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Archives of cardiovascular diseases
Volume 103, n° 1
pages 19-25 (janvier 2010)
Doi : 10.1016/j.acvd.2009.09.005
Received : 1 July 2009 ;  accepted : 17 September 2009
Functional decline in elderly patients presenting with acute coronary syndromes: Impact on midterm outcome
Impact pronostique à moyen terme de la perte d’autonomie chez les sujets âgés hospitalisés pour un syndrome coronaire aigu
 

Clémence Huerre a, Aurélie Guiot a, Sylvestre Maréchaux a, d, Jean-Luc Auffray a, Jean-Jacques Bauchart a, David Montaigne a, d, Frédéric Mouquet a, Martine Lesenne a, François Puisieux b, d, Patrick Goldstein c, Philippe Asseman a, d, Pierre-Vladimir Ennezat a,
a Intensive Cardiology Care Unit, centre hospitalier régional et universitaire de Lille, boulevard Pr.-J.-Leclercq, 59000 Lille, France 
b Gerontology Department, centre hospitalier régional et universitaire de Lille, Lille, France 
c Emergency Department, centre hospitalier régional et universitaire de Lille, Lille, France 
d Faculté de médecine, université de Lille-2, Lille, France 

Corresponding author. Fax: +33 3 20 44 56 04.
Summary
Background

Elderly patients with an acute coronary syndrome (ACS) are less likely to be enrolled into randomized, controlled trials or receive guideline-recommended therapies, because of a higher burden of comorbidity, including functional decline.

Aim

To assess the prognostic value of functional decline in a prospective, observational cohort of elderly ACS patients.

Methods

ACS patients aged ≥70 years were enrolled. The ACS definition included ST- and non-ST-segment elevation myocardial infarction, and unstable angina pectoris. Clinical admission and laboratory data and echocardiographic variables were recorded. Functional decline was defined as needing assisted care in daily life. The study endpoint was all-cause mortality.

Results

Overall, 151 patients were enrolled (mean age 78±5 years; 52% men). Twenty-eight (19%) patients had functional decline. No significant difference in therapeutic management was observed between patients with functional decline and those living independently. Twenty-seven (18%) patients died during follow-up (median 447 days). Functional decline correlated with poor outcome (p =0.008; hazard ratio [HR] 2.87 [1.31–6.25]). Other prognostic markers were diabetes, Killip class ≥II, elevated E/Ea ratio, C-reactive protein, B-type natriuretic peptide, haemoglobin, glycaemia and no coronary angiography. By multivariable analysis, C-reactive protein >13mg/L correlated with poor outcome (p =0.007; HR 4.77 [1.52–14.96]). There was a trend towards correlation between functional decline and poor outcome (p =0.051; HR=2.77 [0.99–7.72]).

Conclusion

Functional decline seems to portend poor prognosis in elderly ACS patients. Larger, community-based studies are needed to confirm these findings in a multivariable model.

The full text of this article is available in PDF format.
Résumé
Introduction

Cette étude a pour but d’évaluer l’impact pronostique de la perte d’autonomie chez des sujets âgés de plus de 70 ans hospitalisés pour un syndrome coronaire aigu (SCA).

Méthode

Cent cinquante et un patients de plus de 70 ans hospitalisés pour un SCA ont été inclus. L’ensemble des données cliniques, biologiques et échocardiographiques du patient a été recueilli prospectivement. La perte d’autonomie était définie par la nécessité d’un recours à une ou des aides extérieures dans la vie quotidienne. Le critère principal était le décès toutes causes confondues.

Résultats

L’âge moyen était de 78±5 années avec 52 % d’homme. La perte d’autonomie était constatée chez 28 patients (19 %). Aucune différence significative de thérapeutique n’a été mise en évidence entre les deux populations (avec ou sans perte d’autonomie). Vingt-sept patients (18 %) sont morts durant un suivi moyen de 447 jours. La perte d’autonomie ressort comme un facteur de mauvais pronostic de manière significative (p =0,008 ; HR 2,87 [1,31–6,25]). Les autres marqueurs pronostiques mis en évidence sont le diabète (p =0,016 ; HR 2,57 [1,19–5,54]), le stade Killip supérieur ou égal à 2 (p =0,008 ; HR 2,89 [1,32–6,31]), l’élévation du rapport E/Ea (p =0,025 ; HR 1,07 [1,01–1,13]), ainsi que des marqueurs biologiques tels que la C-reactive protein (p <0,0001 ; HR 1,85 [1,37–2,51]), le B-type natriuretic peptide (p =0,023 ; HR 1,41 [1,05–1,91]), le taux d’hémoglobine (p =0,002 ; HR 0,73 [0,60–0,89]), la glycémie (p =0,012 ; HR 2,95 [1,27–6,82]), et l’absence de coronarographie (p =0,012 ; HR 1,62 [1,19–1,82]). En analyse multivariée, un taux de C-reactive protein supérieur à 13mg/L émerge comme facteur pronostique indépendant (p =0,007 ; HR=4,77 [1,52–14,96]). Une tendance à la limite de la significativité est observée dans l’association entre perte d’autonomie et mortalité (p =0,051 ; HR=2,77 [0,99–7,72]).

Conclusion

La perte d’autonomie semble donc être un facteur de mauvais pronostic chez les sujets âgés présentant un SCA. Cependant, une plus large étude sera nécessaire pour valider ces résultats préliminaires et les intégrer dans un modèle multivarié.

The full text of this article is available in PDF format.

Abbreviations : ACS

Keywords : Acute coronary syndromes, Elderly, Functional decline, Prognosis

Mots clés : Syndrome coronarien aigu, Perte d’autonomie, Sujets âgés, Marqueurs pronostiques


Introduction

Ageing is a major risk factor for ACS and is also associated with worse prognosis [1]. However, because of a higher burden of comorbid conditions, including functional decline, elderly patients who present with an ACS are enrolled much less frequently into randomized, controlled trials [2, 3] and are less likely to receive guideline-recommended therapies [4]. Accordingly, we aimed to evaluate whether functional decline correlates with outcome in older people (aged70 years) presenting with an ACS. In addition, we studied whether functional decline impacts on ACS therapeutic management in daily clinical practice.

Methods
Population

The study cohort consisted of ACS patients (≥70 years) who were admitted to the cardiac intensive care unit of the Centre Hospitalier Régional et Universitaire de Lille. Elderly patients with non-ST-segment elevation and ST-segment elevation ACS according to the European Society of Cardiology guidelines were included in the study. Elderly ACS patients in cardiac arrest or with cardiogenic shock requiring mechanical ventilation (n =12), severe primary cardiac valvular disease (n =39), Takotsubo syndrome (n =9) or normal coronary angiograms despite elevated cardiac troponin (n =4), were ineligible for the study.

Clinical data

Medical history, admission heart rate, systolic blood pressure, Killip classification, medications and laboratory tests (including glucose level [normal 65–100mg/dL] and haemoglobin [normal 13–18g/dL for men, 12–16g/dL for women]) performed on admission were recorded. Clinical data included age, sex, history of smoking, documented diagnosis of hypertension (patients receiving antihypertensive medications or having known, but untreated, hypertension [blood pressure140/90mmHg]), hypercholesterolaemia (patients on cholesterol-lowering medication or in the absence of such medication, low-density lipoprotein cholesterol level>160mg/dL) and diabetes (fasting blood glucose level>126mg/dL on two occasions or patients currently receiving oral hypoglycaemic medication or insulin). Body mass index was calculated as weight (kg)/height2 (m2). Activity level was assessed systematically using the Katz Basic Activities of Daily Living questionnaire [5]. On the first day of admission, patients were asked about feeding, bathing, continence, dressing, toileting and transferring. Functional status was classified as functional decline (needing assisted care for at least one of the basic activities mentioned above) or as living independently. Electrocardiographic findings on admission were classified according to the presence or absence of ST-segment elevation. Cardiac troponin I levels were measured using the ADVIA Centaur TnI-Ultra assay (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA) with a 99th percentile upper reference limit for cardiac troponin of <0.05ng/L. Plasma levels of B-type natriuretic peptide were measured using the ACS:180 BNP assay (Bayer®) (normal100pg/mL). C-reactive protein levels were measured using a turbidimetric immunoassay (normal<4mg/L). The glomerular filtration rate (normal60mL/min/1.73m2) was estimated using the four-component Modification of Diet in Renal Disease equation, incorporating age, race, sex and serum creatinine level: estimated glomerular filtration rate=186×(serum creatinine level in mg/dL)1.154×(age in years)0.203. For women, the product of this equation was multiplied by a correction factor of 0.742 [6]. At hospital discharge, echocardiograms were carried out by staff cardiologists using the HP SONOS 5500 ultrasound system (Philips, Andover, MA, USA) with a 2–4MHz transducer. Left ventricular ejection fraction, tissue Doppler-derived diastolic function and mitral regurgitation were assessed as described previously [7].

Patient follow-up

After hospital discharge, the vital status of patients were monitored by telephone calls to referring cardiologists and primary care physicians, and by review of medical records. The primary endpoint of the study was death from all causes.

Statistical analysis

Continuous variables are expressed as means±standard deviations or medians [25th–75th percentiles], as appropriate. Categorical variables are presented as absolute numbers and percentages. B-type natriuretic peptide and C-reactive protein were log-transformed to remove skewness of data distribution. Comparisons between groups were made using Student’s t test or the Mann-Whitney U test, as appropriate. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Event-free survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Threshold values for biological variables were obtained using receiver operating characteristic curve analysis. Given the low number of events with regard to the univariate predictors of poor outcome, a Cox stepwise forward multivariable analysis was performed, with entry and retention set at 0.05. A two-tailed type I error rate < 0.05 was considered for statistical significance. Analyses were conducted using SPSS 13.0 (Chicago, IL, USA) and the SAS System Version 9.0 for Windows® (SAS Institute, Cary, NC, USA).

Results
Patient characteristics

Between 01 January and 31 December 2007, 151 patients aged70 years presenting with an ACS were enrolled in this study. There were 79 (52%) men and 72 (48%) women; the mean age was 78±5 years. Clinical and echocardiographic characteristics at admission are shown in Table 1. Forty-eight (32%) patients had ST-segment elevation ACS. History of coronary artery disease was reported in 31 (20%) patients and history of stroke in 23 (15%) patients. Twenty-three (15%) patients had a history of cancer. The use of glycoprotein IIb/IIIa receptor blockers was 15%, the use of clopidogrel was 77% and the use of aspirin was 94%. Percutaneous coronary interventions with stenting were performed in 99 (65%) patients.

At hospital discharge, 79% of patients received a beta-blocker, 95% received aspirin, 77% received clopidogrel, 89% received a statin, 77% received an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, 3% received an aldosterone antagonist and 12% received a vitamin K antagonist. Three patients underwent coronary artery bypass graft surgery during follow-up. Functional decline was found in 28 (19%) patients. The specific contributors that led to restriction in the ability to perform normal activities of daily living are shown in Table 2. It was noteworthy that there was no significant difference in therapeutic management between patients with functional decline and those living independently (Table 3).

Patient follow-up

Vital status was available for all patients. During follow-up (median 447 [271–524] days), 27 (18%) patients died and reached the primary endpoint of the study. By univariate analysis, functional decline correlated with poor outcome (p =0.008; hazard ratio [HR] 2.87 [1.31–6.25]). Event-free survival curves according to functional status are depicted in Figure 1. The other clinical factors associated with development of a primary event were diabetes (p =0.016; HR 2.57 [1.19–5.54]), Killip classII (p =0.008; HR 2.89 [1.32–6.31]), elevated E/Ea ratio (p =0.025; HR 1.07 [1.01–1.13]), C-reactive protein (p <0.0001; HR 1.85 [1.37–2.51]), B-type natriuretic peptide (p =0.023; HR1.41 [1.05–1.91]), haemoglobin (p =0.002; HR 0.73 [0.60–0.89]), glycaemia (p =0.012; HR 2.95 [1.27–6.82]) and no coronary angiography (p =0.012; HR 1.62 [1.19–1.82]). Univariate analysis with biological variables expressed in dichotomous format identified C-reactive protein>13mg/L (p =0.001; HR 4.12 [1.72–9.87]), B-type natriuretic peptide>190pg/mL (p =0.007; HR 3.92 [1.45–10.55]), haemoglobin11.4g/dL (p =0.001; HR 5.17 [1.93–13.86]) and glycaemia>102mg/dL (p =0.05; HR 2.56 [1.01–6.54]). By Cox forward stepwise multivariable analysis, including variables in continuous format, only C-reactive protein emerged as an independent predictor of poor outcome. Using biological data in dichotomous format, C-reactive protein>13mg/L correlated with a poor outcome (p =0.007; HR=4.77 [1.52–14.96]). There was a trend towards borderline significance for correlation between functional decline and poor outcome (p =0.051; HR=2.77 [0.99–7.72]).



Figure 1


Figure 1. 

Event-free survival curves according to functional status.

Zoom

Discussion

Our data indicate that functional decline occurs frequently in elderly patients presenting with an ACS and does not alter the hospital therapeutic management of these patients significantly in our daily practice. In addition, functional decline might be considered as a marker of poor prognosis in ACS management.

The high mortality rate of 18% at 1.2 years in our series underscores that ageing is in itself an exceedingly high-risk marker. However, the elderly patient population that represents a growing proportion of patients with an ACS [8] is underrepresented in randomized trials and is less likely to receive invasive and evidence-based therapies. More than half of all trials for coronary disease failed to enrol any patient older than 75 years [3]. Patients older than 75 years enrolled in VIGOUR trials constituted 18% of the randomized population but were about twice as prevalent in community registries (32% in GRACE; 38% in CRUSADE) [9, 10], indicating that older people are more likely to be excluded from randomized trials. In addition, comparison of baseline characteristics of trial and community populations by age subgroup show that elderly people included in trials have fewer comorbid conditions and better admission haemodynamic presentation and renal function than community populations. Of note in the present series, in comparison with our previous report [7], the rates of use of pharmacological and invasive treatment were diminished markedly overall (beta-blockers 79% vs 87%, aspirin 95% vs 97%, clopidogrel 77% vs 93%, statins 89% vs 93%, renin-angiotensin-aldosterone system inhibitors 77% vs 95%, coronary angiography 70% vs 94%), the estimated renal function was further reduced (median creatinine clearance 61 vs 73mL/min/1.73m2) and the clinical presentation was more severe (Killip classII 39% vs 19%). These data confirm that closer attention to ACS treatment should be paid in the high-risk elderly population.

Functional decline represents a major public health burden associated with an increasing cost because of ageing in Western countries. Functional decline leads primarily to inactivity. Several studies have shown that preserving physical activity, in addition to improving quality of life, correlates inversely with mortality [11]. Physical activity in daily living does indeed have antiatherogenic and anti-inflammatory effects, reduces the risk of thrombosis and of ventricular arrhythmias and improves vascular endothelial dysfunction [12]. In addition to other comorbid conditions, altered functional and cognitive status associated with ageing reduces activity and is therefore likely to reduce life expectancy after an ACS. Functional decline reached 20% in our series and worsened prognosis despite patients receiving similar management to that of patients who lived independently. In the study by Vaccarino et al., 56 (25%) people reported limitations in at least one activity of daily living and were classified as disabled in a cohort of 360 subjects aged65 years who had a discharge diagnosis of myocardial infarction. Our findings are consistent with this study, which found that functional disability in activities of daily living emerged as a prognostic factor after myocardial infarction in elderly patients (adjusted relative risk of death for patients with disability vs patients without disability 2.01 [1.23–3.28]) [13]. However, in comparison with our study, Vaccarino et al. studied more severe patients, as demonstrated by the higher proportion of disabled patients and the higher rate of mortality: 40% of their population sample and 59% of their patients with disability died within six months of admission to the hospital. Acute illness such as an ACS can indeed hasten and worsen functional decline. During hospitalization, reduced mobility and other factors may decrease rapidly an older patient’s ability to perform activities that are crucial for independent living [14]. Therefore, one expects a specific therapeutic strategy, including immediate rehabilitation, to improve the prognosis of these patients.

Of note in our series, we found various clinical indicators that have been correlated previously with poor outcome after an ACS, including Killip class [15], diabetes mellitus [16], low haemoglobin [17], hyperglycaemia [18], C-reactive protein [19], increased B-type natriuretic peptide [20, 21] and E/Ea ratio [7, 22].

Limitations

The small size of the study population and the single-centre nature of the study clearly limit its clinical implications. A better assessment of frailty, nutritional, functional and cognitive status, is warranted to better separate age-related health issues from ACS-related risk.

Conclusion

Prognosis of elderly ACS patients remains clearly severe. Functional decline occurs frequently in this setting and emerges as an univariate predictor of poor outcome in these older patients. Further, larger, community-based studies are needed to ascertain the impact of functional decline on outcome with regard to other prognostic factors in elderly patients with an ACS.

Conflicts of interest

None.


Acknowledgements

Clémence Huerre and Aurélie Guiot both contributed equally to the preparation of the manuscript.

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