Arterial Wave Reflection Research Articles

Arterial Stiffness and Wave Reflections in Marathon Runners

Regular aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is an aerobic and extremely vigorous exercise. Arterial stiffness and wave reflections are independent predictors of cardiovascular risk. We investigated the acute effect of marathon race on aortic stiffness and wave reflections, as well as possible chronic alterations of these indexes in marathon runners. We studied 49 marathon runners (age 38 +/- 9 years) and 46 recreationally active control subjects (age 37 +/- 5 years). To investigate the acute effect of marathon race, a subgroup of 20 runners was evaluated after the race as well. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV) and wave reflections with augmentation index (AIx). Marathon runners had significantly higher systolic, diastolic, pulse (both aortic and brachial), and mean pressures compared to controls (P < 0.05 for all). Marathon runners had significantly higher PWV (6.89 m/s vs. 6.33 m/s, P < 0.01), whereas there was no difference in AIx and AIx corrected for heart rate (AIx@75) compared to controls (13.8% vs. 13.9%, P = 0.985 and 8.2% vs. 10.3%, P = 0.340, respectively). Marathon race caused a significant fall in both AIx (12.2% vs. -5.8%, P < 0.001) and AIx@75 (7.0% vs. 0.0%, P = 0.01), whereas PWV did not change significantly (6.66 m/s vs. 6.74 m/s, P = 0.690). Aortic and brachial systolic, diastolic, and mean pressures were also decreased (P < 0.05). A significant fall in wave reflections was observed after marathon race, whereas aortic stiffness was not altered. Moreover, marathon runners have increased aortic stiffness and pressures, whereas wave reflections indexes do not differ compared to controls.

Clinical Potential of Combined Organic Nitrate and Phosphodiesterase Type 5 Inhibitor in Treatment-Resistant Hypertension

NO donor drugs (eg, isosorbide mononitrate; ISMN) and phosphodiesterase 5 inhibitors (eg, sildenafil) have antihypertensive properties, and the combination can markedly reduce blood pressure (BP). The objective of this "proof-of-concept" study was to investigate the effect on BP of a combination of single oral doses of sildenafil (50 mg) and ISMN (10 mg) in patients with treatment-resistant hypertension. Six subjects with treatment-resistant hypertension were included, and their usual antihypertensive medication was continued during the study. Sildenafil alone, ISMN alone, and the combination all reduced brachial and central aortic BPs compared with placebo. The combination of sildenafil and ISMN produced the largest fall in BP (maximum brachial BP reduction of 26/18 mm Hg compared with placebo), without producing significant adverse effects. ISMN, alone and in combination with sildenafil, also reduced arterial wave reflection and central BP. In summary, in patients with treatment-resistant hypertension maintained on their usual antihypertensive treatment, sildenafil given alone and ISMN given alone both acutely reduced BP. There was additional BP reduction when these drugs were given in combination. In this therapeutically challenging group of patients, the combination of an NO donor drug and a phosphodiesterase 5 inhibitor may represent an effective treatment. Longer studies in larger numbers of patients are now justified.

Environmental determinants of blood pressure, arterial stiffness, and central hemodynamics

Arterial stiffness and wave reflection alterations may be implicated in the association between cardiovascular mortality, meteorological variables and ambient particulate matter air pollution. The present study explored the cross-sectional relations between ambient environmental parameters, arterial stiffness, peripheral and central hemodynamics in a large-scale cohort of hypertensive patients and normotensive controls. The study comprised 1222 consecutive individuals who sought medical consultation in the hypertension outpatient clinics of the Hippokration' and 'Onassis' Hospitals (Athens, Greece) during a 3-year period (2004-2006). All individuals underwent a complete clinical and lipid-profile assessment at drug-free baseline. Carotid radial, carotid-femoral pulse wave velocity measurements and aortic pressure waveform analysis were performed noninvasively to all participants. Data from the National Technical University of Athens and the air quality department of the Hellenic Ministry for the Environment were used to estimate daily meteorological conditions and PM10 exposure. In the total population, multiple-linear regression analysis revealed no significant associations between environmental variables and arterial stiffness. However, in men, the mean 5 day PM10 air concentration was independently associated with the augmentation pressure [2.0 mmHg (95% confidence interval (CI) 0.56-3.39) per 43.4 microg/m3] and the aortic-pulse pressure [2.78 mmHg (95% CI 3.91-5.12)] denoting a significant effect of particulate matter on the aortic-wave reflection magnitude and central hemodynamics. In addition, globally, the mean-daily temperature was related to the aortic-pulse pressure [-2.38 mmHg (95% CI -4.51 to -0.26) per 23.6 degrees C change] and the subendocardial viability ratio [5.85% (95% CI 1.1-10.6 per 23.6 degrees C)]. The exposure to lower environmental temperatures is related to impaired hemodynamics not only to the periphery but also to the aorta. In men, PM10 air-pollution levels are associated with heightened amplitude of the reflection wave leading to significant alterations in central-pulse pressure.

Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients

The optimal combination treatment for hypertension has not been established. We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers (ARBs) on the augmentation index (AI), as a marker of arterial stiffness and wave reflection, in hypertensive patients. Thirty-seven patients treated with ARBs were randomly allocated to either of the 2 groups receiving an ARB plus azelnidipine (AZ group) or trichlormethiazide (TCM group). Changes in brachial blood pressure (BP), AI, high-sensitive C-reactive protein (hsCRP), and serum asymmetric dimethylarginine, as an endogenous nitric oxide synthase inhibitor, were determined. Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly; however, after adjustment for baseline covariates, the extent of the reduction in AI (%) in the AZ group was significantly greater than in the TCM group (between-group difference was 3.2; 95%CI: 0.2-6.3; P = 0.03). The reduction of high-sensitive C-reactive protein (mg/L) and serum asymmetric dimethylarginine (micromol/L) was significantly greater in the AZ group than in the TCM group (between-group difference was 0.18 and 0.05; 95%CI: -0.01 to 0.36 and -0.01 to 0.11; P = 0.04 and 0.02, respectively). Further, when patients were analyzed according to age younger than 60 years or older than 60 years, the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group. The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide.

Medical semiology of mechanical factors and vascular aging in the elderly

Systolic hypertension in the elderly involves increased arterial stiffness and disturbed wave reflections, both of them causing a predominant or selective increase of systolic blood pressure. The development of systolic hypertension includes constantly an age-related increase of sodium sensitivity and endothelial dysfunction, both responsible for phenotypic changes of aortic smooth muscle cells, with collagen accumulation and increased stiffness of wall material. In the presence of a high sodium diet and under the influence of angiotensin II and aldosterone, a higher number of attachments between vascular smooth muscle cells and collagen fibers develop, causing a supplementary increase in stiffness independent of the mean blood pressure, together with the occurrence of early wave reflections. This process contributes to accelerate the increase in pulse pressure and arterial stiffness with age, and thus to favor the development of cardiovascular risk.

Hypertrophic remodeling and increased arterial stiffness in patients with intracranial aneurysms

Objective Because an underlying arteriopathy might contribute to the development of intracranial aneurysms (IAs), we assessed the elastic properties of proximal conduit arteries in patients with IA. Methods In 27 patients with previous ruptured IA and 27 control subjects matched for age, gender and BMI, we determined arterial pressure, internal diameter, intima-media thickness (IMT), circumferential wall stress (CWS) and elastic modulus (wall stiffness) in common carotid arteries using applanation tonometry and echotracking. Moreover, carotid augmentation index (AIx, arterial wave reflections) and carotid-to-femoral pulse wave velocity (PWV, aortic stiffness) were assessed. Results Compared with controls, patients with IA exhibited higher brachial and carotid systolic and diastolic blood pressures, with similar brachial but higher carotid artery pulse pressure (35 ± 6 mm Hg vs. 41 ± 8 mm Hg, P = 0.014). Moreover, patients have higher PWV (7.8 ± 1.2 m s −1 vs. 8.3 ± 1.1 m s −1, P = 0.048) and AIx (15.8 ± 10.8% vs. 21.1 ± 8.5%, P < 0.001) which contributes to increase carotid blood pressures. Furthermore, carotid IMT was higher in patients (546 ± 64 μm vs. 642 ± 70 μm, P < 0.001) without difference in diameter suggesting an adaptive hypertrophy. However, patients display a lower CWS (61.6 ± 9.2 kPa vs. 56.9 ± 10.3 kPa, P = 0.007) and no correlation between IMT and pulse pressure ( r = 0.152, P = NS) in contrast to controls ( r = 0.539, P < 0.001) showing the contribution of a pressure-independent process. Finally, despite this lesser CWS, elastic modulus was increased in patients (310 ± 105 kPa vs. 383 ± 174 kPa, P = 0.026). Conclusion This study demonstrates that patients with IA display a particular carotid artery phenotype with an exaggerated hypertrophic remodeling and altered elastic properties. Thus, a systemic arteriopathy might contribute, together with the arterial wall fatiguing effect of the increased pulsatile stress, to the pathogenesis of IA.

Effects of Prehypertension on Arterial Stiffness and Wave Reflections

The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classifies blood pressure (BP) as normal, prehypertension, and hypertension. Although it has been shown that there is a relationship between hypertension and arterial stiffness, there is not sufficient data about arterial stiffness in patients with prehypertension. The present study was designed to evaluate arterial stiffness and wave reflections in subjects with prehypertension. We evaluated arterial stiffness and wave reflections of 45 subjects with prehypertension and an age-matched control group of 40 normotensive individuals, using applanation tonometry (Sphygmocor, AtCor Medical, Sydney, Australia). Aortic pulse wave velocity (PWV) was measured as indices of elastic-type aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a composite marker of wave reflections and arterial stiffness. Aortic PWV (10 ± 2.5 vs. 8.6 ± 1.7, m/s, p = 0.004) and AIx@75 (21 ± 8.3 vs. 10 ± 9.1, %, p = 0.0001) were significantly higher in subjects with prehypertension than in the control group. In multiple linear regression analysis, we found that the presence of the prehypertension was a significant predictor of aortic PWV (β = 0.26, p = 0.009) and AIx@75 (β = 0.46, p = 0.0001). Our results suggest that arterial functions were impaired even at the prehypertensive stage.

Ankle Blood Pressure: A Novel Measure Affecting Central Arterial Wave Reflection?

ObjectiveThere is an increasing recognition that central aortic pressure is more relevant than peripheral (brachial) measure for the prediction and pathophysiology of cardiovascular disease. Central pressure is greatly influenced by the phenomenon of arterial wave reflections returning from the peripheral vasculature, which can be quantified by augmentation index. Primary wave reflections returning to the heart are thought to come from the lower body (e.g., lower limbs). Accordingly, the primary aim of the present study was to determine the association between central augmentation index and arterial blood pressures recorded in both the upper and lower limbs.MethodsA total of 1,189 apparently healthy adults (567 males and 622 females) of varying ages were studied. Brachial and ankle blood pressure, carotid augmentation index, and brachial‐ankle pulse wave velocity were measured.ResultsAll of the blood pressure (brachial and ankle, systolic, mean, and diastolic) measurements were significantly associated with carotid augmentation index. Among them, ankle mean arterial pressure was the strongest correlate of carotid augmentation index (r=0.56, P&lt;0.05). This relation remained highly significant even after the influence of brachial blood pressure or age was accounted for in the partial correlation analyses. Moreover, stepwise regression analyses revealed that ankle mean arterial pressure was the strongest independent predictor of carotid augmentation index among all of the blood pressure measurements.ConclusionAnkle blood pressure is strongly associated with the augmentation of central blood pressure, and this relation is independent of other blood pressure measures (brachial blood pressure).

Changes in aortic augmentation index following systemic β‐adrenergic blockade are dependent on heart rate

We examined the effects of acute β‐adrenergic blockade on central artery hemodynamics and wave reflection characteristics in young healthy humans. High‐fidelity radial artery waveforms were recorded non‐invasively by applanation tonometry before and after intravenous propranolol (0.25 mg/kg bolus for 5 min followed by a maintenance infusion of 0.004/mg/kg/min for 20–30 min) in fourteen subjects (9 F/5M; 27 ± 2 years). Radial blood pressure (BP) was calibrated from the brachial BP (arterial catheter). Aortic augmentation index (AIa; a measure of amplitude and timing of arterial pressure wave reflection) and roundtrip travel time of the reflected wave to and from the periphery (Δtp; inverse of pulse wave velocity) were calculated from the generated aortic pressure waveform and are indices of central arterial stiffness. Systemic β‐blockade reduced heart rate (HR; 60 ± 2 vs. 53 ± 2 bpm, P &lt; 0.001) and increased AIa (9.9 ± 4.3% vs. 4.3 ± 4.4%, P &lt; 0.05), but did not alter Δtp (156 ± 4 msec vs. 152 ± 2 msec, P = 0.34). The AIa normalized to a HR of 75bpm (AIa@75) was not increased following β‐blockade (P = 0.67). Taken together, our data indicate that the increase in AIa following systemic β‐blockade is a result of a slower HR and not due to changes in β‐ mediated vascular tone.Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150

Arterial Pressure Wave Reflection Site Shifts Periphery with Aging

Early return of reflection wave from the periphery to the heart relates to the augmentation of central pulse pressure, a risk for cardiovascular disease. We determined the impact of aging on the location of a major reflection site which would directly affect the timing of the reflected wave. Arterial length (via 3‐D artery tracing of MRI) and carotid‐femoral pulse wave velocity (PWV) were measured in 218 adults. Aortic blood pressure was estimated via the radial pressure waveform analysis. The major reflection site was detected by carotid‐femoral PWV and the time of return of the reflected wave (Δt) (via carotid pressure waveform analysis). The major reflection sites were located at abdominal aorta (e.g., proximally to aortic bifurcation) in most of subjects (82%). The length from heart to the major reflection site (Lref) gradually increased with aging (r=0.53). Multi‐regression analyses revealed that Lref was significant independent determinant of aortic systolic and pulse pressure (β=−0.24 and β=−0.19). These results suggest that the major reflection site shifts periphery with aging, and that such age‐related shift of reflection site may partly attenuate the augmentation of central pulse pressure.

Pulse waveform characteristics predict cardiovascular events and mortality in patients undergoing coronary angiography

Pulse waveform characteristics (Augmentation Index--AIx and pulse wave transit time) are measures of the timing and extent of arterial wave reflections. Although previous studies reported an independent association with cardiovascular morbidity, it remains to be established that waveform characteristics, derived from noninvasive pulse waveform analysis, predict cardiovascular outcomes independent of and additional to brachial blood pressure. We prospectively assessed AIx, heart-rate corrected AIx, and pulse wave transit time, using radial applanation tonometry and a validated transfer function to generate the aortic pressure curve, in 520 male patients undergoing coronary angiography. Primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, cardiac, cerebrovascular, and peripheral revascularization. During a follow-up of 49 months, 170 patients reached the primary endpoint. On the basis of Cox proportional hazards regression models, all pressure waveform characteristics predicted the primary endpoint. A 10% increase of AIx and heart-rate corrected AIx was associated with a 20.5% (95% confidence interval 6.5-36.4, P = 0.003) and 31.4% (95% confidence interval 13.2-52.6, P = 0.0004) increased risk of the primary endpoint, respectively. A 10-ms increase of pulse wave transit time was associated with a 20.8% (95% confidence interval 10.8-29.6, P = 0.0001) lower risk of the primary endpoint. In multiple adjusted models, AIx, heart-rate corrected AIx, and pulse wave transit time were independently associated with the combined endpoint even after adjustments for brachial blood pressure, age, extent of coronary artery disease, clinical characteristics, and medications. The study provides evidence that pulse waveform characteristics consistently and independently predict cardiovascular events in coronary patients.

Relationship between total peripheral resistance and measures of central artery wave reflection

We examined the relationship between total peripheral resistance (TPR) and central artery pressure and indices of wave reflection in 16 subjects (10F/6M; 26 ± 1 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity radial pressure waveforms obtained from applanation tonometry of the radial artery. Radial blood pressure (BP) was calibrated from brachial artery BP (catheter). Central artery pressures, aortic augmentation index (AIa), roundtrip travel time of the reflected wave to and from the periphery (Δtp; inverse of pulse wave velocity), and wasted left ventricular energy (Ew) were calculated from the generated aortic pressure waveform. Cardiac output (CO) was measured using an open‐circuit acetylene uptake technique and used to calculate total peripheral resistance (mean arterial pressure/CO). TPR was positively related to aortic pulse pressure (r = 0.49), augmented pressure of the central artery wave (r = 0.60), pulse pressure amplification (r =0.54), AIa (r = 0.53), and Ew (r = 0.66), (P &lt; 0.05 for all). Additionally, TPR was inversely related to Δtp (r = − 0.51, P &lt; 0.05). Our data suggests that increased levels of TPR are related to measures of central artery pressure, wave reflection characteristics and indices of central artery stiffness.Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150

Amino-terminal pro-C-type natriuretic peptide is associated with arterial stiffness, endothelial function and early atherosclerosis

Objective C-type natriuretic peptide (CNP) is a paracrine molecule with effects on endothelial integrity, vascular tone and atherosclerotic process. Arterial stiffness, wave reflections, endothelial dysfunction and carotid intima-media thickness (IMT) are predictors of cardiovascular events. We investigated whether CNP is related to arterial structure and function in men. Methods We evaluated arterial structural and functional characteristics in 117 consecutive men (mean age 57.3 ± 9.2 years), with and without cardiovascular risk factors, who had no established cardiovascular disease. Arterial elastic properties were evaluated with carotid-femoral pulse wave velocity (PWV), wave reflections with augmentation index (AIx), endothelial function with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid IMT. Amino-terminal proCNP (NT-proCNP) was assessed in venous blood. Results The number of cardiovascular risk factors was inversely related to levels of NT-proCNP ( P < 0.01) and there was a progressive increase in Framingham risk score according to decreasing tertiles of NT-proCNP ( P < 0.001). In multivariable regression analysis NT-proCNP exhibited significant negative associations with PWV and IMT and positive association with FMD (all P < 0.05) that were independent of age, blood pressure, smoking habits, body mass index, blood glucose, total triglycerides, low-density lipoprotein and endothelin-1 or high-sensitivity C-reactive protein. There was no relation between NT-proCNP and AIx. Conclusion The present study is the first to demonstrate in a global arterial approach relationship between CNP and functional and early structural arterial changes. These findings elucidate pathophysiological links and may have important clinical implications for the estimation of cardiovascular risk in men.

Racial differences in relation between carotid and radial augmentation index

Background Augmented central artery wave reflection is a cardiovascular disease risk factor. Augmentation index (AI) obtained from peripheral artery waveforms provides qualitatively similar information to AI from central artery waveforms. Little information is available, however, regarding the influence of racial difference in association between central and peripheral AI. Methods We studied 47 White adults (45 ± 17 yr, 20 women) and 94 age-matched Asian adults (45 ± 14 yr, 42 women). Results The White group was significantly taller than the Asian group, whereas there were no significant group differences in blood pressure and heart rate. Carotid and radial AI tended to be lower in White compared with Asian adults ( P < 0.10 for both). Such tendency disappeared when the difference in height was taken into account using ANCOVA ( P = 0.84 and P = 0.77, respectively). Radial AI was strongly and positively correlated with carotid AI in White adults ( r = 0.75, P < 0.0001) as well as in Asian adults ( r = 0.82, P < 0.0001). The slope and intercept of linear regression line between radial and carotid AI of White adults were highly comparable with those of Asian adults. Conclusion AI in the conveniently located peripheral vasculature may provide a surrogate measure of central AI irrespective of difference in race (e.g., Asian vs. White populations).

Arterial Stiffness and Cardiovascular Events

Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community. We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P=0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models. Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community.

Wave reflection and arterial stiffness in the prediction of 15-year all-cause and cardiovascular mortalities: a community-based study.

The value of increased arterial wave reflection, usually assessed by the transit time-dependent augmentation index and augmented pressure (Pa), in the prediction of cardiovascular events may have been underestimated. We investigated whether the transit time-independent measures of reflected wave magnitude predict cardiovascular outcomes independent of arterial stiffness indexed by carotid-femoral pulse wave velocity. A total of 1272 participants (47% women; mean age: 52+/-13 years; range: 30 to 79 years) from a community-based survey were studied. Carotid pressure waveforms derived by tonometry were decomposed into their forward wave amplitudes, backward wave amplitudes (Pb), and a reflection index (=[Pb/(forward wave amplitude+Pb)]), in addition to augmentation index, Pa, and reflected wave transit time. During a median follow-up of 15 years, 225 deaths occurred (17.6%), including 64 cardiovascular origins (5%). In univariate Cox proportional hazard regression analysis, pulse wave velocity, Pa, and Pb predicted all-cause and cardiovascular mortality in both men and women, whereas augmentation index, reflected wave transit time, and reflection index were predictive only in men. In multivariate analysis accounting for age, height, and heart rate, Pb predicted cardiovascular mortality in both men and women, whereas Pa was predictive only in men. Per 1-SD increment (6 mm Hg), Pb predicted 15-year cardiovascular mortality independent of brachial but not central pressure, pulse wave velocity, augmentation index, Pa, and conventional cardiovascular risk factors with hazard ratios of approximately 1.60 (all P<0.05). In conclusion, Pb, a transit time-independent measure of reflected wave magnitude, predicted long-term cardiovascular mortality in men and women independent of arterial stiffness.

Radial Arterial Wave Reflection is Associated with the MEGA Risk Prediction Score, an Indicator of Coronary Heart Disease Risk, in Middle-Aged Men with Mild to Moderate Hypercholesterolemia

The present study examined the association between the radial augmentation index (AI), a marker of arterial wave reflection, and the MEGA risk prediction score (MEGA score), an indicator of coronary heart disease (CHD) risk, in middle-aged men with mild to moderate hypercholesterolemia. Radial AI was measured during a company health examination in 266 men (age: 47+/-5 years) with total cholesterol levels ranging 220-270 mg/dL who were not taking antihypertensive, lipid-lowering, or antidiabetic agents. The MEGA score was calculated based on sex, age, low- and high-density lipoprotein cholesterol, blood pressure, glucose level, and smoking status. The higher MEGA score indicates increased CHD risk. A MEGA score > or = 22 corresponds to a 5-year CHD risk > or = 2.5% and we defined a MEGA score > or = 22 as a high estimated CHD risk. The mean AI was 74.4+/-12.6%. A high estimated CHD risk was seen in 32 subjects (12.0%). After adjusting for height and heart rate, the AI was higher in subjects with a high estimated CHD risk (81.5+/-10.6%) than in those without (73.4+/-10.4%, p<0.001). The odds ratio for high estimated CHD risk in the highest tertile of AI was 8.14 (p=0.002) in comparison to the lowest tertile, after adjusting for multiple potential confounders which did not constitute the MEGA score. The radial AI was positively associated with the estimated risk of CHD. These results suggest the usefulness of radial AI as a risk marker for future onset of CHD in middle-aged men with mild to moderate hypercholesterolemia.

Change in Augmentation Index during NOS Inhibition, an Index of Basal NO Production, Is an Independent Determinant of Large-Artery Function

Background/Aims: Arterial wave reflection, measured as augmentation index (AIx), and central pulse pressure (PP) closely predict cardiovascular events. We hypothesized that basal nitric oxide (NO) production would be a determinant of AIx and central PP. Methods: AIx and central PP were assessed at baseline by pulse wave analysis in 86 male subjects across a wide range of age, blood pressure and lipid values. The basal NO production in the cardiovascular system was then determined as change in AIx during NO synthase blockade with N^G-monomethyl-L-arginine (L-NMMA, 3.25 mg/kg). Results: AIx increased from 17.5 ± 14.6 to 23.1 ± 14.2 during L-NMMA infusion (p < 0.001). The increase in AIx during NO synthase blockade, an index of basal NO production, was inversely related to baseline central AIx and PP, and positively to PP amplification. Multiple linear regression analyses disclosed that in addition to age and mean blood pressure, change of AIx to L-NMMA is a strong and independent determinant of baseline central AIx, central PP and PP amplification. Conclusion: Greater change of AIx to L-NMMA, an index of basal NO production, is associated with better large-artery function. Therefore, therapeutic interventions which increase the basal NO production might be particularly effective in reducing cardiovascular risk.

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.

Aortic Augmentation Index: Reference Values in a Large Unselected Population by Means of the SphygmoCor Device

Arterial stiffness and pulse wave reflection are associated with cardiovascular disease (CVD). Pulse wave analyses (PWAs) allow the estimation of the central augmentation index (AIx), a measurement of pulse wave reflection. To understand the predictive role of AIx, reference values for AIx are needed. This population study is based on 4,561 subjects from The Copenhagen City Heart Study, an ongoing epidemiological survey started in 1976, including subjects randomly chosen from the population in Copenhagen, Denmark. We calculated and internally validated reference values of AIx measured by the SphygmoCor device in a cohort without known CVD or diabetes, and with low risk of CVD according to HeartScore using gender-specific multiple regression analyses adjusting for age, heart rate, and height. AIx was significantly higher in women than in men, 30% vs. 22%, (P < 0.001) and the increase in AIx with age was curvilinear. There were 972 subjects in the low-risk cohort with mean AIx 28% in women (N = 565) and 18% in men (N = 407) (P < 0.001). We report the following internally validated reference equations for AIx: men: AIx = 79.20 + 0.63 (age) - 0.002 (age(2)) - 0.28 (heart rate) - 0.39 (height). Women: AIx = 56.28 + 0.90 (age) - 0.005 (age(2)) - 0.34 (heart rate) - 0.24 (height). AIx appeared to increase with increasing risk of CVD according to HeartScore. We report a novel and internally validated gender-specific equation including age, heart rate, and height to calculate reference values for AIx.