OBJECTIVES: (1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.

METHODS: 422 subjects (mean age±SD = 43.2±11.9 years) of whom 207 had low HDL-c concentrations (HDL-c <1.0 mmol/L and <1.3 mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3 mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].

RESULTS: Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.

OBJECTIVE: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting.

METHODS: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the "think-aloud" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool.

RESULTS: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023.

CONCLUSIONS: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease.

METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis.