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 toFRSand the Joint Interim Statementinto 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.

Different reference ranges affect the prevalence of osteoporosis and osteopenia in an urban adult Malaysian population

Objectives@#To determine the prevalence of osteopenia (OPe) and osteoporosis (OP) in an urban adult population in Malaysia, and to compare the change in the prevalence when using a Caucasian compared to an Asian reference range. @*Methods@#A cross-sectional random sample of the population aged between 45 and 90 years from the state of Selangor, Malaysia, was invited to attend a bone health check-up. Participants with diseases known to affect bone metabolism or who were on treatment for OP were excluded. Bone mineral density was measured using dual energy X-ray absorptiometry. Based on the World Health Organization definitions, the prevalence of OPe and OP was calculated using the Asian and Caucasian T-scores. @*Results@#A total of 342 subjects (222 females, 120 males), with a mean age of 59.68 (standard deviation: 8.89) years, who fulfilled the study criteria were assessed. Based on the Asian reference range, there were 140 (40.9%) subjects with OPe and 48 (14.0%) with OP. On applying the Caucasian reference range, there were 152 (44.4%) subjects with OPe and 79 (23.1%) with OP, with significant increases in males, females, and Chinese ethnic groups. Overall, 75 (21.9%) of subjects had a change in their diagnostic status. T-scores were consistently lower when the Caucasian reference range was used. @*Conclusions@#In a healthy urban Malaysian population, the prevalence of OP is 14.0% and OPe is 40.9%. Application of a Caucasian reference range significantly increased the number of subjects with OP and may potentially lead to over-treatment.

Bone Turnover Markers and Sphingosine-1-phosphate levels among the Chinese Community in Selangor, Malaysia and its Correlation with Bone Density

@#Introduction: Prevention of osteoporotic fracture requires identification of individuals at high risk. Bone mineral density(BMD) is commonly used to estimate fracture probability despite inadequate predictive discrimination ability. Sphingosine-1-phosphate(S1P), a new marker of bone metabolism and bone turnover markers(BTM) such as procollagen-type-1 amino-terminal propeptide(P1NP) and C-terminal telopeptide of type I collagen(CTX) may complement current assessment. The study determined P1NP, CTX and S1P levels and their correlation with BMD, 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone(PTH) in selected subjects. Method: A cross-sectional study involving Malaysian Chinese men and women aged 50-90 years old from Puchong and Kajang, Selangor. Each subject had BMD determined by dual-energy x-ray absorptiometry and blood samples taken for 25(OH)D, PTH, P1NP, CTX and S1P. Results: A total of 131 subjects [45(34.4%) males and 86(65.6%) post-menopausal women] with median age of 65(IQR=17) were recruited. P1NP and CTX were significantly higher in post-menopausal women (P1NP=61.71 ng/ml, CTX=0.489 ng/ml) compared to men (P1NP=46.94 ng/ml, CTX=0.381 ng/ml). P1NP and CTX differed significantly according to BMD categories with values highest in osteoporosis. S1P between men (2.12±0.75 µmol/L) and post-menopausal women (1.96±0.68 µmol/L) did not differ significantly and did not differ according to BMD categories. S1P did not correlate with BMD, P1NP, CTX and 25(OH)D. P1NP and CTX negatively correlated with BMD at all measured sites but not 25(OH)D. Conclusion: CTX and P1NP, but not S1P negatively correlated with BMD. CTX and P1NP were highest in those with osteoporosis. In this group of Malaysian Chinese subjects, CTX and P1NP rather than S1P reflects bone health.

Derivation and Internal Validation of an Equation for Albumin-adjusted Calcium at a Tertiary Hospital in Selangor, Malaysia

@#Introduction: Total calcium concentration is widely used to assess body calcium status although limited by many confounding factors. Thus, this study aimed to derive and internally validate an albumin-adjusted calcium equation for a selected Malaysian population. Method: This cross-sectional study involved 1011 adults at an emergency department of a tertiary hospital. Patients who had total calcium, ionised calcium and albumin measurements taken simultaneously were included. Derivation of the albumin-adjusted calcium equation was based on the adjustment equation obtained from the Association for Clinical Biochemistry and Laboratory Medicine 2015 position paper. Additionally, the equation was internally validated and compared with ionised calcium (gold standard) and the conventional Payne’s equation. Results: The newly derived equation = total calcium + 0.017 (41.35 – albumin). Internal validation exhibited the amount of shrinkage of 0.049. It tends to overestimate the adjusted calcium by a mean difference of 0.029 mmol/L compared to Payne’s equation. The comparison between Payne’s equation and the new equation with ionised calcium reclassified 402 and 486 patients, respectively into different calcium status. When both equations were compared, calcium status classification significantly differed in all and hypoalbuminaemic subjects by 90 and 16 patients, respectively. Conclusion: Locally derived albumin-adjusted calcium equation differed statistically in calcium status classification when compared to the Payne’s equation. However, to confirm this significance, the result must be compared to ionised calcium under strict, controlled preanalytical conditions. In terms of clinical significance, there was no difference in classification of calcium status between Payne’s and the new equation at medical decision limits.

Different reference ranges affect the prevalence of osteoporosis and osteopenia in an urban adult Malaysian population

Objectives@#To determine the prevalence of osteopenia (OPe) and osteoporosis (OP) in an urban adult population in Malaysia, and to compare the change in the prevalence when using a Caucasian compared to an Asian reference range. @*Methods@#A cross-sectional random sample of the population aged between 45 and 90 years from the state of Selangor, Malaysia, was invited to attend a bone health check-up. Participants with diseases known to affect bone metabolism or who were on treatment for OP were excluded. Bone mineral density was measured using dual energy X-ray absorptiometry. Based on the World Health Organization definitions, the prevalence of OPe and OP was calculated using the Asian and Caucasian T-scores. @*Results@#A total of 342 subjects (222 females, 120 males), with a mean age of 59.68 (standard deviation: 8.89) years, who fulfilled the study criteria were assessed. Based on the Asian reference range, there were 140 (40.9%) subjects with OPe and 48 (14.0%) with OP. On applying the Caucasian reference range, there were 152 (44.4%) subjects with OPe and 79 (23.1%) with OP, with significant increases in males, females, and Chinese ethnic groups. Overall, 75 (21.9%) of subjects had a change in their diagnostic status. T-scores were consistently lower when the Caucasian reference range was used. @*Conclusions@#In a healthy urban Malaysian population, the prevalence of OP is 14.0% and OPe is 40.9%. Application of a Caucasian reference range significantly increased the number of subjects with OP and may potentially lead to over-treatment.

Light chain multiple myeloma: an evaluation of its biochemical investigations

Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein ormonoclonal (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 multiplemyeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heraldedby hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions,reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free lightchain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. Thiscase 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.

A Brief Review on Free Light Chain Assays: From Conventional to Current

Free light chains (FLCs) are tumour markers of monoclonal gammopathies. Detection of urinary FLC or also known as Bence-Jones protein through urinary protein and its immunofixation electrophoreses (UPE and uIFE, respectively) have been considered the gold standard for its biochemical diagnosis. This is mainly due to their superior detection limits compared to their counterpart investigations in serum. However, urinalysis is limited in many ways. The emergence of serum FLC assay with markedly improved detection limit circumvents many of these problems and has gained much importance in biochemical investigations of monoclonal gammopathies. Nevertheless, they are not without limitations. This review discusses the advantages and limitations of serum and urinary FLC assays.

Trends in post osteoporotic hip fracture care from 2010 to 2014 in a private hospital in Malaysia

OBJECTIVE: Following an osteoporotic fracture, pharmacological treatment is recommended to increase bone mineral density and prevent future fractures. However, the rate of starting treatment after an osteoporotic hip fracture remains low. The objective of this study was to survey the treatment rate following a low-trauma hip fracture at a tertiary private hospital in Malaysia over a period of 5 years. METHODS: The computerised hospital discharge records were searched using the terms “hip,”“femur,”“femoral,”“trochanteric,”“fracture,” or “total hip replacement” for all patients over the age of 50, admitted between 2010 and 2014. The medical charts were obtained and manually searched for demographic data and treatment information. Hip operations done for non–low-trauma-related fracture and arthritis were excluded. RESULTS: Three hundred seventy patients over the age of 50 years were admitted with a hip fracture, of which 258 (69.7%) were low trauma, presumed osteoporotic, hip fractures. The median age was 79.0 years (interquartile range [IQR], 12.0). Following a hip fracture, 36.8% (95 of 258) of the patients received treatment, but out of these, 24.2% (23 of 95) were on calcium/vitamin D only. The median duration of treatment was 1 month (IQR, 2.5). In 2010, 56.7% of the patients received treatment, significantly more than subsequent years 2011–2014, where approximately only 30% received treatment. CONCLUSIONS: Following a low-trauma hip fracture, approximately 72% of patients were not started on active antiosteoporosis therapy. Of those who were, the median duration of treatment was 1 month. This represents a missed opportunity for the prevention of future fractures.

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.

Practice Of Self-Monitoring Blood Glucose Among Insulin-treated Diabetic Patients In Hospital Serdang

Background: Diabetes Mellitus (DM), characterised by chronic hyperglycaemia, exposes patients to acute and chronic complications, such as hypoglycaemia and vascular complications, respectively. The latter is associated with the degree of glycaemic control. Glycated haemoglobin (HbA1c) indicates long-term glycaemic control of the preceding 2-3 months. The practice of self-monitoring blood glucose (SMBG) is essential for insulin-treated diabetic patients to achieve optimum glycaemic control and prevent hypoglycaemia. Aim: The study aimed to determine the SMBG practice and frequency and its association with HbA1c and factors in insulin-treated diabetic patients. Methods: This was a cross-sectional study of insulin-treated diabetic patients attending follow-up at the diabetic clinic of Hospital Serdang from April 2015 to August 2015. Consented eligible patients completed validated selfadministered questionnaires. Patients’ HbA1c results were obtained from the hospital information system. Results: Ninetyone of 137 (66%) patients practiced SMBG and 46 (34%) did not. Although 82% had seen diabetic nurses, 54% of patients did not alter their treatment accordingly. Neither the practice nor the frequency of SMBG was significantly associated with differences in HbA1c levels (p=0.334 and p=0.116 respectively). Ethnicity and household income significantly affected SMBG practice. The presence and frequency of hypoglycaemia significantly increased the likelihood of SMBG practice (p<0.001) and frequency (p<0.001). Conclusions: The prevalence of SMBG practice in diabetic patients on insulin was 66%. However, SMBG was not followed by proper treatment alteration in 54% of patients. There was no association between SMBG practice and frequency with good glycaemic control. Hypoglycaemia significantly affected the practice and frequency of SMBG.

A Case of Familial Phaechromocytoma- Was It?

With advancement in genetic studies, familial phaeochromocytoma (PCC) and paraganglioma (PGL) are increasingly being recognized. Characteristically, correlations exist between genotypes and clinical and biochemical phenotypes. We report a phaeochromocytoma in a young patient with intriguing family histories, raising the possibility of his being a familial case.

Subclinical Hypothyroidism among Patients with Depressive Disorders

Subclinical hypothyroidism (SHT) is a biochemical diagnosis, defined as an elevated Thyroid Stimulating Hormone (TSH) with normal free thyroxine (FT4). It affects 4-10% of the adult population and is more prevalent in elderly women. Its commonest cause is autoimmune thyroiditis, detected by antithyroid peroxidase antibody (TPO-Ab). About 2-5% of SHT patients progress to overt hypothyroidism annually. The SHT prevalence among depressed patients ranges between 3% and 17%. This study aimed to determine the prevalence of SHT and TPO-Ab positivity among patients diagnosed with depressive disorders. It was a cross-sectional study carried out in the Universiti Kebangsaan Malaysia Medical Centre over a 12 months period. Serum TSH, FT4 and TPO-Ab were measured. Results showed that 82% of depressed patients were euthyroid, 4% had SHT, 11% had subclinical hyperthyroidism and 2% had discordant thyroid function. TPO-Ab positivity among the subjects was 7%, one of whom had SHT. In conclusion, the prevalence of SHT and TPO-Ab positivity in the study population, at 4% and 7%, respectively, were comparable to previous findings.