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Biomarker User Guide and Glossary

1. Seccareccia E Brodt P The role of the insulin like growth factor I receptor in malignancy An update Growth Hormone amp IGF Research 22 2012 193 199 3 Troncoso R Ibarra C Vicencio JM Jaimovich E Lavandero S New insights into IGF 1 signaling in the heart Trends Endocrinol Metab 2014 25 128 37 Version 1 December 2014 46 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 17 IGF 1 reference values nmol L in men and women by age Age groups Men Women 17 18 yrs 20 56 35 73 19 20 yrs 21 85 21 51 21 25 yrs 18 42 12 44 26 39 yrs 15 37 12 44 40 54 yrs 14 32 12 44 55 88 yrs 11 30 12 44 What should be considered in analyses To our knowledge there are no factors that require consideration in the analysis Distribution in Understanding Society Figure 13 Distribution of Insulin like growth factor 1 IGF 1 nmol I by gender Males 5 739 Females 7 118 Kernel density estimate 08 06 204 02 T 0 20 40 insulin like growth factor 1 ids method nmol l kernel epanechnikov bandwidth 0 9632 06 04 Kernel density estimate T T T T 0 20 40 60 insulin like growth factor 1 ids method nmol l kernel epanechnikov bandwidth 1 1523 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Version 1 D
2. Biomarker Variable Valid Detecti non _ ANAER CCOA CHOHD CLO FCOA HASTN INSUF NOCLO NB SDI UNAV UNAV UNAV UNUS name on missing R G U T G D F T A S B H L Limit Cholesterol amp triglycerides Cholesterol chol 12 895 98 4 2 132 3 71 4 HDL cholesterol hdl 12 876 98 2 15 2 132 3 79 Triglycerides trig 12 898 98 4 2 1 132 3 71 Glycated haemoglobin hbatc 12 162 92 8 1 1 934 1 8 Inflammatory markers C reactive protein hserp 12 530 381 98 5 2 2 132 3 3 45 9 Cytomegalovirus IgG uscmg 12 896 98 4 2 4 132 3 70 Cytomegalovirus IgM uscmm 12 896 98 4 2 4 132 3 70 CMV avidity tests cmvavc 371 100 0 Clauss fibrinogen cfib 12 837 1 97 9 1 9 1 3 15 215 4 21 Markers of anaemia Haemoglobin hgb 12 156 92 7 8 6 2 933 2 Ferritin rtin 12 894 1 98 4 2 5 132 3 70 Liver function Albumin alb 12 920 98 6 2 2 132 3 44 4 Alkaline phosphatase alkp 12 785 1 97 6 2 132 3 184 Alanine transaminase alt 12 778 1 97 5 2 1 132 3 183 8 Aspartate transaminase ast 12 386 94 5 2 3 132 3 575 6 Gamma glutamyl transferase ggt 12 816 10 97 9 2 132 3 142 2 Kidney function Creatinine ecre 12 918 98 6 2 2 132 3 46 4 Urea ure 12 923 98 6 2 132 3 44 3 Hormones Testosterone testo 7 835 5 054 98 3 2 4 132 3 79 3 Insulin like growth factor 1 igfi 12 831 97 9 2 45 135 2 92 Dihydroepiandrosterone dheas 12 873 23 98 4 2 5 132 3 69 sulphate Test only done on those positive or indeterminant on the CMV IgM test 12 736 not applicable Below
3. Clauss fibrinogen 0 5 g l 1 Ferritin 3 ug l 1 ALP 5 u l 1 ALT 4 u l 1 GGT 5 u l 10 Testosterone 1 nmol l 5 049 52 nmol l 5 DHEAs 0 1 umol l 20 27 umoll l 3 Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary ANALYSIS OF BIOMARKER DATA In analysing biomarkers a range of factors need to be considered Biomarkers may be affected by the time of day the blood is taken For example some hormones such as testosterone are much higher in the morning than later in the day Biomarkers can also be affected by the way the blood has been collected how long it has been stored or the quality of the blood when analysed For example while some biomarkers are robust to being stored at room temperature for a number of days between collection posting and processing others may be sensitive Although those biomarkers that cannot be analysed on old blood at all are known others may become less accurate if stored at room temperature for a few days but there is no systematic information on this for different analytes although as outlined above we are planning a set of experiments to investigate this Similarly bloods frozen for a long time may make some analytes less accurate although based on the comparisons with other studies outlined below we do not believe this is a concern with these biomarkers Some biomarkers are affected by health conditi
4. J ss 4 Kol o 4 J a 4 an 4 o4 o4 T T T T T T T T T 0 4 6 8 0 2 4 triglycerides unfasted mmol l triglycerides unfasted mmol l kernel epanechnikov bandwidth 0 1565 kernel epanechnikov bandwidth 0 1151 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Version 1 December 2014 23 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary GLYCATED HAEMOGLOBIN HbA 1c What is its clinical significance HbA1c has recently been highlighted as a gold standard indicator of diabetes risk It can be used both to identify those who might be suffering from diabetes as well as highlight those people who may not be managing their diabetes consistently What is it Glycated haemoglobin HbAic is a measure of the level of sugar in the blood over the previous 8 to 12 weeks before measurement Technically it is the proportion of haemoglobin proteins that have been bound by glucose How is it measured Glycated haemoglobin is measured from whole blood using HPLC cation exchange on a Tosoh G8 analyser HbA1c can be expressed as a percentage or as a value in mmol mol Since 2009 mmol mol has been the default unit to use in the UK Intra and inter assay coefficients of variation were less than 4 Are there clinical cutpoints HbA1c values gt 48 mmol mol 2 6 5 indicates d
5. 4 gs 3 4 t 3 4 x 4 a 4 t 4 o4 of 0 50 100 0 50 100 alanine transaminase u alanine transaminase u kernel epanechnikov bandwidth 1 9299 kernel epanechnikov bandwidth 1 1533 Distribution of Aspartate Transaminase AST IU L by gender Males n 5 878 Females n 7 284 Kernel density estimate Kernel density estimate o S A ae o gs 4 t a 4 3 4 N M4 a 4 o4 of 20 40 60 80 100 20 0 60 100 aspartate transaminase u aspartate transaminase u kernel epanechnikov bandwidth 1 0929 kernel epanechnikov bandwidth 0 9283 Distribution of Alkaline Phosphatase ALP IU L by gender Males n 5 696 Females n 7 078 o Kernel density estimate Kernel density estimate S d a a J wo PS J wo g J 5 4 S 4 t2 8 J S 1 S gt o4 o4 0 150 0 150 50 100 alkaline phosphatase u l kernel epanechnikov bandwidth 2 7728 50 100 alkaline phosphatase u l kernel epanechnikov bandwidth 2 9992 Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Distribution of Gamma Glutamyl Transferase GGT IU L by gender Males n 5 710 Females n 7 111 Kernel density estimate Kernel density estimate 0 100 200 3 4 100 20 gamma glutamyltransferase u l 0 gamma glutamyltransferase u l kernel epanechnikov bandwidth 2 8925 kernel epanechnikov bandwidth 1 7288 Distribution
6. 53 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Steroid hormones testosterone and DHEAs IGF 1 and ferritin and fibrinogen were part of external QA by the UK NEQAS Samples are sent to a range of laboratories the individuals laboratories perform the relevant assays and return the results to NEQAS The results are analysed and a consensus result derived from all laboratory results to provide comparison with the overall median and peer group median i e laboratories using similar assay methodology All results for analytes in Understanding Society met acceptability criteria Table A1 1 Internal quality control data from the Department of Clinical Biochemistry NUTH Level 1 low CV Level 2 high CV standard standard mean mean Total Cholesterol mmol L 2 6 1 4 6 6 1 3 HDL Cholesterol mmol L 0 7 6 0 1 7 4 3 Triglycerides mmol L 0 87 2 6 1 98 1 7 C Reactive Protein mg L 7 0 0 1 53 1 8 Ferritin ug L 33 2 4 388 1 8 ALP U L 29 4 5 233 3 4 ALT U L 23 4 3 172 1 6 AST U L 39 3 2 240 0 6 GGT U L 27 2 2 138 1 3 Albumin g L 26 2 4 45 1 3 Urea mmol L 5 4 2 4 23 1 1 3 Creatinine umol L 55 2 6 586 3 2 Testosterone nmol L 2 8 3 0 34 4 2 3 CMV IgG 1 3 1 4 23 8 2 1 CMV IgM 0 2 3 9 2 2 3 6 DHEAS umol L 3 4 3 3 18 1 3 5 IGF 1 nmol L 3 9 13 6 32 6 7 4 HbA1c mmol mol 34 3 88 86 1 72 Hb g L 62 0 4 164 0 8 Fibrinogen g L 1 82 6 91 2 93 3 48 Version 1 December
7. For those biomarkers affected by time of day it is important to control for this as a confounder in any models For medication data analysts take a range of different approaches Some adjust the biomarker concerned by estimated effect size from the literature for specific medications this is an approach often employed for blood pressure Alternatively analysts may control for medication use in their models or conduct sensitivity analyses excluding those taking the medications of concern for a particular biomarker Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary GLOSSARY In this glossary we provide key information for each biomarker to help users with their analysis and to provide relevant information to be considered when these data are used for publications For each biomarker we outline e the clinical significance of each biomarker e adescription of the role of the biomarker in the body e laboratory methods and procedures used to measure the analyte e guidance on factors to consider when analysing the biomarker e distributions for each biomarker and where available these distributions are compared to equivalent data available from the HSE or ELSA As outlined above NUTH undertake both internal and external quality assurance programmes and have provided the data from these to us Below for each analyte we provide quality control information given by co e
8. lt 20 ug L indicate depletion of iron while levels lt 12 indicate complete absence of stored iron Ferritin levels gt 300 ug L may indicate iron overload in men and postmenopausal women and gt 200 may indicate iron overload in premenopausal women What should be considered in analyses Ferritin levels are influenced by taking aspirins and anti inflammatory medication BNF chapter 2 9 derived variable bnf7_aspirin BNF chapter 10 1 derived variable bnf7_antiinflam Distribution in Understanding Society Figure 8 Distribution of Ferritin ng ml or ug l by gender Males n 5 720 Females n 7 157 Kernel density estimate Kernel density estimate 3 J 8 J 8 J 8 J 8 3 J 0 200 400 600 800 0 200 400 600 800 ferritin ug l ferritin ug l kernel epanechnikov bandwidth 16 1412 kernel epanechnikov bandwidth 8 9778 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed e Fleming et al Aspirin intake and the use of serum ferritin as a measure of iron status Am J Clin Nutr 2001 74 2 219 226 Version 1 December 2014 35 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 13 Ferritin ng ml or ug l by gender and age Males Health Survey for England 2009 n 1 067 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 nee 88
9. 02 0 03 0 01 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 10 shows that mean Fibrinogen values from the England component of Understanding Society are close to those obtained from the HSE 2009 by gender and across age groups Version 1 December 2014 29 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Cytomegalovirus antibody measurement CMV What is its clinical significance Measurement of Cytomegalovirus CMV antibodies provides information about the people s immune function which declines with illness and age What is it Cytomegalovirus CMV is a herpes virus that is often asymptomatic This type of virus is unusual as it is lays dormant in the body approximately half of the general population have ever been infected with it Table 12 below With ageing or weakening of the immune system the virus can develop and this causes the release of antibodies which attempt to protect the body from the virus These antibodies are used as biomarkers for the virus How is it measured There are two antibodies that are important The presence of immunoglobulin G IgG shows that someone has at some time had a CMV infection while Immunoglobulin M IgM indicates recent infection In Understanding Society we have measured IgG and IgM from ser
10. 4 1 4 1 4 1 4 1 4 HDL 0 03 0 02 0 02 0 02 0 02 0 02 0 02 0 01 Females Health Survey for England 2011 n 2 185 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Total sample Mean 1 5 1 6 1 6 1 6 1 7 1 6 1 7 1 6 HDL 0 03 0 02 0 02 0 02 0 02 0 02 0 03 0 01 Understanding Society England sub sample n 5 954 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Total sample Mean 1 6 1 6 1 6 1 7 1 7 1 7 1 7 1 7 HDL 0 03 0 02 0 02 0 02 0 02 0 02 0 02 0 01 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Tables 6 and 7 show that mean total and HDL cholesterol values from the England component of Understanding Society are very close to those obtained from the HSE 2011 by gender and across age groups Version 1 December 2014 21 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Triglycerides What is the clinical significance of Triglycerides Triglycerides levels are predictive of CVD What is it Triglycerides are fats that are transported in the blood They come from dietary sources or from the liver They may be taken up by cells and used for energy or stored as fat High levels of triglycerides are often found with low levels of HDL cholesterol How is it measured There has been a debate about whether triglyceride levels s
11. 6 710 Kernel density estimate 08 08 04 06 06 04 02 02 Kernel density estimate T T T T T 20 40 60 80 glycated hemoglobin ifcc standardised mmol mol hb kernel epanechnikov bandwidth 0 7299 T T T T T 20 40 60 80 glycated hemoglobin ifcc standardised mmol mol hb kernel epanechnikov bandwidth 0 5829 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Table 8 Glycated Haemoglobin HbA1c mmol mol by gender and age Males Health Survey for England 2011 n 1 713 Age group 16 24 25 34 35 44 45 54 5564 6574 75 Pies 34 9 35 9 37 5 39 6 41 7 41 7 43 4 38 7 Mean HbA1c 0 34 0 40 0 33 0 50 0 53 0 61 0 67 0 20 Understanding Society England sub sample n 4 583 Age group 16 24 25 34 35 44 45 54 5564 65 74 75 saree 32 7 33 6 35 2 36 9 30 3 41 0 40 8 36 8 Mean HbAtc 0 26 0 25 0 20 0 23 0 35 0 48 0 43 0 14 Females Health Survey for England 2011 n 2 173 Age group 16 24 25 34 35 44 45 54 55 64 65 74 754 Bant 344 34 8 36 6 38 8 41 0 42 2 42 9 38 3 Mean HbA1c 0 36 0 29 0 40 0 40 0 48 0 58 0 46 018 Understanding Society England sub sample n 5 604 Age group 16 24 25 34 35 44 45 54 55 64 65 74 754 n 33 2 33 4 34 6 36 4 38 4 396 409 36 3 Mean HbAtc 0 32 0 23 0 31 0 24 0 22 0 25 0 46 0 11 Notes Values
12. M Stage 3 E Stages 48 5 A Kidney Disease Improving Global Outcomes KDIGO CKD Work Group 2013 KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease Kidney International Suppl 3 1 150 Version 1 December 2014 42 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 16 Creatinine umol L by gender and age Males Health Survey for England 2009 n 1 027 Age group ice 25 34 35 44 45 54 55 64 65 74 75 Jota sample Mean 77 4 81 0 81 3 83 0 80 5 85 9 96 2 82 4 Creatinine 1 35 1 25 1 0 1 04 0 96 1 46 2 96 0 55 Understanding Society England sub sample n 4 844 Age group Veet 25 34 35 44 45 54 55 64 65 74 75 toa sample Mean 79 7 82 8 82 6 84 4 84 1 88 2 95 9 84 6 Creatinine 0 67 0 57 0 50 0 48 0 60 0 61 1 21 0 26 Females Health Survey for England 2009 n 1 165 Age group 16 24 4 l i i Total 25 34 35 44 45 54 55 64 65 74 75 sample Mean 60 6 61 3 62 7 64 2 66 1 69 2 74 4 64 9 Creatinine 0 94 0 88 0 73 0 90 1 36 1 73 1 68 0 45 Understanding Society England sub sample n 5 984 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Tora sample Mean 63 2 64 6 64 7 66 8 67 3 70 3 79 6 67 3 Creaiinih 0 61 0 55 0 47 0 38 0 43 0 64 1 24 0 24 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weight
13. SAMPLES AND ANALYSIS All respondents were eligible to give blood except individuals who volunteered that they were HIV positive or had hepatitis B or C and people with clotting or bleeding disorder such as haemophilia or low platelets Clotting disorders did not include a history of thrombophlebitis a deep venous thrombosis a stroke caused by a clot a myocardial infarction or an embolus Finally people who have ever had a fit or those taking anti clotting medication e g warfarin were excluded Aspirin was not counted as an anti clotting medication Respondents gave written consent for their blood to be taken the storage of blood for future scientific analyses and for genetic analysis as outlined in Box 1 below The information leaflet given to respondents about Giving a blood sample can be seen at https www understandingsociety ac uk documentation mainstage fieldwork documents Both the participant and the nurse signed the consent form Respondents aged 16 and 17 years old were asked to consent to their own participation However nurses were advised to check with parents when present as a matter of courtesy before taking a blood sample from this age group Box 1 Consent wording for blood samples consent to a qualified nurse taking a sample of my blood on behalf of the Institute for Social and Economic Research National Centre for Social Research 1 have read and understood the Information for Participants leaflet about the
14. Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Fibrinogen What is its clinical significance Fibrinogen is a marker of inflammation and it helps the body to stop bleeding by helping blood clots to form Higher levels of fibrinogen are implicated in the development of CVD What is it Fibrinogen is a glycoprotein Through a series of enzymatic steps is converted into fibrin in the clotting process Fibrinogen is also an acute phase protein and therefore reflects inflammatory processes How is it measured Fibrinogen was analyzed from citrate plasma samples using a modification of the Clauss thrombin clotting method on the IL ACS TOPS analyser Intra and inter assay coefficients of variation were less than 7 Are there clinical cutpoints Data are continuous and there are no established clinical cutpoints What should be considered in analyses Fibrinogen can be influenced by contraception and hormone replacement therapy BNF chapter 6 4 1 derived variable bnf7_conhrt and antifibrinolytic drugs and haemostatics medications BNF chapter 2 11 derived variable bnf7_antfibs Distribution in Understanding Society Figure 6 Distribution of Fibrinogen g L by gender Males n 5 878 Females n 7 284 Kernel density estimate Kernel density estimate o 4 a 4 o 4 o 4 st 4 4 N 4 N 4 of o4 T T T T T T 2 3 4 5 j 1 anise fibrinogen gi s 5 clauss fibrinogen g l kernel epa
15. blood test health check 14 previous difficulties with venipuncture 14 no information about what blood will be tested for 12 7 no feedback of results 12 2 current illnesses 3 1 and other reasons 8 8 Of those eligible and consenting to give blood samples to be stored for future analysis samples were obtained and successfully processed at least one biomarker available for 13 107 respondents This represents a response of 36 5 of those eligible for the nurse health assessment 68 5 of those who participated in the nurse interview and 90 8 of those who consented All of the response rates were slightly higher among men than women 11 McFall Stephanie L Petersen Jakob Kaminska Olena Lynn Peter 2014 Understanding Society UK Household Longitudinal Study Waves 2 and 3 Nurse Health Assessment 2010 2012 Guide to Nurse Health Assessment Colchester University of Essex https www understandingsociety ac uk documentation health assessment Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 1 Eligibility missing cases and participation in the blood sample Combined GPS and BHPS sample components Gender Whole Male Female sample a Y 35 937 15 864 20 073 Eligible for the nurse visit 100 100 100 Reasons for non participation in nurse visit Pregnant ill died out of scope 349 39 o ae 1 0 0 5 1 3
16. in their analysis Full details about the nurse visit and the other data collected as part of this can be found in the Nurse Health Assessment User Guide CAPI programme and fieldwork protocols More information on the main annual survey can be found in the main user guide all of these guides are available on the Understanding Society website Below we briefly describe the sample who took part in the nurse health assessment and the procedures for taking blood We then outline the criteria for deciding on the biomarkers to be analysed the general approach to their analysis and quality control measures The main part of this guide provides a glossary for the biomarkers included in Understanding Society After an initial overview of issues associated with analysing biomarker data for each biomarker we outline e the clinical significance of each biomarker e a description of the role of the biomarker in the body e laboratory methods and procedures used to measure the analyte e guidance on factors to consider when analysing the biomarker e its distribution in the Understanding Society sample Not all of the blood samples available have been used for these biomarkers Significant samples remain frozen for future use In due course we will both advertise their availability for researchers 1 National Institute of Health Biomarkers Definitions Working Group 1998 referenced in Biomarkers Definitions Working Group 2001 Biomarkers and sur
17. nurse health assessment datat McFall et al 2014 The adjustment comes from a logistic regression model predicting the presence of blood data and for which the base is all sample members who responded to the individual interview at both Waves 2 and 3 and the nurse visit minus those who were ineligible for the collection of blood those who reported a clotting or bleeding disorder taking anticoagulant drugs or having ever had a fit Predictor variables in the model are a range of social demographic and economic indicators from the Wave 3 household and individual questionnaires The adjustment factor is the reciprocal of the model predicted propensity for blood measures to be present Thus the adjustment is designed to deal simultaneously with drop out at each stage in the process of obtaining blood measures viz consent to give blood successfully taking blood and successfully extracting analytes from the blood sample The weighted sample should be representative of the population net of those who would have been ineligible for the nurse visit pregnant or inadequate English to complete a survey interview or for the blood sample clotting or bleeding disorder taking anticoagulant drugs or having had a fit i McFall Stephanie L Petersen Jakob Kaminska Olena Lynn Peter 2014 Understanding Society UK Household Longitudinal Study Waves 2 and 3 Nurse Health Assessment 2010 2012 Guide to Nurse Health Assessment Colchester Universi
18. of Albumin g L by gender Males n 5 710 Females n 7 111 Kernel density estimate Kernel density estimate 2 4 S4 2 2 gt m SI T T T T T oF 35 40 45 50 55 i l y albumin g l 3 a0 abin gil ao 33 kernel epanechnikov bandwidth 0 4810 kernel epanechnikov bandwidth 0 4226 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Version 1 December 2014 40 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary KIDNEY FUNCTION A kidney function panel was undertaken which includes creatinine and urea Creatinine is the main indicator employed to assess kidney function Creatinine What is its clinical significance Creatinine is used to estimate glomerular filtration rate eGFR which is a standard measure of kidney function Chronic kidney disease is an increasing health problem What is it Creatinine is a chemical waste product of muscle function which is passed through the kidneys and excreted in urine Levels therefore indicate how effectively the kidneys are cleaning the blood How is it measured Creatinine was measured from serum samples using an enzymatic method on the Roche P module analyser Inter and intra assay coefficients of variation were less than 4 Are there clinical cutpoints Equations to calculate eGFR based on creatinine have recent
19. of DHEAs umlol L in men and women by age group Age range Men Women 15 19 yrs 1 9 13 4 1 8 10 0 20 24 yrs 5 7 13 4 4 0 11 0 25 34 yrs 4 3 12 2 2 7 9 2 35 44 yrs 2 4 11 6 1 7 9 2 45 54 yrs 1 2 9 0 1 0 7 0 55 64 yrs 1 4 8 0 0 5 5 6 65 74 yrs 0 9 6 8 0 3 6 7 2 75 yrs 0 4 3 3 0 3 4 2 What should be considered in analyses To our knowledge there are no factors that require consideration in the analysis Distribution in Understanding Society Figure 14 Distribution of DHEAS pmol l by gender Males n 5 752 Females n 7 165 Kernel density estimate Kernel density estimate 08 1 15 04 i 05 02 y 0 5 10 15 20 20 didehydroepiandrosterone sulphate mol l kernel epanechnikov bandwidth 0 4143 T 0 5 10 15 didehydroepiandrosterone sulphate pmol l kernel epanechnikov bandwidth 0 6004 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Version 1 December 2014 49 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 20 Dihydroepiandrosterone suphate DHEAs pmol l by age and sex Males ELSA Wave 4 2008 2009 n 2 803 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 3 9 3 7 3 1 2 7 2 3 1 6 2 9 Mean DHEAS 0 11 0 09 0 07 0 08 0 07 0 06 0 04 Understan
20. second stage of the survey The nurse has explained the procedures and have had an opportunity to discuss these with him her 2 consent to my blood being taken stored and used in scientific research understand that all blood test results and related information will be coded so cannot be identified For purposes of scientific analyses links to my name will be held separately and securely from any data collected The sample will not be tested for HIV also understand my right to withdraw consent for storing the blood sample 3 give my consent for a sample of my DNA to be taken from my blood stored and used in scientific research understand that e the DNA samples and related information will be coded to ensure that my personal identity is not revealed to researchers carrying out scientific analysis e links to my name will be held separately and securely for administering the study and data collection e that no personal test results from my DNA will be given to me e the data and samples will be owned by the Study and the ESRC No samples or information will be sold e The DNA analyses will not be used for paternity analysis life insurance mortgage applications or police records also understand my right to withdraw consent for storing the blood sample Following written consent from eligible participants non fasting blood samples were collected into the following tubes 1 x 6 ml red plain tube for subsequent e
21. the nurse health assessment interviews completed physical measures and provided blood samples to improve our understanding of people s health The nurse health assessment interviews were conducted by NatCen we are grateful to the interviewers nurses and fieldwork and survey teams both at NatCen and ISER for all of their efforts to produce high quality data for the study The blood samples were initially received processed and frozen by Fisher BioServices the biomarkers reported here were analysed by Newcastle upon Tyne Hospitals NHS Foundations Trust We are grateful to both laboratories and their staff for the efficient and high quality processing of the samples Version 1 December 2014 2 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary TABLE OF CONTENTS Acknowledgements acct rcs ts State SSSA te teh Sid ic oD tad de ad eld las ibid hd tas ahcail 1 List of Boxes Figures and Tables icccaicvescainicencaiccmecinnseieaiccamecinnseieaideamecinnseieaiaiecinuntes 5 MOCO CTION nesoni a a a a r Ta a E e et eet eee 7 Overview of the nurse health ASSESSMENL cccceeeeeeeeeeeeeeceeeeeeeeeeeeeeaeeeeeeeeeeeeeeeeenaaees 8 The blood samples and anialVSisc c kok nite le ati ain nla art 9 Analysis of samples eeeeeoneennnneeeeeeeeeernnntteseetrtttnnntrteeetttttnnttneeetttttnnnnneeeerttnnnn nenene 10 The respondents who took part esssesssseseenrrseeserrttnnrrrneerrtttnnnrteeerttttnnn
22. 120 2 1320 1312 1264 1298 Mean Hb 0 91 0 60 0 45 0 45 0 40 0 46 0 70 0 22 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 12 shows that mean Hb values from the England component of Understanding Society are close to those obtained from the HSE 2009 by gender and across age groups Ferritin What is it Levels of ferritin reflect the size of the body iron stores and therefore it is indicative of anaemia A low ferritin level is predictive of uncomplicated iron deficiency anaemia However high ferritin levels suggest excess body iron which is also problematic for health How is it measured Ferritin is measured from serum samples by an electrochemiluminescent immunoassay on the Roche Modular E170 analyser Inter and intra assay coefficients of variation were less than 3 Are there clinical cutpoints Both high and low levels of ferritin are associated with adverse outcomes the following cut points are suggested 27 World Health Organisation Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations Vitamin and Mineral Nutrition Information System Geneva World Health Organization 2011 Version 1 December 2014 34 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Ferritin levels below
23. 2014 54 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table A1 2 External quality control data from the Department of Clinical Biochemistry NUTH for analytes measured using the Roche P module analyser Standard deviation index SDI data per month that samples were analysed Date Cholestero HDL Triglyceride HbAic ALT AST ALP GG Albumi Creatinin Urea l mmol L s mmol L mmol mol U L U L U L T n e mmol L mmol L U L g L umol L Dec 0 35 0 45 0 24 0 60 0 38 0 54 0 14 ay 1 33 1 04 0 92 i 0 25 0 62 0 15 0 19 0 53 0 25 0 63 0 37 0 72 0 48 0 35 os 0 39 0 36 0 26 0 47 0 42 0 32 1 05 0 42 0 95 0 94 0 38 ie 0 21 0 36 0 22 0 41 0 42 0 06 1 11 0 19 1 10 0 34 0 85 ye 0 89 0 49 0 26 0 66 0 52 012 0 54 0 24 1 13 0 37 0 70 a 0 31 0 58 0 27 1 12 0 47 0 06 1 09 0 70 0 37 1 22 1 03 lie 0 86 1 24 0 30 0 41 0 16 0 23 0 70 0 26 0 26 0 95 0 81 ie 0 15 0 64 0 23 0 07 0 21 0 20 0 37 1 40 1 06 1 02 0 43 14 Notes A score below 1 SDI is good between 1 2 SDI is acceptable APPENDIX 2 DERIVATION OF ANALYSIS WEIGHTS This appendix describes how the various analysis weights for use with the blood data were derived The Wave 3 longitudinal blood weight for the combined sample c_indbdub_lw is based upon the equivalent nurse weight c_indnsub_lw with an additional adjustment for non response to the blood measures Derivation of the nurse weights is described in the separate User Guide to the
24. 3 147 3 155 0 149 6 1558 1620 130 0 141 5 Mean Ferritin 7 0 9 9 8 4 7 1 8 2 9 1 13 4 3 7 Understanding Society England sub sample n 4 816 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Ree 108 6 166 2 1841 190 8 1948 177 9 168 0 172 02 Mean Ferritin 5 55 6 96 6 45 5 14 5 40 6 18 6 68 2 47 Females Health Survey for England 2009 n 1 217 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 AniS 36 3 46 8 55 3 65 8 93 0 111 0 94 3 70 0 Mean Ferritin 3 3 3 7 4 5 3 7 4 2 7 3 7 5 1 9 Understanding Society England sub sample n 5 985 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Ekra 50 4 60 8 67 3 81 4 1149 1243 110 0 85 2 Mean Ferritin 2 82 2 20 2 24 2 26 3 04 3 84 4 81 121 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 13 shows that mean ferritin values from the England component of Understanding Society differ to those obtained from the HSE 2009 However the analyser employed by NUTH was changed between the HSE analyses and those for Understanding Society which may explain these differences Version 1 December 2014 36 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary LIVER FUNCTION TESTS LF TS What is the clinical significance of liver function tests A panel of liver function tests were
25. 5 534 2 581 2 953 No conan 15 4 16 3 14 7 ste 9 354 4 103 5 251 Refused the nurse visit 26 0 25 9 26 2 People participating in the nurse visit 20 700 9 100 11 600 Reasons for no blood sample On anti coagulant drugs had clotting bleeding disorder or 1 579 750 829 have had a fit in the last 5 years 4 4 4 7 4 1 People eligible for giving blood 19 121 8 350 10 771 4 387 1 900 2 487 No consent to take or store blood sample 12 2 12 0 12 4 No consent to take blood Reported inability to give blood 301 120 181 sample 0 8 0 8 0 9 People eligible to give blood who consented 14 433 6 330 8 103 Unable to give blood sample during the fieldwork no 1105 380 725 suitable palpable veins collapsed veins anxious nervous 3 1 2 4 3 6 felt faint fainted re aan ae roA 221 100 121 Unable to process samples other missing cases 0 6 0 6 0 6 At least one biomarker available 13 107 5 850 7 257 Response rates At least one biomarker available as of total eligible 36 5 36 9 36 2 At least one biomarker available as of people eligible for 3 5 giving blood 68 5 70 0 67 4 At least one biomarker available as of people who gave 90 8 92 4 896 blood consent Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary CHOICE OF BIOMARKERS A number of criteria were considered in identifying biomarkers that should be included in the
26. 6 kernel epanechnikov bandwidth 0 3109 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Table 9 C reactive protein CRP mg l by gender and age Males Health Survey for England 2009 n 1 525 Agegroup 16 24 25 34 35 44 45 54 55 64 65 74 75 ie ean 1 4 1 9 2 0 2 8 3 1 3 7 3 8 25 ts 0 28 0 30 0 21 0 31 0 35 0 40 0 40 0 12 Understanding Society England sub sample n 4 852 Agegroup 16 24 25 34 35 44 45 54 55 64 65 74 75 eae T 1 2 1 8 2 3 2 3 2 8 3 0 3 5 2 3 eee 0 11 0 21 0 13 0 13 0 20 0 21 0 26 0 07 Females Health Survey for England 2009 n 1 271 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 ane 2 8 2 8 27 3 0 3 8 3 3 3 1 pie 0 50 0 31 0 24 0 25 0 34 0 28 39 0 44 0 13 Understanding Society England sub sample n 5 971 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 a 25 2 8 27 2 8 3 6 3 6 3 6 3 1 ee 0 30 0 22 0 20 0 13 0 21 0 20 0 28 0 09 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 9 shows that mean CRP values from the England component of Understanding Society are close to those obtained from the HSE 2009 by gender and across age groups Version 1 December 2014 27 Understanding
27. Inter and intra assay coefficients of variation were less than 5 for all of these assays imdi J Hyde G Evaluation of abnormal liver function tests Postgrad Med J Jun 2003 79 932 307 312 Version 1 December 2014 37 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Are there clinical cutpoints Table 14 Clinical cutpoints for the liver function tests Test Units of measurement Age range Poor liver function level ALT U L gt 40 AST U L gt 40 ALP U L 20 70 yrs lt 30 gt 130 gt 70 yrs lt 30 gt 150 GGT U L M gt 70 F gt 45 Albumin g L lt 35 gt 50 What should be considered in analyses Recent alcohol intake influences the measures of these analytes It is recommended that this is taken into account in analyses using nurse visit question for recent consumption Some medications may be associated with raised LFTs for example anti epilepsy medications BNF chapter 4 8 derived variable bnf7_antiep or statins BNF chapter 2 12 derived variable bnf7_statins Version 1 December 2014 38 Understanding Society The UK Household Longitudinal Study Distribution in Understanding Society Figure 9 Distribution of LFTs by gender Biomarker User Guide and Glossary Distribution of Alanine Transaminase ALT IU L by gender Males n 5 682 Kernel density estimate Females n 7 089 Kernel density estimate
28. ONES Jer t5i cen cica toca c ie Sito Stoo Sli ot te elk oar Sian ete Si Sa eee elk Sa 45 Testosterone ss zu acvevugzcue czas iat exact suet AA eet ua seagate kates este esate ee 45 Insulin like growth factor 1 IGF 1 eeeeeeeeeeeceeeeeeeeeeeneeeeeeeeeeeeeeessnsaeeeeeeeeeeneeneas 46 Dihydroepiandrosterone suphate DHEAS cccceeeeeeeeeeeeeneeeeeeeeeeeeeeeeenneeeeeeees 48 Datafiles weights etc udeck onde cteadecnatende cad tenghdmastendecndnendecndnenddenanenddensenddcnorendlcnonendeensnenbecats 51 Release OF ING Calas a a E A a alice A A A A late 52 Citations and Acknowledgements cccccceeeeeeeeeeeceeeeeeeeeeeeeecaaaeeeeeeeeeeeseessaeeeeeeeees 52 Version 1 December 2014 3 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Appendix 1 Quality control data ccccccceeeeeeeeeeeeeeneeeeeeeeeeeeeeeeeaaeeeeeeeeeeeeseeeeaeeeeeeeeeeeneee 53 Internal quality COMMU Ole iees oie ta seanteicteceehanpeents cteenchinbeatys soon be enneetpeideesetoie pended teeieudaras 53 External quality control cece tech Chee eR ee AN eA eee ke 53 Appendix 2 Derivation of Analysis Weights cccceeeeeeeeeceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeees 55 Version 1 December 2014 4 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary LIST OF BOXES FIGURES AND TABLES Page No Box Box 1 Consent wording for blood samples 9 Figure Figur
29. UK Household Longitudinal Study Biomarker User Guide and Glossary Table 7 HDL Cholesterol levels mmol l by gender and age 21 Table 8 Glycated Haemoglobin HbA1c mmol mol by gender and age 25 Table 9 C reactive protein CRP mg l by gender and age 27 Table 10 Fibrinogen g L by gender and age 29 Table 11 CMV infection and if it recently occurred interpretation of 31 combined variables Table 12 Haemoglobin Hb level g l by gender and age 34 Table 13 Ferritin ng ml or ug l by gender and age 36 Table 14 Clinical cutpoints for the liver function tests 38 Table 15 Classification of kidney function from eGFR equations 42 Table 16 Creatinine umol L by gender and age 43 Table 17 Insulin like growth factor 1 IGF 1 reference values nmol L 47 in men and women by age Table 18 Insulin like growth factor 1 IGF 1 nmol l by gender and age 48 Table 19 Expected ranges of Dihydroepiandrosterone suphate DHEAs 49 umlol L in men and women by age group Table 20 Dihydroepiandrosterone suphate DHEAs mol l by age and sex 50 Table A1 1 Internal quality control data from the Department of Clinical 54 Biochemistry NUTH Table A1 2 External quality control data from the Department of Clinical Biochemistry NUTH for analytes measured using the Roche P module analyser Standard deviation index SDI data per month that samples were analysed 55 Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Bi
30. Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Prepared by Michaela Benzeval Apostolos Davillas Meena Kumari Peter Lynn Institute for Social and Economic Research University of Essex Colchester Essex Version 1 December 2014 BS R L Understanding Society ECONOMIC THE UK HOUSEHOLD LONGITUDINAL STUDY amp OLLA L RESEARCH GONI Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary ACKNOWLEDGEMENTS Understanding Society the UK Household Longitudinal Study is an initiative funded by the Economic and Social Research Council ESRC with scientific leadership by the Institute for Social and Economic Research ISER University of Essex and survey delivery by the National Centre for Social Research NatCen and TNS BMRB The study has also been supported by the Department for Work and Pensions the Department for Education the Department for Transport the Department for Culture Media and Sport the Department for Communities and Local Government the Scottish Government the Welsh Government the Department for Environment Food and Rural Affairs the Food Standards Agency the Office for National Statistics and the Department of Health We are grateful to all of the respondents who gave up their time to take part in
31. a Lynn Peter 2014 Understanding Society UK Household Longitudinal Study Biomarker User Guide and Glossary Colchester University of Essex Version 1 December 2014 52 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary APPENDIX 1 QUALITY CONTROL DATA Brief details of the internal and external quality control information are provided here A more detailed report is being prepared and will be made available on the Understanding Society website in due course Quality control processes are generally conducted internally and externally Internal quality control measures how well measurements compare across time within a laboratory ie does a sample measure the same if the measurement is made on day a as it does on day a 1 These quality control measures are sometimes called intra assay coefficient of variation External quality control reflects how the laboratory compares to other laboratories measuring the same analyte A number of quality assessment schemes which provide sample standards often at more than one concentration for comparison are available The NUTH uses the Welsh External Quality Assessment Scheme WEQAS for some analytes and the United Kingdom National External Quality Assessment Service UK NEQAS for others These quality control measures are sometimes referred to as inter assay coefficient of variation INTERNAL QUALITY CONTROL Internal quality control me
32. above the lowest highest detection limit Includes the valid cases and those cases below above the low high detection limit Explanation of the indicators used for the different types of missing cases ANAERR Unable to perform analysis due to analyser error CCOA Coagulation studies sample coagulated CHOHDU Unable to measure Hdl as trig greater than 10 0 mmol L CLOT Specimen clotted FCOAG Full blood count sample coagulated HASTND Plasma appears haemoglobin stained INSUFF Insufficient sample for analysis NOCLOT No clot detected NBA no relevant type of blood SDIS Sample discarded prior to analysis UNAVB Unavailable due to Bilirubin interference UNAVH Unavailable due to Haemolysis UNAVL Unavailable due to interference by Lipaemia UNUS Unusual chromatography Version 1 December 2014 15 Understanding Society The UK Household Longitudinal Study Table 4 Missing codes for biomarker variables Reason for missingess Biomarker User Guide and Glossary Missing code in data file Inapplicable Tissue sample obtained unable to process sample Below detection limit Above linear range for analytical method No blood serum available No full blood available No blood plasma available 8 22 31 32 41 42 43 Table 5 Lowest and highest detection limits for biomarkers where applicable Biomarker Lowest detection limit Highest detection limit number of individuals in parenthesis CRP 0 2 mg l 381
33. alth low levels are associated with CVD and all cause mortality in older men whereas higher levels are related to better health outcomes such as lower risk of metabolic syndrome What is it Dihydroepiandrosterone DHEA and its sulfate form DHEAs and are the most common steroid hormones in the body and their levels decline with age How is it measured DHEAs measures were performed using serum samples on a competitive immunoassay on the Roche E module analyser Intra and inter assay coefficients of variation were less than 4 38 Barrett Connor E Khaw KT Yen SCC A prospective study of dehydroepiandrosterone sulfate mortality and cardiovascular disease N Engl J Med 315 1986 pp 1519 1524 3 Phillips AC Carroll D Gale CR Lord JM Arlt W Batty GD Cortisol DHEAS their ratio and the metabolic syndrome evidence from the vietnam experience study Eur J Endocrinol 162 2010 pp 919 923 Labrie F Belanger A Luu The V Labrie C Simard J Cusan L Gomez JL Candas B DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues its role during aging Steroids 63 1998 pp 322 328 Version 1 December 2014 48 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Are there clinical cutpoints Data are continuous and there are no established clinical cutpoints The expected ranges are shown in Table 19 below Table 19 Expected ranges
34. asurements allow laboratories to assess how the assay varies from day to day Samples with known values one standard with a low level and one with a high level are measured and the variation in actual measurement is expressed as a co efficient of variation Results for each biomarker are shown in Table A1 1 which shows that these coefficients are generally less than 5 and therefore well within acceptable limits EXTERNAL QUALITY CONTROL External quality control methods use standards across laboratories and results are compared The majority of the biomarkers in the Understanding Society dataset were analysed on a single analyser the Roche P module analyser The NUTH laboratory participates in the WEQAS on a routine basis We report the standard deviation index SDI in Table A1 2 where the SDI is an index of total error including components of inaccuracy and imprecision so lower values suggest more accurate measures It is calculated as laboratory result target value WEQAS standard deviation CF where CF is a method specific comparability factor This adjustment ensures that each laboratory can compare their results with others using their own method the peer reference method and the overall mean of all groups A score below 1 SDI is good and between 1 2 SDI is acceptable The majority of monthly SDI figures for the biomarkers analysed on this machine had good EQA with a few being acceptable only Version 1 December 2014
35. ately as the two samples have very different structures For longitudinal analysis analysis in which for each respondent questionnaire data from at least two different Waves is used in conjunction with the blood data two different longitudinal weights have been created for each of Waves 3 and 4 and will in future be created for each subsequent Wave The first of these is for used with the combined GPS and BHPS sample using questionnaire data from Waves 2 and 3 in conjunction with the blood data c_indbdub_lIw available in the c_indresp file or for using questionnaire data from Waves 2 3 and 4 with the blood data d_indbdub_Iw available in the d_indresp file The second is for using data from 1991 onwards for the BHPS sample in conjunction with the blood data c_indbd91_Iw available in the c_indresp file for 1991 to Understanding Society Wave 3 and d_indbd91_Iw for 1991 available in the d_indresp file to Understanding Society Wave 4 Technical details of how the weights were derived are presented in Appendix 2 Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary RELEASE OF THE DATA The release of the biomarkers conforms to their classification for risk of disclosure as agreed the Understanding Society Data Access Committee and hence they are released in anonymised form through the UKDS via the EUL We request that researchers using the data notify us about err
36. belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 8 shows that mean HbA1c values from the England component of Understanding Society are close to those obtained from the HSE 2011 by gender and across age groups Version 1 December 2014 25 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary INFLAMMATORY MARKERS MARKERS OF INFLAMMATION IMMUNE FUNCTION C reactive protein CRP What is its clinical significance CRP is a marker of inflammatory load high values are associated with adverse CVD and mortality Systemic inflammation is defined as CRP gt 3 mg L levels This dichotomization was selected based on the clinical guidelines of the joint scientific statement from the Centers for Disease Control and Prevention and American Heart Association that CRP levels above 3 mg L be used to indicate high risk of cardiovascular diseases What is it CRP is an acute phase protein in the blood that rises in response to inflammation It is part of the body s defence mechanism against harmful stimulus How is it measured CRP was analyzed from serum using the N Latex CRP mono Immunoassay on the Behring Nephelometer II Analyzer Dade Behring Milton Keynes UK Intra and inter assay coefficients of variation were less than 2 Are there clinical cutpoints Values of
37. d with longer hospitalization and greater risk of mortality and CVD What is it Hb is the iron containing molecule responsible for carrying oxygen from the respiratory organs to the rest of the body and low levels are usually indicative of anaemia How is it measured Hb levels were measured from whole blood samples with a spectrophotometric assay on a Sysmex XE 2100 analyser Inter and intra assay coefficients of variation were less than 1 Are there clinical cutpoints Anaemia status is defined based on WHO guidelines as Hb levels lt 13 g dL for men and lt 12 g dL for women What should be considered in analyses Hb levels are influenced by a number of factors such as pregnancy and high altitude but these are not applicable in our population 4 Nilsson Ehle H Jagenburg R Landahl S Svanborg A Blood haemoglobin declines in the elderly implications for reference intervals from age 70 to 88 Eur J Haematol 65 2000 pp 297 305 5 Culleton BF Manns BJ Zhang JG Tonelli M KlarenbachS Hemmelgarn BR Impact of anemia on hospitalization and mortality in older adults Blood 107 2006 pp 3841 3846 2 WHO World Health Organization Nutritional Anaemias Report of a WHO Scientific Group World Health Organization Geneva 1968 Version 1 December 2014 32 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Distribution in Understanding Society Figure 7 Distribut
38. ding Society England sub sample n 2 744 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 5 4 4 6 4 0 3 6 2 8 2 3 3 8 Mean DHEAS 0 25 0 16 0 15 0 15 0 12 0 11 0 06 Females ELSA Wave 4 2008 2009 n 3 494 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 2 8 2 3 1 9 1 7 1 4 1 2 1 8 Mean DHEAS 0 09 0 06 0 05 0 05 0 05 0 04 0 03 Understanding Society England sub sample n 3 226 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 3 5 2 9 0 12 2 6 2 2 2 1 1 7 2 5 Mean DHEAS 0 12 Seu 0 10 0 08 0 12 0 06 0 04 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 20 shows that mean DHEAs values from the England component of Understanding Society differ to those obtained from the ELSA study 2008 2009 However the analyser employed by NUTH was changed between the ELSA analyses and those for Understanding Society which may explain these differences Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary DATAFILES WEIGHTS ETC The blood analyte data are released as part of the nurse health assessment dataset SN 7251 at the UKDS All of the analyte results are in the xlabblood_ns file which combines both the GPS and BHPS samples The results of the physical measures as well as informa
39. dwidth 0 2406 kernel epanechnikov bandwidth 0 2187 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Version 1 December 2014 44 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Hormones Testosterone What is its clinical significance Testosterone is a steroid that plays a central role in the development of secondary sexual characteristics in men It is related to libido building muscle mass and with aggression and competitive behaviours Evidence suggests that low testosterone levels are associated with diabetes in men In women high levels are associated with conditions such as polycystic ovarian syndrome What is it Testosterone is anabolic steroid which build up muscles and tissues How is it measured Serum testosterone is measured by an electrochemiluminescent immunoassay on the Roche Modular E170 analyser Intra and inter assay coefficient of variation is less than 4 Are there clinical cutpoints Testosterone levels above or below the normal range are considered by many to be out of balance In men testosterone levels are broad and considered within a normal range between 9 25 nmol L and in women testosterone values are low and considered above normal at greater than 3 2 nmol L In Understanding Society the majority of values for women are below the lowest detection lev
40. e 1 Distribution of Total Cholesterol levels mmol l by gender 20 Figure 2 Distribution of HDL Cholesterol levels mmol l by gender 21 Figure 3 Distribution of Triglycerides mmol L by gender 23 Figure 4 Distribution of Glycated Haemoglobin HbA1c mmol mol by gender 25 Figure 5 Distribution of C reactive protein CRP mg I by gender 27 Figure 6 Distribution of Fibrinogen g L by gender 28 Figure 7 Distribution of Haemoglobin Hb g l by gender 33 Figure 8 Distribution of Ferritin ng ml or ug l by gender 35 Figure 9 Distribution of LFTs by gender 39 Figure 10 Stages of kidney disease by age and gender 42 Figure 11 Distribution of Urea mmol L by gender 44 Figure 12 Distribution of Testosterone nmol L by gender 46 Figure 13 Distribution of Insulin like growth factor 1 IGF 1 nmol l by gender 47 Figure 14 Distribution of Dinydroepiandrosterone suphate DHEAs umol l by 49 gender Table Table 1 Eligibility missing cases and participation in the blood sample 12 Combined GPS and BHPS sample components Table 2 Biomarkers available in Understanding Society 14 Table 3 Valid cases for each biomarker and reasons for missingness 15 Combined GPS and BHPS samples with at least one biomarker n 13 107 Table 4 Missing codes for biomarker variables 16 Table 5 Lowest and highest detection limits for biomarkers where applicable 16 Table 6 Total Cholesterol levels mmol l by gender and age 20 Version 1 December 2014 Understanding Society The
41. ecember 2014 47 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 18 Insulin like growth factor 1 IGF 1 nmol I by gender and age Males ELSA Wave 4 2008 2009 n 2 814 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 17 3 16 3 16 7 16 4 16 1 14 1 16 1 Mean IGF1 0 32 0 25 0 23 0 25 0 30 0 28 0 11 Understanding Society England sub sample n 2 737 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 17 1 17 0 16 3 16 3 15 2 14 5 16 1 Mean IGF1 0 27 0 31 0 28 0 27 0 33 0 40 0 13 Females ELSA Wave 4 2008 2009 n 3 466 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 16 8 15 5 15 3 14 6 14 4 13 3 14 8 Mean IGF1 0 34 0 23 0 19 0 22 0 24 0 22 0 10 Understanding Society England sub sample n 3 208 Age group 50 54 55 59 60 64 65 69 70 74 75 Total sample 15 9 15 4 14 8 14 4 14 3 13 6 14 7 Mean IGF1 0 23 0 30 0 24 0 426 0 33 0 29 0 10 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Table 18 shows that mean IGF 1 values from the England component of Understanding Society are close to those obtained from the ELSA study by gender and across age groups Dihydroepiandrosterone suphate DHEAs What is its clinical significance DHEAs has been implicated in cardiovascular he
42. el the conditional response rate was over 96 and hence no adjustment so d_indbd91_ Iw is proportional to c_indbd91_lw For each weight variable the final step was to scale the weights to a mean of 1 00 Lavall e Pierre 2007 Indirect Sampling New York Springer Version 1 December 2014 56
43. el for the analyser of 1 nmol L What should be considered in analyses In Understanding Society we have measured total testosterone which is independently associated with a number of outcomes such as diabetes Testosterone varies by time of day such that values in the morning are higher than those found in the afternoon or evening Users should be aware that testosterone is bound by carrier proteins in the circulation However we have not measured steroid hormone binding globulin the chief carrier protein that binds circulating testosterone Beatrice AM Dutta D Kumar M Kumbenahalli Siddegowda S Sinha A Ray S Chowdhury S Testosterone levels and type 2 diabetes in men current knowledge and clinical implications Diabetes Metab Syndr Obes 2014 Oct 20 7 481 6 33 Brambilla DJ Matsumoto AM Aroujo AB McKinlay JB The effects of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men J Clin Endocrinol Metab 94 907 913 3 Sodergard R Backstrom T Shanbhag V Carstensen H Calculation of free and bound fractions of testosterone and estradiol 17 beta to human plasma proteins at body temperature J Steroid Biochem16 801 810 1982 3 Vermeulen A Verdonck L Kaufman JM A critical evaluation of simple methods for the estimation of free testosterone in serum J Clin Endocrinol Metab 84 3666 3672 1999 Version 1 December 2014 Understanding Society The UK Household Long
44. erol and HDL cholesterol Total cholesterol is a risk factor for cardiovascular disease CVD while HDL cholesterol is thought to be protective against it What are total cholesterol and HDL cholesterol Cholesterol is a steroid that is a vital component of the lining of cells Because it is not soluble in blood it is transported around the body as cargo in cells known as lipoprotein particles There are two kinds of lipoproteins Apolipoprotein A and Apolipoprotein B The first of these Apolipoprotein A contains high density lipoproteins HDL which are involved in the delivery of cholesterol to the liver for breakdown and are hence beneficial for the body Apolipoprotein B carries low density lipoproteins LDL bad cholesterol which are taken up by blood vessels to cause narrowing of arteries How is it measured Total cholesterol and HDL cholesterol were measured from blood serum using enzymatic methods with a Roche Modular P analyser calibrated to the Centre for Disease Control guidelines Intra and inter assay coefficients of variation CV were less than 2 Are there clinical cutpoints Total cholesterol should be 5mmol L or less for healthy adults HDL cholesterol should be above 1mmol L What should be considered in analyses Cholesterol is treated with a number of lipid regulating drugs eg statins BNF chapter 2 12 A derived variables has been created to indicate whether or not respondents reported taking o
45. fficient of variation data This shows the extent of variation within an assay intra and between assays inter Values less than 5 are considered good quality Appendix 1 provides definitions and exact details of internal and monthly external quality control values that are used in each biomarker description The distribution of each biomarker in Understanding Society is illustrated with a Kernel density estimate a non parametric estimator that smooths observed data over local neighbourhood points This shows how each biomarker is distributed so that analysts can consider if and how to transform variables for analysis Additionally where data from HSE or ELSA are available the age sex distributions of the biomarkers are compared to the English sample of Understanding Society only This comparison is to illustrate how well the mean of the biomarkers in the different studies analysed by the same laboratory match where they are differences we have tried to identify the reasons for this All data presented are weighted by sample weights and do not exclude cases because of co morbidities or medications but do exclude top and bottom 0 5 of outliers 12 Not available for triglycerides LFTs Urea CMV Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary CHOLESTEROL AND TRIGLYCERIDES Total cholesterol and HDL cholesterol What is the clinical significance of total cholest
46. first set of blood analytes from the Understanding Society blood samples We felt it was important to include biomarkers where there was e an environmental socioeconomic physical psychosocial and or behavioural effect on marker e evidence of pathways to important health outcomes or it was a marker for important health conditions e areasonable proportion of general population affected by the biomarker and a reasonable prevalence among those affected More practically it was important to ensure that the measures chosen were robust to the sampling and storage processes undertaken by the study i e as noted above the blood was unfasted sent to the storage laboratory by post and therefore at room temperature for a number of days before processing and frozen for 3 4 years before analyzing A long list of possible biomarkers was peer reviewed as part of the ESRC grant application process and considered by the Health and Biomarker Advisory Committee of Understanding Society We also consulted key researchers in this field and those responsible for biomarker data collection and analysis in other major UK longitudinal studies The final set of biomarkers included in this data release are listed in Table 2 and described in more detail in the glossary below Of the 13 107 respondents with at least one biomarker not all measures are available mainly due to problems processing specific samples Table 3 describes valid cases and reasons for miss
47. gt 3 mg L are considered a risk factor for CVD What should be considered in analyses Values gt 10mg L are considered to reflect recent infection It is recommended that these data should be removed prior to analyses CRP is influenced by medication anti inflammatory medications BNF chapter 10 1 derived variable bnf7_antiinflam statins BNF chapter 2 12 derived variable bnf7_statins and contraception and hormone replacement therapy BNF chapter 6 4 1 derived variable bnf7_conhrt 2 Libby P Ridker PM Hansson GK Progress and challenges in translating the biology of atherosclerosis Nature 473 2011 pp 317 325 21 Pearson TA Mensah GA Alexander RW Anderson JL Cannon 3 RO Criqui M et al Markers of inflammation and cardiovascular disease application to clinical and public health practice A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association Circulation 107 2003 pp 499 511 Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Distribution in Understanding Society Figure 5 Distribution of C reactive protein mg l by gender Males n 5 761 Females n 7 140 Kernel density estimate Kernel density estimate T T T 0 0 20 30 40 0 10 20 30 c reactive protein high sens mg l c reactive protein high sens mg l kernel epanechnikov bandwidth 0 228
48. he Wellcome Trust Sanger Institute These data are also available for researchers to analyse information on how to apply for them is on the Understanding Society website OVERVIEW OF THE NURSE HEALTH ASSESSMENT Understanding Society has four samples e the General Population Sample GPS a stratified clustered sample of households representative of the general population of the United Kingdom in 2009 e the Ethnic Minority Boost sample an additional sample of 1 000 adults in each of the five largest ethnic minority groups in the UK e the Innovation Panel 1 500 households a sample for methodological research e the British Household Panel Survey BHPS a longitudinal study begun in 1991 with 8 000 households incorporated into Understanding Society The nurse health assessments were conducted with adult participants from the GPS and BHPS samples only For the GPS sample the nurse health assessment was undertaken in Wave 2 and for the BHPS sample it was conducted in Wave 3 In both cases the nurse visit took place approximately 5 months after the main interview Data collection began in May 2010 and was completed in July 2012 for the Wave 2 nurse assessment For the Wave 3 nurse assessment data collection began in June 2011 and ended in July 2012 Respondents were eligible for a nurse interview if they had completed a full face to face interview in the corresponding Wave were aged 16 or older lived in England Scotland o
49. hould be assessed from participants who have or have not fasted In Understanding Society blood samples were collected from participants that were not requested to fast Levels of triglycerides are influenced by recent food intake however evidence suggests that these changes are small and do not obscure associations with CVD Triglycerides are measured from serum blood using an enzymatic method on a Roche P module analyser Inter and intra coefficients of variation were less than 3 Are there clinical cutpoints The desirable non fasting triglyceride level is lt 2mmol I 4 What should be considered in analyses Triglyceride levels are influenced by statins BNF chapter 2 12 derived variable bnf7_ statins 13 Nordestdgaard BG Varbo A Triglycerides and cardiovascular disease Lancet 2014 384 626 635 14 Kolovou GD Mikhailidis DP Kovar J Lairon D Nordestgaard BG Chye Ooi T Perez Martinez P Bilianou H Anagnostopoulou K Panotopoulos G Assessment and Clinical Relevance of Non Fasting and Postprandial Triglycerides An Expert Panel Statement Current Vascular Pharmacology 2011 9 3 258 270 13 Version 1 December 2014 22 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Distribution in Understanding Society Figure 3 Distribution of Triglycerides mmol L by gender Males n 5 737 Females n 7 155 Kernel density estimate Kernel density estimate oOo 4
50. iagnosis of diabetes Values between 5 7 and 6 4 indicate pre diabetes risk What should be considered in analyses A number of factors are associated with decreased HbA1c measurements chronic liver disease taking aspirin BNF chapter 2 9 derived variable bnf7_aspirin and anti inflammatory medications BNF chapter 10 1 derived variable bnf7_antiinflam High levels of triglycerides may lead to artefactually low measurements International Expert Committee 2009 International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes Diabetes Care 32 1327 1334 16 Nathan DM Kuenen J Borg R Zheng H Shoenfeld D Heine RJ Translating the A1C assay into estimated average glucose values Diabetes Care 2008 31 1473 1478 American Diabetes Association Executive summary standards of medical car in diabetes 2010 Diabetes Care 33 Suppl 1 S4 S10 1 World Health Organisation 2011 Use of glycated haemoglobin HbA1c in the Diagnosis of Diabetes Mellitus Geneva World Health Organisation Gallagher EJ Le Roith D Bloomgarden Z Review of haemoglobin A1c in the management of diabetes J Diabetes 2009 1 9 17 Version 1 December 2014 24 Understanding Society The UK Household Longitudinal Study Distribution in Understanding Society Biomarker User Guide and Glossary Figure 4 Distribution of Glycated Haemoglobin HbA1c mmol mol by gender Males n 5 443 Females n
51. ingness for each biomarker in the combined GPS and BHPS sample On average valid results are available for 97 5 of the samples processed The key reason for missingness column NBA was the lack of availability of a particular type of blood ie serum citrate plasma or whole blood Haemolysis of the serum sample caused the next highest level of invalid results liver function tests were particular susceptible to this problem For a number of biomarkers the analysers had set low or high detection limits column 2 under over which the result could not be measured accurately Table 4 specifies the specific detection limits for each relevant analyte For testosterone this was true for most women where the lower detection limit was 1 nmol l n 4 978 females We note below in the glossary how to accommodate such measurement issues in analyses For CMV as explained in more detail in the glossary an additional CMV avidity test was performed on those who had a positive or indeterminant value on the CMV IgM test This was only done on 371 cases In the data file the missingness above is separately identified as described in Table 5 so researchers can decide how they wish to incorporate and report in their results Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 2 Biomarkers available in Understanding Society Biomarker Applications Fat in the blood associated hea
52. ion of Haemoglobin level g l by gender Males n 5 419 Females n 6 735 Kernel density estimate Kernel density estimate 3 4 8 8 4 N a a 3 3 of o4 80 100 20 140 160 180 50 100 150 200 haemoglobin g l haemoglobin g l kernel epanechnikov bandwidth 1 7047 kernel epanechnikov bandwidth 1 6310 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Version 1 December 2014 33 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 12 Haemoglobin Hb level g l by gender and age Males Health Survey for England 2009 n 1 203 Age group 16 24 2534 35 44 4554 55 64 65 74 754 ee 150 9 1511 1505 1494 1492 1472 1404 149 2 Mean Hb 0 92 0 90 0 64 0 67 0 75 0 87 1 65 0 34 Understanding Society England sub sample n 4 570 Age group 16 24 25 34 35 44 4554 55 64 65 74 75 eni 1485 1490 1475 1468 1451 1428 1355 145 7 Mean Hb 0 71 0 57 0 49 0 41 0 47 0 56 0 88 0 22 Females Health Survey for England 2009 n 1 044 Age group 16 24 2534 35 44 4554 55 64 65 74 754 Pern 1325 1304 1313 41332 1349 4135 131 6 132 7 Mean Hb 1 38 1 18 0 65 0 86 0 58 0 89 1 05 0 36 Understanding Society England sub sample n 5 625 Age group 16 24 2534 35 44 4554 55 64 65 74 754 ni 1292 120 1 1286
53. itudinal Study Biomarker User Guide and Glossary Distribution in Understanding Society Figure 12 Distribution of Testosterone nmol L by gender Males n 5 722 Females n 7 164 Kernel density estimate Kernel density estimate L T T T T T T T T T 0 10 20 30 40 0 10 20 30 testosterone nmol l testosterone nmol l kernel epanechnikov bandwidth 0 9397 kernel epanechnikov bandwidth 0 0806 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Insulin like growth factor 1 IGF 1 What is its clinical significance Low IGF 1 levels have been shown to be associated with heart disease and high levels have been shown to be predictive of some cancers 37 What is it IGF 1 is a hormone specifically an anabolic protein which builds up organs and tissues It plays an important role in growth and development in childhood and continues to affect adult anabolic processes How is it measured Serum IGF 1 is measured by an electrochemiluminescent immunoassay on IDS ISYS analyser Inter and intra assay coefficient of variation was less than 14 Are there clinical cutpoints There are no published clinical cutpoints for insulin like growth factor 1 Normal reference values for IGF 1 vary in men and women and because of the strong association of IGF 1 with age these values are provided by age group in Table 17
54. ity assessments were regularly reviewed by the quality team and any trends identified escalated through internal governance arrangements any non conformities with EQAs were raised and investigated with the scheme provider The results from the IQC and EQA for the period Understanding Society samples were analysed at NUTH are summarised below in Appendix 1 and key points highlighted in the individual biomarker glossary entries A full technical report is being drawn together and will be made available on the Understanding Society website in due course Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary THE RESPONDENTS WHO TOOK PART Full details of the eligibility and exclusions for the overall nurse visit can be found in the Nurse Health Assessment User Guide Here we provide a broad summary of those respondent who were eligible and took part and more detail on the eligibility consent and valid samples for the data arising from the blood samples As shown in Table 1 across both the GPS and BHPS samples of the 35 937 respondents eligible for the nurse health assessment 20 700 took part a response rate of 57 6 Of those participating in the nurse health assessment 1 579 7 6 were ineligible to give blood and a further 22 6 4 688 people refused Reasons given by respondents for non consent not mutually exclusive included dislike fear of needles 42 7 recently had
55. ls NHS Foundations Trust NUTH which has considerable experience of undertaking blood analysis for research purposes having conducted the analysis of samples from the Health Survey for England HSE and English Longitudinal Study of Ageing ELSA for a number of years as well as other studies Batches of frozen samples for 2000 respondents were transferred to NUTH per month between December 2013 and July 2014 On delivery the bar codes were scanned and samples aliquoted into relevant tubes for the different analytical machines and labelled with a unique bar code in the NUTH system In order to minimise the use of blood all serum analytes were run on a single Roche machine requiring 2x250uL of serum with the exception of one biomarker which had to be analysed on a separate analyser and therefore required a further 250uL of serum Two 250 uL of citrated plasma were required and 204uL of whole blood The latter was sampled from the 4mL EDTA storage tube which was then refrozen and returned to the storage facility Results were transferred electronically from the analysers into a patient management information system and exported and sent to ISER All tests were undertaken according to the Standard Operating Procedures by HCPC Registered Biomedical Scientists Internal Quality Controls IQC were run on each machine at regular intervals per day External Quality Assurance EQA systems were in place to monitor all tests Both internal and external qual
56. ly been published to identify increasing levels of kidney disease dependent on age gender and levels e white men with a creatinine level lt 0 9 mg dL 141 x serum creatinine 0 9 x 0 993 2 e for serum creatinine level gt 0 9 mg dL 141 x serum creatinine 0 9 x 0 993 e white women with a serum creatinine level lt 0 7 mg dL 144 x serum creatinine O 7 0 329 x 0 993 2 e for serum creatinine level gt 0 7 mg dL 144 x serum creatinine 0 7 7 x 0 993 Levey AS Stevens LA et al A New Equation to Estimate Glomerular Filtration Rate Ann Intern Med 2009 150 604 612 Version 1 December 2014 41 2 f Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 15 Classification of kidney function from eGFR equations Stage of Kidney function eGFR chronic kidney disease 1 Normal 90 2 Mildly reduced 60 89 3 Moderately reduced 30 59 4 Severely reduced 15 29 5 Very severely reduced lt 15 What should be considered in analyses To our knowledge no other factors require consideration in the analysis Distribution in Understanding Society Figure 10 Stages of kidney disease defined by eGFR by age and gender 8 1 0 White Males White Females ai g SoH o S N 4 0 16 24 25 34 35 44 45 54 55 64 65 74 5 16 24 25 34 35 44 45 54 55 64 65 74 5 HE Staocsig2
57. measured in Understanding Society which can reflect how well the liver is functioning What are these tests e Alanine Transaminase ALT an enzyme mainly found in the liver the best test for detecting hepatitis raised levels indicate liver damage e Aspartate Transaminase AST an enzyme found in the liver and a few other places particularly the heart and other muscles in the body raised levels indicate liver damage e Alkaline Phosphatase ALP an enzyme related to the bile ducts often increased when they are blocked either inside or outside the liver e Gamma Glutamyl Transferase GGT an enzyme raised levels of which help to detect liver disease and bile duct injury e Albumin measures the main protein made by the liver and tells how well the liver is making this protein low levels may be indicative of a loss of liver function How are they measured The liver function tests are conducted with serum samples ALT is measured with the International Federation of clinical chemistry IFCC UV with Pyridoxal phosphate activation method on the Roche P module analyser AST is measured with the IFCC UV with Pyridoxal phosphase activation method on the Roche P module analyser ALP is measured with the IFCC colourimetric PNP method on the Roche P module analyser GGT is measured with an enzymatic method on the Roche P module analyser Albumin is measured with a BCG colourimetric method on the Roche P module analyser
58. nd sub sample n 5 965 Age group 16 24 2534 3544 4554 5564 65 74 75 eee jeanne 4 6 4 8 51 5 6 5 9 5 7 5 3 5 3 ater 0 06 0 04 0 04 0 03 0 04 0 04 0 06 0 02 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Sample weights are employed for each dataset Standard errors of the mean in parentheses Version 1 December 2014 20 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Figure 2 Distribution of HDL Cholesterol levels mmol l by gender Males n 5 759 Females n 7 119 Kernel density estimate Kernel density estimate T T T T T T 3 7 i gt 5 3 5 1 1 5 2 2 5 high density lipoprotein cholesterol mmol l kernel epanechnikov bandwidth 0 0683 1 1 5 2 2 5 high density lipoprotein cholesterol mmol kernel epanechnikov bandwidth 0 0601 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Table 7 HDL Cholesterol levels mmol l by gender and age Males Health Survey for England 2011 n 1 735 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Total sample Mean 1 3 1 4 1 3 1 4 1 3 1 4 1 4 1 3 HDL 0 03 0 02 0 02 0 02 0 02 0 02 0 04 0 01 Understanding Society England sub sample n 4 850 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 Total sample Mean 1 4 1 4 1 4 1
59. ne of these prescribed medications in the previous 7 days variable bnf7_statins Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Distribution in Understanding Society Figure 1 Distribution of Total Cholesterol levels mmol l by gender Males n 5 754 Females n 7 129 Kernel density estimate Kernel density estimate 4 T T 7 L 2 4 6 8 10 2 1 cholesterol total mmol l 6 cholesterol total mmol l kernel epanechnikov bandwidth 0 1698 kernel epanechnikov bandwidth 0 1870 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Table 6 Total Cholesterol levels mmol l by gender and age Males Health Survey for England 2011 n 1 733 Age group 16 24 25 34 35 44 4554 55 64 65 74 75 Sree PEER 4 5 5 0 5 5 5 6 5 3 4 9 4 6 51 an 0 10 0 06 0 06 0 07 0 06 0 07 0 09 0 03 Understanding Society England sub sample n 4 848 Age group 16 24 25 34 35 44 45 54 5564 65 74 75 M TIE 4 3 51 5 6 5 7 5 4 5 0 4 7 5 2 pete ta 0 07 0 06 0 04 0 04 0 04 0 04 0 05 0 02 Females Health Survey for England 2011 n 2 184 Age group 16 24 2534 3544 4554 5564 65 74 75 one A 4 4 4 8 5 1 5 4 5 8 5 7 5 4 5 2 aan 0 07 0 05 0 05 0 05 0 05 0 07 0 08 0 03 Understanding Society Engla
60. nechnikov bandwidth 0 0939 kernel epanechnikov bandwidth 0 0894 Notes Values belonging to the lowest highest 0 5 of the distribution were excluded Understanding Society Waves 2 3 sample weights employed Danesh J Lewington S Thompson SG Lowe GDO Collins R Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality J Am Med Assoc 294 2005 pp 1799 1809 Version 1 December 2014 28 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 10 Fibrinogen g L by gender and age Males Health Survey for England 2009 n 1 033 Age group 16 24 25 34 35 44 4554 55 64 65 74 75 Peni 25 2 9 3 2 3 4 3 5 3 0 Mean 2 7 0 05 3 1 0 04 Fibrinogen 0 06 0 05 0 04 0 05 0 07 0 03 Understanding Society England sub sample n 4 829 Age group 16 24 25 34 35 44 45 54 55 64 65 74 75 De 23 24 26 28 2 9 3 0 27 Mean 2 7 0 02 raat E 0 04 0 03 0 02 0 02 0 02 0 03 0 02 Females Health Survey for England 2009 n 1 176 Age group 16 24 95 34 35 44 45 54 55 64 65 74 75 ae 3 1 3 0 3 0 3 3 3 4 3 5 3 2 Mean 3 2 0 04 eee 0 06 0 05 0 04 0 04 0 04 0 05 0 06 0 02 Understanding Society England sub sample n 5 934 Age group 16 24 25 34 35 44 45 54 55 64 65 74 754 aoe 26 2 9 3 0 3 1 2 8 Mean 2 7 0 03 2 7 0 02 2 8 0 02 Prai 0 04 0 03 0 02 2 8 0 02 02 0
61. nntneeeretnnnnn nenene 11 Ghoice ofi biomarkers ee ee rt Te ee eT 13 analysis Of DIOMANlKEN dala sted a a r a aaa a a ea a a e a AA 17 JOSSA A E A A A A AA 18 Cholesterol and triglycerides cccceccceceeeeeeeeeeeeeeeeeeeeeeeeeeeseaaaaeaeeeeeeeeeesenesneaeeeeeeeees 19 Total cholesterol and HDL cholesterol cccceeeeeeeeeeeeeneeeeeeeeeeeeeeeenneeeeeeeeeeeeeees 19 HR s 9 i e1 diol ceemeneeterenennce ee eee cnet oe reine er a Oa ern ret re Sr 22 Glycated Haemoglobin HOA IC scsi decscs eds inia a a eden 24 Inflammatory markers markers of inflammation immune function eeeeeeeeees 26 C reactive protein GAP s ictitattacti ainsi a hte le cide atta atta tim ttadt maeets me htetse 26 FIBINO 5 beemeertae mane tne Om Pr TnPCa Ptr EAE nt OPT EE POE See CONT Er OPE UI 28 Cytomegalovirus antibody measurement CMV ccccccccccecccceceeeeeeeeeeeeeeeeeeeeeeeess 30 MGNKGTS Ol AMaC illest ii atere saccade er ahi d a aaee i aa adii 32 Haemoglobin HD siins isisisi niia ai ienaa ii aeiiae i aniidae iiaa bee 32 PeNMMstiinthatiomiiiainathata anal A 34 Liver function tests LFTS cc cccceeeeeeeeeeeeeeeeeeeeeeeeeeeeeaaaaaeaeeeeeeeeeeseseeaaeeeeeeeeeeeeneee 37 Kidney fUnCtio Meee eaae mat EEEa a CO ae temo ree Mere Se mE raed Core ee ee One Se eee ee 41 CCAM Garcon en ier en teal An ia oan ill oon Ninn ee ald oe 41 MCC aiene aa a a E eda tet date S Ua ose sd asennad dae Tete E SAE E 43 PIOMM
62. omarker User Guide and Glossary INTRODUCTION Understanding Society the UK Household Longitudinal Study is a large longitudinal survey of households in the United Kingdom Information is collected on the household all young people aged 10 15 are asked to do a self complete questionnaire and all adults 16 and over are invited to take part in an interview Households recruited at the first round of data collection are visited each year to collect information on changes to their household and individual circumstances In 2010 2012 Waves 2 or 3 after the annual survey adult respondents were also invited to take part in a nurse health assessment interview which included a range of physical measures and blood samples With consent the blood samples were frozen for future analysis and DNA extracted Some of the blood samples have now been analysed to produce a set of biomarkers which are characteristics that are objectively measured and evaluated as an indicator of normal biological processes pathogenic processes or pharmacologic responses to a therapeutic intervention We have selected a range of biomarkers that are either measures of key risk factors for diseases which are major public health problems and or reflect key biological pathways between social and environmental factors and health The purpose of this guide is to outline the biomarkers currently available in Understanding Society and some of the factors that require consideration
63. ons not related to those that they are representing This can make it hard to understand which condition the respondent may have It may be important to control for such co morbidities in analyses Other biomarkers may be affected by substances that the respondent has recently consumed such as food drink or medications For example there has been considerable debate as discussed below in whether triglycerides can be accurately measured if someone has recently eaten In many cases biomarker levels are influenced by medications these may be being deliberately prescribed to influence the level of that biomarker for example statins to reduce cholesterol However medications may also affect other biological processes Derived variables for the specific medication categories listed below which need to be considered in the analysis of these biomarkers have been produced In all of these cases the analyst will need to decide how to address factors such as these As noted above some of the analysers employed had set lower and or upper detection limits for specific biomarkers Analysts may choose to exclude cases outwith these limits Alternatively common practice is to include those cases below the lower detection level with values set half way between the detection limit and zero Sensitivity analyses which investigate these factors are advised For example it may be advisable to exclude samples that took a significant amount of time to be processed
64. ors inconsistencies and other problems with the data identified during their use of the data We make use of this information in improving the data Please raise any issues relating to data or data analysis with our user support service https Awww understandingsociety ac uk documentation help We would also be very pleased to receive copies of publications using the data We will communicate information via Frequently Asked Questions on the Understanding Society web page about the data https www understandingsociety ac uk documentation faq CITATIONS AND ACKNOWLEDGEMENTS Users should cite the data set in any publication using these data as below They should also include an acknowledgement to the UK Data Service study funders and Institute for Social and Economic Research The suggested citation is The biomarker data from Understanding Society were collected by NatCen on behalf of the Institute for Social and Economic Research and funded by the Economic and Social Research Council They are made available through the UKDS SN 7251 Citation of the data University of Essex Institute for Social and Economic Research and National Centre for Social Research Understanding Society Waves 2 and 3 Nurse Health Assessment 2010 2012 computer file Colchester Essex UK Data Service distributor April 2013 SN 7251 http dx doi org Citation of the User Manual and Glossary Benzeval Michaela Davillas Apostolos Kumari Meen
65. r Wales completed their interview in English and for women were not pregnant Given limitations with the number of nurse interviewers in the second year of Wave 2 eligibility was further restricted to 0 81 of the primary sampling units PSUs in England Ethical approval for the nurse health assessment was obtained from the National Research Ethics Service Understanding Society UK Household Longitudinal Study A Biosocial Component Oxfordshire A REC Reference 10 H0604 2 Overall 57 9 of those eligible for the nurse health assessment took part from the GPS sample and 56 6 from the BHPS sample The data from the survey questions and physical measures for both Wave 2 and 3 SN 7251 have been deposited at the UK Data Service UKDS under an End User Licence EUL The biomarker variables outlined below have been added to these data files 7 https Awww understandingsociety ac uk 3 Lynn P Sample design for Understanding Society Understanding Society Working Paper Series 2009 Available from https research understandingsociety ac uk publications working paper 2009 01 Respondents could request survey materials and a nurse visit in Welsh as required by the Welsh Language Act However such requests were not made http discover ukdataservice ac uk catalogue sn 7251 amp type Data 20catalogue Version 1 December 2014 8 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary THE BLOOD
66. rogate endpoints preferred definitions and conceptual framework Clin Pharmacol Ther 69 89 95 McFall Stephanie L Petersen Jakob Kaminska Olena Lynn Peter 2014 Understanding Society UK Household Longitudinal Study Waves 2 and 3 Nurse Health Assessment 2010 2012 Guide to Nurse Health Assessment Colchester University of Essex https www understandingsociety ac uk documentation health assessment 3 https www understandingsociety ac uk documentation health assessment questionnaires NatCen 2010 Nurse Protocols for Measurements and samples used by the National Centre for Social Research London NatCen Understanding Society and NatCen 2010 Understanding Society Nurse Visit Nurse Project Instructions Colchester University of Essex https www understandingsociety ac uk documentation health assessment fieldwork documents 5 Knies Gundi 2014 Understanding Society UK Household Longitudinal Study Wave 1 4 2009 2014 User Manual Colchester University of Essex https www understandingsociety ac uk documentation mainstage https www understandingsociety ac uk documentation Version 1 December 2014 7 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary to apply to analyse them but also based on consultation seek further funding ourselves for analyte users tell us are important DNA was also extracted from the blood samples and analysed by a genome wide scan by t
67. rt disease Cholesterol total and HDL amp triglycerides Undiagnosed or poorly managed diabetes Glucose intolerance Glycated haemoglobin HbA1c Measures of inflammation due injury or infection acute or chronic response to stress Inflammatory markers C reactive protein CRP fibrinogen Immunoscenence wear amp tear on immune system chronic stress associated diabetes Cytomegalovirus CMV seropositivity Marker for poor nutrition increases with age sig health consequences Anaemia haemoglobin Hb ferritin Associated alcohol drugs obesity consequence of other diseases Liver function tests LFTs Alkaline phosphatase ALP Alanine transaminase ALT Aspartate transaminase AST Gamma glutamyl transferase GGT albumin Kidney diseases increases with age associated other diseases Kidney function creatinine urea Hormones Associated with stress processes building muscles ageing Testosterone Marker aggression Growth amp development associated diet diabetes and cancer Associated CVD muscle strength cognition Insulin like growth factor 1 IGF 1 Dihydroepiandrosterone sulphate DHEAs Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Table 3 Valid cases for each biomarker and reasons for missingness Combined GPS and BHPS samples with at least one biomarker n 13 107 Missing cases
68. s To our knowledge no other factors require consideration in the analysis Descriptive statistics in Understanding Society Table 11 CMV infection and if it recently occurred interpretation of combined variables CMV IgM CMV IgG CMV Avidity INTERPRETATION N Negative Negative No evidence of past or 6428 49 95 current CMV infection Negative DETECTED Past CMV infection 5998 46 61 No evidence of recent primary CMV infection DETECTED ind DETECTED HIGH Past CMV infection 366 2 84 eterminate No evidence of recent primary CMV infection DETECTED ind DETECTED LOW Consistent with recent 4 0 03 eterminate primary CMV infection DETECTED ind DETECTED Indeterminate Evidence of CMV infection at 3 0 02 eterminate some time Cannot confirm or exclude recent primary CMV infection DETECTED ind DETECTED Evidence of CMV infection at 43 0 33 eterminate some time Further sample needed to confirm samples not available DETECTED ind Negative Possible very recent primary 27 0 21 eterminate CMV infection or non specific result Further sample needed to confirm samples not available Version 1 December 2014 31 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary MARKERS OF ANAEMIA Haemoglobin Hb What is the clinical significance of haemoglobin Low levels of Hb is suggestive of anaemia a lack of iron in the blood which is prevalent in the elderly and associate
69. s are employed for each dataset Standard errors of the mean in parentheses Table 16shows that mean creatinine values from the England component of Understanding Society are close to those obtained from the HSE 2009 by gender and across age groups Urea What is its clinical significance High urea levels indicate poor kidney function which may be due to acute or chronic kidney disease However its use has generally been replaced as a biomarker by the more robust eGFR measure What is it Urea is a waste product of the breakdown of proteins High levels indicate that the kidneys are not functioning effectively How is it measured Urea was measured from serum samples with a kinetic UV assay on a Roche P module analyser Inter and intra assay coefficient of variation was less than 3 Version 1 December 2014 43 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary Are there clinical cutpoints The normal range of urea is 2 5 7 8 mmol L What should be considered in analyses Other conditions besides kidney disease can affect urea levels such as congestive heart failure and recent heart attack Distribution in Understanding Society Figure 11 Distribution of Urea mmol L by gender Males n 5 878 Females n 7 284 Kernel density estimate Kernel density estimate 2 4 2 4 N N 4 of oJ 0 5 10 15 0 5 10 15 urea mmol l urea mmol kernel epanechnikov ban
70. tion that might be required to adjust biomarker data such as medications are in the indresp_ns files xindresp_ns b_indresp_ns and c_indresp_ns within the nurse health assessment data release Individual BNF coded medications are only available under special licence while broad chapter codes and the key medications outlined above that need to be considered in the analysis of the biomarkers are in the EUL versions Some analysis weights have been prepared for the biomarker data to enable estimation samples to be representative of the general population The general principles behind the weights and the weight naming conventions are consistent with those documented in the main Understanding Society User Guide The sample design involves stratification clustering and weighting since these design features affect standard errors they should be taken into account in analysis A detailed discussion of how analyses might account for the complex sample design along with a description of the relevant variables and Stata syntax can be found in the main Understanding Society User Guide A cross sectional weight variable for the combined GPS and BHPS sample indbdub_xw can be found in the xlabblood_ns datafile This should be used for cross sectional analysis combining both samples but using questionnaire data only from the same Wave in which the blood was collected Note that this weight should not be used for analysis of either the GPS or BHPS sample separ
71. ty of Essex https www understandingsociety ac uk documentation health assessment Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary The Wave 3 longitudinal blood weight for the BHPS sample c_indbd91_ Iw is derived in an analogous way The only differences from the above description are that the base for the model is all eligible BHPS sample members who responded to the individual interview at Waves 2 and 3 and the nurse visit and that the adjustment is applied to c_indns91_ lw The cross sectional weight c_indodub_xw is derived from the longitudinal weight c_indbdub_Iw by applying the weight share method within households By this method sample members who do not have a value of c_indbdub_lw by virtue of not having completed the interview at both Waves 2 and 3 are assigned a value of c_indbdub_xw based on an assumption of equal conditional response propensities within households Wave 4 longitudinal blood weights are based on the equivalent Wave 3 longitudinal blood weights with an additional adjustment for conditional non response to the Wave 4 individual interview The adjustment factor is the reciprocal of the model predicted propensity from a logistic regression model of response to the Wave 4 interview conditional on having responded at Waves 2 and 3 and having blood measures Note that in the case of the BHPS sample there were no significant predictors in the mod
72. um samples with an electrochemiluminsecent immunoassay on the Roche E170 analyser A positive CMV IgG result indicates a CMV infection at some point in time while a negative CMV lgG indicates that the participant has never been exposed or been infected with CMV A positive Immunoglobulin M IgM indicates a recent or current infection Indeterminate CMV occurs during current or acute infection or may be due to non specific binding For those people who had a positive IgM test or whose result was indeterminate an additional test was performed to confirm recent CMV infection This confirmatory assay was an avidity test on the Mini VIDAS immunoassay analyser Inter and intra assay coefficients of variation were less than 4 Are there clinical cutpoints No quantitative assessments of viral load were made as these methods are semi quantitative and indirect Data for each antibody are presented as virus detected not detected or indeterminate Data for the avidity test is presented as high low and indeterminate In combination these three variables see Table 11 below demonstrate the presence of the virus in the body and how recently the person experienced an infection 3 Sinclair J Human cytomegalovirus Latency and reactivation in the myeloid lineage J Clin Virol 2008 41 3 180 5 Version 1 December 2014 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary What should be considered in analyse
73. xtraction of serum 1 x 1 8 ml Version 1 December 2014 9 Understanding Society The UK Household Longitudinal Study Biomarker User Guide and Glossary light blue tube with citrate for plasma extraction 3 x 4 ml purple EDTA tubes to prevent clotting for plasma whole blood and DNA The tubes were labelled with the participant s serial number and date of birth before taking the sample They were packed in a 6 tube transport container and despatched using Royal Mail to the Fisher BioServices secure storage facility Storage facility staff reconciled the sample with consent forms and visually inspected the tubes They applied a unique bar code which is used in sample retrieval Samples were processed ie to separate plasma and serum and extract DNA placed in smaller tubes aliquots and stored in freezers at 80 degrees C On average it took 2 6 days from the time of blood collection to the samples being processed by the Lab 90 of samples were processed within 4 days Below we note issues with the length of time to processing and we are planning some small scale experiments to further understand the robustness of analyte measurement to long delays in sample processing The results of which will be made available in due course ANALYSIS OF SAMPLES In 2013 after successfully securing funding ISER issued an invitation to tender for the analysis of the Understanding Society blood samples The tender was won by Newcastle upon Tyne Hospita

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