Invited Commentary: Will Heart Attacks Be "Gone with the Century"?

Véronique L. Roger 

From the Mayo Foundation, Rochester, MN.

Received for publication July 19, 2004; accepted for publication August 16, 2004.


    INTRODUCTION
 TOP
 INTRODUCTION
 MONITORING TRENDS WITH HOSPITAL...
 NEW CRITERIA, NEW CHALLENGES
 IMPLICATIONS AND FUTURE...
 REFERENCES
 
A frequently quoted editorial by Brown and Goldstein (1) speaks to the importance of myocardial infarction trends as indicators of progress in the battle against heart disease. Indeed, the increase in life expectancy in developed societies compounds the burden of coronary disease in the later stages of life, which has a major impact on the health of the US population. Population-based trends in disease rates are the final measures of the effect of interventions aimed at reducing the burden of disease. This underscores the importance of careful monitoring of coronary heart disease trends for public health, policy-making, and health economics. Myocardial infarctions are an essential component of the burden of coronary disease. While they do not represent all manifestations of the disease, the existence of established criteria amenable to standardization have made myocardial infarction one of the indicators of choice for tracking coronary disease over time.


    MONITORING TRENDS WITH HOSPITAL DATA
 TOP
 INTRODUCTION
 MONITORING TRENDS WITH HOSPITAL...
 NEW CRITERIA, NEW CHALLENGES
 IMPLICATIONS AND FUTURE...
 REFERENCES
 
The conceptual straightforwardness of the task of enumerating myocardial infarctions contrasts sharply with the challenges involved in the practical conduct of such measurements. The National Hospital Discharge Survey relies on hospital discharge codes, chiefly code 410 of the International Classification of Diseases, Ninth Revision, to identify myocardial infarctions (2). The documented shift that took place in hospital discharge diagnoses after the introduction of the Diagnosis-Related Groups payment system challenges the validity of these sources for monitoring disease over time (3, 4). Furthermore, these data are based on numbers of events, not persons, allowing multiple hospitalizations for the same individuals to be counted, and they do not differentiate between the first admission and subsequent admissions. Thus, they cannot measure true incidence rates or track these trends over time.

Conversely, community surveillance relies on codes for case-finding and subjects potential cases to rigorous validation procedures using standardized criteria (2, 5).

The Atherosclerosis Risk in Communities (ARIC) Study is one of a few programs in the United States that is currently positioned to conduct surveillance of coronary disease. ARIC investigators have reported important findings on temporal trends in the incidence of myocardial infarction (6). The complexity and dynamic nature of disease patterns and the techniques used to measure them demand periodic evaluation of the validity of surveillance methods. The article by Rosamond et al. in this issue of the Journal (7) is of utmost importance for characterizing the methodological challenges related to the tracking of myocardial infarction over time. The authors acquired data on a large number of events involving hospitalization that occurred in four diverse US communities between 1987 and 2000, enabling them to identify important race- and sex-specific differences in the sensitivity of code 410 for diagnosing myocardial infarction. The sensitivity of code 410 was greater in men than in women and greater in Whites than in Blacks; the ethnic difference was of greater magnitude and more robust than the sex difference (7). The spectrum of the communities studied in ARIC also enabled the authors to uncover a lower sensitivity of code 410 in teaching hospitals compared with nonteaching hospitals, as well as geographic differences in the sensitivity of code 410.

These findings underscore the need to study disease trends in different settings and diverse populations, which is important from a methodological standpoint for epidemiologic studies. However, the implications of these findings extend beyond these obvious methodological considerations and have important clinical and public health implications. Indeed, the lower sensitivity of code 410 among Blacks indicates that clinical events that meet rigorous standardized criteria for myocardial infarction are less likely to be coded as such among Blacks than among Whites. These events, when they occur among Blacks, are more likely to be coded as "heart failure" or "hypertensive heart disease." As Rosamond et al. underscored, this may reflect increased clinical concern about hypertension and heart failure among Blacks, overshadowing the implications of electrocardiographic and biomarker changes. Debating the appropriateness of this clinical interpretation, which remains speculative (as the authors appropriately acknowledged (7)), is beyond the scope of this commentary and arguably of these data. However, these findings resonate with the abundance of reports highlighting racial differences in the delivery of cardiac care (8) and raise the question of whether differences in management may relate, at least in part, to differences in clinical diagnoses. They also underscore that the nature and perhaps severity of the myocardial infarctions tracked by means of code 410 will probably differ by race, which has important public health implications. To this end, the data reported by Rosamond et al. call attention to the fact that the use of discharge diagnoses such as code 410 may not reliably measure race-specific disease burden and hence may not accurately estimate ethnic differences in disease patterns.


    NEW CRITERIA, NEW CHALLENGES
 TOP
 INTRODUCTION
 MONITORING TRENDS WITH HOSPITAL...
 NEW CRITERIA, NEW CHALLENGES
 IMPLICATIONS AND FUTURE...
 REFERENCES
 
Another important contribution of the study by Rosamond et al. is the insight it provides into temporal trends in the validity of code 410. The report of a declining sensitivity of code 410 among teaching hospitals over time is of particular importance, given the fact that the type of biomarker used to diagnose myocardial infarction in clinical practice was gradually changing during the period covered by the authors’ study. The incorporation of troponin in clinical practice led to the recommendation of a new definition for myocardial infarction by the American College of Cardiology and the European Society of Cardiology (9).

This new definition combines the rise and fall of levels of biochemical markers for myocardial necrosis with any of the following conditions: ischemic symptoms, electrocardiographic changes, and coronary intervention. The biochemical markers recommended are the troponins (T or I), which have gradually replaced creatine kinase and its MB fraction in clinical practice since the mid-1990s. Troponin is more specific than creatine kinase and its MB fraction for the diagnosis of myocardial infarction in the setting of associated skeletal muscle damage or injury including surgery. Of critical importance to clinicians and epidemiologists is the fact that the troponins have higher sensitivity, which allows for the detection of very small amounts of myocardial necrosis that would have gone undetected by creatine kinase and its MB fraction. The increase in the number of myocardial infarctions related to the new definition will depend on the threshold of positivity chosen for troponin, which is still evolving and which varies depending on the assays used (10). Thus, the full impact of the new definition of myocardial infarction remains to be quantified. The aforementioned professional societies recognized that the change in myocardial infarction criteria, particularly as they rely highly on more sensitive biochemical markers, "will confuse efforts to follow trends in disease rates and outcomes" (9, p. 964). However, the potential implications of changing the criteria for the diagnosis of myocardial infarction reach far beyond their impact on disease surveillance and the discontinuity in the trends that this change will unavoidably introduce. Indeed, the new definition will increase the number of myocardial infarctions, enrich the population of myocardial infarctions with troponin-positive/creatine kinase-negative cases, and shift the clinical spectrum of the disease. Because of the profound consequences of a myocardial infarction diagnosis on patient care, disease trends, and utilization of health-care resources, it is critically important for clinicians and public health professionals to gain insight into the changes in case mix related to the new criteria.

The period covered by Rosamond et al.’s study represents only the beginning of what has been heralded as a sea change in the diagnosis of myocardial infarction. However, it presents some interesting preliminary information on this important issue. Indeed, the authors reported a trend of a decreasing sensitivity and positive predictive value of code 410 over time, which was noted within teaching hospitals (7). This raises the question of site-specific differences in the adoption of troponin, which may conceivably vary according to the teaching versus nonteaching nature of the hospitals. Furthermore, the widespread belief that the introduction of troponin would lead to increases in the incidence of myocardial infarction as measured by code 410 is anchored in the assumption that hospitals will readily adopt this new marker and that coding practices will readily follow the implementation of troponin. The ARIC data presented by Rosamond et al. (7) provide strong evidence in support of the rapid rate of adoption of troponin in clinical practice in the ARIC communities. However, these data also highlight the fact that episodes meeting the ARIC criteria for myocardial infarction are less likely to have been coded 410 in more recent years, years characterized by the increasing use of troponin. This suggests that coding practices may not have changed in a way commensurate with the increasing use of troponin.


    IMPLICATIONS AND FUTURE DIRECTIONS
 TOP
 INTRODUCTION
 MONITORING TRENDS WITH HOSPITAL...
 NEW CRITERIA, NEW CHALLENGES
 IMPLICATIONS AND FUTURE...
 REFERENCES
 
These important findings underscore that relying on International Classification of Diseases, Ninth Revision, code 410 to characterize the burden of ischemic disease across communities and populations will probably become increasingly misleading. They call attention to the fact that broader sets of codes, validated on a study-per-study basis as illustrated in the paper by Rosamond et al. (7), will be needed to accurately estimate the burden of disease. Additionally, as discussed above, the diversity of the communities studied in ARIC offers investigators the invaluable ability to study race- and sex-specific validity estimates. However, the variety of study centers can get in the way of precisely measuring the changing validity of the codes which results from the introduction of new biomarkers, because diverse communities will unavoidably exhibit heterogeneous clinical practices, adopt different assays, and use different thresholds of positivity for these different assays. These issues, which are challenging within a single study center (11), become exceedingly complex in analyses combining data from several centers. In anticipation of these concerns, when the new criteria for myocardial infarction were published, it was recommended that the previous definition of myocardial infarction be "retained by specific epidemiological centers" (9, p. 965). However, this recommendation is not feasible for most surveillance programs, such as the ARIC Study, which rely on multiple hospitals and health-care systems for case-finding. Indeed, unless creatine kinase and its MB fraction and troponins are measured simultaneously in the same patients in a population-based setting, the shifts in incidence, case mix, and outcomes resulting from the change in criteria will remain incompletely characterized.

To this end, one relevant limitation of the ARIC data is that the ARIC diagnostic algorithm used two times the upper limit of normal to define an abnormal biomarker. It is likely that use of other cutpoints would have a different impact on the measured validity of code 410. Furthermore, this approach is at variance with the current guideline-based definition, which recommends relying on dynamic changes in biomarkers (12). Thus, the impact of this new definition should be examined in future studies.

As the new myocardial infarction criteria generate continued controversy over their appropriateness (13, 14), more data on the clinical and epidemiologic implications of the change, particularly in community studies, are clearly needed. The paper by Rosamond et al. (7) constitutes an important step towards gaining this needed knowledge and underscores the importance of continued monitoring of myocardial infarction trends.


    NOTES
 
Correspondence to Dr. Véronique Roger, Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (e-mail: roger.veronique{at}mayo.edu). Back


    REFERENCES
 TOP
 INTRODUCTION
 MONITORING TRENDS WITH HOSPITAL...
 NEW CRITERIA, NEW CHALLENGES
 IMPLICATIONS AND FUTURE...
 REFERENCES
 

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