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Explore the world of blood, hair, and saliva biomarkers in health research. Learn about lipids, hormones, and their impact on diseases. Discover how measuring these biomarkers can predict cardiovascular risks, hormone imbalances, and overall health conditions.
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Blood, hair and saliva biomarkers David Lee Manchester Metropolitan University
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
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
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
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
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.
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
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)
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…
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
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
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
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…
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…
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
- 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
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
- 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.
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
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)
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
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
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
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
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
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