Midwall fractional shortening identifies extracardiac organ damage in essential hypertension

96A

POSTERS: Cardiac Structure and Function

AJH–April 2002–VOL. 15, NO. 4, PART 2

P-185 BODY MASS INDEX AND LEFT VENTRICULAR MASS ARE THE BEST INDEPENDENT PREDICTORS OF LEFT ATRIAL DIMENSION G. A. Mansoor, W. B. White. Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, CT. Increased left atrial (LA) size is associated with stroke and the likelihood of developing atrial fibrillation. The relationships between clinical and demographic factors and left atrial dimension are not well studied in patients with essential hypertension. Prior studies of blood pressure (BP) have either included patients with treated hypertension or have not used ambulatory BP monitoring. We determined the relationship of LA size to demographic and ambulatory BP parameters in a group of 52 never treated hypertensives (office BP ⱖ 140/90mmHg) and 30 normotensive subjects from Connecticut. Bivariate correlations of LA size were significant with body mass index (r ⫽.44, p⬍.001), and LVM (r ⫽.40, p⬍.001). No ambulatory BP parameter correlated significantly with LA size. The effects of left ventricular mass (LVM), body mass index, race, age, gender, and ambulatory BP and pulse pressure were then examined in a linear regression analysis. Body mass index and LVM were the strongest independent predictors of LA size. Similar results were obtained when the hypertensive subgroup was analyzed separately.Body mass index and LVM but not ambulatory BP are the most significant predictors of LA size in this population of newly diagnosed hypertensive and normotensive subjects. Coefficients

a

Unstandardized Coefficients

Standardized Coefficients

Model

B

Std. Error

Beta

t

Sig.

(Constant) AGE ETHNIC BMI GENDER SBP24H 24hr pulse pressure Lvmass

2.241 1.955E-03 .156 3.600E-02 ⫺.114 ⫺3.529E-03 7.281E-03 1.948E-03

.653 .004 .107 .010 .089 .005 .007 .001

.060 .177 .392 ⫺.128 ⫺.117 .168 .276

3.430 .553 1.457 3.544 ⫺1.277 ⫺.717 1.106 2.248

.001 .582 .149 .001 .206 .476 .272 .027

a

Dependent Variable: LEFT ATRIAL SIZE

Key Words: Left Atrium, Ambulatory Blood Pressure, Heart

P-186 IMPORTANCE OF FORMULAE USED TO CALCULATE BODY SURFACE AREA IN DETERMINING LEFT VENTRICULAR MASS INDEX G. A. Mansoor, W. B. White. Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, CT. Several formulae for the estimation of body surface area (BSA) are used in the medical literature to index a number of biological variables including left ventricular mass (LVM). Most authors estimate BSA using the 1916 Dubois formula {(Weight, kg) 0.425* (Height, cm)0.725* 0.007184} which was developed in only 9 patients. Other formulae such as those by Gehan {(Weight, kg) 0.51456* (Height, cm)0.42246* 0.02350} and Mosteller {[(Height, cm) * (Weight, kg) ⫼ 3600]0.5} were developed in a larger number of subjects but are infrequently used in the cardiology literature. We examined the effects of different methods of LVM indexation to BSA on relationships between LVM index and ambulatory blood pressure. A group of hypertensive (60) and normotensives (32) patients in the untreated state were systematically examined. The three methods of LVM indexation gave similar correlation coefficients of LVMI with ambulatory blood pressure averages with only minor differences (range 0.32 to .42, ⫾ 0.22). However, the different formulae gave very different limits of agreement indicating the lack of interchangeability of the 3

formulae.These results show that different formulae for BSA when used to index LVM may cause important differences in the limits of agreement. Researchers should be explicit about formulae used for calculations of BSA in studies of LVM. Further study is needed regarding the scientific accuracy of the different formulae to estimate BSA and the optimal formulae in obese subjects, children, or patients with skeletal disorders. Bland-Altman limits of LVMI agreement calculated using 3 formulae for BSA.

Dubois-Mosteller Dubois-Gehan Mosteller-Gehan

mean difference

ⴞ2 SD

Range

⫹1.2 ⫹2.3 ⫺1.1

⫹2.3 to ⫹4.7 ⫹2.2 to ⫹6.9 ⫺.01 to ⫹2.27

⫺3.6 to ⫹8.7 ⫺3.4 to ⫹12.8 ⫺4.1 to ⫺.20

Key Words: Body Surface Area, Left Ventricular Mass, Hypertension

P-187 MIDWALL FRACTIONAL SHORTENING IDENTIFIES EXTRACARDIAC ORGAN DAMAGE IN ESSENTIAL HYPERTENSION Maura Ravera, Elena Ratto, Simone Vettoretti, Francesca Viazzi, Giovanna Leoncini, Denise Parodi, Luca Deferrari, Gian Paolo Bezante, Massimo Del Sette, Giacomo Deferrari, Roberto Pontremoli. Internal Medicine, University of Genoa, Genoa, Italy. The severity of blood pressure load is often an unreliable indicator of future cardiovascular (CV) events and the evaluation of subclinal target organ damage (TOD) is an important component in the stratification of global CV risk profile in essential hypertension (EH). Recently, a depressed left ventricular (LV) midwall fractional shortening (MFS) has been showed to be a marker of subclinical impairment of LV function and a predictor of adverse outcome in EH. Aim of the study was to evaluate the relationship between MFS and extracardiac organ damage in a group of 344 untreated hypertensive patients. Left ventricular mass index (LVMI) and function (MFS) were assessed by M-B mode echocardiography (LV hypertrophy LVH⫽ LVMI ⬎ 51g/m 2.7). Albuminuria was measured as albumin to creatinine ratio (ACR) in three first morning urine samples. Microalbuminuria (Mi) was defined as an average ACR between 2.38-19 (males) and 2.96-20 (females). Carotid wall geometry was evaluated by US scan, and retinopathy by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of LVH, carotid plaque, Mi, and retinal changes was 46, 25, 13, and 67% respectively. There were no differences as for blood pressure, lipid profile, and smoking habits among groups of patients examinated on the basis of MFS quintiles. Patients in the bottom quintile of MFS showed a higher LVMI (56 ⫾2.3, 53 ⫾1.9, 54 ⫾2, 48 ⫾1.8 and 48 ⫾1.8 g/m2.7 respectively; P⬍0.01) as well as a higher prevalence of LVH (65, 53, 54, 27, and 32%, respectively; P⬍0.01), especially concentric hypertrophy (65, 45, 36, 15, and 12 %, respectively; P⬍0.001). Moreover hypertensives with subclinical impairment of LV function, i.e. those in the bottom quintile of MFS, showed early signs of extracardiac damage, namely increased carotid surface area (CSA) (19.3 ⫾2.1, 15,3 ⫾0.9, 16.9 ⫾2.3, 14.7 ⫾1.3, and 13.6 ⫾0.9 respectively; P⬍0.01) and ACR (3.1 ⫾0.9, 1.5 ⫾0.4, 1.6 ⫾0.4, 0.9 ⫾0.2, and 0.9 ⫾0.2, respectively; P⫽0.01), a higher prevalence of microalbuminuria (28, 16, 15, 3, and 7%, respectively; P⬍0.05) and retinopathy (P⫽0.02) as compared to patients in the other MFS quintiles. Furthermore, MFS was inversely correlated to mean blood pressure (r⫽-0.15, P⬍0.05) and signs of early TOD, namely LVMI (r⫽-0.23, P⬍0.01), ACR (r⫽-0.2, P⬍0.01), and CSA (r⫽-0.25, P⬍0.02). In conclusion, hypertensive patients with depressed MFS show a higher prevalence of LVH and early signs of extracardiac vascular damage. These findings strengthen the role of MFS as an indicator of

AJH–April 2002–VOL. 15, NO. 4, PART 2

subclinical CV disease. The evaluation of MFS can be helpful in the stratification of CV risk in patients with EH. Key Words: Target Organ Damage, Essential Hypertension, Left Ventricular Function

P-188 DIFFERENT ACTIONS OF IRBESARTAN AND ATENOLOL ON CARDIAC REPOLARIZATION IN HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY Thomas Kahan, Karin Malmqvist, Magnus Edner, Lennart Bergfeldt. Div Internal Medicine, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden; Cardiology, Karolinska Hospital, Stockholm, Sweden. Left ventricular hypertrophy (LVH) is associated with an increased risk for malignant arrhythmias and sudden death. A prolonged QT dispersion is predictive of such events. We evaluated 92 hypertensive patients with echocardiographically verified LVH (age 55⫾9 years, BP 162⫾20/104⫾8 mmHg, LVMI 148⫾32 g/m2) randomized double-blind to receive the AT1-receptor blocker irbesartan (n⫽44) or the beta1-receptor blocker atenolol (n⫽48) for 48 w. At w 0, 12 and 48 echocardiography was performed, and QT and QTc dispersion were calculated from a standard 12 lead ECG (50 mm/s). We also examined 37 age and gender matched hypertensive patients without LVH (BP 148⫾14/97⫾6 mmHg, LVMI 99⫾6 g/m2) once. Patients with LVH had increased QT and QTc dispersion, as compared to those without LVH (52 vs 41 ms, p⫽0.007, and 52 vs 44 ms, p⫽0.032, respectively). LVMI related to QT dispersion (r⫽0.34, p⬍0.001). By similar reductions in BP, the irbesartan group had a greater reduction in LVMI than the atenolol group (-27⫾29 vs -18⫾21 g/m2, p⬍0.031). With irbesartan QT dispersion decreased from 56⫾24 to 52⫾21 (12 w) and 44⫾20 ms (48w; p⬍0.001), and QTc dispersion decreased from 56⫾24 to 54⫾21 (12 w) and 44⫾19 ms (48 w; p⬍0.001). There was little influence of atenolol on QT dispersion (e.g., 48⫾20, 53⫾17 and 53⫾20 ms) and QTc dispersion. The changes in QT and QTc dispersion after 48 w were different (p⫽0.001 and p⫽0.011, respectively) between the irbesartan and atenolol groups. These significant differences remained when changes in LVMI, BP and heart rate were included in multivariate analyses. QT dispersion is related to LVMI. Irbesartan, but not atenolol, reduces QT and QTc dispersion, independent of changes in LVMI, BP or heart rate. We suggest that AT1-receptor blockade may induce both structural and electrical remodeling in a direction that reduces the risk of malignant arrythmias. A reduced QT dispersion by irbesartan may be important in preventing malignant arrhythmias and sudden cardiac death in high-risk hypertensive patients. Key Words: QT Dispersion, Left Ventricular Hypertrophy, Angiotensin II

P-189 EFFECT OF PPAR-␣ ACTIVATORS DOCOSAHEXAENOIC ACID AND FENOFIBRATE ON MYOCARDIAL INFLAMMATION AND COLLAGEN DEPOSITION IN ANGIOTENSIN II-INFUSED RATS Quy N. Diep, Karim Benkiram, Ernesto L. Schiffrin. Experimental Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. To test the hypothesis that PPAR␣ activators docosahexaenoic acids (DHA) and fenofibrate influence cardiac inflammation and collagen deposition in Ang II-infused rats by modulating activity of transcription factors nuclear factor kappa B (NFKappaB) and activating protein 1 (AP-1), and adhesion molecules VCAM-1 and PECAM.

POSTERS: Cardiac Structure and Function

97A

Male Sprague Dawley rats were divided into 6 groups (n⫽6 each): Control, Ang II (120 ng/kg/min s.c), Ang II ⫹ DHA (2.5 mL of oil containing 40% DHA/day p.o), Ang II ⫹ fenofibrate (100 mg/kg/day p.o), DHA and fenofibrate. After 7 days of treatment, tail cuff systolic blood pressure (SBP) was measured and the rats were killed. Activity of NFKappaB and AP-1 in the heart was determined by electrophoretic mobility shift assay. Expression of VCAM-1, PECAM, AT1 receptors, and AT2 receptors was evaluated by Western blot assay. Collagen density was evaluated from tissue sections of the median part of the heart stained with Sirius Red F3BA. SBP (mmHg) was elevated (p⬍0.01) in Ang II-infused rats (176⫾5) vs. controls (109⫾2) and normalized by DHA (112⫾4) and fenofibrate (137⫾5). Ang II caused a slight but not significant increase in cardiac hypertrophy. Electrophoretic mobility shift assay demonstrated that Ang II increased the activity of NFkappaB in the heart by 50% whereas there were no changes in activity of AP-1. Western blot analysis showed that expression of VCAM-1, PECAM, AT1 and AT2 receptors in the heart were significantly increased in Ang II group to 235⫾13%, 457⫾112%, 147⫾26%, and 365⫾150% of controls, respectively. The increases in NFkappaB, VCAM-1, PCAM, and AT1 receptors induced by Ang II infusion was totally or partially normalized by DHA or fenofibrate. Ang II increased collagen deposition in the left and right ventricle. These effects were significantly normalized by DHA or fenofibrate. PPAR␣ activators prevent the development of hypertension, improve myocardial inflammation and collagen deposition in Ang II-infused rats. These effects are associated with prevention of the upregulation of AT1 receptors, and pro-inflammatory mediators NFkappaB, VCAM-1 and PECAM in Ang II-infused rats. In conclusion, PPAR␣ may play an important role by antagonizing myocardial inflammation and collagen deposition in Ang II-induced hypertension. Key Words: Angiotensin II, PPARalpha Activators, Cardiac Inflammation and Collagen Deposition

P-190 CARDIAC EFFECTS OF TRIMETAZIDINE IN ISOLATED DIABETIC RAT HEARTS UNDER HYPOXIC CONDITIONS Ildiko Posa, Erzsebet Kocsis, Ferenc Horkay, Zsofia M. Koltai, Gabor Pogatsa. Department of Experimental Cardiology, Gyorgz Gottsegen National Institute of Cardiology, Budapest, Hungary. Cardiac effects of the antianginal drug, trimetazidine (TMZ) were investigated in Langendorff-perfused hearts of streptozotocin-diabetic rats during hypoxia (n ⫽ 7 , blood glucose ⫽ 8 mmol*l-1). The organ was removed after 3-week diabetes duration and perfused with Krebs-Henseleit solution containing albumin-palmitate complex (0,4 mM), 11 mmol*l-1 glucose and 100 microU*ml-1 insulin. An inflatable balloon was inserted into the left ventricle, which was connected to a Statham pressure transducer. Left ventricular peak-systolic (LVPSP) and enddiastolic (LVEDP) pressures, and heart rate (HR) were measured. Cardiac work was calculated (CW ⫽ LVPSP * HR). Coronary blood flow was characterized by the perfusate outflow. Four experimental groups were formed altogether: normoxia without (C1) and with (C2) trimetazidine, and hypoxia without (H1) or with (H2) trimetazidine. After 10 min equilibration, perfusion was continued with TMZ-containig medium (10-6 M) in the drug-treated groups (C2, H2). 30 min global hypoxia was induced 10 min later in the hypoxic groups (H1, H2) (medium aerated with 95% N2 ⫹ 5 % CO2). Results were expressed as the percentage of the baseline values. LVPSP and LVEDP were altered neither by TMZ, nor by hypoxia (there was no difference between the groups at the end of the hypoxic period). However, both the drug and hypoxia reduced heart rate /in comparison with group C1/ (C2: p⬍0.01; H1: p⬍0. 05) and consequently cardiac work (C2: p⬍0.05; H1: p⬍0.05). Their effect proved to be cumulative (H2: HR: p⬍0.001; CW: p⬍ 0.001). Coronary blood flow also decreased, but not significantly. According to our results, trimetazidine induces bradicardia and reduces cardiac work in the dia-