Germaine Loo

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention

Background— There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. Methods and Results— The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10–2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. Conclusions— OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

OSA and Coronary Plaque Characteristics

BACKGROUND Virtual histology intravascular ultrasound (VH-IVUS) is an intravascular imaging technique that enables the characterization of coronary plaques. We sought to determine the association between OSA and coronary plaque characteristics in patients presenting with coronary artery disease. METHODS We prospectively recruited patients with angiographically proven coronary artery disease for a VH-IVUS examination and home-based sleep study. The total atheroma volume of the entire target coronary artery and the incidence of thin cap fibroatheroma of patients with no to mild and moderate to severe OSA were compared. RESULTS One hundred eighteen patients were recruited from two university-affiliated centers. Among the 93 patients who completed the study, 32 (34.4%) had newly diagnosed moderate to severe OSA (apnea-hypopnea index > 15). Compared with patients with no to mild OSA, those with moderate to severe OSA had a larger total atheroma volume (461.3 ± 250.4 mm³ vs 299.2 ± 135.6 mm³, P < .001), and the association remained after adjustment for age, BMI, hypertension, diabetes mellitus, smoking, and hyperlipidemia (relative mean difference, 1.73; 95% CI, 1.38-2.15). In contrast, there were no significant differences between the patients with moderate to severe OSA and no to mild OSA regarding the prevalence of thin cap fibroatheroma in the culprit lesion (53.1% vs 54.2%, P = .919). CONCLUSIONS In patients presenting with coronary artery disease, moderate to severe OSA was independently associated with a larger total atheroma volume in the target coronary artery. Further studies on the effects of CPAP on total atheroma volume are warranted. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01306526; URL: www.clinicaltrials.gov.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study

BACKGROUND Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Effects of gender on the prevalence of obstructive sleep apnea in patients with coronary artery disease.

STUDY OBJECTIVE Male predominance has been observed in obstructive sleep apnea (OSA) studies conducted in the community and sleep clinics. Due to the different demographic and patient risk profiles of the studies involved, we investigated the effects of gender on OSA prevalence among patients with coronary artery disease (CAD). METHODS We prospectively recruited a cohort of CAD patients for an overnight sleep study using a home testing portable diagnostic device. OSA was defined as apnea-hypopnea index (AHI) ≥ 15. RESULTS One hundred sixty-two consecutive patients (male, n = 81; female, n = 81) were recruited, and most (60%) presented with acute coronary syndrome. The female patients were older (61 ± 10 versus 56 ± 10 years, p < 0.001), less likely to be smokers (8.6% versus 34.6%, p < 0.001), and more likely to have diabetes mellitus (70.4% versus 46.9%, p = 0.002) and chronic renal failure (17.3% versus 4.9%, p = 0.012) than the male patients. The sleep studys success rate was higher in female than male patients (88.9% versus 74.1%, p = 0.047). No significant differences were observed between them in the AHI, oxygen desaturation index, baseline SpO2, lowest SpO2, or total time SpO2 < 90%. The prevalence of OSA for the female and male patients was 40.3% and 35.0%, respectively (p = 0.323). CONCLUSION Prevalence of OSA is high in CAD patients with no evidence of sex predilection. The lack of male predominance could be due to females being older and with more comorbidities.

Determination of the severity of underlying lesions in acute myocardial infarction on the basis of collateral vessel development.

BackgroundWe aimed to address the conflict over whether the underlying lesion that leads to acute myocardial infarction (AMI) is representative of low-grade or high-grade stenosis. Because the development of collateral vessels is an indication of ischemia, their presence was used as a surrogate marker for the existence of a high-grade lesion. MethodsCoronary angiography was used to assess 159 patients, divided into two groups, with (Rentrop 1–3) and without (Rentrop 0) collateral vessels, who had AMI with ST-segment elevation for which they underwent a percutaneous coronary intervention with the implantation of a coronary stent and had baseline thrombolysis in myocardial infarction 0/1 flow. ResultsOf the 159 patients recruited, the presence of collateral vessels was detected in 95 (collateral group; 60%), indicating that the causal lesion was representative of a high-grade stenosis. Among these 95 patients, the Rentrop scores were 1, 2, and 3 in 57 (60%), 33 (34.7%), and six (5.3%) patients, respectively. Logistic regression analysis showed that a baseline thrombolysis in myocardial infarction 0 flow (hazard ratio, 4.6; 95% confidence interval, 1.4–14.6; P=0.01) and a culprit right coronary artery (hazard ratio, 3.0; 95% confidence interval, 1.4–6.2; P=0.007) were independent predictors of the development of collateral vessels. ConclusionThe majority of AMI cases can be attributed to a severe stenosis, as demonstrated by the presence of collateral vessels in 60% of the patients in this study.

Sleep-disordered Breathing in Cardiac Rehabilitation: Prevalence, Predictors, and Influence on the Six-Minute Walk Test

BACKGROUND Identification of non-traditional risk factors is an important component of cardiac rehabilitation (CR). However, the prevalence and predictors of sleep-disordered breathing (SDB) and its influence on exercise performance in patients attending CR remain poorly described. METHODS Patients enrolled in a national CR centre were eligible for a comprehensive SDB screening program. Screening questionnaires for SDB, overnight sleep study, and the 6-minute walk test (6MWT) were conducted. RESULTS We recruited 332 patients (mean age 62±10 years, 62.4% male) attending CR for primary (29.2%) or secondary (70.8%) prevention, of which 209 successfully completed the overnight sleep study. Sleep-disordered breathing group patients (n=68, 32.5%) were older and had a higher body mass index (BMI) and neck and waist circumferences than the non-SDB group patients. After adjusting for neck and waist circumference, age (OR=1.06; 95% CI 1.02-1.10; p=0.001) and BMI (OR=1.19; 95% CI 1.10-1.30; p<0.001) remained independent predictors of SDB. A high risk of SDB based on the Berlin Questionnaire (43.4% versus 35.5%, p=0.277) or STOP-BANG questionnaire (63.2% versus 53.2%, p=0.170) and excessive daytime sleepiness (Epworth Sleepiness Scale >10, 23.9% versus 17.7%, p=0.297) were similar between the groups. The 6MWT scores were significantly lower in the SDB than non-SDB group (mean difference -32 m; 95% CI -57-7; p=0.013). The relationship was no longer significant after adjusting for age, sex, and waist circumference. CONCLUSION Sleep-disordered breathing is prevalent in CR patients and is independently predicted by ageing and obesity. The association between SDB and poorer exercise performance may be explained by age, sex, and waist circumference.

Relationship between CHA65DS2 score and obstructive sleep apnea (CHA65DS2 and OSA)

(CHA65DS2 and OSA)☆ Germaine Loo , Liang Shen , Hee-Hwa Ho , A. Mark Richards , Paul Ong , Chi-Hang Lee a,d,⁎ a Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore b Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore c Department of Cardiology, Tan Tock Seng Hospital, Singapore d Department of Cardiology, National University Heart Centre, Singapore

Myocardial Infarction in Singapore: Ethnic Variation in Evidence-Based Therapy and Its Association with Socioeconomic Status, Social Network Size and Perceived Stress Level

BACKGROUND Singapore is a multiethnic Asian country comprising predominantly Chinese, Malays, and Indians. We sought to study the disparities in evidence-based therapy for people from these three ethnic groups who were admitted to hospital with ST-segment elevation myocardial infarction (STEMI). We also examined its association with socioeconomic level and social network size and the influence on psychological stress level. METHODS In a prospective study, patients admitted with STEMI were recruited for a questionnaire survey. Relevant demographic and clinical data were collected. RESULTS A total of 364 patients were recruited and categorised based on ethnicity: Chinese (222 patients), Malays (72 patients), and Indians (70 patients). Malays and Indians were significantly younger than Chinese at the time of presentation with STEMI. Malays had significantly more children than the Chinese and Indians. Malays were in the lowest socioeconomic class, based on education level (P ≤ .02) and residential type (P ≤ .003). Most (87%) patients were treated with primary percutaneous coronary intervention. There were no significant differences between Chinese, Malays, and Indians in accessibility to primary percutaneous coronary intervention, symptom-to-balloon time, door-to-balloon time, and prescription of evidence-based medications. Malays had larger social networks for information support (P ≤ .05) and financial support (P ≤ .04) than Chinese and Indians. There were no significant differences between the three ethnic groups in satisfaction with social support. The perceived stress level was higher among Malays and Indians than Chinese. CONCLUSIONS Although Malays were underprivileged in the socioeconomic level, no significant difference in healthcare disparities were observed among the three ethnic groups. This may be a reflection of the advancement in Singapores healthcare system. The lower socioeconomic level may also explain the higher perceived stress level in Malays.

Optimal Body Mass Index Cut-offs for Identification of Patients with Coronary Artery Disease at High Risk of Obstructive Sleep Apnoea

BACKGROUND We sought to evaluate the relationship between Body Mass Index (BMI) and obstructive sleep apnoea (OSA) in Chinese patients hospitalised with coronary artery disease, and to determine the optimal BMI cut-off for prediction of OSA. METHODS Consecutive Chinese patients who were hospitalised with symptomatic coronary artery disease were recruited to undergo an in-hospital sleep study. RESULTS A total of 587 patients were recruited. Using cut-off for Asians, 81.2% of the cohort was overweight (BMI ≥23kg/m(2)) and 31.6% was obese (≥27kg/m(2)). A total of 59.5% was diagnosed with OSA, defined as apnoea-hypopnoea index ≥15. Body mass index, hypertension and smoking were predictors of OSA. Multiple logistic regression analysis showed that BMI remains an independent predictor of OSA (odds ratio: 1.11 [95% confidence interval: 1.06 to 1.17], p<0.001) after adjusting for smoking and hypertension. Further analysis using BMI and Apnoea-Hypopnoea Index (AHI) as continuous variables showed significant correlation between BMI and AHI (Pearsons r =0.25, P<0.001). In adjusted models, optimal BMI cut-offs to screen for OSA were 27.3kg/m(2), 23.0-23.9kg/m(2), and 20kg/m(2) for patients with neither, either, or both predictors (smoking and hypertension) respectively. The area under the curve for the adjusted and unadjusted models were similar (0.6013 vs 0.6262, p=0.118). CONCLUSIONS Body mass index represents a convenient and readily available tool for bedside identification of patients at high risk of OSA. Body mass index cut-offs to predict risks of OSA in Chinese patients with symptomatic coronary artery disease are defined in this study.

Culprit versus non-culprit lesion related adverse cardiac events in patients with obstructive sleep apnoea.

Background In patients with obstructive sleep apnoea (OSA), the relative contribution of culprit versus non-culprit lesions to subsequent major adverse cardiac events (MACE) after acute myocardial infarction (AMI) remains unknown. Elucidating this relationship will shed light on the contributions of OSA to the advancement of coronary artery disease. Methods In a cohort of 105 patients who underwent an overnight sleep study after AMI, 98 were diagnosed with OSA (Apnoea–Hypopnoea Index (AHI) ≥5). The clinical outcomes at 5-year follow-up were determined. MACE was defined as a composite of cardiac death, reinfarction and repeat revascularisation. A culprit lesion was defined as the lesion involved in the initial AMI, and a non-culprit lesion as any lesion in the entire coronary tree outside the culprit lesion. Results Eighteen patients (median AHI: 28.1) developed MACE, of whom 12 presented with reinfarction and 6 with repeat revascularisation for stable angina. There was no cardiac death. Based on repeated coronary angiography, the MACE was related to the culprit lesion in 4 patients and the non-culprit lesion in 12 patients. The lesion responsible for the MACE was indeterminate in 2 patients, as coronary angiography was declined. The median duration from index AMI to culprit lesion-related and non-culprit lesion-related MACE were 10.5 and 20 months, respectively. Conclusions The incidence of MACE among patients with OSA and AMI was 18.4%, and most of the events were related to non-culprit lesions rather than the culprit lesion during the initial AMI.