The relationship between Pattern B lipoprotein profile and low-density lipoprotein cholesterol subfractions with Metabolic Syndrome and Framingham Risk Score in adults at health screening in Malaysia.

INTRODUCTION: Traditional cardiovascular (CV) risk factors are constituents of Metabolic Syndrome (MetS) and Framingham Risk Score (FRS). However, CV risk exists even when these risk parameters are normal and have been attributed to the atherogenic small dense low-density lipoprotein cholesterol (sdLDL). This study aimed to determine the association of Pattern B and LDL subfractions with MetS and FRS among selected Malaysian population. MATERIALS AND METHODS: A cross-sectional study of 380 subjects ≥30 years old at health screening. Sociodemographic factors and clinical characteristics were recorded. Fasting serum lipids, LDL subfractions and plasma glucose were analysed. RESULTS: Being older, Malay with Pattern B independently predicted MetS. Being male, Chinese with Pattern B and increased body mass index (BMI) and diastolic blood pressure (DBP) were more likely to be in the intermediate to high risk FRS group. Common independent biochemical predictors include LDL1 and sdLDL: LDL3 in MetS and non-high-density lipoprotein cholesterol in FRS. CONCLUSION: BMI and DBP may provide incremental prognostic value to FRS risk estimates if included. Considering a significant incidence of Pattern B in low FRS risk subjects (13.4%), routine LDL subfraction analysis could identify these individuals that would be overlooked if their risk were predicted solely based on their FRS only. The non-specific lowering of LDL1 by lipid-lowering therapy based on conventional lipid profile might have a negative effect on several physiological processes. Hence, if LDL subfractions are determined, therapy can be targeted towards sdLDL. Recognising asymptomatic individuals who carry high CV risk is pertinent in primary prevention.

An insight of dysregulation of microRNAs in the pathogenesis of diabetic kidney disease.

BACKGROUND: Worldwide, diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) and its successor, the end stage renal disease, both of which constitute major morbidity and mortality concerns. CONTENT: The residual risk of disease progression remains despite the advert of newer therapeutic modalities and current biomarkers. Meanwhile, microRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression post-translationally by binding to specific mRNAs. Circulating miRNAs are increasingly recognised as novel biomarker or therapeutic targets, owing to their unique characteristics, such as their resilience to degradation by endogenous RNases, multiple downstream targets, involvement in biological processes, some degree of tissue specificity, relatively easy access and quantification. Unlike proteins, there are far less miRNAs and mature miRNAs are highly stable, structurally less complex without post-translational modification with high degree of conservation across species. Aberrant expression of miRNAs has been established in both in vitro and in vivo models of DKD. An up-to-date compilation of previous studies involving selected circulating miRNAs in blood and urine samples of DKD patients is discussed herein. SUMMARY: This review highlights the unmet clinical challenges and dysregulation of miRNAs in the pathogenesis of DKD.

Association between bone characteristics and cardiovascular risk factors among adults in selected urban areas in Selangor, Malaysia.

INTRODUCTION: Cardiovascular disease and osteoporosis (OP) have been shown to have similar risk factors but studies have demonstrated contradictory results with regards to their associations. This study evaluated relationships between bone characteristics and cardiovascular risk factors among adults in selected urban areas in Malaysia. MATERIALS AND METHODS: A cross-sectional study was performed involving 331 subjects between 45-90 years recruited at a health screening programme. Sociodemographic and clinical characteristics were recorded. Biochemical analyses on fasting blood samples and dual energy X-ray absorptiometry scan to determine bone mineral density (BMD) were performed. RESULTS: Increased waist circumference (WC) was protective for abnormal BMD status (osteopenia and OP). Males with increased high-density lipoprotein cholesterol (HDL) were more likely to be osteoporotic. WC, fasting blood glucose (FBG) and triglyceride (TG) were positively associated with BMD at all sites but was gender specific. In contrast, WC was negatively associated with trabecular bone score (TBS) for females but this association became attenuated when adjusted for fat percentage. HDL and MetS were negatively and positively associated with BMD, respectively in males. CONCLUSION: The cardiovascular risk factors of raised WC, FBG, TG and low HDL were significantly associated with increased BMD with skeletal site and gender specific differences after adjusting for confounders. However, a higher WC was associated with a weaker skeletal microstructure reflected by lower TBS in females driven by fat percentage. A higher BMD was demonstrated among MetS individuals. These findings suggest that adiposity may have a protective effect on BMD.

High sensitivity C-reactive protein (hsCRP): Its relationship with metabolic syndrome and Framingham Risk Score.

INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death in Malaysia. Identification of asymptomatic at-risk individuals is often achieved by means of a risk prediction algorithm. Traditional CVD risk factors and their associated algorithms are, however, limited by residual CVD risk. High sensitivity C-reactive protein (hsCRP) has emerged as a novel CVD risk factor. This study aimed to evaluate hsCRP as an adjunct CVD risk marker among the adult Malaysian population by determining its correlation with the Framingham Risk Score (FRS). Comparison analyses were done according to sociodemographic, clinical and laboratory factors and between subjects with and without Metabolic Syndrome (MetS). METHOD: This cross-sectional study involved eighty-three (n=83) adults attending a health screening program at Universiti Putra Malaysia (UPM). Demographic data, anthropometric measurements and blood samples for fasting blood glucose (FBG), fasting lipid profile (FSL), glycated haemoglobin (HbA1c) and hsCRP were taken. Respondents were grouped according to FRS and the Joint Interim Statement into 10-year CVD risk categories (low, intermediate and high) and MetS, respectively. RESULTS: hsCRP was significantly increased in patients with high body mass index (BMI) (p=0.001), at-risk waist circumference (WC) (p=0.001) and MetS (p=0.009). Spearman's correlation coefficient showed a significant positive correlation between hsCRP level and total FRS score (r=0.26, p<0.05) and HDL-C score (r=0.22, p<0.05). CONCLUSION: The significant difference of hsCRP levels across obesity levels and MetS with its modest correlation with FRS scores supported the adjunctive role of hsCRP in CVD risk prediction, most likely capturing the inflammatory pathological aspect and thus partly accounting for the residual CVD risk.

Determination of salivary cortisol reference interval in a selected Malaysian population.

INTRODUCTION: Salivary cortisol is used as an indicator of stress level and a recommended screening test for Cushing syndrome. The normal reference interval for salivary cortisol is dependent on the analytical methodology and the population studied and hence, establishment of a local population-based reference interval is recommended. MATERIALS AND METHODS: A total of 129 healthy blood donors and staffs of Penang General Hospital were recruited from June 2018-May 2019. Paired (morning and late-night) saliva samples were collected from individuals aged between 18 and 60 years old with no history of chronic medical illness. Salivary cortisol was assayed using electrochemiluminescence immunoassay technique. Non-parametric statistics were used for calculation of reference interval and 90% confidence intervals (90% CIs). RESULTS: The reference interval for morning and latenight salivary cortisol was 2.09 - 22.63 nmol/L and <12.00 nmol/L, respectively. CONCLUSION: The locally-derived adult reference intervals for morning and late-night salivary cortisol concentration was determined and varied with previous studies emphasising the need in establishing individual laboratory reference interval.

A pilot study on pattern B lipoprotein profile in Malaysia.

INTRODUCTION: Dyslipidaemia is a recognised conventional risk factor for cardiovascular disease (CVD). However, even when traditional lipid parameters are normal, CVD risk can exist. Small dense lowdensity lipoprotein cholesterol (sdLDL) has appeared as a significant risk marker for CVD. This study aimed to determine the prevalence and associated factors of atherogenic lipoprotein Pattern B in the Malaysian population. MATERIALS AND METHODS: This cross-sectional study included 150 subjects aged 30 years and above who attended a health screening in a Malaysian tertiary institution. Sociodemographics, clinical characteristics and laboratory parameters (lipids, glucose, and sdLDL) were obtained. Lipoprotein subfraction was analysed using the polyacrylamide gel electrophoresis method. RESULTS: Malays and females made up the majority of subjects and the median age was 37 years. Normolipidaemic Pattern B was significantly higher in women (p=0.008). Significant independent predictors of Pattern B were gender (p=0.02), race (p=0.01), body mass index (BMI) [p=0.02] and lipid status (p=0.01). Triglyceride was the only independent predictor of sdLDL (p=0.001). CONCLUSION: The prevalence of Pattern B of 33% in this study was comparatively high, of which 6.7% were normolipidaemic. Chinese males with dyslipidaemia and increased BMI independently predicted Pattern B. Differences in triglyceride levels alone among these ethnic groups do not fully explain the differences in the prevalence of Pattern B although it was the only lipid parameter to independently predict sdLDL. Individuals with atherogenic normolipidaemia are at greater risk for a CVD event as they are not included in the protective measures of primary CVD prevention.

Appropriateness of metformin prescription for type 2 diabetes mellitus patients with chronic kidney disease (Stages 3-5).

INTRODUCTION: Metformin is the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM). Guidelines recommend metformin to be given at reduced dosages for those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and omitted in those with eGFR<30 mL/min/1.73m2. Lactic acidosis is a known complication of those on metformin. This study aimed to determine the appropriateness of metformin prescription in T2DM patients with chronic kidney disease (CKD) stages 3-5 in a tertiary centre in Malaysia. MATERIALS AND METHODS: A cross-sectional design using retrospective secondary data of T2DM patients on metformin attending nephrology and diabetic clinics in the year 2017. eGFR calculated using the CKD-EPI formula identified those in CKD stage 3-5 defined using the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Metformin prescription was considered appropriate when the metformin maximum daily dosage does not exceed 1500 mg in CKD stage 3a and 1000 mg in CKD stage 3b and metformin stopped in CKD stages 4 and 5. RESULTS: A total of 143 patients were included. Majority were in the elderly age group (62.9%), male (60.8%) and had concurrent hypertension (85.3%). Median HbA1c was 8.3% (67 mmol/mol) with most patients (88.8%) having HbA1c above 6.5% (48 mmol/ mol). Majority (92.3%) were categorised as stage 3 CKD. Eleven (7.7%) subjects had inappropriate metformin prescription. Seven of nine (78%) subjects in CKD stage 4 were on metformin with a maximum daily dose of 500 mg to1000 mg. Three patients had serum lactate measured. CONCLUSION: The majority of CKD patients had appropriate metformin prescription. However, a considerable number of CKD stage 4 patients continued to be on metformin. The many benefits of metformin may be a reason why it is still continued against recommendations. Only three patients had lactate measured which, although may suggest that lactic acidosis is not a common occurrence, the potential for metformin-associated lactic acidosis especially in those at risk should be considered.

Light chain multiple myeloma: an evaluation of its biochemical investigations.

Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein or monoclonal (M)-protein in serum or urine. The M-protein may consist of an intact immunoglobulin, the heavy chain only or the light chain only. The latter, designated as light chain multiple myeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heralded by hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions, reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free light chain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. This case illustrates a typical presentation of LCMM with focal discussion on its initial and diagnostic, as well as prognostic biochemical investigations.

Determination of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I in Malaysian population.

Introduction of high-sensitivity cardiac troponin I (hscTn I) assays for routine clinical use in Malaysia requires determination of the 99th percentile upper reference limit (URL) for each assay to suit local context. Hence, this study aimed to determine the 99th percentile URL for hscTn I in the Malaysian population. A total of 250 (120 males and 130 females) healthy Malaysian blood donors aged 18 to 60 years old were recruited. Blood samples for hscTn I were measured using Abbott Diagnostics hscTn I assay on Architect i2000sr analyser. The 99th percentile was calculated using a non-parametric method and gender specific results were compared. The 99th percentile URL for hscTn I for the overall population was 23.7 ng/L, with gender specific values being 29.9 ng/L and 18.6 ng/L for male and female, respectively. Females had significantly lower hscTn I compared to males. This study confirms the use of gender specific 99th percentile URL for hscTn I for clinical use in a multi-ethnic Malaysian population.

Relationship between dyslipidaemia and glycaemic status in patients with Type 2 diabetes mellitus.

The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.