Author + information
- Received July 23, 2016
- Revision received September 23, 2016
- Accepted October 4, 2016
- Published online January 2, 2017.
- Isaac R. Whitman, MDa,
- Vratika Agarwal, MDb,
- Gregory Nah, MAa,
- Jonathan W. Dukes, MDc,
- Eric Vittinghoff, PhDd,
- Thomas A. Dewland, MDe and
- Gregory M. Marcus, MD, MASa,∗ ()
- aUniversity of California-San Francisco, Division of Electrophysiology, San Francisco, California
- bDivision of Cardiology, Staten Island University Hospital, Staten Island, New York
- cCardiology Associates Medical Group, Ventura, California
- dDepartment of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, California
- eKnight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon
- ↵∗Reprint requests and correspondence:
Dr. Gregory M. Marcus, Division of Electrophysiology, University of California-San Francisco, 505 Parnassus Avenue, M-1180B, Box 0124, San Francisco, California 94143-0124.
Background Understanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.
Objectives The study sought to investigate the associations among alcohol abuse and atrial fibrillation (AF), myocardial infarction (MI), and congestive heart failure (CHF).
Methods Using the Healthcare Cost and Utilization Project database, we performed a longitudinal analysis of California residents ≥21 years of age who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2009. We determined the risk of an alcohol abuse diagnosis on incident AF, MI, and CHF. Patient characteristics modifying the associations and population-attributable risks were determined.
Results Among 14,727,591 patients, 268,084 (1.8%) had alcohol abuse. After multivariable adjustment, alcohol abuse was associated with an increased risk of incident AF (hazard ratio [HR]: 2.14; 95% confidence interval [CI]: 2.08 to 2.19; p < 0.0001), MI (HR: 1.45; 95% CI: 1.40 to 1.51; p < 0.0001), and CHF (HR: 2.34; 95% CI: 2.29 to 2.39; p < 0.0001). In interaction analyses, individuals without conventional risk factors for cardiovascular disease exhibited a disproportionately enhanced risk of each outcome. The population-attributable risk of alcohol abuse on each outcome was of similar magnitude to other well-recognized modifiable risk factors.
Conclusions Alcohol abuse increased the risk of AF, MI, and CHF to a similar degree as other well-established risk factors. Those without traditional cardiovascular risk factors are disproportionately prone to these cardiac diseases in the setting of alcohol abuse. Thus, efforts to mitigate alcohol abuse might result in meaningful reductions of cardiovascular disease.
Despite advances in prevention and treatments, cardiovascular disease continues to be the most prevalent threat to health and survival in the United States, comprising >25% of all deaths (1,2). More than 500,000 Americans experienced a first-time myocardial infarction (MI) in 2015, there are >870,000 new congestive heart failure (CHF) diagnoses annually, and atrial fibrillation (AF), the most common cardiac arrhythmia in the United States, affects >6 million Americans and imposes a high risk of embolic stroke (3). Furthermore, with an aging population and enhanced detection techniques, prevalent MI and incident CHF and AF are on the rise, with a combined projected annual financial burden approaching $400 billion by 2030 (3–5). As such, defining and understanding modifiable risk factors for cardiovascular disease is of particular importance, and targeting modifiable risk factors common to AF, MI, and CHF could have a particularly broad impact.
Alcohol is the most commonly consumed drug in the United States (6). Several studies suggest that moderate levels of alcohol consumption may help prevent incident MI and CHF (7–15). Conversely, even low to moderate levels of alcohol consumption have been shown to increase the incidence of AF (16–18). Nonetheless, the lay press often highlights the potential health benefits of alcohol consumption (19,20), and in fact, those who think alcohol is heart healthy drink more (21).
Alcohol abuse is present in 10 to 15 million Americans (6). Although particular harms of alcohol abuse are appropriately frequently highlighted, including increased risk of domestic violence, suicide, accidents, cirrhosis, and some cancers (22), to some extent the cardiovascular published literature may justify the moderate consumption of alcohol (23). The cardiovascular effects of alcohol abuse are not well characterized in population-based research. Indeed, this is generally difficult to study as the great majority of epidemiological studies rely on self-reported alcohol consumption, an ascertainment method known to be particularly inaccurate in individuals who drink heavily (24,25).
With evidence supporting cardiovascular protection and harm as a result of alcohol consumption, the question arises as to whether particular subgroups of patients might be more negatively impacted by alcohol consumption in regards to cardiovascular risk. No study has rigorously examined the interactions between alcohol use and known cardiovascular risk factors, likely because such interaction analyses requires substantial statistical power and therefore a particularly large number of subjects. We therefore leveraged data from every ambulatory surgical, emergency department, and inpatient encounter in California from 2005 to 2009 to evaluate the association between alcohol abuse and AF, MI, and CHF. We then identified subgroups most affected by these associations and determined the relative population-level burdens of AF, MI, and CHF that can be attributed to alcohol abuse.
All California residents ≥21 years of age who received care in a California ambulatory surgery unit, emergency department, or inpatient hospital unit between January 1, 2005, and December 31, 2009, were identified using the Healthcare Cost and Utilization Project (HCUP) California State Ambulatory Surgery Databases, Emergency Department Databases, and State Inpatient Databases (26). The individual HCUP databases specific to health care setting and calendar year were merged using an encrypted unique patient identifier to capture repeated visits for a given patient. Participants entered the cohort at first health care encounter and were censored upon incident diagnosis of the given outcome of interest (AF, MI, and CHF in separate analyses), at the time of inpatient death, or, in the absence of either, were administratively censored at the end of follow-up (December 31, 2009). Patients with residence outside of California or with missing visit date information were excluded, as well as patients with prevalent AF, MI, or CHF in the respective analyses (defined as carrying the diagnosis at the first recorded hospital encounter).
We recorded demographic data, including age, sex, race, and income at each health care encounter. Race and Hispanic ethnicity are reported separately in HCUP, and race was coded as either white or other for the vast majority of individuals with Hispanic ethnicity. Therefore, those with Hispanic ethnicity were treated as a distinct group that superseded the coded race. Income level was categorized by quartiles using the median household income for the patient’s zip code; observations with missing data had the value carried forward from the most recent encounter, and those patients without any income data over the study period were excluded. Up to 25 International Classification of Diseases-9th Revision (ICD-9) codes and 21 Current Procedural Terminology (CPT) codes were provided for each encounter. The specific codes used for alcohol abuse, covariates, and each outcome variable are described in Online Table 1.
Because post-operative AF after cardiothoracic surgery may have a different underlying mechanism than AF occurring outside of this acute surgical setting, AF was not recorded if a patient had undergone cardiothoracic surgery during the same hospitalization or within the previous 30 days (27). Such patients remained under observation and could be diagnosed with AF outside of this blanking period. As systolic heart failure is mechanistically different from heart failure with preserved ejection fraction, systolic dysfunction was the primary CHF outcome. A sensitivity analysis using heart failure without systolic dysfunction alone was also performed. MI diagnoses were restricted to acute MI, and an a priori subgroup analysis was performed restricting the endpoint to ST-segment elevation myocardial infarction (STEMI) only. Across each analysis, medical comorbidities postulated to confound or mediate the association among alcohol abuse coding and AF, MI, or CHF, respectively, were also recorded using ICD-9 and CPT codes. Dichotomous medical comorbidity variables were accumulated at each health care encounter and carried forward over time.
Continuous variables with a normal distribution are presented as mean ± SD. The cumulative incidences of AF, MI, and CHF were estimated, treating death as a competing risk in each. Because results treating deaths as a competing risk did not substantially differ from the standard estimates, Cox models were used to assess the independent effects of alcohol abuse, and to estimate cumulative incidence in both groups under a proportional hazards assumption. Cox proportional hazards models were used to investigate associations with incident events both before and after controlling for mediators and confounders. In these models, demographic characteristics and medical comorbidities were treated as time-dependent covariates. All analyses were controlled for potential confounders identified a priori that were available in the dataset. The proportional hazards assumption was assessed using Kaplan-Meier versus predicted survival plots and log-minus-log survival plots and was met for each outcome.
Effect modification of the relationship between alcohol abuse and the outcomes was assessed by testing for interactions with demographic characteristics and established cardiovascular risk factors. To enhance interpretation of these results, race was dichotomized as white versus non-white, and age was dichotomized as <60 years of age or ≥60 years of age. Each interaction term was analyzed separately and adjusted for all other covariates. All interaction terms and potential confounders in each analysis were identified a priori from those available in the administrative dataset. Differences in absolute 3-year risks were calculated for each outcome, stratified by cardiovascular risk factors and presence or absence of alcohol abuse.
The population-attributable risk for each outcome was calculated for all covariates in each model. Population-attributable risk was estimated by calculating the ratio of the total excess risk associated with the exposure of interest to the total observed risk. Each measured comorbid exposure was compared to those in the cohort without that respective comorbidity. Confidence intervals (CIs) for population-attributable risk estimates were obtained using nonlinear combinations of estimators.
To assess the validity of the alcohol abuse codes, we examined the relationship between those codes and the incidence of the first diagnosis (in a separate encounter occurring after the first identification of an alcohol abuse code) of esophageal varices and hepatic cirrhosis using Cox proportional hazards models.
Analyses were performed using Stata version 14 (StataCorp, College Station, Texas) and SAS version 9.4 (SAS Institute, Cary, North Carolina). A 2-tailed p < 0.05 was considered statistically significant. Certification to use deidentified HCUP data was obtained from the University of California, San Francisco Committee on Human Research.
Of the 20,390,778 patients receiving care in California ambulatory surgery centers, emergency departments, and inpatient wards, 14,727,591 patients were included in analyses examining incident AF, MI, and CHF (Online Figure 1). During the study period, 268,084 patients (1.8% of patients, with 6.3 events/1,000 person-years; 95% CI: 6.3 to 6.4) were coded with an alcohol abuse diagnosis. Patient characteristics at baseline are provided in Table 1. The incidences of AF, MI, and CHF in patients with and without alcohol abuse are shown in Table 2. The incidences of AF, MI, and CHF by patient subgroups are shown in Online Table 2.
In an analysis intended to validate alcohol abuse coding in our model, presence of alcohol abuse coding resulted in an approximately 130-fold adjusted hazard of varices or cirrhosis (hazard ratio [HR]: 132.6; 95% CI: 130.7 to 134.4; p < 0.0001) (Online Table 3, Online Figure 2).
Alcohol and AF
After excluding patients with prevalent AF, 14,378,483 patients were included in the AF analysis, exhibiting 358,887 incident AF events (2.5%; 7.4 events/1,000 person-years; 95% CI: 7.4 to 7.4). Alcohol abuse predicted a greater risk of incident AF (HR: 1.93; 95% CI: 1.88 to 1.98; p < 0.0001). After multivariable adjustment for age, sex, race, and presence of hypertension, diabetes, coronary disease, CHF, chronic kidney disease, valvular heart disease, dyslipidemia, current smoking, obesity, obstructive sleep apnea, and income, those with alcohol abuse had a >2-fold higher risk of AF (HR: 2.14; 95% CI: 2.08 to 2.19; p < 0.0001) (Figures 1 and 2). Unadjusted and sex and age adjusted only incidence curves are shown in Online Figures 3 to 5. The increased hazard of AF due to alcohol abuse was higher than the majority of well-established AF risk factors. The specific HRs for each outcome are shown in Online Table 4.
With the exception of male sex and smoking, the relative increased risk of AF associated with alcohol abuse was significantly greater in the absence of established AF risk factors (Figure 3). Although the enhanced risk in the setting of alcohol abuse was substantial in every group (Central Illustration), the lower baseline risk in patients without risk factors accounted for the significant interactions favoring a stronger relative effect in those patients.
Alcohol and MI
Among 14,286,427 patients, incident MI was diagnosed in 157,254 individuals (1.1%; 3.1 events/1,000 person-years; 95% CI: 3.0 to 3.1). Presence of alcohol abuse increased the risk of acute MI both before (unadjusted HR: 2.03; 95% CI: 1.95 to 2.11; p < 0.0001) and after adjustment for age, sex, race, hypertension, diabetes, CHF, chronic kidney disease, dyslipidemia, current smoking, obesity, obstructive sleep apnea, and income exhibited a relative risk similar to multiple well-established risk factors (adjusted HR: 1.45; 95% CI: 1.40 to 1.51; p < 0.0001) (Figures 1 and 2). This increase in risk associated with alcohol was of a magnitude similar to that of diabetes and obesity. When restricting these analyses to only STEMI as the outcome (n = 48,467 events, 0.3% of patients for an incidence rate of 1.1 [95% CI: 1.1 to 1.1] per 1,000 person/years), there remained a 2-fold increase in risk in unadjusted analyses (HR: 2.04; 95% CI: 1.90 to 2.18; p < 0.0001); this was attenuated, but still revealed a 30% increased risk after inclusion in the same adjusted model as used for all acute MIs (HR: 1.30; 95% CI: 1.21 to 1.39; p < 0.0001).
Although the relative risk of alcohol abuse on MI was of lower magnitude compared to AF, a similar pattern was observed in interaction analyses by various subgroups: the relative risk was most prominent in the absence of risk factors (Figure 3), driven primarily by the particularly low baseline risk when conventional risk factors and alcohol abuse were both absent (Central Illustration).
Alcohol and CHF
After exclusions, 14,043,590 patients remained in our model for the CHF outcome, revealing 411,983 incident CHF events (2.9%, 10.0 events/1,000 person-years; 95% CI: 10.0 to 10.0). Alcohol abuse imposed an unadjusted HR of 2.23 (95% CI: 2.19 to 2.28; p < 0.0001) in predicting incident CHF; the risk remained similar after adjusting for potential confounders (HR: 2.34; 95% CI: 2.29 to 2.39; p < 0.0001) (Figure 1), exhibiting a similar relative hazard as well-established predictors such as hypertension and diabetes (Figure 2). In a sensitivity analysis, 858,604 patients exhibited the outcome of heart failure in the absence of systolic dysfunction. Alcohol abuse was associated with a 3-fold higher risk of heart failure with preserved systolic function (adjusted HR: 3.2; 95% CI: 1.86 to 5.51). The results of the interaction analyses using this outcome were also similar to those obtained using the primary outcome of heart failure with systolic dysfunction, again demonstrating that younger age and the absence of hypertension especially enhanced the relative risk in the setting of alcohol abuse.
Although hypertension and CHF were by far the most important contributors to the population-attributable risk for each outcome, the population-attributable risk for alcohol abuse on each outcome was similar in magnitude to the majority of well-established and at least theoretically modifiable risk factors (Figure 4).
Leveraging state-wide ambulatory surgery visits, emergency department encounters, and hospitalizations in California over 5 consecutive years, we found that alcohol abuse was an important predictor of AF, MI, and CHF, exhibiting both relative hazards and population-attributable risks similar to the majority of established modifiable risk factors in each case. Although alcohol abuse substantially heightened the risk in all subgroups, the relative increase in risk was observed most prominently among those without established risk factors.
There is much research into the role of alcohol, the nation’s most consumed drug (28), and its effect on cardiovascular disease, the principle threat to health in the United States (29). Even mild-to-moderate levels of alcohol consumption have been associated with increased risk of AF, yet this level of exposure has been demonstrated in observational studies to decrease the risk of MI and CHF (10,11,13,14,30,31).
A recent study examining access to alcohol as an instrumental variable among counties with various alcohol sales laws in Texas revealed a consistent association between greater alcohol access and AF and inconsistent results regarding MI and CHF (32). Although the study used novel ecological methods to demonstrate important health effects related to alcohol exposure, a major limitation of the study was the inability to examine variable degrees of that exposure. Indeed, the impact of the most extreme form of alcohol consumption, alcohol abuse, on these cardiovascular endpoints across the population has previously remained unknown.
Given the association of AF with cardiovascular complications and death (27,33) and few interventions to this point that modify that risk (34,35), prevention of AF is paramount. Although the data in favor of an association between alcohol consumption and AF are conflicting (14,34,35), the majority of studies suggest that chronic alcohol consumption increases the risk for incident AF (18). The great majority of these studies have relied on participant self-report and none was able to examine interactions by various participant characteristics. Among common risk factors for AF, our data demonstrate that only CHF is a stronger risk factor than alcohol abuse. There was a disproportionate effect of alcohol abuse in predicting AF in patients who lacked other known risk factors for AF, suggesting that alcohol abuse may be a particularly important cause of lone AF. Interaction analyses revealed that younger patients and those without hypertension exhibited a particularly disproportionately heightened relative risk of AF. This demonstrates that the mechanisms of AF in the context of alcohol abuse do not rely on atrial changes that occur with age or hypertension, perhaps suggesting an electrical rather than a structural effect. Conversely, alcohol abuse did not appear to confer increased risk associated with male sex or smoking, perhaps suggesting that these share common mechanistic pathways that promote AF.
Despite the preponderance of observational published literature favoring a protective effect of alcohol on MI risk (11–15), our data demonstrate the reverse—an increased risk of MI (whether including all acute MIs or only STEMIs) both before and after multivariable adjustment. Taken along with prior published literature on gradations of alcohol consumption and MI risk, these data on alcohol abuse therefore suggest that the impact of alcohol consumption on incident MI may mirror the U-shaped curve found with alcohol consumption and overall mortality (36–38) and are consistent with the observation that acute binges of alcohol increase the risk of MI (39). Of interest, a recent analysis suggests that the apparent protective effect of light to moderate drinking on mortality may be confounded by physical activity and perceived health status (40). Therefore, our findings may simply better elucidate the harmful effects of alcohol related to MI by examining alcohol in excess as the predictor. Although the magnitude of increased risk for MI was lower than for AF (30% vs. more than a 2-fold increased risk), again alcohol abuse appears to confer both an increased relative risk and population-attributable risk similar to well-established modifiable risk factors. In no circumstance did the absence of a cardiovascular comorbidity display a protective effect against the increased MI risk among those with alcohol abuse. Alcohol abuse had a negligible impact in increasing the relative risk among those with chronic kidney disease, dyslipidemia, smoking, and obesity, perhaps related to alcohol’s favorable effects on lipid profiles (41–47). Importantly, in each case, although the relative risk of alcohol abuse was not different in those with and without these risk factors, the absolute risk was increased in every case, demonstrating the important impact in these populations. In patients without these diseases, the ill effects of alcohol are especially severe regarding MI risk. Clearly, it is not appropriate to extrapolate from evidence regarding moderate drinking that “more is better” in terms of MI risk, arguing for the importance of moderation even in regard to an outcome where alcohol has demonstrated some benefit.
Although alcoholic cardiomyopathy is known to occur in the setting of alcohol abuse (48,49), the population-level effects of alcohol abuse on incident CHF remain unclear. Indeed, several large studies have demonstrated that moderate alcohol consumption may have a protective effect against CHF (7–9). Our data show a more than 2-fold increased risk of CHF with alcohol abuse in the general population—an even stronger predictive association than many other established risk factors, including hypertension. Interestingly, we were unable to identify any meaningful differences in our sensitivity analyses restricting the outcome to heart failure in the presence or absence of systolic dysfunction, suggesting volume overload due to excessive alcohol may occur due to mechanisms more complicated than simply weakening the ventricles. Stratification by patient characteristics for incident CHF yielded similar results to that of AF and MI: healthier patients tended to exhibit a disproportionately greater relative risk of CHF in the setting of alcohol abuse. Interestingly, just as with AF, the most diametric interactions were observed when stratifying by age and by presence of hypertension, again implicating some distinct mechanistic pathway regarding alcohol-induced myocardial toxicity versus age-related or hypertensive cardiomyopathy.
On a population level, the risk of AF, MI, and CHF that could be attributed to alcohol was on a par with multiple other established risk factors. Extrapolating from our data to the estimated prevalence of each outcome, a theoretical complete eradication of alcohol abuse would result in over 73,000 fewer AF cases, 34,000 fewer MIs, and 91,000 fewer patients with CHF in the United States alone (3).
HCUP relies on physician coding; however, coding for alcohol abuse, AF, MI, and CHF have been shown to be highly specific with variable sensitivity (50–54). Importantly, limited sensitivity would be expected only to decrease power and would not be expected to result in false positives. Research using these methods and particularly the HCUP database in this regard is nonetheless a powerful tool and an accepted approach for large population studies (26,55,56). Some potential confounders are not measured by ICD-9 codes, such as specific diets or levels of activity; however, we adjusted for demographic information, smoking, and obesity, which may parallel and even directly reflect many of these unmeasured factors (57,58). Smoking in particular may be an important confounder underlying the observation that alcohol abuse was associated with a higher risk of MI. However, the prevalence of smoking ascertained from HCUP of 8% is of a similar magnitude to the estimate of 13% provided by the Centers for Disease Control and Prevention in California over that same time period (59); importantly, approximately 18% of those who abused alcohol were coded as smokers in HCUP versus approximately 4% of patients who did not abuse alcohol. Given the effects observed for smoking on MI and assuming underascertainment of smoking (if present) was nondifferential (which we believe to be conservative, as smoking was more likely more often coded among those also coded with alcohol abuse), we calculated that 82% of those with alcohol abuse would have had to also smoke cigarettes to explain the increased hazard of MI observed. Although we cannot exclude this possibility, we do not believe such a high prevalence of smoking in California over this time period, particularly given the Centers for Disease Control and Prevention–based estimates, is likely. In addition, use of physician coding eliminates the important bias of patient self-report that had been prevalent in studies on this topic to this point. We further validated our primary predictor (alcohol abuse) by demonstrating exceedingly strong associations with esophageal varices and cirrhosis; that well-established risk factors predicted AF, MI, and CHF as expected also serves to validate our covariates and outcomes. Our endpoints fail to capture any outpatient encounters, which has particular relevance to the potentially insensitive diagnoses of alcohol abuse and AF. However, by capturing patients treated in ambulatory procedural units, emergency departments, and inpatient settings, we likely studied the sicker cohort of patients with alcohol abuse and these cardiovascular outcomes and certainly captured those responsible for the majority of health care use. As with any observational study, we cannot exclude residual confounding as an explanation for our results. However, we adjusted for conventionally recognized confounders in as exhaustive a fashion as possible and as appropriate. Finally, it is important to emphasize that these data cannot prove causality. In addition, although the population-attributable risk calculations must be interpreted with caution, we believe such estimates provide substantial value in modeling potential public health impacts given a common and theoretically modifiable condition such as alcohol abuse.
Finally, by relying on physician coding of alcohol abuse, the proportion of alcohol abusers identified in our study is approximately one-third of national estimates (6), and we were not able to comment on the quantity of alcohol. Although this limits our ability to determine specific amounts that may be harmful, it also very accurately and specifically identifies patients wherein alcohol abuse was not only recognized but also clinically documented by a health care professional. Therefore, although treating or preventing alcohol abuse is no doubt challenging, in our study the predictor is already recognized by at least 1 health care professional, suggesting that these are the patients already accessible to possible intervention within the current health care system. That some patients who experience alcohol abuse were not identified as such in our study has the likely effect of biasing the results toward the null, suggesting that the association between alcohol abuse and cardiac disease may be even more marked than measured in the current study.
Alcohol abuse increases the risk of incident AF, MI, and CHF, exhibiting magnitudes of risk similar to other well-established risk factors. Although nearly all subgroups exhibited increased risk in the setting of alcohol abuse, those without a given risk factor for each outcome were disproportionately prone to enhanced cardiovascular risk. The risk of AF, MI, and CHF that can be attributed to alcohol abuse is large, suggesting that efforts to mitigate this addictive disease might result in substantial reductions of cardiac disease. Taken together, these data demonstrate that alcohol in excess should not be considered cardioprotective, but rather cardiotoxic, contributing to heightened risk for all 3 major, yet distinct, cardiac adverse outcomes.
COMPETENCY IN MEDICAL KNOWLEDGE: Alcohol abuse increases the risk of AF, MI, and heart failure to an extent similar to that of other strong risk factors, and affects healthier individuals disproportionately. Protective effects of alcohol against MI are outweighed at heavy levels of consumption by its adverse effects.
TRANSLATIONAL OUTLOOK: More research is needed to understand the mechanisms by which alcohol influences the risk of cardiac disease in specific populations.
For supplemental figures and tables, please see the online version of this article.
Research reported in the article was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R01AA022222 (to Dr. Marcus) and 1F32HL129759-01 (to Dr. Whitman). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- atrial fibrillation
- congestive heart failure
- confidence interval
- Current Procedural Terminology
- Healthcare Cost and Utilization Project
- hazard ratio
- International Classification of Diseases-Ninth Revision
- myocardial infarction
- ST-segment elevation myocardial infarction
- Received July 23, 2016.
- Revision received September 23, 2016.
- Accepted October 4, 2016.
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