Summary
Background
Peripheral vascular disease (PVD) is associated with a high risk of cardiovascular events after an acute coronary syndrome (ACS). The impact of suboptimal risk-factor control and drug prescription on morbidity and mortality rates in patients with PVD following an ACS remains to be established.
Aims
To assess whether a global atherosclerosis management programme and optimal secondary prevention could benefit high-risk PVD patients after an ACS.
Methods
A total of 851 ACS patients underwent an intensified intervention focusing on evaluating risk factors and atherosclerosis lesions, and on optimizing treatment and education. We compared its impact on long-term risk factors, medication observance and cardiovascular outcomes in patients with coronary artery disease (CAD) alone ( n = 715, 84.0%) and with both CAD and PVD ( n = 136).
Results
At a median follow-up of 18.6 months, both groups reached recommended secondary prevention goals and showed no significant differences in rates of drug prescription. PVD was not associated with minor cardiovascular events (hazard ratio [HR] 1.32, 95% confidence interval [CI] 0.57–3.02) but remained independently associated with major (HR 2.15, 95% CI 1.12–4.13) and total (HR 1.76, 95% CI 1.05–2.93) cardiovascular events. Compared to patients with CAD alone, this risk was significantly higher in CAD patients with both PVD and diabetes (HR 2.87, 95% CI 1.52–5.43), but not in PVD patients without diabetes (HR 1.35, 95% CI 0.71–2.56) or diabetic patients without PVD (HR 1.11, 95% CI 0.68–1.81).
Conclusion
Despite optimization of risk-factor control and drug prescription after ACS, patients with both PVD and diabetes carry a 2.9-fold higher risk of cardiovascular events at 18-month follow-up versus patients with CAD alone. This excess risk was not significant in PVD patients without diabetes or in diabetic patients without PVD.
Résumé
Introduction
La présence d’une artériopathie périphérique (AP) est associée à un haut risque d’évènement cardiovasculaire (CV) après un syndrome coronarien aigu (SCA). La responsabilité du contrôle insuffisant des facteurs de risque et de la prescription médicamenteuse sur cette morbimortalité élevée n’a pas été établie chez ces patients.
Méthode
Huit cent cinquante et un patients consécutifs ayant présenté un SCA ont bénéficié d’une intervention intensive visant à évaluer les facteurs de risque résiduels, la charge en athérome, et à optimiser les traitements et l’éducation thérapeutique et diététique. Nous avons comparé l’impact de ce programme à long terme sur l’équilibre des facteurs de risque, le maintien du traitement et les événements cliniques dans deux groupes : groupe 1 avec atteinte coronaire seule ( n = 715 ; 84,0 %) ; groupe 2 avec coronaropathie et AP ( n = 136 ; 16,0 %).
Résultats
Au terme d’un suivi médian de 18,6 mois, les objectifs de prévention secondaire ont été atteints dans les deux groupes qui ne présentaient pas de différence en termes de prescriptions médicamenteuses. La présence d’une AP n’est pas associée à un sur-risque d’évènements CV mineurs (HR 1,32 ; 95 % CI 0,57–3,02) mais reste un facteur indépendant de survenue d’évènement CV majeur (HR 2,15 ; 95 % CI 1,12–4,13) et d’évènement CV total (HR 1,76 ; 95 % CI 1,05–2,93) ( p < 0,05). Ce risque est significativement plus élevé chez les patients porteurs d’une AP et d’un diabète (HR 2,87 ; 95 % CI 1,52–5,43 ; p = 0,0012), mais pas chez ceux ayant une AP sans diabète (HR 1,35 ; 95 % CI 0,71–2,56 ; p = 0,35), ni chez ceux ayant un diabète sans AP (HR 1,11 ; 95 % CI 0,68–1,81 ; p = 0,68) en comparaison avec les patients avec atteinte coronaire seule.
Conclusion
Malgré l’optimisation du contrôle des facteurs de risque CV et des prescriptions médicamenteuses, les patients diabétiques avec AP ont un risque d’événement CV à 18 mois d’un SCA 2,9 fois plus élevé que les patients avec coronaropathie seule, mais cet excès de risque n’est pas significatif en cas d’AP chez les non-diabétiques, ni chez les patients diabétiques sans AP.
Background
Peripheral vascular disease (PVD) is associated with a marked increased risk of cardiovascular events . Patients with known coronary artery disease (CAD) have a poorer prognosis when they have coexisting PVD .
While secondary prevention guidelines for patients with CAD and other atherosclerotic vascular diseases are identical in their recommendations , patients with PVD are less likely than those with CAD to be prescribed the recommended therapies . Even in patients with known CAD, contemporary data show a lower rate of drug prescription after myocardial infarction when PVD is present. This could in part explain the higher mortality and morbidity observed in the PVD population . The optimal use of evidence-based therapies for secondary prevention is expected to improve modifiable major risk factors, and subsequently reduce cardiovascular morbidity and mortality. However, evidence of their clinical benefit remains poorly defined in PVD subjects.
The aim of this study was to assess whether a global atherosclerosis management programme combined with optimal secondary prevention could benefit high-risk PVD patients after an acute coronary syndrome (ACS). We hypothesized that an aggressive evidence-based drug and lifestyle intervention programme implemented in patients with an ACS would be equally beneficial, firstly in improving risk profile, and secondly in reducing the higher morbidity and mortality rates observed in ACS patients with versus without coexisting PVD.
Patients and methods
Between January 2002 and June 2005, a cohort of consecutive patients hospitalized for an established ACS in Bordeaux Heart Hospital Intensive Care Unit, and in whom a coronary angiogram during the acute phase was performed, was enrolled at the Center of Exploration, Prevention and Treatment of Atherosclerosis (CEPTA) three days after the ACS. The CEPTA programme has been described elsewhere . Briefly, it comprised initiation of secondary prevention measures before hospital discharge, including prescription of optimal treatment, and an extensive evaluation of cardiovascular risk factors, myocardial disease and atherosclerotic burden at three months. Discharge therapy was adapted to cardiac and vascular status and risk factors in accordance with international guidelines . At follow-up, a questionnaire was sent to each patient to determine lifestyle habits, current treatments and cardiovascular or other outcomes.
Acute-phase management
ACS was defined and treated according to the American College of Cardiology guidelines . An early coronary angiogram was performed in each patient, allowing precise evaluation of coronary lesions and optimized acute-phase management. The most suitable treatment was delivered during the first week, according to the guideline recommendations.
Intervention at three months
Assessment of left ventricular ejection fraction and residual myocardial ischaemia
An echocardiography was performed to assess global systolic ventricular function and wall motion abnormalities, complemented by an isotopic measure of ejection fraction. Residual myocardial ischaemia was evaluated by thallium-201 perfusion single-photon emission computed tomography during exercise.
Assessment of atherosclerosis burden
Atherosclerosis burden was evaluated by measuring coronary, carotid and lower-limb atherosclerosis, as follows:
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coronary atherosclerosis: a reduction of ≥ 50% in the diameter of one epicardial vessel on coronary angiography was considered to be a significant coronary stenosis, in addition to the lesion responsible for the ACS;
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carotid atherosclerosis: carotid ultrasound duplex imaging measured the intima medial thickness of the far wall of the common carotid arteries and the percentage of internal carotid artery stenosis ;
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lower-limb atherosclerosis: ankle brachial index (ABI) measurement was performed with the patient in the supine position after ≥ 5 min of rest .
Risk factor management and medical treatment
Each patient underwent evaluation of their reported lifestyle in relation to smoking habits, diet and physical activity. Family history of myocardial infarction was identified. Height and weight were measured and body mass index (kg/m 2 ) was calculated. Blood pressure was monitored over the course of 1 h with the patient in the supine position, and the mean measurement was used in the data analysis. A blood sample was drawn by vein puncture after a 12-hour fast to measure lipid concentrations (total cholesterol, high-density lipoprotein and low-density lipoprotein [LDL] cholesterol, triglycerides, lipoprotein[a]), glucose (fasting glucose, HbA1c), creatinine clearance and inflammatory markers (high-sensitive C-reactive protein, fibrinogen).
Diabetes mellitus was defined as fasting glycaemia ≥ 7 mmol/L in two consecutive measures or when antidiabetic drugs had been prescribed previously. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Dyslipidaemia was defined as LDL cholesterol > 3.35 mmol/L.
Treatment at hospital discharge was consistently adapted to cardiac and vascular status, to risk factors and to specific goals to be attained, in accordance with international guidelines . The aim of dietary intervention was a total daily intake of fat < 30% of the daily energy intake and an intake of saturated fatty acids < 10% of the daily energy intake. A dietician provided patient-specific weight-management guidance. On two occasions, educational classes lasting 2 h were provided that covered all aspects of coronary artery disease risk, including lifestyle modification, smoking cessation, hypertension and lipid and diabetes management, and provided comprehensive risk-reduction counselling to improve observance to treatment. A smoking cessation specialist was involved for current smokers. Light-to-moderate exercise lasting ≥ 30 min three times a week was recommended.
Definitions of PVD: organization of patient groups
In order to evaluate the impact of the extent of atherosclerosis lesions on outcome after an ACS, patients were categorized into two groups according to the presence (defined as an ABI < 0.9) or absence of PVD: CAD alone and CAD and PVD.
Patient follow-up and definition of endpoints
Follow-up was carried out with a standardized questionnaire, previously validated in clinical trials , sent to each patient and physician 18 months after discharge from the CEPTA evaluation. Nurses in charge of patient education telephoned the patients at their homes and/or their physicians, whenever needed (i.e., when there was an address and/or phone number change or for medical details). The questionnaire covered aspects of lifestyle habits including former or current smoking and level of physical activity. Symptoms of reinfarction, stroke, PVD and surgical treatment (revascularization by angioplasty, coronary artery bypass grafting, carotid endarterectomy) after hospital discharge were researched. The medical records of the subjects who died, or who reported on the questionnaire that they had experienced symptoms or any clinical outcome between baseline evaluation and follow-up, were reviewed by one of the investigators, and patient practitioners were contacted. The patient’s practitioner measured blood pressure and weight. Current medication was noted.
At follow-up, treatments, risk-factor profile and cardiovascular events were evaluated. Events included total events (cardiovascular death, ACS, stroke or transient ischaemic attack [TIA], congestive heart failure, secondary coronary revascularization or peripheral vascular surgery), major adverse cardiovascular events (MACE; cardiovascular death, ACS, stroke or TIA) and minor adverse cardiovascular events (MICE; congestive heart failure, coronary or peripheral vascular revascularization).
Statistical analysis
Baseline characteristics, ACS management, atherosclerotic lesions, treatment and risk factors at follow-up of patients without PVD were compared with those presenting with PVD using the t test and the χ 2 test, as appropriate. A Cox proportional-hazards regression analysis in univariate or multivariable models was used for further analysis of independent variables predicting the occurrence of events at follow-up after adjustment for potentially confounding variables. Covariates that were tested in the model included PVD, non-modifiable risk factors (age, sex) and modifiable risk factors (hypertension, smoking, dyslipidaemia and diabetes). With the aim of determining predictors of events, patients who presented an event during follow-up were compared to those who did not by use of the t test for continuous variables and the χ 2 statistic for categorical variables. Taking these results into account, Cox proportional-hazards regression was used to assess the risk of cardiovascular events in patients with CAD and PVD, with CAD and diabetes, and with CAD and both PVD and diabetes, with hazards ratios given in comparison with CAD alone as a reference group. A p value ≤ 0.05 was considered to be statistically significant. The software for statistical analysis was STATA (StataCorp LP, College Station, Texas).
Results
From January 2002 to June 2005, 851 consecutive men and women presenting with an ACS were hospitalized at CEPTA for an optimized atherosclerosis secondary prevention programme and were enrolled in the study. According to the extent of atherosclerosis, 715 patients (84.0%) presented with CAD alone and 136 patients (16.0%) with CAD and PVD.
Acute phase management and evaluation at three months
Patients with CAD and PVD were more likely than those with CAD alone to receive medical treatment and they had a greater atherosclerotic burden ( Table 1 ).
| Variable | CAD ( n = 715) | CAD + PVD ( n = 136) | p |
|---|---|---|---|
| Revascularization a within first 36 h (%) | 87.7 | 75.6 | < 0.001 |
| Medical b treatment (%) | 12.3 | 24.4 | < 0.001 |
| In-hospital complications c (%) | 20.3 | 21.7 | 0.80 |
| In-hospital heart failure (%) | 3.0 | 3.8 | 0.80 |
| Isotopic ejection fraction (%) | 55.3 ± 12 | 53.7 ± 11 | 0.52 |
| Ejection fraction ≤ 40% (%) | 10.5 | 14.1 | 0.39 |
| Atherosclerosis burden | |||
| Mean number of coronary vessels with ≥ 50% stenosise | 1.45 ± 0.8 | 1.67 ± 0.8 | < 0.01 |
| Ankle brachial index > 1.4 (%) | 7.1 | – | |
| Carotid stenosis ≥ 50% (%) | 5.7 | 19.3 | < 0.0001 |
| Intima medial thickness > 0.7 mm (%) | 41.5 | 63.9 | 0.001 |
a Angioplasty or coronary artery bypass graft.
b No reperfusion therapy delivered for the treatment of ACS.
c Recurrent acute coronary syndrome, ventricular tachycardia, supraventricular arrhythmia, pericarditis, heart failure.
Table 2 shows the demographic and baseline characteristics of patients three months after the index event. In comparison with CAD alone, patients with both CAD and PVD were older and had a higher prevalence of cardiovascular risk factors despite treatment initiated after the ACS.
