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Confounders in Identification and Analysis of Inflammatory Biomarkers in Cardiovascular Diseases
Qurrat Ul Ain1, Mehak Sarfraz2, Gayuk Kalih Prasesti1
1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung 40132, Indonesia.
Insights
Systemic inflammation, measured by biomarkers like C-reactive protein (CRP) and interleukins (IL), is linked to cardiovascular disease. This review examines how demographic, lifestyle, and analytical factors affect these key inflammatory biomarker levels.
Area of Science:
- Biomedical Science
- Epidemiology
- Immunology
Background:
- Proinflammatory biomarkers are crucial for studying systemic inflammation and cardiovascular diseases (CVD).
- While elevated inflammatory biomarkers correlate with CVD pathology, underlying mechanisms remain unclear.
- Identifying biomarkers like cytokines, chemokines, and acute-phase proteins aids early disease diagnosis.
Purpose of the Study:
- To review and summarize the impact of demographic, epidemiological, medication, and analytical factors on serum inflammatory biomarker concentrations.
- To investigate variations in key biomarkers including C-reactive protein (CRP), Interleukin-1 beta (IL-1b), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFa), and soluble TNF receptors.
- To understand how confounding variables influence the measurement and interpretation of inflammatory biomarkers in research.
Main Methods:
- Systematic review of studies investigating inflammatory biomarkers and CVD.
- Analysis of factors influencing biomarker concentrations: age, sex, BMI, medication use, lifestyle, and medical history.
- Examination of pre-analytical (sample collection, storage) and analytical (assay methods, data processing) variations.
- Focus on specific biomarkers: CRP, IL-1b, IL-6, TNFa, and soluble TNF receptors.
Main Results:
- Demographic factors (age, sex) and lifestyle (BMI, substance use) significantly influence biomarker levels.
- Medication use and co-existing medical conditions introduce variability in inflammatory marker concentrations.
- Pre-analytical and analytical inconsistencies can lead to significant variations in reported biomarker results.
- Specific patterns of variation were observed for CRP, IL-1b, IL-6, TNFa, and soluble TNF receptors.
Conclusions:
- Confounding factors, including demographic, epidemiological, and analytical variables, critically affect inflammatory biomarker concentrations.
- Standardization of methodologies is essential to reduce variability and improve the reliability of biomarker studies in CVD research.
- Further research is needed to elucidate the precise mechanisms linking inflammation and CVD, accounting for these influential factors.
Abstract:
Proinflammatory biomarkers have been increasingly used in epidemiologic and intervention studies over the past decades to evaluate and identify an association of systemic inflammation with cardiovascular diseases. Although there is a strong correlation between the elevated level of inflammatory biomarkers and the pathology of various cardiovascular diseases, the mechanisms of the underlying cause are unclear. Identification of pro-inflammatory biomarkers such as cytokines, chemokines, acute phase proteins, and other soluble immune factors can help in the early diagnosis of disease. The presence of certain confounding factors such as variations in age, sex, socio-economic status, body mass index, medication and other substance use, and medical illness, as well as inconsistencies in methodological practices such as sample collection, assaying, and data cleaning and transformation, may contribute to variations in results. The purpose of the review is to identify and summarize the effect of demographic factors, epidemiological factors, medication use, and analytical and pre-analytical factors with a panel of inflammatory biomarkers CRP, IL-1b, IL-6, TNFa, and the soluble TNF receptors on the concentration of these inflammatory biomarkers in serum.
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