium and arterial) function, resting blood pressure, plasma lipids and biochemical markers of inflammation. Total plasma cholesterol levels were significantly lower following 12 weeks of both casein A1 and A2 interventions but the decrease was not different between intervention. Plasma insulin, homocysteine, C-reactive protein, fibrinogen, protein C and S and von Willebrand factor levels were not different between the two casein supplements. Endothelium function, measured as a vascular response using venous occlusion plethysmography to intra-arterial infusions of the endothelium-dependent agonist acetylcholine, were not different between the two casein interventions. Similarly, neither blood pressure nor measures of large artery stiffness were affected by differing the casein variant. We therefore conclude that there is no evidence from the present study that supplementation with casein A1 has any cardiovascular health disadvantage over consumption of casein A2.

Beyond Blood Pressure

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Schillaci et al1 raise an interesting possibility—that a drug class (protease inhibitors) can have subtle arterial ill effects, which are not apparent from conventional blood pressure recordings. The authors provide evidence of aortic stiffening (measured as carotid–femoral pulse wave velocity [PWV]), increase in wave reflection from peripheral vessels (measured as aortic augmentation index [AIx]), and impairment of left ventricular subendocardial supply/demand ratio (measured as Buckberg index). Studies to date on arterial stiffening and its implications have concentrated on how age, gender, body height, exercise, lifestyle, and disease affects these properties, and how arterial properties, when deranged by disease, can be improved by drug therapy.2 Such adverse arterial hemodynamic changes with drugs have not been sought before. Before approval of a new drug, government regulatory bodies have required only measurements of cuff brachial systolic and diastolic pressures and assurance that these were not significantly altered. The question arises from the study of Schillaci—is this enough? Is it possible that drug classes may have adverse long-term effects that are not exposed by conventional cuff measurements? The question is relevant to the present concerns on long-term ill effects of COX 2 inhibitors (coxibs), with rofecoxib withdrawn from the market and the subject of legal action in US courts.3 See page 2381 The potential importance of the findings of Schillaci et al on protease inhibitors is unquestioned. These drugs have revolutionised the treatment of AIDS and find routine use in persons who are seropositive to the HIV virus. There were no HIV-positive persons in this study who were not treated with protease inhibitors. Studies of the drugs quoted by Schillaci are in recent issues in the world’s highest impact journals. I will not pursue such important implications to HIV and AIDS, …

What do Doppler indices of renal perfusion tell us for the evaluation of renal disease?

What do Doppler indices of renal perfusion tell us for the evaluation of renal disease?

Relationship between arterial stiffness and heart rate recovery in apparently healthy adults

Arterial stiffness and heart rate recovery (HRR) following exercise testing have emerged as variables holding significant prognostic value in a number of populations. The purpose of the present study is to examine the relationship between arterial stiffness and HRR in a group of apparently healthy subjects. Two hundred and nine apparently healthy subjects underwent maximal exercise testing. Heart rate at one and two minutes post exercise was subtracted from maximal heart rate during the exercise test to produce two measures of heart rate recovery. Aortic wave velocity, in meters per second, was obtained via a new magnetic resonance technique. Pearson Product Moment Correlation analysis revealed a significant correlation between aortic wave velocity and heart rate recovery. Stepwise linear regression analysis revealed that age, maximal aerobic capacity, heart rate recovery at one minute, and diastolic blood pressure were all significant predictors of aortic wave velocity (r = 0.63, r2 = 0.40, p < 0.001). The results of the present study indicate that heart rate recovery is significantly correlated with a measure of large artery stiffness and adds predictive value to other clinical variables. This analysis provides further evidence that assessment of heart rate recovery should be considered in subjects undergoing exercise testing in clinical practice.

The Impact of Pedigree Structure on Heritability Estimates for Pulse Pressure in Three Studies

Objectives: Pulse pressure (PP) is a measure of large artery stiffness and has been shown to be an important predictor of cardiovascular morbidity and mortality. The aims of the present study were to investigate the heritability of PP in three studies, the Diabetes Heart Study (DHS), the Insulin Resistance Atherosclerosis Family Study (IRAS FS), and the NHLBI Family Heart Study (FHS), to estimate the residual heritability after inclusion of a common set of covariates, and to investigate the impact of pedigree structure on estimating heritability. Methods and Results: DHS is primarily a sibling pair nuclear family study design, while both IRAS FS and FHS have large pedigrees. Heritability estimates of log-transformed PP were obtained using variance component models. After adjusting for age, gender, ethnicity/center, height, diabetes status, and mean arterial pressure (MAP), heritability estimates of PP were 0.40 ± 0.08 , 0.22 ± 0.05, and 0.19 ± 0.03 in DHS, IRAS FS, and FHS, respectively. The heritability estimate from DHS was significantly different from both IRAS FS and FHS (both p values <0.05). A random re-sampling technique (modified bootstrap) was used to explore the heritability in the IRAS FS and FHS data when these pedigrees were trimmed to mimic the DHS pedigree structure. The re-sampling method (mimicking a sibling pair nuclear family design in all studies) yielded PP heritability estimates of 0.37, 0.34, and 0.27 in DHS, IRAS FS, and FHS, respectively. There was no significant difference among the heritability estimates from the three studies based on the re-sampling method. Conclusion: We have shown that PP has a moderately heritable component in three different studies. These data illustrate the influence of pedigree structure can have on estimating heritability. Thoughtful comparisons of heritability estimates must consider study design factors such as pedigree structure.

Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology.

The association between arterial stiffening and aging is well described and can be observed in almost all populations worldwide. A number of other cardiovascular risk factors including diabetes and cigarette smoking are also associated with increased large artery stiffness, often referred to as “premature arterial stiffening.” It is now apparent that the aortic pulse wave velocity (PWV), a measure of arterial distensibility, predicts outcome in a variety of different populations, including hypertensives,1 diabetics,2 individuals with end-stage renal disease (ESRD),3 and even in older adults.4 Indeed, in some populations, aortic PWV is a better predictor of future events than peripheral blood pressure.4 Moreover, arterial stiffening may be more than just a marker of cardiovascular risk; stiffening may also play a more direct role in the development of atherosclerotic plaques. Thus, arterial stiffness would appear to be a novel therapeutic target for the prevention of excess cardiovascular morbidity and mortality. To exploit such an exciting prospect fully, it is necessary to understand the factors regulating arterial stiffness. Traditionally, the stiffness of a vessel was viewed as simply a function of the structural elements of the vessel wall and distending (mean arterial) pressure. However, the large arteries also have a generous coat of smooth muscle, which can alter the distribution of stresses between the elastic and collagenous fibers of the vessel wall and thus alter arterial stiffness. Because smooth muscle tone is influenced by a number of circulating and local vasoactive mediators, arterial stiffness may be actively regulated, and indeed modifiable, at least in the short-term. The muscular arteries have a rich sympathetic innervation, and catecholamines are known to alter smooth muscle tone. Moreover, removal of the vascular endothelium in animals alters large artery stiffness,5,6 suggesting that endothelial-derived substances regulate arterial stiffness in vivo. However, the endothelium …

Pathophysiology of hypertension in the elderly

The importance of hypertension as a cardiovascular risk factor increases progressively with aging, but diastolic blood pressure plateaus at age 50, which leads to a rise in pulse pressure in the elderly. Thus, isolated systolic hypertension with a widened pulse pressure is the most common type of hypertension seen in persons older than 65 years of age. Pulse pressure is the most robust blood pressure measurement in predicting cardiovascular disease. This rise in systolic blood pressure and pulse pressure with aging is a consequence of arterial stiffness. With aging, both structural and functional changes occur that result in a less compliant aorta and large vessels. Investigators who use pulse-wave velocity and augmentation index as measures of large artery stiffness have repeatedly shown an increase in arterial stiffness with aging. Early return of the reflected pulse wave to the aorta during systole has been shown to be the primary mechanism accounting for the rise in systolic and decline in diastolic pressure that occurs with arterial stiffness. Several factors have been shown to decrease arterial stiffness including aerobic exercise, decreased sodium intake, n-3 fatty acids, estrogen replacement therapy, nitrates, and ACE inhibitors. Drugs that specifically lower systolic blood pressure but not diastolic pressure, such as vasopeptidase inhibitors, are under investigation in treating isolated systolic hypertension.

The Effects of Induced Hypogonadism on Arterial Stiffness, Body Composition, and Metabolic Parameters in Males with Prostate Cancer

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 ± 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 ± 6% (mean ± sd) at baseline to 29 ± 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 ± 7 to 129 ± 10 msec (P = 0.003). Fat mass increased from 20.2 ± 9.4 to 21.9 ± 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 ± 6.8 to 61.5 ± 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6–49.1) to 15.1 (range, 7.3–83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0–85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 ± 7% at 3 months to 29 ± 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.