Non fasting screening bloods in CVD risk assessment: role of HbA1c and non fasting

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Non fasting screening bloods in CVD risk assessment: role of HbA1c and non fasting cholesterol Mrs Susan Prosser Consultant Clinical Scientist Biochemistry Department Withybush General Hospital

Diagnosis of DM WHO Recommendation 2011 HbA1c can be used as a diagnostic test for diabetes providing that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. An HbA1c of 48 mmol/mol is recommended as the cut point for diagnosing gdiabetes. A value of less than 48 mmol/mol does not exclude diabetes diagnosed using glucose tests.

What is HbA1c? f h l i bl d bi d Some of theglucose in blood binds to haemoglobin. This combination of glucose and haemoglobin is called haemoglobin A1c (HbA1c). The amount of HbA1c formed is directly related to the average concentration of glucose in the bloodstream. Red blood cells live for 2 3 months, and because of this, the amount of HbA1c in blood reflects the average level of glucose in the patient s blood during the last 2 3 months.

HbA1c continued If the patient has an abnormal type of haemoglobin, for example sickle cell disease, accurate results will depend on the method used to measure HbA1c. If the patient has haemolysis or heavy bleeding, test results may be falsely low. Finally, if the patient is iron deficient, this may raise the HbA1c result.

HbA1c analysis Tosoh G7/8 HbA1c results are directly measured and not clinically affected by the presence of most haemoglobin variants.

Patient example 41 year old male 24/07/2015 20/10/2015 HbA1c 58 Hb (130 180) 118 144

Patient example 41 year old male 24/07/2015 20/10/2015 31/03/2016 HbA1c 58 25 Hb (130 180) 118 144 131

NG17 Type 1 Diabetes in adults: diagnosis and management 1.6.5 If HbA1c monitoring is invalid because of disturbed erythrocyte y turnover or abnormal haemoglobin type, estimate trends in blood glucose control using one of the following: fructosamine estimation quality controlled blood glucose profiles total glycated haemoglobin estimation (if abnormal haemoglobins). [2015]

NG28 Type 2 Diabetes in adults: management 1.6.3 If HbA1c monitoring is invalid because of disturbed erythrocyte y turnover or abnormal haemoglobin type, estimate trends in blood glucose control using one of the following: quality controlled plasma glucose profiles total glycated haemoglobin estimation (if abnormal haemoglobins) fructosamine estimation. [2015]

Fructosamine Fructosamine is the name given to ketoamine products formed from the non enzymatic attachment of a carbohydrate to a protein It cannot be used to diagnose diabetes It reflects average glucose over last 1 3 weeks Measurements may be invalid when there are significant abnormalities of plasma protein concentrations ti eg in nephrotic syndrome, liver cirrhosis, paraproteinaemias,during an acute phase response and in untreated thyroid disease

Fructosamine Fructosamine in a healthy population: 205 285 umol/l Results greater than this range indicate hyperglycaemia during thepreceding 1 3 weeks or longer There are limited and conflicting data in the literature on both thecorrelation with HbA1c and with clinical outcomes in diabetes

HbA1c summary No fasting required Result affected by anaemia of any cause and may be either increased or decreased depending on the cause of the anaemia HbA1c should not be replaced by fructosamine without good reason HbA1c must not be used as the sole test to diagnose diabetes in symptomatic ti children or patients with symptoms suggesting type 1 DM

Lipid profile reported tdacross Wl Wales Pre June 2015 consisted of Total cholesterol (TC) Triglycerides (TG) HDL cholesterol (HDL) Cholesterol:HDL ratio* LDL cholesterol (LDL)* * calculated result

Calculated lipids Cholesterol:HDL ratio = (TC/HDL) Used in QRISK 2 risk calculator LDL cholesterol = TC HDL (TG/2.17) Requires a fasting specimen Not valid if TG > 4.5 mmol/l

NICE CG181 (2014) Cardiovascular disease: risk assessment and reduction, including lipid modification 1.3.4 Before starting lipid modification therapy for the primary prevention of CVD take at least one lipid sample to measure a full lipid profile. This should include measurement of total cholesterol, HDL cholesterol, non HDL cholesterol and triglyceride concentrations. A fasting sample is not needed. [new 2014]

Lipid profile from June 2015 Cholesterol l Triglyceride HDL Cholesterol Non HDL Cholesterol* Cholesterol:HDL ratio* LDL Cholesterol* l* Non HDL cholesterol is reported in accordance with NICE CG 181 (2014). LDL cholesterol may not be valid for non fasting samples. * calculated

Non HDL cholesterol Non HDL cholesterol = TC HDL (mmol/l) Used as treatment target Aim for 40% reduction in non HDL cholesterol in primary and secondary prevention (from pre treatment level)

When patient must fast for lipids If?familial hypercholesterolaemia (FH) as diagnosis is based on LDL cholesterol If raised triglycerides repeat profile with patient fasting as triglycerides are affected by fasting status

Lipid summary Generally no need to fast for lipids Cholesterol:HDL ratio used in QRISK 2 Non HDL cholesterol used for treatment target Beware?FH Fasting if raised triglycerides