© Borgis - Postępy Nauk Medycznych 9/2016, s. 677-681
*Aleksander Prejbisz, Ewa Warchoł-Celińska, Sylwia Kołodziejczyk-Kruk, Andrzej Januszewicz
Primary hiperaldosteronism – incidence and impact on heart and kidney
Pierwotny hiperaldosteronizm – częstość występowania oraz wpływ na serce i nerki
Department of Hypertension, Institute of Cardiology, Warsaw
Head of Department: Professor Andrzej Januszewicz, MD, PhD
Streszczenie
Na przestrzeni pięciu dekad od czasu pierwszych opisów choroby dokonanych przez Lityńskiego oraz Conna, pierwotny hiperaldosteronizm uznawany był za relatywnie rzadką przyczynę wtórnego nadciśnienia tętniczego, występującą u mniej niż 1% chorych.
Zgodnie z obecnym stanem wiedzy częstość występowania pierwotnego hiperaldosteronizmu w badaniach z wykorzystaniem testów potwierdzających rozpoznanie waha się między 4,6 a 16,5%.
Na przestrzeni ostatnich dekad dokonał się znaczący postęp w zrozumieniu patogenetycznego i genetycznego podłoża, przebiegu klinicznego oraz powikłań sercowo-naczyniowych tej najczęściej występującej przyczyny wtórnego nadciśnienia tętniczego.
Wyniki znaczącej liczby dotychczas przeprowadzonych badań eksperymentalnych i klinicznych wskazują, że podwyższone stężenie aldosteronu ma związek z rozwojem powikłań narządowych, szczególnie w obrębie serca i nerek. Dotychczas zgormadzone dane potwierdzają, że wdrożenie zarówno chirurgicznego, jak i farmakologicznego leczenia pierwotnego hiperaldosteronizmu może korzystnie wpływać na powikłania narządowe, występowanie zdarzeń sercowo-naczyniowych oraz śmiertelność w obserwacji odległej w tej grupie chorych.
Summary
For over five decades after first description of Litynski and clinical characterization by Conn, primary hyperaldosteronism (PA) was generally regarded as a relatively rare cause of hypertension (HT), present in less than 1% of all patients.
Available evidence clearly indicate that the prevalence rate of primary hyperaldosteronism vary from 4.6 to 16.5% in those studies in which confirmatory tests to diagnose were used.
Enormous progress has been made over the past decades in understanding pathogenesis and genetic background, clinical course and cardiovascular complications of this most common cause of secondary HT.
There is also growing body of experimental and clinical studies indicating that prolonged exposure to elevated aldosterone concentration is associated with target organ damage particularly in the heart and kidney. Current evidence convincingly demonstrates that both surgical and medical treatment strategies beneficially affect target organ damage and cardiovascular outcomes and mortality in the long term observation.
Introduction
For over five decades after first description of Litynski and clinical characterization by Conn, primary hyperaldosteronism (PA) was generally regarded as a relatively rare cause of hypertension (HT), present in less than 1% of all patients. However over the past 20 years the prevalence of this clinical condition has been reported to be much higher and is ranging from 10 to 30% in highly selected groups (1-3).
Enormous progress has been made over the past decades in understanding pathogenesis and genetic background, clinical course and cardiovascular complications of this most common cause of secondary HT (3, 4).
Of special note to our current knowledge in PA is the contribution of one of the most distinguished polish clinician and scientist Franciszek Kokot whose classic studies in this field are widely recognized in the world literature. It should be noted that in early 70ties of XX century Kokot et al. presented in Poland the first detailed clinical description of a large group of patients with PA (5, 6).
A substantial body of experimental and clinical evidence about long-term effects of aldosterone excess on the cardiovascular and renal system has been gathered over the last years (3).
Increasing aldosterone levels promote renal sodium retention, potentiate the actions of angiotensin II, impair endothelial function and reduce vascular compliance. Several experimental investigations in salt fed animals documented profibrotic and pro-hypertrophic effects of aldosterone independent of arterial blood pressure (BP) level and circulating plasma volume (1, 2).
Landmark experiments demonstrated that chronic aldosterone infusion causes myocardial fibrosis in rats that are maintained on high-salt diet. In regard of left ventricule hypertrophy (LVH) as an independent risk factor, studies in patients with PA revealed relationship between circulating aldosterone levels and cardiac structure (7-9).
It has been also documented in uninephrectomized and stroke-prone spontaneously hypertensive rats that aldosterone produced intrarenal vascular damage, glomerular injury and tubulointerstitial fibrosis. The animal studies consistently indicate that aldosterone causes tissue damage in the context of inappropriate salt status and might depend on mineralocorticoid receptor (MR) activation reflecting in different tissues increased oxidative stress and impairment of 11 beta-HSD2 activity (10-12).
Therefore, growing body of evidence suggests that exposure to inappropriate aldosterone levels for salt status and/or activation of the MR can produce myocardial and renal tissue injury involving mechanisms that are independent of BP (10).
It has been documented that absolute aldosterone excess in patients with PA has been associated with higher risk of heart, vascular and kidney damage resulting in increased total cardiovascular risk. Also the prevalence of cardiovascular events is higher in patients with PA as compared to those with essential hypertension (EH) (3).
Prevalence
Recent epidemiological studies have shown that serum aldosterone and renin levels and the aldosterone/renin ratio (ARR) correlate with increased BP and the incidence of HT in the general population (3, 13).
Examination of large, community-based sample of nonhypertensive persons showed that increasing aldosterone levels within physiologic range may influence BP and may predispose to hypertension. Recent study documented that in a large cross-sectional cohort of patients ARR determined peripheral and central BP values over a broad range (13).
It is generally accepted that the prevalence of PA varies considerably between different studies among patients with hypertension, depending on patients selection, diagnostic methodology used and severity of arterial HT (3, 14).
Numerous cross-sectional and prospective studies in unselected hypertensive populations have documented that the prevalence of PA is much higher than previously believed and varies significantly between studies ranging from 4.6 to 16.6% when confirmatory tests to diagnose PA were employed (13).
A step-wise increase in the prevalence of PA according to the severity of systolic and diastolic BP elevations has been observed. In the study of Mosso et al. the prevalence of PA varied depending on the severity (stage) of hypertensive disease as defined by the JNC VI. The results showed that the prevalence was similar to that found in normotensive subjects or those with stage 1 (1.99%) but was significantly higher in stages 2 (8.55%) and 3 (13.5%) of the disease (15).
Also PAPY study documented that at the screening test the proportion of patients with PA caused by both APA and IHA increased significantly from 7.2 to 19.5% with the increasing severity of hypertension from grade 1 to grade 3 (16).
However it is still a subject of debate, it has been commonly agreed that resistant hypertension is the condition with the highest probability of detection of PA (3).
Douma et al. documented in a large group of patients with resistant hypertension that although the ARR was positive in about 20% of patients with resistant hypertension, after confirmatory tests the diagnosis resulted in the prevalence of 11.3% in the total study population (17).
Also in the RESIST-Pol study increased ARR was present in 28.4% of and the diagnosis of PA was further confirmed in 15.7% subjects (18).
The results from two German epidemiological studies indicate that the frequency of positive screening results in the subgroup of subjects with resistant hypertension was 11.9% being consistent with other studies (3).
Taken together, many methodological factors may be responsible for the wide variation in the prevalence of PA in hypertensive patients, as they depend on patients selection and can interfere with renin and/or aldosterone measurements affecting the diagnostic accuracy of both screening and diagnostic tests (19, 20). Factors such as posture at the time of sampling, serum potassium levels, renin/aldosterone assays employed, renal function, gender, age and use of antihypertensive drugs are all known to be implicated (21).
Cardiovascular risk and impact on the heart and kidney
A growing body of data coming from longitudinal, retrospective studies supports the presence of increased prevalence of cardiovascular complications in patients with PA as compared with those with EH (7, 8, 10).
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Piśmiennictwo
Funder JW, Carey RM, Fardella C et al.: Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266-3281.
Connell JM, MacKenzie SM, Freel EM et al.: A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocr Rev 2008; 29: 133-154.
Prejbisz A, Warchol-Celinska E, Lenders JW, Januszewicz A: Cardiovascular Risk in Primary Hyperaldosteronism. Horm Metab Res 2015; 47: 973-980.
Asbach E, Williams TA, Reincke M: Recent Developments in Primary Aldosteronism. Exp Clin Endocrinol Diabetes 2016; 124: 335-341.
Kokot F, Kuska J, Luciak M, Gasinski J: Primary hyperaldosteronism syndrome in the light of our own observations. Pol Arch Med Wewn 1971; 47: 33-41.
Kokot F: Primary aldosteronism: facts and suppositions. Kardiol Pol 1971; 14: 1-6.
Rossi GP: Cardiac consequences of aldosterone excess in human hypertension. Am J Hypertens 2006; 19: 10-12.
Catena C, Colussi G, Marzano L, Sechi LA: Aldosterone and the heart: from basic research to clinical evidence. Horm Metab Res 2012; 44: 181-187.
Catena C, Colussi GL, Marzano L, Sechi LA: Predictive factors of left ventricular mass changes after treatment of primary aldosteronism. Horm Metab Res 2012; 44: 188-193.
Sechi LA, Colussi G, Di Fabio A, Catena C: Cardiovascular and renal damage in primary aldosteronism: outcomes after treatment. Am J Hypertens 2010; 23: 1253-1260.
Blasi ER, Rocha R, Rudolph AE et al.: Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63: 1791-1800.
Rocha R, Chander PN, Khanna K et al.: Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998; 31: 451-458.
Piaditis G, Markou A, Papanastasiou L et al.: Progress in aldosteronism: a review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. Eur J Endocrinol 2015; 172: R191-203.
Dekkers T, Prejbisz A, Kool LJ et al.: Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol 2016 Sep; 4(9): 739-746.
Mosso L, Carvajal C, Gonzalez A et al.: Primary aldosteronism and hypertensive disease. Hypertension 2003; 42: 161-165.
Rossi GP, Bernini G, Caliumi C et al.: A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300.
Douma S, Petidis K, Doumas M et al.: Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet 2008; 371: 1921-1926.
Florczak E, Prejbisz A, Szwench-Pietrasz E et al.: Clinical characteristics of patients with resistant hypertension: the RESIST-POL study. J Hum Hypertens 2013; 27: 678-685.
Fischer E, Reuschl S, Quinkler M et al.: Assay characteristics influence the aldosterone to renin ratio as a screening tool for primary aldosteronism: results of the German Conn’s registry. Horm Metab Res 2013; 45: 526-531.
Pilz S, Kienreich K, Gaksch M et al.: Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading. Horm Metab Res 2014; 46: 427-432.
Viola A, Monticone S, Burrello J et al.: Renin and aldosterone measurements in the management of arterial hypertension. Horm Metab Res 2015; 47: 418-426.
Catena C, Colussi G, Nadalini E et al.: Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168: 80-85.
Born-Frontsberg E, Reincke M, Rump LC et al.: Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn’s Registry. J Clin Endocrinol Metab 2009; 94: 1125-1130.
Rossi GP, Cesari M, Letizia C et al.: KCNJ5 gene somatic mutations affect cardiac remodelling but do not preclude cure of high blood pressure and regression of left ventricular hypertrophy in primary aldosteronism. J Hypertens 2014; 32: 1514-1521; discussion 1522.
Milan A, Magnino C, Fabbri A et al.: Left heart morphology and function in primary aldosteronism. High Blood Press Cardiovasc Prev 2012; 19: 11-17.
Indra T, Holaj R, Zelinka T et al.: Left ventricle remodeling in men with moderate to severe volume-dependent hypertension. J Renin Angiotensin Aldosterone Syst 2012; 13(4): 426-434.
Muiesan ML, Salvetti M, Paini A et al.: Inappropriate left ventricular mass in patients with primary aldosteronism. Hypertension 2008; 52: 529-534.
Rossi GP, Cesari M, Cuspidi C et al.: Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension 2013; 62: 62-69.
Gaddam K, Corros C, Pimenta E et al.: Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Hypertension 2010; 55: 1137-1142.
Catena C, Colussi G, Lapenna R et al.: Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007; 50: 911-918.
Sechi LA, Novello M, Lapenna R et al.: Long-term renal outcomes in patients with primary aldosteronism. JAMA 2006; 295: 2638-2645.
Ribstein J, Du Cailar G, Fesler P, Mimran A: Relative glomerular hyperfiltration in primary aldosteronism. J Am Soc Nephrol 2005; 16: 1320-1325.
Reincke M, Rump LC, Quinkler M et al.: Risk factors associated with a low glomerular filtration rate in primary aldosteronism. J Clin Endocrinol Metab 2009; 94: 869-875.
