DOI: 10.1161/CIRCULATIONAHA.114.014145
Atrial Fibrillation and Risk of ST-Segment Elevation versus Non-ST Segment Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study Running title: Soliman et al.; AF and risk of MI by type Elsayed Z. Soliman, MD, MSc, MS1,2; Faye Lopez, MS, MPH3; Wesley T. O’Neal, MD, MPH4; Lin Y. Chen, MD5; Lindsay Bengtson, PhD3; Zhu-Ming Zhang, MD, MPH1; Laura Loehr, MD, PhD6; Mary Cushman, MD, MSc7; Alvaro Alonso MD, PhD3 1
Epidemiological Cardiology Research Centerr (EPICARE), Dept of Epidemiology and Prevention, Wake Forest School off Medicine, Winston Salem, NC; 2Dept p of Internal Medicine, Sect Se ctiionn on Car ct arddiology, Wake Forest School ooff M ar edicine, Wins nsston Sa Sal lem, NC; 3Division of Section Cardiology, Medicine, Winston Salem, E Epidemiology pidemio io ology gy and dC Community ommu om uni nity ty H Health, ealt ea l h,, S lt School c ool ooff Pu ch Public ubl blic ic Hea Health, ealt ea lth, lt h, U University nive ni v rsitty of M Minnesota, inne neso ne sota so ta,, ta M Minneapolis, inneapolis, M MN; N; 4De N; Dept ept off In Int Internal tern nal M Medicine, ed dicin ne, Wak Wake ke Fo Forest stt S School ch hoo ol off M Medicine, ed dic icin ine, W in Winston i stton in nS Salem, a le m ale 5 N NC; C; Card Cardiovascular dio i vasscular ar Division, Div vis isiion, Dept Dep eptt of of Medicine, Meddicine Me nee, Un Univ University iverrsity off Min iv Minnesota nneesootaa Med Medical dic icaal S School, choo ol, Minneapolis, Minn Mi nnea nn eapo ea poli po liss, M li MN; N; 6De Dept pt off Ep Epid Epidemiology, idem id emio em ology lo ogy gy, Gi Gill Gillings l ings in ngs S School ch hoo ool of G Global lo oba bal Pu Publ Public b ic H Health, eaalt lthh, U University niive v rs rsitty 7 of North Carolina at Chape p l Hi Hill, Chap pel H ill, NC; Dept p of Medicine, University y of Vermont, Chapel Chapel Hill, Burlington, VT Address for Correspondence: Elsayed Z. Soliman MD, MSc, MS, FAHA, FACC Epidemiological Cardiology Research Center (EPICARE) Wake Forest School of Medicine Medical Center Blvd Winston Salem, NC 27157 Tel: 336-716-8632 Fax: 336-716-0834 E-mail [email protected]
Journal Subject Codes: Etiology:[8] Epidemiology, Diagnostic testing:[171] Electrocardiology 1 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on April 28, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014145
Abstract
Background—It has recently been reported that atrial fibrillation [AF] is associated with an increased risk of myocardial infarction [MI]. However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with type of MI [ST elevation MI (STEMI) vs. non-ST elevation MI [NSTEMI] might shed light on the potential mechanisms. Methods and Results—We examined the association between AF and incident MI in 14,462 participants [mean age 54 years, 56% women, 26% African Americans] from the Atherosclerosis Risk in Communities study who were free of coronary heart disease at baseline [19 [1987-1989] 1987 19 87-1 87 -198 -1 989] 98 9] w with ith follow-up through December 31, 2010. AF cases were identified from study visits electrocardiogram elec ctr troc ocar oc ardi ar diog di o ram og m and by review of hospital discharge disccha harrge records. Inciden Incident nt MI M and its types were aascertained sceertained by aan n iindependent nde depeend de nden entt ad en adju adjudication judi ju dica di catiion ccommittee. ca omm mittteee. Ov Over er a m median ed dian ian fo ffollow ollow w uup p of 221.6 1 6 ye 1. year years, ars,, ar 1374 13 374 MI events ev ven ents occurred occurrre red [829 [8229 29 NSTEMI, NST TEM EMI, I, 249 2449 49 STEMI, STE EMI, 296 29 96 unclassifiable]. uncl un cllasssifi sifiiab a le]]. In In a multivariable mu ult ltiivar iv riaable adjusted adju ad just sted st ed model, mod odel el, AF [n=1545] el [n=15 1545 15 45]] as a time-varying 45 tim imee-va vary aryin ingg variable in vaari vari riab able ab le was as associated ass ssoc ocia oc iate ia tedd with te wit ithh a 63% it 63% increased incr in crea cr ease ea sedd se risk of MI [HR (95% CI):1.63(1.32-2.02)]. However, AF was associated with NSTEMI [HR (95% CI): 1.80(1.39-2.31)] but not STEMI [HR (95% CI): 0.49(0.18-1.34)]; p-value for hazard ratios comparison=0.004. Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men [interaction p-value55 years) at the time of enrollment as a cut-point. Interactions were tested in incl including clud cl udin ud ingg in multiplicative terms in the models. In the the analysis anaaly lysis by MI type, we excluded th thee unclassifiable MIs.. Ho H However, wever, to examine the effect effe ef ect of the unclassifiable unncl classsiifiab ble MIs MIs onn tthe he as association ssocciati iaat onn bbetween etwe ween we en A AF F an and nd type type ooff MI MI,, we cconducted ondduct on duct cted ed sensitivity which considered the unclassifiable MIs ens nsit itivity analyses it anal an a yse ysses inn w hichh we con onside on dere de r d th he un nclasssiifiab blee M Iss as as STEMI STEM EM MI in i one ne set of analysis anal an alys al ysis sis aand nd aass NS NSTE NSTEMI TEMI TE MI iin n an anot another othe ot herr se he sett of aanalysis. naly na lyssis is. Al Also Also, so, to eensure so nsur ns ure re te temp temporality mpor mp oral or alit al ity (i it (i.e. .e. e oc occu occurrence curr rren rr ence en ce of MI after AF), we conducted another sensitivity analysis in which we excluded participants with an MI event occurring within a short period (within a week) after a documented AF. Other additional analyses included: 1) Examining the association between AF and MI [overall and by type] using Cox proportional models adjusted for variables in model 3 plus other possible confounders [heart rate, beta blocker use, angiotensin converting enzyme inhibitors use, interim revascularization] all included in the models as time-varying covariates; 2) Comparing the association between AF and MI at different times of follow up; 3) Plotting the cumulative incidence of AF from baseline [1987-1989] to the end of follow up [2010]. The results of these
8 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on April 28, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014145
additional analyses are provided in the Online-Only Data Supplement. Statistical significance for all analyses was p
Atrial Fibrillation and Risk of ST-Segment Elevation versus Non-ST Segment Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study Running title: Soliman et al.; AF and risk of MI by type Elsayed Z. Soliman, MD, MSc, MS1,2; Faye Lopez, MS, MPH3; Wesley T. O’Neal, MD, MPH4; Lin Y. Chen, MD5; Lindsay Bengtson, PhD3; Zhu-Ming Zhang, MD, MPH1; Laura Loehr, MD, PhD6; Mary Cushman, MD, MSc7; Alvaro Alonso MD, PhD3 1
Epidemiological Cardiology Research Centerr (EPICARE), Dept of Epidemiology and Prevention, Wake Forest School off Medicine, Winston Salem, NC; 2Dept p of Internal Medicine, Sect Se ctiionn on Car ct arddiology, Wake Forest School ooff M ar edicine, Wins nsston Sa Sal lem, NC; 3Division of Section Cardiology, Medicine, Winston Salem, E Epidemiology pidemio io ology gy and dC Community ommu om uni nity ty H Health, ealt ea l h,, S lt School c ool ooff Pu ch Public ubl blic ic Hea Health, ealt ea lth, lt h, U University nive ni v rsitty of M Minnesota, inne neso ne sota so ta,, ta M Minneapolis, inneapolis, M MN; N; 4De N; Dept ept off In Int Internal tern nal M Medicine, ed dicin ne, Wak Wake ke Fo Forest stt S School ch hoo ol off M Medicine, ed dic icin ine, W in Winston i stton in nS Salem, a le m ale 5 N NC; C; Card Cardiovascular dio i vasscular ar Division, Div vis isiion, Dept Dep eptt of of Medicine, Meddicine Me nee, Un Univ University iverrsity off Min iv Minnesota nneesootaa Med Medical dic icaal S School, choo ol, Minneapolis, Minn Mi nnea nn eapo ea poli po liss, M li MN; N; 6De Dept pt off Ep Epid Epidemiology, idem id emio em ology lo ogy gy, Gi Gill Gillings l ings in ngs S School ch hoo ool of G Global lo oba bal Pu Publ Public b ic H Health, eaalt lthh, U University niive v rs rsitty 7 of North Carolina at Chape p l Hi Hill, Chap pel H ill, NC; Dept p of Medicine, University y of Vermont, Chapel Chapel Hill, Burlington, VT Address for Correspondence: Elsayed Z. Soliman MD, MSc, MS, FAHA, FACC Epidemiological Cardiology Research Center (EPICARE) Wake Forest School of Medicine Medical Center Blvd Winston Salem, NC 27157 Tel: 336-716-8632 Fax: 336-716-0834 E-mail [email protected]
Journal Subject Codes: Etiology:[8] Epidemiology, Diagnostic testing:[171] Electrocardiology 1 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on April 28, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014145
Abstract
Background—It has recently been reported that atrial fibrillation [AF] is associated with an increased risk of myocardial infarction [MI]. However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with type of MI [ST elevation MI (STEMI) vs. non-ST elevation MI [NSTEMI] might shed light on the potential mechanisms. Methods and Results—We examined the association between AF and incident MI in 14,462 participants [mean age 54 years, 56% women, 26% African Americans] from the Atherosclerosis Risk in Communities study who were free of coronary heart disease at baseline [19 [1987-1989] 1987 19 87-1 87 -198 -1 989] 98 9] w with ith follow-up through December 31, 2010. AF cases were identified from study visits electrocardiogram elec ctr troc ocar oc ardi ar diog di o ram og m and by review of hospital discharge disccha harrge records. Inciden Incident nt MI M and its types were aascertained sceertained by aan n iindependent nde depeend de nden entt ad en adju adjudication judi ju dica di catiion ccommittee. ca omm mittteee. Ov Over er a m median ed dian ian fo ffollow ollow w uup p of 221.6 1 6 ye 1. year years, ars,, ar 1374 13 374 MI events ev ven ents occurred occurrre red [829 [8229 29 NSTEMI, NST TEM EMI, I, 249 2449 49 STEMI, STE EMI, 296 29 96 unclassifiable]. uncl un cllasssifi sifiiab a le]]. In In a multivariable mu ult ltiivar iv riaable adjusted adju ad just sted st ed model, mod odel el, AF [n=1545] el [n=15 1545 15 45]] as a time-varying 45 tim imee-va vary aryin ingg variable in vaari vari riab able ab le was as associated ass ssoc ocia oc iate ia tedd with te wit ithh a 63% it 63% increased incr in crea cr ease ea sedd se risk of MI [HR (95% CI):1.63(1.32-2.02)]. However, AF was associated with NSTEMI [HR (95% CI): 1.80(1.39-2.31)] but not STEMI [HR (95% CI): 0.49(0.18-1.34)]; p-value for hazard ratios comparison=0.004. Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men [interaction p-value55 years) at the time of enrollment as a cut-point. Interactions were tested in incl including clud cl udin ud ingg in multiplicative terms in the models. In the the analysis anaaly lysis by MI type, we excluded th thee unclassifiable MIs.. Ho H However, wever, to examine the effect effe ef ect of the unclassifiable unncl classsiifiab ble MIs MIs onn tthe he as association ssocciati iaat onn bbetween etwe ween we en A AF F an and nd type type ooff MI MI,, we cconducted ondduct on duct cted ed sensitivity which considered the unclassifiable MIs ens nsit itivity analyses it anal an a yse ysses inn w hichh we con onside on dere de r d th he un nclasssiifiab blee M Iss as as STEMI STEM EM MI in i one ne set of analysis anal an alys al ysis sis aand nd aass NS NSTE NSTEMI TEMI TE MI iin n an anot another othe ot herr se he sett of aanalysis. naly na lyssis is. Al Also Also, so, to eensure so nsur ns ure re te temp temporality mpor mp oral or alit al ity (i it (i.e. .e. e oc occu occurrence curr rren rr ence en ce of MI after AF), we conducted another sensitivity analysis in which we excluded participants with an MI event occurring within a short period (within a week) after a documented AF. Other additional analyses included: 1) Examining the association between AF and MI [overall and by type] using Cox proportional models adjusted for variables in model 3 plus other possible confounders [heart rate, beta blocker use, angiotensin converting enzyme inhibitors use, interim revascularization] all included in the models as time-varying covariates; 2) Comparing the association between AF and MI at different times of follow up; 3) Plotting the cumulative incidence of AF from baseline [1987-1989] to the end of follow up [2010]. The results of these
8 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on April 28, 2015
DOI: 10.1161/CIRCULATIONAHA.114.014145
additional analyses are provided in the Online-Only Data Supplement. Statistical significance for all analyses was p
