Mike Crilly
email: mike.crilly@abdn.ac.uk

Christoph Coch

Margaret Bruce

Hazel Clark

David R Williams

Indices of cardiovascular function derived from peripheral pulse wave analysis using radial applanation tonometry: a measurement repeatability study

Keywords: applanation tonometry, measurement error, pulse wave analysis, radial artery, reproducibility

Introduction

Routine clinical assessment of cardiovascular function traditionally relies upon evaluation of the radial pulse and the brachial systolic and diastolic blood pressure. Interest in the non-invasive assessment of cardiovascular function has increased over recent times, particularly around the relationship between the stiffness of large arteries and blood pressure. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF][START_REF] Williams | Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study[END_REF] One particularly promising non-invasive method for assessing cardiovascular function that has emerged is the novel technique of pulse wave analysis (PWA) using applanation tonometry. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF][START_REF] Oliver | Noninvasive assessment of arterial stiffness and risk of atherosclerotic events[END_REF][START_REF] Mackenzie | Assessment of arterial stiffness in clinical practice[END_REF][START_REF] O'rourke | Pulse wave analysis[END_REF] Advances in computer technology mean that it is now possible to rapidly assess central aortic pressures and waveforms without the need for cardiac catheterization. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF][START_REF] Williams | Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study[END_REF] Until recently, the use of PWA has largely been restricted to research, but commercial PWA devices such as the SphygmoCor system are now available for use in routine clinical practice. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] Pulse wave analysis (PWA) PWA uses a high-fidelity tonometer to capture electronically the shape of a peripheral arterial pulse. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] The tonometer probe is 'applanated' (applied so as to flatten, but not occlude an artery) at a convenient site such as the radial artery. The shape of the peripheral pulse wave obtained is then calibrated with the brachial systolic and diastolic pressure (measured in the traditional manner with an inflated cuff at the brachial artery) to derive the shape and dimensions of the central aortic pressure wave. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] The SphygmoCor system converts the peripheral waveform to a central waveform using a proprietary algorithm ('general transfer function'). [START_REF] O'rourke | Pulse wave analysis[END_REF][START_REF] Pauca | Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform[END_REF] PWA permits the non-invasive measurement of three main indices of cardiovascular function: augmentation index adjusted to a heart rate of 75 beats per minute (AIX@75), subendocardial viability ratio (SEVR%), and the ejection duration index (ED%). [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] The derivation of these indices are shown schematically in Figure 1 and described below.

Augmentation index (AIX) adjusted to a heart rate of 75 (AIX@75)

In the peripheral arteries the outgoing systolic pulse wave is reflected back towards the heart and adds to ('augments') the central aortic pressure in late systole. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF][START_REF] Oliver | Noninvasive assessment of arterial stiffness and risk of atherosclerotic events[END_REF][START_REF] Mackenzie | Assessment of arterial stiffness in clinical practice[END_REF][START_REF] O'rourke | Pulse wave analysis[END_REF] The amount by which the aortic pressure is increased by this phenomenon is the 'augmentation pressure' (AP). AIX is this aortic AP expressed as a percentage of the aortic 'pulse pressure' (PP). [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF][START_REF] Oliver | Noninvasive assessment of arterial stiffness and risk of atherosclerotic events[END_REF][START_REF] Mackenzie | Assessment of arterial stiffness in clinical practice[END_REF] AIX (ϭAP/PP) indicates the combined influence of large artery pulse wave velocity, peripheral pulse wave reflection and vascular function. [START_REF] Oliver | Noninvasive assessment of arterial stiffness and risk of atherosclerotic events[END_REF][START_REF] O'rourke | Pulse wave analysis[END_REF][START_REF] Wilkinson | Pulse-wave analysis: clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function[END_REF][START_REF] Hayward | Assessment of endothelial function using peripheral waveform analysis: a clinical application[END_REF] AIX is the most widely researched index of PWA, with several studies indicating that AIX is independently predictive of adverse cardiac events. [START_REF] London | Arterial wave reflections and survival in end-stage renal failure[END_REF][START_REF] Weber | Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions[END_REF] Since AIX varies with heart rate it is commonly adjusted to a 'standard heart rate' of 75 beats per minute (AIX@75). 11

Subendocardial viability ratio (SEVR%, Buckberg ratio)

The 'area under the curve' (AUC) of the systolic and diastolic portions of the central aortic pulse wave can be measured using PWA. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] Blood flow within the coronary arteries occurs mainly during diastole and the diastolic-AUC indicates myocardial perfusion ('supply of oxygen'). [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] The systolic-AUC indicates myocardial contraction ('demand for oxygen'). The subendocardial viability ratio (SEVR%), also known as the Buckberg ratio, is a 'supply to demand' ratio of the diastolic-AUC divided by the systolic-AUC. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF][START_REF] Buckberg | Experimental subendocardial ischemia in dogs with normal coronary arteries[END_REF] In normal coronary arteries, subendocardial ischaemia occurs when SEVR% falls below 50%. [START_REF] Hoffman | The myocardial supply:demand ratio -a critical review[END_REF]

Ejection duration index (ED%)

The duration of left ventricular systolic ejection (systolic time interval in milliseconds) can be measured using PWA. [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] The ratio of the duration of systolic ejection to the total duration of a cardiac cycle is the ejection duration index (ED%). Patients with systolic dysfunction have been found to have a higher ED% than those with diastolic dysfunction. 1

Repeatability of PWA indices

It is important that clinical innovations, such as PWA, are carefully evaluated before their widespread introduction into routine clinical practice. The diffusion of previous medical innovations into medical practice has not always produced the benefits anticipated for patients. [START_REF] Mckinlay | From 'promising report' to 'standard procedure': seven stages in the career of a medical innovation[END_REF] For PWA to be clinically useful it must be a clinically reproducible technique, but a recent review concluded that considerable uncertainty still remains concerning the repeatability of peripheral PWA. [START_REF] Simon | May subclinical arterial disease help to better detect and treat high-risk asymptomatic individuals?[END_REF] Only one previous study has reported on the repeatability of AIX@75 and SEVR% [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF] and two further studies have estimated the repeatability of SEVR%, [START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] although one of these studies only addressed betweenobserver repeatability. [START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] No previous studies have reported on the repeatability of ED%.

The recent introduction of PWA into routine clinical cardiovascular assessment of patients at Aberdeen Royal Infirmary (a 1000-bed university teaching hospital) provided the opportunity to assess the repeatability of the method when undertaken by nursing staff with limited previous experience of using the technique. The aim of this study was to estimate the within-and between-observer repeatability for the three main indices of cardiovascular function (AIX@75, SEVR%, and ED%) obtained from PWA using applanation tonometry.

Methods

A consecutive series of 20 ambulant patients in sinus rhythm underwent pulse wave analysis (PWA). They were purposively selected to include 10 patients prescribed medication for essential hypertension and 10 patients without hypertension or known cardiovascular morbidity. Blood pressure (BP) and peripheral PWA were each measured a total of four times at a single hospital visit. Two nurses independently undertook all BP/PWA measurements in alternate order using the same equipment. BP was measured at the left brachial artery and PWA at the right radial artery according to an agreed protocol.

Patients rested supine for 15 minutes before each nurse (A/B) measured BP/PWA twice in alternate order (ABAB or BABA). Each nurse measured BP/PWA alone in a clinical side-room, ensuring that any tonometer pressure mark left at the wrist had disappeared before alternating. Whilst each nurse was aware of their own BP/PWA measurements, each was blind to the measurements obtained by the other. Neither nurse had access to patient medical records nor did they record any other additional clinical information (other than asking patients about their current use of medication for high BP). Patients did not speak or sleep during assessment. They had not been asked to refrain from eating, drinking or smoking prior to assessment. All assessments were undertaken in a quiet temperature-controlled side-room at Aberdeen Royal Infirmary (22 July to 30 September 2004, between 08:30 am to 3:30 pm).

Blood pressure (BP)

BP was measured with a standard adult cuff at the left brachial artery (a large adult cuff was used if the upper arm circumference was greater than 32 cm). Patients had their supine BP measured four times (nurses alternating twice) using the Omron HEM-757 IntelliSense BP monitor (marketed commercially as the M5-I in the UK by Omron Healthcare Inc., Bannockburn, IL, USA). The Omron M5-I/HEM-757 is an automated oscillometric BP monitor that had been successfully validated independently against international criteria. 19

Radial pulse wave analysis (PWA)

A hand-held tonometer probe (Millar tonometer, Houston, Texas, USA) was used to capture the peripheral pulse wave. The tonometer was 'applanated' (applied so as to flatten but not occlude) at the right radial artery with the wrist supported by a pillow. The shape of the peripheral pulse wave was captured electronically using a laptop computer (Toshiba Satellite Pro) linked to a desktop SphygmoCor pulse wave analysis system (SCOR-Px, software version 7.01, AtCor Medical Pty Ltd., Sydney, Australia). [START_REF] Nichols | McDonald's blood flow in arteries: theoretical, experimental and clinical principles[END_REF] The SphygmoCor system generated an average peripheral pulse wave contour from a 10 second recording period. The quality of the pulse waves captured was assessed by the nurse both visually (on the PC screen) and numerically using the SCOR-Px built-in quality index score, QI% (derived from pulse height, pulse height variation and diastolic variation).

The two nurses were registered general nurses, with more than 20 years clinical experience each. Both had previous expertise in intensive care nursing. Prior to the start of this study they had practised PWA around 35 times on a small number of work colleagues after having attended a 2-day PWA theoretical-practical course some 6 months previously. Only high-quality pulse wave traces, both visually (uninterrupted steep upstroke with second systolic shoulder before a sharp incursa inflection and smooth exponential decline in diastole) and numerically (QI% Ն85%; pulse height Ն100 units; pulse height variation Յ5%; and diastolic variation Յ5%) were considered acceptable. 1

Statistical approach

Analysis is based on individual patient data as the unit of analysis. Only anonymized individual patient data were available for this analysis. The 'Bland-Altman 95% limits of agreement' approach (mean difference Ϯ 2 standard deviations, 2SD) was used to assess within-and between-observer differences in paired measurements, [START_REF] Bland | Measuring agreement in method comparison studies[END_REF][START_REF] Bland | Applying the right statistics: analyses of measurement studies[END_REF] with the mean of all four measurements (ED%, AIX@75, SEVR%) assumed to be the best estimate of the true underlying value. [START_REF] Bland | Applying the right statistics: analyses of measurement studies[END_REF] This approach assumes that observer differences are normally distributed over a range of measurements and uses SD as an index of measurement error. [START_REF] Bland | Applying the right statistics: analyses of measurement studies[END_REF] Intraclass correlation coefficients (ICC) were calculated for between-and within-observer repeatability using one-way analysis of variance (ANOVA). Standard methods were used to calculate 95% confidence intervals. [START_REF] Altman | Statistics with confidence: confidence intervals and statistical guidelines[END_REF] All data were double-entered for analysis into SPSS (version 14). No participants or 'outlying values' were excluded from any part of the analysis.

Results

Pulse wave analysis was successfully undertaken in a consecutive series of 20 ambulant patients (four female) in sinus rhythm referred for PWA from among patients attending Aberdeen Royal Infirmary (ARI). Ten patients were on medication for essential hypertension (four mono-therapy, four dual-therapy and two triple-therapy). Mean age was 56 (range 27-82; SD 14.6). Mean brachial BP was 136/79. Excluding the initial 15 minutes rest, PWA took a mean of 30 (range 12-54; SD 11.8) minutes per patient. The quality of PWA recording was high with a mean quality index (QI%) of 97.1% (range 90-100; SD 2.9). Mean QI% was similarly high for both nurses (96.9% and 97.3%). For 12 patients the nurse assessment followed a sequence of 'ABAB' (and 'BABA' for eight patients).

PWA and BP measurements

Both nurses recorded very similar PWA and BP measurements for this group of patients. The values and ranges of the clinical measurements obtained are shown in Table 1. The pulse rate shown is that recorded by the SphygmoCor machine. SEVR% had the widest range of values (extending over 79 points), whilst the ED% had the narrowest range (12 points). SEVR% had a similar range and SD to systolic BP, whilst AIX%@75 had a similar range (43 points) and SD to pulse rate.

Trends in PWA assessment

Each patient had four sequential measurements of BP and PWA. Figure 2 shows the stability of mean BP and PWA measurements over time. Systolic and diastolic BP decreased (by 3.6 and 3.1 mmHg respectively) with the majority of the reduction occurring between the first and second measurements. Pulse rate declined by 1.3 beats per minute, whilst AIX@75 declined by 2.0 points. SEVR% initially declined (by 4.5 points between the first and second measurements) before gradually returning to its initial value. Both ED% and QI% showed no real change over time.

Between-and within-observer repeatability (ED%, AIX@75 and SEVR%) are shown in Tables 2 and3. Pulse rate is included as a comparison measure. The related Bland-Altman plots are shown in Figure 3. For the between-observer differences the solid horizontal line represents the line of no difference, whilst the three dashed horizontal lines represent the mean (and Ϯ2SD) of the difference between measurements. For the within-observer differences the dashed-dotted lines represent nurse-A and the dashed lines nurse-B.

Between-observer repeatability

The ICCs based on the average of two PWA measurements were very high (Ն0.94) (Table 2). They were lower when based on a single PWA measurement, but remained above 0.92 for AIX@75. The upper section of Table 2 shows the between-observer differences (mean difference, SD, limits of agreement) in PWA measurements based on the average of two PWA measurements made on each patient by each nurse. All the differences are small (less than 2 points), but the spread of these differences (indicated by SD) are wider for those indices with a wider range of values. SEVR% has the widest range (79 points) and also the Because of rounding of decimal places the range may not equal the highest minus the lowest value.

Values are based on four measurements (except values for individual nurses based on two measurements). SD, standard deviation; ED%, ejection duration index; bpm, beats per minute; AIX@75, augmentation index adjusted to a pulse rate of 75 bpm using the SphygmoCor machine's inbuilt algorithm; SEVR%, subendocardial viability ratio; mmHg, millimetres of mercury. widest 'limits of agreement' (Ϫ16% to ϩ12%). Both ED% and AIX@75 have narrower limits of agreement (Ϫ2 to ϩ2; Ϫ3 to ϩ5, respectively); limits that are comparable with pulse rate (Ϫ3 to ϩ4). The betweenobserver differences, when expressed as a proportion of the range (mean difference/range of values) were small: 2.2% for ED%, AIX@75 and SEVR%; compared with 1.4% for pulse rate. The lower two sections of Table 2 show the between-observer differences for the first and second PWA measurements. As would be anticipated, the between-observer variability is greater when based on a single measurement as opposed to the average of two readings. For example, the between-observer limits of agreement for ED% was Ϫ3% to ϩ4% when based on the first PWA measurement; Ϫ4% to ϩ5 when based on the second measurement; but Ϫ2% to ϩ2% when based on the average of these two measurements.

Within-observer repeatability

The within-observer differences in PWA measurements for the two nurses (A & B) are shown in Table 3. The ICCs for AIX@75 were high for both nurses (Ն0.93), but somewhat lower for ED% and SEVR (Յ0.86). The actual numerical differences for all three indices were small (less than 2 points). ED% and AIX@75 both had limits of agreement that were broadly comparable with those for pulse rate. For example, the values for nurse-B were Ϫ4 to ϩ4, Ϫ8 to ϩ8, and Ϫ8 to ϩ5 (for ED%, AIX@75 and pulse rate respectively). Nurse-A showed greater variability in the measurement of ED% and SEVR%, whilst nurse-B showed greater variability in the measurement of AIX@75. The widest 'limits of agreement' was for SEVR% measured by nurse-A (Ϫ41 to ϩ37). Focusing on the other PWA measurements, from the nurse with the higher level of variability, withinobserver limits of agreement were Ϫ5 to ϩ5 for ED%, Ϫ8% to ϩ8 for AIX@75, and Ϫ12 to ϩ10 for pulse rate. The within-observer absolute differences, when expressed as a proportion of the range (mean difference/range of values) were small: 0.4% for ED%; 0.1% for AIX@75; 0.8% for SEVR% and 3.1% for pulse rate.

We intentionally attempted to select patients to provide a broad range of PWA values across which we could assess repeatability (as opposed to assessing the ability of PWA to distinguish between different patient groups). Since a wider range of values will have tended to inflate the ICCs, undue emphasis should not be placed on the potential generalizability of the ICCs that we observed. [START_REF] Bland | Measuring agreement in method comparison studies[END_REF][START_REF] Bland | Applying the right statistics: analyses of measurement studies[END_REF] Since we assessed our patients at a single session, we have not accounted for within-patient variability that would operate when assessing the same patient on more than one occasion; for example, in prospectively monitoring clinical changes in PWA.

Comparison with other studies

The 'limits of agreement' approach is the most useful approach to the assessment of measurement error and repeatability. [START_REF] Bland | Measuring agreement in method comparison studies[END_REF][START_REF] Bland | Applying the right statistics: analyses of measurement studies[END_REF] A comparison of our findings with the published literature is shown in Table 4. One additional study has evaluated the repeatability of SEVR%, but provides insufficient information to derive 'limits of agreement' to permit its inclusion. [START_REF] Filipovsky | Reproducibility of radial pulse wave analysis in healthy subjects[END_REF] Whilst several studies have reported on the repeatability of AIX unadjusted for heart rate, [START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF][START_REF] Wilkinson | Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis[END_REF] only one previous study has reported on the repeatability of AIX (mean Ϯ 2SD) adjusted for heart rate (AIX@75). [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF] Two studies have estimated the repeatability of SEVR%, [START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] but no previous studies have reported on the repeatability of ED%.

All three previous studies (Table 4) were hospitalbased. [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF][START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] Two studies measured PWA supine on a single occasion, [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF][START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF] whilst the third study measured PWA seated on three separate days. [START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] Only one study rested patients for as long as 15 minutes supine. [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF] Participants in our study were older (with a higher average brachial blood pressure) than the two studies recruiting healthy hospital volunteers, [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] but had a similar age to the study involving patients with renal failure. [START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF] Differences in patient characteristics, duration of rest before assessment, observer expertise and the influence of diurnal variation at the time of assessment may explain differences in repeatability between studies. [START_REF] Van Bortel | Clinical applications of arterial stiffness, Task Force III: recommendations for user procedures[END_REF] Whilst our analysis is based on individual patients as the 'unit of analysis', the previous studies have used 'all PWA measurements performed' as their unit of analysis (e.g. three PWA measurements on 25 patients contributes 75 units of analysis). Such a 'pooling of PWA measurements' has the effect of artificially inflating the sample size and reducing the influence of individual patient variability.

Our within-observer 'limits of agreement' for AIX@75, SEVR% and heart rate were very similar to those from the study that also rested patients 15 minutes supine before PWA (Table 4). But is narrower for SEVR% than the study involving patients with renal failure. [START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF] Our between-observer LoA were consistently narrower than the other three studies. Two studies reported much wider LoA for SEVR% than ours. [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] The high levels of repeatability seen in our study may relate to our nurses' previous experience in intensive care nursing and use of complex clinical devices, as well as the fact that our patients rested supine for a full 15 minutes before assessment. Whilst our nurses were aware that their performance was being scrutinized, and consequently may have been particularly diligent in their measurements, a similar influence will operate in any formal repeatability studies. [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF][START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF][START_REF] Van Bortel | Clinical applications of arterial stiffness, Task Force III: recommendations for user procedures[END_REF] In conclusion, we found high levels of both withinand between-observer repeatability for the cardiovascular indices of ED%, AIX@75 and SEVR%, even when PWA is undertaken by relatively inexperienced staff. There was no discernable time trend in either the quality or in the variability of PWA measurement, suggesting that PWA is a technique that can be easily and rapidly acquired for use in clinical practice. Our study supports suggestions that peripheral PWA using applanation tonometry has the potential to be included in the routine cardiovascular assessment of ambulant patients.

Figure 1

 1 Figure 1 Cardiovascular indices derived from arterial pulse wave.

Figure 2

 2 Figure 2 Trends in serial blood pressure and pulse wave analysis (PWA) measurements: four measurements on 20 patients made alternately by two nurses.

Figure 3

 3 Figure 3 Between-observer and within-observer repeatability of three cardiovascular indices.

Table 1

 1 Measurements of blood pressure (BP) and pulse wave analysis (PWA) undertaken by two observers, n ϭ 20.

				Range (low	Mean		Mean
		Mean	(SD)	to high)	Nurse-A	(SD)	Nurse-B	(SD)
	Ejection duration ratio, ED%	34	(3.0)	12 (30 to 42)	35	(3.0)	34	(3.1)
	Augmentation index at 75 bpm, AIX@75	19	(11.0)	43 (-3 to 41)	19	(11.4)	18	(10.8)
	Subendocardial viability ratio, SEVR%	158	(20.8)	79 (122 to 201) 157	(21.0)	159	(21.3)
	Pulse rate (bpm)	64	(8.9)	37 (51 to 88)	64	(8.9)	63	(9.1)
	Brachial diastolic blood pressure (mmHg)	79	(8.5)	28 (60 to 88)	79	(8.2)	78	(9.1)
	Brachial systolic blood pressure (mmHg)	136	(19.6)	80 (93 to 173) 136	(18.9)	135	(20.6)

Repeatability of pulse wave analysis (PWA) 191Vascular Medicine 2007; 12:[189][190][191][192][193][194][195][196][197]

Discussion

PWA using radial artery tonometry has very high levels of within-and between-observer repeatability, even when used by nurses with limited previous experience of the technique. Both between-observer and within-observer differences in the measurement of ED%, AIX@75 and SEVR% were small, whether based on a single initial measurement or the average of two readings. Mean absolute differences between measurements were less than 2 points for all three indices. SEVR% had the widest range of values and demonstrated the widest limits of agreement. On the basis of this study we would predict that for 95% of patients assessed in a similar manner, the absolute differences between-observers undertaking a single measurement would fall within a range of Ϫ2 to ϩ2 (ED%), Ϫ3 to ϩ5 (AIX@75), and Ϫ16 to ϩ12 (SEVR%). Based on a conservative estimate, the equivalent limits for absolute differences within-observers are Ϫ5 to ϩ5 (ED%), Ϫ8 to ϩ8 (AIX@75), and Ϫ41 to ϩ37 (SEVR%).

Study strengths and limitations

We adopted a rigorous approach to this evaluation of PWA repeatability, taking account of consensus guidelines on the performance of PWA. We assessed all of our patients supine after 15 minutes of rest. [START_REF] Filipovsky | Reproducibility of radial pulse wave analysis in healthy subjects[END_REF] Our patients had a broad range of PWA values and the number of patients recruited is comparable with other published studies. [START_REF] Frimodt-Moller | Pulse-wave morphology and pulse-wave velocity in healthy human volunteers: examination conditions[END_REF][START_REF] Savage | Reproducibility of derived central arterial waveforms in patients with chronic renal failure[END_REF][START_REF] Siebenhofer | The reproducibility of central aortic blood pressure measurements in healthy subjects using applanation tonometry and sphygmocardiography[END_REF] All BP/PWA measurements were made using the same equipment by two nurses who were blind to each other's measurements, although it was not possible to avoid each nurse being aware of their own BP/PWA measurements and any resulting bias will have tended to reduce withinobserver variability.

The nurses independently and alternately measured PWA on the same patients at a single session. PWA was undertaken to a very high-quality standard and BP was recorded using a validated and automated machine. [START_REF] Assaad | Evaluation of two devices for self-measurement of blood pressure according to the international protocol: the Omron M5-I and the Omron 705IT[END_REF] Both BP and PWA indices remained stable during the assessment period. Our primary interest was the repeatability of PWA, not the ability of PWA to distinguish between patients with or without specific medical conditions. In order to avoid unduly influencing BP/PWA measurement, the nurses collected only limited patient demographic data (age and gender). Other than drug therapy for essential hypertension they were kept blind to the patient's medical history.

A limitation of the study is that the sequence of nurse BP/PWA measurement was not random, but depended pragmatically upon which nurse was most readily available to undertake the first measurement. Consequently, the first PWA/BP measurement was undertaken by nurse-A (sequence ABAB) for 12 (nine male) patients. This is unlikely to have biased our results as those patients assessed initially by nurse-A were similar to those initially assessed by nurse-B (mean age of 57 vs 56; BP 133/78 vs 140/79; and pulse rate 66 vs 61).

We did not confirm that BP was the same in both arms. Radial PWA and brachial BP were measured on opposite arms, as it was more convenient to place the Omron BP machine and SphygmoCor device on opposite sides of the patient. Since both nurses followed the same procedure this will not have influenced our assessment of repeatability. But if any of our patients had significant left subclavian artery stenosis, then the subsequent miscalibration of the SphygmoCor device will have distorted the central aortic values obtained from the true value.


This past year has been one of the most exciting in the history of the Society for Vascular Medicine and Biology. The Society has evolved, improving its administration, focusing its mission, broadening its reach, and enhancing services for its members.

Over the last years, it has become increasingly evident to the membership and Board of Trustees that our society's name did not adequately represent the core of our mission. Originally named at its founding, the SVMB sought to engage in improving the care of patients with vascular disease, through excellence in clinical care and advances in biology. As the Society evolved, its membership grew and its mission crystallized. We engaged in the practice and science of vascular medicine in the broadest context. Our practice includes prevention, diagnosis, medical and endovascular therapies and our science encompasses vascular biology, pathophysiology, epidemiology, clinical trials and outcomes. Indeed, each of these areas represents fundamental components of the field of vascular medicine. When polled by Dr John Cooke, more than 80% of the membership agreed that a more appropriate appellation was the Society of Vascular Medicine. At our annual business meeting, a formal vote was held, and the new name of our society, Society of Vascular Medicine, was adopted.

Perhaps the greatest reflection of this consensus of our mission is our expanding membership. The SVM (first time in print) has grown by 76% over the last 2 years to an all-time high of 663 associates, members, and fellows. The increase in membership allows us to improve the strength of our advocacy, expand the services available to members, and incorporate the expertise of an incredibly dedicated group of professionals.

This expansion in growth has occurred in concert with the expansion in the SVM committee structure. One of Dr Cooke's signature initiatives was the creation of a committee structure designed to galvanize the collective power of our membership into activities to further our joint goals. Dr Cooke created a Communications Committee, ably led by Dr James Froehlich, which reviewed more than 20 guidelines, statements, and consensus documents over the last year. The new Advocacy Committee, led by Dr Heather Gornik, is working diligently to get reimbursement for ankle-brachial index screening in appropriate populations and compensation for supervised exercise training for patients with intermittent claudication. Dr Robert Eberhardt leads the Emerging Leaders Committee which provides a mechanism to recognize the next generation of leaders and get them involved early in their career. Through the creation of these and other committees, Dr Cooke has created a structure to facilitate SVM success over the long term.

It is conceivable that some of the most important changes to the SVM have occurred with little notice by the membership. The Society decided to pursue new management and sent out a Request for Applications. After reviewing more than 20 proposals, interviewing the top six candidates, and re-interviewing the two finalists, the Society's officers unanimously chose the Sherwood Group because of its incredible experience and dedication to specialty societies like our own. Greg Schulz, the Sherwood Group Vice President, will be our Executive Director. The change in administration is facilitating many 'under the hood' improvements, such as a complete overhaul of our website, and a more stable accounting procedure. One unfortunate side effect of our transition is the farewell we say to Lorraine Bell. Lorraine worked diligently, enthusiastically and faithfully to promote the SVM and we wish her all success in her future endeavors.

This past year has also brought about a transition in our journal's publisher. Vascular Medicine was acquired by Sage Publications. Sage publishes more than 460 journals, including the journals of 160 societies. Their administration will improve the editorial process, transitioning the manuscript submission to an electronic/internet-based system. With these improvements and the increasing recognition of the SVM and Vascular Medicine, manuscript submissions, of both original and review articles, are on a course to nearly double over the next year.

Finally, I would be remiss should I not mention this year's outstanding Scientific Sessions and Board Review Course. Organized by Dr Michael Bacharach (Scientific Sessions) and Dr Thom Rooke (Board Review Course), the more than 250 attendees were treated to an incredible program. The Scientific Sessions featured presentations about endovascular strategies, clinical trials updates, health care and practice economics. We were fortunate to have Drs Jeff Olin, Michael Jaff, and Steve Dean create the yearly highlight, Vascular Jeopardy, won this year by Dr Teresa Carman. Finally, I think everyone in

© 2007 SAGE Publications, Los Angeles, London, New Delhi and Singapore 10.1177/1358863x07082372

News from the SVMB -- attendance will remember with awe the presentation by our Keynote Speaker Dr Harry Dietz. His lecture on his laboratory's investigation into the mechanism of aneurysm formation in Marfan disease and its translation from the bench to clinical trials represents the pinnacle of vascular research.

Our Board Review Course was again a smashing success, indicating an ongoing interest in vascular and endovascular medicine. Dr Rooke has improved the pool of speakers over the past 3 years, to create a 'highlight reel' of vascular expertise. In fact, the accumulation of talent was so incredible, that a CD ROM will be produced featuring all of the talks and sold to those who want a permanent record or to those unable to attend. Attendees received the newly published Board Review Course book, created by last year's faculty, which is also available for purchase. The popularity of the course and the request for enduring materials signals a continuing expansion in practitioners interested in vascular medicine and American Board of Vascular Medicine Board certification. The SVM continues to participate in the many initiatives described over the last few years, such as the PAD Coalition and governmental advocacy. In fact, the purview of activities is expanding rapidly and those associates, members, and fellows interested in becoming more active and joining the fun should e-mail Denise Baran (dbaran@svmb.org). She will send these requests to the appropriate committee leader and ensure your participation.


est destinée au dépôt

Preamble

It is my great pleasure to address this 18th Annual Meeting of the Society for Vascular Medicine as the outgoing President. It will be your greater pleasure to know that in this address, I will follow the advice of the seventeenth-century Catalan philosopher Baltasar Gracián who said, "What is good, is doubly so if it be short; and in like manner, what is bad, is less so if there be little of it."

Let me begin by thanking Drs Michael Bacharach and Thom Rooke for their superb work in producing an educational event of high value. Dr Bacharach's Scientific Organizing Committee included Drs Annex, Creager, Hirsch, Jaff and Mohler. Dr Rooke was assisted by Dr Timothy Sullivan. Both the scientific session and the board review course have a spectacular faculty providing topical content. Dr Michael Jaff deserves special mention for his outstanding leadership of the Finance Subcommittee which raised funds for the meeting. I am grateful to our corporate sponsors, who have helped to make possible this educational effort.

Founding of the Society, and its first President, Jay Coffman

The first annual meeting of our Society took place on March 19, 1989 in Anaheim CA, when 13 physicians founded the Society for Vascular Medicine and Biology. One of those founders, Jay Coffman, became the first President of our Society. Jay was professor and head of the section of vascular medicine at Boston's University Hospital. He was an internationally recognized physician-scientist, and made many important contributions to our understanding of the regulation of cutaneous blood flow and the pathophysiology of Raynaud's disease. [START_REF] Khan | Enhanced cholinergic cutaneous vasodilation in Raynaud's phenomenon[END_REF][START_REF] Coffman | The enigma of primary Raynaud's disease[END_REF] Jay passed away this year, and in recognition of his contributions to our field, the Scientific Organizing Committee has named the Young Investigators Competition after him. Jay would have enjoyed the superb presentations that we heard yesterday. It is wonderful to see that the future of our field is in the hands of such promising young investigators, and that Dr Coffman's legacy will continue. Jay would also be delighted to see the continued growth and influence of our Society. In the last 2 years, the Society has grown by 76% from 376 to 663 fellows, members and associates. I am grateful for the hard work of Dr Joshua Beckman and his Membership Committee (Drs Jim Froehlich, Alain Drooz, Pavel Levy and Suman Rathbun) who vetted each of the new applications. The increased interest in our Society and growth of our field is attributable to a number of developments.

Developments driving the emergence of vascular medicine

Vascular diseases account for most of the morbidity and mortality in the USA. [START_REF]Heart Disease and Stroke Statistics -2007 Update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee[END_REF] In addition to the major vascular diseases causing cerebrovascular and myocardial infarction as well as venous thromboembolism, there is a broad spectrum of arterial, venous, and lymphatic diseases, as well as associated medical disorders. This diversity and complexity of vascular diseases requires knowledgeable vascular internists to provide care in a cost-effective manner. [START_REF] Creager | Working Group on Fellowship Training in Vascular Medicine, The Society for Vascular Medicine and Biology. Postgraduate training in vascular medicine: proposed requirements and standards[END_REF] Currently, there is a great shortage of vascular internists in the USA. To address this manpower need, the NHLBI has announced this year that it will fund five new training programs in vascular medicine at Stanford University, University of Pennsylvania, Northwestern University, Wake Forest University, and Boston University. This allocation brings to seven the number of NHLBIfunded training programs in vascular medicine (which include the Mayo Clinic and the Brigham and Women's Hospital). This unprecedented NIH support for a clinical training program was in no small part due to the lobbying efforts and persistent hard work of Society leadership, most notably Dr Mark Creager, who was assisted by Drs Jeffrey Olin and Christopher White. It is very exciting for me to witness the accelerated activity in research and education in vascular medicine and biology in the past few years. I am proud of the major contributions that our SVMB fellows have made, and are continuing to make, in advancing knowledge and clinical care in vascular medicine. The academic vascular internists expected to come from these programs are desperately needed to train a new generation of vascular specialists, who can deal with the epidemic of vascular disease in this country.

Additional developments driving the growth of our field include the rapid advances in peripheral imaging and intervention. These developments have stimulated great interest in endovascular medicine, which is beneficial to our field. Many of our new members and fellows have entered the field by this intravascular route. Nevertheless, there remains much work to be done to establish best practices in the application of peripheral imaging and intervention. We need more randomized clinical trials of endovascular interventions, such as CLEVER, to strengthen the scientific foundation for clinical practice. [START_REF] Hirsch | Treatment of peripheral arterial disease -extending 'intervention' to 'therapeutic choice[END_REF] Furthermore, our medical system needs vascular specialists who understand the natural history of vascular diseases, who are knowledgeable in the medical management of these disorders, and who are involved in the evaluation and application of endovascular technologies.

Certification for vascular medicine specialists

Also, boosting the expansion of our field has been the creation of a certifying process for specialists in vascular medicine. Soon after founding the Society, there was discussion and ultimately a broad consensus regarding the need for certification. The Society leadership formulated a plan for a certifying entity, the American Board of Vascular Medicine, 6 and the Society funded its development. The ABVM held its first certifying exams in September 2005 and again in 2006. Over 500 individuals have taken these national examinations in general vascular medicine or endovascular medicine. The successful launch of the ABVM represents a watershed moment for vascular medicine, as our discipline emerges as a distinct subspecialty. In days hence, when we are gathered round the hearth and remembering times gone by, glasses will be raised to the name of Bruce Gray. I believe that the inception of the ABVM will be seen as an inflection point in the growth and influence of the Society. Bruce Gray has worked tirelessly to organize the ABVM, to oversee its administration, and to execute the certifying examinations in vascular and endovascular medicine.

Of course, Bruce Gray had a band of brothers assisting him in this great effort. Individuals that deserve accolades for their contribution to the success of the ABVM include Past President Dr Michael Jaff, who played a primary role in the founding of ABVM. A number of fellows labored long and hard to make the examination a success, investing many hours of thought and discussion in the development of test questions. These dedicated physicians included Drs Michael Bacharach, Mark Creager, Jon Halperin, Jeffrey Olin, Kenneth Rosenfield, Christopher White, and Krishna Rocha-Singh.

Meeting manpower needs in vascular medicine

This Society has had an influx of interventional cardiologists with a special interest in vascular and endovascular medicine, and this is a very welcome development. Indeed, about half of the growth in our Society in the last 2 years has been due to the entry of these new colleagues. We welcome them and acknowledge the energy and knowledge that they bring to our field and to our Society. However, there remains a global need for vascular internists who are fully trained in all aspects of arterial, venous and lymphatic diseases and the associated medical disorders.

Certification in vascular medicine will encourage more physicians to seek training; will stimulate training programs in vascular medicine; will promote the codification of a lexicon for vascular specialists; and will enhance patient care. In addition, certification in endovascular medicine provides the first multidisciplinary process to provide credentialing in peripheral endovascular procedures. The work of the ABVM will help to increase the number of vascular specialists. These specialists are needed to meet the growing demands of an aging US population where vascular diseases will remain the greatest cause of morbidity and mortality in the future. This is all very hopeful but I remain concerned regarding the manpower needs in vascular medicine. The new NHLBI-funded training programs are limited in number (seven) and limited in the number of years that they will be funded (5). 7 There are also a handful of self-funded training programs. The existing programs are not sufficient to meet the manpower needs of this field. Furthermore, there is not sufficient economic incentive for the extended training that many of our fellows undergo. Many of our trainees have undergone 3 years of internal medicine training and 3 years of subspecialty training. After 6 years of extensive training, we ask them to undergo an additional 1-2 years of training in vascular and/or endovascular medicine. The problem is especially acute for academic physicians, who need to incorporate into their training at least 2 years of research to acquire the tools to be successful clinician-investigators. As a result, young faculty members on average obtain their assistant professor position at the age of 40, and their first major NIH funding at the age of 44. [START_REF] Landis | New Investigators Committee Update[END_REF] I believe that radical changes in training are necessary to reduce the excessive prolongation of training, which has become an obstacle for meeting manpower needs for vascular internists, particularly those in academic medicine. [START_REF] Zemlo | The physician scientist: career issues and challenges at the year 2000[END_REF] One approach is to introduce medical students to the concept of vascular medicine during their first year in medical school, so that they can begin to imagine themselves in this field of specialty. In addition, students would be recruited out of medical school to train in this specialty. The first 2 years would be composed of internal medicine rotations directly applicable to vascular medicine (for example, the hematology/ oncology rotation would focus on thrombosis rather than chemotherapy regimens). The next 2 years might be within a division of cardiovascular medicine, again with rotations directly applicable to vascular medicine (for example, non-invasive imaging of cardiac and vascular structures would receive emphasis over electrophysiology). One year of vascular investigation (clinical, translational or basic) would also be mandatory, together with journal clubs and other mechanisms to train the fellow in evaluation of the literature for continuing lifelong education. At the end of this training, the fellow would be board eligible in internal medicine, vascular medicine and cardiology (once vascular medicine is recognized as a separate subspecialty by third party payors, board eligibility in cardiology may be less of a necessity). An additional year or more of training would be necessary for those fellows who wish to become facile with vascular intervention or plan to become independent investigators.

The Society for Vascular Medicine

To reflect the changes taking place in the field, and within our Society, we have elected to change the name of the Society to reflect its changing role. The Society membership was strongly in favor of the change, with about 80% responding positively in a recent survey. The trustees were unanimous in their support for the name change, and a clear majority of the fellows voted to approve. Dropping 'Biology' from the title is by no means a retreat from the research mission of the Society. More to the point, it is to recognize that vascular medicine includes all aspects of research, including clinical, translational as well as basic vascular biology. Research areas include arterial, venous and lymphatic disease; associated medical disorders of metabolism, coagulation, and hemodynamics; a broad spectrum of imaging and diagnostic tools; and intervention with lifestyle changes, pharmacotherapy and endovascular devices. The broad scope of research activities now being performed by our Society members may not be best characterized as 'Biology'. Another reason to drop the 'B' is to acknowledge the changing composition of our constituency, who are largely endovascular and general vascular practitioners. Nevertheless, there will always be biologists among us; I count myself as one. But I am happy to be in this diverse congregation that includes many types of investigators, educators, and clinicians, all united in their dedication to the field of vascular medicine.

Advocating for the field and our patients

Our Society is engaged at a national level to improve the care of patients with vascular disease. Dr Heather Gornik leads our Advocacy Committee. Current objectives include increasing the public awareness of PAD, as well as securing third party coverage for ABI screening, and supervised exercise rehabilitation. Dr Gornik and our Advocacy Committee, working with Dr Alan Hirsch and the PAD Coalition, have had some major victories in the past year. Most notably, on August 3 2006, the Senate passed a resolution designating Sept 18-22, 2006 as National Peripheral Arterial Disease Awareness Week (to lobby for legislation to make this an annually recurring event, Dr Gornik will soon be asking you to write to your congressmen). Passage of this resolution launched the first national awareness campaign (the 'Stay in Circulation' campaign) to increase public and health care provider awareness about PAD.

A major mechanism for influencing the field is through the creation of scholarly and thoughtful documents regarding guidelines and best practices. An excellent example is the paper last year by Beckman and colleagues 10 to refute the United States Preventive Services Task Force recommendation statement on screening for peripheral arterial disease. The USPSTF recommended against PAD screening, and implied that screening may lead to unnecessary tests, including increased risk associated with use of contrast angiographic studies. Beckman and colleagues provided a compelling rebuttal of the Task Force's recommendation. They point out that the USPSTF statement omitted key peer-reviewed data on the prevalence, screening efficacy, and short-term adverse prognosis of patients with PAD and failed to consider the beneficial outcomes that would result from timely diagnosis and medical therapy. This article should encourage the USPSTF to re-evaluate the data, and reconsider its recommendation.

Parting thoughts

Our field and our Society will continue to grow and to evolve. As the SVM grows, it will be important to preserve the original mission of the Society. Our mission has been and will be, to improve the recognition and care of vascular diseases; to foster education and research in vascular medicine; and to provide leadership to government, industry and the profession regarding issues related to vascular health. The mission has been served very well indeed by individuals, and it will continue to be the commitment and initiative of individuals that drives the Society. However, to channel that energy in a way that preserves the mission of the Society, I have introduced some additional structure. A committee structure has been formalized, and is operating very well indeed, thanks to the inspired work of the committee chairs and members.

If you aspire to involve yourself in the intellectual life and leadership of the Society, please let the leadership know. In particular, you may be interested to become a member of the Emerging Leaders Committee, chaired by Dr Robert Eberhardt. The role of this committee is to introduce emerging leaders to the ongoing activities and operations of the Society, and to integrate these individuals into projects that support the mission of the SVM.

In preparing this address, I am struck by how far we have come. So much has been achieved, so quickly, and by so few. Yet, for continued and future success, we must diversify and expand the leadership. Thank you in advance for answering the call, and joining the effort, as we innovate, expand, and advance the discipline of vascular medicine.


James J Jang
email: james.j.jang@kp.org

Peter D Gorevic

Jeffrey W Olin

Mark A Creager

Images in vascular medicine

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A 75-year-old woman presented with progressive chest pain and bilateral shoulder and arm pain. On presentation, the patient had pulmonary edema and an elevated troponin I of 3.1 ng/ml (0.0-0.4 ng/ml). Additional blood tests revealed a C-reactive protein (CRP) level of 115.0 mg/l (0.0-8.0 mg/l). Subsequently, an erythrocyte sedimentation rate (ESR) was measured and was 95 mm/h (0-20 mm/h).

Coronary angiography was performed and revealed a tapered smooth narrowing (typical of giant cell arteritis) of the left anterior descending coronary artery (arrow, Panel A). The remaining coronary arteries were normal. She underwent percutaneous angioplasty and stent implantation. After the coronary intervention, the patient had resolution of her chest pain; however, she continued to complain of exertional bilateral shoulder pain and arm discomfort when brushing her hair and writing.

Color duplex ultrasonography of the upper extremity arteries revealed severe long segment narrowing of bilateral subclavian arteries with extensive wall thickening (arrow) that was diagnostic of giant cell arteritis (Panel B). Computed tomographic angiography demonstrated bilateral subclavian artery occlusions (arrows, Panel C). The patient was administered oral prednisone 60 mg daily with normalization of the ESR and CRP levels and improvement in her symptoms.


Todd S Perlstein

Joshua A Beckman

Peri-operative cardiac biomarker surveillance

published or not. The documents may come     Peri-operative cardiac biomarker surveillance: a strategy in need of a goal

Cardiovascular complications are the leading cause of morbidity and mortality in patients undergoing noncardiac vascular surgery. [START_REF] Eagle | ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery -executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery)[END_REF] There are several elements to the strategy of minimizing this risk. Pre-operatively, determination of the risk of myocardial infarction (MI) and death begins with a comprehensive evaluation of patient-based indicators of cardiac risk and determination of surgery-specific risks such as the degree of hemodynamic stress associated with the procedure. Current data suggest that in patients with stable coronary artery disease undergoing vascular surgery, pre-operative coronary revascularization does not reduce peri-operative risk for cardiovascular events beyond that accomplished by medical therapy. [START_REF] Mcfalls | Coronary-artery revascularization before elective major vascular surgery[END_REF] Despite appropriate assessment and treatment, a small number of patients undergoing vascular surgery will suffer peri-operative MI and/or death.

Several techniques have been developed to monitor patients to discover myocardial ischemia in time to manage it effectively. Intraoperative and postoperative ST-segment monitoring, serial electrocardiography, and serial monitoring of myocardium-specific markers such as troponin or CK-MB have all been recommended as methods to detect myocardial ischemia/ infarction. The most recent ACC/AHA guidelines (published in 2002) recommend that the use of cardiac biomarkers be reserved for patients at high risk and in those patients with clinical, ECG, or hemodynamic evidence of cardiovascular dysfunction. [START_REF] Eagle | ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery -executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery)[END_REF] The appropriate application of these methods, particularly as a surveillance strategy, remains unclear.

Patients with postoperative troponin elevation are at markedly increased risk of having suffered a postoperative MI. The prognostic significance of a postoperative troponin elevation extends to both short-term and long-term mortality, although the data are not uniform. [START_REF] Lee | Troponin T as a marker for myocardial ischemia in patients undergoing major noncardiac surgery[END_REF][START_REF] Lopez-Jimenez | Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data[END_REF][START_REF] Kim | Cardiac troponin I predicts short-term mortality in vascular surgery patients[END_REF][START_REF] Landesberg | Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery[END_REF] Martinez and colleagues sought to determine the optimal timing of postoperative surveillance troponin determinations in a prospective cohort of 467 high-risk patients requiring non-cardiac surgery, 90% of which was vascular surgery. [START_REF] Martinez | Intermittent cardiac troponin-I screening is an effective means of surveillance for a perioperative myocardial infarction[END_REF] A strategy of measuring surveillance biomarkers on each of postoperative days 1, 2 and 3 appeared to be the most effective strategy, while checking biomarkers on any one day alone was not considered effective.

In this issue of Vascular Medicine, Mohler and colleagues seek to further understand optimal postoperative biomarker surveillance by performing an analysis "to determine if routine serial measurement of [cardiac] biomarkers should be done on the day of and after vascular surgery". [START_REF] Mohler | Should troponin and creatinine kinase be routinely measured after vascular surgery[END_REF] This analysis was performed in a study of 784 patients undergoing vascular surgery and at high risk for cardiovascular events who received a study drug in a placebo-controlled clinical trial of zoniporide therapy to reduce perioperative cardiovascular events, a trial that was discontinued early on the basis of therapeutic futility. [START_REF] Fleisher | Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients[END_REF] Surveillance cardiac biomarkers were drawn the day of surgery, as well as 24, 72, and 120 hours after surgery, and also 24 hours prior to planned hospital discharge. The goal of the present analysis was to examine the performance characteristics of cardiac troponin I (cTnI) and CK-MB measurements in predicting cardiovascular events after surgery.

In this type of analysis, the definitions utilized are critical and will therefore be elaborated. A positive cardiac biomarker (the exposure of interest) was defined as a cTnI Ͼ 3.1 ng/ml or CK-MB Ͼ two times the upper limit of normal with an index Ͼ 5%. A cardiovascular event (the outcome of interest) was defined as MI or cardiovascular death occurring up to 30 days after surgery. A new MI was defined as biomarker evidence of myocardial necrosis (CPK index Ͼ 5% or cTnI Ն 4.0 ng/ml) and one of the following: presence of left bundle-branch block, paced rhythm or non-specific ECG changes, or symptoms consistent with acute myocardial ischemia or acute coronary revascularization procedure. Cardiac death included sudden death, post-resuscitation, definite MI, possible MI, CHF, procedural death, primary intractable serious arrhythmia, or other cardiac death. These definitions were designed for the purposes of the clinical trial within which this analysis is conducted but are not optimal for the purpose of the present study. A consensus (ESC/ACC) definition of acute MI requires a typical rise and fall of cardiac biomarkers and one of the following: (a) ischemic symptoms; (b) development of pathologic Q waves on ECG; (c) ECG changes indicative of myocardial ischemia (ST elevation or depression); or (d) coronary revascularization. [START_REF] Alpert | Myocardial infarction redefined -a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction[END_REF] To better understand the present data it would be helpful to know how often the individual criteria for MI were met. For example, how many patients qualified for MI on the basis of a paced rhythm? However, these data were not provided.

Of the 784 patients in the study, 83 had at least one qualifying event. Of the 83 patients with an event, 42 had a positive cTnI and 29 had a positive CK-MB. Of the 699 patients that did not have an event, 64 had a positive cTnI and 20 had a positive CK-MB. Thus, the performance characteristics can be delineated: cTnI had a sensitivity of 51%, a specificity of 91%, a positive predictive value of 40%, and a negative predictive value of 94%; CK-MB had a sensitivity of 35%, a specificity of 97%, a positive predictive value of 59%, and a negative predictive value of 93%. Interpretation of these performance characteristics is confounded by the fact that the definition of the event includes the exposure of interest.

The authors do not clarify the relative importance of sensitivity versus specificity. In other words, is it more important that impending events are detected early, or that they be accurately predicted without excess false alarm? That the authors place more importance on specificity (accurately predicted without excess false alarm) is implied by their choice of a threshold for cTnI of Ͼ 3.1 ng/ml. This threshold is highly specific for postoperative infarction, [START_REF] Adams | Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I[END_REF] but the prognostic implications of postoperative cTnI begin at a much lower threshold. [START_REF] Kim | Cardiac troponin I predicts short-term mortality in vascular surgery patients[END_REF] It is therefore not surprising that the results demonstrate better specificity than sensitivity. Despite choosing a threshold that encourages specificity, 50% more patients with a positive troponin did not have an event than did have an event. It should also be noted that CK-MB was more specific than cTnI in this study, in contrast to previous data and what would be expected based on the biology of these biomarkers. [START_REF] Lopez-Jimenez | Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data[END_REF][START_REF] Adams | Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I[END_REF] This may be due to chance, but it may be due to the problematic definition of MI used.

The problem with the poor sensitivity and positive predictive value becomes clear once the goal of perioperative cardiac biomarker surveillance is defined. While prognostic information is important, we would argue that, in order to be of significant benefit to patients, the positive biomarkers must stimulate the physician to take an action he/she otherwise would not have. All eligible patients in this study should have been treated with ␤-blockade, and despite more limited data, aspirin and HMG-CoA reductase inhibitor ('statin') therapy as well. [START_REF] Auerbach | Assessing and reducing the cardiac risk of noncardiac surgery[END_REF] It seems positive predictive value is therefore of particular importance: which patient needs additional life-saving therapy? The early diagnosis of an acute coronary syndrome might call for escalation of therapy with additional antiplatelet and/or antithrombotic agents and possibly cardiac catheterization with coronary revascularization if indicated. All of these measures need to be applied judiciously in the postoperative setting when the risk of hemorrhagic complication is high. Cardiac TnI had a positive predictive value of 40%: applying a therapy based on a positive cTnI would therefore be inappropriately applied 60% of the time. The negative predictive value is nearly 95%; however, it is not clear what the treating physician might do with this information.

We would recommend postoperative measurement of cardiac biomarkers when there are symptoms or signs suggestive of myocardial ischemia, but would not recommend surveillance measurement in the absence of these. We interpret the data of Mohler and colleagues as supportive of this approach because positive cardiac biomarkers are more likely to occur in patients without than in patients with an MI or cardiovascular death. More data and evidence of benefit from a subsequent treatment adjustment are needed before routine surveillance of cardiac biomarkers postoperatively can be recommended. Prognostic information provides value when intervention may be applied to affect outcome. A new diagnostic strategy requires proof of benefit, not proof of surveillance.


MD Jay Denton Coffman

Mark A Creager

Jonathan L Halperin

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Jay Denton Coffman, a founder and the second president of the Society for Vascular Medicine and Biology, died on December 12, 2006 at the age of 78. He was a professor of medicine at the Boston University School of Medicine and directed the Peripheral Vascular Disease Section and the house staff training program at University Hospital, now Boston Medical Center. Jay was an outstanding physician and mentor, and a colleague and friend to many members of the SVMB, whose professional careers were greatly influenced by his personal attention and nurturing.

Jay was among the pioneers of Vascular Medicine. He recognized the potential of this area as knowledge of vascular biology advanced and technological developments improved our ability to diagnose and treat vascular disease. He was the Director of the Peripheral Vascular Disease Section of University Hospital in Boston, which was one of the first academic venues for this area of expertise. He chaired the American Heart Association's Council on Circulation in the 1970s and was a founder of the SVMB, serving as our President from 1992 to 1994.

Professionally, Jay was a 'triple threat' -an astute clinician, renowned investigator and cherished teacher. An accomplished clinician-scientist who exemplified the marriage of the science and art of medicine, he devoted his career to the ideal of translating research findings directly to the care of patients, and passed to those he taught not only a wealth of factual knowledge but a set of binding ideals based on intellectual honesty, scientific integrity and personal commitment.

Jay's writings contributed importantly to the field of Vascular Medicine. He published over 100 research studies, book chapters and reviews. His research enhanced our understanding of the physiology and pharmacology of calf muscle and skin blood flow. He investigated the contribution of the sympathetic nervous system to blood flow regulation and the pathophysiological mechanisms that mediate Raynaud's phenomenon. He studied blood flow regulation during ischemia and exercise-induced hyperemia and described why vasodilator drugs are generally ineffective in patients with claudication. He was one of the foremost experts in Raynaud's phenomenon and devoted much of his career to seeking effective therapy for this vascular disorder. He authored three textbooks about vascular disease. Ischemic Limbs: Surgical Approaches and Physiological Principles (1973), written with Dr John Mannick, a vascular surgeon, is an enduring resource on the principles of managing patients with peripheral arterial disease that are still relevant today. Another, the authoritative and comprehensive Raynaud's Phenomenon, is an important resource for all vascular physicians. His last book, Peripheral Arterial Disease, edited with Dr Robert Eberhardt, is another prodigious contribution to the field.

Jay was the consummate mentor and role model -a rare physician who left an indelible mark on those he taught. He brought a disarming humility and objectivity to the bedside and, despite a vast clinical experience and mastery of his specialty, was never self-inflated or arrogant in his approach to research, education or patient care. He emphasized the most basic attributes that make a great physician: attention to detail, careful recording of objective observations, unbiased consideration of all diagnostic possibilities, and engagement of the patient in the selection of treatment. Jay not only ensured his trainees a vast and superb education, he also guided them in career development as would a caring parentstern at times and always forthright -softened by a twinkle in his eye and a wry smile. He took pride in their accomplishments and measured his success as much by their achievements as his own.

© 2007 SAGE Publications, Los Angeles, London, New Delhi and Singapore 10.1177/1358863x07083183

In memoriam

Jay Denton Coffman, MD

In recognition of his substantial contributions to the science, practice, and treatment of vascular disease, the Vascular Disease Foundation designated Jay Coffman as the recipient of the Julius H Jacobsen Award. Further, the SVMB has honored his memory by designating the Young Investigator Awards in his name. We can think of no honor he would have cherished more than to associate his professional legacy with the young physicians and scientists of this Society.

Jay Coffman was a pioneer whose seminal studies of limb circulation, consultative clinical practice and commitment to specialized training nurtured the field of vascular medicine as a distinct clinical discipline. His renowned approach to diagnosis and management was based on astute incorporation of the emerging literature tempered by the critical mind of the quintessential physician-scientist. His legacy will endure through those he trained, through this Society, and through the field of vascular medicine, which has blossomed to include countless physicians and scientists.

Mark


Martin Mory

Jochen Hansmann

Jens-Rainer Allenberg

Dittmar Boeckler

Editor in Chief, Mark A Creager

Images in vascular medicine

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Images in vascular medicine

Rapid expansion of an inflammatory abdominal aortic aneurysm

The growth rate of an AAA is reported to be 2.6 mm on average per year. [START_REF] Brady | Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance[END_REF] This case demonstrates that the rate of AAA expansion is not predictable and varies individually. Inflammation may influence this process and accelerates AAA expansion dramatically. [START_REF] Borris | Rapid growth and early rupture of a primary mycotic aneurysm of the abdominal aorta[END_REF] This may be correlated with specific cellular immune responses. [START_REF] Shimizu | Inflammation and cellular immune responses in abdominal aortic aneurysms[END_REF][START_REF] Hsu | Infected aortic aneurysms: clinical outcome and risk factor analysis[END_REF] In conclusion, ultrasound surveillance of small AAAs is mandatory and requires individualization with more intensive follow-up for suspected inflammatory aneurysm.

Martin

  Mory a , Jochen Hansmann b , Jens-Rainer Allenberg a and Dittmar Boeckler a Departments of a Vascular and Endovascular Surgery and b Radiodiagnostics, University of Heidelberg, Heidelberg, Germany Address for correspondence: Martin Mory, Department of Vascular and Endovascular Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Tel: ϩ49 6221 566249; Fax: ϩ49 6221 565423; E-mail: martin.mory@ med.uni-heidelberg.de Panel A Panel B A 61-year-old patient was hospitalized for unclear abdominal pain, fever and cough for several days. A chest X-ray showed bilateral pneumonia. Further investigation, including computed tomography (CT), revealed an abdominal aortic aneurysm (AAA) with a maximum diameter of 42 mm and without signs of rupture (Panel A). The patient was treated with antibiotics for 8 days and the AAA was observed. The patient presented to the emergency room 3 weeks later with an acute abdomen. A repeat CT scan demonstrated an increase in the size of the infrarenal AAA to a maximum diameter of 100 mm with signs of contained rupture (Panel B; Panel C, white arrow) and a large retroperitoneal hematoma. Immediate open surgery with insertion of a tube graft was performed. The intraoperative findings showed an inflamed, thickened wall of the aneurysm with contained ventrolateral rupture. The patient recovered uneventfully. Microbiological examination of the aortic wall was negative for organisms.