Endothelium-independent vasodilation is impaired at peripheral microcirculatory level in hypertensive patients with left ventricular hypertrophy

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echo-duplex investigation of extracranial CA was performed and far wall intima-media thickness (IMT) was measured one cm proximal and distal to the flow-divider and at bulb. Mean and maximal IMT were assessed. In addition, ultrasonic texture of common CA was evaluated by grey level analysis (1 to 256 scale). Angular second moment (ASM) and entropy of intima-media complex were assessed as indexes of ultrasonic homogeneity/dyshomogeneity. Results: before treatment, in FHC as compared to NL mean IMT was higher (0.63⫾0.06 vs 0.59⫾0.05mm, p⬍0.05), and ultrasonic texture analysis showed significantly higher entropy and lower ASM values (entropy: NL 0.082⫾0.02 vs FHC 0.566⫾0.12 p⬍0.01; and ASM: NL 0.01⫾0.01 vs FHC 0.004⫾0.001 p⬍0.05). After treatment, total cholesterol lowered from 291⫾22.mg/dl to 211⫾32 mg/dl (p⬍0.05), mean IMT from 0.63⫾0.06 to 0.59⫾0.05 mm (p⬍0.01), maximal IMT from 0.72⫾0.10 to 0.66⫾0.09 mm (p⬍0.01). Entropy of intima-media complex decreased from 0.566⫾0.12 to 0.442⫾0.05 (p⬍0.01), while ASM increased from 0.004⫾0.001 to 0.0216⫾0.04 (p⬍0.05). Conclusion: In young subjects with early FHC texture analysis of two-dimensional carotid artery images shows increased intima-media complex thickness and dyshomogeneity, suggestive of early medial infiltration. These alterations are reversed by atorvastatin. Key Words: hypercholesterolemia, arterial remodelling, ultrasonic texure analysis

P-291 PULSE WAVE ANALYSIS TO ASSESS VASCULAR COMPLIANCE CHANGES IN RENAL TRANSPLANT RECIPIENTS Karen Warburton, Debbie L. Cohen, Roy D. Bloom, Raymond R. Townsend. 1Medicine, University of Pennsylvania, Philadelphia, PA, United States An increase in cardiovascular disease (CVD) related deaths has been reported in renal transplant recipients (RTR), with 50-60% of deaths in RTR directly attributable to CVD. The major factors that lead to atherosclerosis in RTR are similar to those in the general population but are exacerbated by immunosuppressive drugs such as cyclosporine (CYA) and tacrolimus (TAC) which are used to prevent allograft rejection. Hypertension (HTN), present in 60-80% of RTR, is independently associated with posttransplant atherosclerotic CVD, manifested in part through changes in vascular compliance (stiffening). Because CYA is reported to cause greater increases in blood pressure compared with TAC, we performed pulse wave analysis (a non-invasive method used to measure large and small vessel compliance (C1, C2) derived from the radial artery) to determine whether vascular compliance differed in stable RTR outpatients on CYA vs TAC. In addition, routine measures of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were performed. We enrolled 22 stable RTR (11 CYA/11 TAC) on a variety of blood pressure medications matched for age and gender. 11 males and 11 females with a mean age of 41.0 ⫾ 11.7 years and a mean weight of 170 ⫾ 11.7 pounds were studied. Results are expressed as mean ⫾SD. pⴝ0.002

CYA

TAC

SBP mmHG(yrs) DBP mmHg C1 ml/mmHgx10 C2 ml/mmHgx100

143⫾13 84⫾7 14.7⫾3.0 4.8⫾2.2

145⫾18 85⫾11 9.9⫾3.3* 4.5⫾2.4

Patients receiving TAC had a decreased C1 when compared with CYA (p⫽0.002) however there were no differences observed in SBP, DBP or C2 between the groups. Conclusion: Although there were no differences in SBP, DBP or C2 between the CYA and TAC groups, the TAC group had a decreased C1 compared with CYA. There data suggest that there are differences in large vessel compliance between these immunosuppressive therapies despite similar blood pressure control. Key Words: arterial compliance ,kidney transplant, calcineurin inhibitors

P-292 WAVE REFLECTION IN HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY Andrew Zambanini , Ben B. Ariff, Stephanie L. Cunningham, Sheila M. Byrd, Elena Martinoli, Jamil Mayet, Kim H. Parker, Simon A. McG Thom, Alun D. Hughes. 1Clinical Pharmacology, National Heart & Lung Institute, St. Mary’s Hospital, London, United Kingdom, 2 Physiological Flow Studies Group, Department of Biological & Medical Systems, Imperial College, London, United Kingdom Wave reflection in the arterial circulation is an important contributor to systolic blood pressure, ventricular load and regional blood flow. Wave Intensity Analysis is a novel non-invasive technique which measures energy transport in the cardiovascular system and also allows regional pulse wave velocity and both forward and reflected pressure waves to be determined. The aim of this study was to determine differences in these haemodynamic parameters in hypertensive subjects associated with the presence or absence of left ventricular hypertrophy (LVH). Thirty-five untreated hypertensive subjects were studied. Sixteen had echocardiographic LVH (10 men, age 54⫾7 years, BP 174⫾27 / 102⫾18, left ventricular mass index (LVMI) 156⫾48 g/m2). The remainder (15 men & 4 women, age 51⫾8 years, BP 156⫾19 / 93⫾10) had a mean LVMI of 109⫾15 g/m2. Pressure and flow velocity were recorded non-invasively at 200Hz in the right common carotid artery using applanation tonometry and pulsed wave Doppler. Carotid pulse wave velocity (c), peak forward pressure (P⫹), peak backward pressure (P- ) and cardiac systolic wave power (dI⫹c1) were calculated using custom written software in the Matlab environment. Reflected cardiac systolic wave energy from the body travelling up the carotid (Ec⫹) and reflected wave energy from the head (Ec- ) were also determined. c (m/s) No 8.36 LVH (7.37-9.36) * LVH 11.24 (9.17-13.31)

dIpc1 (mW/m2) Pⴙ (mmHg) P- (mmHg) Ecⴙ (mJ/m2) Ec- (mJ/m2) 264.2 (211.3-317.1)# 314.5 (255.9-373.1)

122 (116-127)* 142 (130-153)

30 (25-35)* 38 (32-42)

0.42 (0.28-0.55)* 0.71 (0.50-0.91)

2.71 (1.89-3.53)# 3.45 (2.36-4.55)

Data in the table are presented as means (95% CI).*pⱕ0.05, significant.

#

not

The results (Table) indicate that the presence of LVH is associated with changes in arterial haemodynamics including increased pulse wave velocity and enhanced wave reflection, particularly from the body. It is possible that these abnormalities are related to the the development of LVH. Key Words: Wave reflection, Left ventricular hypertrophy, Arterial haemodynamics

P-293 ENDOTHELIUM-INDEPENDENT VASODILATION IS IMPAIRED AT PERIPHERAL MICROCIRCULATORY LEVEL IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY Francesca Vittone, Carmela Morizzo, Marco Ciardetti, Michaela Kozakova, Carlo Palombo. 1CNR, Institute of Clinical Physiology, Pisa, Italy, 2Department of Internal Medicine, University of Pisa, Pisa,, Italy Introduction: in patients with essential hypertension (HBP), left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular events, and it is reported to be associated with structural and functional alterations, both at coronary and peripheral level, which may contribute to the LVH-related risk. Aim of the study : to assess microcirculatory function at peripheral level in HBP patients according to the presence or absence of LVH.

AJH–April 2001–VOL. 14, NO. 4, PART 2

Methods: in 23 untreated mild to moderate HBP patients (mean age 53.7⫾9, mean SBP/DBP 155⫾16/96⫾10 mmHg) and in 10 normotensive control subjects (NL: mean age 51⫾7, mean SBP/DBP 118⫾12/ 72⫾9 mmHg), microcirculatory peripheral vasodilatory function was investigated at the forearm level by means of laser doppler flowmetry at baseline and during five stepwise doses of iontophoretically applied Acetylcholine (ACh) and Sodium Nitroprusside (SNP). At basal echocardiography, 17 HBP pts showed either LVH or concentric LV remodelling (mean LV mass index 129.8⫾36.5 g/sqm), while 12 not (mean LV mass index 94.4⫾17 g/sqm). Mean arterial blood pressure was not different in the two subgroups (98⫾27 and 101⫾11 mmHg respectively). Results: compared to normal, HBP patients showed a lower response to both vasodilators, although it did not reach statistical significance. By contrast, HBP patients with LVH showed a significantly reduced response to SNP as compared to both nonhypertrophic HBP patients and NL ( peak skin blood flow: 28.5⫾18.3 vs 46.4⫾27.5 and 48⫾23 perfusion units, respectively, p⬍.05). The response to ACh did not differ in the three groups. Conclusion: compared to controls, hypertensive patients show a reduced vasodilatory response of skin blood flow to ACh and SNP. This dysfunction is more evident in response to SNP and in presence of left ventricular hypertrophy; these findings further support the hypothesis of peripheral vascular abnormalities (vascular rarefaction?) paralleling LVH, and possibly contributing to the overall ischemic burden in these patients. Key Words: peripheral vascular function, hypertension, left ventricular hypertrophy

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P-295 HEMODYNAMIC CHARACTERIZATION OF SYSTOLIC HYPERTENSION: NEW FINDINGS ON CV PARAMETERS Carlos L. Delgado-Leo´n, Antonio R. Delgado-Almeida, Antonio J. Delgado. 1Hypertension Research Unit, University of Carabobo, Valencia, Carabobo, Venezuela Despite important advances in clinical HT, hemodynamics in Systolic HT (SHT) are not fully defined. To assess such changes in SHT we included non-invasive Arterial Waveform Analysis (DynaPulse 200) in all HT subjects. In one year study, 19 (Female n⫽16, Male n⫽3, aged 68⫾11 yr.) out of 235 Hypertensives had SHT (8 %). Non-Invasive Hemodynamic: LVET, dP/dT max, LV Stroke Volume (LVSV), CO, Cardiac work, LV Stroke Work (LVSW), SV Resistance and Compliance, Brachial Artery (BA) Resistance and Compliance, BP,Pulse Pressure (PP) and HR was recoreded at rest, isometric hand grip and 15 min after. RESULTS: a) BP was 192.6⫾20/ 79.5⫾7 mmHg; PP: 119⫾14 and HR 55⫾12 bbm; b) marked increased LV dP/dT max 1.655⫾441 mmHg /s, LVET 463.6⫾34 msc, Contractility index 19.2⫾5 1/s, Cardiac Work 92.4⫾18 J/min, and increased aortic stiff index (2.28⫾0.7 unit) resulted in 2 peak aortic waveform and increased augmentation index (41⫾9 mmHg); c) increased SV Resistance index 3.208⫾274 dy.s.cm5, decreased SV compliance (0.81⫾0.2 ml/mmHg) and brachial artery compliance (0.026⫾0.026 ml/mmHg) with brachial distensibilty 5.2⫾0.4 %. Conclusion: The results of this study indicates that SHT represents a severe form of HT, with disturbed arterial structure and vascular resistance, occuring more frequent in women. Key Words: Non-invasive hemodynamic, Systolic hypertension, Aortic augmentation index

P-294 IMPROVED LV FUNCTION, SYSTEMIC VASCULAR AND BRACHIAL ARTERY PARAMETERS IN HYPERTENSION: THE VENEZUELAN TELMISARTAN STUDY Antonio J. Delgado, Antonio R. Delgado-Almeida, Susana I. Celis, Carlos L. Delgado-Leo´n. 1Hypertension Research Unit, University of Carabobo, Valencia, Carabobo, Venezuela Despite numerosus advances in pharmacology of HT, few therapeutic approach has been designed to assess drug effects on complex CV functions during measurement of BP. To assess such parameters, noninvasive Arterial Waveform Analysis (Dyna Pulse 200) at rest, isometric hand grip and 15 min later, was recorded in 31 HT subjects (Female n⫽18, Male n⫽13, age 54.1 ⫾9) on Telmisartan. LVET, dP/dT, LV contractility, LV Stroke Volume (LVSV), LV Stroke Work (LVSW), CO, Cadiac Work, SV Resistance and Compliance, Brachial Artery (BA) Compliance, BP, Pulse Pressure (PP) and HR were obtained basal and after 1 month of Telmisartan 40mgr. Paired T-test was perfomed, with statistical significance ␣⫽0.05. RESULTS: With Telmisartan: SBP (165⫾22 vs 132⫾15, p⫽0.00), DBP (90⫾14 vs 77⫾12, p⫽0.00) and PP (75⫾18 vs 55⫾12, p⫽0.00) were reduced, HR unchanged. dP/dTmax (1393⫾332 vs 1134⫾263, p⫽0.00), dP/dT 40 (35⫾8 vs 28⫾7, p⫽0.00), LVSW (90⫾19 vs 71⫾16, p⫽0.00) and Cardiac work (78⫾16 vs 63⫾13, p⫽0.00) were also reduced; while LVET, LVSV and CO unchanged. SVR (1783⫾277 vs 1524⫾275, p⫽0.00) was decreased; SV Compliance (1.16⫾0.3 vs 1.45⫾0.49, p⫽0.00) and BA Compliance (0.073⫾0.022 vs 0.097⫾0.032, p⫽0.00) increased at 1 month. CONCLUSION: This study provided the first integral evaluation of cardiac and vascular functions and BP on hypertensives receiving Telmisartan. Key Words: Arterial waveform analysis, Arterial compliance, Telmisartan

P-296 LATE AORTIC SYSTOLIC PRESSURE AUGMENTATION AND INCREASED PULSE PRESSURE IN HEART TRANSPLANT RECIPIENTS: A MARKER OF INCREASED PERIPHERAL VASCULAR STIFFNESS Brian T. Schuler, Richard S. Schofield, David G. Edwards, Wilmer W. Nichols. 1Cardiovascular Medicine, University of Florida, Gainesville, FL, United States 1. The aim of this study is to investigate the effectiveness of antihypertensive drug therapy on proximal aortic wave reflection in stable hypertensive heart transplant recipients felt to be on optimal medical therapy for hypertension. 2. Brachial artery blood pressure (by sphygmomanometry), and aortic pulse pressure and aortic augmentation index (AIa)(by noninvasive radial artery applanation tonometry and use of a generalized transfer function) were determined in 35 stable cardiac transplant patients with controlled, chronic post-transplant HTN presenting for routine post-transplant evaluation. Patients were divided into 3 groups (Types A, B, and C) based on high, medium or low degrees of peripheral stiffness and wave reflection into the central aorta as measured by the AIa. 3. Mean resting brachial artery pressure was 139(⫾21)/87(⫾11), and mean number of antihypertensive medications was 2.2⫾1.1. Of the 35 patients, 15 were Type A (AIaⱖ12%, range 12 to 38%), 10 were Type B (0ⱕAIa⬍12%, range 2.0 to 11%) and 10 were Type C (AIa⬍0%, range -33 to -2%). Type A patients had wider aortic pulse pressure (41⫾12 mm Hg) than Type B patients (29⫾8 mm Hg ) or Type C patients (30⫾10 mm Hg), (p⬍0.025 for comparison of Type A vs Type B, p⬍0.013 for comparison of Type A vs Type C). Brachial arterial pulse pressure by sphygmomanometry was no different between Type A (55⫾14 mm Hg), Type B (47⫾12 mm Hg), or Type C (55⫾15 mm Hg) patients (p⫽NS for comparison for each group). There was no difference in mean brachial systolic or diastolic pressure as determined by sphygmomanometry between