Abstracts / Atherosclerosis 231 (2013) e1–e10 e7

patients with polygenic hypercholesterolaemia. It is important to distin-guish FH from polygenic hypercholesterolaemia as FH carries significantlyhigher risk of coronary heart disease. We reviewed total cholesterol levelsof 790 healthy individuals who attended voluntary health Check up. Allwere over the age of 40 yrs working either in our health board or in alocal steel plant. 8 healthy individuals with no significant past medicalhistory and no evidence of metabolic syndrome were found to haveelevated total cholesterol of more than 7.5 mmol/L. 4 of them did nothave family history of hypercholesterolaemia or premature ischaemicheart disease. 29 individuals had cholesterol level higher than 6.5 mmol/Lbut less than 7.5mmol/L. 22 of them had no family history ofhypercholesterolaemia.

Conclusion: Reported incidence of heterogenous hypercholesterolaemia is1 in 500. In our study it is 5 in 500. Out of them 2.5 in 500 did not havefamily history of hypercholesterolaemia or premature cardiac disease.These figures indicate significant number of healthy individuals in generalpopulation with no risk factors have elevated cholesterol levels whichwarrants screening for familial hypercholesterolaemia.

IMPLEMENTATION OF A MULTIDISCIPLINARY APPROACH TO DIAGNOSISAND MANAGEMENT OF FAMILIAL HYPERCHOLESTEROLAEMIA (FH) INWALES: THE ROLE OF THE FH SPECIALIST NURSE

R. Edwards 1,*, D. Townsend 1, R. Gingell 1, K. Haralambos 2, B.N. Datta 3, I.F.W.McDowell 3, L. Edmunds 3.

1All Wales FH Cascade Testing Service, UK; 2Cardiff University, UK; 3Cardiffand Vale University Health Board, UK

* Corresponding author.

The Wales FH service, launched in Sept 2010 has been developed based onNICE guidance to provide a coordinated approach to cascade testing for FHand other aspects of diagnosis and clinical management. Prior to this therewas no cascade testing offered and inequitable service provision.

BHF FH nurses have been central to a variety of different developmentsincluding

- Increased awareness of FH and access to specialist services, includinggenetic testing, for index patients and their families

- Multi-disciplinary partnership working across lipidology, genetics,cardiology and primary care.

- Development of an FH primary care pack and web-based teachingguide to support primary care

- A nationwide electronic patient pathway, utilising an IT system toensure an equitable and systematic approach to patient care.

Results: Three specialist BHF FH nurses have helped to develop lipid servicesacross Wales, doubling numbers of FH/lipid clinics from 8 to 16. Referralrates from primary/secondary care have increased by 19% in the first yearand 132% in the second year, with over 1000 index patients assessed clin-ically for FH. Of these, 780 have been genotyped and 270 have received agenetic diagnosis (35%). Family cascade testing by genetic counsellors, usingidentified FH genetic mutations, has led to 222 relatives being diagnosedwith FH and 181 being reassured that they do not have FH.We conclude that FH specialist nurses have a key role to play in thedevelopment and delivery of FH services.

IMPLEMENTATION OF FAMILIAL HYPERCHOLESTEROLAEMIA(FH)NURSE LED ASSESSMENT CLINICS IN SOUTH WALES

R. Edwards 1,*, N. El Farhan 2, S. Woods 2, H. Hopcroft 2, D. Townsend 1, R.Gingell 1, K. Haralambos 3, B.N. Datta 4, I.F.W. McDowell 4, L. Edmunds 4.

1All Wales FH Cascade Testing Service, All Wales Medical Genetics Service,Cardiff, UK; 2Royal Gwent Hospital, Newport, UK; 3Cardiff University,

Cardiff, UK; 4University Hospital of Wales, Cardiff and Vale Health Board,Cardiff, UK

* Corresponding author.

Aneurin Bevan Health Board (ABHB) has an approx population of 561,000.At the time of the launch of the all Wales FH testing service, December2010, there were three lipid clinic sessions a month, seeing on average 12new patients per month. New patient waiting lists were in excessive of6months, managed only by initiative clinics, twice a month.

Patients who were being seen in Lipid clinic, who met the criteria for FHgenotyping, were seen by the FH specialist nurse and offered counsellingand the option of consenting for the FH genetic test, either during theirlipid clinic appointments or at specific community based nurse-led gen-otyping clinics. Due to the excessive lipid clinic waiting list times, no FHawareness sessions were carried out in primary care, to promote referralfor FH assessment/genetic testing.Since March 2012, ABHB has initiated nurse-led FH assessment clinics thatrunalongside consultant led clinics. By identifyingpatients for FHassessmentat the time of referral, waiting times for FH assessment/genotyping havereduced from 6 months to 6-8weeks. This has affected general lipid referraltimes with waiting list held at 6 months, without the use of initiative clinics.Reduction in waiting times have allowed for the promotion of FH withinprimary care. This improves access to FH genetic testing and the cascadetesting of family members, with known pathogenic variants.

TWO CASES OF TANGIER DISEASE MUTATION: CLINICAL RELEVANCEFOR VASCULAR RISK

A. Jain 1, K. Al-Musalhi 1, KoksweeGan 2, J.W. Persaud 1, D.P.Mikhalidis 1, D.R.Nair 1.

1Department of Clinical Biochemistry, Royal Free Hampstead NHS Trust,London NW3 2QG, UK; 2Cheltenham General Hospital, Sandford Road,Gloucestershire, GL53 7AN, UK

Tangier disease (TD) is an autosomal codominant disorder that causes acomplete absence or extreme deficiency of high density lipoprotein (HDL).It is caused by mutations in the adenosine triphosphate binding cassettetransporter 1 (ABC-1) which plays a role in the cholesterol efflux pathway.Two siblings initially presented with undetectable HDL cholesterol (HDL-C) levels. We received the samples through our Supraregional Assay Ser-vice (SAS) centre for Cardiac Biomarkers. The index case was under thecare of dermatologists for acne and a lipid profile was ordered as oralretinoid therapywas considered. Repeat analysis confirmed a lowHDL-C of0.1 mmol/L in both siblings together with low total cholesterol but normaltriglycerides. Apolipoprotein A1 (APO A1) was <0.05 g/L Lipoproteinelectrophoresis showed absence of alpha band which represents the HDLfraction. Lipid profile testing of other family members (both parents and ayounger sibling) was normal with a normal lipoprotein electrophoresispattern. We proceeded to genetic analysis of this family. Both siblings withlow HDL-C were found to be compound heterozygotes for ABC-1 muta-tions described as ABCAI R 587W CGG to TGG in position 1759 in exon 14(allele 1) for the mother and ABCAI G85IR GGA to AAA on position 2552 inexon 18 (allele 2) for the father. Both the parents had HDL-C levels >1mmol/L. Studies showed a 54% risk of developing peripheral neuropathyand a 20% risk of developing cardiovascular disease (CVD) in patient withTD compared with <1% and 5%, respectively for controls. In patients withTD care should be taken when administering drugs that may induce anatherogenic lipid profile. The 2 siblings with compound heterozygote ABC-1 mutations should be monitored for CVD risk factors.

RISK EQUIVALENTS IN HYPERLIPIDAEMIA

Dr Christopher Martin 1,*, Dr Paul Taylor 2.

1Crystallise Ltd., UK; 2CHIME, UCL, London, UK

* Corresponding author.

Abstracts / Atherosclerosis 231 (2013) e1–e10e8

Background: People with familial hypercholesterolaemia (FH) face lifelongmedication and lifestyle choices. An accurate understanding of thecomparative benefits from different preventive strategies can help themmake rational decisions based on individual circumstances.

Methods: We developed a deterministic, risk-factor and cause-of-death-based, longitudinal mortality model to predict mean age of death based onindividual risk factors. The performance of the model has been assessedusing data from epidemiological studies that followed patients over mul-tiple decades. We used the model to estimate, for eight individuals withdifferent profiles, the likely increase in lifespan associatedwith a reductionin total cholesterol to high-density lipoprotein ratio (TC:HDL) of 1.0. Wethen determined what change in smoking rate, systolic blood pressure(SBP) and body-mass index (BMI) would be equivalent to this change inTC:HDL ratio for each individual.Results: Having a TC:HDL ratio typical of FH (7.3) brings forward the meanage of death, compared with 2008 UK population means, by 1.7 to 2.3years, depending on age and gender. The mean increase in age of deathassociated with a 1.0 reduction in TC:HDL from baseline ranged from 0.4years for a 65 year-old woman with FH to 0.9 years for a 35 year-old manwith a population mean TC:HDL ratio of 4.2. This absolute difference insurvival was equivalent to a change in smoking rates of 1–5 cigarettes aday; a decrease in SBP of 5–16 mmHg; and a decrease in BMI from 3.0–8.6kg/m2, depending on age, gender and baseline lipid levels. The absoluteimpact on mortality of smoking, SBP and BMI was higher in people withFH-level lipids than in those with mean lipid levels, regardless of gender orage.

IS NON HDL CHOLESTEROL FREE:TOTAL CHOLESTEROL RATIO A USEFULMEASUREMENT FOR DETECTION OF LIPOPROTEIN-X?

S.J. Pattman 1, B. Askew2, M. Hudson 3, R.D.G. Neely 1.

1Newcastle upon Tyne NHS Hospitals, Department of Clinical Biochemistry,Newcastle upon Tyne, NE1 4LP, United Kingdom; 2 hbinnovations, Cels atNewcastle, Newcastle upon Tyne, United Kingdom; 3 Freeman Hospital,Newcastle upon Tyne, Department of Hepatology, Newcastle upon Tyne,United Kingdom

Aim: Lipoprotein X (LP-X) is abnormal particle containing only freecholesterol and phospholipid which has been described in patients withcholestatic jaundice, lecithin-cholesterol acyltransferase (LCAT) deficiency,and on total parenteral nutrition (TPN). A high ratio of free to totalcholesterol (FC/TC) may indicate the presence of LP-X and be used to es-timate its concentration. Using a novel electrophoretic method to quantifythe FC/TC ratios in the non-HDL fraction we aimed to determine thepresence of LP-X in conditions associated with LCAT deficiency including

Cholesterol results pre an

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patients with elevated bilirubin, renal failure, type 2 diabetes mellitus,hypothyroidism and on TPN.

Method: Agarose gel electrophoresis was performed with enzymatic stainingfor cholesterol to quantitate total and free cholesterol in plasma lipoproteins.Non-HDL FC/TC ratios in 14 patients with elevated bilirubin, 14 with renalfailure,14with type2diabetesmellitus,15withhypothyroidismand3patientson TPN were measured. Ratios were compared to those from a previouslyderived reference range.Gelswereexamined for thepresenceof adistinct LP-Xband,whichwasquantifiedbycalculationassumingaFC/TC ratio in LP-Xof1.0.Results:Median calculated ratios in diabetic patients (0.29; P¼0.0049), hypo-thyroid patients (0.31;P¼0.0018), renal failure patients (0.41;P<0.0001) andTPNpatients (0.28)were all higher than the referencemedian (0.25), howeverthehighest ratiowas inpatientswithelevatedbilirubin (0.56;p<0.0001)and6patients were found to have LP-X present on examination of the electropho-retic gel. These LP-X concentrations ranged from 1.4-20.3mmol/L.Conclusion: In conditions associated with LCAT deficiency there is anincreased proportion of free cholesterol present. Only in patients withelevated serum bilirubin levels was LP-X found and the clinical significanceof the elevated free cholesterol in the other conditions is uncertain. Thismethod shows utility for detection and quantification of LP-X in theroutine clinical laboratory.

A PATIENT WITH HOMOZYGOUS FH AND IMPRESSIVE XANTHOMATA –

A CASE STUDY

A. Pottle*, E. Neves, V. Kale, E. Lee, M. Calam, C. Huggett, V. Ellis, M. Barbir.

Lipoprotein Apheresis Unit Harefield Hospital, Harefield, Middx, UK

* Corresponding author.

ZK is a 23 year old Asian who was referred to Harefield Hospital in 2011 forlipoprotein apheresis therapy. He was originally seen at the age of 5 with‘spots on his knees’ and was told he had raised cholesterol. He came to theUK in 2010 and was seen in the lipid clinic where is great aunt was underfollow-up. Genetic screening found him to have homozygous FH with thesame LDL receptor gene mutation as his aunt. On referral for apheresis hewas taking Rosuvastatin 20mg bd and Bezafibrate 200mg bd. His totalcholesterol (TC) was 16.8mmol/L, LDL cholesterol 15.3mmol/L, Lp(a)1530mg/L and the Apo B was 3.09g/L. On examination he had extensivexanthomata on his elbows, buttock and palmar creases of both hands. Therewere also eruptive lesions on both forearms. He had no cardio-respiratorysymptoms. A CTangiogram demonstrated a soft plaque in the proximal RCAwhichwas causing a tight stenosis. Hewas referred for anMRI scan to assessthe functional effect of the lesion but he was unable to tolerate the scanner.He is now awaiting angiography and myocardial perfusion scanning.

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