Alban Redheuil1, Anne Blanchard2, Helena Pereira3, Zainab Raissouni4, Aurelien Lorthioir5, Gilles Soulat5, Rosa Vargas-Poussou6, Laurence Amar2, Jean-Louis Paul6, Dominique Helley3, Michel Azizi2, Nadjia Kachenoura7, Elie Mousseaux8. 1. Department of Radiology, Hôpital Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Laboratoire d'Imagerie Biomédicale, National Centre for Scientific Research, French Institute of Health and Medical Research, Sorbonne Université, Paris, France; Institute of Cardiometabolism and Nutrition, Paris, France. 2. Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Biological & Statistic, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; Department of Cardiology, Center for Clinical Investigation 1418, French Institute of Health and Medical Research, Paris, France. 3. Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Biological & Statistic, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France. 4. Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; Department of Cardiology, Center for Clinical Investigation 1418, French Institute of Health and Medical Research, Paris, France; Department of Cardiology, Tangier Medical School, Abdelmalek Essaâdi University, Tétouan, Morocco. 5. Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Biological & Statistic, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; Paris Cardiovascular Research Center, French Institute of Health and Medical Research, Paris, France. 6. Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Biological & Statistic, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France. 7. Laboratoire d'Imagerie Biomédicale, National Centre for Scientific Research, French Institute of Health and Medical Research, Sorbonne Université, Paris, France; Institute of Cardiometabolism and Nutrition, Paris, France. 8. Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Biological & Statistic, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; Paris Cardiovascular Research Center, French Institute of Health and Medical Research, Paris, France. Electronic address: elie.mousseaux@aphp.fr.
Abstract
OBJECTIVES: This study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans. BACKGROUND: Experimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake. METHODS: The study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo. RESULTS: Median plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m2 vs. 82 ± 15 ml/m2; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP. CONCLUSIONS: Only primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).
OBJECTIVES: This study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans. BACKGROUND: Experimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake. METHODS: The study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo. RESULTS: Median plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m2 vs. 82 ± 15 ml/m2; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP. CONCLUSIONS: Only primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).