International Journal of Cardiology 176 (2014) 1161–1162
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Association of age and gender with anterior location of STEMI Ville Kytö a,b,⁎, Jussi Sipilä c,d, Päivi Rautava e,f a
Heart Center, Turku University Hospital, Turku, Finland PET Center, University of Turku, Turku, Finland c Division of Clinical Neurosciences, Neurology, Turku University Hospital, Turku, Finland d Department of Neurology, University of Turku, Turku, Finland e Clinical Research Center, Turku University Hospital, Turku, Finland f Public Health, University of Turku, Turku, Finland b
a r t i c l e
i n f o
Article history: Received 18 July 2014 Accepted 27 July 2014 Available online 4 August 2014 Keywords: Myocardial infarction Sex Epidemiology Age-distribution ST-segment elevation
Anterior location of ST-elevation myocardial infarction (STEMI) represents abrupt occlusion of left ascending coronary artery (LAD) causing greater myocardial damage and greater extent of adverse remodeling compared to non-anterior infarctions [1,2] increasing the risk of heart failure [3] and death [4]. Mortality after STEMI increases with age [5] and female gender is also associated with increased mortality after STEMI [6]. Relationships of age and gender with location of STEMI are however largely uncharacterized. We studied whether age and gender are associated with anterior location of STEMI in 25,538 consecutive STEMI patients (66.3% males) aged ≥30 years (mean age 67.7 SD 13.0 years) in 22 hospitals with an angiolaboratory during 2001–2008. Data was retrospectively collected from a Finnish National Institute for Health and Welfare maintained nationwide database and included all Finnish hospitals with an angiolaboratory that treat STEMI patients. The study was approved by the National Institute for Health and Welfare (permission THL/1576/ 5.05.00/2010). Association of patient features with anterior STEMI were analyzed by log-binomial regression models stratified by study year. Factors associated with location of infarction at p b 0.05 in univariate analysis were included in the final regression model.
⁎ Corresponding author at: Heart Center, Turku University Hospital, POB 52, FI-20521 Turku, Finland. Fax: +358 23137206. E-mail address: ville.kyto@utu.fi (V. Kytö).
http://dx.doi.org/10.1016/j.ijcard.2014.07.254 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
p-Values b.05 were considered statistically significant. The SAS system (v.9.3, SAS Institute Inc., Cary, NC, USA) was used for statistical analyses. STEMI was anteriorly located in 54.0% (95% confidence intervals (CI) 53.1–54.9%) of all patients. Proportion of anterior STEMI was however age dependent and increased after 60 years of age up to 65.9% (CI 60.0–72.2%) in nanogerians and older (Fig. 1). The estimated increase rate of the proportion of anterior infarction in total study population was 7% per 10-year increase in age. Women presented with anterior ST-elevation more commonly than their counterparts (Table 1) with an overall relative risk (RR) of 1.04 (CI 1.01–1.06, p = 0.0038) in multivariate analysis. Gender-difference was however confined to patients aged 30–49 years (RR 1.20; CI 1.08–1.33; p b 0.0005), but was not present among the older population (Fig. 1B). Cancer and atrial fibrillation were associated with anterior location of ST-elevation in univariate analysis, but were not independent predictors in multivariate model (Table 1). Hypertension was associated with a lower rate of anterior STEMI in both univariate and multivariate analyses (Table 1). This nationwide study describes associations of age and gender with anterior location of STEMI in a population based cohort. Although men are known to be at higher risk for STEMI and incidence of STEMI increases with age [7], information on effects of age and gender on location of STEMI has been scarce. We found women aged 30–49 years to be at significantly higher risk for anterior STEMI than men. Reasons for this gender-bias are unknown, but may include differences in the coagulation–fibrinolytic pathway, inflammatory response, platelet function, matrix remodeling, and endothelial function [8], in addition to risk factor and to lifestyle differences. Hormonal causes, especially estrogen, may be major contributors for gender-difference [8]. Anterior STEMI is commonly caused by the occlusion of LAD and leads to more widespread myocardial damage and adverse post-infarction remodeling compared to non-anterior infarctions [1,2]. Consequently, anterior STEMI increases the risk of death [4] and post-infarction heart failure [3]. Interestingly, women with STEMI are reported to have higher mortality compared to men [6], which may be associated with current observation of higher proportion of anterior infarction. We also found the proportion of anterior infarction to increase with age. As prevalence of chronic stable coronary artery disease [9], and subsequent development of collateral coronary circulation increases with age, it is plausible that smaller non-anterior infarctions are more likely to go clinically undetected in the elderly population leading to increased proportion of anterior STEMI in admitted patients. This is further supported by
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V. Kytö et al. / International Journal of Cardiology 176 (2014) 1161–1162
hospital discharge registry is however government maintained, mandatory, and automatic capturing information on all hospital admissions and resulting in good accuracy. In order to optimize the accuracy of STEMI diagnosis and localization of infarction we included only hospitals with an angiolaboratory. Thus, diagnostic inaccuracies are unlikely to cause a major bias in our study. In conclusion, women aged 30–49 years with STEMI are significantly more likely to have an anterior infarction compared to men. Likelihood of anterior STEMI increases with aging. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments This study was supported by the Clinical Research Foundation of Turku University Hospital. References
Fig. 1. Proportion of patients with anterior STEMI by age (A). Age-specific gender differences (women vs. men) in relative risk for anterior STEMI (B). Error bars represent 95% confidence intervals.
the fact that the occurrence of coronary chronic total occlusions increases with age, and majority of total occlusions are in the right coronary artery [10]. This study has some limitations. A major limitation is the use of retrospective discharge registry data. The used nationwide
[1] Kandzari DE, Tcheng JE, Gersh BJ, et al. Relationship between infarct artery location, epicardial flow, and myocardial perfusion after primary percutaneous revascularization in acute myocardial infarction. Am Heart J 2006;151:1288–95. [2] Masci PG, Ganame J, Francone M, et al. Relationship between location and size of myocardial infarction and their reciprocal influences on post-infarction left ventricular remodelling. Eur Heart J 2011;32:1640–8. [3] Kelly DJ, Gershlick T, Witzenbichler B, et al. Incidence and predictors of heart failure following percutaneous coronary intervention in ST-segment elevation myocardial infarction: the HORIZONS-AMI trial. Am Heart J 2011;162: 663–70. [4] Petrina M, Goodman SG, Eagle KA. The 12-lead electrocardiogram as a predictive tool of mortality after acute myocardial infarction: current status in an era of revascularization and reperfusion. Am Heart J 2006;152:11–8. [5] Khera S, Kolte D, Palaniswamy C, et al. ST-elevation myocardial infarction in the elderly—temporal trends in incidence, utilization of percutaneous coronary intervention and outcomes in the United States. Int J Cardiol 2013;168: 3683–90. [6] Leurent G, Garlantezec R, Auffret V, et al. Gender differences in presentation, management and inhospital outcome in patients with ST-segment elevation myocardial infarction: data from 5000 patients included in the ORBI prospective French regional registry. Arch Cardiovasc Dis 2014;107:291–8. [7] Yang HY, Huang JH, Hsu CY, Chen YJ. Gender differences and the trend in the acute myocardial infarction: a 10-year nationwide population-based analysis. Sci World J 2012;2012:184075. [8] Barnabas O, Wang H, Gao XM. Role of estrogen in angiogenesis in cardiovascular diseases. Am J Geriatr Cardiol 2013;10:377–82. [9] Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 2014;129: e28-292. [10] Fefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol 2012;59:991–7.
Table 1 Association of patient features with anterior localization of STEMI in univariate and multivariate analyses. Association with anterior STEMI
Female sex Hypertension Diabetes Atrial fibrillation Peripheral or cerebral artery disease Chronic pulmonary disease Malignancy Renal insufficiency Rheumatoid arthritis Age (per 10-year increase)
Incidence
Univariate
Multivariate
% (95% CI)
RR (95% CI)
p
RR (95% CI)
p
33.7 (32.9–34.4) 13.5 (13.0–13.9) 7.1 (6.8–7.4) 4.4 (4.1–4.7) 2.0 (1.8–2.2) 1.8 (1.6–2.0) 0.9 (0.8–1.0) 0.6 (0.5–0.7) 0.5 (0.4–0.6)
1.09 (1.07–1.12) 0.88 (0.84–0.91) 1.02 (0.97–1.06) 1.06 (1.01–1.12) 1.07 (0.99–1.15) 0.94 (0.86–1.03) 1.14 (1.03–1.27) 1.00 (0.86–1.15) 0.90 (0.75–1.08) 1.07 (1.06–1.08)
b0.0001 b0.0001 0.4285 0.0179 0.0715 0.1955 0.0117 0.9627 0.2569 b0.0001
1.04 (1.01–1.06) 0.87 (0.84–0.91)
0.0038 b0.0001
1.01 (0.96–1.07)
0.6333
1.10 (0.99–1.22)
0.0760
1.06 (1.05–1.07)
b0.0001
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Association of age and gender with anterior location of STEMI Ville Kytö a,b,⁎, Jussi Sipilä c,d, Päivi Rautava e,f a
Heart Center, Turku University Hospital, Turku, Finland PET Center, University of Turku, Turku, Finland c Division of Clinical Neurosciences, Neurology, Turku University Hospital, Turku, Finland d Department of Neurology, University of Turku, Turku, Finland e Clinical Research Center, Turku University Hospital, Turku, Finland f Public Health, University of Turku, Turku, Finland b
a r t i c l e
i n f o
Article history: Received 18 July 2014 Accepted 27 July 2014 Available online 4 August 2014 Keywords: Myocardial infarction Sex Epidemiology Age-distribution ST-segment elevation
Anterior location of ST-elevation myocardial infarction (STEMI) represents abrupt occlusion of left ascending coronary artery (LAD) causing greater myocardial damage and greater extent of adverse remodeling compared to non-anterior infarctions [1,2] increasing the risk of heart failure [3] and death [4]. Mortality after STEMI increases with age [5] and female gender is also associated with increased mortality after STEMI [6]. Relationships of age and gender with location of STEMI are however largely uncharacterized. We studied whether age and gender are associated with anterior location of STEMI in 25,538 consecutive STEMI patients (66.3% males) aged ≥30 years (mean age 67.7 SD 13.0 years) in 22 hospitals with an angiolaboratory during 2001–2008. Data was retrospectively collected from a Finnish National Institute for Health and Welfare maintained nationwide database and included all Finnish hospitals with an angiolaboratory that treat STEMI patients. The study was approved by the National Institute for Health and Welfare (permission THL/1576/ 5.05.00/2010). Association of patient features with anterior STEMI were analyzed by log-binomial regression models stratified by study year. Factors associated with location of infarction at p b 0.05 in univariate analysis were included in the final regression model.
⁎ Corresponding author at: Heart Center, Turku University Hospital, POB 52, FI-20521 Turku, Finland. Fax: +358 23137206. E-mail address: ville.kyto@utu.fi (V. Kytö).
http://dx.doi.org/10.1016/j.ijcard.2014.07.254 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
p-Values b.05 were considered statistically significant. The SAS system (v.9.3, SAS Institute Inc., Cary, NC, USA) was used for statistical analyses. STEMI was anteriorly located in 54.0% (95% confidence intervals (CI) 53.1–54.9%) of all patients. Proportion of anterior STEMI was however age dependent and increased after 60 years of age up to 65.9% (CI 60.0–72.2%) in nanogerians and older (Fig. 1). The estimated increase rate of the proportion of anterior infarction in total study population was 7% per 10-year increase in age. Women presented with anterior ST-elevation more commonly than their counterparts (Table 1) with an overall relative risk (RR) of 1.04 (CI 1.01–1.06, p = 0.0038) in multivariate analysis. Gender-difference was however confined to patients aged 30–49 years (RR 1.20; CI 1.08–1.33; p b 0.0005), but was not present among the older population (Fig. 1B). Cancer and atrial fibrillation were associated with anterior location of ST-elevation in univariate analysis, but were not independent predictors in multivariate model (Table 1). Hypertension was associated with a lower rate of anterior STEMI in both univariate and multivariate analyses (Table 1). This nationwide study describes associations of age and gender with anterior location of STEMI in a population based cohort. Although men are known to be at higher risk for STEMI and incidence of STEMI increases with age [7], information on effects of age and gender on location of STEMI has been scarce. We found women aged 30–49 years to be at significantly higher risk for anterior STEMI than men. Reasons for this gender-bias are unknown, but may include differences in the coagulation–fibrinolytic pathway, inflammatory response, platelet function, matrix remodeling, and endothelial function [8], in addition to risk factor and to lifestyle differences. Hormonal causes, especially estrogen, may be major contributors for gender-difference [8]. Anterior STEMI is commonly caused by the occlusion of LAD and leads to more widespread myocardial damage and adverse post-infarction remodeling compared to non-anterior infarctions [1,2]. Consequently, anterior STEMI increases the risk of death [4] and post-infarction heart failure [3]. Interestingly, women with STEMI are reported to have higher mortality compared to men [6], which may be associated with current observation of higher proportion of anterior infarction. We also found the proportion of anterior infarction to increase with age. As prevalence of chronic stable coronary artery disease [9], and subsequent development of collateral coronary circulation increases with age, it is plausible that smaller non-anterior infarctions are more likely to go clinically undetected in the elderly population leading to increased proportion of anterior STEMI in admitted patients. This is further supported by
1162
V. Kytö et al. / International Journal of Cardiology 176 (2014) 1161–1162
hospital discharge registry is however government maintained, mandatory, and automatic capturing information on all hospital admissions and resulting in good accuracy. In order to optimize the accuracy of STEMI diagnosis and localization of infarction we included only hospitals with an angiolaboratory. Thus, diagnostic inaccuracies are unlikely to cause a major bias in our study. In conclusion, women aged 30–49 years with STEMI are significantly more likely to have an anterior infarction compared to men. Likelihood of anterior STEMI increases with aging. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments This study was supported by the Clinical Research Foundation of Turku University Hospital. References
Fig. 1. Proportion of patients with anterior STEMI by age (A). Age-specific gender differences (women vs. men) in relative risk for anterior STEMI (B). Error bars represent 95% confidence intervals.
the fact that the occurrence of coronary chronic total occlusions increases with age, and majority of total occlusions are in the right coronary artery [10]. This study has some limitations. A major limitation is the use of retrospective discharge registry data. The used nationwide
[1] Kandzari DE, Tcheng JE, Gersh BJ, et al. Relationship between infarct artery location, epicardial flow, and myocardial perfusion after primary percutaneous revascularization in acute myocardial infarction. Am Heart J 2006;151:1288–95. [2] Masci PG, Ganame J, Francone M, et al. Relationship between location and size of myocardial infarction and their reciprocal influences on post-infarction left ventricular remodelling. Eur Heart J 2011;32:1640–8. [3] Kelly DJ, Gershlick T, Witzenbichler B, et al. Incidence and predictors of heart failure following percutaneous coronary intervention in ST-segment elevation myocardial infarction: the HORIZONS-AMI trial. Am Heart J 2011;162: 663–70. [4] Petrina M, Goodman SG, Eagle KA. The 12-lead electrocardiogram as a predictive tool of mortality after acute myocardial infarction: current status in an era of revascularization and reperfusion. Am Heart J 2006;152:11–8. [5] Khera S, Kolte D, Palaniswamy C, et al. ST-elevation myocardial infarction in the elderly—temporal trends in incidence, utilization of percutaneous coronary intervention and outcomes in the United States. Int J Cardiol 2013;168: 3683–90. [6] Leurent G, Garlantezec R, Auffret V, et al. Gender differences in presentation, management and inhospital outcome in patients with ST-segment elevation myocardial infarction: data from 5000 patients included in the ORBI prospective French regional registry. Arch Cardiovasc Dis 2014;107:291–8. [7] Yang HY, Huang JH, Hsu CY, Chen YJ. Gender differences and the trend in the acute myocardial infarction: a 10-year nationwide population-based analysis. Sci World J 2012;2012:184075. [8] Barnabas O, Wang H, Gao XM. Role of estrogen in angiogenesis in cardiovascular diseases. Am J Geriatr Cardiol 2013;10:377–82. [9] Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 2014;129: e28-292. [10] Fefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol 2012;59:991–7.
Table 1 Association of patient features with anterior localization of STEMI in univariate and multivariate analyses. Association with anterior STEMI
Female sex Hypertension Diabetes Atrial fibrillation Peripheral or cerebral artery disease Chronic pulmonary disease Malignancy Renal insufficiency Rheumatoid arthritis Age (per 10-year increase)
Incidence
Univariate
Multivariate
% (95% CI)
RR (95% CI)
p
RR (95% CI)
p
33.7 (32.9–34.4) 13.5 (13.0–13.9) 7.1 (6.8–7.4) 4.4 (4.1–4.7) 2.0 (1.8–2.2) 1.8 (1.6–2.0) 0.9 (0.8–1.0) 0.6 (0.5–0.7) 0.5 (0.4–0.6)
1.09 (1.07–1.12) 0.88 (0.84–0.91) 1.02 (0.97–1.06) 1.06 (1.01–1.12) 1.07 (0.99–1.15) 0.94 (0.86–1.03) 1.14 (1.03–1.27) 1.00 (0.86–1.15) 0.90 (0.75–1.08) 1.07 (1.06–1.08)
b0.0001 b0.0001 0.4285 0.0179 0.0715 0.1955 0.0117 0.9627 0.2569 b0.0001
1.04 (1.01–1.06) 0.87 (0.84–0.91)
0.0038 b0.0001
1.01 (0.96–1.07)
0.6333
1.10 (0.99–1.22)
0.0760
1.06 (1.05–1.07)
b0.0001
