Patients hospitalized with sepsis may be predisposed to acute myocardial infarction (AMI). The incidence, treatment, and outcomes of AMI in sepsis have not been studied. We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients with a diagnosis of sepsis. The incidence of AMI as a nonprimary diagnosis was evaluated. Propensity score matching was used to identify a cohort of patients with secondary AMI and sepsis with similar baseline characteristics who were managed invasively (defined as cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) or conservatively. The primary outcome was in-hospital all-cause mortality. A total of 2,602,854 patients had a diagnosis of sepsis. AMI was diagnosed in 118,183 patients (4.5%), the majority with non-ST elevation AMI (71.4%). In-hospital mortality was higher in patients with AMI and sepsis than those with sepsis alone (35.8% vs 16.8%, p <0.0001; adjusted odds ratio 1.24, 95% CI 1.22 to 1.26). In patients with AMI, 11,899 patients (10.1%) underwent an invasive management strategy, in which 4,668 patients (39.2%) underwent revascularization. PCI was performed in 3,413 patients (73.1%), CABG in 1,165 (25.0%), and both CABG and PCI in 90 patients (1.9%). In a propensity-matched cohort of 23,708 patients with AMI, invasive management was associated with a lower mortality than conservative management (19.0% vs 33.4%, p <0.001; odds ratio 0.47, 95% CI 0.44 to 0.50). In subgroups that underwent revascularization, the odds of mortality were consistently lower than corresponding matched subjects from the conservative group. In conclusion, myocardial infarction not infrequently complicates sepsis and is associated with a significant increase in in-hospital mortality. Patients managed invasively had a lower mortality than those managed conservatively.
Background
Sepsis is a common clinical syndrome characterized by a systemic inflammatory response to an infectious process. Although the pathogenesis of severe sepsis is incompletely understood, it is believed to involve an aberrant release of proinflammatory mediators that leads to tissue injury and end organ damage. Among the myriad complications, patients with sepsis may be predisposed to develop myocardial ischemia and acute myocardial infarction (AMI). However, the incidence, treatment, and outcomes of AMI in patients with sepsis have not been studied. Although the American College of Cardiology/American Heart Association guidelines for the management of patients with acute coronary syndromes recommend an early invasive strategy in high risk patients with MI, current clinical practice guidelines do not directly address AMI in sepsis, and the benefit of early invasive versus conservative management in this scenario has not been established. We performed a retrospective observational study of patients included in a large nationwide administrative database to determine the incidence of AMI in sepsis and the association between acute management and in-hospital outcomes.
Methods
We analyzed unweighted data from the Healthcare Cost and Utilization Project National Inpatient Sample (NIS) from 2002 to 2011. The NIS is the largest all-payer inpatient health care database in the United States, with discharge-level data from >1,000 facilities that approximate a 20% stratified sample of all US hospitals. Patients with any diagnosis of sepsis were identified using the Clinical Classifications Software (CCS) diagnosis code 2. The CCS diagnosis and procedure categorization scheme aggregates International Classification of Diseases, Ninth Revision (ICD-9) codes into a smaller number of clinically relevant categories.
AMI was identified using nonprimary ICD-9 diagnosis codes for acute ST elevation MI (410.x1) and non-ST elevation MI (410.71). Invasive management of AMI was defined as the use of diagnostic coronary angiography, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) during the index hospitalization, identified by ICD-9 and CCS diagnosis and procedure codes. Otherwise, patients were considered to be managed conservatively. Trends in the use of PCI and CABG over time were evaluated for patients with sepsis and AMI undergoing invasive management. The primary outcome was in-hospital mortality.
Continuous variables were reported as mean ± SD and compared using the Student t test. Categorical variables were reported as percentages and were compared by chi-square tests. Baseline characteristics associated with management and outcomes were estimated with univariate logistic regression models and reported as odds ratios (ORs) with 95% CIs. Multivariate logistic regression models were built to estimate the ORs adjusted for demographics, cardiovascular risk factors, and relevant co-morbidities.
Propensity score matching was used to identify cohorts of patients with similar baseline characteristics who underwent invasive and conservative management of AMI in sepsis. Propensity score matching was performed using a 1:1 matching protocol without replacement using caliper width of 0.2 of the SD of the logit of the propensity score. Covariates in the model included baseline demographics, cardiovascular risk factors, relevant co-morbidities, and year of hospitalization. Absolute standardized differences were estimated to assess imbalance before and after propensity matching, with absolute standardized differences of >10% denoting imbalance.
Statistical analyses were performed using SPSS 20 (IBM SPSS Statistics, Armonk, New York) and SAS, version 9.3 (SAS Institute Inc., Cary, North Carolina). Statistical tests are 2-sided and p value <0.05 was considered to be statistically significant.
Methods
We analyzed unweighted data from the Healthcare Cost and Utilization Project National Inpatient Sample (NIS) from 2002 to 2011. The NIS is the largest all-payer inpatient health care database in the United States, with discharge-level data from >1,000 facilities that approximate a 20% stratified sample of all US hospitals. Patients with any diagnosis of sepsis were identified using the Clinical Classifications Software (CCS) diagnosis code 2. The CCS diagnosis and procedure categorization scheme aggregates International Classification of Diseases, Ninth Revision (ICD-9) codes into a smaller number of clinically relevant categories.
AMI was identified using nonprimary ICD-9 diagnosis codes for acute ST elevation MI (410.x1) and non-ST elevation MI (410.71). Invasive management of AMI was defined as the use of diagnostic coronary angiography, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) during the index hospitalization, identified by ICD-9 and CCS diagnosis and procedure codes. Otherwise, patients were considered to be managed conservatively. Trends in the use of PCI and CABG over time were evaluated for patients with sepsis and AMI undergoing invasive management. The primary outcome was in-hospital mortality.
Continuous variables were reported as mean ± SD and compared using the Student t test. Categorical variables were reported as percentages and were compared by chi-square tests. Baseline characteristics associated with management and outcomes were estimated with univariate logistic regression models and reported as odds ratios (ORs) with 95% CIs. Multivariate logistic regression models were built to estimate the ORs adjusted for demographics, cardiovascular risk factors, and relevant co-morbidities.
Propensity score matching was used to identify cohorts of patients with similar baseline characteristics who underwent invasive and conservative management of AMI in sepsis. Propensity score matching was performed using a 1:1 matching protocol without replacement using caliper width of 0.2 of the SD of the logit of the propensity score. Covariates in the model included baseline demographics, cardiovascular risk factors, relevant co-morbidities, and year of hospitalization. Absolute standardized differences were estimated to assess imbalance before and after propensity matching, with absolute standardized differences of >10% denoting imbalance.
Statistical analyses were performed using SPSS 20 (IBM SPSS Statistics, Armonk, New York) and SAS, version 9.3 (SAS Institute Inc., Cary, North Carolina). Statistical tests are 2-sided and p value <0.05 was considered to be statistically significant.
Results
A total of 2,602,854 patients with sepsis satisfied our inclusion criteria ( Figure 1 , Supplementary Table 1 ). Among these patients with sepsis, AMI developed in 118,183 patients (4.5%), the majority being non-ST elevation MI (71.4%). The diagnosis of sepsis increased twofold over the study period, with a proportional increase in the frequency of diagnosis of sepsis and AMI ( Figure 2 ). Baseline characteristics of patients with sepsis with and without AMI are displayed in Table 1 . Patients with AMI were older, more likely to be men, and more likely to have cardiovascular risk factors and established coronary artery disease (CAD). Patients with AMI were more likely to have pneumonia, respiratory failure and mechanical ventilation, kidney injury, and shock requiring vasopressors during hospital admission than patients without AMI ( Table 1 ).
| Variable | Acute Myocardial Infarction | P-value | |
|---|---|---|---|
| Yes (n=118,183) | No (n=2,484,248) | ||
| Age, mean ± standard deviation (years) | 73.21 ± 13.55 | 66.33 ± 17.47 | <0.0001 |
| Women | 49.6% | 51.0% | <0.0001 |
| Race | <0.0001 | ||
| White | 60.6% | 55.1% | |
| Black | 10.5% | 13.6% | |
| Hispanic | 6.9% | 7.8% | |
| Asian or Pacific Islander | 2.6% | 2.1% | |
| Native American | 0.4% | 0.5% | |
| Other Race | 2.4% | 2.1% | |
| Race Not Specified | 16.7% | 18.7% | |
| Tobacco Use | 8.2% | 11% | <0.0001 |
| Hypertension | 46.8% | 46.9% | 0.90 |
| Hyperlipidemia | 15.3% | 14.3% | <0.0001 |
| Diabetes Mellitus | 29.3% | 29.4% | 0.71 |
| Chronic Kidney Disease | 22.8% | 18% | <0.0001 |
| Hemodialysis Dependent | 13.8% | 10.7% | <0.0001 |
| Coronary Artery Disease | 31.2% | 17.9% | <0.0001 |
| Prior Myocardial Infarction | 3.8% | 3.1% | <0.0001 |
| Prior Percutaneous Coronary Intervention | 3% | 1.8% | <0.0001 |
| Prior Coronary Bypass | 4.7% | 3.5% | <0.0001 |
| Prior Transient Ischemic Attack / Stroke | 2.3% | 2.2% | 0.13 |
| Prior Heart Failure | 2.6% | 1.7% | <0.0001 |
| Prior Venous Thromboembolism | 1.3% | 2.4% | <0.0001 |
| Valvular Heart Disease s/p Replacement | 0.7% | 0.9% | <0.0001 |
| Atrial Fibrillation | 24.9% | 16.8% | <0.0001 |
| Obstructive Sleep Apnea | 1.8% | 2.1% | <0.0001 |
| Admission Characteristics: | |||
| Pneumonia | 38.1% | 27.9% | <0.0001 |
| Respiratory Failure | 53.5% | 26.8% | <0.0001 |
| Acute Liver Disease | 5.8% | 1.8% | <0.0001 |
| Gastrointestinal Bleed | 8.7% | 5.0% | <0.0001 |
| Acute Kidney Injury | 48.5% | 28.6% | <0.0001 |
| Shock | 38.8% | 17.2% | <0.0001 |
| Vasopressor Use | 3.7% | 1.4% | <0.0001 |
| Mechanical Ventilation | 47.1% | 21.1% | <0.0001 |
| ST Elevation Myocardial Infarction | 28.5% | 0% | |
| Non-ST Elevation Myocardial Infarction | 71.5% | 0% | |
In a multivariate model adjusted for demographic and baseline clinical variables, advanced age, a history of kidney disease, known CAD, heart failure, and atrial fibrillation at baseline were predictors of AMI during hospital admission in patients with sepsis ( Table 2 ).
| Variable | Adjusted Odds Ratio (95% CI) | P value |
|---|---|---|
| Age | 1.024 (1.023 – 1.024) | <0.001 |
| Women | 0.951 (0.938 – 0.963) | <0.001 |
| White | Reference | |
| Black | 0.841 (0.824 – 0.858) | <0.001 |
| Hispanic | 0.928 (0.906 – 0.951) | <0.001 |
| Asian or Pacific Islander | 1.116 (1.075 – 1.158) | <0.001 |
| Native American | 0.948 (0.866 – 1.037) | 0.241 |
| Other Race | 1.122 (1.079 – 1.167) | <0.001 |
| Tobacco Use | 0.891 (0.871 – 0.911) | <0.001 |
| Hypertension | 0.776 (0.765 – 0.787) | <0.001 |
| Hyperlipidemia | 0.961 (0.943 – 0.979) | <0.001 |
| Diabetes Mellitus | 0.969 (0.955 – 0.983) | <0.001 |
| Chronic Kidney Disease | 1.157 (1.137 – 1.178) | <0.001 |
| Hemodialysis | 1.53 (1.497 – 1.563) | <0.001 |
| Coronary Artery Disease | 2.062 (2.028 – 2.096) | <0.001 |
| Prior Myocardial Infarction | 0.709 (0.685 – 0.733) | <0.001 |
| Prior Percutaneous Coronary Intervention | 1.057 (1.018 – 1.099) | 0.004 |
| Prior Coronary Bypass | 0.715 (0.693 – 0.737) | <0.001 |
| Prior Transient Ischemic Attack / Stroke | 0.838 (0.804 – 0.873) | <0.001 |
| Prior Heart Failure | 1.168 (1.122 – 1.216) | <0.001 |
| Prior Venous Thromboembolism | 0.573 (0.544 – 0.604) | <0.001 |
| Atrial Fibrillation | 1.207 (1.189 – 1.226) | <0.001 |
| Obstructive Sleep Apnea | 0.937 (0.894 – 0.981) | 0.006 |
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