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Influence of metabolic syndrome on hypertension-related target organ damage
AJH–May 2005–VOL. 18, NO. 5, PART 2
POSTERS: Metabolic Syndrome
P-533 INFLUENCE OF METABOLIC SYNDROME ON HYPERTENSION-RELATED TARGET ORGAN DAMAGE Giuseppe Mule’, Emilio Nardi, Santina Cottone, Paola Cusimano, Vito Volpe, Giuseppe Piazza, Giovanni Mezzatesta, Giovanni Cerasola. Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Centro Ipertensione - Universita` di Palermo, Palermo, Italy. The aim of our study was to analyze, in a wide group of young and middle-aged essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS), defined according to the NCEPATPIII criteria, on markers of preclinical cardiac, renal and retinal damage. Three hundred fifty three nondiabetic hypertensive subjects (mean age 46⫾10 years), free from cardiovascular and renal diseases (37% of which had MS), underwent echocardiographic examination, microalbuminuria determination and non-mydriatic retinography. Hypertensive patients with MS exhibited higher left ventricular (LV) mass [either normalized by body surface area or by height elevated by a power of 2.7 (LVMH2.7)], myocardial relative wall thickness (RWT), albumin excretion rate (AER) and greater prevalences of LV hypertrophy (LVH), of microalbuminuria and of grade I and grade II hypertensive retinopathy (simplified Keith-Wagener classification) than subjects without MS (see table 1). These results held even after correction for age, duration of hypertension, previous antihypertensive therapy, and gender distribution. The relationships between MS and LV mass and between MS and AER were confirmed in multivariate regression models including MS together with its individual components, as independent variables. MS amplifies hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. Since these markers of target organ damage are well-known predictors of cardiovascular events, our results may partly explain the enhanced cardiovascular risk associated with MS.
RWT LVMH2.7 (g/m2.7) LVH (%) AER (g/min) Microalbuminuria (%) Grade I hypertensive retinopathy (%) Grade II hypertensive retinopathy (%)
MS ⴙ (n ⴝ 130)
MS ⴚ (n ⴝ 223)
p
0.43 ⫾ 0.08 53.1 ⫾ 14.4 57.7 14.3 (6.4–27.9) 36.2 48.5
0.39 ⫾ 0.07 42.3 ⫾ 10.3 25.1 9.7 (6.4–19.3) 19.3 32.7
⫽ ⬍ ⬍ ⫽ ⫽ ⫽
38.4
15.2
⬍ 0.00001
0.0002 0.00001 0.00001 0.006 0.002 0.005
Key Words: Essential Hypertension, Metabolic Syndrome, Target Organ Damage
P-534 THE RENAL MEDULLARY CIRCULATION AND NITRIC OXIDE IN HYPERINSULINEMICHYPERTENSIVE RATS Kazushige Nakanishi, Shizuka Onuma, Mariko Higa, Yoko Nagai. Genaral Medicine, Toho University, Tokyo, Japan; Diabetes, Toho University, Tokyo, Japan. 1. Insulin resistance may play a role in hypertensive patients. The renal medullary blood flow (MBF) is thought to be an important component of blood pressure and sodium balance. Nitric oxide (NO) activity within the renal medulla is the primary characterized factor in the maintenance of MBF and plays an important role in the pressure-natriuresis response. Because MBF, which is strongly influenced by the NO system, is thought to be an important component of blood pressure and sodium balance, we focused on MBF in hypertension being secondary in the development of insulin resistance. This study was designed to test the hypotheses that the
201A
MBF will be decreased and to determine the gene expression of three nitric oxide synthases (eNOS, nNOS, iNOS) in obese zucker rats (OZ). 2. 8-9 weeks male OZ and lean zucker rats (LZ) were divided into two group: Group1; OZ (n⫽7). Group2; LZ (n⫽7). Renal hemodynamic study; Each rat was instrumented with indwelling arterial and venous catheters. The tip of the arterial catheter was advanced to just below the level of left renal artery to permit continuous measurement of renal arterial pressure (RAP). For measurement of changes in renal cortical blood flow (CBF) and MBF in rats by laserDoppler flowmetry, the optical fibers were implanted 2mm beneath the surface of the renal cortex to measure the net flux of red blood cells in the cortex and 6mm deep to monitor changes in the outer medulla. The RAP was adjusted from 160 to 80 mmHg with the use of balloon cuff. Gene expression study; We developed real-time RT-PCR that allows to absolutely quantify the gene expression of eNOS, nNOS, and iNOS in cortex and medulla of rat kidney using the standard curve and delta CT methods. 3. MAP was significantly increased in OZ. MBF was also significantly lower in OZ across a wide range of RAP without the significant change of CBF. The mRNA expression of eNOS and nNOS in renal medulla, which were significantly increased to a greater extent compared in renal cortex, were decreased in OZ compared in LZ. 4. MBF plays an important role in the development of hypertension in OZ. It seems reasonable to suppose that an impaired NO system could contribute to reduced MBF and sodium excretion, which would result in the development of hypertension in insulin resistance. Key Words: Insulin Resistance, Nitric Oxide, Renal Medullary Blood Flow
P-535 ATHEROSCLEROSIS AND MARKERS OF INFLAMMATION IN PATIENTS WITH METABOLIC SYNDROME Giuseppina Novo, Egle Corrado, Ida Muratori, Alfonzo Bellia, Anna Galluzzo, Francesca Bonura, Giustina Vitale, Salvatore Novo. Internal Medicine and Cardiovascular Disease, University of Palermo, Palermo, Italy, Italy. Purpose: To evaluate incidence and prevalence of multifocal, coronary and peripheral atherosclerosis in patients with metabolic syndrome (MS) and to investigate the relationship between atherosclerosis and levels of C Reactive Protein (CRP) and fibrinogen (F). Methods: We studied 568 ambulatory subjects, (M/F⫽ 307/261), aged between 43 and 87 years. Patients were asked about their clinical history and cardiovascular risk factors (CVRF) and underwent carotid artery ultrasound. high sensitivity (hs) CRP and F were measured. Prevalence of MS, defined according to the NCEP-ATP III criteria, was 28% (n⫽163). Female were significantly more than male (F⫽56%, M ⫽45%, p ⬍ 0.05). The most frequent diagnostic criteria were abdominal obesity, hypertension and dyslipidemias. The studied population was divided in two groups: patients with 0-2 CVRF (Group 1; n⫽ 405) and patient with metabolic syndrome (Group 2; n⫽163). Results: Prevalence of asymptomatic carotid lesions (intima media thickening - IMT - and asymptomatic carotid plaque – ACP-) was 74% in patients with MSand 62% in patients with 0-2 RF (p⫽0.002), cardiac events (angina 10% vs 5% p⫽ 0.05 or myocardial infarction, 12% vs 5,6%, p⫽ 0.03) and cerebrovascular events (TIA 7% vs il 3% p⫽0. 01 and stroke 3% vs 1.5%) were also more frequent in group 1 vs group 2. Patients with all five risk factors of MS had significantly more elevated levels of fibrinogen and CRP, of asymptomatic carotid lesions as well as of all cardiovascular events (p ⬍ 0.001). Arterial hypertension was significantly and independently associated with both hs-CRP and F. Hs-CRP and F increased levels were significantly associated with IMT or ACP (p ⫽ 0.0006) and with previous cardiac (angina or MI p⫽0.03), and cerebrovascular events (TIA or stroke, p ⫽ 0.0001).
POSTERS: Metabolic Syndrome
P-533 INFLUENCE OF METABOLIC SYNDROME ON HYPERTENSION-RELATED TARGET ORGAN DAMAGE Giuseppe Mule’, Emilio Nardi, Santina Cottone, Paola Cusimano, Vito Volpe, Giuseppe Piazza, Giovanni Mezzatesta, Giovanni Cerasola. Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Centro Ipertensione - Universita` di Palermo, Palermo, Italy. The aim of our study was to analyze, in a wide group of young and middle-aged essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS), defined according to the NCEPATPIII criteria, on markers of preclinical cardiac, renal and retinal damage. Three hundred fifty three nondiabetic hypertensive subjects (mean age 46⫾10 years), free from cardiovascular and renal diseases (37% of which had MS), underwent echocardiographic examination, microalbuminuria determination and non-mydriatic retinography. Hypertensive patients with MS exhibited higher left ventricular (LV) mass [either normalized by body surface area or by height elevated by a power of 2.7 (LVMH2.7)], myocardial relative wall thickness (RWT), albumin excretion rate (AER) and greater prevalences of LV hypertrophy (LVH), of microalbuminuria and of grade I and grade II hypertensive retinopathy (simplified Keith-Wagener classification) than subjects without MS (see table 1). These results held even after correction for age, duration of hypertension, previous antihypertensive therapy, and gender distribution. The relationships between MS and LV mass and between MS and AER were confirmed in multivariate regression models including MS together with its individual components, as independent variables. MS amplifies hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. Since these markers of target organ damage are well-known predictors of cardiovascular events, our results may partly explain the enhanced cardiovascular risk associated with MS.
RWT LVMH2.7 (g/m2.7) LVH (%) AER (g/min) Microalbuminuria (%) Grade I hypertensive retinopathy (%) Grade II hypertensive retinopathy (%)
MS ⴙ (n ⴝ 130)
MS ⴚ (n ⴝ 223)
p
0.43 ⫾ 0.08 53.1 ⫾ 14.4 57.7 14.3 (6.4–27.9) 36.2 48.5
0.39 ⫾ 0.07 42.3 ⫾ 10.3 25.1 9.7 (6.4–19.3) 19.3 32.7
⫽ ⬍ ⬍ ⫽ ⫽ ⫽
38.4
15.2
⬍ 0.00001
0.0002 0.00001 0.00001 0.006 0.002 0.005
Key Words: Essential Hypertension, Metabolic Syndrome, Target Organ Damage
P-534 THE RENAL MEDULLARY CIRCULATION AND NITRIC OXIDE IN HYPERINSULINEMICHYPERTENSIVE RATS Kazushige Nakanishi, Shizuka Onuma, Mariko Higa, Yoko Nagai. Genaral Medicine, Toho University, Tokyo, Japan; Diabetes, Toho University, Tokyo, Japan. 1. Insulin resistance may play a role in hypertensive patients. The renal medullary blood flow (MBF) is thought to be an important component of blood pressure and sodium balance. Nitric oxide (NO) activity within the renal medulla is the primary characterized factor in the maintenance of MBF and plays an important role in the pressure-natriuresis response. Because MBF, which is strongly influenced by the NO system, is thought to be an important component of blood pressure and sodium balance, we focused on MBF in hypertension being secondary in the development of insulin resistance. This study was designed to test the hypotheses that the
201A
MBF will be decreased and to determine the gene expression of three nitric oxide synthases (eNOS, nNOS, iNOS) in obese zucker rats (OZ). 2. 8-9 weeks male OZ and lean zucker rats (LZ) were divided into two group: Group1; OZ (n⫽7). Group2; LZ (n⫽7). Renal hemodynamic study; Each rat was instrumented with indwelling arterial and venous catheters. The tip of the arterial catheter was advanced to just below the level of left renal artery to permit continuous measurement of renal arterial pressure (RAP). For measurement of changes in renal cortical blood flow (CBF) and MBF in rats by laserDoppler flowmetry, the optical fibers were implanted 2mm beneath the surface of the renal cortex to measure the net flux of red blood cells in the cortex and 6mm deep to monitor changes in the outer medulla. The RAP was adjusted from 160 to 80 mmHg with the use of balloon cuff. Gene expression study; We developed real-time RT-PCR that allows to absolutely quantify the gene expression of eNOS, nNOS, and iNOS in cortex and medulla of rat kidney using the standard curve and delta CT methods. 3. MAP was significantly increased in OZ. MBF was also significantly lower in OZ across a wide range of RAP without the significant change of CBF. The mRNA expression of eNOS and nNOS in renal medulla, which were significantly increased to a greater extent compared in renal cortex, were decreased in OZ compared in LZ. 4. MBF plays an important role in the development of hypertension in OZ. It seems reasonable to suppose that an impaired NO system could contribute to reduced MBF and sodium excretion, which would result in the development of hypertension in insulin resistance. Key Words: Insulin Resistance, Nitric Oxide, Renal Medullary Blood Flow
P-535 ATHEROSCLEROSIS AND MARKERS OF INFLAMMATION IN PATIENTS WITH METABOLIC SYNDROME Giuseppina Novo, Egle Corrado, Ida Muratori, Alfonzo Bellia, Anna Galluzzo, Francesca Bonura, Giustina Vitale, Salvatore Novo. Internal Medicine and Cardiovascular Disease, University of Palermo, Palermo, Italy, Italy. Purpose: To evaluate incidence and prevalence of multifocal, coronary and peripheral atherosclerosis in patients with metabolic syndrome (MS) and to investigate the relationship between atherosclerosis and levels of C Reactive Protein (CRP) and fibrinogen (F). Methods: We studied 568 ambulatory subjects, (M/F⫽ 307/261), aged between 43 and 87 years. Patients were asked about their clinical history and cardiovascular risk factors (CVRF) and underwent carotid artery ultrasound. high sensitivity (hs) CRP and F were measured. Prevalence of MS, defined according to the NCEP-ATP III criteria, was 28% (n⫽163). Female were significantly more than male (F⫽56%, M ⫽45%, p ⬍ 0.05). The most frequent diagnostic criteria were abdominal obesity, hypertension and dyslipidemias. The studied population was divided in two groups: patients with 0-2 CVRF (Group 1; n⫽ 405) and patient with metabolic syndrome (Group 2; n⫽163). Results: Prevalence of asymptomatic carotid lesions (intima media thickening - IMT - and asymptomatic carotid plaque – ACP-) was 74% in patients with MSand 62% in patients with 0-2 RF (p⫽0.002), cardiac events (angina 10% vs 5% p⫽ 0.05 or myocardial infarction, 12% vs 5,6%, p⫽ 0.03) and cerebrovascular events (TIA 7% vs il 3% p⫽0. 01 and stroke 3% vs 1.5%) were also more frequent in group 1 vs group 2. Patients with all five risk factors of MS had significantly more elevated levels of fibrinogen and CRP, of asymptomatic carotid lesions as well as of all cardiovascular events (p ⬍ 0.001). Arterial hypertension was significantly and independently associated with both hs-CRP and F. Hs-CRP and F increased levels were significantly associated with IMT or ACP (p ⫽ 0.0006) and with previous cardiac (angina or MI p⫽0.03), and cerebrovascular events (TIA or stroke, p ⫽ 0.0001).