Hypertension, heart failure and diabetes mellitus

Hypertension, heart failure and diabetes mellitus

AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2 of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation, support the hypothesis that oxidat...

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AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2

of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation, support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity. Key Words: Obesity, endothelium, risk factors E040 ACE-GENE POLYMORPHISM AND INSULIN RESISTANCE IN NEVER TREATED HYPERTENSIVE PATIENTS F. Perticone, R. Ceravolo, S. Iacopino, G. Ventura, R. Maio, M. Candigliota, A. Sciacqua, and C. Spaccarotella. Dpt of Medicina Sperimentale e Clinica “G Salvatore,” University of Catanzaro, Italy The association between angiotensin-converting enzyme (ACE)-gene polymorphism and insulin resistance (IR) in hypertensives remains controversial. Thus, the aim of present study was to evaluate the possible association between IR and ACE-gene polymorphism and in a group of hypertensive patients in comparison with normotensive control group. We enrolled 200 (114M/86F; age ⫽ 45.5 ⫾ 4.7 years) never treated hypertensive patients compared with 96 (54M/42F; age ⫽ 44.0 ⫾ 4.7 years) normotensive subjects. Using a double PCR assay identified ACE genotypes. Blood was analyzed for glucose and insulin levels by using the glucose oxidase method and standard radioimmunoassay technique, respectively. IR was estimated by using the homeostasis model assessment (HOMA IR). Both fasting glucose (5.0 ⫾ 0.3 mmol/L vs 4.7 ⫾ 0.3 mmol/L; p ⬍ 0.0001) and insulin levels (12.3 ⫾ 4.7 ␮U/mL vs 4.9 ⫾ 1.5 ␮U/mL; p ⬍ 0.0001) were significantly higher in hypertensive patients than in normotensive control group. HOMA IR was significantly higher (2.7 ⫾ 1.1 vs 1.1 ⫾ 0.3; p ⬍ 0.0001) in hypertensives than in normotensives. When we subdivided hypertensive patients according to ACE genotype, we observed: fasting insulin levels and HOMA IR were 16.3 ⫾ 3.3 ␮U/mL and 3.6 ⫾ 0.8 in DD genotype, 9.4 ⫾ 3.1 ␮U/mL and 2.1 ⫾ 0.7 in ID, and 8.3 ⫾ 2.8 ␮U/mL and 1.9 ⫾ 0.7 II group (p ⬍ 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. We extended previous data regarding the relationship of hypertension and insulin resistance by demonstrating a dependence of this relationship upon the ACE genotype. Key Words: Hypertension, insulin resistance, reninangiotensin system E041 AFRO-VENEZUELAN HYPERTENSIVE PATIENTS: OBESITY AND CARDIOVASCULAR RISK ACCORDING TO WAIST-TO-HIP RATIO A. Delgado, R. Farias, S. Celis, R. Alvarez, F. Fragacha´n. Arterial Hypertension Unit, Hospital Universitario de Caracas, Universidad Central de Venezuela, Caracas, Venezuela Obesity is associated with Arterial Hypertension and several metabolic complications, and is considered a predictor of risk for cardiovascular disease. The aim of this study is to evaluate the Body mass index (BMI) and Waist-to-hip ratio (WHR) in Afro-Venezuelan communities and determinate the frequency of Obesity and evaluate the cardiovascular

POSTERS: Obesity, Insulin Resistance, Diabetes

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risk according to WHR. The Subjects came from black communities from the Barlovento area, who have 76 –79% of black genetic contribution (Barlovento Study). Blood pressure (BP), BMI and WHR were obtained from each subject. Cardiovascular risk was evaluated according to WHR, age and gender. 241 subjects participated in the study (Female 139, Male 102). 160 subjects (66.39%) were Normotensive (NT) and 81 were (33.61%) Hypertensive (HT). According to BMI: Normal 67.22%, Overweight 26.14% and Obese 6.64%. In Females (F): Normal 62.59%, Overweight 28.56% and Obese 9.35%. In Males (M): Normal 73.53%, Overweight 23.53% and Obese 2.94%. In NT patients: Normal 73.75% (n⫽162), Overweight 21.87% and Obese 4.38%. In HT patients: Normal 54.32%, Overweight 34.57% and Obese 11.11%. Cardiovascular risk according to WHR: Low 14.66% (F: 1.52%, M: 32.00%), Moderate 31.03% (F: 24.24%, M: 40.00%), High 30.17% (F: 36.36%, M: 22.00%) and Very High 24.14% (F: 37.88%, M: 6.00%). According to WHR and BP: Low NT: 22.67% vs HT: 17.07%, Moderate NT: 26.67% vs HT: 21.95%, High NT: 28.00% vs HT: 34.15%, Very High NT: 22.66% vs HT: 26.83%. These Afro-Venezuelan communities have a major percentage of Overweight and Obesity (32.68%). Female have more Overweight and Obesity than Male (F: 37.91% vs M: 26.47%) and achieve more cardiovascular risk according to WHR. HT have more Overweight and Obesity than NT (HT: 45.68% vs NT: 26.25%) and achieve more cardiovascular risk according to WHR. Key Words: Obesity; waist-to-hip ratio; cardiovascular risk; Black communities; Afro-Venezuelan. E042 HYPERTENSION, HEART FAILURE AND DIABETES MELLITUS D. Psirropoulos, N. Lefkos, G. Boudonas, Ap. Efthimiadis, G. Tsapas. Cardiology Unit of 2nd Dept. of Internal Medicine, Hippokration Hospital, Aristotelian University of Thessaloniki, Thessaloniki, Greece The role of hypertension and diabetes mellitus as risk factors in coronary heart disease is known but the role of diabetes mellitus in hypertensive heart failure is diffuse. Sixty eight hypertensive patients under sufficient anti-hypertensive treatment (M⫽42, F⫽26, mean age⫽70⫾8 years) with heart failure (II–IV NYHA class, EF⬍40%, EPSS⬎5mm) and without known history of ischaemic heart disease or hyperlipidaemia, were studied. In all patients at baseline blood pressure and heart rate were measured, an echocardiogram, for determination of systolic indices was performed, and fasting glucose and cholesterol levels were measured. Elevated glucose levels (diabetes mellitus) were found in 21 patients who consisted group A and the remaining 47 patients without diabetes consisted group B. Glucose levels were significantly higher in subgroup A (180mg/dl) compared to subgroup B (106mg/dl), systolic dysfunction was greater, especially in women, than in subgroup B (mean group EF⫽29%, EPSSⱖ6.2mm and mean EF⫽33%, EPSSⱖ5.2mm respectively), and cholesterol levels were higher in subgroup A than in subgroup B (⬎235mg/dl, ⬎201mg/dl respectively). The anti-hypertensive treatment was sufficient without significant differences in both subgroups but the diabetic control was

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ASH XV ABSTRACTS

not efficient in subgroup A. The diabetes mellitus, in our study, shows a clear significant negative effect on the systolic function of the left ventricle in the hypertensive patients. In hypertensive patients with heart failure the endothelial dysfunction and/or the insufficient treatment of diabetes may contribute to appearance of systolic dysfunction of the left ventricle. The coexistence also of diabetes and hyperlipidaemia could indicate underlying coronary arterial disease which may predispose to failure. Key Words: Hypertension; systolic dysfunction; diabetes mellitus E043 PARATHYROID HORMONE AND INSULINRESISTANCE IN ESSENTIAL HYPERTENSION G. Andronico, M.T. Mangano, R. Ferraro-Mortellaro, G. Mule, G. Cerasola. Internal Medicine and Hypertension Centre, University of Palermo, Italy. Some studies have suggested a role of parathyroid hormone (PTH) in hypertension; moreover, insulin-resistance has been found in patients with primary hyperparathyroidism even in absence of hypertension. To observe the relationships between PTH and insulin-resistance in hypertension, we studied 61 patients with mild to moderate essential hypertension without diabetes mellitus, renal failure or hyperparathyroidism and 14 healthy subjects as controls. After at least 2 weeks of pharmacological washout, fasting blood glucose, insulin and intact PTH were measured. PTH levels were higher in hypertensive than in normotensive subjects (29.6⫾1.2 vs 22.6⫾1.1 ng/mL⫺p:0.006). In Hypertensive patients, however, we found no relationship between 24h systolic or diastolic pressure and PTH values. When hypertensives were divided in thirds on the basis of their PTH, in the higher third compared with the lower third we found higher blood glucose levels (90.1⫾2.6 vs 83.1⫾1.9 mg/dL⫺p:0.04) but lower insulin levels (15.7⫾1.2 vs 25.1⫾4.9 mU/L p⬍0.05) and lower insulin/glucose ratio (as insulin-resistance index) (0.17⫾0.01 vs 0.32⫾0.07⫺p:0.02). An inverse relationship, moreover, was found in hypertensives between insulin-resistance index and PTH values (r: ⫺0.29⫺p:0.03). Our results show that hypertensive subjects are characterized by higher PTH levels than healthy people. Insulinresistance appears to be lower in the group with higher PTH values. We need other studies to clarify these aspects of arterial hypertension. Key Words: Insulin-resistance; insulin; parathyroid hormone E044 ACE-INHIBITOR TREATMENT CORRECTS THE DEFECT IN VASCULAR INSULIN RESISTANCE IN HYPERTENSION N.D. Feldman*, N.D. Schmidt. Robarts Research Institute and University of Western Ontario, London, Canada Insulin resistance is a risk factor for hypertension, although the causality of the relationship has not been proved. Systemic insulin resistance parallels resistance to the vasodilat-

AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2

ing effect of insulin. Systemic insulin resistance has been shown to be improved by both lifestyle modification as well as some specific antihypertensive therapies—including ACE-inhibition. Whether vascular insulin resistance can be improved by antihypertensive therapy was unknown. Therefore, we determined the effect of therapy with the ACE-inhibitor, quinapril, on vascular sensitivity to insulin (assessed by the dorsal hand vein linear variable differential transformer—LVDT technique) in 12 hypertensive subjects using a randomized double-blinded, crossover design. At the baseline LVDT assessment, vascular sensitivity to insulin was found to be significantly inversely correlated with BMI and significantly positively correlated with urinary sodium excretion. Three months of therapy with quinapril was associated with a significant improvement in vascular sensitivity to insulin, as determined by a decrease in the ED50 for insulin (Placebo⫽501⫾189 ␮U/min; Quinapril⫽276⫾100 ␮U/min, p⬍0.05). Also, maximal isoproterenol-mediated relaxation was enhanced (Placebo⫽92⫾15% of baseline distension; Quinapril⫽151⫾31% p⬍0.05). There was no effect of ACE-inhibition on nitroglycerin-mediated relaxation. Phenylephrine-mediated vasoconstriction was not altered. ACE-inhibitors have been shown, in both hypertensive patients, and those at high risk of atherosclerotic disease, to delay the appearance of diabetes as well as its complications. The current study suggests the hypothesis that this beneficial effect of ACE-inhibitors may be related to their beneficial effects on vascular function in general, and on insulinmediated vascular responses, in particular. Key Words: Insulin; vascular reactivity; ACE-inhibitors E045 MICROALBUMINURIA AND SYSTOLIC BLOOD PRESSURE IN OBESITY L.X. Cubeddu* and I.S. Hoffmann. Center for the Detection and Treatment of Silent Cardiovascular Risk Factors (SIL-DETECT); Central University of Venezuela, Caracas, Venezuela, Nova Southeastern Univ, School of Pharmacy, Ft. Lauderdale, Florida, USA The presence of microalbuminuria has become an important tool for therapeutic intervention. In this study we investigated whether the dysmetabolic syndrome of obesity was associated with or could occur in the absence of microalbuminuria. The study was conducted in 71 clinically healthy, glucose tolerant Hispanics (age:43⫾1.4 yr, SBP:117⫾2 mmHg, DBP:77⫾1.3 mmHg, urinary albumin excretion (UAE):10.2⫾0.6 mg/24 hr). Subjects were classified as lean (BMI⬍25), overweight (BMI⬎25⬍30) and obese (BMI⬎30 kg/m2). Greater BMI was associated with higher bwt, waist to hip ratio (WHR), BP, fasting insulin, triglyceride, post glucose-load insulin and glucose, and lower HDL levels. No differences in the UAE (mg/24 hr) were found between lean (9.0⫾0.9; median:9.1), overweight (11.3⫾1.2; median:10.5) and obese (11.1⫾1.2; median:9.7) subjects. No microalbuminuria (UAE⬎30 mg/24 hr) was not found in any of the subjects. For all subjects combined, as well as for each of the groups separately, the UAE was unrelated to the BMI, WHR, body weight, triglyceride, cholesterol (total, LDL or HDL),