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STEMI

Delirium is an important predictor of mortality in elderly patients with ST-elevation myocardial infarction: insight from National Inpatient Sample database

Patil, Shivaraja; Gonuguntala, Karthika; Rojulpote, Chaitanyab; Kumar, Manisha; Corradi, John P.c; Chen, Kaia

Author Information
doi: 10.1097/MCA.0000000000000978

Abstract

Introduction

Cardiovascular disease (CVD) is the leading cause of death worldwide, inflicting a societal burden on healthcare in terms of morbidity, mortality, and healthcare costs [1]. The notion of age being a significant risk factor for CVD has been well established. The prevalence of CVD in elderly population over the age of 65 years is seven-fold higher than younger population [2]. According to the Cardiovascular Health Study, the incidence of myocardial infarction in population over the age of 80 years is higher than any other age groups. The absolute numbers of ST-elevation myocardial infarction (STEMI) increase with increasing age [3]. The in-hospital mortality of STEMI has decreased with advancements in technology and early revascularization [4], however, this group continues to have the highest mortality among acute coronary syndrome population [5].

Delirium is a clinical condition that disrupts the normal functioning of the brain by affecting a patient’s orientation, awareness and is seen frequently in hospitalized elderly patients. In fact, the old age is known to be a key risk factor for the development of delirium. It may manifest with cognitive impairment, behavioral changes, reduced awareness of the environment, and emotional disturbances. Delirium is associated with several adverse outcomes such as a longer length of hospital stay, poor functioning status, and a significantly higher mortality rate [6–8]. Importantly, our understanding of delirium being a sequela of critical illness has shifted towards delirium also serving as a prognostic marker. As a result, delirium has gained a formal classification as a type of target organ injury in ICU [9]. It has been extensively studied in the medical intensive care setting, affecting 60–80% of mechanically ventilated and 20–50% of non-mechanically ventilated critically ill patients [10]. However, the impacts of delirium on patients with STEMI, in particular among geriatric population, are largely unexplored. These STEMI patients represent the specific group with the highest mortality and increased incidence of delirium, which has an unmet need for better understanding and care. In this study, we sought to evaluate the impacts of delirium in elderly patients undergoing percutaneous coronary intervention (PCI) following STEMI by using the largest US inpatient care database National Inpatient Sample (NIS).

Methods

Data source

We obtained data from the year 2010 to 2014 NIS that is the largest publicly available all-payer inpatient care database from the USA [11]. It is developed as a part of the Healthcare Cost and Utilization Project (HCUP) and is sponsored by the Agency for Healthcare Research and Quality [11]. The NIS includes data from all nonfederal, short-term, general, and other specialty hospitals in the USA (excluding rehabilitation and long-term acute care hospitals) in the form of de-identified patient information containing demographics, discharge diagnoses, comorbidities, procedures, outcomes, and hospitalization costs. All the states that participate in HCUP provide data to the NIS, covering >95% of the U.S. population. The database was designed to include data from a 20% sample of discharges from all participating hospitals. This design of the NIS reduces the margin of error for estimates and delivers more stable and precise estimations. The study was exempt from an Institutional Review Board approval because HCUP-NIS is a publicly available database containing only de-identified patient information.

Study population

We used the International Classification of Diseases-Ninth Edition-Clinical Modification (ICD-9-CM) diagnosis codes 410.01, 410.11, 410.21, 410.31, 410.41, 410.51, 410.61, 410.81, and 410.91 to identify all patients who were 18 years of age or older, and hospitalized with a primary diagnosis of STEMI. This approach is consistent with previous studies using the NIS database to accurately identify patients with STEMI [12,13]. We identified the patients who underwent PCI using the following ICD-9 procedure codes: 96.06, 96.07, and 0.66. We used the following ICD-9-CM diagnosis codes: 290.3, 290.41, 293.0, 293.1, 348.31, and 780.97 to determine the patients with delirium. We excluded patients who were below the age of 65, did not undergo PCI, underwent coronary artery bypass graft, developed coma or persistent vegetative state, had traumatic brain injury, had intracranial bleeding or acute ischemic stroke during the hospitalization. In addition, we excluded patients with incomplete data for gender and mortality. Also, in order to reduce the possibility of data duplication, the patients with an indicator for transfer to another acute-care facility were excluded.

Outcomes measured

We studied the incidence of delirium in the elderly cohort of patients with STEMI undergoing PCI. All-cause in-hospital mortality, which was defined as ‘died’ during the hospitalization encounter in the NIS database, was the primary outcome of interest and average length of stay (LOS) was used as the secondary outcome.

Patient characteristics

Baseline patient characteristics included demographics (age, sex, and race/ethnicity), Charlson comorbidities and index score [14], and other clinically relevant characteristics (cardiogenic shock, non-cardiogenic shock, arrhythmias, mechanical ventilation, post-procedure bleeding, sepsis, acute kidney injury, fluid and electrolyte disorders, hypertension, dyslipidemia, smoking). Supplementary Table 1, Supplemental digital content 1, http://links.lww.com/MCA/A397 lists the ICD-9-CM and Clinical Classification Software codes used to identify comorbidities and procedures.

Statistical analysis

All analysis was done using weighted national estimates calculated by applying discharge weights to the unweighted discharge data. We initially compared the baseline patient characteristics between STEMI patients undergoing PCI with and without delirium using the Pearson chi-square test for categorical variables, and Student’s t-test and Mann–Whitney U test for continuous variables with normal and skewed distribution respectively. Univariate and multivariate logistic regression analyses were used to compare in-hospital mortality in STEMI patients with and without delirium in the overall cohort of patients. Multivariable linear regression after log transformation of the dependent variable was used to compare average LOS between STEMI patients with and without delirium. Variables included in the regression model were age, sex, race, Charlson comorbidity variables, and other clinically relevant comorbidities.

SPSS Statistics 25.0 (IBM Corp., Armonk, New York, USA) was used to perform the statistical analysis. The R package was used to derive the Quan modified Charlson index [15]. All P values were two-sided with a significance threshold of less than 0.05. Categorical variables are expressed as percentages and continuous variables as mean ± SD for normally distributed data and median with interquartile range for skewed data. Odds ratio, parameter estimate, and 95% confidence intervals (CIs) are used to report the results of logistic regression and linear regression after log transformation, respectively.

Results

Incidence of delirium in patients with ST-elevation myocardial infarction

We included 8596 unweighted records representing a total of weighted 42 980 patients aged ≥65 years and hospitalized with a primary diagnosis of STEMI who underwent PCI between 2010 and 2014. Overall, Delirium was present in 157 of the unweighted records representing total of 774 (1.8%) of the STEMI patients. Incidence stratified by age was 1.4, 2.2, and 3.2% in 65–74 years, 75–84 years, and ≥85 years of age, respectively. Compared with STEMI patients without delirium, those with delirium were more likely to be older and have more underlying comorbidities [Median Charlson score 2 (1; 3) vs. 0 (0; 2); P < 0.001] (Table 1).

Table 1 - Baseline demographics and comorbidities of ST-elevation myocardial infarction patients with and without delirium
Characteristics STEMI patients with delirium STEMI patients without delirium P value
Number of cases (weighted) 774 (1.8%) 42 206 (98.2%)
Age (mean ±SD) 76.0 ± 7.6 73.7 ± 7.0 <0.001
Incidence by age
 65–74 1.4% 98.6%
 75–84 2.2% 97.8%
 ≥85 3.2% 96.8%
Male 65% 63.9% 0.78
White race 74.5% 76.8% 0.47
Cardiogenic shock 49% 10.8% <0.001
Non cardiogenic shock 0% 0.3% <0.001
Mechanical ventilation 29.9% 5.5% <0.001
Ventricular fibrillation 17.2% 5.8% <0.001
Ventricular tachycardia 19.7% 10.5% <0.001
Atrial fibrillation 27.4% 15.3% <0.001
Sepsis 4.5% 0.5% <0.001
Acute kidney injury 12.7% 1.5% <0.001
Electrolyte and acid-base disorder 43.3% 15% <0.001
Post procedure bleeding 7% 2% <0.001
Diabetes without chronic complications 30.6% 26.8% 0.29
Diabetes with chronic complications 3.8%% 2.8% 0.42
Hypertension 55.4% 71.6% <0.001
Hyperlipidemia 100% 67.7% <0.001
Smoking 21.7% 18.8% 0.36
Congestive heart failure 45.9% 20.1% <0.001
Peripheral vascular disease 15.3% 8.7% 0.004
Cerebrovascular disease 3.2% 1% 0.007
Dementia 1.9% 0.8% 0.11
Paralysis 1.3% 0.1% <0.001
Chronic pulmonary disease 29.9% 17% <0.001
Renal disease 28% 13.1% <0.001
Mild liver disease 15.3% 2.4% <0.001
Moderate-severe liver disease 0% 0.2% 0.62
Peptic ulcer disease 1.3% 0.9% 0.61
HIV/AIDS 0% 0% 0.08
Any malignancy, including lymphoma and leukemia 4.5% 2.3% 0.08
Metastatic cancer 1.9% 0.7% 0.08
Rheumatologic disease 3.2% 2.5% 0.6
Median Charlson comorbid index score (25th percentile; 75th percentile) 2 (1;3) 0 (0;2) <0.001
STEMI, ST-elevation myocardial infarction.

In-hospital mortality

The overall in-hospital mortality in the cohort was 8.2%. In-hospital mortality in STEMI patients with delirium was significantly higher than those without delirium [42.7% vs 7.6%; unadjusted odds ratio (OR) 9.07; 95% CI 6.55–12.57; P < 0.001; adjusted OR 1.86; 95% CI 1.13–3.04; P = 0.014]. Delirium was associated with an approximately six-fold increase in mortality among elderly patients (≥65 years) with STEMI managed with PCI (Tables 2 and 3).

Table 2 - In-hospital mortality and length of stay of ST-elevation myocardial infarction patients with and without delirium
Outcome STEMI patients with delirium STEMI patients without delirium Unadjusted odds ratio (95% CI) P value Adjusted odds ratio (95% CI) P value
In-hospital mortality 42.7% 7.6% 9.07 (6.55–12.57) <0.001 1.86 (1.13–3.04) 0.014
Unadjusted parameter estimate (95% CI) Adjusted parameter estimate (95% CI)
Median length of stay (25th percentile; 75th percentile) 5 (3; 10) 3 (2; 4) 1.92 (1.75–2.10) <0.001 1.48 (1.36–1.61) < 0.001
CI, confidence interval; STEMI, ST-elevation myocardial infarction.

Table 3 - Adjusted odds ratios for in-hospital mortality and risk factors in multivariable logistic regression
Characteristics AOR 95% CI P value
Delirium 1.88 1.15–3.07 0.012
Age 1.09 1.08–1.11 <0.001
Female sex 1.61 1.29–2.01 <0.001
Caucasian race 0.74 0.58–0.94 0.015
Cardiogenic shock 12.6 9.95–15.97 <0.001
Non cardiogenic shock 4.65 1.63–13.29 0.004
Mechanical ventilation 13.99 10.13 –19.32 <0.001
Ventricular fibrillation 2.35 1.72–3.21 <0.001
Ventricular tachycardia 1.5 1.12–1.99 0.006
Atrial fibrillation 1.09 0.84–1.41 0.52
Sepsis 4.44 1.89–10.45 0.001
Acute kidney injury 4.08 2.43–6.84 <0.001
Electrolyte and acid base disorders 2.02 1.59–2.56 <0.001
Post procedure bleeding 0.49 0.3–0.83 0.007
Diabetes without chronic complications 1.24 0.97–1.59 0.087
Diabetes with chronic complications 1.29 0.71–2.33 0.4
Hypertension 0.63 0.5–0.8 <0.001
Hyperlipidemia 0.90 0.71–1.15 0.41
Smoking 1.05 0.76–1.46 0.75
Congestive heart failure 0.7 0.54–0.9 0.005
Peripheral vascular disease 1.25 0.89–1.75 0.2
Cerebrovascular disease 2.29 1.07–4.9 0.033
Dementia 2.50 1.12–5.58 0.025
Paralysis 0.63 0.08–5.1 0.66
Chronic pulmonary disease 1.3 1.01–1.74 0.044
Chronic kidney disease 1.23 0.93–1.64 0.154
Mild liver disease 2.52 1.6–3.98 <0.001
Moderate/severe liver disease 2.15 0.37–12.55 0.394
Peptic ulcer disease 0.66 0.23–1.88 0.44
Any malignancy, including leukemia and lymphoma 1.05 0.55–1.99 0.88
Metastatic solid tumor 1.52 0.55–4.22 0.42
Rheumatologic disease 0.49 0.25–1.00 0.049
AOR, adjusted odds ratio; CI, confidence interval.

Length of stay

STEMI patients with delirium had significantly longer median LOS than those without delirium [5 (3; 10) vs. 3 (2; 4) days; unadjusted parameter estimate = 1.92; 95% CI 1.75–2.10; adjusted parameter estimate = 1.48; 95% CI 1.36–1.61; P < 0.001] (Table 2).

Discussion

The present study shows increased incidence of delirium with increasing age, and number of comorbidities in STEMI patients undergoing PCI. Previous studies have shown that the incidence of delirium in patients with an acute myocardial infarction varies widely from 1.4 to 29% [16–22]. A large prospective study investigating delirium outcomes in elderly non-surgical cardiac patients aged ≥65 years admitted to the CICU reported an overall incidence of 15% [18]. In contrast, another retrospective study utilizing the NIS database reported an incidence of 1.4% in patients admitted to the hospital with a diagnosis of acute myocardial infarction [23]. The overall incidence of delirium in our study was 1.8%, slightly higher than 1.4% reported by Abdullah et al. in which same NIS database was utilized but all patients with acute myocardial infarction were included with majority having non-STEMI. We believe the incidence in our study likely under-represents the real-world incidence of delirium due to differences in patient populations, clinical settings, the study design, and delirium assessment methodology [24,25]. In addition, because of the administrative source of our data, under-reporting due to coding errors could also have contributed to the low incidence of delirium observed in our study.

A number of risk factors are known to contribute to the precipitation of delirium. Among them, mechanical ventilation, cardiogenic shock, heart failure, and ventricular arrhythmia appear to be the top predictors based on our results. Notably, all these clinical conditions are associated with hemodynamic instability and increased systemic inflammation – two potential pathophysiological mechanisms contributing to delirium development. For example, the resultant cardiogenic shock by STEMI not only directly impairs cerebral blood flow through hemodynamic derangement but also causes excessive lactate production and acidosis that subsequently lead to cerebral tissue and neuronal injury [26]. In agreement with this notion, our data demonstrated a five-fold increase in delirium in patients with cardiogenic shock. Furthermore, systemic inflammation results in an increased production of pro-inflammatory cytokines and reactive oxygen species that presumably cross the blood-brain barrier and damage cerebral tissue leading to occurrence of delirium [27].

Delirium is linked to poor clinical outcomes. Studies evaluating the relationship between delirium and in-hospital mortality in hospitalized older patients have shown significant association [28,29]. Similarly, studies analyzing older patients with non-surgical acute cardiac diseases who developed delirium have shown adverse in-hospital and long-term clinical outcomes [18,22]. In our study, the overall in-hospital mortality in older patients with STEMI and delirium was 42.7%, approximately six-fold higher than in-hospital mortality in STEMI patients without delirium. Presence of delirium was also associated with a >2-fold increase in LOS after adjusting for potential confounding factors such as age, sex, and comorbid illnesses. Although our study showed a significant association between delirium and higher in-hospital mortality in older STEMI patients who underwent PCI, a directive causative relationship could not be fully established, which is beyond the scope of our study.

In spite of growing evidence that suggests an association of delirium with increased mortality, particularly among severely ill patients admitted to the intensive care setting [16,18,19,22,30], several studies have found no association with mortality [31]. Furthermore, current literature has shown inconsistent results to support that ICU interventions that reduce delirium duration reduce short-term mortality, with some data reporting improvement [32] and others not [33]. Nonetheless, given the rise in CVD burden in an aging population and the significant impact of delirium on in-hospital mortality, our results emphasize the importance of accurately recognizing delirium in elderly patients with STEMI, which may help our understanding of the role of delirium and development of potential target intervention in these clinical settings.

Study limitations

Certain limitations inherent to the retrospective nature of our study must be acknowledged. First, because NIS is an administrative database, the accuracy of the data depends highly on the training and expertise of the coders. Hence, there is the potential of unrecognized miscoding of diagnosis and procedure codes, leading to underestimation or overestimation of STEMI or delirium based on ICD-9-CM coding. As a result, delirium may often be under-coded in ICU patients or patients with STEMI. Second, we were not able to determine the time of onset, duration, type, or severity of delirium occurring during the hospitalization. We were also unable to examine the temporal relation between PCI and the time of occurrence of delirium. Therefore, we could not precisely determine the impact of prompt reperfusion by PCI on the likelihood of developing delirium. Third, data on length of CCU stay, laboratory values, and the use of adjunctive medications were not available, and therefore the impact of these on the occurrence of delirium could not be determined. Also, we were unable to determine the extent of baseline coronary artery disease due to the lack of coding. As it is true for all observational studies, we cannot rule out the possibility that unobserved confound might have occurred, even after accounting for relatively large number of covariates. Lastly, data in NIS are limited to in-hospital events, and information on long-term outcomes is not available.

Conclusion

Older ages and comorbidities are known predisposing factors for delirium which appeared to be associated with higher in-hospital mortality and increased LOS in elderly patients with STEMI. The findings in this study may extend further questions for future studies to define the role of delirium as a key component of complex pathophysiological mechanism during critical cardiac disease process.

Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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Keywords:

delirium; percutaneous coronary intervention; ST-elevation myocardial infarction

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