Downloaded from http://jim.bmj.com/ on January 18, 2016 - Published by group.bmj.com
ORIGINAL ARTICLE
The Relation Between the Degree of Left Ventricular Mass Regression and Serum Potassium Level Change in Patients With Primary Aldosteronism After Adrenalectomy Che-Wei Liao, MD,*† Aaron Chen, MD,‡ Yen-Tin Lin, MD,* Yi-Yao Chang, MD,§ Shuo-Meng Wang, MD, PhD,k Vin-Cent Wu, MD, PhD,* Chi-Sheng Hung, MD,* Kwan-Dun Wu, MD, PhD,* Shih-Chieh Chueh, MD, PhD,¶ Yen-Hung Lin, MD, PhD,* and the TAIPAI Study Group Background: Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy. Methods: We prospectively analyzed 30 patients with aldosteroneproducing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation. Results: Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/ postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (β = −0.287, P = 0.049), ΔSBP (β = 0.518, P = 0.01), and Δserum potassium level (β = −20.471, P = 0.014) were significantly correlated with ΔLVMI. Conclusions: The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression. Key Words: adrenalectomy, aldosteronism, left ventricular hypertrophy, potassium (J Investig Med 2015;63: 816–820)
P
rimary aldosteronism (PA) is characterized by the inappropriate production of aldosterone and is currently considered as the most prevalent cause of secondary hypertension.1–3 The incidence of PA is around 5% to 13% of hypertensive patients.4 From the *Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei; †Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; ‡Woodhull Medical and Mental Hospital, Brooklyn, NY; §Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City; kDepartment of Urology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; and ¶Department of Urology, Cleveland Clinic, Cleveland, OH. Received March 3, 2015, and in revised form April 23, 2015. Accepted for publication April 26, 2015. Supported by the National Taiwan University Hospital (NTUH 102-S2096, NTUH 103-M254, NTUH 103-S2447, NTUH 103-S2347), National Taiwan University (UN102-060), and Taiwan National Science Council (NSC 102-2314-B-002-056, NSC 102-2314-B-002-078-MY3). Reprints: Yen-Hung Lin, MD, PhD, Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei, Taiwan. E-mail: [email protected]. Copyright © 2015 by The American Federation for Medical Research ISSN: 1081-5589 DOI: 10.1097/JIM.0000000000000215
816
Despite the hemodynamic effects derived from high blood pressure (BP), excessive aldosterone directly influences the cardiovascular system, causing larger left ventricular (LV) mass, increased myocardial fibrosis, and increased vascular stiffness in patients with PA.5–10 Therefore, patients with PA suffer more cardiovascular events and atrial fibrillation, which are independent of BP effects, than patients with essential hypertension. Treatment of PA, either by surgical or medical management, results in regression of LV hypertrophy as well as improvement of myocardial fibrosis and vascular stiffness.10–12 Hypokalemia, a major characteristic of PA, plays an important role in various cardiovascular diseases and affects both cardiac structure and function.13 Potassium deficiency not only leads to change in cardiac structure and increased cardiac fibrosis14,15 but also influences myocardial contractile and relaxation responses.16,17 Hypokalemia is also associated with damage in the cardiovascular system in patients with PA. First, patients with hypokalemic PA have been observed to have a higher cardiovascular morbidity than patients with normokalemic PA.18 Second, in our previous study, serum potassium level was significantly associated with LV mass in patients with PA.19 Furthermore, in one of our more recent studies, patients with hypokalemic PA had a greater increase in vascular stiffness compared with patients with normokalemic PA.20 This implies that hypokalemia may therefore play a role in the damage of the cardiovascular system in patients with PA. Although there are many studies demonstrating the effect of adrenalectomy on LV mass regression, the predictive factors still require elucidation. In a retrospective study from our group, preoperative LV mass index (LVMI) and differences between preoperation/postoperation systolic BP (SBP) were associated with the degree of LVMI decrease.21 However, that study was limited by its retrospective setting and irregular follow-up duration. Furthermore, it is also interesting to study whether serum potassium or its change after adrenalectomy influences the degree of LVMI regression after adrenalectomy. For these reasons, we conducted this prospective study to investigate the predictive factors of LVMI regression in patients with PA after adrenalectomy.
MATERIALS AND METHODS Patients This prospective study enrolled 30 patients with aldosteroneproducing adenoma (APA) who were scheduled to receive adrenalectomy and registered in the Taiwan Primary Aldosteronism Investigation (TAIPAI) database from October 2006 to September 2009. The database was constructed for quality assurance by 2 medical centers (National Taiwan University Hospital [NTUH], Taipei; Taipei Medical University Hospital, Taipei), 3 metropolitan hospitals (Cardinal Tien Hospital, New Taipei City; Taipei Tzu Chi Hospital, New Taipei City; YunLin Branch of NTUH, Douliou City), and 2 local hospitals Journal of Investigative Medicine • Volume 63, Number 6, August 2015
Copyright © 2015 American Federation for Medical Research. Unauthorized reproduction of this article is prohibited.
Downloaded from http://jim.bmj.com/ on January 18, 2016 - Published by group.bmj.com
Journal of Investigative Medicine • Volume 63, Number 6, August 2015
TABLE 1. Clinical Data of the Study Patients Patient Characteristics
PA (N = 30)
Age, y Male Creatinine, mg/dL SBP, mm Hg DBP, mm Hg Potassium, mmol/L PAC, ng/dL PRA, ng/mL per h No. hypertension medication type Hypertension medication type CCB ACEI/ARB Diuretics α-Blocker β-Blocker
46 (11) 16 (53) 1.0 (0.2) 152 (21) 94 (13) 3.4 (0.8) 54.7 (30.7) 0.9 (2.4) 1.9 (1.0) 22 (73) 10 (33) 5 (17) 10 (33) 10 (33)
Values are presented as mean (SD). ACEI indicates angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker.
(Hsin-Chu Branch of NTUH, Hsin-Chu City; Zhongxing Branch of Taipei City Hospital, Taipei).22 The serum potassium levels were measured during the first evaluation of these patients and 1 year after adrenalectomy. Plasma renin activity (PRA) was measured as the generation of angiotensin I in vitro using a commercially available radioimmune assay kit (Cisbio, Bedford, MA), and plasma aldosterone concentration (PAC) was measured by radioimmune assay with commercial kits (Aldosterone Maia Kit; Adaltis Italia, Bologna, Italy). Medical histories, including demographics and medication, were carefully recorded. This study was approved by the institutional review board of National Taiwan University Hospital, Taipei, Taiwan, and all patients signed informed consent.
Factors of LVMI Regression in PA
ultrasonography were performed on each patient. Chamber dimensions, wall thickness, and the LV ejection fraction (M-mode) were measured via the parasternal long-axis view. The LVMI was calculated according to the method by Devereux and Reichek.28 The ΔLVMI was defined as the difference of LVMI after operation (postoperative LVMI minus preoperative LVMI).
Statistics Data were expressed as mean (SD). Pearson correlation test was used to analyze the association between LVMI (or ΔLVMI) and their determinants. Data of PAC, PRA, and ARR were log transformed because of non-normality and was tested by the Kolmogorov-Smirnov test. Significant determinants derived from Pearson correlation test (P < 0.05) were then tested by a multivariate linear regression test with stepwise subset selection to identify independent factors predicting ΔLVMI. Statistical analyses were performed with SPSS for Mac version 21 (SPSS Inc, Chicago, IL). A P value of
ORIGINAL ARTICLE
The Relation Between the Degree of Left Ventricular Mass Regression and Serum Potassium Level Change in Patients With Primary Aldosteronism After Adrenalectomy Che-Wei Liao, MD,*† Aaron Chen, MD,‡ Yen-Tin Lin, MD,* Yi-Yao Chang, MD,§ Shuo-Meng Wang, MD, PhD,k Vin-Cent Wu, MD, PhD,* Chi-Sheng Hung, MD,* Kwan-Dun Wu, MD, PhD,* Shih-Chieh Chueh, MD, PhD,¶ Yen-Hung Lin, MD, PhD,* and the TAIPAI Study Group Background: Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy. Methods: We prospectively analyzed 30 patients with aldosteroneproducing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation. Results: Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/ postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (β = −0.287, P = 0.049), ΔSBP (β = 0.518, P = 0.01), and Δserum potassium level (β = −20.471, P = 0.014) were significantly correlated with ΔLVMI. Conclusions: The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression. Key Words: adrenalectomy, aldosteronism, left ventricular hypertrophy, potassium (J Investig Med 2015;63: 816–820)
P
rimary aldosteronism (PA) is characterized by the inappropriate production of aldosterone and is currently considered as the most prevalent cause of secondary hypertension.1–3 The incidence of PA is around 5% to 13% of hypertensive patients.4 From the *Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei; †Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; ‡Woodhull Medical and Mental Hospital, Brooklyn, NY; §Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City; kDepartment of Urology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; and ¶Department of Urology, Cleveland Clinic, Cleveland, OH. Received March 3, 2015, and in revised form April 23, 2015. Accepted for publication April 26, 2015. Supported by the National Taiwan University Hospital (NTUH 102-S2096, NTUH 103-M254, NTUH 103-S2447, NTUH 103-S2347), National Taiwan University (UN102-060), and Taiwan National Science Council (NSC 102-2314-B-002-056, NSC 102-2314-B-002-078-MY3). Reprints: Yen-Hung Lin, MD, PhD, Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei, Taiwan. E-mail: [email protected]. Copyright © 2015 by The American Federation for Medical Research ISSN: 1081-5589 DOI: 10.1097/JIM.0000000000000215
816
Despite the hemodynamic effects derived from high blood pressure (BP), excessive aldosterone directly influences the cardiovascular system, causing larger left ventricular (LV) mass, increased myocardial fibrosis, and increased vascular stiffness in patients with PA.5–10 Therefore, patients with PA suffer more cardiovascular events and atrial fibrillation, which are independent of BP effects, than patients with essential hypertension. Treatment of PA, either by surgical or medical management, results in regression of LV hypertrophy as well as improvement of myocardial fibrosis and vascular stiffness.10–12 Hypokalemia, a major characteristic of PA, plays an important role in various cardiovascular diseases and affects both cardiac structure and function.13 Potassium deficiency not only leads to change in cardiac structure and increased cardiac fibrosis14,15 but also influences myocardial contractile and relaxation responses.16,17 Hypokalemia is also associated with damage in the cardiovascular system in patients with PA. First, patients with hypokalemic PA have been observed to have a higher cardiovascular morbidity than patients with normokalemic PA.18 Second, in our previous study, serum potassium level was significantly associated with LV mass in patients with PA.19 Furthermore, in one of our more recent studies, patients with hypokalemic PA had a greater increase in vascular stiffness compared with patients with normokalemic PA.20 This implies that hypokalemia may therefore play a role in the damage of the cardiovascular system in patients with PA. Although there are many studies demonstrating the effect of adrenalectomy on LV mass regression, the predictive factors still require elucidation. In a retrospective study from our group, preoperative LV mass index (LVMI) and differences between preoperation/postoperation systolic BP (SBP) were associated with the degree of LVMI decrease.21 However, that study was limited by its retrospective setting and irregular follow-up duration. Furthermore, it is also interesting to study whether serum potassium or its change after adrenalectomy influences the degree of LVMI regression after adrenalectomy. For these reasons, we conducted this prospective study to investigate the predictive factors of LVMI regression in patients with PA after adrenalectomy.
MATERIALS AND METHODS Patients This prospective study enrolled 30 patients with aldosteroneproducing adenoma (APA) who were scheduled to receive adrenalectomy and registered in the Taiwan Primary Aldosteronism Investigation (TAIPAI) database from October 2006 to September 2009. The database was constructed for quality assurance by 2 medical centers (National Taiwan University Hospital [NTUH], Taipei; Taipei Medical University Hospital, Taipei), 3 metropolitan hospitals (Cardinal Tien Hospital, New Taipei City; Taipei Tzu Chi Hospital, New Taipei City; YunLin Branch of NTUH, Douliou City), and 2 local hospitals Journal of Investigative Medicine • Volume 63, Number 6, August 2015
Copyright © 2015 American Federation for Medical Research. Unauthorized reproduction of this article is prohibited.
Downloaded from http://jim.bmj.com/ on January 18, 2016 - Published by group.bmj.com
Journal of Investigative Medicine • Volume 63, Number 6, August 2015
TABLE 1. Clinical Data of the Study Patients Patient Characteristics
PA (N = 30)
Age, y Male Creatinine, mg/dL SBP, mm Hg DBP, mm Hg Potassium, mmol/L PAC, ng/dL PRA, ng/mL per h No. hypertension medication type Hypertension medication type CCB ACEI/ARB Diuretics α-Blocker β-Blocker
46 (11) 16 (53) 1.0 (0.2) 152 (21) 94 (13) 3.4 (0.8) 54.7 (30.7) 0.9 (2.4) 1.9 (1.0) 22 (73) 10 (33) 5 (17) 10 (33) 10 (33)
Values are presented as mean (SD). ACEI indicates angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker.
(Hsin-Chu Branch of NTUH, Hsin-Chu City; Zhongxing Branch of Taipei City Hospital, Taipei).22 The serum potassium levels were measured during the first evaluation of these patients and 1 year after adrenalectomy. Plasma renin activity (PRA) was measured as the generation of angiotensin I in vitro using a commercially available radioimmune assay kit (Cisbio, Bedford, MA), and plasma aldosterone concentration (PAC) was measured by radioimmune assay with commercial kits (Aldosterone Maia Kit; Adaltis Italia, Bologna, Italy). Medical histories, including demographics and medication, were carefully recorded. This study was approved by the institutional review board of National Taiwan University Hospital, Taipei, Taiwan, and all patients signed informed consent.
Factors of LVMI Regression in PA
ultrasonography were performed on each patient. Chamber dimensions, wall thickness, and the LV ejection fraction (M-mode) were measured via the parasternal long-axis view. The LVMI was calculated according to the method by Devereux and Reichek.28 The ΔLVMI was defined as the difference of LVMI after operation (postoperative LVMI minus preoperative LVMI).
Statistics Data were expressed as mean (SD). Pearson correlation test was used to analyze the association between LVMI (or ΔLVMI) and their determinants. Data of PAC, PRA, and ARR were log transformed because of non-normality and was tested by the Kolmogorov-Smirnov test. Significant determinants derived from Pearson correlation test (P < 0.05) were then tested by a multivariate linear regression test with stepwise subset selection to identify independent factors predicting ΔLVMI. Statistical analyses were performed with SPSS for Mac version 21 (SPSS Inc, Chicago, IL). A P value of
