Role of ß-blockers in the cardiovascular disease continuum: a collaborative Delphi survey-based consensus from Asia-Pacific.

OBJECTIVE: This Delphi method of consensus was designed to develop scientific statements for ß-blockers in the continuum of cardiovascular diseases with a special focus on the role of bisoprolol. METHODS: Eleven experienced cardiologists from across the Asia-Pacific countries participated in two rounds of the survey. In the first round, experts were asked to rate agreement/disagreement with 35 statements across seven domains regarding the use of ß-blockers for treating hypertension, heart failure, coronary artery diseases, co-morbidities, as well as their safety profile, usage pattern, and pharmacokinetic variability. A consensus for a statement could be reached with >70% agreement. RESULTS: Except for seven statements, all attained consensus in the first round. In the second round that was conducted virtually, the experts re-appraised their ratings for the seven statements along with a critical appraisal of two additional statements that were suggested by experts in the preceding round. At the end of the second round, the final version included 36 statements (34 original statements, two statements suggested by experts, and the omission of one statement that did not attain consensus). The final version of statements in the second round was disseminated among experts for their approval followed by manuscript development. CONCLUSION: Attainment of consensus for almost all statements reconfirms the clinical benefits of ß-blockers, particularly ß1-selective blockers for the entire spectrum of cardiovascular diseases.

Practical guide in using insulin degludec/insulin aspart: A multidisciplinary approach in Malaysia.

Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naive or insulin-naive patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal-bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%-50% and taken during sahur, while the preRamadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.

Current Insights on Dyslipidaemia Management for Prevention of Atherosclerotic Cardiovascular Disease: A Malaysian Perspective.

Dyslipidaemia is highly prevalent in the Malaysian population and is one of the main risk factors for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) is recognised as the primary target of lipid-lowering therapy to reduce the disease burden of ASCVD. Framingham General CV Risk Score has been validated in the Malaysian population for CV risk assessment. The Clinical Practice Guidelines (CPG) on the management of dyslipidaemia were last updated in 2017. Since its publication, several newer randomised clinical trials have been conducted with their results published in research articles and compared in meta-analysis. This underscores a need to update the previous guidelines to ensure good quality care and treatment for the patients. This review summarises the benefits of achieving LDL-C levels lower than the currently recommended target of < 1.8mmol/L without any safety concerns. In most high and very high-risk individuals, statins are the first line of therapy for dyslipidaemia management. However, certain high-risk individuals are not able to achieve the LDL-C goal as recommended in the guideline even with high-intensity statin therapy. In such individuals, lower LDL-C levels can be achieved by combining the statins with non-statin agents such as ezetimibe and PCSK9 inhibitors. Emerging non-statin lipid-lowering therapies and challenges in dyslipidaemia management are discussed in this article. The review also summarises the recent updates on local and international guidelines for dyslipidaemia management.

Attainment of Low-Density Lipoprotein Cholesterol Targets and Prescribing Pattern of Lipid-Lowering Medications among Patients with Familial Hypercholesterolemia Attending Specialist Clinics.

AIMS: Patients with familial hypercholesterolemia (FH) are known to have higher exposure to coronary risk than those without FH with similar low-density lipoprotein cholesterol (LDL-C) level. Lipid-lowering medications (LLMs) are the mainstay treatments to lower the risk of premature coronary artery disease in patients with hypercholesterolemia. However, the LLM prescription pattern and its effectiveness among Malaysian patients with FH are not yet reported. The aim of this study was to report the LLM prescribing pattern and its effectiveness in lowering LDL-C level among Malaysian patients with FH treated in specialist hospitals. METHODS: Subjects were recruited from lipid and cardiac specialist hospitals. FH was clinically diagnosed using the Dutch Lipid Clinic Network Criteria. Patients' medical history was recorded using a standardized questionnaire. LLM prescription history and baseline LDL-C were acquired from the hospitals' database. Blood samples were acquired for the latest lipid profile assay. RESULTS: A total of 206 patients with FH were recruited. Almost all of them were on LLMs (97.6%). Only 2.9% and 7.8% of the patients achieved the target LDL-C of ＜1.4 and ＜1.8 mmol/L, respectively. The majority of patients who achieved the target LDL-C were prescribed with statin-ezetimibe combination medications and high-intensity or moderate-intensity statins. All patients who were prescribed with ezetimibe monotherapy did not achieve the target LDL-C. CONCLUSION: The majority of Malaysian patients with FH received LLMs, but only a small fraction achieved the therapeutic target LDL-C level. Further investigation has to be conducted to identify the cause of the suboptimal treatment target attainment, be it the factors of patients or the prescription practice.

Familial hypercholesterolaemia and coronary risk factors among patients with angiogram-proven premature coronary artery disease in an Asian cohort.

BACKGROUND: Familial hypercholesterolaemia (FH) patients have elevated levels of low-density lipoprotein cholesterol, rendering them at high risk of premature coronary artery disease (PCAD). However, the FH prevalence among angiogram-proven PCAD (AP-PCAD) patients and their status of coronary risk factors (CRFs) have not been reported in the Asian population. OBJECTIVES: This study aimed to (1) determine the prevalence of clinically diagnosed FH among AP-PCAD patients, (2) compare CRFs between AP-PCAD patients with control groups, and (3) identify the independent predictors of PCAD. METHODS: AP-PCAD patients and FH patients without PCAD were recruited from Cardiology and Specialist Lipid Clinics. Subjects were divided into AP-PCAD with FH (G1), AP-PCAD without FH (G2), FH without PCAD (G3) and normal controls (G4). Medical records were collected from the clinic database and standardised questionnaires. FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria. RESULTS: A total of 572 subjects were recruited (males:86.4%; mean±SD age: 55.6±8.5years). The prevalence of Definite, Potential and All FH among AP-PCAD patients were 6%(19/319), 16% (51/319) and 45.5% (145/319) respectively. G1 had higher central obesity, family history of PCAD and family history of hypercholesterolaemia compared to other groups. Among all subjects, diabetes [OR(95% CI): 4.7(2.9,7.7)], hypertension [OR(95% CI): 14.1(7.8,25.6)], FH [OR(95% CI): 2.9(1.5,5.5)] and Potential (Definite and Probable) FH [OR(95% CI): 4.5(2.1,9.6)] were independent predictors for PCAD. Among FH patients, family history of PCAD [OR(95% CI): 3.0(1.4,6.3)] and Definite FH [OR(95% CI): 7.1(1.9,27.4)] were independent predictors for PCAD. CONCLUSION: Potential FH is common among AP-PCAD patients and contributes greatly to the AP-PCAD. FH-PCAD subjects have greater proportions of various risk factors compared to other groups. Presence of FH, diabetes, hypertension, obesity and family history of PCAD are independent predictors of PCAD. FH with PCAD is in very-high-risk category, hence, early management of modifiable CRFs in these patients are warranted.

2022 Malaysian Working Group Consensus Statement on Renal Denervation for management of arterial hypertension.

Hypertension is highly prevalent and a major contributor to cardiovascular mortality and morbidity. In spite of the availability of efficacious, safe and affordable anti-hypertensive drugs, hypertension remains poorly controlled in the majority of hypertensive patients. Various reasons including non-adherence to the anti-hypertensive drugs, account for the poor control. Resistant hypertension is also one of the reasons for poor control of blood pressure (BP). The sympathetic nervous system (SNS) has long been recognized as one of the determinants in the pathophysiology of a raised BP. Overactivity of the SNS is a contributor to sustained arterial hypertension. Renal denervation (RDN) is increasingly recognized as a safe and effective adjunctive therapy to control BP with or without pharmacotherapy. Hence for patients who remain uncontrolled despite all efforts, renal denervation (RDN) is a novel treatment that can potentially improve BP control, hence reducing the major adverse cardiovascular events (MACE). More recent randomized, sham control trials of RDN have shown that RDN produces a sustained lowering of BP. To date, this lowering of BP through RDN is maintained for at least 3 years. Furthermore, this procedure has been found to be safe. Hence this consensus summarises the science behind RDN and the available clinical data to support the use of this therapy. It is hoped that this consensus will offer guidance on the importance of identifying patients who will benefit most from this therapy. A multidisciplinary team approach in the management of the patient undergoing RDN is recommended.

Diagnostic performance of various familial hypercholesterolaemia diagnostic criteria compared to Dutch lipid clinic criteria in an Asian population.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC. METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC. RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p < 0.001) when assessed against the DLCC. The SB Register criteria, the US MEDPED and the JFHMC had low sensitivity (51.1% vs. 25.3% vs. 47.0% respectively). The SB Register criteria showed better diagnostic performance than the other criteria with 98.8% specificity, 28.6% efficiency value, 98.1% and 62.3% for positive and negative predictive values respectively. CONCLUSION: The SB Register criteria appears to be more useful in identifying positive cases leading to genetic testing compared to the JFHMC and US MEDPED in this Asian population. However, further research looking into a suitable diagnosis criterion with high likelihood of positive genetic findings is required in the Asian population including in Malaysia.

Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda.

Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients.

Central and peripheral blood pressure profile of young offspring with hypertensive and normotensive parents.

OBJECTIVES: In this cross-sectional study we compared the central aortic systolic pressure (CASP), peripheral brachial systolic pressure (PSP), peripheral brachial diastolic pressure (PDP) and augmentation index (AIx) between normotensive offspring of nonhypertensive parents (ONT) and normotensive offspring with at least one hypertensive parent (OHT). METHODOLOGY: A total of 100 healthy ONT (mean age 20.95 ± 2.06) and 100 healthy OHT (mean age 20.89 ± 2.12) individuals were recruited. Parental history of hypertension was determined by detailed history taking. CASP, PSP, PDP and AIx were measured using the BPro device. All blood pressure (BP) measurements were calibrated using oscillometric BP readings. RESULTS: The OHT group had higher PSP (117.57 ± 10.06 versus 114.52 ± 8.94, P < 0.05), PDP (72.39 ± 7.28 versus 70.39 ± 6.50, P < 0.05) and CASP (103.72 ± 8.95 versus 101.37 ± 7.74, P < 0.05) compared to the ONT group. There was no significant difference in AIx in the ONT group (57.97 ± 11.02 versus 58.08 ± 12.16, P = 0.95) in comparison to the OHT group. However, following adjustments for certain cardiovascular risk factors, only PSP (117.33 versus 114.76, P < 0.05) remained significantly higher in the OHT group compared to the ONT group. Analysis of adjusted data within sex showed that CASP was higher in the female OHT group compared to the female ONT group, whereas PDP were higher in the male OHT group compared to the male ONT group. CONCLUSION: Alterations in PSP, PDP and CASP are already present in early life in normotensive offspring of hypertensive parents, with possible differences in mechanism between different sexes.

Acute coronary syndrome in women of reproductive age.

BACKGROUND: There is scarce or no data on prevalence and presentation of acute coronary syndrome (ACS) among women of reproductive age. Furthermore, whether women of reproductive age presenting with ACS have the same risk factors as men and older women is not known. OBJECTIVE: To analyze factors associated with ACS in women of reproductive age in comparison with older women and men of a similar age group. METHODOLOGY: A total of 9702 cases of acute coronary syndrome over a 3-year period ( 2006-2008) from the National Cardiovascular Disease database were analyzed, with focus on women of reproductive age (20-<40 years), looking into association with ethnicity, comorbid illness, and the ACS stratum. Comparison with older women (40-<60 years; Control 1) and men of similar age group (Control 2) was made and analyzed using Fisher's exact test and chi-square test when necessary. RESULTS: From a total of 9702 cases, 2344 (24.2%) were women. Of these, 45 (1.9%) were women between 20 and <40 years, which is significantly lower than the two controls (older women 30.8%, and men of same age 6.2%, respectively; P < 0.0001). The distribution of ethnicity shows a similar pattern between the study group and the controls, but patients of Indian ethnicity were over-represented when compared with the Malaysian demographics of general population (31.3% versus 7.1%; P < 0.0001). ACS in women of reproductive age was associated with diabetes mellitus in 37.8%, hypertension in 40.0%, and dyslipidemia in 24.4% of cases, similar to men of the same age but significantly lower than the older women (P < 0.0001). Smoking is not a major risk factor in the study group, where only 6.7% ever smoked, similar to older women (6.8%, P = 1.000) and significantly much less compared with men of the same age (84.1%; P < 0.0001). Regarding the ACS stratum, a significantly higher percentage of women in the study group had ST-segment elevation myocardial infarction compared with older women (P = 0.0085) but less than that of men of similar age (P = 0.0187). CONCLUSION: ACS is rare in women of reproductive age. Diabetes, hypertension, and Indian ethnicity were identified as important contributors.

Addressing the burden of type 2 diabetes and cardiovascular disease through the management of postprandial hyperglycaemia: an Asian-Pacific perspective and expert recommendations.

The world is facing an epidemic of cardiovascular disease (CVD) and type 2 diabetes, with populations in low- to middle-income countries, including many in the Asia Pacific (AP) region, being disproportionately affected. Emerging data identify postprandial hyperglycaemia (PPHG) as an important predictor of CVD, and several professional bodies, including the International Diabetes Federation, have issued guidelines on the management of PPHG in type 2 diabetes. Guidance on how international recommendations could be implemented in Asian populations is currently lacking. Therefore, a panel of experts from the AP region convened to consider the current status of PPHG and CVD in the region, and to develop recommendations for clinical practice. The group concluded that improved awareness of the impact of PPHG on CVD risk, among clinicians and the general public, and more widespread use of routine screening for PPHG, using oral glucose tolerance testing in those without recognised diabetes, are required. Additionally, frequent meal-based testing and effective PPHG management are essential to the management of IGT and type 2 diabetes.