Stability of glycated haemoglobin (HbA1c) measurements from whole blood samples kept at -196°C for seven to eight years in The Malaysian Cohort study.

OBJECTIVE: Glycated haemoglobin (HbA1c) is a standard indication for screening type 2 diabetes that also has been widely used in large-scale epidemiological studies. However, its long-term quality (in terms of reproducibility) stored in liquid nitrogen is still unknown. This study is aimed to evaluate the stability and reproducibility of HbA1c measurements from frozen whole blood samples kept at -196°C for more than 7 years. METHODS: A total of 401 whole blood samples with a fresh HbA1c measurement were randomly selected from The Malaysian Cohort's (TMC) biobank. The HbA1c measurements of fresh and frozen (stored for 7-8 years) samples were assayed using different high-performance liquid chromatography (HPLC) systems. The HbA1c values of the fresh samples were then calculated and corrected according to the later system. The reproducibility of HbA1c measurements between calculated-fresh and frozen samples was assessed using a Passing-Bablok linear regression model. The Bland-Altman plot was then used to evaluate the concordance of HbA1c values. RESULTS: The different HPLC systems highly correlated (r = 0.99) and agreed (ICC = 0.96) with each other. Furthermore, the HbA1c measurements for frozen samples strongly correlate with the corrected HbA1c values of the fresh samples (r = 0.875) with a mean difference of -0.02 (SD: -0.38 to 0.38). Although the mean difference is small, discrepancies were observed within the diabetic and non-diabetic samples. CONCLUSION: These data demonstrate that the HbA1c measurements between fresh and frozen samples are highly correlated and reproducible.

Prevalence of anaemia and associated risk factors amongst The Malaysian Cohort participants.

This study was aimed at determining the prevalence of anaemia amongst the Malaysian Cohort participants and the associated risk factors. This was a cross-sectional study that involved 102,388 participants from The Malaysian Cohort (TMC) aged between 35 and 70 years old recruited from April 2006 to September 2012. Venous blood was taken for the full blood count. The prevalence of anaemia was 13.8% with majority having the microcytic-hypochromic type (59.7%). Comparison between the ethnic groups showed that Indians have the highest prevalence of anaemia (19.9%), followed by Malays (13.1%), and Chinese (12.0%). The prevalence of anaemia was substantially higher in females (20.1%) compared to males (4.9%). Amongst the female participants, the prevalence of anaemia was highest amongst those who were younger than 49 years old and decreased as the age increased. In contrast, the prevalence of anaemia in males increased with age. Gender, ethnicity, age, marital status, presence of platelet disorders and kidney disease were significant risk factors associated with anaemia and contributed to 14.9% of the risk of developing anaemia in this population. The prevalence of anaemia amongst the Malaysian Cohort participants is 13.8% with the majority having the microcytic and hypochromic type implying iron deficiency as the main cause. It is important that those who have anaemia be further investigated and treated.

10-Year Cardiovascular Disease Risk Estimation Based on Lipid Profile-Based and BMI-Based Framingham Risk Scores across Multiple Sociodemographic Characteristics: The Malaysian Cohort Project.

Cardiovascular disease (CVD) leads to high morbidity and mortality rate worldwide. Therefore, it is important to determine the risk of CVD across the sociodemographic factors to strategize preventive measures. The current study consisted of 53,122 adults between the ages of 35 and 65 years from The Malaysian Cohort project during recruitment phase from year 2006 to year 2012. Sociodemographic profile and physical activity level were assessed via self-reported questionnaire, whereas relevant CVD-related biomarkers and biophysical variables were measured to determine the Framingham Risk Score (FRS). The main outcome was the 10-year risk of CVD via FRS calculated based on lipid profile and body mass index (BMI) associated formulae. The BMI-based formula yielded a higher estimation of 10-year CVD risk than the lipid profile-based formula in the study for both males (median = 13.2% and 12.7%, respectively) and females (median = 4.3% and 4.2%, respectively). The subgroup with the highest risk for 10-year CVD events (based on both FRS formulae) was the Malay males who have lower education level and low physical activity level. Future strategies for the reduction of CVD risk should focus on screening via BMI-based FRS in this at-risk subpopulation to increase the cost-effectiveness of the prevention initiatives.

Development of digital health management systems in longitudinal study: The Malaysian cohort experience.

Background: The management of extensive longitudinal data in cohort studies presents significant challenges, particularly in middle-income countries like Malaysia where technological resources may be limited. These challenges include ensuring data integrity, security, and scalability of storage solutions over extended periods. Objective: This article outlines innovative methods developed and implemented by The Malaysian Cohort project to effectively manage and maintain large-scale databases from project inception through the follow-up phase, ensuring robust data privacy and security. Methods: We describe the comprehensive strategies employed to develop and sustain the database infrastructure necessary for handling large volumes of data collected during the study. This includes the integration of advanced information management systems and adherence to stringent data security protocols. Outcomes: Key achievements include the establishment of a scalable database architecture and an effective data privacy framework that together support the dynamic requirements of longitudinal healthcare research. The solutions implemented serve as a model for similar cohort studies in resource-limited settings. The article also explores the broader implications of these methodologies for public health and personalized medicine, addressing both the challenges posed by big data in healthcare and the opportunities it offers for enhancing disease prevention and management strategies. Conclusion: By sharing these insights, we aim to contribute to the global discourse on improving data management practices in cohort studies and to assist other researchers in overcoming the complexities associated with longitudinal health data.

Cardiovascular risk prediction with cardio-ankle vascular index in the malaysian cohort study.

The cardio-ankle vascular index (CAVI) is an important parameter assessing arterial function. It reflects arterial stiffness from the origin of the aorta to the ankle, and the algorithm is blood pressure independent. Recent data have suggested that a high CAVI score can predict future cardiovascular disease (CVD) events; however, to date, no study has been done in Malaysia. We conducted a prospective study on 2,168 The Malaysian Cohort (TMC) CVD-free participants (971 men and 1,197 women; mean age 51.64 ± 8.38 years old) recruited from November 2011 to March 2012. This participants were followed-up until the emergence of CVD incidence and mortality (endpoint between May to September 2019; duration of 7.5 years). Eligible participants were assessed based on CAVI baseline measurement which categorised them into low (CAVI <9.0) and high (CAVI ≥ 9.0) scores. The CVD events in the group with high CAVI (6.5 %) were significantly higher than in the low CAVI (2.6 %) group (p < 0.05). CAVI with cut-off point ≥ 9.0 was a significant independent predictor for CVD event even after adjustment for male, ethnicity, age, and intermediate atherogenic index of plasma (AIP). Those who have higher CAVI have 78 % significantly higher risk of developing CVD compared to those with the low CAVI (adjusted OR [95 % CI] = 1.78 [1.04 - 3.05], p =0.035). In addition, the participants with higher CAVI have significantly lower survival probability than those who have lower CAVI values. Thus, this study indicated that the CAVI can predict CVD event independently among the TMC participants.

Hepatitis B and influenza vaccination coverage in healthcare workers, the elderly, and patients with diabetes in Malaysia.

Adult immunization remains to be a neglected issue in developing countries including Malaysia. This nationwide study determined the vaccination coverage of hepatitis B and influenza among Malaysia's healthcare workers (HCWs), the elderly (aged 60 y and above) and patients with diabetes, who are the participants of The Malaysia Cohort Program. The participants were categorized based on their occupation, age and medical history. Self-reported questionnaire was used to assess the participant's hepatitis B and influenza vaccination status. A Chi-square test and logistic regression analyses were performed to determine the risk factors associated with vaccination behavior. The hepatitis B vaccination coverage for healthcare workers, elderly, and patients with diabetes were 34.6%, 10.1% and 9.8%, respectively. The influenza vaccination coverage rates for healthcare workers, the elderly and patients with diabetes were 26.3%, 5.5% and 6.4%, respectively. The Chinese were more likely to be vaccinated against hepatitis B, while Malay was more likely to be vaccinated against influenza. Individuals with higher education and living in urban areas were more likely vaccinated than those with low education levels and who lived in rural areas. The low vaccination coverage for healthcare workers was alarming because hepatitis B and influenza were subsidized for the healthcare workers. The hepatitis B and influenza vaccination coverage among healthcare workers, elderly and patients with diabetes in Malaysia were low. Specific interventions such as educational and awareness programs should be conducted to increase the vaccination rate among adults, especially those at high risk.

Hypercholesterolemia in the Malaysian Cohort Participants: Genetic and Non-Genetic Risk Factors.

Hypercholesterolemia was prevalent in 44.9% of The Malaysian Cohort participants, of which 51% were Malay. This study aimed to identify the variants involved in hypercholesterolemia among Malays and to determine the association between genetic and non-genetic risk factors. This nested case-control study included 25 Malay participants with the highest low-density lipoprotein cholesterol (LDL-C, >4.9 mmol/L) and total cholesterol (TC, >7.5 mmol/L) and 25 participants with the lowest LDL-C/TC. Genomic DNA was extracted, and whole-exome sequencing was performed using the Ion ProtonTM system. All variants were annotated, filtered, and cross-referenced against publicly available databases. Forty-five selected variants were genotyped in 677 TMC Malay participants using the MassARRAY® System. The association between genetic and non-genetic risk factors was determined using logistic regression analysis. Age, fasting blood glucose, tobacco use, and family history of hyperlipidemia were significantly associated with hypercholesterolemia. Participants with the novel OSBPL7 (oxysterol-binding protein-like 7) c.651_652del variant had 17 times higher odds for hypercholesterolemia. Type 2 diabetes patients on medication and those with PCSK9 (proprotein convertase subtilisin/kexin type 9) rs151193009 had low odds for hypercholesterolemia. Genetic predisposition can interact with non-genetic factors to increase hypercholesterolemia risk in Malaysian Malays.

Discordance between Fasting Plasma Glucose (FPG) and HbA1c in Diagnosing Diabetes and Pre-diabetes in The Malaysian Cohort.

OBJECTIVE: In this present study, we aim to evaluate the accuracy of the HbA1c relative to fasting plasma glucose (FPG) in the diagnosis of diabetes and pre-diabetes among The Malaysian Cohort (TMC) participants. METHODOLOGY: FPG and HbA1c were taken from 40,667 eligible TMC participants that have no previous history of diabetes, aged between 35-70 years and were recruited from 2006 - 2012. Participants were classified as normal, diabetes and pre-diabetes based on the 2006 World Health Organization (WHO) criteria. Statistical analyses were performed using ANOVA and Chi-square test, while Pearson correlation and Cohen's kappa were used to examine the concordance rate between FPG and HbA1c. RESULTS: The study samples consisted of 16,224 men and 24,443 women. The prevalence of diabetes among the participants was 5.7% and 7.5% according to the FPG and HbA1c level, respectively. Based on FPG, 10.6% of the participants had pre-diabetes but this increased to 14.2% based on HbA1c (r=0.86; P<0.001). HbA1c had a sensitivity of 58.20 (95% CI: 56.43, 59.96) and a specificity of 98.59 (95% CI: 98.46, 98.70). CONCLUSION: A higher prevalence of pre-diabetes and diabetes was observed when using HbA1c as a diagnosis tool, suggesting that it could possibly be more useful for early detection. However, given that HbA1c may also have lower sensitivity and higher false positive rate, several diagnostic criteria should be used to diagnose diabetes accurately.

Participants Attrition in a Longitudinal Study: The Malaysian Cohort Study Experience.

The attrition rate of longitudinal study participation remains a challenge. To date, the Malaysian Cohort (TMC) study follow-up rate was only 42.7%. This study objective is to identify the cause of attrition among TMC participants and the measures to curb it. A total of 19,343 TMC participants from Kuala Lumpur and Selangor that was due for follow-up were studied. The two most common attrition reasons are undergoing medical treatment at another government or private health center (7.0%) and loss of interest in participating in the TMC project (5.1%). Those who were inclined to drop out were mostly Chinese, aged 50 years and above, unemployed, and had comorbidities during the baseline recruitment. We have also contacted 2183 participants for the home recruitment follow-up, and about 10.9% agreed to join. Home recruitment slightly improved the overall follow-up rate from 42.7% to 43.5% during the three-month study period.

Development and Relative Validity of a Semiquantitative Food Frequency Questionnaire to Estimate Dietary Intake among a Multi-Ethnic Population in the Malaysian Cohort Project.

Measuring dietary intakes in a multi-ethnic and multicultural setting, such as Malaysia, remains a challenge due to its diversity. This study aims to develop and evaluate the relative validity of an interviewer-administered food frequency questionnaire (FFQ) in assessing the habitual dietary exposure of The Malaysian Cohort (TMC) participants. We developed a nutrient database (with 203 items) based on various food consumption tables, and 803 participants were involved in this study. The output of the FFQ was then validated against three-day 24-h dietary recalls (n = 64). We assessed the relative validity and its agreement using various methods, such as Spearman's correlation, weighed Kappa, intraclass correlation coefficient (ICC), and Bland-Altman analysis. Spearman's correlation coefficient ranged from 0.24 (vitamin C) to 0.46 (carbohydrate), and almost all nutrients had correlation coefficients above 0.3, except for vitamin C and sodium. Intraclass correlation coefficients ranged from -0.01 (calcium) to 0.59 (carbohydrates), and weighted Kappa exceeded 0.4 for 50% of nutrients. In short, TMC's FFQ appears to have good relative validity for the assessment of nutrient intake among its participants, as compared to the three-day 24-h dietary recalls. However, estimates for iron, vitamin A, and vitamin C should be interpreted with caution.

Dengue epidemic in Malaysia: urban versus rural comparison of dengue immunoglobulin G seroprevalence among Malaysian adults aged 35-74 years.

BACKGROUND: A periodic serosurvey of dengue seroprevalence is vital to determine the prevalence of dengue in countries where this disease is endemic. This study aimed to determine the prevalence of dengue immunoglobulin G (IgG) seropositivity among healthy Malaysian adults living in urban and rural areas. METHODS: A total of 2598 serum samples (1417 urban samples, 1181 rural samples) were randomly collected from adults ages 35-74 y. The presence of the dengue IgG antibody and neutralising antibodies to dengue virus (DENV) 1-4 was determined using enzyme-linked immunosorbent assay and the plaque reduction neutralisation test assay, respectively. RESULTS: The prevalence of dengue IgG seropositivity was 85.39% in urban areas and 83.48% in rural areas. The seropositivity increased with every 10-y increase in age. Ethnicity was associated with dengue seropositivity in urban areas but not in rural areas. The factors associated with dengue seropositivity were sex and working outdoors. In dengue IgG-positive serum samples, 98.39% of the samples had neutralising antibodies against DENV3, but only 70.97% of them had neutralising antibodies against DENV4. CONCLUSION: The high seroprevalence of dengue found in urban and rural areas suggests that both urban and rural communities are vital for establishing and sustaining DENV transmission in Malaysia.

Colorectal screening using the immunochemical faecal occult blood test kit among the Malaysian cohort participants.

BACKGROUND: There has been a rapid increase in colorectal cancer (CRC) cases in Asian countries, including Malaysia. CRC is usually diagnosed at a late stage, and early detection of CRC is vital in improving survival. This study was conducted to determine the uptake rate of the immunochemical faecal occult blood test (iFOBT), the response rate to colonoscopy, and the CRC detection rate. We also wanted to identify the association between colorectal neoplasia and the Asia Pacific Colorectal Cancer Screening (APCS) scoring system. METHODS: We recruited 2264 individuals from The Malaysian Cohort participants aged 35-65 years who consented to colorectal screening using the iFOBT kit from July 2017 until January 2019. RESULTS: The response rate and positive iFOBT test rate of this study were 79.6% and 13.1% respectively. Among those with positive results, 125 individuals (52.7%) underwent colonoscopy; CRC was detected in six of them while 45 others (36.0%) had polyps. The overall CRC detection rate was 0.3% while the colorectal neoplasia detection rate (both colorectal cancer and colorectal polyps) was 2.3%. The APCS scoring indicated a significant association with colorectal neoplasia risk, with increasing trend by severity from moderate to high risk (3.46-11.14) compared to low risk. Most of the participants who were positive for iFOBT were those at high risk. CONCLUSIONS: The awareness of CRC risk and iFOBT screening are important strategies for early detection of CRC. We showed a CRC detection rate of 0.3 % among those who volunteered to have the iFOBT screening.

Seroprevalence of hepatitis B virus and hepatitis C virus infection among Malaysian population.

Malaysia is a country with an intermediate endemicity for hepatitis B. As the country moves toward hepatitis B and C elimination, population-based estimates are necessary to understand the burden of hepatitis B and C for evidence-based policy-making. Hence, this study aims to estimate the prevalence of hepatitis B and C in Malaysia. A total of 1458 participants were randomly selected from The Malaysian Cohort (TMC) aged 35 to 70 years between 2006 and 2012. All blood samples were tested for hepatitis B and C markers including hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), antibodies against hepatitis C virus (anti-HCV). Those reactive for hepatitis C were further tested for HCV RNA genotyping. The sociodemographic characteristics and comorbidities were used to evaluate their associated risk factors. Descriptive analysis and multivariable analysis were done using Stata 14. From the samples tested, 4% were positive for HBsAg (95% CI 2.7-4.7), 20% were positive for anti-HBc (95% CI 17.6-21.9) and 0.3% were positive for anti-HCV (95% CI 0.1-0.7). Two of the five participants who were reactive for anti-HCV had the HCV genotype 1a and 3a. The seroprevalence of HBV and HCV infection in Malaysia is low and intermediate, respectively. This population-based study could facilitate the planning and evaluation of the hepatitis B and C control program in Malaysia.

Differing Contributions of Classical Risk Factors to Type 2 Diabetes in Multi-Ethnic Malaysian Populations.

The prevalence of type 2 diabetes is escalating rapidly in Asian countries, with the rapid increase likely attributable to a combination of genetic and lifestyle factors. Recent research suggests that common genetic risk variants contribute minimally to the rapidly rising prevalence. Rather, recent changes in dietary patterns and physical activity may be more important. This nested case-control study assessed the association and predictive utility of type 2 diabetes lifestyle risk factors in participants from Malaysia, an understudied Asian population with comparatively high disease prevalence. The study sample comprised 4077 participants from The Malaysian Cohort project and included sub-samples from the three major ancestral groups: Malay (n = 1323), Chinese (n = 1344) and Indian (n = 1410). Association of lifestyle factors with type 2 diabetes was assessed within and across ancestral groups using logistic regression. Predictive utility was quantified and compared between groups using the Area Under the Receiver-Operating Characteristic Curve (AUC). In predictive models including age, gender, waist-to-hip ratio, physical activity, location, family history of diabetes and average sleep duration, the AUC ranged from 0.76 to 0.85 across groups and was significantly higher in Chinese than Malays or Indians, likely reflecting anthropometric differences. This study suggests that obesity, advancing age, a family history of diabetes and living in a rural area are important drivers of the escalating prevalence of type 2 diabetes in Malaysia.

Utilization of Complementary and Alternative Medicine in Multiethnic Population: The Malaysian Cohort Study.

BACKGROUND: This study aimed to identify the factors of CAM usage for general health and to determine the factors associated with the usage of different types of CAM after the diagnosis of chronic diseases among The Malaysian Cohort participants. METHODS: This was a cross-sectional study derived from The Malaysian Cohort (TMC) project, a prospective population-based cohort aged between 35 to 65 years old that recruited from April 2006 to September 2012. Association between the CAM usage and contributing factors were determined via logistic regression. RESULTS: The sample were mostly female (58.1%), Malays (43.1%), came from urban (71.9%), aged 44 years and below (26.8%) and had secondary education (45.9%). The prevalence of CAM usage varied across diseases; 62.8% in cancer patients, 53.3% in hypercholesterolemia, 49.4% in hypertensives and 48.6% in diabetics. General CAM usage was greater among female (OR: 1.54, 95% CI: 1.49, 1.59), Chinese (OR: 1.15, 95% CI: 1.12, 1.19), those with higher education (OR: 3.12, 95% CI: 3.00, 3.25), urban residents (OR: 1.55, 95% CI: 1.50, 1.61) and older people (OR ranging from 1.15 to 1.75) while for post-diagnosis of chronic diseases usage, the odds were higher among those with lower education and living in rural areas. CONCLUSION: Health status, educational level, age, living location and types of chronic diseases were significant factors that influence CAM usage for the intent of either health maintenance or disease treatment. Further exploration on CAM safety and benefit are crucial to minimize the adverse effect and to ensure the efficacy of CAM product.

Association of job sectors with type 2 diabetes mellitus, hypercholesterolemia and obesity: a cross-sectional study from the Malaysian Cohort (TMC) project.

Background: The investigation of risk factors of cardiovascular disease (e.g., major endocrine, nutritional and metabolic diseases) across job sectors is useful for targeted public health intervention. This study examined the occurrence of type 2 diabetes mellitus (T2DM), hypercholesterolemia and obesity in 21 job sectors in the general population. Methods: A baseline cross-sectional analysis of the Malaysian Cohort was conducted, which included 105 391 adults. Multiple logistic regression analyses were conducted for these three diseases across 20 job sectors compared with the unemployed/homemaker sector. Results: The prevalence of T2DM, hypercholesterolemia and obesity was 16.7%, 38.8% and 33.3%, respectively. The Accommodation & Food Service Activities and Transportation & Storage sectors had significantly higher odds for T2DM (adjusted [adj.] prevalence odds ratio [POR] 1.18, p=0.007 and adj. POR 1.15, p=0.008, respectively). No job sector had significantly higher odds for hypercholesterolemia compared with the unemployed/homemaker sector. Only the Accommodation & Food Service Activities sector had significantly higher odds for obesity (adj. POR 1.17, p≤0.001). Conclusions: Many job sectors were significantly associated with lower odds of having these three diseases when compared with the unemployed/homemaker sector. These differing associations between diverse job sectors and these diseases are important for public health intervention initiatives and prioritization.

Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population.

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100,000 individuals aged 35-70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106,527 participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my).