MEDPED A humanitarian project to find and help persons

with familial hypercholesterolemia (FH)

FH is under-recognized and under-treated! Web site: www.medped.org

A striking family history

45 ♥ 334

47 ♥

42 218

38 ♥ 34 ♥ 347

40 ♥ 373

41 ♥ 34 ♥

16 284

18 94

20 182

42 180

31 158

12 132

17 157

18 285

19 130

21 311

22 135

6 291

13 344

14 118

15 255

40 ♥ 373

Affected MI age 40 Total Chol

Key

Hopkins PN. Clin Lipidol 2010 in press

MEDPED A humanitarian project to find and help persons

with familial hypercholesterolemia (FH)

FH is under-recognized and under-treated! Web site: www.medped.org

What are some of the challenges of FH screening?

♥ Identifying FH patients ● DNA (gold standard) versus clinical?

● Who pays?

♥ There is urgency to finding FH ● Previously, the Dx usually came after MI

● Earlier, aggressive Rx better outcomes • Universal screening of teenagers cost-effective

Additional challenges in US

♥ No current data on: ● How many FH are diagnosed

• <33%? (Williams RR, Am J Cardiol 1993; 72:18D)

● What percent are treated (any Rx)

● How well FH are treated (current LDLs)

● CURRENT CAD RISKS OR OUTCOMES

200

220

240

260

280

300

320

340

360

380

400

<1993 (14) 1993 (21) 1994 (43) 1995 (75) 1996 (176) 1997 (56)

Tota

l cho

lest

erol

(mg/

dL)

Year of entry (n)

Hopkins PN. Clin Lipidol 2010 in press

Entry levels of total cholesterol in the MEDPED Treatment Support Program

Challenges for Dx

♥ Physical findings ● Tendon xanthomas

● Arcus

♥ Serum LDL levels

♥ DNA Dx

Darryl Kile Pitcher for the St. Louis Cardinals

Died June 22, 2002, age 33

Survived by widow and 3 young children.

Autopsy: 80-90% coronary artery stenoses.

FHx: father died of MI age 44.

0

10

20

30

40

50

60

<30 30-39 40-49 50-59 60+Age (years)

Prev

alen

ce (%

) in

346

Uta

h FH

Het

eroz

ygot

esXanthoma Full Arcus

Hopkins PN. Current Treatment Options in Cardiovascular Medicine 2002; 4:121

0.00

0.00

0.00

0.00

0.00

0.01

0.01

0.01

0 50 100 150 200 250 300 350 400 450 500

Prob

abili

ty

LDL cholesterol (mg/dL)

Non-FH FH

False negatives

False positives

80% probability of FH

LDL cholesterol levels mean SD FH 289 63.0 Non-FH 130 31.4

Hopkins PN. Clin Lipidol 2010 in press

Degree of Relation to Closest FH

Age First Second Third General “100%”

<20 220 (155) 230 (165) 240 (170) 270 (200) (240)

20-29 240 (170) 250 (180) 260 (185) 290 (220) (260)

30-39 270 (190) 280 (200) 290 (210) 340 (240) (280)

40+ 290 (205) 300 (215) 310 (225) 360 (260) (300)

Practical LDL Criteria for Diagnosing Heterozygous FH in U.S. Population

Williams RR, et al. Am J Cardiol 1993; 72:171

Predicted total-C and (LDL-C) in mg/dl cut points achieving at least 80% probability for an individual to be affected.

Cumulative Probability of Non-Fatal CAD in Utah FH vs a Random U.S. Population

0

0.01

0.02

0.03

0.04

0.05

Age

Non-FH Women

FH Women

0.00

0.05

0.10

0.15

0.20

0.25

0.30

Cum

ulat

ive

Prob

abili

ty

of C

linic

al C

AD

Age

Non-FH Men

FH Men

Hopkins PN. Clin Lipidol 2010 in press

6-fold greater risk in men

Why focus on FH?

♥ FH provides the only example of a genetic cause of premature CAD for which a systematic, population-based approach to proband identification and family screening is clearly warranted at this time.

Thank You!