Efficacy of losartan in hypertensive obese patients

AJH–May 2003–VOL. 16, NO. 5, PART 2

POSTERS: Obesity, Insulin Resistance, Diabetes

Status Post Test

Normal

HighNormal

Intolerance

Diabetic

N Age (y) Creat clearance EUA (mg/day) PWV (m/seg2) BMI (kg/m2)

23 47 ⫾ 10* 97 ⫾ 30* 6⫾5 13.8 ⫾ 4* 29 ⫾ 4

11 60 ⫾ 11 75 ⫾ 29 5⫾3 18.0 ⫾ 4 29 ⫾ 3

25 63 ⫾ 8 70 ⫾ 29 20 ⫾ 30 16.8 ⫾ 4 29 ⫾ 3

16 65 ⫾ 11 78 ⫾ 34 96 ⫾ 208* 19.1 ⫾ 10 32 ⫾ 6*

* P ⬍ 0.05 vs. other groups

damage. Nevertheless, the clinical significance of this finding needs to be evaluated in further studies. Key Words: glucose overload test, early target organ damage, pulse wave velocity

P-515 ATPIII-DEFINED METABOLIC SYNDROME IS ASSOCIATED WITH PREVALENCE OF LV HYPERTROPHY IN WHITE, BUT NOT IN AFRICAN AMERICAN, TREATED HYPERTENSIVES: THE HYPERGEN STUDY Marcello Chinali, Richard B Devereux, Giovanni de Simone, Jennifer E Liu, Jonathan N Bella, Albert Oberman, Paul Hopkins, Dalane Kitzman, D.C. Rao, Donna Arnett. Medicine, Weill Medical College of Cornell University, New York, NY. Metabolic syndrome (MS) is linked to cardiovascular risk. Recently published Adult Treatment Panel III (ATPIII) criteria provide a definition for diagnosis of MS. We analyzed the impact of the ATPIII-defined MS on left ventricular (LV) hypertrophy in treated hypertensive adults of the HyperGEN study. LV structure was examined by echocardiography in 912 treated hypertensive non-diabetic participants of the HyperGEN study (329 white and 583 African American), without prevalent cardiovascular disease. White participants were older (60⫾9yrs vs 51⫾10yrs; p⬍0.001) and had higher prevalence of MS (53.5% vs 36.2% p⬍0.001) as compared to African Americans. White participants with the metabolic syndrome (50% women) had similar age, blood pressure and heart rate as compared with non-MS participants (all p⫽ns). After controlling for type of hypertensive medication and gender differences, white MS participants exhibited similar LV diastolic diameter (p⫽ns), but higher values of relative wall thickness and LV mass/BSA as compared to non-MS whites (all p⬍0.05), with a significant higher prevalence of LV hypertrophy (27.4% vs 16.9%; p⬍0.05). African American participants with the metabolic syndrome (68.7% women) had similar age, blood pressure and heart rate as compared with non-MS participants (all p⫽ns). After controlling for type of hypertensive medication and gender differences, MS participants exhibited similar LV diastolic diameter, relative wall thickness, LV mass (all p⫽ns) as compared to non-MS. African Americans had a higher prevalence of LV hypertrophy (33%) than whites with no significant difference between the MS and the non-MS group. In treated hypertensive patients, ATPIII defined metabolic syndrome has a higher prevalence in whites than in African Americans. Presence of the MS is also associated with a significant higher prevalence of LV hypertrophy in whites, while no significant effect is found in African Americans where the high prevalence of LV hypertrophy is independent of the presence of ATPIII defined MS. Key Words: Metabolic Syndrome, Echocardiography, Ethnicity

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P-516 IMPACT OF BLOOD PRESSURE ON CARDIAC STRUCTURE AND CARDIOVASCULAR OUTCOME IN THE METABOLIC SYNDROME: THE STRONG HEART STUDY Marcello Chinali, Mary J Roman, Barbara V Howard, Giovanni de Simone, Jonathan N Bella, Jennifer E Liu, Helaine E Resnick, Elisa T Lee, Lyle G Best, Richard B Devereux. Medicine, Weill Medical College Of Cornell University, New York, NY. Metabolic syndrome (MS) is linked to cardiovascular risk. Adult Treatment Panel III (ATPIII) criteria provide a definition for diagnosis of MS. ATPIII defined non-optimal blood pressure (ⱖ130/85mmHg) might provide effective partition to identify cardiac abnormalities in the presence of MS. Echocardiography was performed in 595 non-diabetic MS participants (31.5% men, 59⫾7.8 years) of the Strong Heart Study. Participants with the MS were divided according to the presence of non-optimal blood pressure (ⱖ130/85mmHg). Comparison of quintiles of participants with non-optimal blood pressure was used to assess the effect of increasing values of blood pressure on cardiovascular structure and outcome. MS participants with non-optimal blood pressure (n⫽ 369; 39% men) were older (61 vs 58 y, p⬍0.001), with no significant differences in body mass index, heart rate or fasting glucose compared to MS participants with normal blood pressure. After controlling for age and gender, non-optimal blood pressure was associated with higher left ventricular (LV) diameter, LV indexed mass (both p⬍0.001), as well as with higher relative wall thickness, reduced midwall shortening and prolonged mitral deceleration time (all p⬍0.05). In Cox regression analysis, controlling for age and gender, the presence of non-optimal blood pressure was independently associated with a higher rate of CV events (OR⫽1.58, 95%CI⫽ 1.04 vs 2.42; p⫽0.039). Higher quintiles of blood pressure were associated with older age and higher body mass index (both p⬍0.01), with no significant differences in heart rate and plasma insulin or fasting glucose. After controlling for covariates no differences could be found in cardiac structure or function among quintiles of non-optimal blood pressure. Furthermore in Cox regression analysis, within participants with non-optimal blood pressure, higher blood pressure was not associated with a higher rate of CV events. In the presence of MS, non-optimal blood pressure is related to abnormal LV geometry and function, and associated with increased risk for CV events. When MS is present, blood pressure ⱖ130/85mmHg is as effective a marker to identify individuals with cardiac abnormalities as is the traditional definition of hypertension in individuals without the MS, and should lead to more aggressive treatment. Key Words: Metabolic Syndrome, Echocardiography, Outcome

P-517 EFFICACY OF LOSARTAN IN HYPERTENSIVE OBESE PATIENTS Roberto Fogari, Ettore Malacco, Luca Corradi, Andrea Rinaldi, Elena Fogari, Paola Preti, Amedeo Mugellini. Department of Internal Medicine, University of Pavia, Pavia, Italy; Department of Internal Medicine, Ospedale Sacco, Milano, Italy. Aim of the study was to compare the effect of losartan and felodipine on blood pressure (BP) and plasma norepinephrine (pNE) in hypertensive patients with obesity, a condition characterized by increased sympathetic activity. Fifty-four obese patients (BMI ⬎ 30 Kg/m2) with mild to moderate hypertension (DBP evaluated with appropriate size cuff ⱖ 95 mmHg ⬍ 110 mmHg) aged 32-58 years after a 4 week placebo period were randomized to Losartan 50 mg (n ⫽ 27) or to felodipine 5 mg(n ⫽ 27) for 16 weeks; after the first 4 weeks of treatment there was a titration with dose doubling in non responder (DBP ⬎ 90 mmHg) patients. At the end

226A

POSTERS: Obesity, Insulin Resistance, Diabetes

of the placebo period and of each treatment period BP and BMI were evaluated and a venous sample was drawn in the morning at the same hour to evaluate pNE. No dietary advice was prescribed for the duration of the study. The main results are shown in the table. Both losartan and felodipine significantly decreased BP withouth any differences between the two treatments, however felodipine increased plasma norepinephrine and had no effect on body weight, while Losartan induced a small but significant BMI reduction. These data suggest that Angiotensin II antagonists could be drugs of choice for the treatment of hypertension in obese patients. Main Results SBP DBP BMI pNE

Placebo

Losartan

Placebo

Felodipine

158.2 ⫾ 13.1 100.2 ⫾ 4.9 35.4 ⫾ 3.9 333 ⫾ 118

141.3 ⫾ 12.2** 87.8 ⫾ 4.5** 33.9 ⫾ 3.1* 291 ⫾ 109

159.1 ⫾ 14.1 101.2 ⫾ 4.7 34.9 ⫾ 4.1 323 ⫾ 116

140.4 ⫾ 12.3** 86.3 ⫾ 4.2** 34.6 ⫾ 4.3 448 ⫾ 133*

* P ⬍ 0.05; ** P ⬍ 0.01 vs placebo

Key Words: obesity, norepinephrine, losartan

P-518 EFFECTS OF TOPIRAMATE ON THE PROGRESSION OF EXPERIMENTAL METABOLIC CARDIOVASCULAR SYNDROME Oscar Go´ mez, Esther Ruiz, Paula Vieitez, Olga Gonza´ lez-Albarra´ n, Gema Garcı´a Romero de Tejada, Jose´ M Sancho, Rafael Garcı´a-Robles. Endocrinology Dpt, Hospital Ramo´ n y Cajal, Madrid, Madrid, Spain; Medicina Dpt, Alcala´ de Henares University, Madrid, Madrid, Spain. We have studied the effect of Topiramate (TPM), a neurotherapeutic agent currently indicated for the treatment of epilepsy with significant effects on body weight loss, on the progression of experimental kidney damage in a model of obese Zucker rats. Forty five male Zucker rats of 5-6 weeks of age, were subjected to left unilateral nephrectomy. 2 weeks later, animals were randomly allocated to one of three different groups and followed for 4 months. TPM treatment groups were TPM15 and TPM60 which 15 and 60 mg/Kg/day respectively. Control group was treated only with vehicle. Systemic and renal parameters were measured periodically, and, at the end of 4 months follow-up period, histological renal studies and renal expression of TGF-␤1 were perfomed in order to evaluate kidney damage. In the same way, at the end of 4 months follow-up, we evaluated the insulin resistence by OGTT and the expression of TNF-␣ in white adipose tissue. TPM at the two used doses attenuated the progression of renal injury as estimated by lower urinary albumin excretion and preservation of renal architecture. These finding correlated with lower body weight, lower levels of blood pressure, better lipid profile and improve in insulin-resistance state. The present data pointed clearly to a beneficial effect of TPM on body weight, that are accompanied by an improve in metabolic and cardiovascular parameters. The impressive decrease of TGF-␤1, TNF-␣ expression and the decrease inflammatory infiltrates in kidney tissue, could be correlated with a direct effect of the drug on the inflammatory and fibrotic process. These data need further studies to be confirmed.

Control TPM15 TPM60

Sclerosis of Glomeruli

Atrophy/Dilata Interstittion of Tubulesium

65.3 ⫾ 11 19.4 ⫾ 9* 20.3 ⫾ 12*

66.7 ⫾ 30 52.8 ⫾ 22 29.4 ⫾ 12

Fibrosis 79.2 ⫾ 17 30 ⫾ 11* 35 ⫾ 21*

Mononuclear Cell Infiltrates

Kidney TGF-Content (A.U.)946;

TNF-␣ Content in White Adipose Tissue (A.U.)

52.8 ⫾ 13 16.7 ⫾ 9* 39.4 ⫾ 8

100% 30%* 20%*

100% 21%* 15%*

The results of TNF-␣ and TGF-␤1 content assayed by Western blot are expressed by arbitrary units (A.U.) assigning 100% value to the TGF-␤1

AJH–May 2003–VOL. 16, NO. 5, PART 2

and TNF-a expression in the control group. *p⬍0.05 difference with control group. Key Words: Topiramate, TNF-a, Insulin resistance

P-519 INCIDENCE OF NOCTURNAL BLOOD PRESSURE ALTERATION IN HYPERTENSIVE PATIENTS WITH AND WITHOUT TYPE II DIABETES MELLITUS Ramon C Hermida, Carlos Calvo, Diana E Ayala, Jose E Lopez, Maria J Dominguez, Manuel Covelo. Bioengineering & Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. The lack of nocturnal decline in blood pressure (BP) is frequent in patients with type II diabetes mellitus (DM). The actual incidence of a non-dipping pattern in DM is, however, highly variable among different studies. Recent results have also indicated that non-dipping in treated patients with essential hypertension is markedly related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. Accordingly, we have evaluated the incidence of non-dipping in treated and untreated hypertensive patients with and without DM. We studied 168 hypertensive patients with DM (89 men), 60.4⫾11.7 (mean⫾SD) years of age, and 942 patients with mild-to-moderate essential hypertension (406 men), 52.2⫾14.1 years of age. Among those patients, 56 with DM and 481 hypertensive controls were untreated at the time of the study. BP was measured by ambulatory monitoring (ABPM) at 20-min intervals during the day (07:00 to 23:00 hours) and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-min intervals by wrist actigraphy. Diurnal and nocturnal means of BP obtained according to individual resting time determined by actigraphy were used to classify each patient as dipper or non-dipper (nocturnal BP decline ⬍10%). Among untreated patients, 39.1% were non-dippers, while this percentage was significantly increased to 55.7% among treated patients. In DM, 50% of the untreated patients and 76.8% of the treated patients were non-dippers. More importantly, the percentage of risers (patients with nocturnal BP mean above the diurnal mean) increased from 3.1 % in untreated controls to 14.3% in untreated patients with DM, and from 12.8% among treated hypertensive patients to a very high 30.4% among treated patients with DM. Results from this study on hypertensive patients with and without DM evaluated by 48-hour continuous ABPM and with nocturnal BP mean calculated individually according to actual resting time determined by actigraphy, indicates the high prevalence of an altered circadian BP pattern in DM. The extremely high incidence of risers among both treated and untreated patients with DM indicates the need to establish a proper chronotherapeutic antihypertensive scheme that would not only lower BP but also modify the altered circadian profile into a dipper pattern with a lower cardiovascular risk. Key Words: Diabetes mellitus, Dipper, Non-dipper

P-520 ADIPOSITY DISTRIBUTION PATTERN PREDICTS CHANGES IN NIGHT BLOOD PRESSURE PATTERN AND CARDIORENAL LESIONS Eduardo C Rosa, Maria Teresa Zanella, Na´ rcia EB Kohlmann, Sandra RG Ferreira, Artur B Ribeiro, Osvaldo Kohlmann. Kidney and Hypertension Hospital- Nephrology Division, Federal University of Sa˜ o Paulo, Sa˜ o Paulo, SP, Brazil. Among obeses, those with visceral fat distribution have a greater cardiovascular risk profile than those with peripheral distribution. However, up to now, it is not clear the implication of fat distribution pattern upon cardiac and renal alterations and ambulatory blood pressure monitoring (ABPM) variables in these patients.