Patterns of Alcohol Consumption and Myocardial Infarction Risk: Observations from 52 Countries in the INTERHEART Case-Control Study Darryl P. Leong, Andrew Smyth, Koon K. Teo, Martin McKee, Sumathy Rangarajan, Prem Pais, Lisheng Liu, Sonia S. Anand and Salim Yusuf on behalf of the INTERHEART investigators Circulation. published online June 13, 2014; Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/early/2014/06/13/CIRCULATIONAHA.113.007627
Data Supplement (unedited) at: http://circ.ahajournals.org/content/suppl/2014/06/13/CIRCULATIONAHA.113.007627.DC1.html
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
Patterns of Alcohol Consumption and Myocardial Infarction Risk: Observations from 52 Countries in the INTERHEART Case-Control Study
Running title: Leong et al.; Alcohol use pattern and myocardial infarction risk Darryl P. Leong, MBBS, MPH, PhD1; Andrew Smyth, MB BCh1; Koon K. Teo, MB BCh, PhD1; Martin McKee, MD DSc2; Sumathy Rangarajan, MSc1; Prem Pais, MD3; Lisheng Liu, MD4; Sonia S. Anand, MD, PhD1; Salim Yusuf, MBBS, DPhil1 on behalf of the INTERHEART investigators*
1
Population Popu Po pula pu lati la tion ti o H on Health eaalt l h Research Institute, McMaster McMaast steer University and and Hamilton Haami m lton Health Sciences,
Hamilton, H Hamilton a n, ON ON, Ca Cana Canada; nada na da;; 2Lo da London ond ndon on S School choo ch o l of H oo Hygiene yggienee aand nd T Tropical ro opica caal Me Medi Medicine, d ciine ne,, Lo Lond London, n on nd on, Un Unit United ited it e ed Kingdom; K ingdom; m; 3S St.John’s t.JJohnn’ss Me Medical ediicall Co Coll College, lleg eg ge, B Bangalore, angalo lorre, In Indi India; dia; di a 4Fuu W Wai ai H Hospital, osppitaal,, Be Beijing, eijiing g, C China hin na
*a Supplemental Material *a complete compllete te list lis istt of the the INTERHEART INT NTER ERHE HEAR ART T investigators inve in vest stig igat gator orss can caan be found fou ound nd iin n th thee Su Supp ppple leme ment ntall M ateriiall
Address for Correspondence: Darryl P. Leong, MBBS, MPH, PhD C2-5B DBRI, Hamilton General Hospital 237 Barton Street East Hamilton, ON, L8L 2X2, Canada Tel: +1-905-521-2100, ext 40382 Fax: +1-905-297-3781 Email: [email protected]
Journal Subject Code: Atherosclerosis:[135] Risk factors
1 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
Abstract
Background—While moderate alcohol use is associated with protection against myocardial infarction (MI), it is not known whether this effect is generalizable to populations worldwide. It is also uncertain whether differences in the pattern of alcohol use (and in particular heavy episodic consumption) between different regions negates any beneficial effect. Methods and Results—We included 12,195 cases of first MI and 15,583 age- and sex-matched controls from 52 countries. Current alcohol use was associated with a reduced risk of MI (compared to non-users, adjusted odds ratio 0.87; 95% CI 0.80-0.94, p=0.001), however the strength (region-alcohol interaction trength of this assocation was not uniform across different regions (region-alco ohol hol in inte tera te ract ra ctio ct ionn io p65 >65 years, yeear ears, odds odds ratio odd rattio 5.3; 5..3; 95% 95% CI CI 1.6-18, 1.66--18 18,, p=0.008). p= =0. 0 00 008)). Conclusions—In moderate Co onc nclu lusi lu sion on ns—I —Inn most most mos st participants, par artici c paant ci nts, s, low low w levels lev evel elss off alcohol alc l ohol ohol use usee are aree associated ass ssoc occiaate tedd with with a m odeerat eratee reduction MI, may uniform eduction in tthe he rrisk iskk off M is I,, hhowever owev ow ever ev err the he sstrength t en tr engt gthh ooff th gt tthis iss aassociation ssoc ss o ia oc iati tion ti onn m ay nnot o bbee un ot unif ifor if o m across or different countries. An episode of heavy drinking is associated with an increased risk of acute MI in the subsequent 24 hours, particularly in older individuals.
Key words: myocardial infarction, alcohol, risk factor, epidemiology
2 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
Introduction Alcohol use is implicated as a cause in over 2.5 million deaths worldwide in 2010, primarily from injuries, cirrhosis, cardiovascular disease (CVD) and cancer, and was ranked the fifth most important risk factor contributing to the global burden of disease1. The relationship between alcohol consumption and myocardial infarction (MI) is complex. Several studies have reported that low or moderate alcohol use is protective against MI 2-5 but these studies have mostly been conducted in high-income countries so it is not known whether such a protective association is generalizable world-wide. Also, the pattern (i.e. frequency and amount) of alcohol use may be an important modifier of the association between alcohol and MI. Regular moderate consumption and episodic heavy drinking have differing physiological effects on lipids, and oon n pl pplatelet attel elet et aand nd nd endothelial function6. There is now considerable evidence that episodic heavy drinking is associated as ssooci ciat ated at ed with with it myocardial myoocardial damage and is a riskk factor my factor for suddenn card cardiac rd dia iacc death7, however the ev vid den e ce linki ing eepisodes piso pi soodees of hheavy eavy ea vy ddrinking riinkingg tto o co onfirm onf med ed M I (as Is (as opposed oppposed to the op the constellation coons onstel st lla lati tionn of ti evidence linking confirmed MIs conditions co ond ndit itio it i ns that io tha hatt include in nclud udee sudden suddeen sudd en cardiac car ardi diac di ac deaths) dea eath ths)) is th i contradictory. contrrad dic icttory tory ry. One One pr prior rio iorr ca case-control asee-c -con onttrol on tr l st study tudy tudy y eported thatt consuming cons co nsum ns umin um in ng >44 alcoholic alc lcoh ohooli oh licc beverages beve be vera ve rage ra gess was ge was associated asso as soci so ciat ci ated at ed w itth a rreduced educ ed u ed uc d rrisk iskk of is o MI in the reported with subsequent 24 hours8, whereas a case-crossover study found that any alcohol use (including heavy episodic use) increased risk of MI in the following 12 hours9. It is not known whether regular alcohol use protects against MI across different geographic regions given that the prevalence of episodic heavy drinking varies. INTERHEART was a case-control study of MI undertaken in 12,461 individuals with a first MI and 14,637 age- and sex-matched controls from 52 countries in Asia, Europe, the Middle East, Africa, Australia, North and South America. This study provides an opportunity to 1) assess whether the protective association of alcohol consumption with MI is consistent in
3 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
different regions of the world, 2) assess whether the protective association between alcohol consumption and MI differs in people with varying demography, and 3) determine whether episodic heavy consumption of alcohol may be an acute trigger for MI. We hypothesized that regular alcohol use is protective, but that an acute episode of heavy drinking may increase the risk of MI within the 24 hours after consumption.
Methods Participants The INTERHEART study was a case-control study of first acute MI undertaken in 262 centres across 52 countries. The details of this study have been published previously10, 11. In brief, bri rief ef,, ef consecutive cases of first MI presenting within 24 hours of symptom onset were eligible. MI was defined defi fine need by tthe h ppresence he rese re s nce of characteristic sympto se symptoms oms accompanied by is ischaemic sch chae a mic electrocardiographic el lecctr trocardiiog ogra raaphicc cchanges hang ha ngges ((webappendix weba we bapp ba ppen pp en ndi dixx 1 of R Ref. ef. 100). F For or eeach achh ca ac case case, se, at se at least lea eaast one one sexsex ex- and and ageag ma atcche hed (± ((±5 5 ye yyears) ars) control conttrol ol with witth noo history hissto ory of of hheart eart ea rt ddisease issease oorr ex xerrtion onal al ch hest ppain hest a n wa ai was matched exertional chest simultaneously imu mult ltan lt aneo an eous eo usly us ly recruited rec ecru ruit ru ited it ed from fro rom m the the hospital hosp ho spit sp ital it al or or community. com ommu muni mu nity ni ty. Hospital ty Hosp Ho spit sp ital it al controls con ontr trol tr olss (5 ol (58% (58%) 8%)) we 8% were re identified from patients at the same centre with illnesses not obviously related to coronary heart disease or its risk factors. Community controls (36%) were visitors or relatives of a patient from a non-cardiac ward, or an unrelated visitor of another cardiac patient. A further 3% of controls were from the WHO MONICA study12, and the remaining 3% were from an undocumented source10. Data on alcohol consumption were not recorded for 54 controls and 266 cases. The following analysis is based on the remaining 14,583 controls and 12,195 cases. Procedures Trained staff administered a structured questionnaire and performed a standardised physical
4 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
examination on participants. Alcohol exposure was characterised by asking all participants whether they consumed any alcoholic beverage within the past 12 months, and if so, how frequently (4 times per week (Figure 2). This relationship was evident in the unadjusted analysis and persisted after adjustment (Figure 2). Alcohol as an Acute Trigger of MI Data on alcohol consumption in the 48 hours prior to the MI were available for a total of 11,652 MI cases. Of these, 9177 (78.8%) consumed no alcohol during either the hazard or the control
9 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
period, 527 (4.5%) consumed alcohol during the hazard period but not the control period, 514 (4.4%) consumed alcohol during the control period but not the hazard period, and 1434 (12.3%) consumed alcohol during both periods. There was no excess risk of MI if any alcohol was consumed within the hazard period (odds ratio 1.0; 95% CI 0.91-1.2, p=0.7). In contrast to the neutral effect of any alcohol consumption during the hazard period, heavy drinking (6 drinks) during the hazard period was associated with a significant elevation in the risk of MI (OR 1.4; 95% CI 1.1-1.9, p=0.01). The harmful association of heavy episodic drinking was also evident when heavy drinking was defined using an alternative definition of 5 drinks in men or 4 drinks in women within a 24 hour period18, where the OR was 1.4 (95% CI 1.2-1.8, p=0.001). This harmful effect was particularly notable among older ind individuals div vid dua uals lss compared with younger individuals (respective ORs for those aged 65 >6 65 years yeaars ye ars were w re 0.84, we 0.8 .84, 84 95% CI 0.51-1.4, p=0.5; 1.6, 1.66, 95% 95% CI 1.1-2.2, 2 p=0.01; p=0 =0 0.0 .01; 0 and 5.3, 95% CI 1.6heavy interaction Figure 118, 8, p= pp=0.008; 0.008; aage-episodic gee-eepiisodi dicc he heav avyy dr av ddrinking i kinng in in nteeracttioon pp
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/early/2014/06/13/CIRCULATIONAHA.113.007627
Data Supplement (unedited) at: http://circ.ahajournals.org/content/suppl/2014/06/13/CIRCULATIONAHA.113.007627.DC1.html
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
Patterns of Alcohol Consumption and Myocardial Infarction Risk: Observations from 52 Countries in the INTERHEART Case-Control Study
Running title: Leong et al.; Alcohol use pattern and myocardial infarction risk Darryl P. Leong, MBBS, MPH, PhD1; Andrew Smyth, MB BCh1; Koon K. Teo, MB BCh, PhD1; Martin McKee, MD DSc2; Sumathy Rangarajan, MSc1; Prem Pais, MD3; Lisheng Liu, MD4; Sonia S. Anand, MD, PhD1; Salim Yusuf, MBBS, DPhil1 on behalf of the INTERHEART investigators*
1
Population Popu Po pula pu lati la tion ti o H on Health eaalt l h Research Institute, McMaster McMaast steer University and and Hamilton Haami m lton Health Sciences,
Hamilton, H Hamilton a n, ON ON, Ca Cana Canada; nada na da;; 2Lo da London ond ndon on S School choo ch o l of H oo Hygiene yggienee aand nd T Tropical ro opica caal Me Medi Medicine, d ciine ne,, Lo Lond London, n on nd on, Un Unit United ited it e ed Kingdom; K ingdom; m; 3S St.John’s t.JJohnn’ss Me Medical ediicall Co Coll College, lleg eg ge, B Bangalore, angalo lorre, In Indi India; dia; di a 4Fuu W Wai ai H Hospital, osppitaal,, Be Beijing, eijiing g, C China hin na
*a Supplemental Material *a complete compllete te list lis istt of the the INTERHEART INT NTER ERHE HEAR ART T investigators inve in vest stig igat gator orss can caan be found fou ound nd iin n th thee Su Supp ppple leme ment ntall M ateriiall
Address for Correspondence: Darryl P. Leong, MBBS, MPH, PhD C2-5B DBRI, Hamilton General Hospital 237 Barton Street East Hamilton, ON, L8L 2X2, Canada Tel: +1-905-521-2100, ext 40382 Fax: +1-905-297-3781 Email: [email protected]
Journal Subject Code: Atherosclerosis:[135] Risk factors
1 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
Abstract
Background—While moderate alcohol use is associated with protection against myocardial infarction (MI), it is not known whether this effect is generalizable to populations worldwide. It is also uncertain whether differences in the pattern of alcohol use (and in particular heavy episodic consumption) between different regions negates any beneficial effect. Methods and Results—We included 12,195 cases of first MI and 15,583 age- and sex-matched controls from 52 countries. Current alcohol use was associated with a reduced risk of MI (compared to non-users, adjusted odds ratio 0.87; 95% CI 0.80-0.94, p=0.001), however the strength (region-alcohol interaction trength of this assocation was not uniform across different regions (region-alco ohol hol in inte tera te ract ra ctio ct ionn io p65 >65 years, yeear ears, odds odds ratio odd rattio 5.3; 5..3; 95% 95% CI CI 1.6-18, 1.66--18 18,, p=0.008). p= =0. 0 00 008)). Conclusions—In moderate Co onc nclu lusi lu sion on ns—I —Inn most most mos st participants, par artici c paant ci nts, s, low low w levels lev evel elss off alcohol alc l ohol ohol use usee are aree associated ass ssoc occiaate tedd with with a m odeerat eratee reduction MI, may uniform eduction in tthe he rrisk iskk off M is I,, hhowever owev ow ever ev err the he sstrength t en tr engt gthh ooff th gt tthis iss aassociation ssoc ss o ia oc iati tion ti onn m ay nnot o bbee un ot unif ifor if o m across or different countries. An episode of heavy drinking is associated with an increased risk of acute MI in the subsequent 24 hours, particularly in older individuals.
Key words: myocardial infarction, alcohol, risk factor, epidemiology
2 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
Introduction Alcohol use is implicated as a cause in over 2.5 million deaths worldwide in 2010, primarily from injuries, cirrhosis, cardiovascular disease (CVD) and cancer, and was ranked the fifth most important risk factor contributing to the global burden of disease1. The relationship between alcohol consumption and myocardial infarction (MI) is complex. Several studies have reported that low or moderate alcohol use is protective against MI 2-5 but these studies have mostly been conducted in high-income countries so it is not known whether such a protective association is generalizable world-wide. Also, the pattern (i.e. frequency and amount) of alcohol use may be an important modifier of the association between alcohol and MI. Regular moderate consumption and episodic heavy drinking have differing physiological effects on lipids, and oon n pl pplatelet attel elet et aand nd nd endothelial function6. There is now considerable evidence that episodic heavy drinking is associated as ssooci ciat ated at ed with with it myocardial myoocardial damage and is a riskk factor my factor for suddenn card cardiac rd dia iacc death7, however the ev vid den e ce linki ing eepisodes piso pi soodees of hheavy eavy ea vy ddrinking riinkingg tto o co onfirm onf med ed M I (as Is (as opposed oppposed to the op the constellation coons onstel st lla lati tionn of ti evidence linking confirmed MIs conditions co ond ndit itio it i ns that io tha hatt include in nclud udee sudden suddeen sudd en cardiac car ardi diac di ac deaths) dea eath ths)) is th i contradictory. contrrad dic icttory tory ry. One One pr prior rio iorr ca case-control asee-c -con onttrol on tr l st study tudy tudy y eported thatt consuming cons co nsum ns umin um in ng >44 alcoholic alc lcoh ohooli oh licc beverages beve be vera ve rage ra gess was ge was associated asso as soci so ciat ci ated at ed w itth a rreduced educ ed u ed uc d rrisk iskk of is o MI in the reported with subsequent 24 hours8, whereas a case-crossover study found that any alcohol use (including heavy episodic use) increased risk of MI in the following 12 hours9. It is not known whether regular alcohol use protects against MI across different geographic regions given that the prevalence of episodic heavy drinking varies. INTERHEART was a case-control study of MI undertaken in 12,461 individuals with a first MI and 14,637 age- and sex-matched controls from 52 countries in Asia, Europe, the Middle East, Africa, Australia, North and South America. This study provides an opportunity to 1) assess whether the protective association of alcohol consumption with MI is consistent in
3 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
different regions of the world, 2) assess whether the protective association between alcohol consumption and MI differs in people with varying demography, and 3) determine whether episodic heavy consumption of alcohol may be an acute trigger for MI. We hypothesized that regular alcohol use is protective, but that an acute episode of heavy drinking may increase the risk of MI within the 24 hours after consumption.
Methods Participants The INTERHEART study was a case-control study of first acute MI undertaken in 262 centres across 52 countries. The details of this study have been published previously10, 11. In brief, bri rief ef,, ef consecutive cases of first MI presenting within 24 hours of symptom onset were eligible. MI was defined defi fine need by tthe h ppresence he rese re s nce of characteristic sympto se symptoms oms accompanied by is ischaemic sch chae a mic electrocardiographic el lecctr trocardiiog ogra raaphicc cchanges hang ha ngges ((webappendix weba we bapp ba ppen pp en ndi dixx 1 of R Ref. ef. 100). F For or eeach achh ca ac case case, se, at se at least lea eaast one one sexsex ex- and and ageag ma atcche hed (± ((±5 5 ye yyears) ars) control conttrol ol with witth noo history hissto ory of of hheart eart ea rt ddisease issease oorr ex xerrtion onal al ch hest ppain hest a n wa ai was matched exertional chest simultaneously imu mult ltan lt aneo an eous eo usly us ly recruited rec ecru ruit ru ited it ed from fro rom m the the hospital hosp ho spit sp ital it al or or community. com ommu muni mu nity ni ty. Hospital ty Hosp Ho spit sp ital it al controls con ontr trol tr olss (5 ol (58% (58%) 8%)) we 8% were re identified from patients at the same centre with illnesses not obviously related to coronary heart disease or its risk factors. Community controls (36%) were visitors or relatives of a patient from a non-cardiac ward, or an unrelated visitor of another cardiac patient. A further 3% of controls were from the WHO MONICA study12, and the remaining 3% were from an undocumented source10. Data on alcohol consumption were not recorded for 54 controls and 266 cases. The following analysis is based on the remaining 14,583 controls and 12,195 cases. Procedures Trained staff administered a structured questionnaire and performed a standardised physical
4 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
examination on participants. Alcohol exposure was characterised by asking all participants whether they consumed any alcoholic beverage within the past 12 months, and if so, how frequently (4 times per week (Figure 2). This relationship was evident in the unadjusted analysis and persisted after adjustment (Figure 2). Alcohol as an Acute Trigger of MI Data on alcohol consumption in the 48 hours prior to the MI were available for a total of 11,652 MI cases. Of these, 9177 (78.8%) consumed no alcohol during either the hazard or the control
9 Downloaded from http://circ.ahajournals.org/ at BIBLIOTHEQUE DE L'UNIV LAVAL on June 14, 2014
DOI: 10.1161/CIRCULATIONAHA.113.007627
period, 527 (4.5%) consumed alcohol during the hazard period but not the control period, 514 (4.4%) consumed alcohol during the control period but not the hazard period, and 1434 (12.3%) consumed alcohol during both periods. There was no excess risk of MI if any alcohol was consumed within the hazard period (odds ratio 1.0; 95% CI 0.91-1.2, p=0.7). In contrast to the neutral effect of any alcohol consumption during the hazard period, heavy drinking (6 drinks) during the hazard period was associated with a significant elevation in the risk of MI (OR 1.4; 95% CI 1.1-1.9, p=0.01). The harmful association of heavy episodic drinking was also evident when heavy drinking was defined using an alternative definition of 5 drinks in men or 4 drinks in women within a 24 hour period18, where the OR was 1.4 (95% CI 1.2-1.8, p=0.001). This harmful effect was particularly notable among older ind individuals div vid dua uals lss compared with younger individuals (respective ORs for those aged 65 >6 65 years yeaars ye ars were w re 0.84, we 0.8 .84, 84 95% CI 0.51-1.4, p=0.5; 1.6, 1.66, 95% 95% CI 1.1-2.2, 2 p=0.01; p=0 =0 0.0 .01; 0 and 5.3, 95% CI 1.6heavy interaction Figure 118, 8, p= pp=0.008; 0.008; aage-episodic gee-eepiisodi dicc he heav avyy dr av ddrinking i kinng in in nteeracttioon pp
