Variability in lipid profile among patients presented with acute myocardial infarction, unstable angina and stable angina pectoris

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1 Europen Review for Medicl nd Phrmcologicl Sciences 2014; 18: Vribility in lipid profile mong ptients presented with cute myocrdil infrction, unstble ngin nd stble ngin pectoris N. YANG, J.-P. FENG, G. CHEN, L. KOU, Y. LI, P. REN, L.-L. ZHAO, Q. QIN 1 Deprtment of Crdiology, nd 1 Deprtment of Crdiology Medicine, Tinjin Chest Hospitl, Tinjin, Chin Abstrct. OBJECTIVE: Despite the mply evidence nd guidelines in treting coronry rtery disese (CAD) with lipid-lowering therpy, physicins still hve concerns in treting cute myocrdil infrction (AMI) ptients who hve the low serum lipid level. We explored the dequcy of lipid-lowering therpy in treting AMI ptients. PATIENTS AND METHODS: Over 3000 CAD lipid profile dt were collected, their dt were divided into 3 groups (AMI; stble ngin pectoris (SAP) nd unstble ngin pectoris (UAP) group) bsed their clinicl chrcteristics. Sttisticl nlyses were performed to compre their bseline lipid levels nd clinicl feture. RESULTS: The totl cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) nd highdensity lipoprotein cholesterol (HDL-c) level in AMI ptients were the lowest, followed by UAP ptient group nd SAP ptient group. There were significnt differences in white blood count (WBC) nd ejection frction (EF) between 3 groups. A good correltion ws confirmed between EF% nd the lipid prmeters of TC, LDLc, HDL-c, non-hdl-c. WBC did not correlte with the lipid except HDL-c. AMI is n cute inflmmtory rection tht is ccompnied with the chnge of lipid level. CONCLUSIONS: Although the level of TC, LDLc nd HDL-c re lower in AMI, but it is relted with cute inflmmtory rection during the rupture of therosclerotic plques. Lipid-lowering therpy should not be delyed in treting AMI ptients with lower lipid level. Key Words: Lipid, Coronry Artery disese, Inflmmtory. Introduction Aberrnt serum totl cholesterol (TC) nd low-density lipoprotein cholesterol (LDL-c) contribute significntly to the development of therosclerosis 1 ; they re lso clinicl mnifesttions of coronry rtery disese. Numerous studies hve demonstrted tht lipid-lowering therpy reduces the risk of first or recurrent crdiovsculr events nd improves survivl in ptients with coronry rtery disese (CAD) 2,3. Despite the convincing evidence nd guidelines, lipid-lowering therpy hs been less thn optiml, especilly in ptients hd cute myocrdil infrction. Fyfe et l 4 noted pprent decreses of TC in hospitliztion of ptients with n cute coronry syndrome (ACS) in 1971, lter studies demonstrted tht cute myocrdil infrction (AMI) cuses n cute-phse response, which includes incresed cholesterol synthesis s well s concomitnt increse in low-density lipoprotein cholesterol receptor ctivity, which results in reduction of LDL-c 5-7. Pn et l 8 reported seril mesurements result of 75 cses of AMI; they indicted decline of ll lipids level except lipoprotein () in plsm fter ptients were dmitted to hospitl. Mo 9 found high level of lipid in erly stge of AMI. Wu et l 10 reported tht serum level of LDL-c hs no difference mong cute myocrdil infrction (AMI), unstble ngin pectoris (UAP) nd stble ngin pectoris (SAP) ptients. The differences of lipid levels were reported by studies derived from reltive smll popultion. Therefore, mny physicins discount serum lipids obtined immeditely upon dmission for AMI, in prt becuse of their understnding tht such mesurements re unrelible due to n erly decrese in TC nd LDL-c fter AMI. Recently, Wng et l 11 investigted 1242 AMI ptients from 12 hospitls in Beijing, Chin, nd they reported tht lipid regulting gents were used only 43.6%. Accurte knowledge of bseline lipid levels my ffect the selection of lipidlowering therpy, nd recognition of the potentil need for djunctive lipid therpy. This knowledge my lso influence the ptient s willingness to dhere to recommendtion for long-term lipidlowering therpy. Corresponding Author: Qin Qin, MD; e-mil: qinqin6999@163.com 3761

2 N. Yng, J.-P. Feng, G. Chen, L. Kou, Y. Li, P. Ren, L.-L. Zho, Q. Qin Thus, to better understnd the role of lipid regulting gent, it is necessry to collect dditionl observtion dt to shed light on the chrcteristics of presenting lipid levels of AMI ptients. Here we report the retrospective nlyses of lrge dt set of CAD collected from crdiology deprtment in Tinjin Chest Hospitl, Chin, to explore the reltion between bseline lipid levels nd clinicl mnifesttions of coronry rtery disese. Ptients nd Methods This study ws pproved by n Institutionl Review Bord of Tinjin Chest Hospitl, Chin (TXH ). The study ws conducted in ccordnce with good clinicl prctice, ll pplicble regultory requirements nd the guiding principles of the Declrtion of Helsinki. Written informed consent ws obtined from ll subjects prior to dmission to the study. Between November 2007 nd July 2011, totl of 3245 ptients dmitted to crdic deprtment of our Hospitl. Blood smples were obtined fter ptients were fsting on the first morning fter dmission. The serum lipid profile, blood routine, troponin I, cretine kinse, cretinine, liver function, were mesured using stndrd hospitl protocols. The blood routine, troponin I, cretine kinse nd cretinine were performed immeditely when the dmitted ptient ws suspected s n AMI cse. The demogrphic dt of ge, gender, cigrette smoking, hypertension (dignose criteri 12 ), dibetes mellitus (dignose criteri 13 ), nd echocrdiogrphy were obtined from ech ptient. According to their clinicl chrcteristics, the ptients were divided into 3 groups: AMI group included ptients with cute myocrdil infrction, who were dignosed ccording to the criteri of Myocrdil Infrction 14. UAP group included ptients who confirmed with dignosis of unstble ngin pectoris ccording to Brundwrd s clssifiction 15, nd ngiogrphic evidence (documented stenosis > 50% by the Americn Hert Assocition clssifiction in one or more principle coronry rteries). SAP group included ptients with stble ngin pectoris who ws defined bsed on symptoms, specificlly typicl precordil chest pin from crdic ischemi during exercise nd from the findings of coronry ngiogrphy (documented severe stenosis of > 50% by the Americn Hert Asso- cition clssifiction in one or more principl coronry rteries). Ptients dt were excluded if they were: (1) the onset of AMI ws more thn 24 hours; (2) lipid-lowering therpy for t lest the preceding 3 months; (3) cute liver disese or heptic dysfunction; (4) serum cretinine 2.0 mg/dl; (5) severe nemi; (6) systemic or pulmonry embolus; (7) cute infectious diseses nd chronic inflmmtory diseses; (8) hyperthyroidism nd hypothyroidism. Sttisticl Anlysis Ptients were divided into 3 groups of AMI, SAP nd UAP. Wilcoxon rnk sum tests were used for continuous vribles nd Chi-squre tests for ctegoricl vribles. Dt re presented s mens ± stndrd division (SD), or s percentge of bseline vlue. The differences of the lipid levels between the tretment groups were evluted by Kruskl-Wllis Test. The reltionships between the white blood count (WBC), ejection frction (EF) nd the lipid, lipoprotein vribles were evluted by liner correltion. p vlues < 0.05 were considered s sttisticlly significnt. Results Bsic Dt The dt from 3245 ptients were included in the finl nlysis. The men ge of the popultion ws 60 ± 10, nd 63.8% were mle. The clinicl chrcteristics of the ptients in the three groups were shown in Tble I. There ws no significnt difference mong the 3 groups regrding their ge nd lcohol consumption hbits, while ll other ptient chrcteristics were significnt difference (p 0.01). Demogrphic Dt Comprison Results For AMI ptients, 36.5% of them hve dibetes mellitus nd 60.6% being smokers, which were higher thn the other 2 groups. The serum levels of the lipids, lipoproteins, nd polipoproteins t dmission re shown in Tble II. We observed higher level of TC, TG, HDL-c, Apo A1, Apo B100, Non-HDL/HDL nd LDL/HDL in SAP nd UAP group s compred with AMI group (p 0.05). The differences were significntly (p 0.01) in TC, LDL-c, non-hdl-c, Apo A1, Apo B100, Non-HDL/HDL, TC/HDL nd LDL/HDL in SAP group s compred with AMI group. 3762

3 Lipid profile mong coronry rtery disese Tble I. Demogrphic dt of 3 groups recruited ptients. AMI (n = 876) UAP (n = 1875) SAP (n = 494) Age (ys) 61 ± ± 9 60 ± 9 Gender (M/F) 650/ / /208 Hypertension (%) 490 (55.9) 1142 (60.9) 314 (63.6) Dibetes mellitus (%) 320 (36.5) 524 (27.9) 102 (20.6) Drinking (%) 146 (16.7) 365 (19.5) 89 (18.0) Smoking (%) 531 (60.6) 967 (51.6) 261 (52.8) Prior Stroke (%) 82 (9.4) 241 (12.9) 36 (7.3) Atorvsttin clcium user (40 mg) 458 (52.3%) 803 (42.8%) 256 (51.8%) Fluvsttin user (80 mg QN) 418 (47.7%) 1072 (57.2%) 238 (48.2%) Significnt difference mong the 3 groups (p 0.01). Tble II. Comprison of different lipid levels between groups. AMI (n = 876) UAP (n = 1875) SAP (n = 494) Totl cholesterol (mg/dl) ± ± ± 46.8,c Triglycerides (mg/dl) ± ± ± LDL cholesterol (mg/dl) ± ± ± 41.9,c HDL cholesterol (mg/dl) 40.7 ± ± ± 13.2 Non-HDL cholesterol (mg/dl) ± ± ± 45.2,c Apolipoprotein A1 (mg/dl) 98.6 ± ± ± 20.7,c Apolipoprotein B100 (mg/dl) 90.6 ± ± ± 25.2,c Lp (mg/dl) 30.7 ± ± ± 23.4 Non-HDL/HDL 3.7 ± ± ± 1.5,c TC/HDL 4.9 ± ± ± 2.3 b,c LDL/HDL 3.1 ± ± ± 1.2,c Significnt difference mong the 3 groups (p 0.01). Lbortory Mesurement Results As we cn see from Tble III, routine blood tests nd EF comprison between groups reveled there were significnt differences in WBC, neutrophils, lymphocytes nd EF mong 3 groups. Ptients in AMI group hd higher WBC nd neutrophils level while SAP group hd the lowest. There ws significntly different EF between the 3 groups (p 0.05), while the others mesurements prmeters (monocytes, hemoglobin, Pltelet) were not significntly different. Correltion Anlysis We nlyzed the correltion between WBC, EF nd lipids prmeters of TC, LDL-c, HDL-c, non-hdl-c, the results were listed in Tble IV, s we cn see, nd good correltion ws con- Tble III. Different blood count nd EF between groups. AMI (n = 876) UAP (n = 1875) SAP (n = 494) p vlue WBC ( 10 9 /L) 9.3 ± ± ± Neutrophils (%) 71.5 ± ± ± Lymphocytes (%) 19.9 ± ± ± Monocytes (%) 7.0 ± ± ± Hemoglobin (g/ L) ± ± ± Pltelet ( 10 9 /L) ± ± ± EF (%) 56.2 ± ± ± Significnt difference mong the 3 groups. 3763

4 N. Yng, J.-P. Feng, G. Chen, L. Kou, Y. Li, P. Ren, L.-L. Zho, Q. Qin Tble IV. Correltions (R) between lipid profile nd WBC nd EF. TC LDL-c HDL-c non-hdl-c Lipoprotein WBC b EF (%) b b b Correltion significnt t 0.05; b Correltion significnt t firmed between EF nd the lipids prmeters, while WBC ws not correlted with other lipids prmeter except for HDL-c. Discussion Fyfe et l 4 firstly reported the decreses in TC during hospitliztion of ptients with n ACS, lter studies reported TC levels decresed in 2 dys, the gretest decresing occurs during dys 4 to 12, nd the levels rnged from 24% to 70% below bseline from different studies 16-20, nd remin stble fter AMI when compred with bseline level 21,22. However, these erlier reports cnnot led to cler conclusion or explin why ischemi my cuse the chnges of lipid profile. Our mjor finding in this study ws tht TC nd LDL-c were the lowest in AMI group, followed by UAP nd SAP group. UAP ptient group hd the intermedite level of TC nd LDL-c; these findings imply tht the level of TC nd LDL-c were negtively relted with stbility of therosclerotic plque. Although no myocrdil dmge occurred in UAP ptients, the level of TC nd LDL-c in UAP were between the AMI nd SAP. Some erly studies hve shown tht AMI cuse n cute-phse response, which includes incresed cholesterol synthesis s well s concomitnt increse in LDL-c receptor ctivity, which results in reduction of LDL-c 5,17,23,24. Myocrdil necrosis produces n inflmmtory process tht results in migrtion of neutrophils into the injured region 25,26. Our results lso confirmed tht the WBC nd neutrophils in AMI group were highest in 3 groups, which imply tht the inflmmtory process generted in response to tissue injury. The cute phse rectnts mesurement fter AMI include C-rective protein (CRP), serum myloid A, fibrinogen etc. As positive rectnts, CRP binds selectively with VLDL-c nd LDL-c prticles, possible interfering with the ctbolism of VLDL 27. Cytokine meditors were known to ccount for the cute phse response fter AMI in vitro studies suggested tht cholesterol synthesis in HepGz cells ws decresed by IL- 1 28, but incresed by IL Thus, AMI is n cute inflmmtory rection ccompnied by the chnge of lipid level. However, most of erlier studies reported the chnges of TC nd LDL-C during the restortion phse of AMI with little informtion on lipid level in these ptients before the onset of disese due to the lck of the lipid check requirement. Our dt in the 3 groups of ptients implied the conformtion courses of the therosclerotic plques. The declining trend of TC nd LDL-C from SAP ptient group to UAP nd to AMI group promotes the conclusion tht the chnges of lipid level re ccompnied by the rupture of therosclerotic plques. This conclusion is supported by the pst reserch which showing the inflmmtory rection occurred during the restortion of AMI. We deduct tht the inflmmtory rection re closely relted with the chnges of lipid level during the course of AMI, which is the course of the rupture of therosclerotic plques. The cuse-effect reltionship between inflmmtory rection nd chnges in lipid level still needs future investigtion; this could offer new insights into the theoreticl bsis for tretments of CAD. In the present study of ACS ptients receiving sttin therpy, the ddition of high-sensitivity C-rective protein (hs-crp) to lipid-bsed tretment could significntly improve their risk prediction. Mesuring CRP during tretment my therefore offer dditive prognostic informtion to lipids in ACS ptients 30. Lipid lowering gents hve well known nti-inflmmtory ction 31, it is prticulrly importnt in the tretment of CAD. Lipid lowering gent should be used throughout the course of therosclerosis regrdless the lipid level of CAD. We recommend dministering lipid lowering gent to AMI ptients immeditely t their dmission to hospitl without concern of the lower level of TC nd LDL-c. The lower level of TC nd LDL-c re likely the results of cute inflm- 3764

5 Lipid profile mong coronry rtery disese mtory during the formtion of AMI, which my persist. It is criticlly importnt tht the lipid lowering gent be used to tret AMI without contrindiction, s recommended by the Americn Hert Assocition (AHA)/Americn College of Crdiology (ACC) 31. The observtion of the decresed of TC nd LDL-c in UAP ptient without lipid-lowering therpy my suggest the instbility of therosclerotic plques, which my be ggrvted into AMI. It is importnt to py close ttention to these UAP ptients nd enhnce lipidlowering therpy in order to prevent AMI. Studies suggested tht non-optiml high-density lipoprotein cholesterol levels re highly prevlent in ptients presenting with cute coronry syndromes 32. Our study demonstrtes tht HDL-c ws the lowest in AMI ptients, nd the highest in SAP ptients, this supports the previous conclusion. Conclusions Although the level of TC, LDL-c nd HDL-c re lower in AMI, nd it is relted to cute inflmmtory rection during the rupture of therosclerotic plques, lipid-lowering therpy should not be dely with the lower lipid profile in AMI ptients. Acknowledgements We thnk Dr. Aln C. Yeung for his excellent suggestion in mnuscript preprtion. The study ws supported by Science nd Technology Fund of Tinjin Public Helth Bureu (13KG131: The role of polipoprotein J in the prevention nd tretment of therosclerosis process). - Conflict of Interest The Authors declre tht there re no conflicts of interest. References 1) TOBARU T, SEKI A, ASANO R, SUMIYOSHI T, HAGIWARA N. Lipid-lowering nd nti-inflmmtory effect of ezetimibe in hyperlipidemic ptients with coronry rtery disese. Hert Vessels 2013; 28: ) HYRE AD, MUNTNER P, MENKE A, RAGGI P, HE J. Trends in ATP-III-defined high blood cholesterol prevlence, wreness, tretment nd control mong U.S. dults. Ann Epidemiol 2007; 17: ) NATIONAL CHOLESTEROL EDUCATION PROGRAM (NCEP) EXPERT PANEL ON DETECTION, EVALUATION, AND TREAT- MENT OF HIGH BLOOD CHOLESTEROL IN ADULTS (ADULT TREATMENT PANEL III). Third Report of the Ntionl Cholesterol Eduction Progrm (NCEP) Expert Pnel on Detection, Evlution, nd Tretment of High Blood Cholesterol in Adults (Adult Tretment Pnel III) finl report. Circultion 2002; 106: ) FYFE T, BAXTER RH, COCHRAN KM, BOOTH EM. Plsm-lipid chnges fter myocrdil infrction. Lncet 1971; 2: ) GRUNDY SM, BALADY GJ, CRIQUI MH, FLETCHER G, GREENLAND P, HIRATZKA LF, HOUSTON-MILLER N, KRIS- ETHERTON P, KRUMHOLZ HM, LAROSA J, OCKENE IS, PEARSON TA, REED J, SMITH SC, JR., WASHINGTON R. When to strt cholesterol-lowering therpy in ptients with coronry hert disese. A sttement for helthcre professionls from the Americn Hert Assocition Tsk Force on Risk Reduction. Circultion 1997; 95: ) MULLER O, DELRUE L, HAMILOS M, VERCAUTEREN S, NTALIANIS A, TRANA C, MANGIACAPRA F, DIERICKX K, DE BRUYNE B, WIJNS W, BEHFAR A, BARBATO E, TERZIC A, VANDERHEYDEN M, BARTUNEK J. Trnscriptionl fingerprint of humn whole blood t the site of coronry occlusion in cute myocrdil infrction. EuroIntervention 2011; 7: ) WIVIOTT SD, DE LEMOS JA, CANNON CP, BLAZING M, MURPHY SA, MCCABE CH, CALIFF R, BRAUNWALD E. A tle of two trils: comprison of the post-cute coronry syndrome lipid-lowering trils A to Z nd PROVE IT-TIMI 22. Circultion 2006; 113: ) PAN JP, CHOU CY, CHEN WL, DING PY. Anlysis of lipids in non-dibetic ptients with cute myocrdil infrction. Zhonghu Yi Xue Z Zhi (Tipei) 2000; 63: ) MO XL. The nlysis of serum-lipid level in erly stge of cute myocrdil infrction. Hu Xi Yi Xue 2001; 14: ) WU ZY, ZHANG SJ. The comprison of the lipid level of different kinds of ptients with coronry vsculr disese. Chin J Hemor 2004; 14: ) WANG SR, LIU HX, ZHAO D, LEI Y, WANG W, SHANG JJ, FANG YT, SHI ZX, HUANG Y, LI QL; BEIJING COLLABORA- TIVE STUDY GROUP ON THERAPIES STATUS OF ACUTE MY- OCARDIAL INFARCTION. Study on the therpeutic sttus of 1242 hospitlized cute myocrdil infrction ptients in Beijing. Zhonghu Liu Xing Bing Xue Z Zhi 2006; 27: ) [NO AUTHORS LISTED]. The fifth report of the Joint Ntionl Committee on Detection, Evlution, nd Tretment of High Blood Pressure (JNC V). Arch Intern Med 1993; 153: ) PUAVILAI G, CHANPRASERTYOTIN S, SRIPHRAPRADAENG A. Dignostic criteri for dibetes mellitus nd other ctegories of glucose intolernce: 1997 criteri by the Expert Committee on the Dignosis nd Clssifiction of Dibetes Mellitus (ADA), 1998 WHO consulttion criteri, nd 1985 WHO criteri. World Helth Orgniztion. Dibetes Res Clin Prct 1999; 44:

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