Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Open Access

Peer-reviewed

Research Article

Likelihood and Predictors of ST-Elevation in Patients Hospitalized for Myocardial Infarction

  • Ville Kytö ,

    ville.kyto@utu.fi

    Affiliations Heart Center, Division of Clinical Neurosciences, Neurology and Clinical Research Center, Turku University Hospital, Turku, Finland, PET Center, Medicine, Neurology and Public Health, University of Turku, Turku, Finland

    ⨯
  • Jussi Sipilä,

    Affiliations Heart Center, Division of Clinical Neurosciences, Neurology and Clinical Research Center, Turku University Hospital, Turku, Finland, PET Center, Medicine, Neurology and Public Health, University of Turku, Turku, Finland

    ⨯
  • Päivi Rautava

    Affiliations Heart Center, Division of Clinical Neurosciences, Neurology and Clinical Research Center, Turku University Hospital, Turku, Finland, PET Center, Medicine, Neurology and Public Health, University of Turku, Turku, Finland

    ⨯

Abstract

Importance

Emergency treatment options in myocardial infarction are guided by presence or absence of ST-elevations in electrocardiography. Occurrence and factors associated with ST-presentation in different population groups are however inadequately known.

Objective

To determine likelihood and patient features associated with ST-elevations in myocardial infarction.

Design

Nationwide registry study including 22 hospitals with angiolaboratory during an eight year period in Finland.

Setting

Hospitalized care.

Participants

68,162 consecutive patients aged ≥30 with myocardial infarction.

Measures

Likelihood and patient features associated with presence of ST-elevations.

Results

Myocardial infarction presented with ST-elevation in 37.5% (CI 37.0–37.9%) and without in 62.5% (CI 61.9–63.1%) of patients, p<0.0001. Majority of patients aged 30–59 years with myocardial infarction had ST-elevation, but among octogenarians ST-elevations were present in only 24.7%. Presence of ST-elevations decreased with age by estimated 15.6% (CI 15.0–16.2%) per 10 year increase (p<0.0001). Men aged 40–79 years had significantly higher rate for ST-elevation myocardial infarction compared to women. Sex-based difference in presentation of myocardial infarction declined with increasing age. Overall, men had a 13% (CI 11–15%, p<0.0001) higher relative risk for ST-elevations compared to women when adjusted for age and co-morbidities. Diabetes, atrial fibrillation, peripheral or cerebral artery disease, chronic pulmonary disease, malignancy, and renal insufficiency were associated with absence of ST-elevations in myocardial infarction in multivariate analysis.

Conclusions and Relevance

Myocardial infarction presents with ST-elevations more commonly in men. Presence of ST-elevations decreases with increasing age. Diabetes, atrial fibrillation, peripheral or cerebral artery disease, chronic pulmonary disease, malignancy, and renal insufficiency are associated with absence of ST-elevations in myocardial infarction. These findings may help to predict likelihood of ST-elevations in a patient with myocardial infarction.

Citation: Kytö V, Sipilä J, Rautava P (2014) Likelihood and Predictors of ST-Elevation in Patients Hospitalized for Myocardial Infarction. PLoS ONE 9(9): e108440. https://doi.org/10.1371/journal.pone.0108440

Editor: Qing Song, Morehouse School of Medicine, United States of America

Received: June 22, 2014; Accepted: August 28, 2014; Published: September 25, 2014

Copyright: © 2014 Kytö et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data are available from the Finnish National Institute for Health and Welfare Institutional Data Access/Ethics Committee for researchers who meet the criteria for access to confidential data. Requests may be sent to Mrs. Katariina Peltonen. Finnish National Institute for Health and Welfare. E-mail: katariina.peltonen@thl.fi.

Funding: This study was supported by the clinical research foundation of Turku University Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Emergency treatment strategies of patients with myocardial infarction (MI) are based on ST-segment presentation in electrocardiography. In ST-elevation myocardial infarction (STEMI), an acute total coronary occlusion is present and immediate reperfusion therapy, preferably by primary percutaneous coronary intervention, is required [1], [2]. When ST-elevations are not present, but circulating troponin levels are elevated, patient has a non-ST-elevation myocardial infarction (NSTEMI) requiring intensive medical therapy and invasive assessment of coronary arteries should be conducted during the next 24 hours [3], [4]. Although the majority of all MI patients are known to have NSTEMI [5], factors associated with ST-presentations are less well known. We studied the likelihood of ST-segment elevation in myocardial infarction and patient features predicting it using a large multihospital registry.

Methods

Study Patients and Data Collection

We studied 68,162 consecutive patients aged ≥30 years admitted to hospital with myocardial infarction as primary discharge diagnosis (ICD-10 code I21) in 22 hospitals during a period of 8 years. Infarction was classified as STEMI or NSTEMI based on ICD-10 coding (I21.0x–I21.3x vs. I21.4x–I21.9x, respectively). Data was retrospectively collected from the Finnish Hospital Discharge Register, a nationwide database maintained by the Finnish National Institute for Health and Welfare containing hospital discharge diagnosis codes (ICD-10) of all medical admissions in Finland. Hospital transfers (10.8% of admissions) during the same treatment period were combined as one. All 22 hospitals in Finland that treat emergency patients and have a coronary catheterization laboratory were included. Admissions that begun between January 1st 2001– December 31st 2008 were included. The study was approved by the National Institute for Health and Welfare (permission nro THL/1576/5.05.00/2010). Patient data was received anonymized and de-identified and informed consents were thus not obtained.

Statistical Analysis

Scale variables are presented as mean±SD or median with interquartile range (IQR) as appropriate. Categorical variables are presented as percentages or relative risks (RR) with 95% confidence interval (95% CI) as appropriate. Differences in continuous variables were analyzed with student t-test. Overall distribution of myocardial infarction by presenting ST-change was tested with Chi-square test. Factors associated with the type of myocardial infarction were studied by using a log-binomial regression model. Patient characteristics associated with type of infarction at p<0.05 in univariate analysis (stratified for study year) were included in the final regression model. Two-sided p-values <.05 were considered statistically significant. The SAS system (v.9.3, SAS Institute Inc, Cary, NC, USA) was used for statistical analyses.

Results

Incidence of ST-Elevations in Myocardial Infarction

Myocardial infarction presented with ST-elevation in 25,538 patients (37.5%; CI 37.0–37.9%) and without ST-elevation in 42,624 patients (62.5%; CI 61.9–63.1%), p<0.0001. Mean age of all patients was 71.2±12.6 years. STEMI patients were significantly younger than patients with NSTEMI (67.7±13.0 vs. 73.3±11.8 years, p<0.0001). Presence of ST-elevations in MI decreased with age (Figure 1). Majority of patients aged 30–59 years of age had ST-elevation MI, but of octogenarians only 24.7% (CI 22.9–26.6%) had STEMI. Although the proportion of STEMI did not differ between beginning and end of study period, there was significant annual variation during the study period (Figure 2). Proportion of MI with ST-elevation decreased by estimated 3.3% (CI 2.2–4.4%) annually during 2001–2004 (p<0.0001) followed by an estimated increase of 3.2% (CI 2.3–4.0%, p<0.0001) per year from 2004 onwards.

thumbnail
Download:
Figure 1. Proportion of patients with ST-elevation myocardial infarction by age.

Error bars represent upper limits of 95% confidence interval.

https://doi.org/10.1371/journal.pone.0108440.g001

thumbnail
Download:
Figure 2. Annual variation of the presence of ST-elevation in patients with myocardial infarction.

Error bars represent 95% confidence interval. ** p<0.005, *** p<0.0005 (vs. year 2001). Please note the origin of y-axis.

https://doi.org/10.1371/journal.pone.0108440.g002

Patient Characteristics Associated with ST-Elevation

Majority of both STEMI and NSTEMI patients were male (Table 1). Men had a 32% (CI 30–35%, p<0.0001) higher unadjusted rate for ST-elevations compared to women. Sex-based likelihood for ST-elevation varied however significantly with age, as men aged 40–79 had significantly higher rate than women, and sex-based likelihood decreased with increasing age (Figure 3). After adjustment for age and other characteristics, the overall rate of ST-elevations was 13% (CI 11–15%, p<0.0001) higher in men. The adjusted likelihood of ST-elevation decreased by 15.6% (CI 15.0–16.2%) per 10 increase in age (p<0.0001). Diabetes, atrial fibrillation, peripheral or cerebral artery disease, chronic pulmonary disease, malignancy, and renal insufficiency were all associated with absence of ST-elevation in MI in both univariate (Table 1) and multivariate analyses (Table 2).

thumbnail
Download:
Figure 3. Sex-related likelihood of ST-elevations (STEMI) in myocardial infarction by age.

Relative risk is calculated as men vs. women and adjusted for significant baseline characteristics. Error bars represent 95% confidence interval.

https://doi.org/10.1371/journal.pone.0108440.g003

thumbnail
Download:
Table 1. Characteristics of myocardial infarction patients with (STEMI) and without ST-elevation (NSTEMI).

https://doi.org/10.1371/journal.pone.0108440.t001

thumbnail
Download:
Table 2. Association of patient features with ST-elevation in myocardial infarction in multivariate analysis.

https://doi.org/10.1371/journal.pone.0108440.t002

Discussion

This multi-hospital study of all-comer MI patients describes likelihood and patient characteristics associated with ST-elevations in myocardial infarction. In agreement with previous studies [5] we found the majority of all MIs to be NSTEMI. However, MI presented with ST-elevations more commonly than without in patients less than 59 years of age, and the proportion of STEMI declined with increasing age. This finding may reflect the fact that prevalence of chronic coronary artery disease (CAD) increases with aging [5], [6] and the occlusion of a small, already stenotic small coronary side branch will not result in ST-elevation in electrocardiography. Furthermore, presence of already developed coronary collaterals in patients with stable coronary disease may prevent total ischemia and ST-elevations in vascular territory of totally occluded coronary [7], [8]. Age-related changes in platelet structure and function [9], [10] may also contribute for decreasing proportion of STEMI with age, but significance and pathophysiology of age-related platelet function and thrombogenesis are yet unclear.

Previous studies have found males to be overrepresented by 5–9% among STEMI patients compared to NSTEMI [11]–[17]. Sex-based likelihood for ST-elevation is however rarely presented in literature. A study using Euro-Heart Survey 2004 data found women under 65-years of age to have an odds ratio of 0.62 for ST-elevation compared to men while sex did not affect the risk in older patients, but results were not adjusted for co-founders [18]. We found men to have a relative risk of 1.13 for ST-elevations compared to women after adjustment for age and co-morbidities. Reasons for this gender-bias are unknown, but may include differences in platelet function [19], coagulation-fibrinolytic pathway [20], inflammatory response [21], coronary plaque composition [22], matrix remodeling [23], endothelial function [24], and angiogenesis [25] in addition to lifestyle and risk factors differences [26]. Estrogen is found to play a pivotal role in sex-differences in coronary artery disease [19], [23]–[25], [27]. In agreement, we found the sex-based likelihood for ST-elevation in myocardial infarction to decrease with increasing age.

We found the known markers for the likelihood of CAD, such as atherosclerotic disease of cerebral or peripheral arteries, diabetes, chronic pulmonary disease, and renal insufficiency [5] to be associated with absence of ST-elevations. This most likely reflects the protective role of coronary collaterals [8] from ST-elevation in addition to an increased likelihood for small side branch occlusion. In addition to a higher likelihood for development of chronic CAD [5], diabetes has multiple effects on risk of myocardial infarction including alterations in artery wall and plaque remodeling [28] and thrombogenesis [29]. Atrial fibrillation was also associated with MI without ST-elevations in our study. This may be due to ongoing oral anticoagulation therapy for stroke prevention [30] that also prevents formation of totally occlusive coronary thrombus. Our finding of association between malignancy and absence of ST-elevations is in agreement of a previous study of MI in cancer patients [31], and is likely to be due to cancer related abnormalities in coagulation and thrombosis [32], and the effects of anticancer therapies [33].

Previous studies originating from US [11], Ireland [14], and Italy [34] have reported constantly declining proportions of STEMI among MI patients in recent years. We found the proportion of STEMI to slightly decline during 2001–2004, but contradictory to previous findings, proportion of STEMI steadily increased from 2004 onwards. Reasons for this discrepancy require further study, but the end in the decline of blood pressures in addition to increase in obesity [26] and binge drinking [35] during recent years in Finland are potential contributors.

The current study has limitations associated with use of retrospective hospital registry data. Thus, diagnoses were made by treating physicians, which may have affected the included patient population. Hospital discharge data has, however, proved to be a valuable source of information on cardiovascular disease [36]. The nationwide hospital discharge registry utilized here is government maintained, automatic, and mandatory thus capturing information of all hospital admissions and resulting in accurate information on cardiovascular disease [37], [38]. In addition to a small number of inevitable coding inaccuracies [38], diagnostic inaccuracies may be a potential source of error. As treatment choices in MI rely heavily on distinction between STEMI and NSTEMI, the correct interpretation of electrocardiography and resulting diagnostic classification are however major priorities among physicians treating patients with an acute coronary syndrome. In order to minimize misdiagnosis of MI in chest pain patients with non-coronary causes such as extra-cordial pain, myocarditis, aortic dissection, or pulmonary embolism [39], [40] we included only patients treated in hospitals with coronary angiolaboratory. Therefore, patients who did not reach hospital due to e.g. sudden cardiac death associated with myocardial infarction were not included.

In conclusion, myocardial infarction presents with ST-elevations more commonly in men and the presence of ST-elevations decreases with increasing age. Diabetes, atrial fibrillation, peripheral or cerebral artery disease, chronic pulmonary disease, malignancy, and renal insufficiency are associated with absence of ST-elevations in myocardial infarction. These findings may help to predict likelihood of ST-elevations in a patient with myocardial infarction.

Author Contributions

Conceived and designed the experiments: VK JS PR. Performed the experiments: VK JS. Analyzed the data: VK JS. Contributed reagents/materials/analysis tools: VK JS PR. Contributed to the writing of the manuscript: VK JS PR.

References

  1. 1. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, et al. (2013) 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 127: e362–425.
  2. 2. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), Steg PG, James SK, Atar D, Badano LP, et al (2012) ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33: 2569–2619.
  3. 3. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, et al. (2013) 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 127: e663–828.
  4. 4. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, et al. (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32: 2999–3054.
  5. 5. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, et al. (2014) Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation 129: e28–e292.
  6. 6. Davies AR, Smeeth L, Grundy EM (2007) Contribution of changes in incidence and mortality to trends in the prevalence of coronary heart disease in the UK: 1996 2005. Eur Heart J 28: 2142–2147.
  7. 7. Bahrmann P, Rach J, Desch S, Schuler GC, Thiele H (2011) Incidence and distribution of occluded culprit arteries and impact of coronary collaterals on outcome in patients with non-ST-segment elevation myocardial infarction and early invasive treatment strategy. Clin Res Cardiol 100: 457–467.
  8. 8. Macdonald RG, Hill JA, Feldman RL (1986) ST segment response to acute coronary occlusion: coronary hemodynamic and angiographic determinants of direction of ST segment shift. Circulation 74: 973–979.
  9. 9. Gilstad JR, Gurbel PA, Andersen RE (2009) Relationship between age and platelet activation in patients with stable and unstable angina. Arch Gerontol Geriatr 48: 155–159.
  10. 10. Mohebali D, Kaplan D, Carlisle M, Supiano MA, Rondina MT (2014) Alterations in platelet function during aging: clinical correlations with thromboinflammatory disease in older adults. J Am Geriatr Soc 62: 529–535.
  11. 11. Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, et al. (2010) Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med 362: 2155–2165.
  12. 12. McManus DD, Gore J, Yarzebski J, Spencer F, Lessard D, et al. (2011) Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am J Med 124: 40–47.
  13. 13. Zhang Z, Fang J, Gillespie C, Wang G, Hong Y, et al. (2012) Age-specific gender differences in in-hospital mortality by type of acute myocardial infarction. Am J Cardiol 109: 1097–1103.
  14. 14. Jennings SM, Bennett K, Lonergan M, Shelley E (2012) Trends in hospitalisation for acute myocardial infarction in Ireland, 1997–2008. Heart 98: 1285–1289.
  15. 15. Peterson ED, Shah BR, Parsons L, Pollack CV Jr, French WJ, et al. (2008) Trends in quality of care for patients with acute myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006. Am Heart J 156: 1045–1055.
  16. 16. Nauta ST, Deckers JW, Akkerhuis M, Lenzen M, Simoons ML, et al. (2011) Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008. PLoS One 6: e26917.
  17. 17. Roe MT, Messenger JC, Weintraub WS, Cannon CP, Fonarow GC, et al. (2010) Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol 56: 254–263.
  18. 18. Rosengren A, Wallentin L, A KG, Behar S, Battler A, et al. (2004) Sex, age, and clinical presentation of acute coronary syndromes. Eur Heart J 25: 663–670.
  19. 19. Wang TY, Angiolillo DJ, Cushman M, Sabatine MS, Bray PF, et al. (2012) Platelet biology and response to antiplatelet therapy in women: implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease. J Am Coll Cardiol 59: 891–900.
  20. 20. Braunstein JB, Kershner DW, Bray P, Gerstenblith G, Schulman SP, et al. (2002) Interaction of hemostatic genetics with hormone therapy: new insights to explain arterial thrombosis in postmenopausal women. Chest 121: 906–920.
  21. 21. Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, et al. (1999) Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 100: 717–722.
  22. 22. Mautner SL, Lin F, Mautner GC, Roberts WC (1993) Comparison in women versus men of composition of atherosclerotic plaques in native coronary arteries and in saphenous veins used as aortocoronary conduits. J Am Coll Cardiol 21: 1312–1318.
  23. 23. Tayebjee MH, Lip GY, Tan KT, Patel JV, Hughes EA, et al. (2005) Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease. Am J Cardiol 96: 339–345.
  24. 24. Wu Q, Chambliss K, Umetani M, Mineo C, Shaul PW (2011) Non-nuclear estrogen receptor signaling in the endothelium. J Biol Chem 286: 14737–14743.
  25. 25. Barnabas O, Wang H, Gao XM (2013) Role of estrogen in angiogenesis in cardiovascular diseases. J Geriatr Cardiol 10: 377–382.
  26. 26. Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Männistö S, et al. (2010) Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol 39: 504–518.
  27. 27. Crandall CJ, Barrett-Connor E (2013) Endogenous sex steroid levels and cardiovascular disease in relation to the menopause: a systematic review. Endocrinol Metab Clin North Am 42: 227–253.
  28. 28. Spinetti G, Kraenkel N, Emanueli C, Madeddu P (2008) Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies. Cardiovasc Res 78: 265–273.
  29. 29. Morel O, Jesel L, Abbas M, Morel N (2013) Prothrombotic changes in diabetes mellitus. Semin Thromb Hemost 39: 477–488.
  30. 30. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, et al. (2012) 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33: 2719–2747.
  31. 31. Yusuf SW, Daraban N, Abbasi N, Lei X, Durand JB, et al. (2012) Treatment and outcomes of acute coronary syndrome in the cancer population. Clin Cardiol 35: 443–450.
  32. 32. Levi M (2014) Cancer-related coagulopathies. Thromb Res 133 Suppl 2S70–75.
  33. 33. Yeh ET, Bickford CL (2009) Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 53: 2231–2247.
  34. 34. Ortolani P, Marino M, Melandri G, Guastaroba P, Corzani A, et al. (2013) Recent temporal trends for first-time hospitalization for acute myocardial infarction. Treatment patterns and clinical outcome in a large cohort study. Am Heart J 166: 846–854.
  35. 35. Härkönen JT, Mäkelä P (2011) Age, period and cohort analysis of light and binge drinking in Finland, 1968–2008. Alcohol Alcohol 46: 349–356.
  36. 36. Salomaa V, Havulinna AS, Koukkunen H, Karja-Koskenkari P, Pietilä A, et al. (2013) Aging of the population may not lead to an increase in the numbers of acute coronary events: a community surveillance study and modelled forecast of the future. Heart 99: 954–959.
  37. 37. Pajunen P, Koukkunen H, Ketonen M, Jerkkola T, Immonen-Räihä P, et al. (2005) The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease. Eur J Cardiovasc Prev Rehabil 12: 132–137.
  38. 38. Sund R (2012) Quality of the Finnish Hospital Discharge Register: a systematic review. Scand J Public Health 40: 505–515.
  39. 39. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, et al. (2012) Third universal definition of myocardial infarction. J Am Coll Cardiol 60: 1581–1598.
  40. 40. Kytö V, Sipilä J, Rautava P (2013) The effects of gender and age on occurrence of clinically suspected myocarditis in adulthood. Heart 99: 1681–1684.