deteting familial hyperholesterolaemia in general pratie

7/27/2019 Deteting Familial Hyperholesterolaemia in General Pratie

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clinical

Detecting familialhypercholesterolaemia in

general practice

Andrew Kirke

Gerald F Watts

Jon Emery

yars and won a 30% risk y th ag of 60

yars.2 Athrosclrosis causd y FH starts in

childhood and adolscnc, highlighting th nd

to idntify cass arly and conc prvntiv

asurs.3 Th frquncy of causativ utations

in th low dnsity lipoprotin (LDL) rcptor

gn is stiatd to on in 500 in th gnral

population, and up to on in 100 in crtain thnic

groups such as Ashknazi Jws fro South Africa,Christian Lans and Dutch Afrikaanrs, du to a

gntic foundr ffct.4

In Australia, it is stiatd that thr ar ovr

45 000 cass of FH, with lss than 10% of cass

forally diagnosd.5 Intrnational data show

that of thos diagnosd, any ar inadquatly

tratd.6 For a gnral practic of 12 000 patints

thr ay up to 25 cass.7 Of ths cass, th

rat of diagnosis and tratnt could as low as

1525%, and this is particularly so in childrn.810

Failial hyprcholstrolaia can diagnosd

with phnotypic critria (Table 1) or a DNA tst.1

Screening for familialhypercholesterolaemia

Failial hyprcholstrolaia ts all of th

World Halth Organization scrning critria as

dfind y Wilson and Jungnr11 (Table 2). Failia

hyprcholstrolaia confrs a lif long risk of

CHD and is hnc ost appropriatly scrnd for

in a priary prvntion stting in th counity.

Th ost cost ffctiv thod of scrning

for FH is cascad scrning faily rs ofknown indx cass of FH12 ut at a population

lvl this rquirs that an fficint thod

adoptd to dtct indx cass. Othr approachs

ar thrfor rquird for scrning th gnral

population to idntify indx cass, whos

rlativs can thn scrnd. On of th

challngs, particularly in todays nvironnt

with an pidic of osity, is diffrntiating

cass of ordrlin FH fro acquird

Familial hypercholesterolaemia (FH) is

a relatively common inherited cause of

premature coronary artery disease. However,

a significant number of people remain

undiagnosed in the community.1 Several

clinical guidelines on FH have been published

recently, including an Australian model of

care,1 but these need to be placed in context

for general practitioners. In this article we

review approaches to screening for FH in thegeneral practice setting.

What is familialhypercholesterolaemia?

Failial hyprcholstrolaia is an autosoally

doinant inhritd lipid disordr, which causs

pratur hart disas and dath in affctd

individuals. Untratd, n hav a 50% chanc of

coronary hart disas (CHD) for th ag of 50

Background

Familial hypercholesterolaemia (FH) is a relatively common inherited cause of

premature coronary artery disease. However, a significant number of people

remain undiagnosed. Several clinical guidelines on FH have been published

recently, but these need to be placed in context for Australian general

practitioners.

Objective

We review four possible approaches to screening for FH in the general practice

setting: two opportunistic and two systematic. Evidence for these screening

approaches is drawn from the current literature on FH.

Discussion

General practitioners are well placed to institute screening for FH in the general

practice setting. Screening approaches could include opportunistic screening for

family history, opportunistic screening of lipids, systematic searching of general

practice electronic records, and universal screening of children. The role of

specialist lipid clinics is important in the GP management of patients with FH.

Keywords

genetics; lipid metabolism disorders; mass screening; preventive medicine; heart

diseases

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Detecting familial hypercholesterolaemia in general practiceclinical

hyprcholstrolaia du to poor dit and lack

of xrcis, and this is particularly rlvant in

childrn and adolscnts.

It is in this contxt that gnral practic has

a potntial advantag in idntifying cass of FH.

In Australia, 83% of popl attnd a GP at last

onc a yar,13 and as for othr chronic disas and

halth prvntion, this is a grat opportunity for

scrning. Four possil approachs to scrning

for FH in th gnral practic stting ar outlind

in Table 3.

Opportunistic scrning is vry uch within

th ral of vryday gnral practic activitis.14

Raising th profil of FH ans that th GP is or

likly to considr th diagnosis whn scrning for

undiagnosd disas.

Systatic sarching of gnral practic

lctronic rcords is a or rcnt approach, which

is incrasingly ing usd, notaly in anagingchronic disas such as diats and astha. Us

of data xtraction softwar within th lctronic

gnral practic rcord allows idntification of a

sust within th total patint population at highr

risk of th targt disas. Data fro th Unitd

Kingdo suggsts that this ay an ffctiv

thod of discovring nw cass of FH.15

Univrsal scrning of childrn agd 911

yars and young popl agd 1921 yars is th

position takn y xprt guidlins in th Unitd

Stats,16 ut this is not rcondd in Th

Royal Australian Collg of Gnral Practitionrs

Guidelines for preventive activities in general

practice(rd ook).14 Introduction of univrsal

Tabe 1. Duth lipid cii network riteria for makig a pheotypi

diagosis of famiia hyperhoesteroaemia i aduts17

Criteria Score

Family history

First degree relative with known premature coronary and/or vascular

disease (men aged


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clinicalDetecting familial hypercholesterolaemia in general practice

scrning for hyprcholstrolaia rcogniss

th shortfall in systatic dtction of indx

cass of FH in priary and scondary car

sttings, particularly whr diagnosis rlis on

otaining an accurat faily history of CHD and/

or hyprcholstrolaia as a condition of tsting

for FH. Altrnativly, scrning of all popl

agd 16 yars is anothr approach that has nadvocatd as ing cost ffctiv.12

Th proaility of a prson having FH can

dtrind using th Dutch Lipid Clinic Ntwork

Critria17 (DLNC) which scors popl for thir

clinical history, physical faturs (g. tndon

xanthoata and cornal arcus), and th plasa

lvl of LDL-cholstrol. Gnral practitionrs,

or a traind nurs, can thrfor apply this

scoring syst to idntify thos patints ostlikly to hav FH. Patints with a DLNC scor

of gratr than fiv hav proal FH and

ay nfit fro rfrral to a spcialist

lipid clinic. Th DLNC should not usd in

childrn, who should idntifid as having

FH according to LDL-cholstrol thrsholds. At

a practical lvl, childrn should initially

scrnd using a nonfasting lipid profil, with

a rpat fasting tst if FH is still suspctd.On intrsting ut untstd approach to

Tabe 3. Four possibe modes of sreeig for famiia hyperhoesteroaemia i geera pratie

Opportunistic screening for family history Patients with a positive family history should have their lipid profile measured and be

examined for clinical features of FH (Table 1)

Opportunistic screening of lipids As recommended in the RACGP red book,14 those with LDL-C >4.0 or total cholesterol

>7.5 should be reviewed for family history and clinical features of FH

Systematic searching of general practice

electronic records

Use of search engines to systematically search general practice electronic records

and extract patients at higher risk of FH for further review. A possible model has been

trialled in the UK15

Universal screening of children More controversial but recommended in the US, all children age 911 years should

have their lipid levels measured.19 Alternatively, screening of all those aged 16 years12

Response

Received by clinical

service

Send second letter/

telephone

Family member

No

response

No

response

No Yes

No

Index case consents

to risk notification of

relatives

Risk notification

Send letter and

information sheet to

family member and/or

give to index cases todistribute to relatives

Continue to build

rapport

Consider referring

to clinical genetics

service and/or patientsupport group

counselling

Is there is a strong

clinical indication for

risk notifying relatives

without consent?

Consult

Commonwealth/state

legislation and NHMRC

guidelines about

disclosure of medical

information without

consent

Family member

consents to screening

Family member

does not consent to

screening

Arrange appointmentwith FH service

As per local protocol

Accept decision not to

be tested

But encourage risk

notification of their

first and second

degree relatives

Figure 1. Process of cascade screening family members of index case of familial hypercholesterolaemia

Reprinted with permission from Watts GF, Sullivan DR, Poplawski N, et al. Familial hypercholesterolaemia: A model care for Australasia.

Atherosclerosis Supplements 2011;2:22163

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Detecting familial hypercholesterolaemia in general practiceclinical

augnting th dtction of childrn with FH,

is to rcond that all coupls planning a

prgnancy tstd for hyprcholstrolaia

for concption.

It is iportant to not that for

aking a phnotypic diagnosis of FH in

adults and childrn, scondary causs of

hyprcholstrolaia such as hypothyroidis,

nphrosis, cholstasis and us of stroids

ust xcludd. It should also notd that

if plasa triglycrids ar >4 ol/L, LDL-

cholstrol cannot calculatd and ust

asurd y a dirct laoratory thod.

The role of specialistlipid clinics in familialhypercholesterolaemia

Thr ar svral iportant rasons for rfrring

patints with proal FH to a spcialist lipid clinic: Confirmationofthediagnosis.TheDLNC

scor will confird y or xtnsiv

clinical and laoratory assssnt, including

DNA tsting for causativ utations in th

LDL rcptor and othr gns. So patints

with classic phnotypic faturs of FH ay

still not hav a utation idntifid (g. 10%

childrn with dfinit phnotypic FH),18

rflcting liitations of th currnt DNA tst

and ultipl utations causing th disas.

Howvr, idntification of a spcific utation

is iportant in confiring th diagnosis and in

cascad scrning

Cascadescreeningoffamilymembers,either

through an idntifid gntic utation or

phnotypic assssnt using th DLNC

critria. Th procss of cascad scrning

can coplx (Figure 1), and whil gnral

practic ay hav a rol, a cntralisd srvic

coordinatd via a lipid clinic is proaly

st placd to undrtak xtndd cascad

scrning of scond and third dgr rlativs.

Cascad scrning ay a fasil optionfor parnts and childrn undr th car of th

sa GP

Cardiovasculardiseaseassessmentand

disas prvntion. A lipid clinic can dtrin

appropriat invstigations to dtct xisting

cardiovascular disas, dtrin th st

pharacological rgin to anag th

anoral lipid profil, and rinforc th

iportanc of a halthy lifstyl

Ifthereisnospecialisedlipidclinicavailable,

rfrral to a cardiologist or ndocrinologist

with spcial intrst in l ipid disordrs would

altrnativ rfrral pathways.

Summary

Failial hyprcholstrolaia is an iportant ut

undrdiagnosd caus of pratur coronary artry

disas. Gnral practic could play an iportant

rol in idntifying failis with this condition and, in

collaoration with spcialist lipid clinics, instituting

ffctiv disas prvntion. Scrning progras

in priary car ai to idntify indx cass and

ncopass univrsal, targtd and opportunistic

approachs. Indx cass should also vigorously

idntifid in scondary prvntion sttings (such

as cardiac rhailitation) and onc idntifid,

ths cass can intgratd into a coordinatd,

cntralisd cascad scrning progra.

AuthorsAndrw Kirk mbbS, FRACGP, FACRRm, is

Associat Profssor, Rural Clinical School

of Wstrn Australia, Univrsity of Wstrn

Australia, bunury, Wstrn Australia. andrw.

[email protected]

Grald F Watts DSc, mD, PhD, FRACP, is

Winthrop Profssor, Dpartnt of mdicin and

Pharacology, Univrsity of Wstrn Australia,

Prth, Wstrn Australia

Jon ery mA, mbbCh(Oxon), FRACGP, mRCGP,

DPhil, is Winthrop Profssor and Had, Schoolof Priary, Aoriginal and Rural Halth Car,

Univrsity of Wstrn Australia.

Conflict of intrst: ICmJe fors hav n

copltd y all authors. Grard Watts has

rcivd funding for consultancy and lcturs fro

Agn, Gnzy-Sanofi and Roch.

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deteting familial hyperholesterolaemia in general pratie

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