The influence of pressure injury risk on the association between left ventricular ejection fraction and all-cause mortality in patients with acute myocardial infarction 80 years or older

Abstract

BACKGROUND:

We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction (LVEF) with all-cause death in patients with acute myocardial infarction (AMI) aged 80 years or older.

METHODS:

This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups (low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome.

RESULTS:

Over a median follow-up period of 1,176 d (interquartile range [IQR], 722–1,900 d), 226 (33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury (adjusted hazard ratios [HR]=1.81, 95% confidence interval [CI]: 1.03–3.20; P=0.040), but not in the low/minimal- (adjusted HR=1.29, 95%CI: 0.80–2.11; P=0.299) or intermediate-risk groups (adjusted HR=1.14, 95%CI: 0.65–2.02; P=0.651). Significant interactions were detected between pressure injury risk and LVEF (adjusted P=0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups.

CONCLUSIONS:

In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management.

INTRODUCTION

Pressure injuries are common in hospitalized older patients, and the prevalence is positively correlated with age.[1] Nearly 80% of pressure ulcer-related deaths involve individuals older than 75 years.[2] The high risk of pressure injury in older individuals is due to changes associated with physiological factors that accompany aging, such as limited mobility, skin aging, impaired sensory perception, concomitant diseases and nutritional deficiency, along with mechanical forces and local humidity.[3,4] The negative prognostic relevance of pressure injuries in several conditions, including higher medical expenses, longer lengths of stay, and increased risk of mortality and readmission, has been reported.[5,6] A prospective cohort study found that 16.3% of patients with acute myocardial infarction (AMI, mean age 67.5 years) who were admitted to the intensive cardiac care unit experienced pressure injuries.[7] The Norton’s functional score, a crucial instrument initially intended to assess the risk of pressure injury, was used to predict long-term outcomes in a study of 6,964 patients with AMI who had a mean age of 67.3 years. The findings revealed a dose-response relationship between the Norton’s functional score and all-cause mortality among MI survivors with up to 10 years of follow-up.[8] However, it is unclear whether the risk of pressure injury, which is a reflection of chronic health status, influences recovery following an acute attack and impacts long-term outcomes in older patients with AMI.

Following AMI, adverse left ventricular (LV) remodeling and impaired LV ejection fraction (LVEF) can be associated with an increased risk of cardiac or non-cardiac mortality and ventricular arrhythmias.[9-11] Nevertheless, the trajectories of LV systolic function do vary, as myocardial stunning might be a significant component in the acute period, and standard treatment for secondary prevention promotes the recovery of the compromised myocardium.[12-15] It has been reported that more than 40% of young patients with MI were likely to have EF recovery, with a lower risk of both all-cause and cardiovascular mortality.[16] Few studies have examined the post-MI trajectories of LV function in elderly individuals over the age of 80. However, a study on the prediction factors of the persistence of LV systolic dysfunction after MI failed to discover an association between chronological age and the recovery of heart function following MI.[17]

It is widely believed that people with depressed EF have a worse prognosis than people with preserved EF. However, this association may be modified by a patient’s baseline health status because the long-term prognosis of MI patients is correlated with both acute attack and chronic health issues.[18,19] The present study aimed to investigate the potential influence of pressure injury risk on the association of EF measured during index hospitalization with all-cause mortality after hospital discharge in patients with MI aged ≥ 80 years.

METHODS

Study design and study population

AMI patients who were hospitalized from 2012 to June 2019 at West China Hospital of Sichuan University were the subjects of this retrospective observational study. Baseline characteristics, clinical features, pharmaceutical and invasive therapy, and clinical outcomes for coronary heart disease under real-world situations were evaluated. We chose 80 as the cut-off age for this study since it has been predicted that the number of people aged 80 and older will rise 3.5-fold globally between 2015 and 2050. The very elderly will face difficulties managing their health and making medical decisions.[20] The study was approved by the local institutional review boards. Informed consent was waived due to the retrospective chart review study design.

All patients with AMI who were admitted to the study location during the study period were included. The diagnosis was verified in the patients’ discharge records, and the definition of AMI complied with the universal criteria of MI.[21] Clinical follow-up was completed in January 2021. The primary endpoint of this study was all-cause death, which was confirmed by the population administrative system.

The clinical outcome of all-cause death in patients having an initial echocardiographic assessment of reduced EF (<50%) versus preserved EF (≥50%) after discharg was examined in this study. Patients without echocardiographic results or pressure injury risk assessment forms were excluded from the analysis. A stratified analysis was carried out based on the patients’ risk of pressure injuries at admission to determine the influence of pressure injuries on LVEF. We compared the association between the initial measured LVEF and long-term follow-up all-cause mortality among subgroups with various pressure injury risks.

Study definition

With a cut-off value of 50%, we used LVEF measurements obtained during echocardiography to identify EF reduction or preservation.[22] Echocardiography was performed during hospitalization, and quantitative measurement and analysis were performed in real-time, following the recommendations of the American Society of Echocardiography.[23] Depending on the patient’s clinical condition, the examination was conducted in the echo lab or at the cardiac care unit. LV volume was measured using two-dimensional echocardiography, and LVEF was calculated by the modified biplane Simpson’s method. Image acquisition, interpretation, and reporting were completed by qualified physicians. Philips IE 33, CX50 or GE Vivid i ultrasound machine were the most commonly used models.

The Braden scale, as one of the crucial components of nursing safety and quality management, was applied by registered nurses to determine the risk of pressure injuries at admission.[24] Earlier research has demonstrated the accuracy of the Braden score in predicting the prognosis of hospitalized heart failure patients.[25] This score included six dimensions: sensory perception, moisture, activity, mobility, nutrition, friction and shear.[26] Each dimension had three to four levels of severity, and a score was given based on how severe the functional restrictions were. The patient was at greater risk if the number was lower. A total score of ≥15 indicated low or minimal risk, a score of 13–14 indicated intermediate risk, and a score of ≤12 indicated high or very high risk.[24,27]

The primary outcome of this study was all-cause death following hospital discharge. The events were confirmed by the population administrative system, and the date of death was recorded.

The electronic medical record system was used to gather information on the patient’s demographics, cardiovascular risk factors, comorbidities, medical history, vital signs, laboratory results, echocardiography, coronary angiography findings, invasive procedures, and medications.

Statistical analysis

According to the pressure injury scores, we initially categorized the patients into low-/minimal-, intermediate-, and high-risk groups.[24] Baseline differences between the reduced EF and preserved EF groups were compared among different subgroups. The normality of the continuous variables was examined with the Kolmogorov-Smirnov test. Since the continuous variable in this study was not normally distributed, they were expressed as the median and interquartile range (IQR), and the Wilcoxon rank-sum test was used for comparison. The categorical variables were expressed as counts and percentages, and the Chi-square test was used to assess group differences. The Kaplan-Meier method was used to calculate the cumulative incidence from the index hospitalization for AMI until death, and the log-rank test was used to assess differences between groups with reduced EF and preserved EF. To assess the correlations between LVEF and all-cause death stratified by various pressure injury risks, restricted cubic spline logistic regressions were carried out. Interaction testing was utilized to examine the effects of pressure injury risk on the association between baseline LVEF and all-cause mortality. We used the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After adjusting for age, sex, current smoking status, cerebrovascular disease, diastolic blood pressure, heart rate, serum creatinine, aspirin, clopidogrel, and spironolactone, which were unbalanced among groups with different LVEF, we explored the independent association between LVEF and all-cause death among different pressure injury risk subgroups, as well as the interactions between pressure injury risk and LVEF. All statistical analyses were conducted using IBM SPSS Version 20 and R software. Two-sided P-values of <0.05 were considered statistically significant.

RESULTS

Supplementary Figure 1 shows the inclusion process of the study population. From 2012 to June 2019, there were a total of 999 elderly patients aged 80 years or older. After excluding 162 patients without echocardiographic data, 71 patients without risk assessment of pressure injuries, and 1 patient with data of logical error (the household registration of the patient was cancelled before the time of discharge, and the patient was essentially lost to follow-up), and 88 patients who died in the hospital or were discharged from the hospital after forgoing treatment due to their critical condition, 677 elderly AMI patients who survived hospitalization were enrolled. Supplementary Table 1 illustrates the comparison of baseline characteristics between individuals included and excluded in the research.

Table 1.

Demographics and baseline characteristics of patients survived hospitalization for AMI with 80 years or older

The baseline characteristics of the study population are shown in Table 1. The median age of the patients was 83 years (IQR, 81–85 years). The population’s age distribution and the aging trends of elderly patients with AMI are depicted in supplementary Figures 2 and 3. The age range was primarily between 80 and 86. The age distribution of hospitalized patients remained largely constant between 2012 and 2019. The median Braden score was 14.0 (IQR, 12.0–16.0), and showed a decreasing trend in recent years (supplementary Figure 4). The median LVEF was 52% (IQR, 43% to 61%). According to the risk stratification of pressure injuries, 239 (35.3%) patients were classified as “low or minimal risk”, 256 (37.8%) as “intermediate risk” and 182 (26.9%) as “high risk”. Across the prespecified subgroups of pressure injury risk, patients with reduced EF had a higher heart rate and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level were more likely to be treated with spironolactone. In the low/ minimal-risk group, the reduced EF patients had a higher proportion of male gender and current smokers (P<0.05). In the high risk group, the preserved EF patients had a higher proportion of cerebrovascular disease (P=0.017). Patients in the intermediate- and high-risk pressure injury group with reduced EF had higher diastolic blood pressure (P<0.001). Patients in the low-/ minimal-risk group with the reduced EF had higher serum creatinine levels and troponin T (TnT) levels (P<0.05). The use of aspirin and clopidogrel was lower in the reduced EF patients in the low-/minimal- risk group and intermediate-risk group (P<0.05).

During a median follow-up of 1,176 d (IQR, 722–1,900 d), a total of 226 (33.4%) patients died. Among them, the death rates of patients with low/minimal-risk, intermediate-risk and high-risk pressure injuries were 36.0%, 25.0% and 41.8%, respectively. Kaplan–Meier survival analysis showed that in the low/minimal-risk and intermediate-risk pressure injury subgroups, the risk of death in the reduced EF group was not significantly different from those in the preserved EF group; however, in the high-risk pressure injury subgroup, patients with reduced EF had a 72% higher risk of death than those with preserved EF (Crude HR=1.72, 95% CI: 1.08–2.73; P=0.021) (Figure 1). The results of the interaction test revealed that the risk of pressure injury modified the relationship between EF and all-cause mortality (P<0.001). Multivariate Cox regression analysis suggested no statistically significant association between EF and all-cause death in the low/minimal- and intermediate-risk subgroups of pressure injuries; however, in the subgroup of high-risk pressure injuries, EF reduction was independently associated with an increased risk of all-cause death (adjusted HR=1.81, 95%CI: 1.03–3.20; P=0.040). In line with earlier findings, EF and pressure injury risk interacted to affect all-cause mortality (P=0.003) (Table 2). Intriguingly, restricted cubic spline models revealed that in the low/minimal-risk group for pressure injury, the relationship between LVEF and all-cause death followed a U-shaped curve, whereas in the high-risk group, the risk of all-cause death increased with lower LVEF, and an inverted J-shaped relationship was seen between LVEF and all-cause death in the intermediate-risk group (Figure 2).

Figure 1.

Kaplan–Meier survival curves of patients with different pressure injury risks stratified by reduced or preserved EF. A: low/minimal pressure injury risk; B: intemediate pressure injury risk; C: high pressure injury risk. LVEF: left ventricular ejection fraction; EF: ejection fraction.

Table 2.

Crude and risk-adjusted hazard ratios of long-term all-cause death

Figure 2.

Restricted cubic spline curves of the associations between LVEF and risk of all-cause death. A: low/minimal pressure injury risk; B: intermediate pressure injury risk; C: high pressure injury risk. LVEF: left ventricular ejection fraction; HR: hazard ratio; CI: confidence interval.

DISCUSSION

Although the prevalence of older patients with AMI has been rising annually, only a small percentage of these patients have been included in previous large trials, which has resulted in a dearth of research on the topics of treatment decision-making and improving prognostic classifications.[28,29] It takes more time for elderly people who have AMI to seek urgent or emergency care after the onset of their symptoms.[30,31] Even when patients are admitted to hospitals, older patients receive much less invasive revascularization therapy than younger patients.[32] Frail patients may suffer three separate trends after a critical disease: cancer trajectories, chronic organ/system failure trajectories, and frailty trajectories, and the forecast of this tendency may impact aggressive medical decisions for older patients.[33] For the reasons indicated above, older patients with AMI have a worse clinical prognosis than younger patients.[34,35] The median survival time for elderly patients with MI was 3.5 years for those aged 80–84 years, 2 years for those aged 85–89 years, and 1 year for those aged 90 years, according to Kochar et al’s analysis of CRUSADE and linked Medicare data.[34] Nevertheless, as demonstrated in an observational study from the UK, recent advancements in PCI and surgery techniques, innovations in devices, and the emergence of new drugs have resulted in a stabilization of the long-term mortality rate over the last decade and the absence of a discernible change in older patients (average age was 84.2 years) with AMI and complex clinical conditions.[36] In an emergency, the time from the onset of symptoms to presentation at the emergency department, cardiac functional status, health background, complications, and patient/family expectations must all be carefully taken into account while making treatment plan decisions and prognostic assessment.[37-40]

LVEF is the most classical and recognized indicator of cardiac function, with the best clinical evidence.[41] Reduced LVEF was linked to an increased risk of adverse events in hospitalized MI patients as well as an increased risk of all-cause death, cardiac death, stroke, and readmissions to the hospital for non-cardiovascular reasons during the course of long-term follow-up.[42-44] Due to myocardial injury and stunning, prompt blood flow restoration, and appropriate medication and rehabilitation treatment, both detrimental remodeling and reverse remodeling processes occur in post-MI hearts.[9,45,46] Observational studies have demonstrated that between 40% and 75% of patients with AMI experience an improvement in LVEF during the follow-up period, depending on the population studied and the length of follow-up, and that this improvement in LVEF was associated with a decreased risk of all-cause and cardiac death at up to 11 years of follow-up.[11,16] Patients in their advanced years are more complicated due to underlying chronic medical issues.[47] After suffering from acute illnesses, they are more difficult to recover from and more prone to developing adverse events and death.[48] Several studies have focused on how chronic health status affects the relationship between deteriorated left ventricular systolic performance and long-term prognosis in AMI patients in old age.[49,50]

In routine clinical care, pressure injury assessment is a straightforward, effective procedure for minimizing skin damage, shortening hospital stays, and reducing the likelihood of complications while being hospitalized.[1] The patient’s age, underlying illnesses, nutritional status, cognitive function and other factors all impact the development of pressure injuries.[51] Individuals over 80 years have a 3.9-fold or higher risk of acquiring pressure ulcers while being hospitalized compared to patients under 40 years.[52] In this way, an older patient’s risk of pressure injury may be a good indicator of their overall health.[51] Our investigation demonstrated that the probability of baseline pressure injury affected the relationship between lower LVEF and long-term all-cause mortality in older patients with AMI. In the group of older patients with a high risk of pressure injury, a decreased LVEF measured during hospitalization for AMI was associated with an increased risk of long-term all-cause mortality; however, for patients at risk of low/minimal or intermediate pressure injury, a decreased LVEF measured during hospitalization was not associated with long-term mortality. The reason why the correlation between cardiac systolic function and prognosis varied across different pressure injury risk stratifications was not established. We postulated that this might be caused by the following reasons. Patients at high risk of pressure injury may have a higher likelihood of continuing adverse cardiac remodeling due to the effect of neuromodulation, hormonal regulation, nutritional deficiency, and complications; in contrast, older patients with low/minimal or intermediate risk of pressure injury may have a greater chance of myocardial repair and reverse cardiac remodeling after the acute phase.

Intriguingly, in the low-risk group for pressure injury in this investigation, a non-linear relationship between EF and death risk was explored by restricted cubic spline analysis. Our findings implied that both higher and lower EF levels were related to an elevated risk of death during long-term follow-up for patients at low risk of pressure injury, which was similar to the findings of a sizable heterogeneous clinical cohort study in the U.S. published in 2019.[53] In that study, Wehner et al[53] examined 403,977 echocardiographic results from 203,135 patients who underwent echocardiography for a variety of reasons, and their analysis revealed a “U-shaped” correlation between the risk of all-cause death and LVEF. The ejection fraction has conventionally been used to categorize different forms of heart failure. It is important to note that the guidelines indicate that heart failure is distributed in various LVEF ranges as a normally distributed variable.[54] Gevaert et al[55] discovered via cluster analysis that clinical phenotypic classification of heart failure based on comorbidity could offer more thorough prognostic information than classification based on LVEF. In the present investigation, we found that the slope of the curve between LVEF and mortality was significantly different between the low/minimal-risk and intermediate-risk groups with pressure injuries, and we hypothesized that this was because pressure injury risk itself had an impact on prognosis. The correlation between lower EF and death in the higher- risk subgroup might be lessened since pressure injury risk itself was inversely correlated with overall mortality risk. As a result, the EF decrease had a lower slope in the intermediate-risk and high-risk groups than in the low-risk group regarding its association with death. Even though patients in the low-risk group of pressure injuries might also have better heart regeneration and repair after suffering from MI, because the mortality was significantly different between patients with different EF values, reverse heart remodeling might not be able to weaken this relationship significantly.

We can not decide of whether aggressive revascularization or conservative treatment should be given to elderly patients with AMI on their biological age, which has also been observed in other studies.[56] With well-established emergency systems for acute chest pain, more sophisticated PCI technology, and an increase in the availability of complementary therapies, older patients with AMI and complex baseline illness might obtain clinical outcomes that are generally favorable.[57]

This study has limitations. First, individuals who did not have a risk of pressure injuries evaluated at admission or who did not have an echocardiogram during hospitalization were excluded. Second, the time of echocardiography may vary slightly depending on the study population. For STEMI patients and high-risk NSTEMI patients, echocardiography was often conducted between the time after the patient had received cardiac catheterization and before hospital discharge. However, patients with non-high-risk NSTEMI were more likely to undergo echocardiography before cardiac catheterization. Third, repair and regeneration of myocardial tissue occur after MI, and the stunned cardiac function may recover. However, how cardiac structure and function changed over the course of the follow-up period was not exactly clear in the present study population. Fourth, frailty affects both the prognosis of cardiovascular disease as well as the incidence rate in the elderly.[33] In older people, frailty also increases the risk of pressure injuries.[58] To improve patients’ outcomes following acute cardiovascular events, medical personnel should be better equipped to make more tailored therapeutic decisions that integrate cardiac rehabilitation, nutritional support, exercise, and electronic health management.[59] Unfortunately, because routine screening programs at admission were not employed in our hospital to assess frailty using techniques such as the 5-m gait speed test, and the handgrip strength test, we were unable to provide specialized data for the assessment of frailty. Fifth, the nutritional state of patients may be indirectly and partially reflected in our study by indicators such as body mass index or hemoglobin. However, this study did not collect data on nutritional risk assessment and socio-economical parameters. Sixth, diastolic function and strain were not always measured during echocardiographic examinations at the study location, and echocardiographic assessment of LV diastolic function in patients with atrial fibrillation was challenging in routine testing. Last, we were unable to differentiate between cardiac mortality and non-cardiac death because of the methodological limitations in this investigation.

CONCLUSIONS

In a cohort of patients with AMI who are 80 years of age or older, pressure injury risk influences the relationship between the initial LVEF assessment during hospitalization and all-cause death followin hospital discharge. Pressure injury risk assessment might potentially be of interest in tailoring prediction models concerning the likelihood of mortality in older patients. More research is anticipated on how pressure injury risk assessment can help clinical decision-making.