Unique characteristics of Asians with hypertension: what is known and what can be done?

Hypertension remains the leading modifiable risk factor for cardiovascular disease worldwide. Over the past 30 years, the prevalence of hypertension has been increasing in East and Southeast Asia to a greater extent as compared with other Western countries. Asians with hypertension have unique characteristics. This can be attributed to increased impact of obesity on Asians with hypertension, excessive salt intake and increased salt sensitivity, loss of diurnal rhythm in blood pressure and primary aldosteronism. The impact of hypertension on cardiovascular (particularly strokes) and chronic kidney disease is greater in Asians. These unique characteristics underpinned by the diverse socioeconomic backgrounds pose its own challenges in the diagnosis and management of hypertension in Asia.

Impact of Diabetes on Myocardial Fibrosis in Patients With Hypertension: The REMODEL Study.

BACKGROUND: Compared with patients with hypertension only, those with hypertension and diabetes (HTN/DM) have worse prognosis. We aimed to characterize morphological differences between hypertension and HTN/DM using cardiovascular magnetic resonance; and compare differentially expressed proteins associated with myocardial fibrosis using high throughput multiplex assays. METHODS: Asymptomatic patients underwent cardiovascular magnetic resonance: 438 patients with hypertension (60±8 years; 59% males) and 167 age- and sex-matched patients with HTN/DM (60±10 years; 64% males). Replacement myocardial fibrosis was defined as nonischemic late gadolinium enhancement on cardiovascular magnetic resonance. Extracellular volume fraction was used as a marker of diffuse myocardial fibrosis. A total of 184 serum proteins (Olink Target Cardiovascular Disease II and III panels) were measured to identify unique signatures associated with myocardial fibrosis in all patients. RESULTS: Despite similar left ventricular mass (P=0.344) and systolic blood pressure (P=0.086), patients with HTN/DM had increased concentricity and worse multidirectional strain (P<0.001 for comparison of all strain measures) compared to hypertension only. Replacement myocardial fibrosis was present in 28% of patients with HTN/DM compared to 16% of those with hypertension (P<0.001). NT-proBNP (N-terminal pro-B-type natriuretic peptide) was the only protein differentially upregulated in hypertension patients with replacement myocardial fibrosis and independently associated with extracellular volume. In patients with HTN/DM, GDF-15 (growth differentiation factor 15) was independently associated with replacement myocardial fibrosis and extracellular volume. Ingenuity Pathway Analysis demonstrated a strong association between increased inflammatory response/immune cell trafficking and myocardial fibrosis in patients with HTN/DM. CONCLUSIONS: Adverse cardiac remodeling was observed in patients with HTN/DM. The novel proteomic signatures and associated biological activities of increased immune and inflammatory response may partly explain these observations.

A case report of bidirectional ventricular tachycardia secondary to aconitum toxicity.

We present a case of malignant ventricular arrhythmia secondary to unintentional aconite poisoning. Healthcare workers need to be vigilant regarding cases of aconitum toxicities, especially in atypical presentations. There is also a need to educate the public regarding the consumption and preparation of potent TCM herbs that may result in lethal toxicity.

Echocardiographic Global Longitudinal Strain Is Associated With Myocardial Fibrosis and Predicts Outcomes in Aortic Stenosis.

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.

Awareness and Attitudes of Community-Dwelling Individuals in Singapore towards Participating in Advance Care Planning.

INTRODUCTION: Advance care planning (ACP) is an important aspect of end-of-life care that has been shown to improve patient autonomy in decision-making and reduce stress for surviving family members. Given the rapidly ageing population in Singapore, a greater emphasis on end-of-life care planning is needed. This study therefore sought to examine the awareness and attitudes of the general Singaporean community towards participating in ACP, which are not known hitherto. MATERIALS AND METHODS: A 24-item interviewer-administered questionnaire was constructed and administered via door-to-door survey amongst community-dwelling residents living in Housing and Development Board (HDB) flats across Singapore, selected via a two-stage stratified random sampling. RESULTS: Of the 406 completed surveys, 14.4% of respondents had heard of ACP (n = 58), mostly through the media (67.9%), from family and friends (21.4%) and healthcare providers (21.4%). Only 26.8% of those who had previously heard of ACP knew how to begin an ACP discussion and 12.5% of them had a prior ACP discussion. After education, the majority of respondents were willing to begin an ACP discussion (n = 236, 60.1%). Being of an older age, having a life threatening illness, and having more knowledge about ACP were significant factors associated with willingness to have an ACP discussion. Barriers included perceiving oneself as still healthy and preferring the family to make decisions instead. CONCLUSION: There is a low awareness but high expressed willingness to engage in an ACP discussion amongst the Singaporean community. More efforts are needed to educate the public about ACP, engage the family unit and correct the present misconceptions.

Screening for Obstructive Sleep Apnea in the Assessment of Coronary Risk.

There is increasing awareness that health screening may prevent some acute coronary events. Yet, obstructive sleep apnea (OSA) is seldom screened for and its relation with coronary risk markers is not well established. Consecutive adults (n = 696) enrolled in a cardiovascular health screening program were approached to determine the feasibility of incorporating OSA screening. Screening included questionnaires and a home-based sleep study. High-sensitivity C-reactive protein was the primary coronary risk marker, and other laboratory- and exercise treadmill-based markers were also reported. Two thirds of the participants (66%) agreed to undergo OSA screening and most (78%) successfully completed the sleep study. The prevalence of OSA (apnea-hypopnea index ≥15/hour) was 38.0%. The Berlin Questionnaire (53%) and Epworth Sleepiness Scale (26%) had low sensitivity in identifying OSA. After full adjustment for age, gender, body mass index, hypertension, and diabetes mellitus, OSA remained an independent predictor of serum levels of high-sensitivity C-reactive protein (relative mean difference 1.29, 95% CI 1.03 to 1.62; p = 0.025), triglyceride (relative mean difference 1.15, 95% CI 1.03 to 1.28; p = 0.014), and exercise time (mean difference -26.4 seconds; 95% CI -51.6 to -1.2; p = 0.04). The INTERHEART Risk Score analysis suggested more participants with (31%) than without (14%, p <0.001) OSA will develop future cardiovascular events. In conclusion, based on the acceptance for OSA screening, high prevalence of OSA and independent associations between OSA and coronary risk markers, incorporation of sleep studies into cardiovascular health screening programs appears feasible.

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.

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.

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 (Pearson's 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.

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.

Cardiac Rehabilitation After Percutaneous Coronary Intervention in a Multiethnic Asian Country: Enrollment and Barriers.

OBJECTIVE: To determine the enrollment or barriers to cardiac rehabilitation (CR) among Asian patients who have undergone percutaneous coronary intervention (PCI). DESIGN: Prospective observational study. SETTING: Department of cardiology at a university hospital. PARTICIPANTS: Patients (N=795) who underwent PCI between January 2012 and December 2013 at a tertiary medical institution. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Data on enrollment in phase 2 CR and its barriers were collected by dedicated CR nurses. RESULTS: Of 795 patients, 351 patients (44.2%) were ineligible for CR because of residual coronary stenosis, while 30 patients (3.8%) were not screened because of either early discharge or death. Of the remaining 416 patients (90.8% men; mean age, 55 y), 365 (87.7%) declined CR participation and 51 (12.3%) agreed to participate. Of these 51 patients, 20 (39%) did not proceed to enroll and 4 (8%) dropped out, leaving 27 patients (53%) who completed at least 6 sessions of the CR program. The top 3 reasons provided by patients who declined to participate in CR were (1) busy work schedules (37.5%), (2) no specific reason (26.7%), and (3) preference for self-exercise (20.1%). Nonsmokers were more likely to participate in CR (P=.001). CONCLUSIONS: CR participation of Asian patients after PCI was found to be lower than that reported in Western countries. The exclusion criteria used in the institution under study differed from those provided by international associations. A busy work schedule was the most common reason for declining CR after PCI.

Relationship between severity of obstructive sleep apnea and adverse cardiac outcomes in non-diabetic patients presenting with myocardial infarction.

Previous studies that have reported an association between obstructive sleep apnea and adverse cardiac events were confounded by a high prevalence of diabetes mellitus. We investigated the relationship between obstructive sleep apnea and the occurrence of major adverse cardiac events in non-diabetic patients who presented with ST-segment elevation myocardial infarction. A total of 41 patients who underwent overnight sleep screening within 5 days after admission for myocardial infarction from January 2007 to December 2008 were identified. Major adverse cardiac events-defined as a composite of cardiac death, non-fatal myocardial infarction, hospitalization for angina and congestive heart failure at 5-year follow-up-were determined. The patients were divided into two groups: those who experienced major adverse cardiac events and those who did not. In the overall cohort, the prevalence of obesity was 4.9 %. A total of 13 (31.7 %) patients had major adverse cardiac events. The mean apnea-hypopnea index was 25.4 ± 20.3. The group that experienced major adverse cardiac events had a higher apnea-hypopnea index than the group that did not (36.1 ± 21.0 vs 20.4 ± 18.2; P = 0.016). After adjusting for the resolution of ST-segment elevation and the use of a glycoprotein IIb/IIIa inhibitor, logistic regression analysis revealed that the apnea-hypopnea index remained an independent predictor of major adverse cardiac events (odds ratio 1.044; 95 % confidence interval 1.003-1.086; P = 0.033). In non-diabetic patients, the severity of obstructive sleep apnea was associated with the occurrence of major adverse cardiac events at 5-year follow-up after ST-segment elevation myocardial infarction.

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 study's 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.

Incidence and predictors of side-branch compromise in primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVE: We aimed to determine the incidence and predictors of side-branch compromise (SBC) in patients who underwent primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Little data exist on SBC in AMI patients, especially in the drug-eluting stent era. METHODS: We recruited 174 patients who underwent primary PCI over a 12-month period. After reviewing their coronary angiograms, we included for analysis 102 patients with a side branch >2 mm arising from the culprit lesion and that was spanned by a coronary stent. SBC was defined as post-stent implantation TIMI flow of <3 in the side branch. RESULTS: Among the 102 patients analyzed, drug-eluting stents (n = 77), bare-metal stents (n = 17), and bioresorbable vascular scaffolds (n = 8) were used to treat the culprit lesions. Final TIMI flow of the main vessel was 2 or 3 in 101 patients (99%). SBC occurred in 23 patients (final side branch TIMI flow 0, n = 6; TIMI 1, n = 4; TIMI 2, n = 13), giving an incidence of 22.5%. Multivariate analysis showed non-left anterior descending (LAD) culprit vessel (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.22-10.95; P=.02), higher peak creatine kinase level (OR, 1.03 for every 100-unit increase; 95% CI, 1.01-1.05; P=.01), and Rentrop score of 2/3 (OR, 3.57; 95% CI, 0.98-13.04; P=.055) to be independent predictors of SBC. CONCLUSIONS: The incidence of SBC was 22.5%. The independent predictors of SBC were non-LAD culprit vessel, larger infarct size, and good collateral vessel formation.

Impact of obstructive sleep apnea on cardiovascular outcomes in patients treated with percutaneous coronary intervention: rationale and design of the sleep and stent study.

Elucidating the effects of obstructive sleep apnea (OSA) on cardiovascular outcomes is crucial in risk assessments and therapeutic recommendations for affected individuals. The Sleep and Stent Study is a multicenter observational study investigating the relationships between OSA and cardiovascular outcomes in patients treated with percutaneous coronary intervention (PCI). Eight centers in 5 countries (Singapore, China and Hong Kong, India, Myanmar, and Brazil) are participating in the study, and the recruitment target is 1600 patients. Adult patients age 18 to 80 years who have undergone successful PCI are eligible. Recruited patients will undergo an overnight sleep study using a level-3 portable diagnostic device before hospital discharge. The sleep tracings will be analyzed by a certified sleep technologist and audited by a sleep physician, both of whom will be blinded to other study data. The patients will be divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The primary study endpoint of cardiovascular death, myocardial infarction, stroke, and unplanned revascularization will be compared between the OSA and non-OSA groups at a median follow-up of 2 years. Secondary endpoints include all-cause mortality, target-vessel revascularization, stent thrombosis, and hospitalization for heart failure. As of December 31, 2013, a total of 1358 patients have been recruited. Based on the complete preliminary results of the first 785 recruited patients, the prevalence of OSA was 48.3%. We expect the follow-up for primary endpoint to be completed in late 2015; study results will be presented in 2016.