Higher Augmentation Index Research Articles

Exploration of Association of 1,25-OH2D3 with Augmentation Index, a Composite Measure of Arterial Stiffness

Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness. In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx. The median eGFR was significantly different between clinics (range 25-81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant. This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.

Association of beta-blocker use with increased aortic wave reflection

Studies have found less cardiovascular risk reduction in patients treated with beta-blockers (BBs) compared with other agents. We compared the severity of aortic atherosclerosis, arterial stiffness, and wave reflection in patients treated and not treated with BBs. Seventy-two patients, 37 treated with BBs and 35 not treated, referred for transesophageal echocardiography were studied. Augmentation index (AI), heart-rate-corrected AI (AI-75), aortic systolic (SBP) and diastolic blood pressure, pulse wave velocity (PWV), and aortic intima-media thickness (MAIMT) were measured. There were no differences in MAIMT (2.8 ± 1.6 mm vs. 2.4 ± 1.2 mm, P = .20) and PWV (8.9 ± 2.0 m/s vs. 8.5 ± 2.6 m/s, P = .46) between the BB and non-BB groups. The BB group had higher AI (28.7 ±11.9% vs. 22.3 ± 14.1%, P = .04), AI-75 (27.7 ± 10.7% vs. 20.1± 11.0%, P = .005), aortic SBP (140 ± 21 mm Hg vs. 125 ± 21 mm Hg, P = .01), and aortic pulse pressure (62 ± 20 mm Hg vs. 47 ± 19 mm Hg, P = .01) than the non-BB group despite similar brachial blood pressure. BB use was associated with increased aortic wave reflection despite similar degree of aortic atherosclerosis.

Pathogenesis of Elevated Peripheral Pulse Pressure

“Ashes to ashes, dust to dust, if the cancer don’t get us, the arteriosclerosis must” — —Richard Gordon in The Alarming History of Medicine, 1993 Substantial evidence suggests that arterial remodeling evolves over a life course under the conjoint influence of genes, environmental factors (including vascular risk factors), and lifestyle characteristics (such as diet and physical activity).1 Such arterial remodeling involves multiple vascular territories and is panarterial, ie, it involves all layers of the arterial wall.1 More recently, considerable attention has focused on the physiological aspects of propagation of blood within the aorta, and several important concepts have evolved. First, the aorta is no longer regarded as just a passive conduit that transports blood to the vital organs. Rather, it is a complex organ that remodels in dynamic fashion in response to biomechanical stresses that accumulate over the life course.1 The different segments of the aorta vary in their relations to risk factors, underscoring the heterogeneity in remodeling characteristics across the arterial tree.2 Second, age-associated changes in the aortic wall include fragmentation of the elastin fibers, increased synthesis of collagen, and calcification. The molecular epidemiology of these vascular remodeling changes have been well characterized, and are complex, being mediated via the interaction of vascular smooth muscle cells, integrins, metalloproteinases, endothelial function, and the renin-angiotensin axis, inflammation, and other pathways.1 Third, vascular flow propagation is the combination of steady flow (mean arterial pressure) and pulsatile (pulse pressure) components. The proximal (central) aorta stiffens with age, and these changes are associated with an increase in the pulsatile component (increased central pulse pressure), which in turn places a burden of increased afterload on the left ventricle. There is widespread agreement that elevated pulsatile load is associated with increased risk of cardiovascular disease, including myocardial infarction, stroke, and heart …

Impact of aortic stenting on peripheral vascular function and daytime systolic blood pressure in adult coarctation

Objectives:To determine the relation of ambulatory systolic blood pressure to aortic obstruction and more extensive vascular dysfunction, assessed by central aortic, peripheral conduit arterial and resistance vessel function.Methods:12 adults (5...

Increased arterial stiffness in remote Indigenous Australians with high risk of cardiovascular disease

To assess central and peripheral arterial stiffness in Indigenous and European Australians with and without type 2 diabetes using applanation tonometry to obtain the augmentation index (AI) and pulse wave velocity (PWV). AI was assessed in 162 Indigenous Australians (60 with type 2 diabetes) participating in a population-based study and 121 Australians of European ancestry (38 with diabetes) of similar age and sex. PWV was assessed in a subgroup: n = 62 indigenous, n = 118 European participants. The indigenous group had higher AI than the European group [mean (SD) 32 (12) versus 24 (12)%, P < 0.0001] and carotid-femoral PWV [8.4 (1.8) versus 7.1 (2.2) ms(-1), P < 0.0001]. There were no significant differences between groups regarding blood pressure and total cholesterol; however, indigenous individuals had higher fasting glucose, insulin, haemoglobin A1c, triglycerides, waist circumference (despite lower body mass index), and a higher prevalence of cigarette smoking. Fifty-five per cent of the variance in AI was explained on multiple regression analysis by age, sex, indigenous participant, heart rate, mean arterial pressure, height, triglycerides and waist circumference. Age, indigenous participant, heart rate, mean arterial pressure and antihypertensive medication explained 56% of the variance in PWV. Variables of the metabolic syndrome and smoking, C-reactive protein (CRP), homocysteine and heart rate clustered with indigenous status on factor analysis. Indigenous Australians have higher indices of peripheral and central arterial stiffness than European Australians of similar age and sex. Factor analysis revealed that metabolic syndrome variables, smoking, CRP, homocysteine and heart rate clustered with 'indigenous participant' and may explain increased arterial stiffness in this group.

Effect of physical activity and muscle morphology on endothelial function and arterial stiffness

Physically active persons have a reduced risk of atherosclerotic disease. Arterial stiffness and endothelial dysfunction are important risk factors for cardiovascular disease. A high proportion of type I (slow-twitch) muscle fibers in skeletal muscle is associated with a favorable cardiovascular risk profile. We tested physical activity and muscle fiber-type distribution as determinants of endothelial function and arterial stiffness in middle-aged men. Fifty-four men (median age 58) who underwent a muscle biopsy in 1984 were re-studied in 2003. Aortic pulse wave velocity (PWV) and pulse wave reflection were assessed by applanation tonometry. Endothelial function was tested by examining the effects of salbutamol and nitroglycerin on pulse wave reflection. In multiple regression analyses aortic PWV (R2=0.51) correlated positively with age (P=0.017), BMI (P=0.001), and systolic blood pressure (P=0.004). A high augmentation index (R2=0.33) was associated with smoking (P<0.001), high LDL cholesterol (P=0.02), and elevated diastolic blood pressure (P=0.03). Impaired endothelial function (R2=0.37) was associated with high age (P=0.04), high LDL cholesterol (P=0.017), high triglycerides (P=0.027), and high physical activity (P=0.005). Muscle fiber-type distribution is not a determinant of arterial stiffness or endothelial function. Impaired endothelial function was observed in physically active men, underlining the need for further research.

Effect of chronic coffee consumption on aortic stiffness and wave reflections in hypertensive patients

Aortic stiffness and wave reflections are important markers and prognosticators of cardiovascular risk. Caffeine increases acutely aortic stiffness and wave reflections. Furthermore, chronic coffee consumption is associated with increased aortic stiffness and wave reflections in normotensive subjects. In the present study, we aimed to assess the association between chronic coffee consumption, and aortic stiffness and wave reflections in hypertensive patients. Epidemiological survey. Hypertension Unit, University Hospital. SUBJECTS-METHODS: We examined 259 never-treated hypertensives (age 50+/-12 years, 165 males) without diabetes mellitus, who were asked to describe in detail the type and amount of coffee they consumed. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) were measured non-invasively as indices of aortic stiffness and wave reflections, respectively. When controlled for gender, age, height, smoking status, heart rate, mean pressure, HDL cholesterol and hsCRP, AIx was found to be higher with increasing daily coffee consumption. Post hoc analysis revealed that all groups of coffee consumption had higher AIx compared to no-consumption. PWV did not differ among groups of daily coffee consumption. Each participant had 35% higher relative risk of having high AIx for each cup (150 ml) of coffee per day, and 40% higher relative risk for each 10 cup-years. Coffee consumption is associated with increased wave reflections, but not aortic stiffness in never-treated hypertensive patients. This finding may have important clinical implications for cardiovascular health in hypertensive subjects.

Spurious systolic hypertension in youth: what does it really mean in clinical practice?

In clinical practice, brachial blood pressure measurement remains the classical reference for identifying hypertension, but this has been challenged recently. Indeed, estimation of central aortic pressure has been shown to be a stronger predictor of coronary artery disease [1,2] and even brings new insights regarding the effect of different antihypertensive drugs, as documented in the Conduit Artery Function Evaluation (CAFE) study. CAFE is a sub-study of the large Anglo-Scandinavian Cardiac Outcomes trial (ASCOT) in which, despite the similar control of brachial blood pressure, aortic blood pressure was significantly lower in the amlodipine-perindopril arm compared to the betablocker-diuretic arm [3,4].

The combined effect of augmentation index and carotid intima-media thickness on cardiovascular risk in young and middle-aged men without cardiovascular disease

Carotid artery intima-media thickness (IMT) has been used as a surrogate marker of atherosclerosis and is related to cardiovascular risk. Indices of arterial stiffness are also associated with cardiovascular risk and atherosclerosis. The aim of this study was to assess the prognostic value of the combination of surrogate markers of cardiovascular disease measured non-invasively in subjects without cardiovascular disease. In this cross-sectional study, 81 young and middle aged males (39.2+/-6.3 years) without evidence of overt cardiovascular disease or diabetes mellitus were enrolled. High-resolution B-mode ultrasonography and pulse wave analysis were used to measure carotid artery IMT and augmentation index (AI), a measure of arterial stiffness. Framingham risk score (FRS) was used as an estimate of the risk for development of cardiovascular disease. Regional differences were observed in the carotid arteries' IMT regarding their relationship with FRS: combined (average from all sites) IMT and IMT in the carotid bulb (CB), but not in the common (CC) and internal carotid artery (IC), and AI showed significant increases of FRS by their tertiles. However, subjects with both AI and IMT at any site in the highest tertile (AI>15%, CC>0.65 mm, CB>0.8 mm, IC>0.65 mm) had an increased FRS compared to subjects with one or none of these parameters in the highest tertile. In conclusion, young and middle-aged men without overt cardiovascular disease with both high IMT and AI are in high cardiovascular risk, as assessed by FRS. Epidemiological studies are needed to further validate this combination.

Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease

Pulse pressure (PP), a marker of arterial stiffness, is a cardiovascular risk predictor. Prospective studies have not evaluated other markers of arterial stiffness as predictors of major adverse cardiovascular events (MACE) in patients with established coronary artery disease (CAD). We aimed to determine whether the aortic augmentation pressure (AP, derived from the aortic pressure waveform) predicts MACE and death independently of the PP. We prospectively followed 297 males undergoing coronary angiography at the Miami VA Medical Center for 1186±424 days. We analyzed ascending aortic pressure tracings obtained during catheterization. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak. Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP (adjusted for PP) and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke or death), and all-cause mortality. We used Cox regression; AIx and AP were adjusted for mean aortic pressure, ejection fraction and heart rate in all models. During the follow-up, 43.1% of patients had MACE and 19.5% died. Both the AP (adjusted for PP) and AIx significantly predicted the risk of MACE. The Hazard ratio (HR) per 10 mmHg increase in AP was 1.20 (95%CI=1.08-1.34; p<h0.001); the HR for each 10% in AIx was 1.28 (95%CI=1.11-1.48; p=0.004). After adjusting for other univariate predictors, the PP-adjusted AP remained a significant predictor of MACE (adjusted HR=1.19; 95%CI=1.07–1.33; p= 0.001), as did the AIx (adjusted HR=1.27; 95%CI=1.10–1.48; p=0.001). AP was a significant predictor of death (HR per 10 mmHg increase=1.18; 95%CI=1.02-1.39; p=0.03). Higher AIx was associated with a trend towards increased all-cause mortality (HR=1.22; 95%CI=0.98–1.52; p=0.056). Central AP predicts MACE and death in patients with established CAD independently of pulse pressure and other risk markers. Further studies are needed to determine the prognostic value of central pressure augmentation in other populations, further understand the mechanisms affecting it, and define its role as a therapeutic target.

Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease

Pulse pressure (PP), a marker of arterial stiffness, predicts cardiovascular risk. We aimed to determine whether augmentation pressure (AP) derived from the aortic pressure waveform predicts major adverse cardiovascular events (MACE) and death independently of PP in patients with established coronary artery disease (CAD). We prospectively followed-up 297 males undergoing coronary angiography for 1186+/-424 days. Ascending aortic pressure tracings obtained during catheterization were used to calculate AP (difference between the second and the first systolic peak). Augmentation index (AIx) was defined as AP as a percentage of PP. We evaluated whether AP and AIx can predict the risk of MACE (unstable angina, acute myocardial infarction, coronary revascularization, stroke, or death) and death using Cox regression. All models evaluating AP included PP to assess whether AP adds to the information already provided by PP. Both AP and AIx significantly predicted MACE. The hazard ratio (HR) per 10 mm Hg increase in AP was 1.20 (95% confidence interval [CI], 1.08 to 1.34; P<0.001); the HR for each 10% increase in AIx was 1.28 (95% CI, 1.11 to 1.48; P=0.004). After adjusting for other univariate predictors of MACE, age, and other potential confounders, AP remained a significant predictor of MACE (HR per 10 mm Hg increase=1.19; 95% CI, 1.06 to 1.34; P=0.002), as did AIx (adjusted HR, 1.28; 95% CI, 1.09 to 1.50; P=0.003). AP was a significant predictor of death (HR per 10 mm Hg increase=1.18; 95% CI, 1.02 to 1.39; P=0.03). Higher AIx was associated with a trend toward increased mortality (HR=1.22; 95% CI, 0.98 to 1.52; P=0.056). Aortic AP predicts adverse outcomes in patients with CAD independently of PP and other risk markers.

Systolic hypertension in the elderly: pushing the frontiers of therapy--a suggested new approach.

In elderly patients with systolic hypertension resistant to treatment with conventional therapy, increased aortic pulse wave reflection and a high augmentation index are often present. These findings are indicative of endothelial dysfunction and deficient generation of nitric oxide, a potent vasodilator in the arterial tree. In such patients, treatment with the nitric oxide donor extended-release isosorbide mononitrate characteristically produces prompt and sustained falls in both pulse wave reflection and systolic blood pressure. The adjunct use of this nitrate produces useful additional decreases in systolic blood pressure ranging from 10 to 45 mm Hg, often achieving target blood pressure goals in isolated systolic hypertension. By combining this endothelium-independent nitric oxide donor with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the potential exists to address both the nitric oxide deficiency and endothelial dysfunction of the vascular endothelium in these patients. Other possibilities for synergism with this combination include complementary hemodynamic, circadian, and metabolic actions together with prevention of nitrate tolerance. Isosorbide mononitrate may also be used successfully with calcium channel blockers, beta blockers, and diuretics.

Large‐Artery Stiffness Contributes to the Greater Prevalence of Systolic Hypertension in Elderly Women

To determine whether sex differences in large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women than in elderly men. During a single visit arterial stiffness was assessed in the unmedicated state using four parameters. Three hundred seventy-four women with a mean age+/-standard deviation of 72+/-5 and 296 men aged 71+/-5 participated. Hypertensive patients were recruited from general practice as part of the second Australian National Blood Pressure Study in Melbourne, Australia. Large-artery stiffness was assessed using multiple methodologies, including aortic arch stiffness (beta-index) using M-mode ultrasound and arterial compliance and augmentation index using noninvasive carotid pressure and aortic flow measurements. Women had greater carotid and brachial pulse pressure (PP) than men (P<.001), despite higher mean arterial pressure in men. Mean arterial compliance was lower in women (0.20+/-0.12 vs 0.28+/-0.16 mL/mmHg, P<.001) even after correction for aortic area, and aortic arch stiffness was higher (30+/-36 vs 23+/-22; P<.01). Consistent with both a stiffer proximal circulation and a shorter distance to reflection sites, women had higher augmentation index (38+/-11% vs 29+/-12%, P<.001). In multivariate analysis, sex was an independent determinant of all arterial stiffness indices. Independently of known confounders, elderly hypertensive women have stiffer large arteries, greater central wave reflection, and higher PP than elderly men. Stiffer large arteries likely contribute to the greater prevalence of systolic hypertension in elderly women and may partly explain the acceleration in postmenopausal cerebrovascular and cardiac complications.

Arterial stiffness, wave reflections, and the risk of coronary artery disease.

Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P<0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P<0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P<0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P<0.05). AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.

Physical activity reduces genetic susceptibility to increased central systolic pressure augmentation: a study of female twins

ObjectivesWe sought to examine associations between the augmentation index (AI) and metabolic, adiposity, and lifestyle factors, independent of genetic influences, and to determine whether gene-environment interactions modulate these relationships. BackgroundReported associations between AI, an index of systemic arterial stiffness, and metabolic, adiposity, and lifestyle factors remain contradictory. The modulating effect of genetic risk is unknown. MethodsWe studied 684 female twins (age 18 to 71 years); AI was derived from the pressure waveform measured at the radial artery by applanation tonometry. Percentage of total body fat (TBF) and percentage of central abdominal fat (CAF) were assessed by dual-energy X-ray absorptiometry. ResultsIn univariate analysis, age-adjusted AI was significantly associated with fasting triglyceride levels (r = 0.1, p = 0.03), apolipoprotein-B/A1 (r = 0.1, p = 0.04), percentage of TBF (r = 0.11, p = 0.006), and percentage of CAF (r = 0.11, p = 0.004). In co-twin case-control (monozygotic twin) analysis, a 3.1% absolute within-pair difference in percentage of CAF accounted for a 6% within-pair difference in AI, independent of genetic effects. Smokers and subjects with alcohol intakes >15 U/week had higher AI than nonsmokers (p = 0.01) and nondrinkers (p = 0.02), respectively. Forty percent of the variance in AI was explained by age, central mean arterial pressure, heart rate, height, percentage of CAF, and smoking. In gene-environment interaction analysis, subjects at high genetic risk of increased AI participating in regular leisure-time physical activity had AI values similar to low genetic risk subjects. ConclusionsCentral abdominal adiposity is a significant determinant of AI in female twins, independent of hemodynamic, lifestyle, and, importantly, genetic effects. Smoking is associated with increased AI, even after controlling for abdominal obesity and other AI determinants. Physical activity reduces genetic predisposition to increased AI.

The influence of the peripheral reflection wave on left ventricular hypertrophy in patients with essential hypertension.

The objective of this study was to clarify the relationship between afterload, which consists mainly of the vascular reflection wave, and left ventricular hypertrophy in patients with untreated essential hypertension using the fingertip photoplethysmogram (PTG) and second derivative wave (SDPTG) methods, the simplest and most convenient tools for pulse wave analysis. The augmentation index (AI) is defined as the ratio of the height of the late systolic peak, augmented by the peripheral reflection wave, to that of the early systolic peak caused mainly by left ventricular ejection in the pulse. Increased AI of the PTG and negative d/a, obtained by multiplying the ratio of the late re-decreasing wave (d wave) to the initial positive wave (a wave) of the SDPTG by -1, have the same meaning as increased ascending aortic AI. The left brachial artery blood pressure was measured in 60 patients. The PTG and SDPTG of the right second finger were recorded by a digital photoplethysmograph. The left ventricular mass index (LVMI) was investigated by ultrasonography. Subjects were assigned to one of two groups: a low AI (AI of PTG<1.6; group 1) or a high AI (AI of PTG> or =1.6; group 2) group. LVMI was significantly higher in group 2 than in group 1. In the study group as a whole, the LVMI was positively correlated with both the AI of PTG (r=0.60, p<0.0001) and negative d/a (r=0.63, p<0.0001). An increase in the LVMI was seen in subjects with an augmented late systolic component in the waveform. It was concluded that an increase in the peripheral reflection wave on the left ventricle is one of the important factors causing cardiac hypertrophy in patients with hypertension.