Journal of Geriatric Cardiology (2019) 16: 121128 ©2019 JGC All rights reserved; www.jgc301.com Research Article  Open Access  Clinical and prognostic implications of delirium in elderly patients with non–ST-segment elevation acute coronary syndromes Miquel Vives-Borrás1, Manuel Martínez-Sellés2, Albert Ariza-Solé3, María T. Vidán4, Francesc Formiga3, Héctor Bueno5, Juan Sanchís6, Oriol Alegre3, Albert Durán-Cambra1, Ramón López-Palop7, Emad Abu-Assi8, Alessandro Sionis1, LONGEVO-SCA Investigators 1 Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research IIB Sant Pau, CIBERCV, Universitat Autònoma de Barce- lona, Barcelona, Spain 2 Department of Cardiology, Hospital General Universitario Gregorio Marañón, CIBERCV, Universidad Complutense, Universidad Europea, Madrid, Spain 3 Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain 4 Hospital General Universitario Gregorio Marañón, IiSGM, CIBERFES, Universidad Complutense, Madrid, Spain 5 Hospital Doce de Octubre, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain 6 Hospital Clínico de Valencia, INCLIVA, Universidad de Valencia, CIBERCV, Spain 7 Hospital Universitario San Juan, Alicante, Spain 8 Hospital Álvaro Cunqueiro, Vigo, Spain Abstract Background Elderly patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) may present delirium but its clinical relevance is unknown. This study aimed at determining the clinical associated factors, and prognostic implications of delirium in old-aged patients admitted for NSTE-ACS. Methods LONGEVO-SCA is a prospective multicenter registry including unselected patients with NSTE-ACS aged  80 years. Clinical variables and a complete geriatric evaluation were assessed during hospitalization. The associa- tion between delirium and 6-month mortality was assessed by a Cox regression model weighted for a propensity score including the potential confounding variables. We also analysed its association with 6-month bleeding and cognitive or functional decline. Results Among 527 patients included, thirty-seven (7%) patients presented delirium during the hospitalization. Delirium was more frequent in patients with dementia or depression and in those from nursing homes (27.0% vs. 3.1%, 24.3% vs. 11.6%, and 11.1% vs. 2.2%, respectively; all P < 0.05). Delirium was significantly associated with in-hospital infections (27.0% vs. 5.3%, P < 0.001) and usage of diuretics (70.3% vs. 49.8%, P = 0.02). Patients with delirium had longer hospitalizations [median 8.5 (5.514) vs. 6.0 (4.010) days, P = 0.02] and higher incidence of 6-month bleeding and mortality (32.3% vs. 10.0% and 24.3% vs. 10.8%, respectively; both P < 0.05) but similar cognitive or functional decline. Delirium was independently associated with 6-month mortality (HR = 1.47, 95% CI: 1.022.13, P = 0.04) and 6-month bleeding events (OR = 2.87; 95% CI: 1.984.16, P < 0.01). Conclusions In-hospital delirium in elderly patients with NSTE-ACS is associated with some preventable risk factors and it is an independent predictor of 6-month mortality. J Geriatr Cardiol 2019; 16: 121128. doi:10.11909/j.issn.1671-5411.2019.02.008 Keywords: Acute coronary syndromes; Delirium; Prognosis; The elderly 1 Introduction foreseen in the coming years.[3] These patients frequently associate comorbidities such as dementia and frailty,[4] and Elderly patients represent roughly one-third of all admis- they are known to have higher mortality,[1] and to receive sions for non-ST-segment elevation acute coronary syn- less evidence-based treatments.[5] Therefore, identifying drome (NSTE-ACS),[1,2] and an increase in this proportion is clinical predictors of worse outcomes in this specific popu- lation is mandatory. Correspondence to: Miquel Vives-Borrás, MD, Department of Cardiology, Delirium is an acute disturbance of attention and cogni- Hospital de la Santa Creu i Sant Pau, Sant Quintí, Barcelona, Spain. E-mail: tive functioning that frequently complicates hospitalization mvives@santpau.cat of old-aged patients.[6] Although this condition and its sig- Telephone: +34-93556-5940 Fax: +34-93556-5603 Received: January 16, 2019 Revised: January 31, 2019 nificance has been extensively studied in critical, medical, Accepted: February 10, 2019 Published online: February 28, 2019 and even surgical care populations,[7–9] little is known about http://www.jgc301.com; jgc@jgc301.com | Journal of Geriatric Cardiology 122 Vives-Borrás M, et al. Delirium in elderly ACS patients its frequency in elderly patients admitted for NSTE-ACS graphic and previous clinical history including comorbid- and its impact on their clinical evolution. Given that risk- ities; (2) case history and physical examination; (3) ECG, stratification tools for acute coronary syndrome (ACS) do laboratory blood test and echocardiography at admission; (4) not consider specific geriatric factors,[10,11] analysis of these coronary angiography and coronary angioplasty when per- conditions, such as delirium, may be of potential utility in formed; and (5) medical treatment and clinical evolution. clinical practice. Standard criteria were used to define each variable. Delir- This study aimed to describe the clinical associated fac- ium was defined as an acute and transient disorder of atten- tors and the prognostic implications of delirium in a large tion, and cognition and its diagnosis was made by the pa- multicenter cohort of unselected elderly patients; aged ≥ tient’s medical team following the current recommendations 80 years, admitted for NSTE-ACS. and methods.[13,14] Bleeding events were defined as signifi- cant hemorrhages requiring surgery, hospitalization or anti- thrombotic therapy withdrawal. A baseline geriatric assess- 2 Methods ment was made during admission in all patients through 2.1 Study population interview with the patient, family or caregivers and referring to the patient’s status prior to admission. The complete The study population consists of 527 patients from the in-hospital geriatric evaluation included the Barthel index LONGEVO-SCA registry. The detailed study design and vari- (functional capacity), the Lawton-Brody Index (instrumen- ables have been published previously.[12] Briefly, LON- tal activities), the Pfeiffer test (cognitive status), the FRAIL GEVO-SCA is a Spanish multicenter, prospective, observa- scale (frailty), the Short Physical Performance Battery tional study conducted between March 2016 and September (SSPB) (frailty), the Charlson Comorbidity Index and the 2016. We enrolled consecutive elderly patients admitted for Nutritional Assessment–Short Form.[15–21] NSTE-ACS in 44 tertiary and secondary hospitals. The in- clusion criteria were: (1) age ≥ 80 years; (2) chest pain con- 2.3 Follow-up sistent with ACS; and (3) changes on ECG (negative T- Follow-up data was obtained by telephone contact at wave or ST-segment decline) and/or elevation of myocardial 6-month, and from the event reports by electronic records of damage biomarkers. The exclusion criteria were: (1) patient each hospital. The occurrence of death, major bleeding or refusal to participate in the registry; and (2) impossibility of the need of new coronary interventions was registered. Ad- obtaining the geriatric tests. Patients with severe comorbid- ditionally, a new geriatric evaluation was also determined ities were only excluded if symptoms of myocardial ische- by assessing the Barthel and Lawton indexes and the Pfeif- mia were clearly triggered only by other conditions, such as fer test. Cognitive decline was defined as a loss of at least acute anemia, severe decompensated respiratory insuffi- one point in the 6-month Pfeifer test. Functional decline was ciency, active infectious diseases or severe coexisting val- defined as a loss of at least ten points in the 6-month Barthel vular disease (type 2 myocardial infarction). The inclusion score or two points in the 6-month Lawton-Brody test.[22] in the study did not imply any change in patients’ clinical management; therefore, the medical treatment, the comple- 2.4 Statistical analyses mentary examinations including the need for coronary an- Categorical variables were described by frequencies and giography or the choice of stents were decided by the percentages, and statistical differences were analyzed using medical team. Informed consent was obtained from the pa- the χ2 test or Fisher exact test when any expected cell fre- tients or their next of kin. The study was approved by the quency was < 5. The continuous variables were described ethics committees of each center and the investigation con- either by the mean and standard deviation, or by the median forms to the principles outlined in the Declaration of Hel- and interquartile range. The statistical differences among the sinki. The project was supported and coordinated by the continuous variables were analyzed using student’s t test in Section of Geriatric Cardiology, Spanish Society of Cardi- case of a normal distribution, or the Wilcoxon rank-sum test ology. in case of a non-normal distribution. Kaplan-Meier estima- tors of survival were built comparing patients who suffered 2.2 Study variables delirium and those who did not. Finally, to evaluate the in- Data were collected using specifically designed web dependent effect of delirium on 6-month mortality, a Cox forms (http://www.adknoma.com/LONGEVO-SCA), and regression model was implemented adjusting for propensity quality controls were undertaken every month. We recorded score weights (inverse probability of assignment weighting) the following clinical variables at study inclusion: (1) demo- including the potential confounding variables.[23] For ana- Journal of Geriatric Cardiology | jgc@jgc301.com; http://www.jgc301.com Vives-Borrás M, et al. Delirium in elderly ACS patients 123 lyzing the association between delirium and the secondary performed. Patients who presented delirium were more fre- end-point (6-month bleeding events), we used a logistic quently referred from nursing homes. At admission, they regression adjusted by the previously described method. had a higher Killip class, higher CRUSADE score punc- Multiple imputation using chained equations method was tuation; and presented more frequently elevated troponin applied when necessary (n = 5) applying the “mice” pack- levels. With respect to in-hospital complications, patients age in the R Project for Statistical Computing.[24] A P value who developed delirium presented a higher incidence of < 0.05 was considered significant. All analyses were per- atrial fibrillation, infections requiring antibiotic treatment; formed using STATA v.13 (StataCorp. 2013. Stata Statisti- and they were more often treated with invasive mechanical cal Software: Release 13. College Station, TX: StataCorp ventilation, diuretic therapy, amiodarone, and benzodiaze- LP) and R software (R Foundation for Statistical Computing, pines. On the other hand, both groups had similar rate of version 3.3.2). invasive treatment and coronary revascularization therapy during the admission. 3 Results 3.2 Geriatric evaluation 3.1 Clinical characteristics Table 3 summarizes the baseline and 6-month geriatric From 527 patients, 37 (7%) presented delirium during evaluation data. Patients who developed delirium were more hospitalization. Table 1 summarizes the baseline clinical comorbid, they had worse functional and instrumental ca- characteristics of the study population. Patients who deve- pacities, and they also presented a poorer cognitive function loped delirium had more frequently a previous diagnosis of and cognitive status. Remarkably, the prevalence of frailty dementia or depression. We did not find statistically signi- (FRAIL score ≥ 3) in the entire cohort was 27%, and re- ficant differences in any other main clinical characteristics sulted higher in patients with delirium (44% vs. 26%, P = between the two groups. Of note, there was a tendency 0.04). towards a higher frequency of previous diagnosis of cere- brovascular disease and heart failure in those who presented 3.3 Outcome delirium. As shown in Figure 1, patients who developed delirium Table 2 shows the main features regarding the index had higher non-adjusted overall 6-month mortality (24.3% hospitalization, the ACS characteristics and the procedures vs. 10.8%, P = 0.01). Table 4 describes in-hospital and Table 1. Characteristics of the study population. All patients (n = 527) Delirium (n = 37) No delirium (n = 490) P-value Age, yrs 84.1 (82.187.1) 84.7 (82.187.7) 84.0 (82.187.0) 0.58 Female 205 (39.8%) 19 (51.4%) 186 (38.0%) 0.11 CV risk factors Smoker 194 (36.8%) 16 (43.2%) 178 (36.3%) 0.40 Hypertension 454 (86.2%) 33 (89.2%) 421 (85.9%) 0.58 Dyslipidemia 337 (64.0%) 21 (56.8%) 316 (64.5%) 0.35 Diabetes mellitus 210 (39.9%) 18 (48.7%) 192 (39.2%) 0.26 Medical history Peripheral arterial disease 71 (13.5%) 5 (13.5%) 66 (13.5%) 1.00 Cerebrovascular disease 80 (15.2%) 9 (24.3%) 71 (14.5%) 0.11 Chronic kidney disease 168 (31.9%) 14 (37.8%) 154 (31.4%) 0.42 Myocardial infarction 184 (34.9%) 12 (32.4%) 172 (35.1%) 0.74 Previous PCI 152 (28.8%) 12 (32.4%) 140 (28.6%) 0.62 Heart failure 92 (17.5%) 10 (27.0%) 82 (16.7%) 0.12 Atrial fibrillation 102 (19.4%) 5 (13.5%) 97 (19.8%) 0.35 Malignancy 89 (16.9%) 4 (10.8%) 85 (17.4%) 0.31 Dementia 25 (4.7%) 10 (27.0%) 15 (3.1%) < 0.01 Depression 66 (12.5%) 9 (24.3%) 57 (11.6%) 0.04 Data are presented as n (%) or median (interquartile range). CV: cardiovascular; PCI: percutaneous coronary intervention. http://www.jgc301.com; jgc@mail.sciencep.com | Journal of Geriatric Cardiology 124 Vives-Borrás M, et al. Delirium in elderly ACS patients Table 2. Acute coronary syndrome characteristics, care and procedures. All patients (n = 527) Delirium (n = 37) No delirium (n = 490) P-value Admission source Home 511 (97.2%) 32 (88.9%) 479 (97.8%) 0.02 Institutionalized 15 (2.9%) 4 (11.1%) 11 (2.2%) Admission unit CCU/ICU 154 (29.2%) 14 (37.8%) 140 (28.6%) Cardiology ward 315 (59.8%) 19 (51.3%) 296 (60.4%) 0.42 Internal medicine/Geriatrics 58 (11.0%) 4 (10.8%) 54 (11.0%) ACS and hospitalization characteristics Killip class > I 149 (28.7%) 15 (42.9%) 134 (27.7%) 0.06 GRACE score 165 ± 28 172 ± 32 165 ± 28 0.16 CRUSADE score 41 ± 13 47 ± 12 41 ± 13 0.02 Positive troponin 446 (84.6%) 36 (97.3%) 410 (83.7%) 0.03 3-vessel disease 107 (27.4%) 11 (40.7%) 96 (26.4%) 0.11 LVEF 55 (4561) 55 (4060) 55 (4562) 0.42 In-hospital AF episode 52 (9.9%) 8 (21.6%) 44 (9.0%) 0.02 Infection 36 (6.8%) 10 (27.0%) 26 (5.3%) < 0.01 Blood test parameters Hemoglobin, g/dL 12.8 (11.514.0) 12.5 (11.213.6) 12.8 (11.514.0) 0.32 Creatinine peak, mg/dL 1.1 (0.91.4) 1.0 (0.91.4) 1.1 (0.91.4) 0.94 Glucose peak, mg/dL 143 (113200) 168 (132218) 140 (112199) 0.05 Procedures Coronary angiography 398 (75.5%) 27 (73.0%) 371 (75.7%) 0.71 Coronary revascularization 290 (72.7%) 20 (74.1%) 270 (72.6%) 0.87 Orotracheal intubation 9 (1.7%) 3 (8.1%) 6 (1.2%) 0.02 IABP 6 (1.1%) 1 (2.7%) 5 (1.0%) 0.35 In-hospital medical therapy Aspirin 503 (95.5%) 36 (97.3%) 467 (95.3%) 1.00 ADP-receptor blocker 483 (91.7%) 34 (91.9%) 449 (91.6%) 1.00 LMWH 420 (79.7%) 33 (89.2%) 387 (79.0%) 0.14 Unfractionated heparin 80 (15.8%) 8 (21.6%) 72 (14.7%) 0.26 ACEI/ARB 395 (75.0%) 25 (67.6%) 370 (75.5%) 0.28 Beta-blocker 415 (78.8%) 31 (83.8%) 384 (78.4%) 0.44 Statins 481 (91.3%) 34 (91.9%) 447 (91.2%) 0.89 Diuretic 270 (51.2%) 26 (70.3%) 244 (49.8%) 0.02 Amiodarone 28 (5.3%) 7 (18.9%) 21 (4.3%) < 0.01 Neuroleptic 78 (14.8%) 32 (86.5%) 46 (9.4%) < 0.01 Benzodiazepines 261 (49.5%) 23 (62.2%) 238 (48.6%) 0.11 Data are presented as means ± SD or n (%) or median (interquartile range). ACEI: angiotensin-converting-enzyme inhibitor; ACS: acute coronary syndrome; ADP: adenosine diphosphate; AF: atrial fibrillation; ARB: angiotensin II receptor blocker; CCU: coronary care unit; IABP: intra-aortic balloon pump; ICU: intensive care unit; LMWH: low-molecular-weight heparin; LVEF: left ventricular ejection fraction. 6-month outcomes. Patients with delirium had more fre- vious heart failure, depression, institutionalization, positive quent in-hospital and 6-month bleeding events and longer troponin, 3-vessel coronary artery disease, revascularization hospitalization. Our data did not reveal significant differ- during admission, CRUSADE score, Killip class, atrial fib- ences in the proportion of patients presenting 6-month func- rillation episodes, need for mechanical ventilation, infection tional decline or 6-month cognitive decline. After a Cox during hospitalization, diuretic treatment requirement, treat- regression analysis with propensity score weighting includ- ment with amiodarone, treatment with benzodiazepines and ing the following well balanced confounding factors: pre- frailty; delirium persisted as an independent risk factor Journal of Geriatric Cardiology | jgc@jgc301.com; http://www.jgc301.com Vives-Borrás M, et al. Delirium in elderly ACS patients 125 Table 3. In-hospital and 6-month geriatric evaluation. All patients (n = 527) Delirium (n = 37) No delirium (n = 490) P-value In-hospital geriatric evaluation Charlson (comorbidity) 2 (13) 3 (24) 2 (13) 0.01 Barthel (daily activities) 100 (85100) 90 (58100) 100 (90100) < 0.01 Lawton-Brody (instrumental) 6 (48) 4 (26) 6 (48) < 0.01 Pfeifer (cognitive function) 1 (03) 4 (27) 1 (03) < 0.01 MNA-FS (nutritional) 11 (1013) 10 (911) 11 (1013) < 0.01 SPPB test (Frailty) 6 (29) 2 (15) 6 (39) < 0.01 Frailty (FRAIL) No frailty (FRAIL = 0) 178 (34.2%) 8 (22.2%) 170 (35.1%) Pre-frailty (FRAIL 12) 202 (38.9%) 12 (33.3%) 190 (39.3%) 0.04 Frailty (FRAIL ≥ 3) 140 (26.9%) 16 (44.4%) 124 (25.6%) Frailty (SPPB < 10) 372 (81.8%) 28 (96.6%) 344 (80.8%) 0.03 6-month geriatric evaluation Barthel 95 (80100) 90 (5095) 95 (80100) < 0.01 Lawton-Brody 5 (37) 2.5 (04) 5 (37) < 0.01 Pfeifer (cognitive function) 1 (03) 5 (29) 1 (02) < 0.01 Data are presented as n (%) or median (interquartile range). MNA-FS: Mini Nutritional Assessment-Short Form; SPPB: short physical performance battery. associated with 6-month mortality (HR = 1.47; 95% CI: 1.022.13, P = 0.04). Finally, a logistic regression analysis adjusted by the previously mentioned method showed that delirium was also independently associated with 6-month- bleeding events (OR = 2.87; 95% CI: 1.984.16, P < 0.01). 4 Discussion 4.1 Main findings Our large multicenter prospective cohort provides reli- able data about the frequency, clinical characteristics and prognostic implications of delirium in patients aged 80 or older admitted for NSTE-ACS. Our results show that up to Figure 1. Kaplan-Meier estimators of survival comparing 7% of octogenarians with NSTE-ACS develop delirium and patients who presented delirium or not. Kaplan-Meier survival that its appearance is a robust independent predictor of curves of mortality data comparing those patients who developed 6-month mortality. Additionally, delirium identified patients delirium or not during the admission with a follow-up duration of 6 with higher risk of bleeding events and longer hospitali- months (total n = 527), P-value is a log-rank test. zation. Table 4. In-hospital and 6-month outcome. Univariate analysis All patients (n = 527) Delirium (n = 37) No delirium (n = 490) P-value In-hospital mortality 12 (2.3%) 2 (5.4%) 10 (2.0%) 0.20 6-month mortality 62 (11.8%) 9 (24.3%) 53 (10.8%) 0.01 In-hospital bleeding 41 (7.8%) 8 (21.6%) 33 (6.7%) < 0.01 6-month bleeding 56 (11.5%) 10 (32.3%) 46 (10.0%) < 0.01 Length of stay, d 6 (410) 8.5 (5.514) 6 (410) 0.02 Cognitive decline* 122 (29.2%) 8 (36.4%) 114 (28.8%) 0.45 Functional decline# 148 (33.3%) 13 (48.2%) 135 (32.4%) 0.09 Data are presented as n (%) or median (interquartile range). *Gain of at least 1 point in the 6-month Pfeifer test; #Loss of at least 5 points in the 6-month Barthel score. http://www.jgc301.com; jgc@mail.sciencep.com | Journal of Geriatric Cardiology 126 Vives-Borrás M, et al. Delirium in elderly ACS patients 4.2 Delirium incidence retrospective cohort study. In accordance with the above, The incidence of delirium in hospitalized patients de- Noriega, et al.[28] found that delirium was associated with pends on the setting of the study population. The highest higher adjusted 12-month mortality in old patients admitted rates have been described in postoperative populations for acute cardiac conditions; however, only a third of them (46%),[25] and in intensive-care unit ventilated patients were admitted due to ACS and all patients were included in (82%).[7] More specifically, an incidence of 20% has been the cardiology department of a single university hospital. reported in patients admitted to cardiac intensive care Finally, in critical cardiac care settings, Pauley, et al.[26] and units,[26,27] and 17% in elderly patients admitted due to acute Sato, et al.[27] reported that delirium was independently as- cardiac conditions.[28] In our study, the lower observed rate sociated with in-hospital and 60-day mortality, respectively. could be explained by the fact that the majority of our pa- To our knowledge, this is the first study addressing the short tients were admitted to the regular ward and they were and long-term prognostic implications of delirium in elderly overall in better clinical condition. For example, only 25% patients admitted for NSTE-ACS in a large multicenter and presented heart failure. Moreover, our study is based in a non-selected population. We found that delirium is a robust very recent cohort and it could be influenced by the growing independent predictor of 6-month mortality and thus, this interest and interventions designed for the prevention of information could be useful for risk stratification in this specific geriatric complications.[29] growing and complex population. Moreover, delirium also seems to be associated with a higher risk of bleeding and 4.3 Predisposing and precipitant factors for delirium longer hospitalization. The appearance of delirium depends on the coexistence Validated risk scores are useful tools to predict outcomes of several predisposing characteristics and the presence of in ACS,[10,11] and their use has been generalized in the last distinct insults that play the role of precipitating factors.[30] decade.[40] However, elderly NSTE-ACS patients have spe- We identified depression, dementia or institutionalization as cific geriatric syndromes; such as frailty or delirium that baseline characteristics that may help to recognize those may influence the prognosis,[41] and they are not considered patients more prone to present delirium. In addition, the in risk-stratification tools. In a recent cohort study in old geriatric tests show that the comorbidity, frailty and the patients admitted for ACS, frailty and comorbidity were diminution of the functional or cognitive capacities are var- identified as mortality predictors, and they were found to iables closely related to its appearance. All these findings significantly reclassify risk beyond age.[42] Nonetheless, the are consistent with the previously published evidence,[31–34] specific impact of delirium was not studied and its potential and it could potentially be used to screen and identify those predictive utility has not been tested. Based on our data, the elderly patients admitted with NSTE-ACS, these patients appearance of delirium is related to a poorer prognosis and need more a proactive implementation of preventive strate- it should be useful when estimating the risk of death in these gies for delirium. Regarding the latter, our study shows patients. Besides, since it is a potentially preventable and some potentially preventable precipitants, such as infections treatable cause, further research in this field would be of or the use of diuretics. For instance, early removal of uri- special interest. nary or venous catheters, and minimizing the duration of Finally, our findings show a high proportion of patients mechanical ventilation could be useful to prevent delir- presenting 6-month cognitive and functional decline, but it ium.[30] Additionally, excessive depletion of these patients did not result to be significantly associated with delirium. leading to uremia or dyselectrolytemia are known to be re- Delirium has a transient nature,[13] and these patients have a lated with delirium, and it should be reconsidered daily.[9] correct recovery after the index hospitalization. Therefore, Finally, non-pharmacological multicomponent approaches the cognitive or functional decline observed may be associ- for prevention of delirium are effective strategies likely ap- ated to other important factors, such as age or previous cog- plicable to this specific population.[35,36] nitive impairment.[43] 4.4 Delirium and outcomes 4.5 Study limitations Delirium has been related to higher mortality in different Our study has some limitations. This is a post-hoc analy- medical and surgical populations,[37,38] and it has also been sis, and it could be influenced by the usual biases of these evaluated in patients with acute cardiac conditions. Uthama- types of studies. Additionally, given the descriptive nature lingam, et al.[39] observed that delirium was independently of the study, there might be residual confusion affecting the associated with higher in-hospital and 90-day mortality in association between delirium and mortality despite the ad- patients admitted with acute heart failure in a single center justment by the propensity score. Moreover, some signifi- Journal of Geriatric Cardiology | jgc@jgc301.com; http://www.jgc301.com Vives-Borrás M, et al. Delirium in elderly ACS patients 127 cant clinical variables as the presence of other geriatric syn- older medical patients with delirium. J Am Geriatr Soc 1992; dromes, such as immobility or urinary incontinence, and 40: 601–606. data about the use of physical restraints or central vein or 9 Sanders RD, Pandharipande PP, Davidson AJ, et al. Antici- urinary catheters are lacking. Finally, delirium was not pating and managing postoperative delirium and cognitive de- cline in adults. BMJ 2011; 343: d4331–d4331. screened daily; thus, it possibly lead to underdetection of 10 De Araújo Gonçalves P, Ferreira J, Aguiar C, et al. TIMI, hypoactive delirium. PURSUIT, and GRACE risk scores: sustained prognostic In conclusion, our study provides the first description re- value and interaction with revascularization in NSTE-ACS. garding the unfavorable effect of delirium on the prognosis Eur Heart J 2005; 26: 865–872. of elderly patients with NSTE-ACS. Our data, based on a 11 Subherwal S, Bach RG, Chen AY, et al. Baseline risk of ma- broad and systematic geriatric assessment both on admis- jor bleeding in non-sT-segment- elevation myocardial infarc- sion and 6 months after discharge, are of clinical interest tion the CRUSADE (Can Rapid risk stratification of Unstable and it may potentially pave the way to the addition of spe- angina patients Suppress ADverse outcomes with Early im- cific geriatric syndromes to currently existing risk scores in plementation of the ACC/AHA Guidelines) bleeding score. this population. Circulation 2009; 119: 1873–1882. 12 Alegre O, Ariza-Solé A, Vidán MT, et al. Impact of frailty and other geriatric syndromes on clinical management and Acknowledgments outcomes in elderly patients with non–ST-segment elevation acute coronary syndromes: rationale and design of the LON- The authors thank Andreu Ferrero-Gregori for assistance GEVO-SCA Registry. Clin Cardiol 2016; 39: 373–377. with statistical analysis. This study was supported by the 13 Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confu- funding from the Spanish Society of Cardiology. There is sion: the confusion assessment method. A new method for no conflict of interests to be declared. detection of delirium. Ann Intern Med 1990; 113: 941–948. 14 Rabe-Jabłońska J. A new draft of the mental disorders classi- References fication prepared by the American Psychiatric Association: diagnostic and statistical manual of mental disorders-IV, Op- 1 Rosengren A, Wallentin L, Simoons M, et al. Age, clinical tions Book. Psychiatr Pol 1993; 27: 109–119. presentation, and outcome of acute coronary syndromes in the 15 Mahoney FI, Barthel DW. Functional evaluation: the Barthel Euroheart acute coronary syndrome survey. Eur Heart J 2006; index. Md State Med J 1965; 14: 61–65. 27: 789–795. 16 Lawton MP, Brody EM. Assessment of older people: self- 2 Alexander KP, Newby LK, Cannon CP, et al. Acute coronary maintaining and instrumental activities of daily living. Ger- care in the elderly, part I: non-ST-segment-elevation acute ontologist 1969; 9: 179–186. coronary syndromes: a scientific statement for healthcare pro- 17 Pfeiffer E. A short portable mental status questionnaire for the fessionals from the American Heart Association Council on assessment of organic brain deficit in elderly patients. J Am Clinical Cardiology: in collaboration with the Society of Geri- Geriatr Soc 1975; 23: 433–441. atric Cardiology. Circulation 2007; 115: 2549–2569. 18 Abellan van Kan G, Rolland Y, Bergman H, et al. The 3 Dégano IR, Elosua R, Marrugat J. Epidemiology of acute I.A.N.A Task Force on frailty assessment of older people in coronary syndromes in Spain: estimation of the number of clinical practice. J Nutr Health Aging 2008; 12: 29–37. cases and trends from 2005 to 2049. Rev Esp Cardiol (Engl 19 Guralnik JM, Ferrucci L, Pieper CF, et al. Lower extremity Ed) 2013; 66: 472–481. function and subsequent disability: consistency across studies, 4 Ekerstad N, Swahn E, Janzon M, et al. Frailty is independ- predictive models, and value of gait speed alone compared ently associated with short-term outcomes for elderly patients with the short physical performance battery. J Gerontol A Biol with non-ST-segment elevation myocardial infarction. Circu- Sci Med Sci 2000; 55: M221–M231. lation 2011; 124: 2397–2404. 20 Charlson ME, Pompei P, Ales KL, et al. A new method of 5 Zaman MJ, Stirling S, Shepstone L, et al. The association classifying prognostic comorbidity in longitudinal studies: between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myo- development and validation. J Chronic Dis 1987; 40: 373– cardial Ischaemia National Audit Project (MINAP). Eur Heart 383. J 2014; 35: 1551–1558. 21 Rubenstein LZ, Harker JO, Salvà A, et al. Screening for un- 6 Inouye SK, Westendorp RG, Saczynski JS. Delirium in eld- dernutrition in geriatric practice: developing the short-form erly people. Lancet 2014; 383: 911–922. mini-nutritional assessment (MNA-SF). J Gerontol A Biol Sci 7 Ely EW, Shintani A, Truman B, et al. Delirium as a predictor Med Sci 2001; 56: M366–M372. of mortality in mechanically ventilated patients in the inten- 22 Arnau A, Espaulella J, Serrarols M, et al. Risk factors for sive care unit. JAMA 2004; 29: 1753–1762. functional decline in a population aged 75 years and older 8 Francis J, Kapoor WN. Prognosis after hospital discharge of without total dependence: a one-year follow-up. Arch Geron- http://www.jgc301.com; jgc@mail.sciencep.com | Journal of Geriatric Cardiology 128 Vives-Borrás M, et al. Delirium in elderly ACS patients tol Geriatr 2016; 65: 239–247. 34 Marcantonio ER. Postoperative delirium a 76-year-old woman 23 Austin PC. An introduction to propensity score methods for with delirium following surgery. JAMA 2012; 308: 73–81. reducing the effects of confounding in observational studies. 35 Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multi- Multivariate Behav Res 2011; 46: 399–424. component intervention to prevent delirium in hospitalized 24 Buuren S van, Groothuis-Oudshoorn K. Mice: multivariate older patients. N Engl J Med 1999; 340: 669–676. imputation by chained equations in R. J Stat Softw 2011; 45: 36 Vidán MT, Sánchez E, Alonso M, et al. An intervention inte- 1–67. grated into daily clinical practice reduces the incidence of de- 25 Saczynski JS, Marcantonio ER, Quach L, et al. Cognitive lirium during hospitalization in elderly patients. J Am Geriatr trajectories after postoperative delirium. N Engl J Med 2012; Soc 2009; 57: 2029–2036. 367: 30–39. 37 Leslie DL, Zhang Y, Holford TR, et al. Premature death asso- 26 Pauley E, Lishmanov A, Schumann S, et al. Delirium is a ciated with delirium at 1-year follow-up. Arch Intern Med robust predictor of morbidity and mortality among critically ill 2005; 165: 1657–1662. patients treated in the cardiac intensive care unit. Am Heart J 38 Marcantonio ER, Flacker JM, Michaels M, et al. Delirium is 2015; 170: 79–86. independently associated with poor functional recovery after 27 Sato K, Kubota K, Oda H, et al. The impact of delirium on hip fracture. J Am Geriatr Soc 2000; 48: 618–624. outcomes in acute, non-intubated cardiac patients. Eur Hear J 39 Uthamalingam S, Gurm GS, Daley M, et al. Usefulness of Acute Cardiovasc Care 2017; 6: 553–559. acute delirium as a predictor of adverse outcomes in patients 28 Noriega FJ, Vidan MT, Sánchez E, et al. Incidence and im- >65 years of age with acute decompensated heart failure. Am J pact of delirium on clinical and functional outcomes in older Cardiol 2011; 108: 402–408. patients hospitalized for acute cardiac diseases. Am Heart J 40 Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for 2015; 170: 938–944. the management of acute coronary syndromes in patients pre- 29 Buckinx F, Rolland Y, Reginster JY, et al. Burden of frailty in senting without persistent ST-segment elevation: Task Force the elderly population: perspectives for a public health chal- for the Management of Acute Coronary Syndromes in Patients lenge. Arch Public Health 2015; 73: 19–19. Presenting without Persistent ST-Segment Elevation of the 30 Inouye SK, Charpentier PA. Precipitating factors for delirium European Society of Cardiology (ESC). Eur Heart J 2016; 37: in hospitalized elderly persons. Predictive model and interre- 267–315. lationship with baseline vulnerability. JAMA 1996; 275: 41 Sanchez E, Vidan MT, Serra JA, et al. Prevalence of geriatric 852–857. syndromes and impact on clinical and functional outcomes in 31 Rudolph JL, Jones RN, Levkoff SE, et al. Derivation and older patients with acute cardiac diseases. Heart 2011; 97: validation of a preoperative prediction rule for delirium after 1602–1606. cardiac surgery. Circulation 2009; 119: 229–236. 42 Sanchis J, Ruiz V, Bonanad C, et al. Prognostic value of geri- 32 Kalisvaart KJ, Vreeswijk R, De Jonghe JF, et al. Risk factors atric conditions beyond age after acute coronary syndrome. and prediction of postoperative delirium in elderly hip-surgery Mayo Clin Proc 2017; 92: 934–939. patients: implementation and validation of a medical risk fac- 43 McCusker J, Kakuma R, Abrahamowicz M. Predictors of tor model. J Am Geriatr Soc 2006; 54: 817–822. functional decline in hospitalized elderly patients: a systematic 33 Inouye SK. Delirium in older persons. N Engl J Med 2006; review. J Gerontol A Biol Sci Med Sci 2002; 57: M569– 354: 1157–1165. M577. This article is part of “Prognostic and management of ACS in the elderly” Special Issue. Guest Editors: Prof. Albert Ariza Solé Journal of Geriatric Cardiology | jgc@jgc301.com; http://www.jgc301.com