LONG-TERM EFFECTS OF SURGICAL MENAGEMENT OF PRIMARY ALDOSTERONISM ON THE CARDIOVASCULAR SISTEM

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1 LONG-TERM EFFECTS OF SURGICAL MENAGEMENT OF PRIMARY ALDOSTERONISM ON THE CARDIOVASCULAR SISTEM Riccardo Marsili, Pietro Iacconi, Massimo Chiarugi, Giampaolo Bernini*, Alessandra Bacca*, Paolo Miccoli Department of Surgery and Internal Medicine* of Pisa University, Pisa Dipartimento di Chirurgia Generale Università di Pisa

2 INTRODUCTION Primary aldosteronism (PA) is the most common form of endocrine hypertension, and PA has a prevalence of 11 % in hypertensive patients who are admitted into the referral treatment centre for hypertension. The chronically elevated levels of aldosterone (ALD) determine: I. Inappropriate salt status with volume hypertension I. The activation of inflamatory cytokines and growth factors with relevant cardiovascular sequelae: cell adhesion and migration, vascular inflammation, and resulting cardiovascular hypertrophy and remodelling Rossi GP et al (26) A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Amer Coll Cardiol 48: Lemarié CA et al (28) New insights on signaling cascades induced by cross-talk between angiotensin II and aldosterone. J Molecular Med 86:

3 Consequentially, these determine a high rate of cardio-cerebrovascular events in respect to patients with essential hypertension, independent of blood pressure: stroke (RR 4.2, C.I ) myocardial infarction (RR 6.5, CI ) atrial fibrillation (RR 12.1, CI )

4 There are two options in the treatment of PA: specific pharmacological therapy using ALD receptor blockade or, only in the case of monolateral autonomous secretion of ALD, adrenalectomy. The most common approach to the monolateral form of PA is the adrenalectomy, although each procedure improves blood pressure values. Howewer, to date, there has not been sufficient data available on long-term follow-up in the comparison of pharmacological therapy with surgery, and therefore, there is not sufficient evidence to suggest that one is superior to the other. The aim of our work was to compare the long-term cardiovascular effects of the two types of treatments.

5 GROUP A ADRENALECTOMY 58 PATIENTS AFFECTED BY MONOLATERAL SECRETION GROUP B SPIRONOLACTONE (5 TO 2 mg/die) 41 PATIENTS AFFECTED BY BILATERAL SECRETION Possibly other antihypertensive drugs (therapeutic gold BP < 14/9) FOLLOW-UP (MONTHS) GROUP A: 52.6 ± 6.3 GROUP B: 47.5 ± 3.7 P: NS

6 INCLUSION CRITERIA Preoperative and follow-up assessment conducted at the Hypertension Center of Pisa University No use of ALD receptor antagonists before the basal evaluation and adrenalectomy DIAGNOSTIC WORK-UP: Wash-out for at least 2 weeks Screening test: ALD/PRA ratio on at least two occasions over 69 and plasma ALD higher than 15 ng/dl Confirmatory test: CAPTOPRIL (5 mg per os) and SALINE LOADING TEST (2 ml of saline infusion) considered positive when ALD values remained higher than 15 ng/dl and 7 ng/dl respectively Detection of the source of autonomous ALD hypersecretion: CT or RMI of the adrenal glands Adrenal veins sampling (n. 55) 131 I -6β-norcholesterol scintigraphy (n. 24) Normalization of the ALD/PRA ratio after adrenalectomy

7 DEMOGRAPHIC, HEMODYNAMIC AND METABOLIC DATA IN BASAL CONDITION IN PATIENTS WHO UNDERWENT SURGERY (GROUP A) AND IN PATIENTS TREATED WITH PHARMOCOLOGICAL THERAPY (GROUP B). SURGERY (A) SPIRONOLACTONE (B) P< Gender 2M, 38F 32M, 9F Age, yrs. (range) 47.8 ± 1.5 (2-75) 5.4 ± 1.5 (33-74) NS Duration of HT, yrs. 7.4 ± ±.9 NS Clinic SBP, mmhg ± ± 3.1 NS Clinic DBP, mmhg 98.2 ± ± 1.6 NS Medication number 1.84 ± ±.17 NS Serum K, meq/l 3.1 ± ±.6,438 Ur Na, meq/ 24 h 85. ± ± 8.6 NS ALD/PRA ratio ± ± 34.4 NS PRA, ng/ml/h.33 ±.4.37 ±.6 NS Plasma ALD, ng/ml 53.6 ± ± 12.5 NS Captopril test (ALD 4h), ng/dl 41.9 ± ± 4.3 NS Saline load (ALD 2h), ng/dl 42.5 ± ,4 ± 2,,4 BMI, kg/m² 26.2 ±, ±.7,54 Plasma Glucose, mg/dl 92.4 ± ±2. NS Total Cholesterol, mg/dl 19.2 ± ± 4.7 NS HDL Cholesterol, mg/dl 53.5 ± ±2.1 NS LDL Cholesterol, mg/dl 118. ± ± 4.3 NS Triglycerides, mg/dl 17.4 ± ± 8.6 NS Data are given as mean ± SE M=male, F=female, BMI=body mass index, HT=Hypertension, SBP and DBP=systolic and diastolic blood pressure, PRA = Plasma Renin Activity, ALD= aldosterone, K= potassium,na= sodium

8 ECHOCARDIOGRAPHIC DATA AND CAROTID ULTRASOUND IN GROUP A AND GROUP B LVDd, mm SURGERY (A) SPIRONOLACTONE (B) P< ± ±.61 NS LV mass, g/mq ± ± 4.5 NS LV mass/height 2.7, g/m ± ± 1.68 NS PWd, mm 1.27 ± ±.22 NS IVSd, mm 1.89 ± ±.28 NS L Ad, mm ± ±.63 NS Carotid IMT*, mm 1.14 ± ±.1.2 Data are given as mean ± SE LVDd= left ventricular diastolic dimension, LV = left ventricular, PWd= posterior wall dimension, IVSd= intraventricular septum dimension, LAd= left atrial dimension, IMT= intima media thickness,* the greater thickness between common and internal carotid arteries of both sides is reported

9 DEMOGRAPHIC, HEMODYNAMIC AND METABOLIC DATA IN BASAL CONDITION IN PATIENTS WHO UNDERWENT SURGERY (GROUP A) AND IN PATIENTS TREATED WITH PHARMOCOLOGICAL THERAPY (GROUP B). SURGERY (A) SPIRONOLACTONE (B) P< Gender 2M, 38F 32M, 9F Age, yrs. (range) 47.8 ± 1.5 (2-75) 5.4 ± 1.5 (33-74) NS Duration of HT, yrs. 7.4 ± ±.9 NS Clinic SBP, mmhg ± ± 3.1 NS Clinic DBP, mmhg 98.2 ± ± 1.6 NS Drugs number 1.84 ± ±.17 NS Serum K, meq/l 3.1 ± ±.6,438 Ur Na, meq/ 24 h 85. ± ± 8.6 NS ALD/PRA ratio ± ± 34.4 NS PRA, ng/ml/h.33 ±.4.37 ±.6 NS Plasma ALD, ng/ml 53.6 ± ± 12.5 NS Captopril test (ALD 4h), ng/dl 41.9 ± ± 4.3 NS Saline load (ALD 2h), ng/dl 42.5 ± ,4 ± 2,,4 BMI, kg/m² 26.2 ±, ±.7,54 Plasma Glucose, mg/dl 92.4 ± ±2. NS Total Cholesterol, mg/dl 19.2 ± ± 4.7 NS HDL Cholesterol, mg/dl 53.5 ± ±2.1 NS LDL Cholesterol, mg/dl 118. ± ± 4.3 NS Triglycerides, mg/dl 17.4 ± ± 8.6 NS Data are given as mean ± SE M=male, F=female, BMI=body mass index, HT=Hypertension, SBP and DBP=systolic and diastolic blood pressure, PRA = Plasma Renin Activity, ALD= aldosterone, K= potassium,na= sodium

10 RESULTS

11 SISTOLIC AND DIASTOLIC BLOOD PRESSURE BEFORE AND AFTER TREATMENT: GROUP A versus GROUP B Clinic SBP (mmhg) Clinic DBP (mmhg) ± ± 2.9 P<.6 between groups (NS) P <.1 vs Basal Basal Follow-up ± 2.5 P<.1 vs basal ± 1.7 P<.1 vs basal P<.8 between groups Basal Follow-up % Reduction % Reduction GROUP A GROUP B P< % 9.8 % P< % 7.4 %

12 OUTCOMES IN BLOOD PRESSURE VALUES AFTER ADRENALECTOMY (A) AND PHARMACOLOGICAL THERAPY (B). GROUP A GROUP B % 7% 5% CURE (BP <14/9, no drugs) 38% 36% 47% MARKED IMPROVEMENT (BP <14/9 on the same or reduced amount medication) 5% 17% MILD IMPROVEMENT (reduction in SBP or DBP > 1%, without achieving normotension) UNCHANGED Medication Number Basal Medication Number Follow-up GROUP A 1.84 ± ±.12.1 GROUP B 1,78 ± ±.16.2 P<

13 COMPARISON BETWEEN MEAN ABSOLUTE REDUCTION AND MEAN PERCENTAGE REDUCTION IN LV MASS AND LV MASS/h AFTER RECEIVING BOTH TREATMENTS ± 3.5 GROUP A GROUP B NS vs basal 3 P <.19 LV mass (g/mq) LV mass/h ( g/m 2.7 ) ± 4. P<.4 vs basal P<.9 between groups (NS) Basal Follow-up ± 1.4 NS vs basal ± 2.5 P<.5 vs basal P<.2 between groups % Reduction % Reduction %.6 % P < % 1.57 % Basal Follow-up

14 PERCENTAGE OF LV HYPERTROPHY IN BASAL CONDITION AND FOLLOW-UP: GROUP A versus GROUP B 9 8 LV HYPERTROPHY % % 79 % 38 % 8 % GROUP A GROUP B 1 Basal Follow-up HYPERTROPHY = LVMI > 125 M/11F LVMI/h > 51

15 CONCLUSION Surgical treatment of Conn s Disease result in: Better blood pressure control Improvement of echocardiographic parameters Low percentage of complications

16 THANK YOU FOR YOUR ATTENTION