Abstract
Background
Acute myocardial infarction (AMI), a leading cause of death in the US, is associated with significant clinical and economic burden. Systemic inflammation is a risk factor for worse cardiovascular outcomes, but the role of systemic inflammation in patients with AMI is not well established.
Objective
To evaluate clinical, health care resource utilization (HCRU), and economic outcomes in patients with type 1 AMI, and explore results based on systemic inflammation status.
Methods
Data from the Premier Healthcare Database were retrospectively analyzed, including adults with ≥1 inpatient hospitalization for type 1 AMI (using ICD-10-CM codes) from January 1, 2017, to August 31, 2023. Data were analyzed at index and within 30 and 90 days after index discharge. Demographics, clinical and HCRU outcomes, and costs were described for all patients with AMI and compared between those with and without evidence of systemic inflammation. Inflammation status was based on C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP) levels, such that patients with CRP/hsCRP between 2 and 10 mg/L were considered to have evidence of systemic inflammation. Patients with levels <2 mg/L or without CRP/hsCRP test results were considered to have no evidence of systemic inflammation. CRP/hsCRP test results were available in a limited number of patients.
Results
Among patients with AMI (N = 1,078,572), in-hospital mortality was 7.6 % during index hospitalization. The mean index length of stay was 5 days, and average cost of care was $23,648. Readmission rates were 7.9 % and 12.9 % within 30 and 90 days after discharge, respectively. Patients with evidence of systemic inflammation (n = 1673) had higher mortality and longer index stays as well as increased readmission rates compared with patients without evidence of systemic inflammation (n = 1,076,899) (all, P < 0.01).
Conclusion
Patients experiencing AMI, and especially those with evidence of systemic inflammation, experience persistently high risk of mortality, morbidity, recurrence, and large economic burdens. Greater attention is needed to optimize the care of this at-risk population.
Keywords: Acute myocardial infarction, Systemic inflammation, C-reactive protein, High-sensitivity C-reactive protein, Health care resource utilization, clinical burden, economic burden
Graphical abstract
Glossary
- ACC
American College of Cardiology
- AHA
American Heart Association
- AKI
acute kidney injury
- AMI
acute myocardial infarction
- APR-DRG
all patient refined diagnosis related group
- CCI
Charlson Comorbidity Index
- CRP
C-reactive protein
- CVD
cardiovascular disease
- ER
emergency room
- ESC
European Society of Cardiology
- HCRU
health care resource utilization
- hsCRP
high-sensitivity C-reactive protein
- ICD-10-CM
-
International Statistical Classification of Diseases and Related Health
Problems, 10th Revision
- ICU
intensive care unit
- ITT
intention-to-treat
- MI
myocardial infarction
- STEMI
ST-elevation myocardial infarction
- VSD
ventricular septal defect
1. Introduction
Acute myocardial infarction (AMI) significantly contributes to cardiovascular disease (CVD)-related mortality [1], which is a leading cause of death globally [2]. In the United States, the National Institutes of Health-funded Atherosclerosis Risk in Communities Study estimated that approximately 800,000 people experience AMI each year, with 600,000 incident cases and 200,000 recurrent cases [3,4]. Related to the high prevalence of AMI, the resulting economic burden – estimated to be nearly $85 billion annually – has a substantial impact on patients and health systems in the United States [5].
The American College of Cardiology and the American Heart Association (ACC/AHA) highlight that while in-hospital and 30-day mortality has improved for patients with myocardial infarction (MI), significant morbidity and mortality remain [6]. Current clinical guideline recommendations emphasize timely, complete revascularization, dual antiplatelet therapy, and high-intensity statins for patients presenting with AMI [6]. Despite improvements in care, and even in the setting of appropriate management, patients remain at increased risk of recurrent cardiovascular events following AMI, possibly due in part to systemic inflammation [6]. The presence of inflammation following an AMI event has been highlighted as a risk factor for adverse outcomes, but the role of the systemic inflammation preceding AMI is not well established [[7], [8], [9], [10], [11]]. However, many studies have shown that systemic inflammation is a risk factor for worse CVD outcomes [[12], [13], [14], [15]]. Specifically, various guidelines, including 2025 ACC/AHA Clinical Practice Guidelines and 2023 European Society of Cardiology (ESC) Guidelines, have recognized inflammation as a risk enhancer for CVDs and recommend anti-inflammatory therapies as a strategy for secondary prevention of cardiovascular events [6,16,17]. Despite this recognition, there remains a gap in the literature regarding the role of systemic inflammation in patients with AMI, particularly in understanding how prior systemic inflammation affects health outcomes in this population. A better understanding of the impact of systemic inflammation on AMI-related clinical and economic burdens for both patients and the health care system would assist in strategizing treatment in this area and improving future clinical care in the population of patients with AMI.
The aim of this study was to enhance understanding of the current burden of AMI on patients and hospitals by evaluating detailed in-hospital and readmission clinical outcomes, costs, and health care resource utilization (HCRU) in patients hospitalized for type 1 AMI and to explore the role of systemic inflammation in those AMI outcomes. Given the known role of the inflammation pathway in the pathophysiology of type 1 AMI, this study limited its focus to patients with type 1 presentation [9]. This relationship highlights the importance of elucidating the full impact of systemic inflammation on AMI-related clinical and economic burdens for both patients and the health care system.
2. Methods
2.1. Patient selection criteria
This study was exempted from Institutional Review Board (IRB) oversight by the Advarra IRB (IRB #00000971, case number Pro00079882). Patient data from the Premier Healthcare Database were retrospectively evaluated. Included patients were aged ≥18 years, with ≥1 inpatient hospitalization for AMI (type 1; International Statistical Classification of Diseases and Related Health Problems, 10th Revision [ICD-10-CM] code I21, excluding I21.A and I21.A9 to omit patients with non–type 1 AMI) recorded between January 1, 2017, and August 31, 2023. The first eligible hospitalization was set as the index hospitalization. The admission date of the index hospitalization for AMI was used as the index date. The 12-month period prior to the index date was defined as the baseline period. Patients were followed for 90 days after the index discharge.
Patients were excluded if they had an AMI, coronary artery bypass graft, or percutaneous coronary intervention in the year preceding the index date or a diagnosis of stroke, transient ischemic attack, unstable angina, or cardiomyopathy within 30 days before index. Patients with any type of cancer (with the exception of nonmelanoma skin cancers); chronic kidney disease stage 5 or evidence of dialysis; chronic heart failure; and chronic infections, including hepatitis B, hepatitis C, HIV, tuberculosis, and severe liver conditions (including hepatic encephalopathy, ascites, jaundice, esophageal/gastric variceal bleeding, and hepatic cirrhosis) were also excluded. Finally, this analysis excluded patients who experienced general or cardiogenic shock, were hospitalized for heart failure within 30 days before index, were pregnant, or had an elective hospital admission during index hospitalization.
2.2. Study variables
Patient comorbidities and characteristics of the patients and their admitting hospitals were assessed within the baseline period and during the index visit. The Charlson Comorbidity Index (CCI) at the index visit was determined based on the Quan et al., 2011, modification [18]. Clinical outcomes assessed at index included in-hospital mortality or discharge to hospice, diagnosis of any stroke, pacemaker implant/defibrillator insertion, any ventricular arrhythmia, any ischemic muscle rupture/ventricular septal defect (VSD)/rupture of cardiac wall, acute pericarditis, stent thrombosis, acute kidney injury, major bleeding, or cardiac arrest at index. These clinical outcomes were also assessed during the 30- and 90-day post-index period.
AMI-related HCRU outcomes were assessed during the index visit and within 30 and 90 days of index discharge. Specific HCRU outcomes included total and intensive care unit (ICU) length of stay during index and for all-cause inpatient hospital readmissions to the same hospital system or network; all patient refined diagnosis related groups (APR-DRGs) severity of illness and APR-DRG risk of mortality during the readmissions, which were determined by the physician at the time of readmission; number of readmissions, outpatient visits, and emergency room (ER) visits; number of stroke/MI-related readmissions (total and ICU); and length of stay for stroke/MI-related inpatient hospital readmissions (total and ICU).
Cost was assessed at index and during the 30- and 90-day follow-up periods. Cost-related outcomes included total cost of the index visit, total cost of the inpatient hospitalization, and total hospital-based outpatient costs. All cost variables were adjusted to 2023 price level to account for potential inflation during the study period.
2.3. Exploratory subgroup
An exploratory subgroup analysis examined the effect of systemic inflammation among the subset of patients with available high-sensitivity C-reactive protein (hsCRP) or standard C-reactive protein (CRP) laboratory data within the year prior to the indexing AMI event. CRP and hsCRP test results collected prior to the AMI admission were exclusively captured to enable insights into the temporal relationship between systemic inflammation and the AMI event. With advancements in testing accuracy, standard CRP tests are now able to detect low-range CRP levels, similar to hsCRP testing [19]. Evidence of systemic inflammation was defined as CRP levels between 2 and 10 mg/L in the year prior to index, based on either hsCRP or standard CRP testing. Patients with hsCRP or CRP levels <2 mg/L [12,20,21] or no recorded hsCRP/CRP values were considered to have no evidence of systemic inflammation. Those with hsCRP or CRP test values >10 mg/L were excluded from the exploratory analyses, as levels above this limit are often a sign of infection or other acute conditions [19,22]. Given the small sample size of patients with hsCRP or CRP levels lower than 2 mg/L (n = 324), a comparison between this group and the cohort of patients with systemic inflammation was not explored due to insufficient powering for key outcomes.
The criteria used to define systemic inflammation in this study may differ from other publications. Because hsCRP is most often used by cardiologists to assess systemic inflammation, a sensitivity analysis was conducted by including patients with evidence of systemic inflammation as determined by hsCRP only. Notably, the sample of patients with a baseline hsCRP or CRP test was small (approximately 0.2 % of the overall study population), limiting the generalizability of related results (see Discussion section).
2.4. Statistical methods
All analyses were conducted using R Studio 4.1.3 (RStudio: Integrated Development Environment for R. Posit Software, PBC, Boston, MA). Patient, hospital, visit, and clinical characteristics and outcomes were analyzed descriptively for the overall AMI sample. Subgroup analyses were performed for the subsets of patients with and without evidence of systemic inflammation. Outcomes were compared between subgroups. All analyses were compared using appropriate tests for continuous and categorical variables to inform statistical significance. Chi-square tests were used to evaluate differences in categorical variables, while Wilcoxon rank sum tests were applied to cost variables due to the non-normal distribution of cost data. A two-sided statistical significance level of 0.05 determined whether to reject the null hypotheses.
3. Results
Of all patients eligible for this analysis (N = 1,078,572, Fig. 1), most patients with AMI were White, non-Hispanic, and male, with a mean age of 67 years and a mean CCI of 2.5 (Table 1). Patients with evidence of systemic inflammation (n = 1673) were slightly older (68.0 years vs 67.0 years; P = 0.005), with a greater proportion of female patients (52.7 % vs 39.0 %, respectively; P < 0.001) compared with those without evidence of systemic inflammation (n = 1,076,899). Patients with evidence of systemic inflammation were also more likely to be White and Non-Hispanic (P < 0.001), use Medicare insurance (66.3 % vs 57.9 %; P < 0.001), and have a higher mean CCI (3.3 vs 2.5; P < 0.001).
Fig. 1.
Patient identification and attrition. AMI, acute myocardial infarction; CRP, C-reactive protein; hsCRP, high-sensitivity C-reactive protein; ICD-10-CM, International Statistical Classification of Diseases and Related Health Problems, 10th Revision.
Table 1.
Baseline demographics and characteristics among patients with AMI.
| All patients with AMI | Patients with AMI stratified by evidence of systemic inflammation |
|||
|---|---|---|---|---|
| Patients with evidence of systemic inflammation | Patients without evidence of systemic inflammation | P valuea | ||
| Patients, n | 1,078,572 | 1673 | 1,076,899 | |
| Unique hospitals, n | 1102 | 200 | 1102 | |
| Age, mean (SD), y | 67.0 (13.6) | 68.0 (13.4) | 67.0 (13.6) | 0.005 |
| Sex, n (%) | <0.001 | |||
| Female | 421,163 (39.0) | 881 (52.7) | 420,282 (39.0) | |
| Male | 657,160 (60.9) | 792 (47.3) | 656,368 (60.9) | |
| Unknown | 249 (0) | 0 (0) | 249 (0) | |
| Race, n (%) | <0.001 | |||
| Asian | 24,679 (2.3) | 16 (1.0) | 24,663 (2.3) | |
| Black | 106,434 (9.9) | 172 (10.3) | 106,262 (9.9) | |
| White | 846,527 (78.5) | 1373 (82.1) | 845,154 (78.5) | |
| Other/unknown | 100,932 (9.4) | 107 (6.7) | 100,825 (9.4) | |
| Ethnicity, n (%) | <0.001 | |||
| Hispanic | 77,890 (7.2) | 87 (5.2) | 77,803 (7.2) | |
| Non-Hispanic | 843,352 (78.2) | 1415 (84.6) | 841,937 (78.2) | |
| Unknown | 157,330 (14.6) | 171 (10.2) | 157,159 (14.6) | |
| Index CCI, mean (SD) | 2.5 (2.3) | 3.3 (2.3) | 2.5 (2.3) | <0.001 |
| Health care coverage, n (%) | <0.001 | |||
| Commercial insurance | 256,794 (23.8) | 238 (14.2) | 256,556 (23.8) | |
| Medicaid | 104,360 (9.7) | 208 (12.4) | 104,152 (9.7) | |
| Medicare | 624,883 (57.9) | 1110 (66.3) | 623,773 (57.9) | |
| Uninsured | 54,352 (5.0) | 43 (2.6) | 54,309 (5.0) | |
| Other/unknown | 38,183 (3.5) | 74 (4.4) | 38,109 (3.5) | |
aCompared across all groups.
AMI, acute myocardial infarction; CCI, Charlson Comorbidity Index.
3.1. Clinical outcomes
3.1.1. Index
At the index event, in-hospital mortality was 7.6 %, and 2.9 % of all patients with AMI were discharged to hospice (Table 2). Acute kidney injury (AKI) (25 %), major bleeding (12.0 %), and ventricular tachycardia (7.9 %) were common diagnoses among patients during index. Patients with evidence of systemic inflammation exhibited greater in-hospital mortality (9.7 % vs 7.6 %; P = 0.002), higher rate of discharge to hospice (4.8 % vs 2.9 %; P < 0.001), and higher rate of AKI (32.1 % vs 25.4 %; P < 0.001) compared with patients without evidence of systemic inflammation. The rates of pacemaker implant/defibrillator insertion, ventricular fibrillation, and ventricular tachycardia were numerically lower in patients with evidence of systemic inflammation, but differences were not clinically significant.
Table 2.
Clinical outcomes at index and within 30 and 90 days of index discharge among patients with AMI.
| All patients with AMI | Patients with AMI stratified by evidence of systemic inflammation |
|||
|---|---|---|---|---|
| Patients with evidence of systemic inflammation | Patients without evidence of systemic inflammation | P valuea | ||
| INDEX | ||||
| Patients, n | 1,078,572 | 1673 | 1,076,899 | |
| In-hospital mortality, n (%) | 82,342 (7.6) | 162 (9.7) | 82,180 (7.6) | 0.002 |
| Discharged to hospice, n (%) | 31,542 (2.9) | 80 (4.8) | 31,462 (2.9) | <0.001 |
| In-hospital mortality or discharged to hospice, n (%) | 113,884 (10.6) | 242 (14.5) | 113,642 (10.6) | <0.001 |
| Diagnosis of stroke, n (%) | 36,752 (3.4) | 49 (2.9) | 36,703 (3.4) | 0.3 |
| Pacemaker implant/defibrillator, n (%) | 15,154 (1.4) | 13 (0.8) | 15,141 (1.4) | 0.029 |
| Any ventricular arrhythmia, n (%) | ||||
| Ventricular fibrillation | 40,297 (3.7) | 41 (2.5) | 40,256 (3.7) | 0.006 |
| Ventricular tachycardia | 85,484 (7.9) | 102 (6.1) | 85,382 (7.9) | 0.006 |
| Ventricular flutter | 180 (<0.1) | 0 | 180 (<0.1) | >0.9 |
| Supraventricular tachycardia | 31,911 (3.0) | 39 (2.3) | 31,872 (3.0) | 0.13 |
| Any ischemic muscle rupture/VSD/rupture of cardiac wall, n (%) | 2415 (0.2) | 3 (0.2) | 2412 (0.2) | >0.9 |
| Acute pericarditis, n (%) | 2125 (0.2) | 2 (0.1) | 2123 (0.2) | 0.8 |
| Stent thrombosis, n (%) | 39,198 (3.6) | 52 (3.1) | 39,146 (3.6) | 0.2 |
| AKI, n (%) | 273,715 (25.4) | 537 (32.1) | 273,178 (25.4) | <0.001 |
| Major bleeding, n (%) | 129,486 (12.0) | 201 (12.0) | 129,285 (12.0) | 0.8 |
| Cardiac arrest, n (%) | 58,271 (5.4) | 102 (6.1) | 58,169 (5.4) | 0.2 |
| WITHIN 30 DAYS OF INDEX DISCHARGE | ||||
| Patients, n | 996,230 | 1511 | 994,719 | |
| Pacemaker implant/defibrillator, n (%) | 2285 (0.2) | 4 (0.3) | 2281 (0.2) | 0.8 |
| Any ventricular arrhythmia, n (%) | ||||
| Ventricular fibrillation | 1611 (0.2) | 2 (0.1) | 1609 (0.2) | >0.9 |
| Ventricular tachycardia | 5971 (0.6) | 8 (0.5) | 5963 (0.6) | 0.7 |
| Ventricular flutter | 17 (<0.1) | 0 | 17 (<0.1) | >0.9 |
| Supraventricular tachycardia | 3197 (0.3) | 4 (0.3) | 3193 (0.3) | >0.9 |
| Any ischemic muscle rupture/VSD/rupture of cardiac wall, n (%) | 208 (<0.1) | 0 | 208 (<0.1) | >0.9 |
| Acute pericarditis, n (%) | 443 (<0.1) | 2 (0.1) | 441 (<0.1) | 0.15 |
| Stent thrombosis, n (%) | 2624 (0.3) | 5 (0.3) | 2619 (0.3) | 0.6 |
| AKI, n (%) | 29,564 (3.0) | 91 (6.0) | 29,473 (3.0) | <0.001 |
| Major bleeding, n (%) | 19,473 (2.0) | 44 (2.9) | 19,429 (2.0) | 0.007 |
| Cardiac arrest, n (%) | 3783 (0.4) | 11 (0.7) | 3772 (0.4) | 0.028 |
| WITHIN 90 DAYS OF INDEX DISCHARGE | ||||
| Patients, n | 996,230 | 1511 | 994,719 | |
| Pacemaker implant/defibrillator, n (%) | 4966 (0.5) | 6 (0.4) | 4960 (0.5) | 0.6 |
| Any ventricular arrhythmia, n (%) | ||||
| Ventricular fibrillation | 2548 (0.3) | 2 (0.1) | 2546 (0.3) | 0.6 |
| Ventricular tachycardia | 10,165 (1.0) | 15 (1.0) | 10,150 (1.0) | >0.9 |
| Ventricular flutter | 35 (<0.1) | 0 | 35 (<0.1) | >0.9 |
| Supraventricular tachycardia | 5709 (0.6) | 8 (0.5) | 5701 (0.6) | 0.8 |
| Any ischemic muscle rupture/VSD/rupture of cardiac wall, n (%) | 351 (<0.1) | 0 | 351 (<0.1) | >0.9 |
| Acute pericarditis, n (%) | 654 (0.1) | 3 (0.2) | 651 (0.1) | 0.079 |
| Stent thrombosis, n (%) | 4206 (0.4) | 5 (0.3) | 4201 (0.4) | 0.6 |
| AKI, n (%) | 48,495 (4.9) | 161 (10.7) | 48,334 (4.9) | <0.001 |
| Major bleeding, n (%) | 33,301 (3.3) | 81 (5.4) | 33,220 (3.3) | <0.001 |
| Cardiac arrest, n (%) | 6137 (0.6) | 15 (1.0) | 6122 (0.6) | 0.061 |
aCompared across all groups.
AKI, acute kidney injury; AMI, acute myocardial infarction; VSD, ventricular septal defect.
3.1.2. Postdischarge outcomes
Within 30 and 90 days of index discharge, the rates of all-cause readmission for all patients who were discharged alive following the index visit were 7.9 % and 12.9 %, respectively (Fig. 2). Stroke/AMI-related readmission rates for all patients with AMI were 7.2 % and 11.7 % within 30 and 90 days of index discharge, respectively. Patients with evidence of systemic inflammation had higher all-cause and stroke/AMI-related 30- and 90-day readmission rates compared with patients without evidence of systemic inflammation (P < 0.001).
Fig. 2.
(A, B) Rate of readmission 30 days (A) and 90 days (B) after index discharge in patients with AMI (n = 996,230), patients with AMI and systemic inflammation (n = 1511), and patients with AMI and no evidence of systemic inflammation (n = 994,719). (C, D) Rate of stroke/AMI-related readmission 30 days (C) and 90 days (D) after index discharge in patients with AMI (n = 996,230), patients with AMI and systemic inflammation (n = 1511), and patients with AMI and no evidence of systemic inflammation (n = 994,719). AMI, acute myocardial infarction.
Within 30 days of initial discharge, 39.1 % of all readmitted patients were at severe risk of mortality; 26.4 % were at extreme risk of mortality, which was evaluated by physicians at the time of the readmission (Fig. 3). Within 90 days of initial discharge, 37.1 % and 24.8 % were at severe and extreme risk of mortality, respectively. Patients with evidence of systemic inflammation were more likely to have more severe risk of mortality within 90 days of discharge compared with patients without evidence of systemic inflammation (P = 0.014).
Fig. 3.
(A, B) Rate of mortality 30 days (A) and 90 days (B) after index discharge in patients with AMI and patients with AMI and with or without evidence of systemic inflammation. AMI, acute myocardial infarction.
3.2. HCRU and cost outcomes
3.2.1. HCRU
During the index visit, most patients were admitted to emergency care (78.5 %), and 72.7 % of patients were admitted from a non-health care facility (such as the patient’s home or workplace) (Table 3). Patients with evidence of systemic inflammation were likely to be admitted to emergency care (91.2 % vs 78.5 %; P < 0.001) and admitted through a non-health care facility (85.3 % vs 72.7 %; P < 0.001) compared with patients without evidence of systemic inflammation.
Table 3.
Index visit characteristics of patients with AMI.
| All patients with AMI | Patients with AMI stratified by evidence of systemic inflammation |
|||
|---|---|---|---|---|
| Patients with evidence of systemic inflammation | Patients without evidence of systemic inflammation | P valuea | ||
| Patients, n | 1,078,572 | 1673 | 1,076,899 | |
| Admission type, n (%) | <0.001 | |||
| Emergency | 846,762 (78.5) | 1526 (91.2) | 845,236 (78.5) | |
| Trauma or injury center | 4174 (0.4) | 5 (0.3) | 4169 (0.4) | |
| Urgent care | 215,647 (20.0) | 139 (8.3) | 215,508 (20.0) | |
| Other/unknown | 11,989 (1.1) | –b | 11,986 (1.1) | |
| Admission point of entry, n (%) | <0.001 | |||
| Non-health care facility | 784,258 (72.7) | 1427 (85.3) | 782,831 (72.7) | |
| Clinic | 48,355 (4.5) | 48 (2.9) | 48,307 (4.5) | |
| Transfer from acute facility | 224,058 (20.8) | 150 (9.0) | 223,908 (20.8) | |
| Transfer from ICF or SNF | 11,292 (1.0) | 43 (2.6) | 11,249 (1.0) | |
| Other/unknown | 10,609 (1.0) | 5 (0.3) | 10,604 (1.0) | |
| Hospital teaching status, n (%) | <0.001 | |||
| Teaching | 561,362 (52.0) | 944 (56.4) | 560,418 (52.0) | |
| Non-teaching | 517,210 (48.0) | 729 (43.6) | 516,481 (48.0) | |
| Population served, n (%) | <0.001 | |||
| Urban | 962,934 (89.3) | 1296 (77.5) | 961,638 (89.3) | |
| Rural | 115,638 (10.7) | 377 (22.5) | 115,261 (10.7) | |
| Discharge status, n (%) | <0.001 | |||
| Home/home health | 760,426 (70.5) | 1074 (64.2) | 759,352 (70.5) | |
| Transfers to other facilityc | 151,255 (14.0) | 303 (18.1) | 150,952 (14.0) | |
| Deathd | 82,409 (7.6) | 162 (9.7) | 82,247 (7.6) | |
| Other/unknown | 84,482 (7.8) | 134 (8.0) | 84,348 (7.8) | |
aCompared across all groups. bn<5. cDischarge categories: long-term care facility, SNF, ICF, acute care facility, hospice. dAs recorded in Premier Healthcare Database.
AMI, acute myocardial infarction; ICF, intermediate care facility; SNF, skilled nursing facility.
Among all patients with AMI, the mean index visit length of stay was 4.9 days (Table 4). Patients with evidence of systemic inflammation stayed longer during the index visit compared with patients without evidence of systemic inflammation (5.2 days vs 2.9 days; P < 0.001).
Table 4.
HCRU outcomes at index and within 30 and 90 days of index discharge.
| All patients with AMI | Patients with AMI stratified by evidence of systemic inflammation |
|||
|---|---|---|---|---|
| Patients with evidence of systemic inflammation | Patients without evidence of systemic inflammation | P valuea | ||
| INDEX | ||||
| Patients, n | 1,078,572 | 1673 | 1,076,899 | |
| Mean (SD) index LOS, days | 4.9 (5.0) | 5.2 (5.1) | 4.9 (5.0) | <0.001 |
| Mean (SD) index ICU LOS, days | 3.2 (3.6) | 3.4 (3.8) | 3.2 (3.6) | 0.5 |
| WITHIN 30 DAYS OF INDEX DISCHARGE | ||||
| Patients, n | 996,230 | 1511 | 994,719 | |
| Additional care within 30 days of index discharge, n (%) | ||||
| Revisits | 206,581 (21) | 622 (41) | 205,959 (21) | <0.001 |
| ER visits | 120,783 (12) | 371 (25) | 120,412 (12) | <0.001 |
| Mean (SD) visits within 30 days of index | ||||
| Readmissions | 1.1 (0.3) | 1.1 (0.4) | 1.1 (0.3) | 0.2 |
| Outpatient revisits | 1.5 (1.1) | 2.0 (1.5) | 1.5 (1.1) | <0.001 |
| ER visits | 1.2 (0.5) | 1.3 (0.9) | 1.2 (0.5) | <0.001 |
| WITHIN 90 DAYS OF INDEX DISCHARGE | ||||
| Patients, n | 996,230 | 1511 | 994,719 | |
| Additional care within 90 days of index discharge, n (%) | ||||
| Revisits | 324,056 (33) | 867 (57) | 323,189 (32) | <0.001 |
| ER visits | 189,980 (19) | 576 (34) | 189,404 (18) | <0.001 |
| Mean (SD) visits within 90 days of index | ||||
| Readmissions | 1.3 (0.6) | 1.4 (0.8) | 1.3 (0.6) | 0.002 |
| Outpatient revisits | 2.4 (2.9) | 3.7 (3.9) | 2.4 (2.9) | <0.001 |
| ER visits | 1.4 (1.0) | 1.8 (1.6) | 1.4 (1.0) | <0.001 |
aCompared across all groups.
AMI, acute myocardial infarction; ER, emergency room; HCRU, health care resource utilization; ICU, intensive care unit; LOS, length of stay.
Within 30 and 90 days of index discharge, the mean number of outpatient visits for a patient with AMI was 1.5 and 2.4 visits, respectively, and the mean number of ER visits was 1.2 and 1.4 visits, respectively (Table 4). Patients with evidence of systemic inflammation had more outpatient and ER visits compared with patients without evidence of systemic inflammation (all, P < 0.001).
3.2.2. Costs
The mean index cost for all patients with AMI exceeded $23,000, and the median index cost exceeded $15,000 (Table 5). The mean total inpatient cost across all visits was $50,172, and the median total inpatient cost was $33,122. Patients with evidence of systemic inflammation had higher median outpatient visit costs but similar median inpatient costs and lower median index costs compared with those without evidence of systemic inflammation. Outliers were observed for both index and inpatient cost analyses, representing notably high costs for certain individuals with AMI.
Table 5.
Cost outcomes at index and across all visits among patients with AMI.
| All patients with AMI | Patients with AMI stratified by evidence of systemic inflammation |
|||
|---|---|---|---|---|
| Patients with evidence of systemic inflammation | Patients without evidence of systemic inflammation | P valuea | ||
| Index costs | ||||
| Patients, n | 1,078,572 | 1673 | 1,076,899 | |
| Mean (SD), USD | 23,648 (23,648) | 21,215 (21,385) | 23,651 (23,471) | |
| Median (IQR), USD | 15,620 (9532–28,027) | 14,385 (9227–23,601) | 15,622 (9533–28,036) | <0.001 |
| Total inpatient hospitalization costsb | ||||
| Patients, n | 1,073,698 | 1669 | 1,072,029 | |
| Mean (SD), USD | 50,172 (49,128) | 46,928 (45,369) | 50,178 (49,133) | |
| Median (IQR), USD | 33,122(20,146–60,776) | 33,192 (20,138–53,938) | 33,122 (20,146–60,786) | 0.14 |
| Total outpatient visit costsb | ||||
| Patients, n | 315,528 | 845 | 314,683 | |
| Mean (SD), USD | 2887 (4495) | 3188 (4824) | 2886 (4494) | |
| Median (IQR), USD | 1110 (345–3353) | 1192 (417–3784) | 1109 (345–3352) | 0.04 |
aMean cost difference and associated P values were not calculated because costs were not normally distributed. A nonparametric approach was used to compare the median difference across two groups. bIncluding all index and follow-up visits.
AMI, acute myocardial infarction; USD, US dollars.
3.3. Additional analyses
A full comparison of clinical, HCRU, and cost results for patients with evidence of systemic inflammation as defined by hsCRP alone vs those with CRP/hsCRP-defined systemic inflammation are included in Appendix A. These differences align with those observed in the group of patients with or without evidence of systemic inflammation as defined by either CRP or hsCRP; however, due to the small sample size of patients with hsCRP-confirmed systemic inflammation, statistical significance could not be established (Tables A1-A3 and Figures A1, A2).
To better understand the impact of systemic inflammation on costs, more detailed cost data, including index, inpatient, and outpatient costs, as well as cost distributions were stratified by hsCRP (≥2 mg/L) and hsCRP/CRP (≥2 mg/L). Those results were included in Appendix B. Similar to the main results, this comparison revealed no significant differences between the 2 groups in terms of costs.
Sensitivity analyses were conducted to further classify the HCRU, clinical, and cost outcomes among patients with AMI (Appendix C). While the main analyses related to readmissions were conducted using data from patients who were discharged alive from the index visit, sensitivity analyses were completed using the full cohort, regardless of mortality status at discharge. These results were generally consistent with those of the main analyses (Fig. 3 and Table 4). Within 30 and 90 days of initial discharge, most patients were at severe or extreme risk of mortality (Table C1), and readmission rates were 7.9 % and 12.9 %, respectively (Table C2). The mean all-cause length of stay was 5.8 days for all patients with AMI, reaching 6.2 days for patients with evidence of systemic inflammation.
4. Discussion
This study details the persistently high clinical burden and HCRU of AMI encountered by both patients and the health care system. Patients with AMI experienced high mortality, morbidity, and readmittance within 30 and 90 days after hospital discharge. HCRU and cost of care were consistently high among patients with AMI, and this burden is elevated among patients with evidence of systemic inflammation. These findings highlight an opportunity to improve the care of all patients with AMI, but particularly those with evidence of systemic inflammation.
In-hospital mortality exceeded 7 % for all patients with AMI at index hospitalization, and more than a quarter of all patients with AMI experienced AKI. Most patients readmitted within 30 or 90 days of index discharge were at severe or extreme risk of mortality. These results align with previous reports of mortality with rates up to 6 % in patients with type 1 AMI during the incident hospitalization [23,24] and up to 14 % within the first year of the event [23]. In the context of the literature, these results indicate a continued unmet need to optimize the care of patients with AMI.
Patients with evidence of systemic inflammation experienced increased clinical burdens compared with those without evidence of systemic inflammation, including higher rates of morbidity and mortality and higher rates of readmission. One contributing factor may be the release of inflammatory cytokines in patients during the acute stage, which may exacerbate existing chronic inflammation and may be associated with worse AMI outcomes, as observed in this study [10]. Additionally, the increased age and higher prevalence of comorbidities (such as CVD and chronic kidney disease) in the cohort of patients with evidence of systemic inflammation may have reduced the overall health of these patients, which could be associated with more severe AMI-related outcomes [9,10]. A cohort-matching method would help to provide a better understanding of the underlying causes. However, given the small sample size and small number of patients with CRP and hsCRP test results at baseline, this type of analysis was not feasible as part of this study, limiting the generalizability of these results (for additional details, refer to the Limitations section). A recent US study of over 1.5 million patients with ASCVD revealed similarly low rates of hsCRP testing, with yearly testing rates ranging from 0.87 % to 0.98 % in patients with ASCVD and from 0.90 % to 1.17 % in patients with ASCVD and chronic kidney disease, indicating an unmet need to identify patients with systemic inflammation [25]. More advanced studies with different data sources are needed to validate these hypotheses and understand the role of systemic inflammation in patients with AMI. Future studies should perform these analyses adjusted for potential confounding factors, such as age, comorbidities, and AMI severity; should account for the temporal relationship between post-AMI inflammation when not investigating hospital-based outcomes; and should be adjusted to confirm the independent impact of systemic inflammation on outcomes.
Reflective of the clinical burden, HCRU-related burden was high in patients who experienced an AMI. The mean length of stay at index was nearly 5 days. Up to 8 % of all patients with AMI required a readmission within 30 days of index discharge. These readmission rates are somewhat low in comparison with previous studies. In an analysis of clinical outcomes of patients with type 1 or 2 AMI from the 2017 Nationwide Readmissions Database, the median length of stay for patients with type 1 AMI was 3 days, and the 30-day readmission rate was 14 % [26]. A separate analysis of the Nationwide Readmissions Database between January and November 2013 revealed an overall 30-day readmission rate of 14.5 %, with variable rates across age groups (9.7 %, 11.2 %, and 17.3 % in patients aged 18 to 44, 45 to 64, and ≥65 years, respectively) [27]. Data collected from this database also revealed that, between 2010 and 2019, 30-day all-cause readmission rates decreased from 12.8 % to 11.6 % (P = 0.0001) and 90-day all-cause readmission rates decreased from 20.6 % to 18.8 % (P = 0.0001) [28]. Finally, a 2019 systematic literature review and meta-analysis found that the 30-day AMI readmission rate was 12 % across 14 included studies [29]. Overall, our findings align with the current literature. Differences in readmission rates between studies may be attributable to the data source – the Premier Healthcare Database only captures readmissions within the same health care system where the initial admission occurred; readmissions to other systems are not recorded. As a result, the present study likely underestimates the true readmission rates among all patients with AMI, including patients with systemic inflammation. Patients with evidence of systemic inflammation had significantly greater overall HCRU, experiencing longer stays and a higher rate of readmission after index. The 30-day readmission rate for patients with evidence of systemic inflammation was 14.4 %, which is consistent with previously reported values among patients with type 1 AMI [26]. Notably, the existing literature has not yet reported the admission rates for patients with type 1 AMI who present with underlying systemic inflammation at baseline. Given that the readmission rates may have been underestimated in this particular dataset, the differences between subgroups may be even greater in clinical practice.
Notably, patients with evidence of systemic inflammation exhibited statistically significant lower rates of pacemaker implant/defibrillator insertion, ventricular fibrillation, and ventricular tachycardia at the index visit compared with those without evidence of systemic inflammation. However, these differences were small, and incidence rates were low, and this observation was inconsistent with both 30-day and 90-day readmissions results, suggesting that the results may have occurred at random.
This study also showed the significant costs associated with AMI-related admissions and is the first study to describe the costs associated with AMI-related hospitalizations among patients with evidence of systemic inflammation. On average, health care costs for a patient with AMI were nearly $24,000 at index and more than $50,000 across all inpatient hospitalizations (during index and beyond). The median index cost for all patients with AMI reported here (approximately $15,600) is similar to the costs reported through the 2017 Nationwide Readmissions Database (more than $17,000) [26]. While patients with evidence of systemic inflammation demonstrated higher outpatient costs ($1192 vs $1109), index costs were lower compared with those without evidence of systemic inflammation ($14,385 vs $15,622). The inconsistencies observed between HCRU and cost in patients with or without evidence of systemic inflammation may be attributable to differences in hsCRP testing practices across hospital systems, which may have introduced bias in this study. For instance, patients with evidence of systemic inflammation were more likely to be admitted to rural and teaching hospitals – where costs may be lower – compared with patients without evidence of systemic inflammation. Reluctance of physicians to use hsCRP testing may be attributed to uncertainty surrounding the current diagnosis and treatment landscape for systemic inflammation [30]. Nevertheless, given the variance between costs, small sample size, and low real-world utilization and acceptance of the overall efficacy of hsCRP testing [25,30], further investigation is needed to better understand the role of systemic inflammation in the cost of health care for patients with AMI.
Despite the small sample size and the varied characteristics between patients with and without evidence of systemic inflammation, this study is among the first to investigate the role of systemic inflammation prior to AMI events. Furthermore, it provides an in-depth analysis of AMI outcomes that have not been extensively explored in previous research. This new evidence provides initial insights and enhances our understanding of the role of systemic inflammation and suggests a need for additional research to explore the impact of this significant risk factor on outcomes among patients with AMI.
Clinical trials have been completed or are currently underway to investigate the impact of emerging anti-inflammatory therapies on outcomes in patients who have experienced a cardiovascular event. The Canakinumab Anti-Inflammatory Thrombosis Outcome Study, or CANTOS trial, investigated the effect of the anti-inflammatory drug canakinumab on patients with established atherosclerotic disease who had experienced AMI [31]. Findings from this study demonstrated that the incidence of a recurrent cardiovascular event (ie, nonfatal AMI, stroke, or cardiovascular death) was significantly reduced in patients receiving 150 mg canakinumab compared with placebo (14 % vs 16 %, respectively). Inflammation, as determined by hsCRP levels, was markedly reduced in patients receiving canakinumab vs placebo [31]. Similarly, the Colchicine Cardiovascular Outcomes Trial, or COLCOT, investigated the effect of colchicine treatment on clinical outcomes in patients who had experienced AMI within 30 days before enrollment [32]. The risk of recurrent cardiovascular event was significantly reduced in patients receiving 0.5 mg daily colchicine compared with placebo (5.5 % vs 7.1 %, respectively) [32]. These results were expanded upon by the LoDoCo2 trial, which investigated the effect of daily 0.5 mg colchicine on cardiovascular outcomes in patients with chronic coronary disease and again demonstrated reduced risk of recurrent cardiovascular events with colchicine compared with placebo [33]. Currently underway, the ARTEMIS trial aims to investigate the effect of ziltivekimab, and IL-6 antibody, on time to first major adverse cardiovascular event in patients who had previously experienced an AMI [34].
While these trials have the potential to offer important results related to the treatment of patients with cardiovascular complications, they differ from the current analysis in several ways. First, they do not investigate outcomes in patients with preexisting inflammation and, therefore, cannot inform on the temporal relationship between systemic inflammation and the AMI event. Indeed, this study is one of the few studies that examine the association between baseline systemic inflammation and clinical outcomes after AMI admission. Second, these trials did not establish hsCRP/CRP test-confirmed systemic inflammation in patients before the primary AMI, indicating differences in the representative cohorts compared with this study. Finally, these trials investigate the usefulness of pharmaceutical interventions with the goal of lowering systemic inflammation before, during, and after the cardiovascular event. In contrast, this study investigated the cumulative effect of chronic baseline inflammation and the acute inflammatory response to the AMI event on clinical outcomes but was unable to account for the impact of medications on such outcomes.
4.1. Limitations
The current study used ICD-10-CM codes to identify patients with type 1 AMI; however, misclassification may have occurred if patients with type 1 AMI were not assigned the appropriate codes. Second, the Premier Healthcare Database may not have captured cases involving readmissions to a different hospital network, which could result in an underestimation of readmission rates. To minimize bias, this study excluded patients admitted through elective admission, defined as those who chose the hospital of their admission, indicating that their AMI visits were non-urgent, and they are more likely to go to other hospitals in case of recurrent emergency visits. However, future studies using other data sources may be necessary to provide a more accurate estimation on readmission. Third, patients with ST-segment elevation myocardial infarction (STEMI) may demonstrate different clinical manifestations compared with patients with non-STEMI, contributing to variations within the dataset. While evaluation of the differences between these two groups of patients is outside of the scope of this study, future studies would benefit from further classification of the clinical, HCRU, and economic differences between these groups. Another important limitation of this study was the limited number of patients with baseline CRP or hsCRP test results, which may have hindered our classification of patients with or without systemic inflammation. Although this percentage is consistent with other real-world studies and likely reflects a general low rate of testing [25], it indicates a high probability that some patients may have been misclassified because they were never tested. Consequently, the effect of systemic inflammation on AMI-related outcomes may be significantly underestimated, and more accurate classification may have resulted in even greater observed differences. Despite these limitations, to our knowledge, Premier is the only database that offers extensive in-hospital data and clinical outcomes among patients with AMI. Through propensity matching, patients with systemic inflammation could be matched to those without evidence of systemic inflammation (including patients without a recorded test) based on similarities in clinical characteristics, but this analysis would pose the same risk as the current analysis to misclassify patients who were not tested. Additionally, patient characteristics may not be adequately assessed among those with limited interactions with the hospital during baseline, leading to misestimation of certain key characteristics and failure to adequately adjust models to account for those characteristics. Conversely, the small sample size of patients with lab-confirmed systemic inflammation status (only 324 patients had CRP/hsCRP <2 mg/L) represents an inherent selection bias. Consequently, a comparison of patients with and without lab-confirmed systemic inflammation may be misleading, and propensity matching may offer limited additional value to this study. The current analysis provides valuable insights into the relationship between baseline systemic inflammation and AMI outcomes in the hospital setting and can therefore act as a guide for future studies in this important area. Finally, although hsCRP is the standard for assessing inflammatory risk in cardiology, limited hsCRP testing in this sample led to the inclusion of both hsCRP and standard CRP tests to identify patients with evidence of systemic inflammation. Evidence in the published literature has suggested overlapping ranges for these assays [19,35], and our sensitivity analysis provided similar results using hsCRP test results alone. Future research is required in datasets with greater hsCRP testing volumes to validate the study results.
5. Conclusion
The present study reinforces that patients who experience AMI continue to face significant clinical, HCRU, and economic burdens related to their care, including elevated risks of mortality, morbidity, and readmission, despite current standards of care. Additionally, patients with systemic inflammation may have greater unmet needs. These findings underscore the urgent need to enhance care for all patients with AMI, especially those with evidence of systemic inflammation.
Funding sources
This study was funded by Novo Nordisk Inc.
Data availability
The data that support the findings of this study are available from Premier Applied Sciences, Premier Inc., but restrictions apply to the availability of these data, which were used under license for the current study and are not publicly or freely available. Any researchers interested in obtaining the data used in this study can access the database through Premier Applied Sciences, Premier Inc., under a license agreement, including the payment of appropriate license fee.
All statistical analyses were conducted using RStudio V4.1.3 (Posit, PBC, Boston, MA). The programs are proprietary materials of Premier Applied Sciences, Premier Inc.; therefore, restrictions apply to the access of these codes, which cannot be made available publicly. Reasonable requests or questions related to the analysis will be addressed by the authors.
Author statement
All authors have read and approved the final version of the manuscript for submission. This work is the authors’ original work, has not been previously published as a manuscript, and is not being considered for publication elsewhere.
CRediT authorship contribution statement
Lei Lv: Writing – review & editing, Supervision, Project administration, Methodology, Conceptualization. Jeffrey R. Skaar: Writing – review & editing, Methodology, Conceptualization. Carey Robar: Writing – review & editing, Methodology, Conceptualization. Sunday Ikpe: Writing – review & editing, Formal analysis, Data curation. Shanthi Krishnaswami: Writing – review & editing, Project administration, Methodology, Formal analysis, Data curation. Zhun Cao: Writing – review & editing, Methodology, Formal analysis, Data curation. Weilong Li: Writing – review & editing, Resources, Project administration. Michael G. Nanna: Writing – review & editing, Methodology, Conceptualization.
Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
Lei Lv, Carey Robar, and Weilong Li are employed by Novo Nordisk Inc. Jeffrey R. Skaar is employed by and holds stock in Novo Nordisk Inc. and holds equity in Trinity Life Sciences. Sunday Ikpe, Shanthi Krishnaswami, and Zhun Cao are full-time employees of Premier Inc, which received payment from Novo Nordisk Inc. to conduct this study. Michael G. Nanna reports research support from the American College of Cardiology Foundation, the Patient-Centered Outcomes Research Institute, the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging (K76AG088428) and consulting for Novo Nordisk Inc., Merck, and HeartFlow, Inc.
Acknowledgements
This study was funded by Novo Nordisk Inc. The authors thank Amy Ryan, PhD, of Precision AQ (Bethesda, Maryland) for providing writing and editing assistance in accordance with Good Publication Practice (GPP 2022) guidelines. This assistance was financially supported by Novo Nordisk Inc.
Footnotes
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajpc.2025.101320.
Appendix. Supplementary materials
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from Premier Applied Sciences, Premier Inc., but restrictions apply to the availability of these data, which were used under license for the current study and are not publicly or freely available. Any researchers interested in obtaining the data used in this study can access the database through Premier Applied Sciences, Premier Inc., under a license agreement, including the payment of appropriate license fee.
All statistical analyses were conducted using RStudio V4.1.3 (Posit, PBC, Boston, MA). The programs are proprietary materials of Premier Applied Sciences, Premier Inc.; therefore, restrictions apply to the access of these codes, which cannot be made available publicly. Reasonable requests or questions related to the analysis will be addressed by the authors.