Prospective Study on Primary Aldosteronism in Resistant Hypertension

Atrial Fibrillation Clinical Trial

— PrePARe  

Official title:

Prospective Cross-sectional Study on Prevalence of Primary Aldosteronism in Resistant Hypertension and Association With Cardiometabolic Complications

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04213963
• Other study ID #: The PrePARe Study
• Status: Recruiting
• Start date: September 1, 2011
• Est. completion date: October 31, 2025

Study information

• Verified date: November 2020
• Source: University of Turin, Italy
• Contact: Mauro M Maccario, MD
• Phone: 00390116709559
• Email: mauro.maccario[@]unito.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Prevalence of primary aldosteronism (PA) in resistant hypertension is not clear. In addition, emerging evidence supports the role of elevated serum aldosterone in promoting cardiovascular disease, independently from high blood pressure (BP) levels, but current data on this issue are heterogeneous.

Description:

PA is the most frequent form of secondary hypertension, with a prevalence that increases with the severity of hypertension. The wide variation of the reported PA prevalence is due to different study design and population. Very few data derive from well designed prospective study. Additional problems in the interpretation of study results are the different diagnostic cut-off used in various centers and the low diffusion of the adrenal vein sampling, that has a central role in the PA diagnosis. Resistant hypertension (RH) is a condition of insufficient BP control, despite appropriate lifestyle measures and treatment with at least 3 drugs at full dose, including a diuretic, in patients whose adherence to therapy has been confirmed. The primary aim of our study is define prospectively the prevalence of PA in RH. Moreover, emerging evidence supports the crucial role of elevated serum aldosterone in promoting cardiovascular disease, independently from high BP levels. Aldosterone improves oxidative stress, inflammation, impairs insulin metabolic signaling, reduced endothelial-mediated vasorelaxation and is associated to cardiovascular and renal abnormalities. However, current data on the contribution of PA on cardiometabolic complications have heterogeneous results. The secondary outcome of our study is to investigate prospectively the association of PA with cardiometabolic complications in a cohort of patients with RH.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 31, 2025
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• age over 18 and under 80 years old;
• diagnosis of resistant hypertension defined as: uncontrolled blood pressure at ambulatory blood pressure measurement (ABPM), despite the use of at least 3 antihypertensive drugs at full dose, including a diuretic.

Exclusion Criteria:

• age under 18 or over 80 years old;
• pseudo-resistant hypertension (poor medication adherence, high salt intake);
• previous cardiovascular disease;
• insulin treated diabetes mellitus;
• other than primary aldosteronism cause of secondary hypertension (obstructive sleep apnea, renal artery stenosis, pheochromocytoma/paraganglioma, primary hyperparathyroidism, autonomous cortisol secretion or over hypercortisolism);
• liver cirrhosis;
• chronic heart failure;
• known malignant neoplasm;
• chronic disease with major organ involvement;
• excessive alcohol ingestion;
• current steroids assumption;
• use of sympathomimetic drugs;
• use of contraceptives.

Related Conditions & MeSH terms

• Aortic Ectasia
• Atrial Fibrillation
• Hyperaldosteronism
• Hypertension
• Hypertensive End-Organ Damage
• Primary Aldosteronism
• Refractory Hypertension
• Resistant Hypertension

Locations

Country	Name	City	State
Italy	Division of Endocrinology, Diabetology and Metabolism; University of Turin	Torino	Piemonte

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (24)

Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002 Dec;40(6):892-6. — View Citation

Chandran P. Resistant or difficult-to-control hypertension. N Engl J Med. 2006 Nov 2;355(18):1934; author reply 1934. — View Citation

Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N, Papadopoulos N, Vogiatzis K, Zamboulis C. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet. 2008 Jun 7;371(9628):1921 — View Citation

Eide IK, Torjesen PA, Drolsum A, Babovic A, Lilledahl NP. Low-renin status in therapy-resistant hypertension: a clue to efficient treatment. J Hypertens. 2004 Nov;22(11):2217-26. — View Citation

Fallo F, Della Mea P, Sonino N, Bertello C, Ermani M, Vettor R, Veglio F, Mulatero P. Adiponectin and insulin sensitivity in primary aldosteronism. Am J Hypertens. 2007 Aug;20(8):855-61. — View Citation

Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M, Rabbia F, Federspil G, Mulatero P. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab. 2006 Feb;91(2):454-9. Epub 2005 Nov 15. — View Citation

Fiebeler A, Luft FC. The mineralocorticoid receptor and oxidative stress. Heart Fail Rev. 2005 Jan;10(1):47-52. Review. — View Citation

Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 Ma — View Citation

Giacchetti G, Sechi LA, Rilli S, Carey RM. The renin-angiotensin-aldosterone system, glucose metabolism and diabetes. Trends Endocrinol Metab. 2005 Apr;16(3):120-6. Review. — View Citation

Iacobellis G, Petramala L, Cotesta D, Pergolini M, Zinnamosca L, Cianci R, De Toma G, Sciomer S, Letizia C. Adipokines and cardiometabolic profile in primary hyperaldosteronism. J Clin Endocrinol Metab. 2010 May;95(5):2391-8. doi: 10.1210/jc.2009-2204. Ep — View Citation

Lucatello B, Benso A, Tabaro I, Capello E, Caprino MP, Marafetti L, Rossato D, Oleandri SE, Ghigo E, Maccario M. Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion. Eur J — View Citation

Marzano L, Colussi G, Sechi LA, Catena C. Adrenalectomy is comparable with medical treatment for reduction of left ventricular mass in primary aldosteronism: meta-analysis of long-term studies. Am J Hypertens. 2015 Mar;28(3):312-8. doi: 10.1093/ajh/hpu154 — View Citation

Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, Gabetti L, Mengozzi G, Williams TA, Rabbia F, Veglio F, Mulatero P. Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice. J Am Coll Cardiol — View Citation

Morrow JD. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86. Epub 2004 Dec 9. Review. — View Citation

Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, Gomez-Sanchez CE, Veglio F, Young WF Jr. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004 — View Citation

Prior RL, Cao G. In vivo total antioxidant capacity: comparison of different analytical methods. Free Radic Biol Med. 1999 Dec;27(11-12):1173-81. Review. — View Citation

Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, M — View Citation

Rossi GP, Maiolino G, Flego A, Belfiore A, Bernini G, Fabris B, Ferri C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Muiesan ML, Mannelli M, Negro A, Palumbo G, Parenti G, Rossi E, Mantero F; PAPY Study Investigators. Adrenalectomy Lowers Incident A — View Citation

Rossi GP, Sechi LA, Giacchetti G, Ronconi V, Strazzullo P, Funder JW. Primary aldosteronism: cardiovascular, renal and metabolic implications. Trends Endocrinol Metab. 2008 Apr;19(3):88-90. doi: 10.1016/j.tem.2008.01.006. Epub 2008 Mar 7. Review. — View Citation

Schmidt BM, Schmieder RE. Aldosterone-induced cardiac damage: focus on blood pressure independent effects. Am J Hypertens. 2003 Jan;16(1):80-6. Review. — View Citation

Strauch B, Zelinka T, Hampf M, Bernhardt R, Widimsky J Jr. Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region. J Hum Hypertens. 2003 May;17(5):349-52. — View Citation

Vassalle C, Pratali L, Boni C, Mercuri A, Ndreu R. An oxidative stress score as a combined measure of the pro-oxidant and anti-oxidant counterparts in patients with coronary artery disease. Clin Biochem. 2008 Oct;41(14-15):1162-7. doi: 10.1016/j.clinbioch — View Citation

Vogt B, Burnier M. Aldosterone and cardiovascular risk. Curr Hypertens Rep. 2009 Dec;11(6):450-5. Review. — View Citation

Whaley-Connell A, Johnson MS, Sowers JR. Aldosterone: role in the cardiometabolic syndrome and resistant hypertension. Prog Cardiovasc Dis. 2010 Mar-Apr;52(5):401-9. doi: 10.1016/j.pcad.2009.12.004. Review. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of diagnosis (prevalence) of primary aldosteronism in prospective cohort of patients with resistant hypertension.	Basal Aldosterone (pg/mL) at baseline.	Baseline.
Primary	Number of diagnosis (prevalence) of primary aldosteronism in prospective cohort of patients with resistant hypertension.	Basal Plasma Renin Activity (PRA, ng/mL/h) at baseline.	Baseline.
Primary	Number of diagnosis (prevalence) of primary aldosteronism in prospective cohort of patients with resistant hypertension.	Aldosterone (pg/mL) post saline infusion test, performed at baseline.	Baseline.
Secondary	Left ventricular hypertrophy in primary aldosteronism and essential resistant hypertension	Left ventricular mass evaluation with Echocardiogram at baseline.	Baseline.
Secondary	Microalbuminuria in primary aldosteronism and essential resistant hypertension.	Albuminuria/Creatininuria ratio (mg/mmoL) at baseline.	Baseline.
Secondary	Intima media thickness > 0.9 mm rate in primary aldosteronism versus essential resistant hypertension.	Intima media thickness values (mm) evaluation with carotid Doppler ultrasound at baseline.	Baseline
Secondary	Chronic kidney disease in primary aldosteronism versus essential resistant hypertension.	Serum creatinine (mg/dL) at baseline.	Baseline.
Secondary	Aortic ectasia in primary aldosteronism versus essential resistant hypertension.	Aortic size (mm) determined with echocardiogram at baseline.	Baseline.
Secondary	Atrial fibrillation in primary aldosteronism versus essential resistant hypertension.	Electrocardiogram (ECG) at baseline.	Baseline.
Secondary	Insulin resistance in primary aldosteronism versus essential resistant hypertension.	Oral glucose tolerance test (OGTT) for determination of glucose (mg/dL) at time 0', 30', 60', 90' and 120' at baseline.	Baseline
Secondary	Insulin resistance in primary aldosteronism versus essential resistant hypertension.	Oral glucose tolerance test (OGTT) for determination of insulin (mg/dL) at time 0', 30', 60', 90' and 120' at baseline.	Baseline.
Secondary	Diabetes mellitus rate in primary aldosteronism versus essential resistant hypertension.	Oral glucose tolerance test (OGTT) for determination of glucose (mg/dL) at time 0' and 120' at baseline.	Baseline.
Secondary	Diabetes mellitus rate in primary aldosteronism versus essential resistant hypertension.	HbA1c (mmol/mol) at baseline.	Baseline.
Secondary	Sodium levels in primary aldosteronism versus essential resistant hypertension.	Serum Sodium (mmol/L) at baseline.	Baseline.
Secondary	Potassium levels in primary aldosteronism versus essential resistant hypertension.	Serum Potassium (mmol/L) at baseline.	Baseline.
Secondary	Oxidative stress in primary aldosteronism versus essential resistant hypertension.	Blood determination of 8-isoprostane (UI/L) at baseline.	Baseline.
Secondary	Oxidative stress in primary aldosteronism versus essential resistant hypertension.	Blood determination of total antioxidant capacity (UI/L) at baseline.	Baseline.
Secondary	Dyslipidemia in primary aldosteronism versus essential resistant hypertension.	Serum triglycerides (mg/dL) at baseline.	Baseline.
Secondary	Dyslipidemia in primary aldosteronism versus essential resistant hypertension.	Serum total-Cholesterol (mg/dL) at baseline.	Baseline.
Secondary	Dyslipidemia in primary aldosteronism versus essential resistant hypertension.	Serum HDL-Cholesterol (mg/dL) at baseline.	Baseline.
Secondary	Dyslipidemia in primary aldosteronism versus essential resistant hypertension.	Serum LDL-Cholesterol (mg/dL) at baseline.	Baseline.