ABSTRACT
Background
Percutaneous coronary intervention (PCI) is safe and effective in very elderly patients, defined as those who are age ≥85 years, with acute coronary syndrome (ACS). However, the prognostic factors remain unknown. The association between activities of daily living (ADL) and the prognosis after PCI has not yet been investigated.
Hypothesis
Better ADL is associated with better 1‐year prognosis.
Methods
This retrospective study included 91 consecutive very elderly patients with ACS. We calculated the Barthel Index (BI) as an indicator for ADL. Patients were classified into 2 groups according to BI: high BI (≥85) and low BI (<85). The BI was assessed both on admission (pre‐BI) and at discharge (post‐BI).
Results
In the 91 patients (mean age, 88.2 ± 3.0 years, 52% male), 1‐year mortality was 33%. The Cox regression model demonstrated that low pre‐BI was not a risk factor for 1‐year mortality (hazard ratio: 0.73, 95% confidence interval [CI]: 0.30‐1.78, P = 0.490). However, post‐BI was significantly associated with 1‐year mortality (hazard ratio: 0.25, 95% CI: 0.11‐0.57, P = 0.001). The 1‐year mortality of the high and the low post‐BI group was estimated as 21% (95% CI: 12%‐35%) and 62% (95% CI: 42%‐82%), respectively. A 5‐unit decrease in post‐BI was related to a 1.10‐fold increased risk for 1‐year mortality (95% CI: 1.05‐1.15, P < 0.001).
Conclusions
Activities of daily living at discharge, although not before admission, may be a useful predictor for 1‐year mortality in very elderly patients undergoing PCI for ACS.
Introduction
In elderly patients who are affected by comorbidities, primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) seems to be a promising strategy.1 As PCI has become a safer and less invasive procedure, the very elderly population—defined as those age ≥85 years—is increasingly being referred for PCI, particularly in the setting of ACS. Although evidence on ACS in very elderly patients is scarce, a few studies have reported clinical outcomes related to this topic. A retrospective cohort study reported that long‐term survival of patients age ≥90 years who underwent PCI was not inferior to those who were included in a Minnesota cohort matched by age and sex.2 Other studies have also reported that PCI for patients with ACS who were ≥85 years was safe, feasible, and effective.3, 4 However, most patients with advanced age have disabilities such as dementia, cerebral infarction sequelae, and muscle weakness, all of which can influence their prognosis. This study aimed to confirm the hypothesis that better activities of daily living (ADL) is associated with better prognosis in very elderly patients with ACS who underwent PCI.
Methods
Study Design
This study retrospectively included 91 consecutive patients, age ≥85 years, who were admitted to our hospital for ACS and underwent primary PCI between January 2007 and January 2014. We reviewed the medical records of all patients for data on clinical characteristics such as age, sex, vital signs, comorbidity, and factors related to ADL. Findings of electrocardiography and blood examination at the time of admission were also collected.
The study was approved by the institutional ethical review board of Kyorin University School of Medicine and was in accordance with the Declaration of Helsinki.
Activities of Daily Living Score
We calculated the Barthel Index (BI; range, 0–100, lower scores indicate greater disability) as an indicator of ADL. The BI consists of 10 items: feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation, and stair climbing. Each item is rated based on the amount of assistance required to complete each activity.5 Patients were classified into 2 groups according to their BI: to the high‐BI group if the BI was ≥ the cutoff value, and to the low‐BI group if the BI was < the cutoff value. In previous studies, the BI cutoff ranged between 50 and 95.6, 7 We analyzed the association between ADL and in‐hospital or 1‐year mortality using cutoff values of 75, 80, 85, 90, 95, and 100. We evaluated a cutoff value of 85 at first because capability of daily life, except climbing up stairs and walking without assistance, indicates score values ≥85. Next, we evaluated whether other cutoff values are useful for risk stratification. The BI at each cutoff value was expressed as “BI (cutoff value).” The minimum cutoff value was set at 75 because patients who were able to perform ADL except walking and climbing stairs were included in the group with a BI of at least 75. The BI on admission (pre‐BI) and BI at discharge (post‐BI) were assessed. At the time of admission, each item of the BI was recorded based on responses from the patient or a family member. We calculated the pre‐BI retrospectively. Among patients who were alive at discharge, the post‐BI was evaluated by the rehabilitation staff.
Clinical Outcome
We surveyed in‐hospital and 1‐year mortality and assessed the factors that influenced mortality. In‐hospital mortality was analyzed by variables that were acquired on admission, such as vital signs, blood examination, electrocardiographic findings and echocardiographic findings. On the other hand, 1‐year mortality was evaluated using variables acquired at discharge.
Statistical Analysis
Numerical data are presented as mean ± SD if the data followed a normal distribution. Otherwise, data are displayed as median and interquartile range (Q1–Q3) values. Categorical variables are expressed as absolute numbers or percentages. Continuous variables were analyzed using the unpaired Student t test and Mann‐Whitney U test. The Fisher exact test and the χ2 test were used for categorical variables. Kaplan‐Meier statistics were used to estimate the cumulative in‐hospital and 1‐year mortality. The risk of mortality was assessed using Cox regression analysis, which was adjusted for age and sex and expressed as a hazard ratio (HR), 95% confidential interval (CI), and P value. Statistical significance was set at P < 0.05. All statistical analyses were carried out using Stata software, version 10 (StataCorp, College Station, TX).
Results
The Association Between Activities of Daily Living and Mortality
A total of 91 very elderly patients (mean age, 88.2 ± 3.0 years; range, 85–99 years; 52% male) were recruited retrospectively. The median of pre‐BI and post‐BI was 100 (90–100) and 90 (70–100). Clinical characteristics of patients according to pre‐BI (85) and post‐BI (85) are shown in Tables 1 and 2, respectively. The number of patients with low BI increased at discharge despite a decrease in the number of patients. There were no significant differences in age, sex, vital signs, coronary risk factors, prevalence of ST‐segment elevation myocardial infarction (STEMI), and complications between the high and low pre‐BI (85) groups. Length of stay (LOS) was significantly longer in those with low post‐BI than in those with high post‐BI. Acute coronary syndrome included 3 clinical settings: STEMI, 60; non–ST‐segment elevation myocardial infarction, 29; and unstable angina pectoris, 2. There were 22 in‐hospital deaths, indicating 24% in‐hospital mortality. Of these, 18 patients (86%) died of heart disease, which included 15 mechanical complications, such as right ventricular infarction (RVI) and free wall rapture; 7 of the 10 patients (70%) who developed RVI and 8 of the 9 patients (89%) with free wall rapture died during hospitalization. The Kaplan‐Meier survival estimate showed a 33% (95% CI: 23%‐46%) 1‐year mortality rate. In‐hospital mortality and 1‐year mortality were similar between the high and the low pre‐BI (85) groups (22% and 33%, P = 0.270; 36% and 40%, P = 0.270, respectively). The Cox regression model demonstrated that a low pre‐BI (85) was not a risk factor for in‐hospital mortality (HR: 0.59, 95% CI: 0.22‐1.59, P = 0.295) or 1‐year mortality (HR: 0.73, 95% CI: 0.30‐1.78, P = 0.490). The relationship between pre‐BI and mortality persisted at any cutoff value that was evaluated. On the other hand, post‐BI (85) was significantly related to 1‐year mortality (HR: 0.25, 95% CI: 0.11‐0.57, P = 0.001). The mortality of the high and the low post‐BI (85) groups was estimated as 21% (95% CI: 12%‐35%) and 62% (95% CI: 42%‐82%), respectively. As the cutoff was set at 85, better post‐BI was associated with better 1‐year prognosis (Figure 1). The result was similar at the other cutoff values. As the cutoff was set at a value between 75 and 100, the age‐ and sex‐adjusted model indicated that a high post‐BI was associated with lower 1‐year mortality (Table 3). A 5‐unit decrease in the post‐BI (85) correlated with a 1.10‐fold increased risk for 1‐year mortality (95% CI: 1.05‐1.15, P < 0.001).
Table 1.
Comparison of Clinical Characteristics Between the High and Low Pre‐BI Groups
| Total, N = 91 | High BI, n = 76 | Low BI, n = 15 | P Value | |
|---|---|---|---|---|
| Background | ||||
| Age, y | 88.2 ± 3.0 | 88.1 ± 2.9 | 88.7 ± 3.5 | NS |
| Male sex | 47 (52) | 42 (55) | 5 (33) | NS |
| BMI, kg/m2 | 21.1 ± 3.1 | 21.3 ± 3.0 | 20.6 ± 3.1 | NS |
| SBP, mm Hg | 125 ± 33 | 127 ± 33 | 119 ± 33 | NS |
| DBP, mm Hg | 69 ± 21 | 70 ± 22 | 66 ± 21 | NS |
| HR, bpm | 83 ± 31 | 80 ± 27 | 96 ± 45 | NS |
| Coronary risk factors | ||||
| Hypertension | 73 (80) | 61 (80) | 12 (80) | NS |
| Dyslipidemia | 31 (34) | 25 (33) | 6 (40) | NS |
| DM | 25 (27) | 19 (25) | 6 (40) | NS |
| Current smoker | 10 (11) | 10 (13) | 0 (0) | NS |
| CKD stage | 2 (2–3) | 2 (2–3) | 2 (2–4) | NS |
| Examination | ||||
| Hb, g/dL | 11.6 ± 1.7 | 11.7 ± 1.8 | 11.5 ± 1.7 | NS |
| Cr, mg/dL | 0.9 (0.7–1.3) | 0.9 (0.7–1.3) | 0.8 (0.6–1.4) | NS |
| CRP, mg/dL | 0.3 (0.2–1.3) | 0.3 (0.2–1.2) | 0.5 (0.1–5.3) | NS |
| CK, IU/L | 1014 (351–3056) | 969 (359–2853) | 1191 (298–4613) | NS |
| BNP, pg/mL | 350 (143–823) | 350 (143–823) | 380 (100–863) | NS |
| LVEF, % | 46 ± 14 | 46 ± 14 | 46 ± 14 | NS |
| Complications | ||||
| CHF | 60 (66) | 48 (63) | 12 (80) | NS |
| RVI | 10 (11) | 8 (11) | 2 (15) | NS |
| Free wall rupture | 9 (10) | 7 (9) | 2 (15) | NS |
| AKI on admission | 12 (13) | 9 (12) | 3 (23) | NS |
| CI‐AKI | 13 (14) | 12 (15) | 1 (8) | NS |
| Procedure, complete vascularization | 48 (53) | 39 (51) | 9 (60) | NS |
| Medication at discharge | ||||
| ASA | 86 (95) | 72 (95) | 14 (93) | NS |
| Thienopyridine | 85 (93) | 71 (93) | 14 (93) | NS |
| ACEI/ARB | 59 (65) | 50 (66) | 9 (60) | NS |
| β‐Blocker | 54 (59) | 45 (59) | 9 (60) | NS |
| Statin | 45 (49) | 38 (50) | 7 (47) | NS |
Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; ASA, aspirin; BI, Barthel Index; BNP, brain natriuretic peptide; CHF, congestive heart failure; CI‐AKI, contrast‐induced acute kidney injury; CK, creatine kinase; CKD, chronic kidney disease; Cr, creatinine; CRP, C‐reactive protein; DBP, diastolic blood pressure; Hb, hemoglobin; DM, diabetes mellitus; IQR, interquartile range; LVEF, left ventricular ejection fraction; NS, not significant; RVI, right ventricular infarction; SBP, systolic blood pressure.
Data are presented as n (%), mean ± SD, or median (IQR). P < 0.05 is considered statistically significant. Continuous variables were analyzed using the unpaired Student t test and Mann‐Whitney U test. Categorical variables were analyzed using the χ2 test or Fisher exact test. High BI = ≥85; low BI = <85.
Table 2.
Comparison of Clinical Characteristics Between the High and Low Post‐BI Groups
| Total, N = 69 | High BI, n = 48 | Low BI, n = 21 | P Value | |
|---|---|---|---|---|
| Background | ||||
| Age, y | 88.3 ± 3.1 | 87.8 ± 2.7 | 89.5 ± 3.6 | NS |
| Male sex | 36 (52) | 29 (60) | 7 (33) | NS |
| BMI, kg/m2 | 21.3 ± 2.8 | 21.5 ± 2.8 | 20.9 ± 3.0 | NS |
| SBP, mm Hg | 134 ± 26 | 137 ± 21 | 127 ± 33 | NS |
| DBP, mm Hg | 73 ± 17 | 74 ± 16 | 71 ± 21 | NS |
| HR, bpm | 83 ± 30 | 81 ± 24 | 89 ± 42 | NS |
| Administration | ||||
| Length of stay, d | 16 (11–23) | 15 (10–18) | 24 (13–46) | <0.001 |
| BI on admission <85, n (%) | 10 (14) | 0 (0) | 10 (48) | <0.001 |
| BI | 100 (90–100) | 100 (90–100) | 85 (60–100) | <0.001 |
| Coronary risk factors | ||||
| Hypertension | 57 (83) | 38 (79) | 19 (90) | NS |
| Dyslipidemia | 25 (36) | 18 (38) | 7 (33) | NS |
| DM | 19 (28) | 12 (25) | 7 (33) | NS |
| Current smoker | 6 (9) | 5 (10) | 1(5) | NS |
| CKD stage | 3 (2–3) | 3 (2–3) | 3 (2–4) | NS |
| Examination | ||||
| Hb, g/dL | 11.8 ± 1.8 | 11.9 ± 1.9 | 11.6 ± 1.6 | NS |
| Cr, mg/dL | 0.9 (0.7–1.2) | 0.9 (0.7–1.2) | 0.8 (0.7–1.5) | NS |
| CRP, mg/dL | 0.3 (0.1–1.1) | 0.3 (0.2–0.9) | 0.3 (0.1–9.8) | NS |
| CK, IU/L | 794 (315–1817) | 589 (205–1346) | 1191 (687–2031) | 0.040 |
| BNP, pg/mL | 350 (143–832) | 329 (130–789) | 592 (226–912) | NS |
| LVEF, % | 47 ± 13 | 46 ± 13 | 50 ± 15 | NS |
| Complications | ||||
| CHF | 44 (64) | 25 (52) | 19 (90) | 0.002 |
| RVI | 3 (4) | 0 (0) | 3 (14) | 0.030 |
| Free wall rupture | 1 (1) | 0 (0) | 1 (5) | NS |
| AKI on admission | 6 (9) | 1 (2) | 5 (24) | 0.009 |
| CI‐AKI | 5 (7) | 3 (6) | 2 (10) | NS |
| Procedure, complete vascularization | 40 (58) | 30 (63) | 10 (48) | NS |
| Medication at discharge | ||||
| ASA | 65 (94) | 46 (96) | 19 (90) | NS |
| Thienopyridine | 64 (93) | 47 (98) | 17 (81) | 0.027 |
| ACEI/ARB | 56 (81) | 42 (88) | 14 (67) | 0.048 |
| β‐Blocker | 52 (75) | 39 (81) | 13 (62) | NS |
| Statin | 39 (57) | 29 (60) | 10 (48) | NS |
Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; ASA, aspirin; BI, Barthel Index; BNP, brain natrurietic peptide; CHF, congestive heart failure; CI‐AKI, contrast‐induced acute kidney injury; CK, creatine kinase; CKD, chronic kidney disease; Cr, creatinine; CRP, C‐reactive protein; DBP, diastolic blood pressure; Hb, hemoglobin; DM, diabetes mellitus; IQR, interquartile range; LVEF, left ventricular ejection fraction; NS, not significant; RVI, right ventricular infarction; SBP, systolic blood pressure.
Data are presented as n (%), mean ± SD, or median (IQR). P < 0.05 is considered statistically significant. Continuous variables were analyzed using the unpaired Student t test and Mann‐Whitney U test. Categorical variables were analyzed using the χ2 test or Fisher exact test. High BI = ≥85; low BI = <85.
Figure 1.
Unadjusted 1‐year mortality according to BI at discharge. The association between 1‐year mortality and ADL according to BI was assessed. Cutoff value was set at 85. Kaplan‐Meier estimate disclosed that better ADL was associated with lower mortality. Abbreviations: ADL, activities of daily living; BI, Barthel Index.
Table 3.
Analysis of 1‐Year Mortality According to Various BI Cutoff Values
| Cutoff Value | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| HR (95% CI) | P Value | HR (95% CI) | P Value | ||
| 75 | <75 | 1.00 | 1.00 | ||
| ≥75 | 0.22 (0.09‐0.49) | <0.001 | 0.16 (0.07‐0.40) | <0.001 | |
| 80 | <80 | 1.00 | 1.00 | ||
| ≥80 | 0.20 (0.09‐0.47) | <0.001 | 0.14 (0.05‐0.35) | <0.001 | |
| 85 | <85 | 1.00 | 1.00 | ||
| ≥85 | 0.25 (0.11‐0.57) | 0.001 | 0.19 (0.08‐0.46) | <0.001 | |
| 90 | <90 | 1.00 | 1.00 | ||
| ≥90 | 0.30 (0.13‐0.71) | 0.006 | 0.26 (0.11‐0.62) | 0.003 | |
| 95 | <95 | 1.00 | 1.00 | ||
| ≥95 | 0.25 (0.09‐0.68) | 0.007 | 0.24 (0.09‐0.66) | 0.006 | |
| 100 | <100 | 1.00 | 1.00 | ||
| 100 | 0.27 (0.10‐0.73) | 0.010 | 0.26 (0.09‐0.70) | 0.008 | |
Abbreviations: BI, Barthel Index; CI, confidence interval; HR, hazard ratio.
The multivariate model was adjusted for age and sex.
Change of ADL and the Contribution
Of 59 patients with high pre‐BI, 11 patients changed to be in low post‐BI. On the other hand, no patients in low pre‐BI recovered to be in high post‐BI. Congestive heart failure and acute kidney injury were significantly related to the change of pre‐ and post‐BI (P = 0.020 and P = 0.003, respectively). Among them, LOS was longer in those with change of BI than those without (15 [10–18] days, 41 [21–72] days, respectively; P < 0.001).
Other Predictors of In‐hospital Mortality
Among the variables we examined, cardiac complications such as RVI, free wall rapture, and ventricular tachycardia/fibrillation were significant predictors of in‐hospital mortality (RVI, HR: 4.82, 95% CI: 1.95‐11.93, P = 0.001; free wall rapture, HR: 7.85, 95% CI: 3.21‐19.22, P < 0.001; ventricular tachycardia/fibrillation, HR: 6.20, 95% CI: 2.57‐14.97, P < 0.001). A 1‐unit increase in the Killip classification was associated with 1.84‐fold increased risk for 1‐year mortality (95% CI: 1.30‐2.60, P = 0.001).
Other Predictors of 1‐Year Mortality
Age, sex, vital signs, and ejection fraction were not significantly associated with 1‐year mortality.
Discussion
Prognostic Impact of the Barthel Index at Discharge
Our study is the first report to reveal an association between the BI and 1‐year mortality in very elderly patients presenting with ACS. The present study indicates that better ADL at discharge is associated with lower 1‐year mortality. The BI, one of the most widely used scales, has been shown to be valid and reliable for assessing disability in stroke patients.5, 8 We adapted this useful index in the field of cerebrovascular disease to evaluate the prognosis of very elderly patients with ACS. The relationship between better exercise capacity and better prognosis is well known9, 10; however, it has been unclear whether mortality in very elderly patients with ACS is influenced by ADL. This study revealed the clinical impact of ADL on mortality in patients age ≥85 years, followed by treatment with PCI for ACS. We evaluated each cutoff value of BI between 75 and 100 in age‐ and sex‐adjusted models and found that low post‐BI is a poor prognostic factor at any cutoff value. In addition, further adjustment for AKI or CHF did not change the risk estimate (data are not shown), suggesting the association between post‐BI and 1‐year mortality might not be affected by such risk factors for mortality. Low post‐BI was related to longer LOS. Indeed, delayed recovery from acute illness would shift those with high pre‐BI to those with low post‐BI. The results imply that patients who were not bedridden after recovering from ACS had promising outcomes. Bedridden patients usually present with impaired function of various organs. Not only cardiopulmonary insufficiency, but also impaired function of swallowing and intestinal function can adversely affect prognosis in the elderly.11, 12 Furthermore, patients with disuse syndrome easily develop decubitus ulcer and infections, such as pneumonia and urinary tract infection. Those morbidities occasionally indicate grave implications on the prognosis. Younger patients and even elderly patients age ≥65 years can recover from disability by undergoing vigorous rehabilitation.13 It must be difficult for the very elderly to overcome disability and improve their ADL once they develop disuse syndrome. Thus, maintenance of good ADL is important, particularly for very elderly patients. As shown in Tables 1 and 2, the number of patients with low post‐BI increased at discharge. Patients in the low post‐BI group had a higher prevalence of complications. Even if these patients recovered from such complications, the adverse cardiac events may have left them bedridden for a long time, and thus lowered their ADL. Therefore, it may be effective that very elderly patients undergo cardiac rehabilitation to avoid low ADL as soon as possible.
Prognostic Impact of the Barthel Index on Admission and Critical Cardiac Complication
The pre‐BI just before ACS did not influence in‐hospital mortality; rather, cardiac complications such as RVI and free wall rapture had an influence. It stands to reason that complications that can lead to severe hemodynamic instability are strongly associated with mortality. Even in the younger population, critical complications such as RVI and free wall rapture worsen prognosis.14, 15 Mortality due to RVI seemed to be higher in very elderly patients than in younger patients.16, 17 Once the very elderly patients develop hemodynamic instability, they may not easily recover from this critical condition, compared with younger patients. Another reason for the lower influence of pre‐BI on mortality could be that, as this study comprised many patients with good pre‐BI (median, 90 [90–100]), the number of patients with low BI may be insufficient to indicate the clinical impact of pre‐BI. An evaluation of frailty may contribute the stratification of in‐hospital mortality. To evaluate frailty of the elderly, some scores are proposed.18, 19 The system reported by Fried et al contains unintentional weight loss, self‐reported exhaustion, weakness, slow walking speed, and low physical activity.18 The system that evaluates frailty includes not only ADL but physical and mental state. An observational multicenter registry to assess the clinical impact of frailty in the elderly patients with STEMI has been planned.20 A result of the study may bring any findings in the geriatrics field.
Incidence and Prognostic Impact of Heart Failure
The incidence of CHF complicating acute MI declined to approximately 30% in the last decade.21, 22 The recent study disclosed that the in‐hospital and 1‐year mortality for those with CHF and acute MI was 13% and 31%, respectively.21, 22 The incidence of CHF in our study was >60%, which was much higher than that reported in previous studies.21, 22 One of the causes of the higher in‐hospital mortality may be the higher incidence of CHF in our study.
Study Limitations
Our study potentially had a selection bias, because patients with poor ADL were less likely to undergo invasive treatment such as PCI. Among these patients, physicians may carefully select patients who can survive, and then undertake PCI in such patients. Therefore, the mortality of patients with poor ADL may be underestimated, which could bring the observed association between ADL and prognosis toward the null. The small sample size with the unmatched and nonrandomized design in the present study was another limitation, which may not be adequate to detect factors indicating poor prognosis other than ADL and cardiac complications. Furthermore, there could be possible confounding factors of the association between post‐BI and mortality that we were not able to take into account appropriately because the number of participants was too small to perform multivariate analyses. Well‐designed prospective studies with a sufficient number of very elderly patients may be required to confirm our findings.
Conclusion
Activities of daily living at discharge, although not before admission, may be a useful predictor for 1‐year mortality in very elderly patients undergoing PCI for ACS.
The authors have no funding, financial relationships, or conflicts of interest to disclose.
References
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