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Blood, hair and saliva biomarkers

Blood, hair and saliva biomarkers. David Lee Manchester Metropolitan University.

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Blood, hair and saliva biomarkers

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  1. Blood, hair and saliva biomarkers David Lee Manchester Metropolitan University

  2. BiomarkersA biomarker is a biological characteristic that is objectively measured and evaluated as an indicator of normal biological or pathological processes, or a response to a therapeutic intervention.Examples include patterns of gene expression, levels of a particular protein in body fluids, or changes in electrical activity in the brain.nature.com

  3. Overview • Lipids(saturated and unsaturated fats, triglycerides and phospholipids) • Hormones(signalling molecules secreted from glands and travel through bloodstream) • Inflammatory markers(raised levels may indicate chronic underlying disease) • Biological time-varying measures

  4. Lipids

  5. Lipid profile • Complete test called a lipid profile or lipid panel • Current guidelines typically recommend measuring lipid levels in a fasting state • Recent data suggest nonfasting lipid profiles change minimally

  6. Lipid measurement • Total cholesterol (TC) • High-density lipoprotein cholesterol (HDL-C) • Low-density lipoprotein cholesterol (LDL-C) • Triglycerides • Cholesterol levels are fairly constant • Triglyceride levels fluctuate considerably from day to day • Levels tends to increase with age • Premenopausal women tend to have higher HDL-C and lower LDL-C/triglycerides than men

  7. Lipids levels • Various guidelines exist on ‘healthy’ lipid levels • National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) • LDL-C typically calculated from total & HDL-C and fasting triglycerides* *Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18(6):499-502.

  8. Biological significance • Multiple epidemiologic studies have shown that increased levels of total cholesterol and LDL-C strongly related to greater incidence of CHD • Elevated triglycerides and LDL-C are associated with the risk of atherosclerotic heart disease • High levels of HDL-C protective factor for the development of atherosclerotic heart disease - so decreased levels of HDL-C constitute a risk factor

  9. Research implications • Many survey datasets will contain at least some blood lipid measurements • Can be investigated in isolation – longitudinal trends, associations with obesity etc… • Can also be used in a variety of validated algorithms to predict 10-year risk of developing CHD or experiencing a CVD event • Framingham risk score • Systemic Coronary Risk Evaluation (SCORE)

  10. Endocrine function

  11. Hormones • Signalling molecules secreted from endocrine glands • Travel in the bloodstream to tissues or organs • Control many processes including: growth and development, metabolism, sexual function, reproduction, mood…

  12. Hormone measurement • Typically measured from blood (serum) sample • Can also be measured in saliva, urine and hair • Endocrine glands release more than 20 major hormones directly into the bloodstream • Assay techniques continue to evolve with improvements in sensitivity and validity • Latest analytical techniques based on mass spectrometry

  13. Biological significance • Individual hormones are typically one part of a more complex hormonal axis or system • hypothalamic–pituitary–adrenal axis (HPA axis) • hypothalamic–pituitary–gonadal axis (HPG axis) • High levels of HDL-C protective factor for the development of atherosclerotic heart disease - so decreased levels of HDL-C constitute a risk factor

  14. Research implications • Behavioural research has focused on both levels and changes in specific hormones • Social sciences research has also become increasingly interested in hormones • Cortisol, testosterone and DHEAS have received most attention in economics and social research • Speculated to be involved in risk aversion, work stress and persistence of poverty

  15. Cortisol • Typically measured from salivary samples • Glucocorticoid hormone (stress hormone) • Cortisol is the primary hormone responsible for the stress response (HPA axis) • HPA axis transduces subjective social-environmental experience into physiological changes relevant to health • Work stress, family problems, sleep deprivation can all lead to chronic elevation of cortisol • Increased cortisol levels linked to higher blood sugar, weakened immune response, depression, frailty, obesity, CVD, memory loss…

  16. Testosterone (T) • Primary male sex steroid and an anabolic steroid • Levels typically an order of magnitude lower in females but of vital physiological importance • T typically declines with age (particularly in men) • Declining T may influence ageing-related deteriorations in body function e.g. frailty, obesity, osteopaenia, cognitive decline, erectile failure… • Low T low testosterone associated with adverse health outcomes among men, but high T has been linked to adverse outcomes among women…

  17. Keevil BG1, MacDonald P, Macdowall W, Lee DM, Wu FC; NATSAL Team. Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females. Ann Clin Biochem. 2014 May;51(Pt 3):368-78

  18. - Hair cortisol is a proxy measure of the total retrospective activity of the HPA axis over the preceding months • - Hair cortisol analysis offers an innovative approach to measuring HPA axis activity in response to chronic stressors

  19. Insulin-like growth factor 1 (IGF-1) • Plays a central role in childhood growth and continues to have anabolic effects in adults • Levels of IGF-1 influenced by genetic make-up, time of day, age, sex, exercise status, stress levels, nutrition level and body mass index (BMI), disease state, ethnicity… • Mixed data that IGF-1 modulates the ageing process in humans and whether the direction of its effect is positive or negative

  20. - Lower SEP was associated with lower free T among men, higher free T among women, and lower IGF-I and higher evening cortisol in both sexes • - SEP differences in endocrine function may partly underlie inequalities in health and function in later life, and may reflect variations in biological rates of ageing.

  21. Glucose (+Insulin) • Measured in a fasting blood sample • Aside from diagnosed diabetes, measurement of fasting glucose can pick up undiagnosed diabetes and impaired-fasting glucose (IFG) • ADA criteria: fasting plasma glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL) • Dysregulated glucose levels associated with poor health outcomes including CVD

  22. Glucose and the Metabolic Syndrome • Clustering of risk factors associated with CVD risk • When 3 of 5 of the listed characteristics are present, a diagnosis of metabolic syndrome can be made. ATP III criteria for metabolic syndrome (2004)

  23. Inflammation

  24. Inflammatory markers • Inflammation can result from a variety of factors including infections, trauma and malignancy • Inflammatory response initiated when inflammatory cytokines released from distressed tissue • Systemic markers of inflammation useful for indicating elevated disease risk in mid- and late-life

  25. Assessing inflammation • Inflammatory markers typically measured from blood sample • Also measurable in saliva and hair • Inflammatory process is complex and not fully understood • Small number of inflammatory markers usually measured in population-based surveys

  26. Biological significance • Tissue inflammation is part of the complex biological response to harmful stimuli • These stimuli are varied and can include pathogens, injury, smoking, obesity, cancer… • Inflammation can be classified as acute or chronic • Chronic inflammation is of primary interest in ageing-related research

  27. Research implications • Social sciences research has become increasingly interested in inflammatory markers and SES • Research suggests that atherosclerosis is primarily an inflammatory disease • In men below 60 years of age inflammatory markers typically have a significant inverse association with socio-economic status • In older age, the SES differences in the levels of inflammatory markers may be masked by the common occurrence of longstanding diseases in all SES groups

  28. C-reactive protein (CRP) • Typically measured from blood samples • Most frequently studied inflammatory marker in epidemiologic studies • Classified as an acute phase reactant, meaning its levels will rise in response to inflammation • Epidemiologic research in middle-aged samples has shown that differences in CRP, even within the “normal” range, discriminate those at high and low risk of atherosclerotic disease

  29. Fibrinogen • Has a critical role in both inflammation and coagulation • Acute phase reactant like CRP • Epidemiologic research has shown elevated fibrinogen is associated with disease severity of chronic pulmonary hypertension • Association between plasma fibrinogen concentration and the risk of cardiovascular disease has been demonstrated in several studies

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