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Altered circadian blood pressure profile in patients with active acromegaly. relationship with left ventricular mass and hormonal values
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
other clues. The purpose of the study was to determinate the incidence of RVHT among patients with Severe AH (according to WHO 1999) consulting the Arterial Hypertension Unit during 1998 –1999. Participants came from the Arterial Hypertension Unit. Clinical, laboratory procedure and Renal Duplex Doppler Ultrasonography (RDDUS) was performed in all patients. Twenty-six (n ⫽ 26) with Severe AH (SBP ⬎ 180 mm Hg or DBP ⬎ 120 mm Hg) were included in study. All of then were treated with 3 antihypertensive drugs (ACE inhibitors among them), with poor control of the blood pressure. All reported accentuated smoking habit and presented proteinuria. RDDUS showed 7 patients (27%) with RVD, 5 with unilateral renal arterial lesion and 2 with bilateral renal arterial lesion. Among the patients with unilateral lesion, all reported other atherosclerotic compromise. Among the patients with bilateral disease, all reported abdominal bruit. RVD has a high incidence among selected patients like those that consults Hypertension Units. RDDUS is practical, noninvasive technique with good sensitivity and that does not require discontinuing any antihypertensive medication. Key Words: Renovascular disease; renovascular hypertension; Renal Duplex Doppler Ultrasonography M018 URINARY FREE CORTISOL/CORTISONE RATIO AS INDEX OF 11 HSD2 ACTIVITY IN “ESSENTIAL” HYPERTENSION 1 G. Giacchetti, 1G. Lucarelli, 1C. Sardu, 3P.M. Stewart, 1F. Mantero, 2M. Palermo. 1Div. of Endocrinology, Un. of Ancona, “Umbertolo” Hospital, Italy, Dep. of Medicine, 2Un. of Sassari, Italy, 3Dep. of Medicine, Un. of Birmingham, UK The 11 hydroxysteroid dehydrogenase type 2 (11-HSD2) regulates glucocorticoid access to renal mineralo- and glucocorticoid receptors by a selective conversion of cortisol to biologically inactive cortisone. Mutations in the 11-HSD gene have been detected in all patients affected by apparent excess of mineralocorticoid (AME). Moreover the 11-HSD gene has been potentially considered a candidate gene for essential hypertension. We have previously demonstrated that the frequency of shorter alleles (length ⬍153 bp) of a CA repeat polymorphism in the first intron of 11-HSD gene was significantly higher among salt-sensitive individuals. In particular, blood pressure changes, as a response to salt loading and salt depletion, were different in subjects carrying 0, 1 or 2 “short alleles”. The aim of this study was to evaluate urinary free cortisol/free cortisone ratio (UFF/ UFE), as a direct index of 11-HSD activity, in hypertensive patients characterized by sensitivity to salt, maintained at normal and high salt diet, and in normotensive subjects. Sixty seven untreated hypertensive patients, from Salt Sensitivity Italian Study Group (11 women, 56 men aged 46 ⫾ 12 yrs) and 18 normotensive subjects were studied. Salt sensitivity test (Grim and Weinberger protocol) was performed in all patients. The analysis of urinary steroids has been performed by gas chromatography/mass spectrometry, using a stable isotope-labelled internal standard. Results: UFF/UFE ratio was significantly higher in the hypertensive patients compared to normotensive subjects
POSTERS: Secondary Hypertension
305A
(0.79 ⫾ 0.04 vs 0.57 ⫾ 0.04, p ⬍ 0.02). During normal salt diet, the salt-sensitive hypertensives (n ⫽ 33) had a higher UFF/UFE ratio when compared to salt-resistant patients (n ⫽ 34) (0.89 ⫾ 0.05 vs 0.71 ⫾ 0.06, p ⬍ 0.05). UFF/UFE ratio was decreased after high salt diet to 0.59 ⫾ 0.03 in the whole group of hypertensive patients, furthermore the values of UFF/UFE ratio remain higher in salt sensitivity (0.63 ⫾ 0.04) than in the salt resistant (0.54 ⫾ 0.06) hypertensives. In conclusion, our data show that the 11-HSD2 activity is reduced in hypertensives with respect to normotensive subjects and that it is lower in salt-sensitive than in salt-resistant patients. High salt diet is able to increase the activity of the enzyme, but with a lower degree in salt sensitive patients. Key Words: Urinary free cortisol; urinary free cortisone; hypertension; salt-sensitivity M019 ALTERED CIRCADIAN BLOOD PRESSURE PROFILE IN PATIENTS WITH ACTIVE ACROMEGALY. RELATIONSHIP WITH LEFT VENTRICULAR MASS AND HORMONAL VALUES D.J. Pietrobelli, M. Akopian, A. Renauld, A.O. Olivieri, D. Garrido, and C.A. Feldstein*. Hypertension Program, Hospital San Martin Buenos Aires School of Medicine and Instituto Universitario de Ciencias de la Salud (Fundacion Barcelo), Las Heras 2191, Buenos Aires, Argentina The aim of the study was to determine blood pressure values and 24-hour ambulatory blood pressure (ABPM) profile in patients with active acromegaly and the relationship with left ventricular hypertrophy, serum GH and IGF-I, fasting and mean insulin values during 2 h oral glucose (75 g)-tolerance test (OGTT). Twenty four patients with active acromegaly (16 women, 8 men, mean age 48.1 ⫾ 15.8 years) were included. Patients were off antihypertensive drug therapy for at least three weeks and none had been using any medical treatment for acromegaly for at least 3 months before the study. Casual blood pressure were measured in triplicate and 24-hour ABPM were obtained. A two-dimensional echocardiogram was obtained and left ventricular mass index (LVMI) was calculated. Fourteen patients (58.33%) were considered hypertensives according sphygmomanometric measurements (systolic/diastolic ⱖ 140/90 mm Hg). Hypertension tended to increase with age: according to clinical measurements was diagnosed in 4 of 10 patients aged ⱕ40 years and in 10 of 14 patients aged ⬎40 years. Non dipping profile (patients with a decline in nocturnal BP ⬍10%) was observed at ABPM in 63% of hypertensives and in 61,53% of normotensives. There was a significant correlation between the age of the patients and the casual SBP and the mean 24-hour SBP (r ⫽ 0.547 and 0.511, both P ⬍ 0.01), respectively. No correlations were found between BP and gender, BMI, LVMI, serum GH and IGF-I, serum fasting insulin levels and the values obtained during OGTT expressed as area under the curve. Hypertensive acromegalic patients had greater LVMI and lower serum levels of IGF-I than normotensives (148.6 ⫾ 44.9 vs 120.7 ⫾ 33.8 g/m2; 447.6 ⫾ 183.9 vs 598.4 ⫾ 213.7 g/L, both of them P ⬍ 0.05), respectively. In conclusion, non
306A
ASH XV ABSTRACTS
dipping had a high prevalence among acromegalic patients, even in the normotensives. The greater values of IGF-I in normotensive than in hypertensive acromegalic patients and the correlation between casual SBP and the mean 24-hour SBP and the age of patients suggest that a
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
significant subset of acromegalics may suffer from essential hypertension. Key Words: Acromegaly; ABPM; left ventricular mass index; dipping
other clues. The purpose of the study was to determinate the incidence of RVHT among patients with Severe AH (according to WHO 1999) consulting the Arterial Hypertension Unit during 1998 –1999. Participants came from the Arterial Hypertension Unit. Clinical, laboratory procedure and Renal Duplex Doppler Ultrasonography (RDDUS) was performed in all patients. Twenty-six (n ⫽ 26) with Severe AH (SBP ⬎ 180 mm Hg or DBP ⬎ 120 mm Hg) were included in study. All of then were treated with 3 antihypertensive drugs (ACE inhibitors among them), with poor control of the blood pressure. All reported accentuated smoking habit and presented proteinuria. RDDUS showed 7 patients (27%) with RVD, 5 with unilateral renal arterial lesion and 2 with bilateral renal arterial lesion. Among the patients with unilateral lesion, all reported other atherosclerotic compromise. Among the patients with bilateral disease, all reported abdominal bruit. RVD has a high incidence among selected patients like those that consults Hypertension Units. RDDUS is practical, noninvasive technique with good sensitivity and that does not require discontinuing any antihypertensive medication. Key Words: Renovascular disease; renovascular hypertension; Renal Duplex Doppler Ultrasonography M018 URINARY FREE CORTISOL/CORTISONE RATIO AS INDEX OF 11 HSD2 ACTIVITY IN “ESSENTIAL” HYPERTENSION 1 G. Giacchetti, 1G. Lucarelli, 1C. Sardu, 3P.M. Stewart, 1F. Mantero, 2M. Palermo. 1Div. of Endocrinology, Un. of Ancona, “Umbertolo” Hospital, Italy, Dep. of Medicine, 2Un. of Sassari, Italy, 3Dep. of Medicine, Un. of Birmingham, UK The 11 hydroxysteroid dehydrogenase type 2 (11-HSD2) regulates glucocorticoid access to renal mineralo- and glucocorticoid receptors by a selective conversion of cortisol to biologically inactive cortisone. Mutations in the 11-HSD gene have been detected in all patients affected by apparent excess of mineralocorticoid (AME). Moreover the 11-HSD gene has been potentially considered a candidate gene for essential hypertension. We have previously demonstrated that the frequency of shorter alleles (length ⬍153 bp) of a CA repeat polymorphism in the first intron of 11-HSD gene was significantly higher among salt-sensitive individuals. In particular, blood pressure changes, as a response to salt loading and salt depletion, were different in subjects carrying 0, 1 or 2 “short alleles”. The aim of this study was to evaluate urinary free cortisol/free cortisone ratio (UFF/ UFE), as a direct index of 11-HSD activity, in hypertensive patients characterized by sensitivity to salt, maintained at normal and high salt diet, and in normotensive subjects. Sixty seven untreated hypertensive patients, from Salt Sensitivity Italian Study Group (11 women, 56 men aged 46 ⫾ 12 yrs) and 18 normotensive subjects were studied. Salt sensitivity test (Grim and Weinberger protocol) was performed in all patients. The analysis of urinary steroids has been performed by gas chromatography/mass spectrometry, using a stable isotope-labelled internal standard. Results: UFF/UFE ratio was significantly higher in the hypertensive patients compared to normotensive subjects
POSTERS: Secondary Hypertension
305A
(0.79 ⫾ 0.04 vs 0.57 ⫾ 0.04, p ⬍ 0.02). During normal salt diet, the salt-sensitive hypertensives (n ⫽ 33) had a higher UFF/UFE ratio when compared to salt-resistant patients (n ⫽ 34) (0.89 ⫾ 0.05 vs 0.71 ⫾ 0.06, p ⬍ 0.05). UFF/UFE ratio was decreased after high salt diet to 0.59 ⫾ 0.03 in the whole group of hypertensive patients, furthermore the values of UFF/UFE ratio remain higher in salt sensitivity (0.63 ⫾ 0.04) than in the salt resistant (0.54 ⫾ 0.06) hypertensives. In conclusion, our data show that the 11-HSD2 activity is reduced in hypertensives with respect to normotensive subjects and that it is lower in salt-sensitive than in salt-resistant patients. High salt diet is able to increase the activity of the enzyme, but with a lower degree in salt sensitive patients. Key Words: Urinary free cortisol; urinary free cortisone; hypertension; salt-sensitivity M019 ALTERED CIRCADIAN BLOOD PRESSURE PROFILE IN PATIENTS WITH ACTIVE ACROMEGALY. RELATIONSHIP WITH LEFT VENTRICULAR MASS AND HORMONAL VALUES D.J. Pietrobelli, M. Akopian, A. Renauld, A.O. Olivieri, D. Garrido, and C.A. Feldstein*. Hypertension Program, Hospital San Martin Buenos Aires School of Medicine and Instituto Universitario de Ciencias de la Salud (Fundacion Barcelo), Las Heras 2191, Buenos Aires, Argentina The aim of the study was to determine blood pressure values and 24-hour ambulatory blood pressure (ABPM) profile in patients with active acromegaly and the relationship with left ventricular hypertrophy, serum GH and IGF-I, fasting and mean insulin values during 2 h oral glucose (75 g)-tolerance test (OGTT). Twenty four patients with active acromegaly (16 women, 8 men, mean age 48.1 ⫾ 15.8 years) were included. Patients were off antihypertensive drug therapy for at least three weeks and none had been using any medical treatment for acromegaly for at least 3 months before the study. Casual blood pressure were measured in triplicate and 24-hour ABPM were obtained. A two-dimensional echocardiogram was obtained and left ventricular mass index (LVMI) was calculated. Fourteen patients (58.33%) were considered hypertensives according sphygmomanometric measurements (systolic/diastolic ⱖ 140/90 mm Hg). Hypertension tended to increase with age: according to clinical measurements was diagnosed in 4 of 10 patients aged ⱕ40 years and in 10 of 14 patients aged ⬎40 years. Non dipping profile (patients with a decline in nocturnal BP ⬍10%) was observed at ABPM in 63% of hypertensives and in 61,53% of normotensives. There was a significant correlation between the age of the patients and the casual SBP and the mean 24-hour SBP (r ⫽ 0.547 and 0.511, both P ⬍ 0.01), respectively. No correlations were found between BP and gender, BMI, LVMI, serum GH and IGF-I, serum fasting insulin levels and the values obtained during OGTT expressed as area under the curve. Hypertensive acromegalic patients had greater LVMI and lower serum levels of IGF-I than normotensives (148.6 ⫾ 44.9 vs 120.7 ⫾ 33.8 g/m2; 447.6 ⫾ 183.9 vs 598.4 ⫾ 213.7 g/L, both of them P ⬍ 0.05), respectively. In conclusion, non
306A
ASH XV ABSTRACTS
dipping had a high prevalence among acromegalic patients, even in the normotensives. The greater values of IGF-I in normotensive than in hypertensive acromegalic patients and the correlation between casual SBP and the mean 24-hour SBP and the age of patients suggest that a
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
significant subset of acromegalics may suffer from essential hypertension. Key Words: Acromegaly; ABPM; left ventricular mass index; dipping