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Fulltext Retinol-Binding Protein-4-A Predictor of Insulin Resistance and the Severity of Coronary Artery Disease in Type 2 Diabetes Patients with Coronary Artery Disease

Perumalsamy S, Ahmad WAW, Huri HZ

Biology (Basel), 2021 Sep 01;10(9).
PMID: 34571734 DOI: 10.3390/biology10090858

(1) Background: Insulin resistance (IR) is the fundamental cause of type 2 diabetes (T2D), which leads to endothelial dysfunction and alters systemic lipid metabolism. The changes in the endothelium and lipid metabolism result in atherosclerotic coronary artery disease (CAD). In insulin-resistant and atherosclerotic CAD states, serum cytokine retinol-binding protein-4 (RBP-4) levels are elevated. The adipocyte-specific deletion of glucose transporter 4 (GLUT4) results in higher RBP-4 expression and IR and atherosclerotic CAD progression. (2) Aim: This study aimed to investigate the association of RBP-4 and clinical factors with IR and the severity of CAD. (3) Methods: Patients were recruited from diabetes and cardiology clinics and divided into three subgroups, namely (i) T2D patients with CAD, (ii) T2D-only patients, and (iii) CAD-only patients. The severity of CAD was classified as either single-vessel disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD). An enzyme-linked immunosorbent assay was conducted to assess the concentration of serum RBP-4. Univariate (preliminary analysis) and multivariate (secondary analysis) logistic regressions were applied to assess the associations of RBP-4 and clinical factors with IR and the severity of CAD. (4) Results: Serum RBP-4 levels were associated with IR and the severity of CAD in all the three groups (all p-values are less than 0.05). Specifically, serum RBP-4 levels were associated with IR (p = 0.030) and the severity of CAD (SVD vs. DVD, p = 0.044; SVD vs. TVD, p = 0.036) in T2D patients with CAD. The clinical factors fasting plasma glucose (FPG) and angiotensin-converting-enzyme inhibitor (ACEI) were also associated with both IR and the severity of CAD in T2D patients with CAD. (5) Conclusion: RBP-4, FPG, and ACEI are predictors of IR and severity of CAD in T2D patients with CAD.
Fulltext Anti-cyclic citrullinated peptide antibody is highly associated with rheumatoid factor and radiological defects in rheumatoid arthritis patients

Sulaiman FN, Wong KK, Ahmad WAW, Ghazali WSW

Medicine (Baltimore), 2019 Mar;98(12):e14945.
PMID: 30896663 DOI: 10.1097/MD.0000000000014945

Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosisThere was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.
Fulltext Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?

Rahim MAA, Rahim ZHA, Ahmad WAW, Bakri MM, Ismail MD, Hashim OH

Acta Pharmacol Sin, 2018 Jul;39(7):1197-1207.
PMID: 29417940 DOI: 10.1038/aps.2017.141

An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma proteins in T2DM patients following onset of AMI in comparison with those without AMI. Volunteer T2DM patients without AMI (control; n=10) and T2DM patients with AMI (n=10) were recruited. Plasma samples from these patients were evaluated via two-dimensional gel electrophoresis (2DE) to screen for proteins with level changes between the two groups. The abundance of spots on gel images was analyzed using Progenesis SameSpots and subjected to false discovery rate (FDR) analysis. Protein spots with statistically significant changes of at least 1.5 fold were selected for mass spectrometry (MS) analysis. Due to strong cardiac connections, tetranectin and titin were evaluated by enzymelinked immunosorbent assay (ELISA). The adjusted P-values and fold changes between the two groups resulted in identification of 34 protein spots with significantly altered abundance. Upon MS analysis, 17 plasma proteins were identified: tetranectin, titin, clusterin, haptoglobin, myosin-13, zinc fnger protein 445, DNA repair protein RAD50, serum albumin, apolipoprotein A-IV, caspase-6, aminoacyl tRNA synthase complex-interacting multifunctional protein 1, serotransferrin, retinol-binding protein 4, transthyretin, alpha-1-antitrypsin, apolipoprotein A-I and serum amyloid A. Comparable patterns of changes in tetranectin and titin between the control and AMI groups were confirmed using ELISA. In summary, tetranectin and titin in plasma appeared to be closely associated with the onset of AMI among T2DM patients and can be used as potential biomarkers for prediction of a cardiac event, though this requires validation in a prospective cohort study.
Fulltext Impact of Coronary Stent Architecture on Clinical Outcomes: Do Minor Changes in Stent Architecture Really Matter?

Nuruddin AAB, Ahmad WAW, Waliszewski M, Heang TM, Bang LH, Yusof AKM, et al.

Cardiol Ther, 2021 Jun;10(1):175-187.
PMID: 33275200 DOI: 10.1007/s40119-020-00204-4

INTRODUCTION: The objective of this study was to compare the accumulated clinical outcomes of two Malaysian all-comers populations, each treated with different polymer-free sirolimus-eluting stents (PF-SES) of similar stent design.
METHODS: The Malaysian subpopulation of two all-comers observational studies based on the same protocol (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were combined and compared to a Malaysian-only cohort which was treated with a later-generation PF-SES. The PF-SES's used differed only in their bare-metal backbone architecture, with otherwise identical sirolimus coating. The primary endpoint was the accumulated target lesion revascularization (TLR) rate at 12 months. The rates of major adverse cardiac events (MACE), stent thrombosis (ST) and myocardial infarction (MI) were part of the secondary endpoints.
RESULTS: A total of 643 patients were treated with either the first-generation PF-SES (413 patients) or second-generation PF-SES (230 patients). Patient demographics were similar in terms of age (p = 0.744), male gender (0.987), diabetes mellitus (p = 0.293), hypertension (p = 0.905) and acute coronary syndrome (ACS, 44.8% vs. 46.1%, p = 0.752) between groups. There were no differences between treatment groups in terms of lesion length (20.8 ± 7.3 mm vs. 22.9 ± 7.9, p = 0.111) or vessel diameter (2.87 ± 0.39 vs. 2.93 ± 0.40, p = 0.052) despite numerically smaller diameters in the first-generation PF-SES group. The second-generation PF-SES tended to have more complex lesions as characterized by calcification (10.3% vs. 16.2%, p = 0.022), severe tortuosity (3.5% vs. 6.9%, p = 0.041) and B2/C lesions (49.2% vs. 62.8%, p
Fulltext In-hospital risk stratification algorithm of Asian elderly patients

Kasim S, Malek S, Cheen S, Safiruz MS, Ahmad WAW, Ibrahim KS, et al.

Sci Rep, 2022 Oct 20;12(1):17592.
PMID: 36266376 DOI: 10.1038/s41598-022-18839-9

Limited research has been conducted in Asian elderly patients (aged 65 years and above) for in-hospital mortality prediction after an ST-segment elevation myocardial infarction (STEMI) using Deep Learning (DL) and Machine Learning (ML). We used DL and ML to predict in-hospital mortality in Asian elderly STEMI patients and compared it to a conventional risk score for myocardial infraction outcomes. Malaysia's National Cardiovascular Disease Registry comprises an ethnically diverse Asian elderly population (3991 patients). 50 variables helped in establishing the in-hospital death prediction model. The TIMI score was used to predict mortality using DL and feature selection methods from ML algorithms. The main performance metric was the area under the receiver operating characteristic curve (AUC). The DL and ML model constructed using ML feature selection outperforms the conventional risk scoring score, TIMI (AUC 0.75). DL built from ML features (AUC ranging from 0.93 to 0.95) outscored DL built from all features (AUC 0.93). The TIMI score underestimates mortality in the elderly. TIMI predicts 18.4% higher mortality than the DL algorithm (44.7%). All ML feature selection algorithms identify age, fasting blood glucose, heart rate, Killip class, oral hypoglycemic agent, systolic blood pressure, and total cholesterol as common predictors of mortality in the elderly. In a multi-ethnic population, DL outperformed the TIMI risk score in classifying elderly STEMI patients. ML improves death prediction by identifying separate characteristics in older Asian populations. Continuous testing and validation will improve future risk classification, management, and results.
Fulltext Ethnic disparities and its association between epicardial adipose tissue thickness and cardiometabolic parameters

Mohamed W, Ishak KN, Baharum N, Zainudin N, Lim HY, Noh M, et al.

Adipocyte, 2024 Dec;13(1):2314032.
PMID: 38373876 DOI: 10.1080/21623945.2024.2314032

Excessive deposit of epicardial adipose tissue (EAT) were recently shown to be positively correlated with cardiovascular disease (CVD). This study aims to investigate the thickness of EAT and its association with the components of metabolic syndrome among multi-ethnic Malaysians with and without acute coronary syndrome (ACS). A total of 213 patients were recruited, with the thickness of EAT were quantified non-invasively using standard two-dimensional echocardiography. EAT thickness among the Malaysian population was prompted by several demographic factors and medical comorbidities, particularly T2DM and dyslipidaemia. ACS patients have significantly thicker EAT compared to those without ACS (4.1 mm vs 3.7 mm, p = 0.035). Interestingly, among all the races, Chinese had the thickest EAT distribution (4.6 mm vs 3.8 mm), with age (p = 0.04 vs p
Fulltext Drug-coated balloon treatment in coronary artery disease: Recommendations from an Asia-Pacific Consensus Group

Her AY, Shin ES, Bang LH, Nuruddin AA, Tang Q, Hsieh IC, et al.

Cardiol J, 2021;28(1):136-149.
PMID: 31565793 DOI: 10.5603/CJ.a2019.0093

Coronary artery disease (CAD) is currently the leading cause of death globally, and the prevalence of this disease is growing more rapidly in the Asia-Pacific region than in Western countries. Although the use of metal coronary stents has rapidly increased thanks to the advancement of safety and efficacy of newer generation drug eluting stent (DES), patients are still negatively affected by some the inherent limitations of this type of treatment, such as stent thrombosis or restenosis, including neoatherosclerosis, and the obligatory use of dual antiplatelet therapy (DAPT) with unknown optimal duration. Drug-coated balloon (DCB) treatment is based on a leave-nothing-behind concept and therefore it is not limited by stent thrombosis and long-term DAPT; it directly delivers an anti-proliferative drug which is coated on a balloon after improving coronary blood flow. At present, DCB treatment is recommended as the first-line treatment option in metal stent-related restenosis linked to DES and bare metal stent. For de novo coronary lesions, the application of DCB treatment is extended further, for conditions such as small vessel disease, bifurcation lesions, and chronic total occlusion lesions, and others. Recently, several reports have suggested that fractional flow reserve guided DCB application was safe for larger coronary artery lesions and showed good long-term outcomes. Therefore, the aim of these recommendations of the consensus group was to provide adequate guidelines for patients with CAD based on objective evidence, and to extend the application of DCB to a wider variety of coronary diseases and guide their most effective and correct use in actual clinical practice.
Prospective, large-scale multicenter trial for the use of drug-coated balloons in coronary lesions: The DCB-only All-Comers Registry

Rosenberg M, Waliszewski M, Chin K, Ahmad WAW, Caramanno G, Milazzo D, et al.

Catheter Cardiovasc Interv, 2019 02 01;93(2):181-188.
PMID: 30280482 DOI: 10.1002/ccd.27724

OBJECTIVES: This prospective, observational all-comers registry assessed the safety and efficacy of a Drug Coated Balloon-only strategy (DCB-only) in patients with coronary lesions.
BACKGROUND: Data regarding the performance of a DCB-only approach, especially in patients with previously untreated de-novo coronary artery disease (CAD), are still limited.
METHODS: This study was conducted as an international, multicenter registry primarily enrolling patients with de-novo CAD. However, it was also possible to include patients with in-stent restenosis (ISR). The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 9 months.
RESULTS: A total of 1,025 patients with a mean age of 64.0 ± 11.2 years were enrolled. The majority of treated lesions were de-novo (66.9%), followed by drug-eluting-stent ISR (DES-ISR; 22.6%) and bare-metal-stent ISR (BMS-ISR; 10.5%). The TLR rate was lower in the de-novo group (2.3%) when compared to BMS- (2.9%) and DES-ISR (5.8%) (P = 0.049). Regarding MACE, there was a trend toward fewer events in the de-novo group (5.6%) than in the BMS- (7.8%) and DES-ISR cohort (9.6%) (P = 0.131). Subgroup analyses revealed that lesion type (95% CI 1.127-6.587); P = 0.026) and additional stent implantation (95% CI 0.054-0.464; P = 0.001) were associated with higher TLR rates.
CONCLUSIONS: Our results show that DCB-only angioplasty of de-novo coronary lesions is associated with low MACE and TLR rates. Thus, DCBs appear to be an attractive alternative for the interventional, stentless treatment of suitable de-novo coronary lesions.
Fulltext Cost of elective percutaneous coronary intervention in Malaysia: a multicentre cross-sectional costing study

Lee KY, Ong TK, Low EV, Liow SY, Anchah L, Hamzah S, et al.

BMJ Open, 2017 05 28;7(5):e014307.
PMID: 28552843 DOI: 10.1136/bmjopen-2016-014307

OBJECTIVES: Limitations in the quality and access of cost data from low-income and middle-income countries constrain the implementation of economic evaluations. With the increasing prevalence of coronary artery disease in Malaysia, cost information is vital for cardiac service expansion. We aim to calculate the hospitalisation cost of percutaneous coronary intervention (PCI), using a data collection method customised to local setting of limited data availability.

DESIGN: This is a cross-sectional costing study from the perspective of healthcare providers, using top-down approach, from January to June 2014. Cost items under each unit of analysis involved in the provision of PCI service were identified, valuated and calculated to produce unit cost estimates.

SETTING: Five public cardiac centres participated. All the centres provide full-fledged cardiology services. They are also the tertiary referral centres of their respective regions.

PARTICIPANTS: The cost was calculated for elective PCI procedure in each centre. PCI conducted for urgent/emergent indication or for patients with shock and haemodynamic instability were excluded.

PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measures of interest were the unit costs at the two units of analysis, namely cardiac ward admission and cardiac catheterisation utilisation, which made up the total hospitalisation cost.

RESULTS: The average hospitalisation cost ranged between RM11 471 (US$3186) and RM14 465 (US$4018). PCI consumables were the dominant cost item at all centres. The centre with daycare establishment recorded the lowest admission cost and total hospitalisation cost.

CONCLUSIONS: Comprehensive results from all centres enable comparison at the levels of cost items, unit of analysis and total costs. This generates important information on cost variations between centres, thus providing valuable guidance for service planning. Alternative procurement practices for PCI consumables may deliver cost reduction. For countries with limited data availability, costing method tailored based on country setting can be used for the purpose of economic evaluations.

REGISTRATION: Malaysian MOH Medical Research and Ethics Committee (ID: NMRR-13-1403-18234 IIR).

Study site: 5 hospitals (unnamed) of which 1 is a university teaching hospital
Fulltext Renal Denervation in Asia: Consensus Statement of the Asia Renal Denervation Consortium

Kario K, Kim BK, Aoki J, Wong AY, Lee YH, Wongpraparut N, et al.

Hypertension, 2020 Mar;75(3):590-602.
PMID: 32008432 DOI: 10.1161/HYPERTENSIONAHA.119.13671

The Asia Renal Denervation Consortium consensus conference of Asian physicians actively performing renal denervation (RDN) was recently convened to share up-to-date information and regional perspectives, with the goal of consensus on RDN in Asia. First- and second-generation trials of RDN have demonstrated the efficacy and safety of this treatment modality for lowering blood pressure in patients with resistant hypertension. Considering the ethnic differences of the hypertension profile and demographics of cardiovascular disease demonstrated in the SYMPLICITY HTN (Renal Denervation in Patients With Uncontrolled Hypertension)-Japan study and Global SYMPLICITY registry data from Korea and Taiwan, RDN might be an effective hypertension management strategy in Asia. Patient preference for device-based therapy should be considered as part of a shared patient-physician decision process. A practical population for RDN treatment could consist of Asian patients with uncontrolled essential hypertension, including resistant hypertension. Opportunities to refine the procedure, expand the therapy to other sympathetically mediated diseases, and explore the specific effects on nocturnal and morning hypertension offer a promising future for RDN. Based on available evidence, RDN should not be considered a therapy of last resort but as an initial therapy option that may be applied alone or as a complementary therapy to antihypertensive medication.
Orthostatic blood pressure changes and physical, functional and cognitive performance: the MELoR study

Saedon NI, Frith J, Goh CH, Ahmad WAW, Khor HM, Tan KM, et al.

Clin Auton Res, 2020 04;30(2):129-137.
PMID: 31696333 DOI: 10.1007/s10286-019-00647-3

PURPOSE: Consensus definitions currently define initial orthostatic hypotension (IOH) as ≥ 40 mmHg systolic (SBP) or ≥ 20 mmHg in diastolic blood pressure (DBP) reductions within 15 s of standing, while classical orthostatic hypotension (COH) is defined as a sustained reduction ≥ 20 mmHg SBP or ≥ 10 mmHg SBP within 3 min of standing. The clinical relevance of the aforementioned criteria remains unclear. The present study aimed to determine factors influencing postural blood pressure changes and their relationship with physical, functional and cognitive performance in older adults.
METHODS: Individuals aged ≥ 55 years were recruited through the Malaysian Elders Longitudinal Research (MELoR) study and continuous non-invasive BP was monitored over 5 min of supine rest and 3 min of standing. Physical performance was measured using the timed-up-and-go test, functional reach, handgrip and Lawton's functional ability scale. Cognition was measured with the Montreal Cognitive Assessment. Participants were categorized according to BP responses into four categories according to changes in SBP/DBP reductions from supine to standing:
Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial

Verdoia M, Suryapranata H, Damen S, Camaro C, Benit E, Barbieri L, et al.

J Thromb Thrombolysis, 2021 Oct;52(3):797-807.
PMID: 33847862 DOI: 10.1007/s11239-021-02439-x

BACKGROUND: Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study.
METHODS: REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months.
RESULTS: From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow

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