Clinical predictors and outcomes of ST-elevation myocardial infarction related cardiogenic shock in the Asian population.

Background: Cardiogenic shock (CS) complicating myocardial infarction is associated with poor outcomes. Data among Asian populations are scarce. We aimed to investigate the long-term outcomes, prognostic factors, and predictors of CS among Asian ST elevation myocardial infarction (STEMI) patients. Methods: This was a retrospective cohort study of consecutive patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI within our regional STEMI network between 2015 and 2019. The long-term outcomes of those with and without CS were compared. Clinical predictors of outcomes and development of CS were investigated. Results: A total of 1791 patients who underwent PPCI were included. Patients completed at least 2 years' follow-up with a median follow-up period of 2.6 years (IQR 1.0, 3,9). Overall, 208/1791 (11.6 %) STEMI patients developed CS. These patients were older (61.1 ± 12.5 vs 57.8 ± 12.2, P < 0.001) and mostly men (87.0 %). All-cause mortality (59.9 % vs 4.7 % P < 0.001), cardiac mortality (43.8 % vs 2.2 %, P < 0.001) and major adverse cardiovascular events (MACE) was significantly higher in the CS group (59.1 % vs 14.0 %, P < 0.001). Independent predictors of survival were higher index LVEF (adjusted hazards ratio [aHR] 0.967, 95 %CI 0.951-0.984, p < 0.001) and higher arterial pH at onset of shock (aHR 0.750, 0.626-0.897, p = 0.002). Increased serum lactate concentration independently predicts poor prognosis (aHR 1.084, 95 % CI 1.046-1.124, p < 0.001). Conclusion: In Asian STEMI patients who underwent PPCI, CS was associated with poor outcomes. Higher LVEF on index admission was associated with better outcomes; while lactic acidosis independently predicted mortality.

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions.

Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).

Long-term effect of obstructive sleep apnoea management on blood pressure in patients with resistant hypertension: the SARAH study.

BACKGROUND: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking. METHODS: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed. RESULTS: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h-1. The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up. CONCLUSION: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Remote intensive management to improve antiplatelet adherence in acute myocardial infarction: a secondary analysis of the randomized controlled IMMACULATE trial.

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.

Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting.

STUDY OBJECTIVES: In coronary artery bypass grafting (CABG), abnormal cardiac repolarization is associated with adverse cardiovascular events that can be measured via the QTc interval. We investigated the impact of obstructive sleep apnea on the change in repolarization after CABG and the association of change in repolarization with the occurrence of major adverse cardiac and cerebrovascular events. METHODS: A total of 1,007 patients from 4 hospitals underwent an overnight sleep study prior to a nonemergent CABG. Electrocardiograms of 954 patients (median age: 62 years; male: 86%; mean follow-up: 2.1 years) were acquired prospectively within 48 hours before CABG (T1) and within 24 hours after CABG (T2). QTc intervals were measured using the BRAVO algorithm by Analyzing Medical Parameters for Solutions LLC. The change in T2 from T1 for QTc (ΔQTc) was derived, and Cox regression was performed. RESULTS: Compared with those without, patients who developed major adverse cardiac and cerebrovascular events (n = 115) were older and had (1) a higher prevalence of smoking, hypertension, diabetes mellitus, and chronic kidney disease; (2) a higher apnea-hypopnea index and oxygen desaturation index; and (3) a smaller ΔQTc. Cox regression analysis demonstrated a smaller ΔQTc to be an independent risk factor for major adverse cardiac and cerebrovascular events (hazard ratio: 0.997; P = .032). In the multivariable regression model, a higher oxygen desaturation index was independently associated with a smaller ΔQTc (correlation coefficient: -0.58; P < .001). CONCLUSIONS: A higher preoperative oxygen desaturation index was an independent predictor of a smaller ΔQTc. ΔQTc within 24 hours after CABG could be a novel predictor of occurrence of major adverse cardiac and cerebrovascular events at medium-term follow-up. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Undiagnosed Sleep Apnea and Bypass OperaTion (SABOT); URL: https://classic.clinicaltrials.gov/ct2/show/NCT02701504; Identifier: NCT02701504. CITATION: Teo YH, Yong CL, Ou YH, et al. Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting. J Clin Sleep Med. 2024;20(1):49-55.

Global Registry of Acute Coronary Events Score Underestimates Post-Acute Coronary Syndrome Mortality among Cancer Patients.

Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore. A total of 24,529 eligible patients had in-hospital and 1-year all-cause mortality risk calculated using the GRACE score (2471 prior cancer; 22,058 no cancer). Results Patients with prior cancer had two-fold higher all-cause mortality compared to patients without cancer (in-hospital: 22.8% versus 10.3%, p < 0.001; 1-year: 49.0% vs. 18.7%, p < 0.001). Cardiovascular mortality did not differ between groups (in-hospital: 5.2% vs. 4.8%, p = 0.346; 1-year: 6.9% vs. 6.1%, p = 0.12). The area under the receiver operating characteristic curve of the GRACE score for prediction of all-cause mortality was less for prior cancer (in-hospital: 0.64 vs. 0.80, p < 0.001; 1-year: 0.66 vs. 0.83, p < 0.001). Among patients with prior cancer and a high-risk GRACE score > 140, in-hospital revascularization was not associated with lower cardiovascular mortality than without in-hospital revascularization (6.7% vs. 7.6%, p = 0.50). Conclusions The GRACE score performs poorly in risk stratification of patients with prior cancer and ACS.

Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol.

Background: Diffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD. Methods: Role of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan. Discussion: REVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort.

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

Obstructive sleep apnoea and coronary revascularisation outcomes.

Obstructive sleep apnoea (OSA) is a chronic sleep disorder characterised by recurrent cyclical episodes of upper airway collapse causing apnoea or hypopnoea. Despite being highly prevalent in patients with cardiovascular conditions, OSA has been a neglected component in cardiovascular practice. Fortunately, in the past few decades, increasing acknowledgement of the vulnerability of cardiac patients to OSA-related stressors and its adverse cardiovascular outcomes has made it a recognised cardiovascular risk factor in practice guidelines. Consequences of OSA include oxidative stress, endothelial dysfunction, autonomic dysfunction, and increased catecholamine release. The perturbations caused by OSA not only provide a clear mechanistic link to cardiovascular disease but also to poor outcomes after coronary revascularisation. This review article focuses on the correlation of OSA to coronary revascularisation outcomes. Our team reported that OSA is present in approximately 50% of patients undergoing coronary revascularisation. Importantly, untreated OSA was found to be an independent predictor of adverse events after both percutaneous coronary intervention and coronary artery bypass grafting. Although randomised trials did not confirm the benefits of OSA treatment in improving cardiovascular outcomes, these early trials were limited by poor treatment adherence. For now, systematic screening for OSA in patients undergoing coronary revascularisation is not indicated. Yet, with the proven benefit of OSA treatment in improving blood pressure control and quality of life, screening for and treatment of OSA is still indicated if patients have reported excessive daytime sleepiness and/or suboptimally controlled hypertension.

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.

Mandibular advancement device versus CPAP in lowering 24-hour blood pressure in patients with obstructive sleep apnoea and hypertension: the CRESCENT trial protocol.

INTRODUCTION: Although treatment of obstructive sleep apnoea (OSA) using continuous positive airway pressure (CPAP) reduces blood pressure (BP), adherence to CPAP is often suboptimal. A mandibular advancement device (MAD) is a guideline-endorsed alternative therapy for OSA. Still, there is limited evidence on the relative efficacy between MAD and CPAP on BP reduction. We evaluate whether treatment of moderate-to-severe OSA using MAD can improve BP and other health-related outcomes compared with CPAP. METHODS AND ANALYSIS: This is a randomised, controlled, non-inferiority trial conducted. We will recruit 220 Asians with a history of hypertension and high cardiovascular risk for an overnight polysomnography screening. Those with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events/hour) will be randomised to treatment with either MAD or CPAP in a 1:1 ratio. Stratified by age (60 vs <60 years old), body mass index (25 vs <25 kg/m2) and apnoea-hypopnoea index (30 vs <30 events/hour), an adaptive randomisation scheme with permuted blocks constructed in real-time is implemented to restrict imbalance. The overall study duration is 12 months. The primary endpoint is the 24-hour mean arterial BP difference between baseline and 6-month follow-up. The secondary endpoints include other measures of ambulatory BP monitoring, arrhythmia based on a 4-day electrocardiographic monitoring, biomarker and proteomic analysis, cardiovascular magnetic resonance-derived myocardial fibrosis and remodelling and quality-of-life questionnaires. Recruitment began in October 2019 and ended in December 2022. Comparison between MAD and CPAP will be performed using covariance (ANCOVA) analysis of the changes in 24-hour mean arterial BP while adjusting for the baseline 24-hour mean arterial BP. We will compare the 95% CIs around the treatment difference point estimate with the prespecified non-inferiority margin (1.5 mm Hg). If the upper limit of the 95% CI is <1.5 mm Hg and crosses 0, non-inferiority of the MAD relative to CPAP will be established. ETHICS AND DISSEMINATION: The Domain Specific Review Board-C, National Healthcare Group under approved the study protocol (NHG DSRB Ref: 2019/00359, approved on 28 August 2019). Study findings will be disseminated to various local, national, and international audiences through abstract presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04119999.

The Belun sleep platform to diagnose obstructive sleep apnea in patients with hypertension and high cardiovascular risk.

STUDY OBJECTIVE: Current hypertension guidelines recommend that at-risk individuals be screened for obstructive sleep apnea (OSA). The Belun Ring is a wearable OSA diagnostic device worn on the palmar side of the proximal phalanx of the index finger. METHODS: We recruited 129 participants (age: 60 ±â€Š8 years, male sex: 88%, BMI: 27 ±â€Š4 kg/m 2 ) with hypertension and high cardiovascular risk for a simultaneous polysomnography and Belun Ring monitoring for one night. Epworth Sleepiness Scale score more than 10 was detected in 27 (21.0%) participants. RESULTS: In the 127 participants who completed the study, the apnea-hypopnea index (AHI) derived from polysomnography was 18.1 (interquartile range: 33.0) events/h and that derived from the Belun Ring was 19.5 (interquartile range: 23.3) events/h [intraclass correlation coefficient: 0.882, 95% confidence interval (95% CI): 0.837-0.916]. A Bland-Altman plot showed the difference between the Belun Ring and polysomnography AHIs to be -1.3 ±â€Š10.4 events/h. Area under the receiver operating characteristic for the Belun Ring AHI was 0.961 (95% CI: 0.932-0.990, P  < 0.001). When the Belun Ring AHI of at least 15 events/h was used to diagnose OSA, the sensitivity, specificity, positive predictive value, and negative predictive value were 95.7, 77.6, 85.3, and 93.8%, respectively. The overall accuracy was 87.4%. The Cohen's kappa agreement was 0.74 ±â€Š0.09 ( P  < 0.001). Similar results were obtained when the oxygen desaturation index was used to diagnose OSA. CONCLUSION: A high prevalence of OSA was detected in patients with hypertension and high cardiovascular risk. The Belun Ring is a reliable device for OSA diagnosis similar to polysomnography.

Clinical profile and outcomes in patients with moderate to severe aortic stenosis with or without concomitant chronic kidney disease.

Introduction: Management of aortic stenosis (AS) in patients with chronic kidney disease (CKD) may often be overlooked, and this could confer poorer outcomes. Methods: Consecutive patients (n = 727) with index echocardiographic diagnosis of moderate to severe AS (aortic valve area <1.5 cm2) were examined. They were divided into those with CKD (estimated glomerular filtration rate < 60 mL/min) and those without. Baseline clinical and echocardiographic parameters were compared, and a multivariate Cox regression model was constructed. Clinical outcomes were compared using Kaplan-Meier curves. Results: There were 270 (37.1%) patients with concomitant CKD. The CKD group was older (78.0 ± 10.3 vs. 72.1 ± 12.9 years, P < 0.001), with a higher prevalence of hypertension, diabetes mellitus, hyperlipidaemia and ischaemic heart disease. AS severity did not differ significantly, but left ventricular (LV) mass index (119.4 ± 43.7 vs. 112.3 ± 40.6 g/m2, P = 0.027) and Doppler mitral inflow E to annular tissue Doppler e' ratio (E: e' 21.5 ± 14.6 vs. 17.8 ± 12.2, P = 0.001) were higher in the CKD group. There was higher mortality (log-rank 51.5, P < 0.001) and more frequent admissions for cardiac failure (log-rank 25.9, P < 0.001) in the CKD group, with a lower incidence of aortic valve replacement (log-rank 7.12, P = 0.008). On multivariate analyses, after adjusting for aortic valve area, age, left ventricular ejection fraction and clinical comorbidities, CKD remained independently associated with mortality (hazard ratio 1.96, 95% confidence interval 1.50-2.57, P < 0.001). Conclusion: Concomitant CKD in patients with moderate to severe AS was associated with increased mortality, more frequent admissions for cardiac failure and a lower incidence of aortic valve replacement.

Management of hypertension in obstructive sleep apnea.

Obstructive sleep apnea (OSA) plays an important role in the development of hypertension. Thus, this review summarizes pharmacological and non-pharmacological approaches to blood pressure (BP) control in patients with OSA. Current treatments for OSA, such as continuous positive airway pressure, are effective at lowering BP. However, they only provide a modest BP reduction, and pharmacological treatment remains important for achieving optimal BP control. Furthermore, current guidelines for the treatment of hypertension do not make specific recommendations on pharmacological treatment protocols for controlling BP in patients with OSA. Moreover, the BP-lowering effects of various classes of antihypertensives may be different in hypertensive patients with OSA than in those without OSA due to the underlying mechanisms that promote hypertension in OSA. The acute and chronic increase in sympathetic nerve activity in patients with OSA explain the effectiveness of beta blockers in controlling BP in these patients. As activation of the renin-angiotensin-aldosterone system may also promote hypertension in OSA, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have generally been found effective for lowering BP in hypertensive patients with OSA. The aldosterone antagonist spironolactone also produces a good antihypertensive response in patients with OSA and resistant hypertension. However, there are limited data available that compare the effects of various classes of antihypertensive medication on BP control in those with OSA, and most data have been obtained from small-scale studies. This demonstrates the need for large-scale randomized controlled trials to evaluate a range of BP-lowering regimens in patients with OSA and hypertension.

Vascular smooth muscle cells in low SYNTAX scores coronary artery disease exhibit proinflammatory transcripts and proteins correlated with IL1B activation.

BACKGROUND AND AIMS: The SYNTAX score is clinically validated to stratify number of lesions and pattern of CAD. A better understanding of the underlying molecular mechanisms influencing the pattern and complexity of coronary arteries lesions among CAD patients is needed. METHODS: Human arterial biopsies from 49 patients (16 low-SYNTAX-score (LSS, <23), 16 intermediate-SYNTAX-score (ISS, 23 to 32) and 17 high-SYNTAX-score (HSS, >32)) were evaluated using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray. The data were validated by Next-Generation Sequencing (NGS). Primary VSMC from patients with low and high SYNTAX scores were isolated and compared using immunohistochemistry, qPCR and immunoblotting to confirm mRNA and proteomic results. RESULTS: The IL1B was verified as the top upstream regulator of 47 inflammatory DEGs in LSS patients and validated by another sets of patient samples using NGS analysis. The upregulated expression of IL1B was translated to increased level of IL1ß protein in the LSS tissue based on immunohistochemical quantitative analysis. Plausibility of idea that IL1B in the arterial wall could be originated from VSMC was checked by exposing culture to proinflammatory conditions where IL1B came out as the top DEG (logFC = 7.083, FDR = 1.38 × 10-114). The LSS patient-derived primary VSMCs confirmed higher levels of IL1B mRNA and protein. CONCLUSIONS: LSS patients could represent a group of patients where IL1B could play a substantial role in disease pathogenesis. The LSS group could represent a plausible cohort of patients for whom anti-inflammatory therapy could be considered.

Hour-to-hour variability of respiratory sleep indices and ambulatory blood pressure.

STUDY OBJECTIVES: Respiratory sleep indices are traditionally reported on the basis of the average total sleep time. The relationship between the hour-to-hour variability of these parameters and blood pressure (BP) has not been reported. METHODS: We evaluated the associations of the hour-to-hour variability of the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and lowest oxygen saturation with the 24-h ambulatory BP in patients with hypertension and newly diagnosed obstructive sleep apnea. A total of 147 patients underwent polysomnography, based on which obstructive sleep apnea was diagnosed in 106 patients; these patients underwent 24-h ambulatory BP monitoring within the next 30 days. Each polysomnogram was divided into hourly reports to calculate the variability of the respiratory sleep indices. Variability independent of the mean was considered the primary measure of variability. RESULTS: The median number of hourly polysomnogram reports was 7 (range, 4-8). The hour-to-hour variability of both AHI and ODI, but not of the lowest oxygen saturation, was correlated with the 24-h pulse pressure, 24-h systolic BP, and awake systolic BP (p < 0.05 for all). The fully adjusted linear regression analysis indicated that the hour-to-hour variability of AHI and ODI remained associated with the 24-h pulse pressure (AHI: ß coefficient, 0.264 [95% CI = 0.033-0.495], p = 0.026; ODI: ß coefficient, 0.450 [95% CI = 0.174-0.726], p = 0.002). CONCLUSIONS: The hour-to-hour variability of AHI and ODI is independently associated with the 24-h pulse pressure. Further investigations are warranted to evaluate the clinical relevance of this new-found association.