Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study.

AIM: The aim of this long-term prospective study was to evaluate the effect of treating obstructive sleep apnoea (OSA) on the rate of cardiovascular events in coronary artery disease (CAD). METHODS AND RESULTS: We prospectively studied 54 patients (mean age 57.3 +/- 10.1 years) with both CAD (> or = 70% coronary artery stenosis) and OSA (apnoea-hypopnoea index > or = 15). In 25 patients, OSA was treated with continuous positive airway pressure (n=21) or upper airway surgery (n=4); the remaining 29 patients declined treatment for their OSA. The median follow-up was 86.5 +/- 39 months. The two groups were similar at baseline in age, body mass index, smoking history, hypertension, hypercholesterolaemia, diabetes mellitus, number of diseased vessels, left ventricular ejection fraction, and CAD therapy. Treatment of risk factors other than OSA was similar in the two groups. The endpoint (a composite of cardiovascular death, acute coronary syndrome, hospitalisation for heart failure, or need for coronary revascularisation) was reached in 6 (6/25, 24%) and 17 (17/29, 58%) patients with and without OSA treatment, respectively (P<0.01). OSA treatment significantly reduced the risk of occurrence of the composite endpoint (hazard ratio 0.24; 95% confidence interval, 0.09-0.62; p<0.01) and of each of its components. CONCLUSIONS: Our data indicate that the treatment of OSA in CAD patients is associated with a decrease in the occurrence of new cardiovascular events, and an increase in the time to such events.     

Influence of obstructive sleep apnoea in coronary artery disease: A 10-year follow-up

In patients with coronary artery disease (CAD) the prevalence of obstructive sleep apnoea (OSA) is found to be about 14-65%. In this study, the influence of OSA in 50 patients with CAD was prospectively compared during a follow-up period of 10 years. In the follow-up period 4 of 25 patients with OSA and 5 of the 25 without OSA died by cardiovascular complications. The proportion survival curve showed no significant difference for patients with CAD and with versus without OSA. The results of this rather small 10-year follow-up study failed to give further evidence for an increased mortality in patients with CAD and OSA.     

An independent association between obstructive sleep apnoea and coronary artery disease.

Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Sk?vde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease.     

Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up

The incidence of a cardiovascular disease (CVD) was explored in a consecutive sleep clinic cohort of 182 middle-aged men (mean age, 46.8 +/- 9.3; range, 30-69 years in 1991) with or without obstructive sleep apnea (OSA). All subjects were free of hypertension or other CVD, pulmonary disease, diabetes mellitus, psychiatric disorder, alcohol dependency, as well as malignancy at baseline. Data were collected via the Swedish Hospital Discharge Register covering a 7-year period before December 31, 1998, as well as questionnaires. Effectiveness of OSA treatment initiated during the period as well as age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) at baseline, and smoking habits were controlled. The incidence of at least one CVD was observed in 22 of 60 (36.7%) cases with OSA (overnight oxygen desaturations of 30 or more) compared with in 8 of 122 (6.6%) subjects without OSA (p < 0.001). In a multiple logistic regression model, significant predictors of CVD incidence were OSA at baseline (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.8-13.6) and age (OR 23.4; 95% CI, 2.7-197.5) after adjustment for BMI, SBP, and DBP at baseline. In the OSA group, CVD incidence was observed in 21 of 37 (56.8%) incompletely treated cases compared with in 1 of 15 (6.7%) efficiently treated subjects (p < 0.001). In a multiple regression analysis, efficient treatment was associated with a significant risk reduction for CVD incidence (OR 0.1; 95% CI, 0.0-0.7) after adjustment for age and SBP at baseline in the OSA subjects. We conclude that the risk of developing CVD is increased in middle-aged OSA subjects independently of age, BMI, SBP, DBP, and smoking. Furthermore, efficient treatment of OSA reduces the excess CVD risk and may be considered also in relatively mild OSA without regard to daytime sleepiness.     

Increased long-term mortality in heart failure due to sleep apnoea is not yet proven.

Previous small-scale studies of the effect of sleep-disordered breathing (SDB) on prognosis in congestive heart failure (CHF) are either lacking or conflicting. The aim of this study was to assess the impact of the presence and type of SDB on mortality in a patient group with severe CHF referred to a specialised heart failure centre. Out of 78 patients ((mean +/- SD) 53 +/- 9 yrs, left ventricular ejection fraction 19.9 +/- 7.2% and pulmonary capillary wedge pressure 16.5 +/- 8.3 mmHg) followed-up over a median period of 52 months, 29% had no apnoea (CHF-N), 28% had obstructive sleep apnoea (CHF-OSA) and 42% had central sleep apnoea (CHF-CSA). At 52 months, their overall mortality was 40%, and combined mortality and transplantation was 72%. Mortality rates were similar between the three apnoea groups. Survivors had a similar prevalence of SDB (71%) as the nonsurvivors (70%). Although a significant increase in mortality was evident at 500 days in those patients with either CHF-SDB or CHF-CSA as compared with CHF-N, this was not significant at final follow-up (52 months) using Kaplan Meier analysis. Multivariate analysis identified transplantation but not SDB type or severity as a significant predictor of survival. In conclusion, sleep-disordered breathing impacts upon early (500 day), but not long-term (52 month), mortality in a specialised heart failure centre.     

Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: a long-term follow-up study

OBJECTIVES: The purpose of this study was to evaluate the efficacy of an intravascular ultrasound (IVUS)-guided strategy for patients with angiographically indeterminate left main coronary artery (LMCA) disease. BACKGROUND: The assessment of LMCA lesions using coronary angiography is often challenging; IVUS provides useful information for assessment of coronary disease. METHODS: Intravascular ultrasound was performed on 121 patients with angiographically normal LMCAs to determine the lower range of normal minimum lumen area (MLA), defined as the mean - 2 SD. We conducted IVUS studies on 214 patients with angiographically indeterminate LMCA lesions, and deferral of revascularization was recommended when the MLA was larger than this predetermined value. RESULTS: The lower range of normal LMCA MLA was 7.5 mm(2). Of the patients with angiographically indeterminate LMCAs, 83 (38.8%) had an MLA <7.5 mm(2), and 131 (61.2%) an MLA > or =7.5 mm(2). Left main coronary artery revascularization was performed in 85.5% (71 of 83) of patients with an MLA <7.5 mm(2) and deferred in 86.9% (114 of 131) of patients with an MLA > or =7.5 mm(2). Long-term follow-up (mean 3.3 +/- 2.0 years) showed no significant difference in major adverse cardiac events (target vessel revascularization, acute myocardial infarction, and death) between patients with an MLA <7.5 mm(2) who underwent revascularization and those with an MLA > or =7.5 mm(2) deferred for revascularization (p = 0.28). Based on outcome, the best cut-off MLA by receiver operating characteristic was 9.6 mm(2). Multivariate predictors of cardiac events were age, smoking, and number of non-LMCA vessels diseased. CONCLUSIONS: Intravascular ultrasound is an accurate method to assess angiographically indeterminate lesions of the LMCA. Furthermore, deferring revascularization for patients with a minimum lumen area > or =7.5 mm(2) appears to be safe.     

Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment

Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known about the effect of OSA and continuous positive airway pressure (CPAP) on the incidence of long-term, nonfatal cardiovascular events (CVE) in stroke patients. A prospective observational study was made in 223 patients consecutively admitted for stroke. A sleep study was performed on 166 of them. 31 had an apnoea/hypopnoea index (AHI) <10 events · h(-1); 39 had an AHI between 10 and 19 events · h(-1) and 96 had an AHI ≥ 20 events · h(-1). CPAP treatment was offered when AHI was ≥ 20 events · h(-1). Patients were followed up for 7 yrs and incident CVE data were recorded. The mean ± SD age of the subjects was 73.3 ± 11 yrs; mean AHI was 26 ± 16.7 events · h(-1). Patients with moderate-to-severe OSA who could not tolerate CPAP (AHI ≥ 20 events · h(-1); n = 68) showed an increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes (hazard ratio 2.87, 95% CI 1.11-7.71; p = 0.03), compared with patients with moderate-to-severe OSA who tolerated CPAP (n = 28), patients with mild disease (AHI 10-19 events · h(-1); n = 36) and patients without OSA (AHI <10 events · h(-1); n = 31). Our results suggest that the presence of moderate-to-severe OSA is associated with an increased long-term incidence of nonfatal CVE in stroke patients and that CPAP reduces the excess of incidence seen in these patients.     

Increased neutrophil aggregability in coronary artery disease

The purpose of this investigation was to study neutrophil (PMN)aggregation in the aorta and coronary sinus of 20 patients withangiographically documented coronary artery disease (group I)compared with eight patients with normal coronary arteries (groupII). PMNs were separated from the other blood components andtheir aggregation response to Ca²⁺ ionophore A 23187 1 x 10^–5M (final concentration) was measured. Group I patients had higher aggregating activity in the coronarysinus than in the aorta (24.9± 3.7 vs 18.7± 3.4average maximum T, P<0.01), while no difference was foundin group II (coronary sinus 16.7±3.5; aorta 16.3±2.4average maximum TP = NS). Among group I patients, smokers hada significantly higher aggregating activity than non-smokers,whereas no correlation was found between aggregation responseand blood cholesterol values. These data suggest that the presence of atherosclerotic plaquesin coronary vessels may prime PMNs so that they show greateraggregating response to subsequent stimulation.     

Catheter ablation of ventricular tachycardia in 136 patients with coronary artery disease: Results and long-term follow-up

Objectives. This study attempted to determine the feasibility and long-term efficacy of catheter ablation by means of either radiofrequency or direct current energy in a selected group of patients with coronary artery disease.Background. Catheter ablation of ventricular tachycardia has proved to be highly effective in patients with idiopathic and bundle branch reentrant ventricular tachycardia. In patients with coronary artery disease and recurrent sustained ventricular tachycardia resistant to medical antiarrhythmic management, the value of catheter ablation has not yet been established.Methods. One hundred thirty-six patients with coronary artery disease and one configuration of monomorphic sustained ventricular tachycardia underwent radiofrequency (72 patients) or direct current catheter ablation (64 patients). The mapping procedure to localize an adequate site for ablation included pace mapping during sinus rhythm, endocardial activation mapping, identification of isolated mid-diastolic potentials and pacing interventions during ventricular tachycardia.Results. Primary success was achieved in 102 (75%) of 136 patients (74% of 72 undergoing radiofrequency and 77% of 64 with direct current ablation). Complications were noted in 12% of patients. During a mean (± SD) follow-up period of 24 ± 13 months (range 3 to 68), ventricular tachycardia recurred in 16% of patients.Conclusions. Catheter ablation of ventricular tachycardia in coronary artery disease is feasible in patients with one configuration of monomorphic sustained ventricular tachycardia. There is no significant difference with respect to the type of energy applied. The follow-up data show that in a selected group of patients with coronary artery disease, catheter ablation offers a therapy alternative.     

Endovascular management of patients with coronary artery disease and diabetic foot syndrome: A long-term follow-up

Background To investigate the long-term results of global coronary and peripheral interventional treatment of diabetic foot patients. Methods We retrospectively included 220 diabetic patients (78.5 ± 15.8 years, 107 females, all with Fontaine III or IV class) who were referred to our centre for diabetic foot syndrome and severe limb ischemia from January 2006 to December 2010. Patients were evaluated by a team of interventional cardiologists and diabetologists in order to assess presence of concomitant coronary artery disease (CAD) and eventual need for coronary revascularization. Stress-echo was performed in all patients before diagnostic peripheral angiography. Patients with indications for coronary angiography were submitted to combined diagnostic angiography and then to eventual staged peripheral and coronary interventions. Doppler ultrasonography and foot transcutaneous oximetry of transcutaneous oxygen pressure (TcPO2) before and after the procedure were performed as well as stress-echocardiography and combined cardiologic and diabetic examination at 1 and 6 month and yearly. Results Stress-echocardiography was performed in 94/220 patients and resulted positive in 56 patients who underwent combined coronary and peripheral angiography. In the rest of 126 patients, combined coronary and peripheral angiography was performed directly for concomitant signs and symptoms of coronary heart disease in 35 patients. Coronary revascularization was judged necessary in 85/129 patients and was performed percutaneously after peripheral interventions in 72 patients and surgically in 13 patients. For Diabetic foot interventions the preferred approach was ipsilateral femoral antegrade in 170/220 patients (77.7%) and contralateral cross-over in 40/220 patients (18.8%) and popliteal retrograde + femoral antegrade in 10/220 patients (4.5%). Balloon angioplasty was performed in 252 legs (32 patients had bilateral disease): the procedure was successful in 239/252 legs with an immediate success rate of 94.8% and a significant improvement in TcPO2 and ABI with ulcer healing in 233/252 legs (92.4%). Freedom from major amputation was 82.8% at a mean follow-up of 3.1 ± 1.8 years (range 1 to 5 years) whereas survival was 88%. Conclusions Global coronary and peripheral endovascular management of diabetic foot syndrome patients seems to lead to an high immediate success and limb salvage rates and increasing survival compared to historical series.     

Increased serum neopterin: a marker of coronary artery disease activity in women

OBJECTIVE: To assess whether neopterin concentrations in women with unstable angina differ from those in women with chronic stable angina. DESIGN: Prospective cohort study. SETTING: University hospital in south west London. PATIENTS: 114 consecutive women with angina were studied: 82 had chronic stable angina (typical exertional chest pain, positive exercise ECG testing, and/or abnormal myocardial scintigraphy; symptoms stable for at least three months), and 32 had unstable angina (Braunwald class III). All patients with chronic stable angina (100%) and 18 with unstable angina (56.3%) underwent digital coronary angiography; neopterin concentrations were determined using a commercially available immunoassay. MAIN OUTCOME MEASURES: Major clinical events during one year follow up were readmission with Braunwald's class IIIb unstable angina, non-fatal myocardial infarction, and cardiac death. RESULTS: Major events occurred in 12 women with chronic stable angina (14.6%) and nine women with unstable angina (28.1%). Mean (range) neopterin concentrations were significantly higher in women with unstable angina than in those with chronic stable angina (7.6 (5.1-11.5) nmol/l v 5.9 (4.4-7.5) nmol/l; p = 0.003), even after adjustment for variables which were significantly different on univariate analysis. In women with chronic stable angina, baseline neopterin concentrations were higher in those with cardiac events than in those without events (7.1 (5.9-9.1) nmol/l v 5.7 (3.9-7.3 nmol/l); p = 0.010), even after adjustment for variables with significant differences between both groups on univariate analysis. CONCLUSIONS: On average, women with unstable angina had significantly higher neopterin concentrations than women with chronic stable angina. Women with chronic stable angina with events during follow up had higher neopterin concentrations than those without events. Neopterin concentrations were similar in patients with unstable angina and women with chronic stable angina who developed events. Neopterin concentrations may therefore be a marker of risk in women with coronary artery disease.     

Left main coronary artery aneurysm: sealing by stent graft and long-term follow-up.

We describe the implantation of a stent graft to seal off the left main coronary artery aneurysm of a 64-year-old man with guidance by intravascular ultrasound. The aneurysm was successfully sealed off. At 6-month and 1-year follow-up, a small residual aneurysm reappeared, which was treated conservatively. The technical issues in closing this aneurysm and the management of the residual aneurysm are discussed.     

Inflammatory markers in a 2-year follow-up of coronary artery disease

Our study was designed in an attempt to determine the dynamics of changes in serum tumor necrosis factor (TNF)-α, soluble forms of its receptors (sTNFR 1, sTNFR 2), and adhesion molecules (sE-selectin, sP-selectin, sVCAM-1, sICAM-1) over a 2-year follow-up of patients with coronary artery disease (CAD). The study involved 70 patients with stable CAD (stable angina class II/III according to the Canadian Cardiovascular Society) and 20 apparently healthy subjects. Over the follow-up period a marked attenuation of angina (P < 0.001) was observed. Interventional treatment (percutaneous coronary intervention, coronary artery bypass grafting) was used in 53 CAD patients. Laboratory analysis revealed a significant decrease of serum TNF-α and sTNFR1 at 2 years (TNF-α: 12.1 ± 0.7 pg/ml; sTNFR 1: 1306 ± 46 pg/ml) as compared to baseline levels (16.5 ± 0.7 pg/ml, P = 0.030; 1551 ± 82 pg/ml, P = 0.048, respectively). The levels of sP-selectin (159 ± 7 vs 201 ± 14 ng/ml, P < 0.01) and sICAM-1 (133 ± 4 vs 153 ± 6 ng/ml, P < 0.05) were found to be significantly increased as compared to the baseline. Interventional procedures resulted in suppression of both cytokine (TNF-α, sTNFR 2) and adhesion molecule (sE-selectin, sP-selectin) activation in the CAD group. The baseline and post-follow-up TNF-α and sTNFR 1 levels showed persistent elevation in CAD patients as compared to the controls (9.0, 956.3 pg/ml, respectively; P < 0.01). There were no differences between baseline and final cytokines and adhesion molecules in healthy subjects. The course of CAD as modified by a clinically effective therapy is characterized by changes of immune markers activation. Revascularization seems to be an important factor suppressing both cytokine and adhesion molecule activation in CAD patients.     

Angioplasty in ulcerative coronary artery disease: acute results and early follow-up.

The safety and efficacy of percutaneous transluminal coronary angioplasty (PTCA) for stenoses involving ulcerative lesions were retrospectively studied. Seventy-seven patients (62 men and 15 women, mean age 62 +/- 10 years) representing 3.4% of 2,250 patients treated with PTCA during the period January 1, 1988 and June 30, 1990, had pre-PTCA stenoses defined as ulcerated. Twenty-eight (36%) of the stenoses were localized in the left anterior descending coronary artery, 9 (12%) in the left circumflex and 40 (52%) in the right coronary artery. During angioplasty, percent diameter stenosis was reduced from 73 +/- 14% to 22 +/- 13% and transstenotic gradient decreased from 48 +/- 18 to 12 +/- 6 mm Hg. Clinical success (freedom from angina at discharge without coronary bypass surgery, infarction or death) was achieved in 70 patients (90.9%). There were seven unsuccessful cases: three underwent elective coronary bypass surgery, one was managed medically, and three developed a major flow interrupting dissection during the procedure requiring emergency coronary bypass surgery. There were no deaths. At mean follow-up of 7.6 months, 45 of 61 patients (73.7%) remained asymptomatic. One patient needed an elective coronary bypass surgery and five patients had a successful repeat PTCA. In conclusion, PTCA for an ulcerated stenosis can be performed safely with a high primary success rate and a favorable early clinical course.     

Incidence of coronary artery disease in siblings of patients with premature coronary artery disease: 10 years of follow-up

Although family history of premature coronary artery disease (CAD) confers increased risk of CAD, the magnitude of this increase beyond that expected from the risk factors incorporated in the Framingham Risk Equation (FRE) remains unknown. We prospectively determined the accuracy of the FRE 10-year incident CAD events prediction in initially healthy siblings of patients with documented premature CAD. We recruited 784 siblings (30 to 59 years) of 449 patients hospitalized with CAD <60 years of age (1983 to 1995). We compared the estimated 10-year incidence of total CAD events by the gender-specific FREs at baseline, to the observed incidence at 10 years of follow-up. In men, the 10-year actual CAD event rate was 20%, only half of which was predicted by the FRE (12% vs 20%, p <0.001). In women, the observed CAD event rate was 7.1% (p <0.001 vs men), modestly but not significantly greater than the 6.3% predicted by the FRE (p = 0.34). Thus, there was a significant 66.6% excess risk in men, and a nonsignificant 12.7% excess risk in women beyond the risk predicted by the FRE for total CAD events. The FRE and its known classic risk factor profile failed to accurately predict total incident 10-year CAD events in individuals with a sibling history of premature CAD, most particularly in men. In conclusion, in families with a history of premature CAD, the excess risk observed cannot be attributed to traditional risk factors, suggesting a major role for as yet undetermined genetic and other susceptibility factors.     

Obstructive sleep apnea as a risk marker in coronary artery disease

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with a range of cardiovascular sequelae and increased cardiovascular mortality. The aim of our study was to assess the prevalence of OSA in patients with symptomatic angina and angiographically verified coronary artery disease (CAD). In addition, we analyzed the association of OSA and other coronary risk factors with CAD and myocardial infarction. METHODS: Overnight non-laboratory-monitoring-system recordings for detection of OSA was performed in 223 male patients with angiographically verified CAD and in 66 male patients with exclusion of CAD. A logistic regression analysis was performed to assess associations between risk factors and CAD and myocardial infarction. RESULTS: CAD patients were found to have OSA in 30.5%, whereas OSA was found in control subjects in 19.7%. The mean apnea/hypopnea index (AHI) was significantly higher (p < 0.01) in CAD patients (9.9 +/- 11.8) than in control subjects (6.7 +/- 7.3). Body-mass-index (BMI) was significantly higher in patients with CAD and OSA than in patients with CAD without OSA (28. 1 vs. 26.7 kg/m(2); p < 0.001). No significant difference was found with regard to other risk factors and left ventricular ejection fraction (LVEF) between both groups. Hyperlipidemia (OR 2.3; CI 1. 3-3.9; p < 0.005) and OSA defined as AHI >/=20 (OR 2.0; CI 1.0-3.8, p < 0.05) were independently associated with myocardial infarction. CONCLUSIONS: There is a high prevalence of OSA among patients with angiographically proven CAD. OSA of moderate severity (AHI >/=20) is independently associated with myocardial infarction. Thus, in the care of patients with CAD, particular vigilance for OSA is important.