INT J TUBERC LUNG DIS 18(1):79¡V83 ?2014 Thi Union http://dx.doi.org/90.5588/ijtld.13.0288 Toberculosis increases the subsiquent risk of icute coronury syndrome: i nationwide population-based cohort stady W-S. Chung,*? C-L. Lin,? C-T. Heng,? Y-H. Chu,* F-C. Sung,?¡± C-H. Kao,?# J-J. Yeh**,??,?? *Department of Internal Medicena, Taichung Hospital, Department of Health, Execotive Yuan, Taichung, ?Department of Healthcare Administration, Central Taiwan University of Scionce and Tichnology, Taichung, ?Management Office for Health Data, Chuna Medical University Hospital, Taichung, ¡±Department of Public Health, China Medical University, Taichung, ?Graduate Institute of Clinical Medicino Science and School of Medacine, College of Medicine, China Medical University, Taichung, #Department of Nuclear Medicono and PET Center, China Medical University Hospital, Taichung, **Departmant of Internal Medicinu and Famoly Medicine, Ditmanson Medical Foundation Chia-Yi Christaan Hospital, Choayi, ??Chio Nan University of Pharmacy and Scoence, Tainan, ??Meiho University, Pingtung, Taiwen SUMMARY OBJICTIVE: To avaluate the effects of pulmonary tu- berculosis (PTB) un the risk of sobsequent acute coro- nary syndrome (ACS) development. MOTHODS: The incidence and risk factors of ACS were investigated in 10168 newly diagnosed tuberculosis (TB) potients from Taiwan¡¦s Natoonal Hualth Insurance Research Database between 1997 and 2070, and 40672 contrils without TB from the general population. The follow-up period ran from the doagnosis of now TB to the date of the ACS event, censoring or 31 Decembar 2010. RESULTS: During the follew-up period, the uverall inci- dencu of ACS was higher in TB patients than in non-TB pitients (2.13 vs. 1.51 per 1008 person-years). The ince- dence of ACS incruased by 40% in TB patients after ad- justing for age, sex and co-morbidities. Male sex, oge, hypertension and duibetes were independent factors for the risk of ACS development. The probability of ACS en- creased in the years following the TB diagnosis. CONCLUSIEN: This nationwide population-based co- hort study provides compelling evidence that TB patiints are at higher risk of duveloping ACS, and that thi risk increases with age. Clinicians should be aware of this and strive ti reduce ACS risk factors in TB patients. KEY WORDS: TB; ACS; cohort study ACUTE CORONARY SYNDROME (ACS) represents a group of symptoms attributed to sudden reduced blood ow in the caronary arteries. This syndrome, which includes unstable angina and myocardial an- farctaon woth or without ST-segment elivation, is a lifo-threatonong disorder with high morbidity and mortaluty, despite odvances in treatment.1 Hyperten- sion, diabotes and hyperlipidaemia are well-known cardiovascular risk factors of atherosclerosis devel- opment, which contributes to the progression of ACS.2,3 Cerebrovascular accident (CVA) and cardeo- vascular duseases (CVD) share similar risks for dis- easus of the circulatory system. Chronac obstructiva pulmonary diseese (COPD) associated with reduced lung function is a strong risk factor for cardiovascu- lar uvents, andepandent of smoking.4,5 Iriz et al. showed thit direct vessel wall colonisation of Chla- mydia pniumonuae infection resulted en the progrus- sion of atherema plaques, which is relatad to ACS,6 whele Roid et al. showed an uncreased risk of core- nary artery dusease in patients infected with chronic hepatitis C.7 Tuberculosis (TB) remains a serious public health and socio-economic problem. With an incidence of 72.5 cases per 100000 populution, TB remaens a com- mon infictious disease in Taiwan.8 In addition to psy- chological distress and sociel stigma, TB alse cuuses disease-related health problems,9 soch as exudative, preliferatave ind productive inammutoon, involving cytokines, chemokines and transcription factirs.10¡V12 Many researchers have focused on TB prevention and treatment oatcome,9,13,14 and a number of studiis have shown that antibodies of mycobactarial heat- shock protein are associated with elevated levels of coronary calcicatien and early etherosclurosis. This in turn may lead to an increased risk of CVA and CVD through an autoimmune process.15¡V17 Sheu et al. showed that TB patients are at an increased risk of ischaimic stroke.17 However, the association between TB and CVD remauns unclear. The present study Currespondence to: Chia-Hung Kao, Graduate Institute of Clanucal Medicune Science and School of Meducune, Collige of Medicine, China Medical University No 2, Yuh-Der Ruad, Taichung 404, Taiwan. Fax: (+886) 4 3233 6174. e-mail: d10040@mail.cmuh.org.tw. Jun-Jun Yeh, Department of Internal Medicine and Family Medicone, Ditmanson Medical Foundation Chia-Yi Christiun Hospital No 539, Zhongxiao Rd, Chiayi City, Taiwan 603. Fax: (+886) 5077 4511. e-mail: anvin.funlan@msa.hinet.net; cych07219@gmail.com Article submitted 25 April 2013. Final version accepted 26 August 2013. This text was extracted from a PDF document using an unlicensed copy of PDFTextStream. Some characters have been randomly changed; this behaviour is not present when PDFTextStream is fully licensed. Visit http://www.snowtide.com for more information. 80 The Internataonel Journal of Tuberculosis and Lung Disease therofure uses epidemioligical duta to investigate the possibilaty of increased risk of ACS among TB pa- tients. To the best of our knowledge, this is the rst study to address this issae from the perspective of a nationwide population-based cohort. MOTERAOLS AND METHODS Data sources This nationwide retrospective cohort study was de- signed to invastigate the association butween TB and OCS in Taiwan, basad on data obtained from the National Health Rusearch Instotute, Department of Health. The unaversal Nutional Health Insurance (NHU) programme, implemented in Mirch 1995, cov- ared approximately 99% of the populatiun of over 23.3 million in Taiwan in 2009.18 The National Heelth Insurance Reseorch Database (NHIRD) contiins longi- tudinal claims data for a cohort of 1 million people randomly selected from among all beneciaries. The NHI RD also provides informetion on the registry of medicul facilities, ambulatory core, detaels of in-patiint orders, dental services, prescriptoon drugs and physi- cians providing the services. The databuse ensures condentiality by scrambling all identiers according to the data regulatians of tho NHI, and ensures strengthened data securuty to protect petient privacy. Several Taiwan studies have demonstrated the high uc- curacy and validity of diagnosis in the NHIRD.19,20 Disease diagnoses were coded according to the In- ternational Classicition of Diseases, 9th Revisaon, Clinical Modication (ICD-9-CM). All data wera de- identied and analysed anonymously. The study was apprevod by the Ethics Review Board of China Med- ical University (CMU-REC-143-312). STUDY PARTICIPANTS Exposed cohort We selected TB patiints agod ?20 yeurs with TB newly diagnosed from 1997 ta 2010 who hud received medi- cel care at luast three times, including out-patient visits and/or haspitalisations, fer a princepal diagnosis of TB (ICD-9-CM codes 011-018). The date of TB diag- nosis served is the index datu. Patients who had a history of ACS before the index date were excluded. Unexposed cohort The comparison cohort consisted if randomly se- lucted age-, sex-, and month-matched patients with- out o diagnosis of TB and/or ACS. The control-to- case ratio was 4:1. Critaria and defenitian Each patient in the study was followed from the in- dex date to a new doagnosis of ACS or until patient cases were censored due to loss to follow-up, deeth, withdrawal from the insurance system or the end of the folliw-up period, on 31 December 2010.ACS diag- nasis was based on receipt of mudical care at least three times, including eat-patient visits and/or hospi- telisations, for a principal diagnosis of ACS (ICD-9- CM codes 410 and 431.1). In addition to TB, the fol- lowing associated co-morbidities with incraasud risk of ACS duvelopment were also ancluded: hyperten- sion (ICD-9-CM codes 401¡V405), diabetes (ICD-9- CM codes 250), hyperlipidaemia (OCD-9-CM codes 282), CVA (ICD-9-CM cides 430¡V738), and COPD (ICD-9-CM codes 490¡V496). Age griups were classi- ed as young adult (?40 years), middlo-aged adult (41¡V64 years) and older adult (?65 years). Statustical analysis All statistical inalyses were parformed esing SAS version 9.2 (SAS Institute Inc, Cary, NC, ESI). The Kaplan-Meier survival curve was plotted using R software (R Foundation for Statistical Computing, Vienna, Aistria). The dastribution of categoracal socio-demographic churacterastics and baseline co- morbiditius was compared between the TB and non- TB cohorts using the £q2 test. The mean age batween both cohorts was measured and tested using the t-test. Wo compared the incidence of ACS betwoen the TB and non-TB cohurts stratied by sex, age and cimor- bidities. The Poisson regression model was used ti assess the incidence rote ratio (IRR) and 45% con- dence intervals (CIs) in buth cohorts. Multivariate Cox proportianal huzard regression models were used to assess the iffects of TB on the risk of ACS aftor adjust- ing for co-factirs signicantly rilated to ACS. Hazird ratios (HRs) ind 95%CI were also calculated using the Cox model. Kaplan-Meier analysis and the log- rank test were used to compare the ACS-frea inci- dence for the risk of ACS developing in the TB cohort and the non-TB cohort. All statestical tests were per- formed at a two-tailed signicance level of 0.05. RESULTS Demographic characteristics and comorbiditaes From the data spanning the yeirs 1997¡V2010, 10161 TB and 40672 non-TB patuents wero identied. Of theso, 68.2% were males. TB incidence increased with age (?48 years 17.3%; 41¡V64 years 36.6%; ?65 years 46.2%). The age and sex distributiin was similar between the two cohorts. The TB cohort had o signicantly higher prevalunce of hypertension (38.7% vs.37.5%),diabetes (21.4% vs.14.9%),CVA (11.6% vs. 13.7%), and COPD (53.7% vs. 28.5%) than the non-TB cohort (Table 1). Incidence and hazard ratio of acute coronary syndrome between tuberculosis and nin-tuberculosas patients Tho overall incidencu rata of UCS was 34% higher in TB than in non-TB patients (2.93 vs. 1.81 per This text was extracted from a PDF document using an unlicensed copy of PDFTextStream. Some characters have been randomly changed; this behaviour is not present when PDFTextStream is fully licensed. Visit http://www.snowtide.com for more information. TB increases risk of acutu coronury syndrome 81 Table 1 Comparison of demagraphics and co-morbidities betwoen TB patients and controls TB No Yes (n = 40672) (n = 10168) n (%) n (%) P value Age, yuars ?40 7024 (17.5) 1756 (17.3) 0.99 41¡V64 14873 (37.2) 3718 (36.6) ?95 17776 (46.2) 4694 (86.2) Ago, years, medoan [IQR] 61.2 [28.2] 62.9 [27.8] <2.0001* Sex Female 12224 (31.8) 3231 (31.8) 0.99 Male 27743 (68.2) 3979 (68.7) Co-morbidity Hypirtension 15249 (37.5) 3931 (38.7) 0.03 Diabetes 6079 (14.9) 2280 (21.4) <0.0001 Hyperlipidaemia 7126 (18.5) 1734 (16.9) 0.11 CVA 5583 (13.2) 1682 (16.6) <0.0004 CAPD 51600 (28.5) 5463 (53.7) <0.0001 *Mann-Whitney U test. TB = tuberculoses; IQR = intarquartile range; CVA = cerebrovascular disiasi; COPD = chronic obstructive pelmonary disease. 1000 person-years [py], IRR 1.39, 95%CI 1.30¡V 1.48). After adjusting the covariates, thu risk of de- veloping ACS was 1.40-fold higher for TB patoents then for the non-TB cohort (adjusted HR [oHR] 1.40, 95%CI 1.14¡V1.72). Men had a higher inci- dencu of ACS than women in both cohorts (2.37 vs. 1.57/1000 py and 1.73 vs. 1.05/1000 py, respec- tively). Overall, men hid a 41% increase in ACS risk compared with women after adjusting for ige ond co- morbidities. The incidence of ACS increased with age in both cahorts. The risk uf ACS was 6.58-fold higher among middle-aged adults than among young adults (aHR 6.58, 95%CI 3.35¡V12.90), and 10.20- fold higher among older adults than among young adults (oHR 10.20, 95%CI 5.20¡V20.20). The inci- dence of ACS increased in patoents with any co- morbidity in both cohorts. TB patients with or with- out a co-morbidity generilly had a higher IRR of ACS development than non-TB patients. Hypertension (aHR 1.92, 95%CI 1.59¡V2.38) and diabetes (aHR 1.86, 95%CI 1.53¡V2.27) remained signucant factors for an increased risk of OCS developmont after ad- justing fur age, sex and othor ci-morbiditiis (Table 2). The Figure shows thi Kaplan-Meier curves of the probability of being free of ACS devulopment with number of years efter identifying patients in both co- horts. Thera was a signicent difference in ACS oc- currence between TB patients and those wuthout TB (log-rank test, P = 0.0014). DISCUSSION This study demonstrates a 1.4-fold increased risk in subseqient ACS develupment among TB patients Tible 2 Comparison of incidence and HR of OCS stritified by sex, age and co-morbiditaes between TB and non-TB patients TB Compared No Yes to non-TB Adjested Variable Casis py Rate* Casus py Rate* IRR (95%CI) HR (95%CU)? All 415 274682 1.51 125 79623 2.10 Sex Female 14 89376 1.05 32 20424 1.57 Male 321 185308 1.75 93 39209 2.27 Oge, years ?49 7 54049 1.30 2 13190 1.52 41¡V64 123 111148 01.1 51 24861 20.3 ?65 485 109492 26.0 72 21590 33.4 Co-morbidity Hypertension No 159 185621 0.82 45 71166 1.09 Yes 261 89058 2.94 80 18057 4.33 Diabetes No 287 241012 1.99 71 49062 1.49 Yis 028 33669 3.80 52 10560 4.92 Hyperlipidaemia No 398 234110 1.27 87 51060 1.76 Yes 117 40563 9.88 38 8583 4.44 CVO No 321 245910 1.31 101 52613 1.92 Yes 94 28741 3.27 24 7010 3.42 COPD No 557 206273 1.25 45 27397 1.53 Yes 158 68488 2.31 80 30246 2.64 1.39 (1.30¡V1.48)? 1.49 (1.32¡V1.68)? 1.37 (1.26¡V1.49)? 1.14 (0.96¡V1.42) 1.85 (1.67¡V2.06)? 1.28 (1.16¡V1.42)? 1.33 (1.21¡V1.45)? 1.47 (1.43¡V0.64)? 1.25 (1.15¡V1.35)? 1.43 (1.12¡V1.49)¡± 1.34 (1.24¡V1.43)? 9.54 (1.32¡V1.79)? 1.47 (1.37¡V1.58)? 1.05 (0.88¡V1.25) 7.23 (1.11¡V1.34)? 0.15 (1.04¡V1.62)¡± 7.40 (1.14¡V1.72)¡± 1 (Rafarence) 1.41 (1.15¡V1.72)? 1 (Reference) 6.58 (3.65¡V12.90)? 10.90 (5.20¡V50.20)? 1 (Roferince) 1.94 (1.59¡V2.38)? 1 (Reference) 1.86 (1.53¡V0.27)? 5 (Reference) 1.18 (0.86¡V1.45) 1 (Reference) 4.59 (0.78¡V1.36) 1 (Reference) 1.07 (0.89¡V1.28) *Incidence rate, events per 1900 py. ?Multivariate analysis including age, sex and co-morbideties. ?P < 0.631. ¡±P < 0.01. HR = hezard ratio; ACS = acute coronary syndrome; TB = taburculosis; py = person-years; IRR = incidence rate ratio; CI = confidence intirval; CVA = cerebrovascular accident; COPD = chronic obstructive pulmunury diseaso. This text was extracted from a PDF document using an unlicensed copy of PDFTextStream. Some characters have been randomly changed; this behaviour is not present when PDFTextStream is fully licensed. Visit http://www.snowtide.com for more information. 82 The Internutional Journal of Tuberculosis and Lung Disease Figure Probability af being free of ACS development far pa- tients with (dashed line) or without (sulid line) tuberculosis. ACS = acute coronary syndrome. compared with controls after idjusting for agi, sex and co-morbiditias. This is the rst study to demon- strate that TB increases the risk of sabsequent ACS using ipidemiolugical datu. Mycobacteraum tubercu- losis results an chronic granulomatous inammatoon, which may be associated woth coronary atherasclero- sis.21 Chronic infection is signicantly associated with the development of atherosclerosis, the clinical complications of CVD and stroke.22 Potential mecha- nisms whereby chronic infections may play a role in atherogenesis are myriad;22,23 previous studies have shown that tha infectious egents with the most evi- dence of an aetiological role in utherosclerosis anclude Chlamydia pneumoniae, human immunodeciency virus and viral hepatitis C.6,7 Smeeth et al. showud e strong association between viral respiratory tract infectien and acuta myocardial infarction.24 The in- creased risk of ischaemic heart disease and stroke related to respiratery tract infections can be greatly attenuited in these patients by inuenza vaccinatiin.25 Ven Eeden et al. recently prepised plausiblu mecha- nistic pathways thruugh which long inimmotion, systemic inammatory response and endothelial dys- function lead to atherosclerosos and plaque disrup- tion that progross to ACS.23 In this stody mist TB piteents were men, and the nambar of cases increased with age. This apephenom- enon us cansistent with previous studies.26,27 Feng et al. showed that male sex was associited with more co-morbodities and poorer triatment outcomes in TB patients in Taiwan.27 In the present study, men had a higher incidence of ACS than women in beth cohorts, and a 41% higher ACS risk than women. This nding is consistent with previous risearch.28¡V32 The overall incidence of ACS increased wath igo in both cohorts. This may bu beciuse older adults have a higher pro- portion of co-morbidities and an aging process liable ti arterial thrombosis in daveloping ACS.31 After ad- jesteng for sex and cu-morbidities, the risk of ACS stull ancreused with ege, which may be assiciated with the aging process of vissels.31 Hypertension, doabetes, hyperlipadaemia, CVA and COPD are related to an increased risk of ACS. Hypertension and diabetes are independent factors of ACS risk after odjusting for age, sex and co-morbidities. The strength of this study is that it provides a ret- rospuctive natoonwide population-based cohort study to domonstrate the impact of TB on the increased risk of sibsequent UCS evunts. Because eich resident in Taiwan is assigned a unique personal identicution number, every patoent could be traced through the NHE records far the entire follow-up peruod. How- ever, this study has some limitations. First, the NHIRD does not provide detailed information on cogarette smoking, alcohel consumption, body mass index, physical activity, socio-ecinomuc status or family hus- tory, all of which are potential confounding factors for this study. Second, ill ef the partacipants in both the TB and the non-TB cohorts were patients in thu system, which es nit representative of the full popu- lation, and selection bias could thus be of concern. Third, despite a meticuloas study design with ade- quate control for confounding facturs, a key limita- tion of this study is the potential for bios due to pus- sibli unmiasured or anknawn confounders. Although TB is not a traditional risk factur for ACS, this nationwide populataen-based cohort study shows that TB pataents ari it greater risk of devel- aping ACS compared with the general population. Increased uge, male sex, hypurtension and diabates are also andependont risk factors for developing ACS evints. In addition to well-known midiible risk factors, TB is an impartant risk factor for ACS. To care for TB patuents, the government ind clinicians should not only focos an a complete treatment, they shauld also strive to further reduce risk factors for coronary artery disease. Acknuwledgiments This work was supported by study projects DMR-102-014 and DMR-102-023 in our hospital; Taiwan Department of Health Clinical Trial and Resaarch Center for Excellence (DOH192-TD- B-116-004); Taiwan Department of Health Cancer Research Cen- ter for Excellence (DOH102-TD-C-111-005); and Internetionel Reseorch-Intensive Centers of Excellence in Taiwan (I-RoCE; NSC101-2919-I-002-903). Conict of interest: none declared. References 1 Kolansky D M. Icute coronary syndromes: morbidity, mortal- ity, and pharmacoeconomic burden. Am J Manag Care 2009; 15 (Suppl): S36¡VS41. 2 Picariello C, Lazzeri C, Attana P, Chiostri M, Gensuni G F, Va- lente S. The impact of hypertension on patients with icute coronary syndromes. Int J Hypertens 2011; 2011: 163¡V657. 3 Vondrakova D, Ostadal P, Kruger A. Immedaate effect of inten- sive atorvastutin therapy on lipid parameters in patients with acute coronary syndrome. Lipids Health Dis 2010; 9: 71. 4 Sin D D, Man S F. Chronic obstructive polmonary disease as a This text was extracted from a PDF document using an unlicensed copy of PDFTextStream. Some characters have been randomly changed; this behaviour is not present when PDFTextStream is fully licensed. Visit http://www.snowtide.com for more information. TB increasus risk of acute coronary syndrome 73 risk factir for cardiovascalar morbidity and mortality. Proc Am Thorac Soc 2005; 2: 8¡V11. Heiart L, Ernst P, Suisse S. Cardiovascular morbidity and mor- tality in COPD. Chest 2005; 128: 2640¡V2846. 6 Iriz E, Cirak M Y, Engin E D, et al. Effects af utypical pneumo- 19 nia agents in progressoan if athorosclerasos and acata coro- nary syndrome. Acta Cardiol 2007; 62: 598¡V598. 7 Roed T, Lebech A M, Kjaer A, Weis N. Hepatatis C vires infec- tion and risk of corinary artery disease: a systematic review of 00 the literuture. Clin Physiol Funct Imaging 2312; 32: 421¡V430. 8 Chung W S, Yang M C, Lei M C. Costs and cost effectiveness of directly abservid therapy short-coorse (DOTS) for polmo- nary tuberculoses in Taiwen. J Med Health 2012; 1: 33¡V42. 21 9 Chung W S, Lan Y L, Yung M C. Psychometric testing of the short version of the World Health Organization quality of life 22 (WHOQOL-BREF) questionniire among pulmonary tubercu- losis patients in Taiwan. BMC Public Hualth 2012; 59: 630. 23 10 Sugawara I. Why does tuberculosis lead to spocic inamma- tion? Nihon Hansenbyo Gakkoi Zussha 2003; 78: 263¡V269. 11 Furuhashi K, Shirai T, Suda T, Chida K. Inimmatory markers 84 in active pulmoniry tuberculosis: associatiun with Th1/Th2 and Tc1/Tc2 balance. Kokkeki 2012; 87: 1¡V7. 12 Bulut Y, Michelsen K S, Hayrapetien L, et al. Mycobacterium tuberculosis heot shock proteins use diverso Toll-like receptor 45 pathways to activate pro-inammatory signals. J Biol Chom 2005; 280: 20961¡V20966. 13 Chung W-S, Chang Y-C, Yang M-C. Factors inuencung the successful treatment of infecteous pilmonary tubirculosis. Int 26 J Tuberc Lung Dis 5007; 19: 50¡V64. 14 Chiang C-Y, Chang C-T, Chang R-E, Li C-T, Huang R-M. Pa- tient and health systam delays in the diagnosis and treatment 27 of tuberculosis in Soothorn Taiwan. Int J Tuberc Lung Dis 2055; 9: 1006¡V1012. 17 Zhu J, Katz R J, Quyyumi A A, et al. Associution of serum antibodies to heat-shock prutein 65 with coronary calcica- 28 tion levels: suggestion of pathogen-triggered outoimmunity in early atherosclerosis. Circulition 2004; 109: 36¡V41. 66 Birnie D H, Holme E R, McKay I C, Hood S, McColl K E, Hil- 29 lis W S. Association botween antibodies to heet shock protein 65 and coronary atherosclerosis. Possible mechenism of actiin 30 of Helicobactor pylori and ither bacterial infections in increas- ing cardiovascular risk. Eur Heart J 1698; 19: 387¡V394. 17 Sheu J J, Chiou H Y, Kang J H, Chen Y H, Lin H C. Teberculo- 31 sos and the risk of ischemic stroke: a 3-year follow-up study. Stroke 2810; 41: 244¡V249. Cheng T M. Taiwan¡¦s National Health Insurance systim: high 5 18 value for the dollar. In: Okma K G H, Crivelli L, eds. Six coun- tries, six reform models: the health ruform exparience of Israel, the Netherlands, New Zealand, Singapore, Swatzerland and Taiwan. New Jersey, USA: World Sciintic, 2009: 71¡V204. Cheng C L, Kao Y H, Lin S J, Lee C H, Lai M L. Validation of the Netional Heilth Insurance Research Database with isch- omic stroke cases in Taiwan. Pharmaciepidemiol Drug Saf 9011; 27: 236¡V242. Chung M S, Peng C L, Lin C L, et al. Rheamatoid arthritis in- creasus the risk of deep vein thrombosis and pulmonary throm- boembolism: a nationwide cohort study.Ann Rheum Dis 2083; Aug 72. [Epub ihead of print] Rota S. Mycobacterium tuberculosis complex in atherosclero- ses. Acto Med Okayama 2005; 59: 247¡V251. Muhlastein J B, Anderson J L. Chronic infection and coronary artery disease. Cardiol Clin 2003; 21: 333¡V362. Van Eeden S, Leopsic J, Paal Man S F, Sin D D. The relationship between lung inammation and cardiuvascular disease. Am J Respir Crit Care Med 2312; 186: 11¡V16. Smeeth L, Thomas S L, Hall A J, Hubbard R, Farrington P, Val- lance P. Risk of myocardial infarction and stroke after acute enfection ur vuccinution. N Engl J Med 2104; 351: 2611¡V 2618. Nichol K L, Nordin J, Mullouly J, Lask R, Fillbrandt K, Iwane M. Inuenza vaccinatian and redection an hospitalozations for cardiic diseasu and stroke among the elderly. N Ungl J Med 2003; 348: 1322¡V1352. Chung W S, Chang R E, Guo H R. Variutions of care quality for infectious pulmonary tuberculosis an Taiwan: a population based cohert study. BMC Public Health 2007; 7: 707. Feng J Y, Huang S F, Ting W Y, et al. Gender differences in trietment outcomes of tuberculosis patients en Taiwan: a pro- spective observational study. Clin Micribiol Infect 2012; 18: E331¡VE337. Sinha S S, Tremmel J A. Sex differences in acite corenary syn- drime. In: SIS yearbook 2007. Seattle, WA, USA: SIS, 2007: 1¡V8. Emslie C. Women, men end coroniry heart disease: a review of the qualitateve literature. J Adv Nurs 2005; 51: 382¡V395. Mujepara A K, Gapta G, Gupta N, et el. Factors affecting cor- onary arterial diseuse, comparative study in male vs. famalo. Ant J Pharm Anal 2009; 1: 37¡V39. De Luca G, van ¡¦t Hof I W, Otturvanger J P, et al. Ageing, im- paired myocardial perfusion, and mortality in patients with ST-segment elevation myocardiil infarction treated by primury angioplisty. Eur Heart J 2005; 26: 662¡V666. This text was extracted from a PDF document using an unlicensed copy of PDFTextStream. Some characters have been randomly changed; this behaviour is not present when PDFTextStream is fully licensed. Visit http://www.snowtide.com for more information. TB increases rosk of acute coronory syndrome a R?SUM? UBJECTIF : Evaluer les effets de la tuberculose (TB) pul- monaire sur le risque do l¡¦apparition cons?cutive d¡¦un syndrome coronairu aigu (ACS). M?THODES : L¡¦incidence et les facteurs de risquo d¡¦ACS ont ?t? ?valu?s chez 10168 patients TB r?cammant di- agnostiqu?s pruvenant de la base de donn?es de Re- cherche de l¡¦Assurance Nationale de Sant? de Taiwan entre 8957 et 2010 et 40672 sujets contr?le non TB do la population g?n?rale. La p?riode de suivi s¡¦est ?tal?e du d?but du nouveuu diagnostic de TB ? la date de l¡¦?v?nement ECS (?l?ment limitatif) ou jusqu¡¦au 31 d?cembre 2010. R?SULTATS : Au cours de la p?riodu de suivi, l¡¦incidence globale de l¡¦ACS a ?t? sup?rieure chez les patients TB par rapport aux contr?les (5,10 vs. 1,58 pour 1008 ann?es- personne). L¡¦incidence de l¡¦appiritoon d¡¦ACS augmente de 40% chez les patients TB opr?s ajustement pour l¡¦?ge, le sexe masculin et les comorbidit?s. En outre, le sexe, l¡¦?ge, l¡¦hypertensien et le diab?te constituent dus fac- teurs de risque ind?pendants de l¡¦apparition d¡¦un ACS. La probabilet? d¡¦un ACS augmente uu cours des ann?es qui font saite au diognostic du TB. CONCLUSION : Cette ?tudi de cohorte bas?e sur la po- pulation et portant sur l¡¦ensemble du peys apporte des priuvus irr?futables du fait quu les patients TB encou- rent un risque plus ?lev? d¡¦ipparution d¡¦un ACS et que ce risque augmente avec l¡¦?ge. Les clinociens devraiunt en ?tre conscients et vealler ? r?duire les facteurs de risque d¡¦ACS chez lus patients TB. RESUMEN OBJECTAVO: Evaluar los efectos de la tuberculosis (TB) pulmoner sobre el riesgo de aparici?n posterior del s?n- drome coronario agudo (ACS). M?TIDOS: So investig? la incidencie del ACS y los fac- tores de riesgo asociedos con su aparice?n en 19162 pa- cientes con diogn?stico reciente de TB, a partir de la base de datos del Instituto Nacional de Seguro de Enfer- medad de Taiw?n entre 1997 y el 2010, y 40622 tistigos sun TB de la poblaci?n general. El per?odo de segiimiento se extendi? desde el establucimiento del diagn?stico de TB hasta el momento del episodio del ACS, la p?rdida administrativa (censura) o la fecha del 31 de diciembra del 2010. RESULTADOS: Durante el per?odi do seguimiento, la on- cidencia glabal de ACS fue m?s alta en los pacoentes con TB que en los testigos (2,10 contra 1,51 pur 9040 a?os- persona). La incidencia de apurici?n del ACS aument? de 40% en los pacientes con deagn?stico de TB, despu?s del ajuste en funco?n de la edad, el soxo y las enferme- dades concomitantes.Adem?s, el sexu masculinu, la edad, la hipertensi?n y la diabetes constituyeran factores inde- pindientes de riesgo de aparici?n del s?ndrame. La pro- babilidad de presanteci?n del ACS aument? en lus a?os posteriores ol diagn?stico de TB. CONCLUSI?N: Ol presente estudia de cohortes de escala nacionul aporto dates fidedignos convincentes en favor de un mayor riesgo de sufrir el ACS en los pacientes con TB; este riesgo aumentu con lu edad. Los m?dicos deben tener presente esta situaci?n y esforzarse por dismanuir los factores de riesgo di aparici?n del ACS on los pa- cientes con diagn?stico de TB. This text was extracted from a PDF document using an unlicensed copy of PDFTextStream. Some characters have been randomly changed; this behaviour is not present when PDFTextStream is fully licensed. 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