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.

Effects of the COVID-19 pandemic on the management of ST-Segment elevation myocardial infarction in Indonesia: a cohort study.

Background: ST-segment elevation myocardial infarction (STEMI) is a form of acute coronary syndrome with high mortality rate. Management of STEMI should be performed as soon as possible to prevent further damage. With the emergence of coronavirus disease 2019 (COVID-19), it may face obstacles. To overcome those problems, some changes in policy focusing on fibrinolytic therapy in STEMI patients have been applied. This study aimed to identify the effects of COVID-19 in management of STEMI patients in Indonesia. Methods: This retrospective study was conducted in Dr. Cipto Mangunkusumo Hospital (CMH), the national referral center in Indonesia. We compared data between 2018 to 2019 and 2020 to 2021 as before and during COVID-19 pandemic period, respectively. We analyzed the effects of COVID-19 on STEMI patients' visits to hospital i.e., monthly hospital admission and symptoms-to-hospital, management of STEMI i.e., the strategies and time of reperfusion, and clinical outcomes of STEMI patients i.e., major adverse coronary event and mortality. Results: There was a significant statistically reduced mean of monthly hospital admissions from 11 to 7 (p = 0.002) and prolonged duration of symptoms-to-hospital during COVID-19 from 8 to 12 hours (p = 0.005). There was also a decrease in primary percutaneous coronary intervention (PPCI) procedures during COVID-19 (65.2% vs. 27.8%, p<0.001), which was accompanied by an increased number of fibrinolytic (1.5% vs. 9.5%, p<0.001) and conservative therapy (28.5% vs. 55.6%, p <0.01). Moreover, there was also a prolonged duration of diagnosis-to-wire-crossing time (160 vs. 186 minutes, p = 0.005), meanwhile, percentage of urgent PCI, door-to-needle time, and clinical outcomes were not statistically significant. Conclusions: During COVID-19 pandemic, the number STEMI patients declined in monthly hospital admission, delays in symptoms-to-hospital time, changes in type of reperfusion strategy, and delays in PPCI procedures in CMH. Meanwhile, fibrinolytic time and clinical outcomes were not affected.

Perception of hypertension management by patients and doctors in Asia: potential to improve blood pressure control.

BACKGROUND: Hypertension is one of the world's most common health conditions and is a leading risk factor for mortality. Although blood pressure can be modified, there is a large proportion of patients whose blood pressure remains uncontrolled. The aim of this study, termed Edvantage 360°, was to gain a deeper understanding of hypertension management in Asia from the perspective of patients and doctors, and to propose strategies to improve blood pressure control. METHODS: Conducted in Hong Kong, Indonesia, Malaysia, the Philippines, South Korea, Taiwan, and Thailand, Edvantage 360° was a mixed-methods observational study that used both qualitative and quantitative elements: qualitative interviews and focus groups with patients (N = 110), quantitative interviews with patients (N = 709), and qualitative interviews with doctors (N = 85). RESULTS: This study found that, although there is good understanding of the causes and consequences of hypertension among Asian patients, there is a lack of urgency to control blood pressure. Doctors and patients have different expectations of each other and a divergent view on what constitutes successful hypertension management. We also identified a fundamental gap between the beliefs of doctors and patients as to who should be most responsible for the patients' hypertension management. In addition, because patients find it difficult to comply with lifestyle modifications (often because of a decreased understanding of the changes required), adherence to medication regimens may be less of a limiting factor than doctors believe. CONCLUSIONS: Doctors may provide better care by aligning with their patients on a common understanding of successful hypertension management. Doctors may also find it helpful to provide a more personalized explanation of any needed lifestyle modifications. The willingness of the doctor to adjust their patient interaction style to form a 'doctor-patient team' is important. In addition, we recommend that doctors should not attribute ineffectiveness of the treatment plan to patient non-adherence to medications, but rather adjust the medication regimen as needed.

Peripheral blood gene expression profile of atherosclerotic coronary artery disease in patients of different ethnicity in Malaysia.

The molecular basis of coronary artery disease (CAD) has been widely studied in the western world but there is no published work on the Malaysian population. This study looked at the global gene expression profiling of the peripheral blood of patients with CAD from the 3 main ethnic groups in Malaysia. Male subjects selected were based on angiographically confirmed CAD (≥50% stenosis) and normal control subjects (0% stenosis) with age range of 55.6±5.3 and 51.0±5.5 years, respectively. The global gene expression of 12 angiographically documented CAD patients and 11 matched control subjects were performed. The combined group samples identified 6 up regulated differential expression (DE) genes (GHRL, LTA, CBS, HP, ITGA2B, and OLR1) and 12 down regulated DE genes (IL18R1, ITGA2B, IL18RAP, HP, OLR1, SOD2 ITGB3, IL1B, MMP9, PLA2G7, UTS2, and CBS) to be involved in CAD at the fold change of 1.3 with fault discovery rate (FDR) of 1%. Three genes, MMP9, IL1B, and SOD2 were down regulated in all the 3 ethnic groups making them potential biomarker candidates for CAD across all three ethnicities. Further verification in a cohort study is needed.

Effect of rosiglitazone and ramipril on macrovasculopathy in patients with type 2 diabetes: needs longer treatment and/or higher doses?

INTRODUCTION: The aim of the study is to investigate whether standard doses of rosiglitazone (4 mg/daily) and ramipril (5 mg/daily) can reverse pre-clinical macrovasculopathy in newly diagnosed never treated type 2 diabetes (T2DM) patients. METHODS: In this randomized, double-blind, placebo-controlled study, 33 T2DM patients were randomized to rosiglitazone (4 mg/daily) or ramipril (5 mg/daily) or placebo for 1 year. Hemodynamic variables were measured at 3 treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period. RESULT: In diabetic patients, PWV (P = 0.037) and AI (P = 0.005) with ramipril and AI (P < 0.001) with rosiglitazone were significantly reduced during overall treatment period from the baseline; however, these differences were not significant in comparison to placebo. DISCUSSION AND CONCLUSION: The present study showed that treatment with standard doses of rosiglitazone and ramipril are not adequate to reverse pre-clinical vasculopathy in T2DM. The lack of benefit in newly diagnosed T2DM may be because of the relatively short-term intervention and/or the use of lower doses of rosiglitazone/ramipril. Further trials are needed for a longer period of time, possibly with higher doses, to show whether rosiglitazone/ramipril can reverse pre-clinical vasculopathy in T2DM (ClinicalTrials.gov number, NCT00489229).

Prevalence of beta-2 adrenergic receptor (beta 2 AR) polymorphisms and its influence on a model used to assess endothelial function using pulse wave analysis (PWA).

BACKGROUND: Pulse wave analysis (PWA) combined with beta(2)-agonist challenge has recently been used to assess endothelial function. beta-2 adrenergic receptor (beta(2)AR) polymorphisms may affect response to beta(2)-agonist. We determined whether beta(2)AR polymorphisms influence endothelial response in our model using PWA and salbutamol. METHODS: 388 healthy Malay subjects (177 males, 211 females) were genotyped for 5 functionally important single nucleotide polymorphisms (SNPs) of beta(2)AR; 298 subjects proceeded with assessment of endothelial function. The parameter augmentation index (AIx) was recorded non-invasively using SphygmoCor. Recording of AIx at baseline was followed by administration of 500 microg sublingual glyceryl trinitrate (GTN). AIx recordings were repeated at 3, 5, 10, 15 and 20 min post-GTN. Subjects then inhaled 400 microg of salbutamol before AIx recordings at 5 min intervals up to 20 min. Maximum changes in AIx after GTN and salbutamol represented endothelium independent and endothelium dependent vasodilatation (EDV) respectively. RESULTS: Allele frequencies of mutated Gly16, Glu27, Ile164, -20C and -47C were 47%, 6.8%, 0%, 30% and 9.3% respectively. No significant differences in EDV were noted between genotype groups of each studied SNPs. CONCLUSIONS: Assessment of endothelial function using PWA and salbutamol was not influenced by beta(2)AR polymorphisms.

Early manifestation of macrovasculopathy in newly diagnosed never treated type II diabetic patients with no traditional CVD risk factors.

Type II diabetes patients have increased risk of macrovascular complications compared with the general population. Arterial stiffness is considered as an independent predictor of macrovascular events. This study investigated arterial stiffness in newly diagnosed never treated diabetes and impaired glucose tolerance (IGT) patients without any traditional cardiovascular diseases (CVD) risk factors. After preliminary screening of 1620 individuals, 30 diabetic and 30 IGT patients were recruited and compared with age- and sex-matched 30 normoglycaemic subjects. The subjects were newly diagnosed, never treated, normotensive, non-obese, non-hyperlipidaemic and non-smoker. Haemodynamic variables, pulse wave velocity (PWV) and augmentation index (AI) were measured. The PWV was significantly higher in diabetic patients (10.37+/-2.64m/s vs. 8.70+/-1.29m/s; p=0.035) and was of borderline significant in IGT subjects (9.54+/-1.56m/s vs.8.70+/-1.29m/s, p=0.078) compared to normoglycaemic individuals. Augmentation index was higher of borderline significant in diabetic (134.53+/-17.32% vs. 129.17+/-11.18%, p=0.055) and IGT patients (132.02+/-16.11% vs. 129.17+/-11.18%, p=0.059) compared to normoglycaemic individuals. The study demonstrated that newly diagnosed never treated diabetic patients without any CV complications had early manifestation of macrovascular diseases as evident by increased arterial stiffness. The findings also revealed early manifestations of preclinical vasculopathy and potentially increased risk for development of macrovascular diseases at an early age in diabetic patients.

Method optimization on the use of postocclusive hyperemia model to assess microvascular function.

INTRODUCTION: Recent development had allowed non-invasive assessment of microvascular function in vivo; however, the method has not been fully optimized and standardized. In this study, we aimed to characterize the "effective" occlusion duration needed to elicit sufficient postocclusive hyperemia (PORH) responses in forearm skin using laser Doppler fluximetry (LDF), in subjects with differing age, gender and menstrual phases. MATERIALS AND METHODS: A total of 120 healthy subjects were studied (20 subjects each in the age ranges of 21-30, 31-40, 41-50 for both genders). Male subjects were randomized to receive 1, 2 or 3 min occlusion on three study days. Females attended six study days: the first three days (with different occlusion times) were performed during low estrogenic phase of menstrual cycle and subsequent three visits were done during high estrogenic phase. Skin perfusion was measured before, during and after occlusion using LDF. The magnitude and temporal courses of PORH were expressed as PORH max (absolute maximal increase in hyperemia perfusion) and Tp (time-to-peak), respectively. RESULTS: For PORH max analysis, the occlusion duration should be applied based on one's age, gender and menstrual phase. The PORH responses were more consistent during high estrogenic phase with 2 min found as the "effective" occlusion duration in all female groups. For Tp analysis, 3 min occlusion produced the significant change in all age ranges for both genders irrespective of menstrual phase. CONCLUSION: This study revealed that for assessment of microvascular function using PORH+LDF model, the occlusion duration for PORH max is influenced by age, gender and menstrual phase. Measurement based on Tp is however independent of these factors.

Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among malay hypertensive subjects with a known genetic profile.

BACKGROUND: Data comparing the effect of losartan and perindopril on aortic stiffness among hypertensive subjects without A(1166)C polymorphism was not available. METHODS: The short-term and long-term effects of losartan (50 mg) and perindopril (4 mg) on aortic stiffness measured as carotid femoral pulse wave velocity (PWV) were compared in 39 middle-aged Malay subjects with mild-to-moderate hypertension in a 4-month, double-blind, randomized, controlled, parallel-design study. RESULTS: Four-month treatment with both drugs showed a significant reduction in blood pressure (BP) (P < .005) and PWV (P < .05) as compared to the baseline. On the other hand 1-month treatment showed a significant reduction in BP only in perindopril group (P < .05) but not in the losartan group. There was no significant reduction in pulse pressure and PWV after 1 month treatment by both drugs. No significant difference was seen in reduction in BP after 1 month and 4 months treatment between the two drugs. Similarly no significant difference was seen in reduction in PWV between the two drugs after 1 month (P = .613) and 4 months (P = .521) of treatment. Reduction in PWV by losartan (r = 0.470) and perindopril (r = 0.457) correlated significantly only with reduction in DBP (P < .05) and remained significant even after controlling for reduction in DBP (P < .05). Reduction in PWV by both losartan and perindopril was independent of reduction in BP by these drugs. CONCLUSIONS: These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.

Noninvasive assessment of cutaneous vascular function in vivo using capillaroscopy, plethysmography and laser-Doppler instruments: its strengths and weaknesses.

Given that functional abnormalities of the microcirculation are one of the primary abnormalities in cardiovascular disease pathogenesis, various noninvasive clinical tools have been developed recently to assess the microvascular function, particularly at the skin. The common techniques used to assess cutaneous microvascular function in vivo include capillaroscopy, venous occlusion plethysmography, and laser-Doppler instruments (laser-Doppler fluximetry and laser-Doppler imaging). These noninvasive techniques can be used as an early measure of functional abnormalities within the microvascular tree, predominantly in population at high risk for cardiovascular events. This review discusses some underlying application principle of these techniques, including its clinical significance, method reproducibility and limitations.

Reproducibility of different laser Doppler fluximetry parameters of postocclusive reactive hyperemia in human forearm skin.

INTRODUCTION: Postocclusive reactive hyperemia in forearm skin is a commonly used model for studying microvascular reactivity function, particularly in the assessment of vascular effect of topically applied pharmacological substances. In this study, we investigated the reproducibility of several different laser-Doppler-derived parameters in the measurement of postocclusive reactive hyperemia at forearm skin in healthy subjects. METHODS: Eighteen young healthy male volunteers were recruited and studied in a supine position while fasted. Forearm blood flow was occluded at suprasystolic pressure for 3 min. Microvascular perfusion was measured continuously using laser Doppler fluximetry. Parameters studied were maximum increase in hyperemia perfusion (PORHmax), time-to-peak (Tp), amplitude of peak perfusion (PORHpeak), percentage of hyperemic response (PORH%) and mean velocity of the hyperemia increase (PORHmax/Tp). Measurement was performed twice within each study day for 2 study days. Coefficient of variation and intraclass correlation coefficient (ICC; with 95% confidence interval) were calculated for each parameter. An ICC value above 0.75 was interpreted as "excellent reproducibility". RESULTS: ICC analysis showed that all studied parameters, except for PORH%, demonstrated excellent reproducibility for both within- and between-day measurements. Satisfactory intraday and interday coefficients of variation (<10%) were also obtained for these parameters. CONCLUSION: Laser-Doppler-derived PORHmax, Tp, PORHpeak and PORHmax/Tp were highly reproducible parameters for measuring microvascular reactivity during reactive hyperemia, with PORHmax shown as the most reproducible index. PORH% is, however, less reproducible. These findings have implications for the use of laser Doppler fluximetry coupled with 3-min-occlusion PORHmax as a useful and reliable noninvasive clinical measurement index of microvascular function.

Dependence of human forearm skin postocclusive reactive hyperemia on occlusion time.

INTRODUCTION: Human postocclusive forearm skin reactive hyperemia is not only a potential means of identifying early signs of cardiovascular diseases, it can also be used in the assessment of local microvascular response to topically applied compounds on skin. The method is not fully characterized. In this study, we investigated the influence of occlusion time on postocclusive forearm skin reactive hyperemia using laser Doppler fluximetry (LDF). METHODS: Twenty healthy male volunteers were studied on three separate days (at least 24 h apart) via a randomized design. Volunteers were studied in a supine position while fasted. Laser Doppler probes were placed on the volar surface of the antebrachium. In preliminary studies, 3 min of upper arm blood flow occlusion at suprasystolic pressure was found to be the upper limit of tolerability. Subsequently, volunteers were randomized to receive 1, 2, or 3 min occlusion on 3 different days. Skin blood flux was measured before, during, and after occlusion using LDF. The primary outcome calculated was maximal change in skin blood flux before and after occlusion, expressed in arbitrary units (AU). RESULTS: Skin blood flux changes (mean+/-S.E.M.) after 1, 2, and 3 min occlusion period were 15.39+/-1.27 AU, 24.84+/-1.62 AU, and 32.14+/-1.73 AU, respectively. Using repeated-measures analysis of variance (ANOVA), significant difference (P<.05) in skin blood flux changes were revealed between these three occlusion durations, where 3 min occlusion produced significantly greater in skin blood flux occlusion change compared to 1 and 2 min occlusion. DISCUSSION: Three minutes of occlusion produces the greater postocclusive reactive hyperemia. It is recommended that studies using postocclusive forearm skin reactive hyperemia should occlude the forearm for at least 3 min.

Effect of different curcumin dosages on human gall bladder.

Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.