高血压人群原发性醛固酮增多症患者代谢改变的性别特异性研究

doi:10.12114/j.issn.1007-9572.2019.00.636

摘要/Abstract

摘要： 背景　多项研究报道原发性醛固酮增多症（PA）与糖代谢紊乱和代谢综合征的发生密切相关，然而有些研究并未发现PA和原发性高血压病（EH）患者中代谢紊乱的差异。研究报道在肥胖男性中醛固酮与胰岛素敏感性无关，通过盐皮质激素受体拮抗剂（MRA）阻断醛固酮作用好像在女性中更有效。PA患者的代谢改变可能存在性别特异性。目的　回顾性对比分析不同性别PA与EH患者代谢紊乱的特点及差异。方法　选择2009—2010年新疆维吾尔自治区人民医院高血压诊疗中心连续住院的高血压患者为研究对象。按照美国内分泌学会PA诊疗指南，最终确诊127例患者为PA，259例为不确定PA，672例为EH。根据性别和年龄（±1岁）的匹配标准，将PA患者与EH患者以1∶3的比例进行匹配，有124例PA患者与372例EH患者完成了匹配。比较不同性别PA与EH患者各代谢指标水平，并采用线性回归分析PA对代谢相关指标的影响。结果　男性PA患者血压水平明显高于EH患者〔（151±19）/（101±12）mm Hg比（142±20）/（97±15）mm Hg，P<0.05〕，女性患者两者间血压水平未见明显差异〔（139±14）/（91±10）mm Hg比（139±19）/（92±12）mm Hg，P>0.05〕。女性PA患者的总胆固醇水平明显低于EH患者（P<0.05）。总体上，不同性别PA和EH患者间代谢综合征和糖代谢紊乱的检出率未见明显差异（P>0.05）。但在肥胖女性患者中，PA高血糖症的检出率明显高于EH（60.0%比25.0%，P<0.05）。未在男性中发现PA与EH患者间代谢紊乱的明显差异（P>0.05）。多元线性回归分析结果显示，在纳入年龄、收缩压、舒张压、肌酐、尿酸、三酰甘油为自变量的模型中，仅在肥胖女性个体中，盐水后醛固酮与血糖独立相关。结论　男性PA患者血压水平明显高于EH，而血脂水平较低。肥胖女性PA患者糖代谢异常的比例明显高于EH患者，男性患者没有这种差异。肥胖女性盐水后醛固酮水平与高血糖症独立相关，PA中的代谢改变可能存在性别特异性。

关键词: 醛固酮增多症, 代谢紊乱, 糖代谢, 性别因素

Abstract: Background　Many studies have reported that primary aldosteronism（PA） is associated with the development of glycometabolic disorders and metabolic syndrome（MS）．However，some studies have not found differences in metabolic disorders between patients with PA and essential hypertension（EH）．Recent studies have reported that aldosterone is not associated with insulin sensitivity in obese men，and blockade of aldosterone action via mineralocorticoid receptor antagonists（MRA） appears to be more effective in women.There may be exist sex-specific differences in metabolic changes in PA patients.Objective　To compare and analyze retrospectively the characteristics and differences of metabolic disorders in PA patients and EH patients with different genders.Methods　Patients with hypertension who were hospitalized continuously in Hypertension Center of the People's Hospital of the Xinjiang Uygur Autonomous Region from 2009 to 2010 were included in this study.According to the guidelines of the American Endocrine Society，127 patients were diagnosed as PA；259 patients were diagnosed as undetermined PA；and 672 patients were diagnosed as EH.According to the matching criteria of sex and age（±1 year old），PA patients and EH patients were matched in a ratio of 1∶3 and finally 124 PA patients were matched with 372 EH patients.Metabolic indicators of PA patients and EH patients with different genders were compared，and the effect of PA on related metabolic indicators was analyzed by linear regression.Results　The blood pressure of PA patients was significantly higher than that of EH patients in males〔（151±19）/（101±12） mm Hg vs.（142±20）/（97±15） mm Hg，P<0.05〕，but no significant difference was found between PA patients and EH patients in females〔（139±14）/（91±10）mm Hg vs.（139±19）/（92±12）mm Hg，P>0.05〕．The levels of total cholesterol in PA patients were significantly lower than those in EH patients in females（P<0.05）．Overall，there was no significant difference in the prevalence of MS and glycometabolic disorders between PA patients and EH patients with different genders.However，the prevalence of hyperglycemia in PA patients was significantly higher than that in EH patients in obese females（60.0% vs. 25.0%，P<0.05）．There were no significant differences in metabolic disorders between PA patients and EH patients in males（P>0.05）．Multivariate linear regression analysis showed that aldosterone in post-saline infusion test was independently associated with blood glucose only in obese females in the model which age，systolic blood pressure，diastolic blood pressure，creatinine，uric acid and triglyceride were included as independent variables.Conclusion　The blood pressure of PA patients is significantly higher than that of EH patients in males，while the blood lipid level is lower.The proportion of abnormal glucose metabolism in obese female PA patients is significantly higher than that in EH patients，but no difference is found in male patients.Aldosterone level in post-saline infusion test is independently associated with hyperglycemia in obese females.There may be sex-specific differences in metabolic changes in PA patients.

Key words: Hyperaldosteronism, Metabolic disorders, Glycometabolism, Sex factors

荣利伟,骆秦,王梦卉,等. 高血压人群原发性醛固酮增多症患者代谢改变的性别特异性研究[J]. 中国全科医学, 2019, 22(34): 4225-4233. DOI: 10.12114/j.issn.1007-9572.2019.00.636.
RONG Liwei,LUO Qin,WANG Menghui, et al. Sex Specificity of Metabolic Changes in Hypertensive Patients with Primary Aldosteronism　[J]. Chinese General Practice, 2019, 22(34): 4225-4233. DOI: 10.12114/j.issn.1007-9572.2019.00.636.

参考文献

［1］PIADITIS G，MARKOU A，PAPANASTASIOUL L，et al．Progress in aldosteronism：a review of the prevalence of primary aldosteronism in pre-hypertension and hypertension［J］．European Journal of Endocrinology，2015，172（5）：R191-203．DOI：10.1530/EJE-14-0537.
［2］DOUMA S，PETIDIS K，DOUMAS M，et al．Prevalence of primary hyperaldosteronism in resistant hypertension：a retrospective observational study［J］．Lancet，2008，371（9628）：1921-1926．DOI：10.1016/S0140-6736（08）60834-X.
［3］MONTICONE S，D'ASCENZO F，MORETTI C，et al．Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension：a systematic review and meta-analysis［J］．Lancet Diabetes & Endocrinology，2017，6（1）：41-50．DOI：10.1016/S2213-8587（17）30319-4.
［4］BLASI E R，ROCHA R，RUDOLPH A E，et al．Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats［J］．Kidney International，2003，63（5）：1791-1800．DOI：10.1046/j.1523-1755.2003.00929.x.
［5］HANSLIK G，WALLASCHOFSKI H，DIETZ A，et al．Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn's Registry［J］．European Journal of Endocrinology，2015，173（5）：665-675.
［6］SCHMIDT B M W，SCHMIEDER R E．Aldosterone-induced cardiac damage：focus on blood pressure independent effects［J］．American Journal of Hypertension，2003，16（1）：80-86．DOI：10.1530/EJE-15-0450.
［7］MILLIEZ P，GIRERD X，PLOUIN P F，et al．Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism［J］．Journal of the American College of Cardiology，2005，45（8）：1243-1248．DOI：10.1016/j.jacc.2005.01.015.
［8］MONTICONE S，BURRELLO J，TIZZANI D，et al．Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice［J］．Journal of the American College of Cardiology，2017，69（14）：1811-1820．DOI：10.1016/j.jacc.2017.01.052.
［9］LIM J S，PARK S，PARK S I，et al．Cardiac dysfunction in association with increased inflammatory markers in primary aldosteronism［J］．Endocrinology & Metabolism，2016，31（4）：567-576．DOI：10.3803/EnM.2016.31.4.567.
［10］PETRAMALA L，VIOLI F，LETIZIA C．Aldosterone-induced oxidative stress：a potential mechanism of aldosterone autonomy in primary aldosteronism［J］．Journal of Hypertension，2014，32（11）：2280-2281．DOI：10.1097/HJH.0000000000000376.
［11］LUTHER J M．Effects of aldosterone on insulin sensitivity and secretion［J］．Steroids，2014，91：54-60．DOI：10.1016/j.steroids.2014.08.016.
［12］CHATTERJEE R，YEH H C，SHAFI T，et al．Serum and dietary potassium and risk of incident type 2 diabetes mellitus［J］．Archives of Internal Medicine，2010，170（19）：1745-1751．DOI：10.1001/archinternmed.2010.362.
［13］JIN H M，ZHOU D C，GU H F，et al．Antioxidant N-acetylcysteine protects pancreatic β-cells against aldosterone-induced oxidative stress and apoptosis in female db/db mice and insulin-producing MIN6 cells［J］．Endocrinology，2013，154（11）：4068-4077．DOI：10.1210/en.2013-1115.
［14］LUTHER J M，LUO P，KREGER M T，et al．Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets［J］．Diabetologia，2011，54（8）：2152-2163．DOI：10.1007/s00125-011-2158-9.
［15］RONCONI V，TURCHI F，RILLI S，et al．Metabolic syndrome in primary aldosteronism and essential hypertension：relationship to adiponectin gene variants［J］．Nutrition Metabolism & Cardiovascular Diseases，2010，20（2）：93-100．DOI：10.1016/j.numecd.2009.03.007.
［16］MOSTBECK G．Is primary aldosteronism associated with diabetes mellitus? Results of the German Conn's Registry［J］．Hormone and Metabolic Research，2010，42（6）：435-439．DOI：10.1055/s-0029-1246189.
［17］MATROZOVA J，STEICHEN O，AMAR L，et al．Fasting plasma glucose and serum lipids in patients with primary aldosteronism［J］．Hypertension，2009，53（4）：605-610．DOI：10.1161/HYPERTENSIONAHA.108.122002.
［18］EHRHART-BORNSTEIN M，LAMOUNIER-ZEPTER V，SCHRAVEN A，et al．Human adipocytes secrete mineralocorticoid-releasing factors［J］．Proceedings of the National Academy of Sciences，2003，100（24）：14211-14216．DOI：10.1073/pnas.2336140100.
［19］SCHüTTEN M T J，KUSTERS Y H A M，HOUBEN A J H M，
et al．Aldosterone is not associated with metabolic and microvascular insulin sensitivity in abdominally obese men［J］．Journal of Clinical Endocrinology & Metabolism，2017，103（2）：759-767．DOI：10.1210/jc.2017-01541.
［20］GOODFRIEND T L，KELLEY D E，GOODPASTER B H，et al．Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women［J］．Obesity Research，1999，7（4）：355-362．DOI：10.1002/j.1550-8528.1999.tb00418.x.
［21］KHOSLA N，KALAITZIDIS R，BAKRIS G L．Predictors of hyperkalemia risk following hypertension control with aldosterone blockade［J］．American Journal of Nephrology，2009，30（5）：418-424．DOI：10.1159/000237742.
［22］HUBY A C，OTVOS L J R，BELIN DE CHANTEMèLE E J，et al．Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice［J］．Hypertension，2016，67（5）：1020-1028．DOI：10.1161/HYPERTENSIONAHA.115.06642.
［23］FUNDER J W，CAREY R M，MANTERO F，et al．The management of primary aldosteronism：case detection，diagnosis，and treatment：an endocrine society clinical practice guideline［J］．The Journal of Clinical Endocrinology & Metabolism，2016，101（5）：1889-1916．DOI：10.1210/jc.2015-4061.
［24］ALBERTI K G M M，ECKEL R H，GRUNDY S M，et al．Harmonizing the metabolic syndrome a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention；National Heart，Lung，and Blood Institute；American Heart Association；World Heart Federation；International Atherosclerosis Society；and International Association for the Study of Obesity［J］．Circulation，2009，120（16）：1640-1645．DOI：10.1161/CIRCULATIONAHA.109.192644.
［25］中华医学会糖尿病学分会代谢综合征研究协作组．中华医学会糖尿病学分会关于代谢综合征的建议［J］．中华糖尿病杂志，2004，12（3）：156-161．DOI：10.3321/j.issn.1006-6187.2004.03.002．http：//www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgtnbzz200403002.
［26］SOMLóOVá Z，WIDIMSKY J，ROSA J，et al．The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism［J］．Journal of Human Hypertension，2010，24（10）：625-630．DOI：10.1038/jhh.2010.65.
［27］SHAMISS A，CARROLL J，ROSENTHAL T．Insulin resistance in secondary hypertension［J］．American Journal of Hypertension，1992，5（1）：26-28．DOI：10.1093/ajh/5.1.26．
［28］CATENA C，LAPENNA R，BAROSELLI S，et al．Insulin sensitivity in patients with primary aldosteronism：a follow-up study［J］．The Journal of Clinical Endocrinology & Metabolism，2006，91（9）：3457-3463．DOI：10.1210/jc.2006-0736.
［29］GIACCHETTI G，RONCONI V，TURCHI F，et al．Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism：an observational study［J］．Journal of Hypertension，2007，25（1）：177-186．DOI：10.1097/HJH.0b013e3280108e6f.
［30］STRAUCH B，WIDIMSKY J，SINDELKA G，et al．Does the treatment of primary hyperaldosteronism influence glucose tolerance?［J］．Physiological Research，2003，52（4）：503-506．DOI：10.1086/367939．
［31］RANADE K，WU K D，RISCH N，et al．Genetic variation in aldosterone synthase predicts plasma glucose levels［J］．Proceedings of the National Academy of Sciences，2001，98（23）：13219-13224．DOI：10.1073/pnas.221467098.
［32］COLUSSI G，CATENA C，LAPENNA R，et al．Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients［J］．Diabetes Care，2007，30（9）：2349-2354．DOI：10.2337/dc07-0525.
［33］GARG R，HURWITZ S，WILLIAMS G H，et al．Aldosterone production and insulin resistance in healthy adults［J］．Journal of Clinical Endocrinology & Metabolism，2010，95（4）：1986-1990．DOI：10.1210/jc.2009-2521.
［34］CALLE C，CAMPIóN J，GARCíA-ARENCIBIA M，et al．Transcriptional inhibition of the human insulin receptor gene by aldosterone［J］．Journal of Steroid Biochemistry and Molecular Biology，2003，84（5）：543-553．DOI：10.1016/S0960-0760（03）00072-4．
［35］HUBY A C，ANTONOVA G，GROENENDYK J，et al．The adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion，which promotes endothelial dysfunction and cardiac fibrosis［J］．Circulation，2015，132（22）：2134-2145．DOI：10.1161/CIRCULATIONAHA.115.018226.
［36］BELIN D C E J，MUTA K，MINTZ J，et al．Protein tyrosine phosphatase 1b，a major regulator of leptin-mediated control of cardiovascular function［J］．Circulation，2009，120（9）：753-763．DOI：10.1161/CIRCULATIONAHA.109.853077.
［37］BOSTICK B，HABIBI J，DEMARCO V G，et al．Mineralocorticoid receptor blockade prevents western diet-induced diastolic dysfunction in female mice［J］．American Journal of Physiology-Heart and Circulatory Physiology，2015，308（9）：H1126-1135．DOI：10.1152/ajpheart.00898.2014.
［38］JIA G，HABIBI J，AROOR A R，et al．Endothelial mineralocorticoid receptor mediates diet induced aortic stiffness in females［J］．Circulation Research，2016，118（6）：935-943．DOI：10.1161/CIRCRESAHA.115.308269．
［39］JIA G，HABIBI J，DEMARCO V G，et al．Endothelial mineralocorticoid receptor deletion prevents diet-induced cardiac diastolic dysfunction in females［J］．Hypertension，2015，66（6）：1159-1167．DOI：10.1161/HYPERTENSIONAHA.115.06015.
［40］DAVEL A P，LU Q，MOSS M E，et al．Sex-pecific mechanisms of resistance vessel endothelial dysfunction induced by cardiometabolic risk factors［J］．J Am Heart Assoc，2018，7（4）：e007675． DOI：10.1161/JAHA.117.007675.
［41］CHADDERDON S M，BELCIK J T，BADER L，et al．Temporal changes in skeletal muscle capillary responses and endothelial-derived vasodilators in obesity-related insulin resistance［J］．Diabetes，2016，65（8）：2249-2257．DOI：10.2337/db15-1574.
［42］LEOPOLD J A，DAM A，MARON B A，et al．Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity［J］．Nature Medicine，2007，13：189-197．DOI：10.1038/nm1545.
［43］LASTRA G，DHUPER S，JOHNSON M S，et al．Salt，aldosterone，and insulin resistance：impact on the cardiovascular system［J］．Nature Reviews Cardiology，2010，7（10）：577-584．DOI：10.1038/nrcardio.2010.123.
［44］CHEN A H，LI H Y，WU V C，et al．Serum dehydroepiandrosterone sulfate concentration is lower in women with primary aldosteronism［J］．Journal of the Renin-Angiotensin- Aldosterone System，2015，16（1）：137-144．DOI：10.1177/1470320313483843.
［45］TRAISH A M，KANG H P，SAAD F，et al．Dehydroepiandrosterone（DHEA）：a precursor steroid or an active hormone in human physiology（CME）［J］．Journal of Sexual Medicine，2011，8（11）：2960-2982．DOI：10.1111/j.1743-6109.2011.02523.x.

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