李秀梅,許澎
? 論著 ?
男性急性冠狀動(dòng)脈綜合征患者性激素、血脂和hs-CRP相關(guān)性研究
李秀梅,許澎
目的探討男性急性冠狀動(dòng)脈綜合征患者性激素睪酮水平、血脂及高敏C反應(yīng)蛋白(hs-CRP)的相關(guān)性。方法連續(xù)收集2012年3月~10月于上海市第五人民醫(yī)院心內(nèi)科因胸悶、胸痛住院的男性患者共284例,年齡50~80歲。根據(jù)冠狀動(dòng)脈(冠脈)造影結(jié)果分為急性冠脈綜合征組(97例)和穩(wěn)定性心絞痛組(105例),非冠心病組(82例)。根據(jù)冠狀動(dòng)脈造影結(jié)果分為三支病變、兩支病變、單支病變。檢測(cè)所有患者血脂、性激素睪酮和hs-CRP水平。并分析各檢測(cè)指標(biāo)間的相關(guān)性。結(jié)果與急性冠脈綜合征組比較,穩(wěn)定性心絞痛組睪酮和三酰甘油(TG)水平升高,差異有統(tǒng)計(jì)學(xué)意義(P均<0.05),hs-CRP降低,差異有顯著統(tǒng)計(jì)學(xué)意義(P<0.01)。與急性冠脈綜合征組比較,非冠心病組睪酮和TG升高,hs-CRP降低,有顯著統(tǒng)計(jì)學(xué)差異(P均<0.01)。非冠心病組較穩(wěn)定性心絞痛組總膽固醇(TC)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)以及睪酮水平升高,hs-CRP降低,差異有統(tǒng)計(jì)學(xué)意義(P均<0.05)。男性冠心病睪酮與血脂、hs-CRP水平無(wú)明顯相關(guān)(P均>0.05)。單支病變、雙支病變以及三支病變睪酮水平無(wú)統(tǒng)計(jì)學(xué)差異(P均>0.05)。結(jié)論男性急性冠脈綜合癥患者睪酮水平下降、hs-CRP升高,未發(fā)現(xiàn)睪酮與血脂、hs-CRP相關(guān),不同冠狀動(dòng)脈病變程度睪酮水平亦無(wú)統(tǒng)計(jì)學(xué)差異。
冠狀動(dòng)脈粥樣硬化性疾病;雄激素;CRP;血脂
男性較同年齡女性冠狀動(dòng)脈硬化性心臟?。ü谛牟。┌l(fā)病率高,激素起著重要的作用。大量文獻(xiàn)證實(shí)雌激素對(duì)女性冠心病發(fā)展有保護(hù)作用,而男性雄激素睪酮是否影響冠心病發(fā)生發(fā)展,尚不清楚。研究證實(shí)雄激素睪酮與男性冠心病相關(guān),冠心病患者較對(duì)照組睪酮水平降低[1]。冠心病患者游離睪酮(FT)、總睪酮(TT)與總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白膽固醇(LDL-C)呈顯著負(fù)相關(guān),與高密度脂蛋白膽固醇(HDL-C)呈正相關(guān)[2]。高敏C反應(yīng)蛋白(hs-CRP)是冠心病的危險(xiǎn)因素。本研究旨在探討男性急性冠狀動(dòng)脈(冠脈)綜合征患者雄激素睪酮水平與血脂、hs-CRP的關(guān)系,進(jìn)一步了解其在男性冠心病中的作用。
1.1 研究對(duì)象和分組連續(xù)收集2012年3月~10月于上海市第五人民醫(yī)院心內(nèi)科因胸悶、胸痛住院的男性患者共284例,年齡50~80歲。根據(jù)冠狀動(dòng)脈造影結(jié)果分為急性冠脈綜合征組(97例)和穩(wěn)定性心絞痛組(105例)以及結(jié)果陰性的非冠心病組(82例)。所有冠心病患者均符合1979年WHO專家委員會(huì)確定的診斷標(biāo)準(zhǔn),并且均行冠脈造影證實(shí)。排除風(fēng)濕性心臟病、心肌病、先天性心臟病等其他心臟病,嚴(yán)重肝腎功能不全、既往口服激素類以及降血脂藥物的患者。根據(jù)冠狀動(dòng)脈造影結(jié)果,冠心病診斷標(biāo)準(zhǔn)以主要血管(即左前降支、左回旋支、右冠狀動(dòng)脈、左主干)管腔狹窄≥50%和(或)其一級(jí)分支>70%,分為單支病變,雙支病變及三支病變。
1.2 方法收集所有患者年齡、高血壓以及糖尿病病史。所有患者入院后在行冠狀動(dòng)脈造影術(shù)前抽血檢測(cè)性激素、血脂及hs-CRP。性激素為血清睪酮,測(cè)定采用放射免疫法(GC-911X放射免疫計(jì)數(shù)儀、T放射免疫試劑盒),按說(shuō)明書要求進(jìn)行操作。酶聯(lián)免疫吸附法檢測(cè)hs-CRP。
1.3 統(tǒng)計(jì)學(xué)方法所有數(shù)據(jù)使用SPSS 13.0進(jìn)行分析。計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差(±s)表示,組間均數(shù)的比較采用方差分析,計(jì)數(shù)資料采用例數(shù)(構(gòu)成比)表示,組間比較采用χ2檢驗(yàn)。相關(guān)分析采用Pearson's相關(guān)。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1 三組激素和血脂水平三組年齡、合并高血壓比例以及合并糖尿病比例差異無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)。與急性冠脈綜合征組比較,穩(wěn)定性心絞痛組睪酮和TG水平升高,差異有統(tǒng)計(jì)學(xué)意義(P均<0.05),hs-CRP降低,差異有顯著統(tǒng)計(jì)學(xué)意義(P<0.01)。與急性冠脈綜合征組比較,非冠心病組睪酮和TG升高,hs-CRP降低,有顯著統(tǒng)計(jì)學(xué)差異(P均<0.01)。非冠心病組較穩(wěn)定性心絞痛組TC、HDL-C、LDL-C以及睪酮水平升高,hs-CRP降低,差異有統(tǒng)計(jì)學(xué)意義(P均<0.05)(表1)。
2.2 血脂、hs-CRP和激素相關(guān)性相關(guān)性分析,男性急性冠脈綜合癥睪酮與血脂、hs-CRP水平無(wú)明顯相關(guān)(P均>0.05)(表2)。
2.3 冠狀動(dòng)脈不同病變程度激素水平比較單支病變、雙支病變以及三支病變睪酮水平無(wú)統(tǒng)計(jì)學(xué)差異(P均>0.05)(表3)。
冠心病危險(xiǎn)因素除高血壓、吸煙、高血脂、肥胖外,不同性別罹患風(fēng)險(xiǎn)存在差別[3]。研究已證實(shí)男性冠心病患者睪酮水平降低[1],與本研究結(jié)果一致。有研究表明雄激素降低增加了冠心病死亡率[4],其與冠心病預(yù)后的相關(guān)性尚不清楚。本研究未顯示冠狀動(dòng)脈不同病變程度的睪酮水平有統(tǒng)計(jì)學(xué)差異,這與新近一項(xiàng)研究結(jié)果相似[5]。但也有研究顯示三支病變患者睪酮水平更低[7]。
健康男性青春期后血漿HDL-C水平下降,LDL-C和TG水平升高,隨著年齡的增長(zhǎng)體內(nèi)睪酮水平逐漸下降,HDL-C輕度升高,提示睪酮影響血脂水平[6]。有研究表明冠心病患者游離睪酮、總睪酮與TC、TG和LDL-C呈顯著負(fù)相關(guān),與HDL-C呈正相關(guān)[2],Blouin等[8]認(rèn)為雄激素對(duì)調(diào)節(jié)脂肪分布起關(guān)鍵作用,可減少脂肪生成,降低脂肪酸合成,增強(qiáng)脂解作用等。有些研究則認(rèn)為睪酮與血脂無(wú)相關(guān)性,而與雌激素有關(guān)[7],其機(jī)制為睪酮轉(zhuǎn)為雌激素導(dǎo)致睪酮水平降低,雌激素激發(fā)了LDL-C的降解,減少了LDL-C的氧化[9]。雌激素通過(guò)和受體結(jié)合,作用于血管產(chǎn)生舒張作用,同時(shí)還參與調(diào)節(jié)前列腺素、一氧化氮的分泌、抑制血管平滑肌細(xì)胞的增生[10]。
hs-CRP是冠心病的獨(dú)立危險(xiǎn)因子。本研究中急性冠脈綜合征患者h(yuǎn)s-CRP顯著升高。研究認(rèn)為睪酮也參與了炎癥過(guò)程,可能的機(jī)制為中性粒細(xì)胞表達(dá)CD11/CD18,可刺激炎癥因子的分泌,睪酮通過(guò)與受體結(jié)合,影響核因子NF-κB和活化蛋白-1的活化,間接抑制中性粒細(xì)胞表達(dá)CD11/ CD18,從而抑制炎癥因子的分泌[11]。
有實(shí)驗(yàn)表明,不穩(wěn)定型心絞痛患者游離睪酮水平與白介素-6、腫瘤壞死因子-α呈負(fù)相關(guān)[12]。冠心病合并糖尿病患者,總睪酮與hs-CRP呈負(fù)相關(guān)(r=0.21,P=0.01),而且胰島素治療的患者較未接受胰島素治療者游離睪酮更低[13]。而另外一些研究則表明老年男性睪酮替代治療后,睪酮對(duì)hs-CRP并未產(chǎn)生影響,而絕經(jīng)后女性雌激素和hs-CRP的相關(guān)性更加明確,雌激素治療后hs-CRP降低[14]。本研究顯示冠心病組hs-CRP較非冠心病組升高,而且急性冠脈綜合征患者h(yuǎn)s-CRP升高更明顯,但冠心病組睪酮和hs-CRP無(wú)明顯相關(guān)(P=0.836)。
急性冠脈綜合征患者睪酮下降,與其死亡率升高有關(guān),而且動(dòng)脈粥樣硬化患者睪酮下降[15]。睪酮對(duì)冠心病的影響可通過(guò)其他冠心病危險(xiǎn)因素起作用,男性性腺功能減退導(dǎo)致了代謝綜合癥,增加了冠心病的發(fā)生[16],男性前列腺癌性腺功能減退者舒張壓升高,而經(jīng)過(guò)9個(gè)月的睪酮替代治療后可使舒張壓降低[17]。
總之,急性冠脈綜合征患者睪酮下降、hs-CRP升高,男性睪酮可能通過(guò)血脂、炎癥等過(guò)程參與冠心病的發(fā)生發(fā)展,但本研究未發(fā)現(xiàn)睪酮與血脂、hs-CRP的相關(guān)性。
[1] Sieminska L,Wojciechowska C,Swietochowska E,et al. Serum free testosterone in men with coronary artery atherosclerosis[J]. Med Sci Monit,2003,9(5):CR162-CR6.
[2] Wu FC,von Eckardstein A. Androgens and coronary artery disease[J]. Endocrin Rev,2003,24(2):183-217.
[3] Ng MK. New perspectives on Mars and Venus: unravelling the role of androgens in gender differences in cardiovascular biology and disease[J]. Heart Lung Circ,2007,16(3):185-92.
[4] Laughlin GA,Barrett-Connor E,Bergstrom J. Low serum testosterone and mortality in older men[J]. J Clin Endocrinol Metab,2008,93(1):68-75.
[5] Davoodi G,Amirezadegan A,Borumand MA,et al. The relationship between level of androgenic hormones and coronary artery disease in men[J]. Cardiovascular J Afr,2007,18(6):362-6.
[6] 胥學(xué)偉,李小鷹. 雄性激素和血脂的關(guān)系[J]. 中華老年心腦血管病雜志,2003,5(4):283-4.
[7] Wranicz JK,Cygankiewicz I,Rosiaka M,et al. The relationship between sex hormones and lipid profile in men with coronary artery disease[J]. Int J Cardiol,2005,101(1):105-10.
[8] Blouin K,Boivin A,Tchernof A. Androgens and body fat distribution[J]. J Steroid Biochem Mol Biol,2008,108(3-5):272-80.
[9] Wagner JD,Clarkson TB,St Clair RW,et al. Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys[J]. J Clin Invest,1991,88(6):1995-2002.
[10] Tolbert T,Oparil S. Effects of estrogen on cardiovascular responses of premenopausal monkeys[J]. Am J Hypertens,2001,14:186S-93S.
[11] Pfeilschifter J,Koditz R,Pfohl M,et al. Changes in proinflammatory cytokine activity after menopause[J]. Endor Rev,2002,23(1):90-119.
[12] 夏大勝,曹晶,王彥歐,等. 男性不穩(wěn)定型心紋痛患者血清雄激素與中性粒細(xì)胞表達(dá)CD11/CD18及其與細(xì)胞因子的關(guān)系[J]. 天津醫(yī)科大學(xué)學(xué)報(bào),2005,33(10):632-5.
[13] Ponikowska B,Jankowska EA,Maj J,et al. Gonadal and adrenal androgen deficiencies as independent predictor of increased cardiovascular mortality in men with type II diabetes mellitus and stable coronary artery disease[J]. Int J Cardiol,2010,143(3):343-8.
[14] Cushman M,Legault C,Barrett-Connor E,et al. Effect of postmenopausal hormones on in ammation-sensitive proteins.The PostmenopausalEstrogen/ProgestinInterventions (PEPI)Study[J]. Circulation,1999,100:717-22.
[15] Hak A,Witteman J,de Jong F,et al. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study[J]. J Clin Endocrinol Metab,2002,87(8):3632-9.
[16] Traish AM,Guay A,Feeley R,et al. The dark side of testosterone de ciency: I. metabolic syndrome and erectile dysfunction[J]. J Androl,2009,30(1):10-22.
[17] Smith MR,Bennett S,Evans L,et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer[J]. J Clin Endocrinol Metab,2001,86(9):4261-7.
Correlation among sex hormones, blood fat and high-sensitivity C-reactive protein in male patients with acute coronary syndrome
LI Xiu-mei*, XU Peng.*Department of Cardiology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
ObjectiveTo investigate the correlation among sex hormones, blood fat and high-sensitivity C-reactive protein (hs-CRP) in male patients with acute coronary syndrome (ACS).MethodsMale patients (n=284, aged from 50 to 80) hospitalized due to chest oppression and chest pain were chosen from Mar. 2012 to Oct. 2012. All patients were divided, according to outcomes of coronary angiography (CAG), into acute coronary syndrome group (ACS group, n=97), stable angina pectoris group (SAP group, n=105) and non-CHD group (n=82). The outcomes of CAG showed that coronary artery lesion included 3-vessel lesion, 2-vessel lesion and 1-vessel lesion. The levels of blood fat, testosterone and hs-CRP were detected and correlation among these indexes was analyzed.ResultsThe levels of testosterone and triglyceride (TG) increased (all P<0.05), and hs-CRP level decreased (P<0.01) in SAP group compared with ACS group. The levels of testosterone and TG increased and hs-CRP level decreased in non-CHD group compared with ACS group (all P<0.01). The levels of total cholesterol (TC), high-density lipoproteincholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and testosterone increased, and hs-CRP level decreased in non-CHD group compared with SAP group (all P<0.05). The level of testosterone was not correlated to levels of blood fat and hs-CRP (all P>0.05). The level of testosterone had no statistical difference in patients with 1-vessel lesion, 2-vessel lesion or 3-vessel lesion (all P>0.05).ConclusionThe level of testosterone decreases and hs-CRP level increases in male patients with ACS. The correlation has not been found among testosterone, blood fat and hs-CRP. There is no statistical difference in patients with different severity of coronary lesion.
Coronary atherosclerosis; Androgens; C-reactive protein; Blood fat
R541.4
A
1674-4055(2015)02-0242-03
2014-12-03)
(責(zé)任編輯:姚雪莉)
200240 上海,復(fù)旦大學(xué)附屬上海市第五人民醫(yī)院心內(nèi)科
李秀梅,E-mail:lxm388256@163.com
10.3969/j.1674-4055.2015.02.27