1. The FH Foundation CASCADE FH RegistryTM
Need to insert a slide in this intro section referencing name-brand sponsors and collaboration with DCRI
The FH Foundation
CASCADE FH RegistryTM

2. CASCADE FH Registry data to: Evaluate trends in therapy
clinical outcomes
patient reported outcomes
___improve quality of lige, clinical outcomes, show gaps in care, costs in life years and productivity

3. https://thefhfoundation.org/fh-research/registry/
CASCADE FH Registry
Multicenter US registry to increase awareness, characterize treatment, monitor outcomes in FH
Key initiatives of FH Foundation; major data gap in the US
CAscade SCreening for Awareness and Detection of FH, national initiative to increase FH awareness, characterize trends in treatment, and monitor clinical and patient-reported outcomes over time

4. CASCADE-FH Registry Design
Lipid Clinic
Patient Portal
Eligibility
Clinical or genetic diagnosis of FH
Data collection
Prospective/retrospective
Entered by research staff
Abstracted from medical records from routine care
Prospective
Entered by patient, with follow-up verification by research staff
Data captured
Demographics
Familial hypercholesterolemia diagnosis
Cardiovascular history
Family history
Medications
Physical examination
Laboratory studies
Participating Lipid Clinic, Online Patient Portal
we conducted a cross-sectional analysis of 1295 adult FH patients who were enrolled in the CASCADE-FH Registry prospectively through 11 participating lipid clinics between September 2013 and April 2015 (n=436) or for whom retrospective data were abstracted by reviewing historical medical charts (n=859) (Supplementary Figure).24 Institutional review boards at each site reviewed and approved the protocol. Signed informed consent was required for all prospectively enrolled patients, and a waiver was approved for retrospective data abstraction. Clinical and laboratory data obtained locally for routine clinical care were abstracted from patient medical records and entered by trained research staff
O’Brien. Am Heart J 2014;167:342

5. Growth
Summit 2014
Summit 2015

6. Preventive Cardiology Inc.
Patient Enrollment
U Penn
deGoma, 356
Thomas Jefferson
Duffy, Whellan, 44
Oregon Health & Science University –
Shapiro/Duell, 238
Maine
MGH
Hemphill, 33
Geisinger
Boston
Childrens
Lancaster
Anderson, 40
Mayo
Kullo, 0 NY
(8)
NYU
Underberg, 5
Rogosin
Hudgins, 66
Stanford -
Knowles, 108
Chicago
Atlantic
Ohio State
The University of Kansas Moriarty, 504
JHU
WVU
Neal, 68 CA
(28)
UCSF NC
(4)
Nemours
Gidding, 36
ULCA-
Watson, 3
UC Irvine
Wong, 1 GA
(10)
Duke
Baylor
Ballantyne, 118
UT Southwestern Ahmad, 312
Vanderbilt
Linton, 239
Preventive Cardiology Inc.
Baum, 41

7. Patient Demographic – Clinical Portal

8. Patient Demographic – Clinical Portal

9. Diagnostic criteria
*MEDPED denotes Make Early Diagnosis, Prevent Early Death; DLCN Dutch Lipid Clinic Network
Data are being refined

10. Insights from initial characterization
Patients enrolled in the CASCADE-FH Registry through one of 14 participating lipid centers (n=1565)
Excluded patients (n=270) due to:
Below 18 years of age (n=202)
Homozygous FH (n=43)
Missing statin dosage (n=25)
Cross-sectional
Homozygous FH: genetic diagnosis, untreated LDL-C>500, use of mipomersen or lomitapide
Adult patients with heFH eligible for analysis of cardiovascular status and treatment patterns treated at one of 11 lipid centers (n=1295)

11. Exclusion criteria for initial characterization of of adult HeFH patients
Excluded patients not on lipid-lowering therapy or missing entry LDL-C data (n=211)
Treated adult patients with heFH eligible for analysis of goal attainment of treated LDL-C<100 mg/dl (n=1084)
Excluded patients missing untreated LDL-C data or with the same LDL-C value recorded at both time points (n=432)
Treated adult patients with heFH eligible for analysis of goal attainment of ≥50% LDL-C reduction (n=652)

12. Age at enrollment, years, median (IQR), n=1265 57 Female, % 59
Demographics
Age at enrollment, years, median (IQR), n=1265 57
(43-66)
Female, % 59
Ethnicity, %
White 80
Black 7
Hispanic 2
Other 10

13. Late Diagnosis and Treatment
Guidelines*
2-11
CASCADE-FH 47
DIAGNOSIS
AGE
8-10
Statin 21
ACC/AHA
Adult Guidelines 39
CASCADE-FH
TREATMENT
American Association of Pediatrics 2008
US National Lipid Association 2011
International FH Foundation 2011
European Atherosclerosis Society 2013

14. Lipids Untreated Total cholesterol mg/dl, n=949 329 LDL-C, n=888 239
Total cholesterol, n=1097
215
LDL-C, n=1084
134
Triglycerides, n=1092
113
HDL-C, n=1096 52
‘Untreated’ LDL-C: highest documented values prior to initiation of drug therapy or occasionally when a patient was on a drug holiday
‘Treated’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry among patients on LDL-lowering medication(s)
‘Entry’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry, regardless of treatment status
‘Untreated’ LDL-C: highest documented values prior to initiation of drug therapy or occasionally when a patient was on a drug holiday
‘Treated’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry among patients on LDL-lowering medication(s)

15. Additional CHD Risk Factors
39% 1
38% 2
16% 3+ 7%
Diabetes, n=1280
13%
Current smoker, n=1272
Hypertension, n=1283
43%
Low HDL-C, n=1285
31%
Obesity, n=1223
32%
BMI, kg/m2, median, n=1223 27
Additional modifiable cardiovascular risk factors defined as diabetes, current smoker, hypertension, and low HDL-C

16. Cardiovascular Disease
ASCVD, n=1273
38%
Age at onset, years 52
CHD, overall cohort
36% 51
CHD, men
47% 47
CHD, women
29% 55
Stroke or TIA, n=1282 5%
Aortic valve disease, n=1284 3%
ASCVD includes any history of CHD, stroke, TIA, peripheral artery disease

17. Not statin-treated n=326, 25% of overall
Statin and Non-Statin Medications
Statin-treated
n=969
Not statin-treated n=326, 25% of overall
Statin intensity†
High
544 (56%) -
Low/Moderate
425 (44%)
No statin
326 (100%)
Statin
Rosuvastatin
475 (49%)
Atorvastatin
334 (35%)
Non-statin
Ezetimibe
438 (45%)*
82 (25%)
Bile acid sequestrant
141 (15%)
48 (15%)
Niacin
135 (14%)*
30 (9%)
Fibrate
44 (5%)
20 (6%)
Ezetimibe p<0.0001, niacin p=0.0234

18. Reasons for sub-maximal statin use
Statin intolerance or allergy (60%)
Patient preference (11%)
Physician preference (11%)
Pregnancy (3%)
Cost (1%)
Clinical trial participation (1%)
Among the 326 patients not receiving statin treatment, reasons for the lack of statin use included

19. Combination Therapy & Apheresis
Statin-treated
n=969
Not statin-treated n=326
Statin + ezetimibe
438 (45%) -
LDL-lowering meds*
196 (60%) 1
428 (44%)
87 (27%) 2
353 (36%)
36 (11%) 3+
188 (19%)
7 (2%)
Apheresis*
37 (4%)
40 (12%)
p<0.0001

20. Treated LDL-C Values & Reduction
Statin-treated
Not statin-treated
Treated LDL-C*
n=959
n=125
<70 mg/dl
58 (6%)
5 (4%)
70-99 mg/dl
194 (20%)
11 (9%)
mg/dl
238 (25%)
7 (6%)
mg/dl
153 (16%)
35 (28%)
mg/dl
113 (12%)
22 (18%)
≥190 mg/dl
203 (21%)
45 (36%)
LDL-C reduction*
n=576
n=76
≥50%
257 (45%)
9 (12%)
Table 4: Treated LDL-C levels and magnitude of LDL-C reductions compared with untreated levels among adults with heterozygous FH taking LDL-lowering medications
P<0.0001
† Chi-square test comparing statin users to statin nonusers.
‡ n=1084 on LDL-lowering therapy for whom treated LDL-C values were available.
§ n=652 on LDL-lowering therapy for whom untreated and treated LDL-C values were available.

21. Treated LDL-C Values
‡ n=1084 on LDL-lowering therapy for whom treated LDL-C values were available.

22. Magnitude of LDL-C Reduction
§ n=652 on LDL-lowering therapy for whom untreated and treated LDL-C values were available.

23. US CASCADE-FH US NHANES
High Prevalence of CHD
5-7-Fold Higher
US CASCADE-FH
US NHANES
CASCADE FH median age at diagnosis of CHD: M 47 years, W 55 years
AHA Heart Disease and Stroke Statistics 2014 Update: NHANES prevalence of CHD age

24. Importance of CHD Risk Factors
Prevalence
Unadjusted OR
Adjusted OR
Hypertension
43%
5.4 ( )
2.7 ( )
Diabetes
13%
4.0 ( )
1.7 ( )
Low HDL-C
31%
1.6 ( )
1.5 ( )
Smoking 7%
1.6 ( )
1.4 ( )

25. High Prevalence of CHD (Global)
CASCADE-FH
Denmark
2012
Canada
2014* UK
2008
Netherlands
2010*
Spain
2011*
France
2011*
Age 57 59 61 51 50 46
LDL-C
239
251
262
259
258
192
TC 389
134
182 -
128
124
194
* Prevalence of ASCVD. Allard Lipids in Health and Disease 2014;13:65. Benn JCEM 2012;97:3956. Beliard Atherosclerosis 2014;234:136. Pijlman Atherosclerosis 2010;209:189. Mata Lipids in Health and Disease 2011;10:94. Hadfield Annals Clin Biochem 2008;45:199.

26. Treated LDL-C<100 mg/dl
Goal attainment
UK 2008
CASCADE-FH
Netherlands 2010
Treated LDL-C<100 mg/dl
Reduction in LDL-C≥50%
Pijlman Atherosclerosis 2010;209:189. Hadfield Annals Clin Biochem 2008;45:199.

27. Growth
Summit 2014
Summit 2015

28. Self-reported Quality of Life

29. FH Understanding (Patient Reported)

30. Gaps and future plans More patient-centric data needed
Limited data on non-White populations, more generalizablity
More longitudinal data needed
Track effects as PCSK9 are introduced
Integrate more historical data
Launch patient portal V2.0
More sites, more patients from diverse backgrounds and areas of the country, leverage EHR data
Convert retrospective to prospective enrollment
Get updated snapshot so we can see what happens within 1 year of FDA approval
MEDPED integration

31. Conclusions High CHD prevalence among adult FH patients
Poor LDL goal attainment (<100 mg/dl, >50%)
Opportunities to improve care of FH patients:
Early diagnosis of FH
Early initiation of LDL-lowering therapy
Use of high-intensity statin therapy
Use of combination therapy
Management of other risk factors
Careful elicitation of family history
Please contribute to the CASCADE-FH Registry!

32. Acknowledgments Publications Committee and site PIs for CASCADE FH
Zahid S. Ahmad, MD*
Emily O’Brien, PhD
Iris Kindt, MD, MPH
Peter Shrader, PhD
Joshua W. Knowles, MD, PhD
Patrick M. Moriarty, MD
Connie B. Newman, MD
Yashashwi Pokharel, MD, MSCR
Seth J. Baum, MD
Linda C. Hemphill, MD
Lisa C. Hudgins, MD
Catherine D. Ahmed, MBA
Samuel S. Gidding, MD
Danielle Duffy, MD
William Neal, MD
Katherine Wilemon, BS
Matthew T. Roe, MD, MHS
Daniel J. Rader, MD
Christie M. Ballantyne, MD
MacRae F. Linton, MD
P. Barton Duell, MD
Michael D. Shapiro, MD
University of Pennsylvania
Tracey Sikora, Kristen Dilzell
Anna Raper, Joyce Ross
UT Southwestern
Chandna Vasandani
Stanford University
Aleks Pavlovic
Vanderbilt University
Misty Hale, Beth Medor
Oregon Health & Science University
Jill Rose
Our FH patients, family, and friends

33. CASCADE FH Registry Sponsorship

34. Lipids Untreated Total cholesterol mg/dl, n=949 329 LDL-C, n=888 239
Total cholesterol, n=1097
215
LDL-C, n=1084
134
Triglycerides, n=1092
113
HDL-C, n=1096 52
Entry
Total cholesterol, n=1292
224
LDL-C, mg/dl, n=1278
141
Triglycerides, n=1286
HDL-C, n=1291
‘Untreated’ LDL-C: highest documented values prior to initiation of drug therapy or occasionally when a patient was on a drug holiday
‘Treated’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry among patients on LDL-lowering medication(s)
‘Entry’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry, regardless of treatment status

35. Not statin-treated (n=326)
Statin and Non-Statin Medication
Overall cohort
(n=1295)
Statin-treated
(n=969)
Not statin-treated (n=326)
Statin intensity†
High
544 (42%)
544 (56%) -
Low/Moderate
425 (33%)
425 (44%)
No statin
326 (25%)
326 (100%)
Statin
Rosuvastatin
475 (37%)
475 (49%)
Atorvastatin
334 (26%)
334 (35%)
Non-statin
Ezetimibe
520 (40%)
438 (45%)*
82 (25%)
Bile acid sequestrant
189 (15%)
141 (15%)
48 (15%)
Niacin
165 (13%)
135 (14%)*
30 (9%)
Fibrate
64 (5%)
44 (5%)
20 (6%)
Ezetimibe p<0.0001, niacin p=0.0234

36. Combination Therapy & Apheresis
Overall cohort
(n=1295)
Statin-treated
(n=969)
Not statin-treated (n=326)
Statin + ezetimibe
438 (34%)
438 (45%) -
LDL-lowering meds*
196 (15%)
196 (60%) 1
515 (40%)
428 (44%)
87 (27%) 2
389 (30%)
353 (36%)
36 (11%) 3+
195 (15%)
188 (19%)
7 (2%)
Apheresis*
77 (6%)
37 (4%)
40 (12%)
p<0.0001

37. Treated LDL-C Values & Reduction
Overall cohort
Statin-treated
Not statin-treated
Treated LDL-C*
n=1,084
n=959
n=125
<70 mg/dl
63 (6%)
58 (6%)
5 (4%)
70-99 mg/dl
205 (19%)
194 (20%)
11 (9%)
mg/dl
245 (23%)
238 (25%)
7 (6%)
mg/dl
188 (17%)
153 (16%)
35 (28%)
mg/dl
135 (13%)
113 (12%)
22 (18%)
≥190 mg/dl
248 (23%)
203 (21%)
45 (36%)
LDL-C reduction*
n=652
n=576
n=76
≥50%
266 (41%)
257 (45%)
9 (12%)
Table 4: Treated LDL-C levels and magnitude of LDL-C reductions compared with untreated levels among adults with heterozygous FH taking LDL-lowering medications
P<0.0001
† Chi-square test comparing statin users to statin nonusers.
‡ n=1084 on LDL-lowering therapy for whom treated LDL-C values were available.
§ n=652 on LDL-lowering therapy for whom untreated and treated LDL-C values were available.

38. Coronary Heart Disease

39. Coronary Heart Disease
* Adjusted for age at enrollment, diabetes, current smoking, hypertension, untreated total cholesterol, and low HDL-C.
† Median (IQR) shown. For age, OR shown per 10-year increment. For untreated total cholesterol and LDL-C, OR shown per 10-mg/dl increment. For modified CYS, OR shown per 1000-mg/dl*years increment.
‡ Low HDL-C defined as <40 mg/dl for men and <50 mg/dl for women.
§ Cholesterol-years score was calculated as [untreated total cholesterol * age at initiation of lipid-lowering therapy] + [baseline total cholesterol * (age at enrollment - age at initiation of lipid-lowering therapy)]. Total cholesterol is not adjusted for in multivariable OR.
|| Statin intensity is defined according to the 2013 ACC/AHA Cholesterol Guidelines.

40. Coronary Heart Disease
Characteristic
No CHD
(N=833)
CHD
(N=449)
Unadjusted OR
(95% CI)
Adjusted OR
Age at enrollment, yrs
53 (36-62)
63 (55-70)
1.75 ( )
1.53 ( )
Male
278 (33.7%)
243 (52.3%)
2.15 ( )
2.68 ( )
Family history of early MI
356 (57.6%)
227 (70.9%)
1.80 ( )
1.83 ( )
Diabetes
59 (7.2%)
108 (23.5%)
3.97 ( )
1.66 ( )
Current smoking
47 (5.8%)
41 (9.0%)
1.62 ( )
1.36 ( )
Hypertension
233 (28.4%)
316 (68.3%)
5.42 ( )
2.68 ( )
Low HDL-C, mg/dl
222 (27.1%)
176 (37.8%)
1.64 ( )
1.53 ( )
Obesity
221 (28.1%)
164 (37.6%)
1.54 ( )
1.10 ( )
Untreated total cholesterol
324 ( )
341 ( )
1.02 ( )
1.02 ( )
Untreated LDL-C, mg/dl
238 ( )
242 ( )
1.01 ( )
1.01 ( )
Age at FH diagnosis, yrs
43 (25-56)
55 (42-64)
1.46 ( )
0.95 ( )
Cholesterol-years, mg*dl/yrs
25393
( )
31175
( )
1.05 ( )
0.99 ( )
Age at initiation of LDL-lowering medication, yrs
36 (22-48)
44 (33-53)
1.35 ( )
0.86 ( )
Low/moderate-statin
298 (35.9%)
127 (27.3%)
0.73 ( )
0.76 ( )
High-intensity statin
326 (39.3%)
218 (46.9%)
1.15 ( )
1.34 ( )
* Adjusted for age at enrollment, diabetes, current smoking, hypertension, untreated total cholesterol, and low HDL-C.
† Median (IQR) shown. For age, OR shown per 10-year increment. For untreated total cholesterol and LDL-C, OR shown per 10-mg/dl increment. For modified CYS, OR shown per 1000-mg/dl*years increment.
‡ Low HDL-C defined as <40 mg/dl for men and <50 mg/dl for women.
§ Cholesterol-years score was calculated as [untreated total cholesterol * age at initiation of lipid-lowering therapy] + [baseline total cholesterol * (age at enrollment - age at initiation of lipid-lowering therapy)]. Total cholesterol is not adjusted for in multivariable OR.
|| Statin intensity is defined according to the 2013 ACC/AHA Cholesterol Guidelines.

41. Treated LDL-C≤100 mg/dl

42. Treated LDL-C≤100 mg/dl
* Adjusted for untreated LDL-C, CHD, statin use, and use of >1 LDL-lowering medication
† Median (IQR) shown.
‡ OR compared with no statin use.

43. Treated LDL-C≤100 mg/dl Characteristic LDL-C≥100 (N=816) LDL-C <100
Unadjusted OR (95% CI)
Adjusted OR (95% CI)
Age at enrollment, yrs
55 (42-65)
60 (49-67)
1.26 ( )
1.23 ( )
Male
325 (40.1%)
136 (50.7%)
1.54 ( )
1.28 ( )
Coronary heart disease
273 (33.5%)
122 (45.5%)
1.66 ( )
1.36 ( )
Family history of early MI
365 (61.9%)
129 (66.5%)
1.22 ( )
1.88 ( )
Diabetes
93 (11.5%)
42 (15.8%)
1.44 ( )
1.21 ( )
Untreated LDL-C, mg/dl
245 ( )
225 ( )
0.95 ( )
0.93 ( )
Confirmed FH mutation
32 (3.9%)
3 (1.1%)
0.28 ( )
0.16 ( )
High-intensity statin
374 (45.8%)
162 (60.4%)
2.95 ( )
4.66 ( )
Low/moderate-statin
333 (40.8%)
90 (33.6%)
1.84 ( )
2.29 ( )
>1 lipid-lowering medication
407 (49.9%)
171 (63.8%)
1.77 ( )
1.88 ( )
* Adjusted for untreated LDL-C, CHD, statin use, and use of >1 LDL-lowering medication
† Median (IQR) shown.
‡ OR compared with no statin use.

44. Reduction in Treated LDL-C≥50%

45. Reduction in Treated LDL-C≥50%
* Adjusted for current age, gender, untreated LDL-C, family history of premature MI, statin use, and use of >1 LDL-lowering medication
† Median (IQR) shown.
‡ OR compared with no statin use.

46. Reduction in Treated LDL-C≥50%
Characteristic
↓LDL-C<50%
(N=386)
↓LDL-C≥50%
(N=266)
Unadjusted OR (95% CI)
Adjusted OR (95% CI)*
Age at enrollment, yrs
55 (40-65)
57 (45-66)
1.12 ( )
1.26 ( )
Male
131 (34.0%)
117 (44.2%)
1.53 ( )
1.26 ( )
Coronary heart disease
112 (29.0%)
89 (33.5%)
1.23 ( )
0.63 ( )
Family history of early MI
152 (53.5%)
145 (71.1%)
2.13 ( )
1.90 ( )
Diabetes
37 (9.7%)
28 (10.5%)
1.10 ( )
0.78 ( )
Untreated LDL-C, mg/dl
230 ( )
265 ( )
1.10 ( )
1.06 ( )
Confirmed FH mutation
10 (2.6%)
13 (4.9%)
1.93 ( )
0.71 ( )
High-intensity statin
142 (36.8%)
170 (63.9%)
3.22 ( )
3.55 ( )
Low/moderate-statin
177 (45.9%)
87 (32.7%)
1.77 ( )
1.83 ( )
>1 lipid-lowering medication
150 (38.9%)
179 (67.3%)
3.24 ( )
1.79 ( )
* Adjusted for current age, gender, untreated LDL-C, family history of premature MI, statin use, and use of >1 LDL-lowering medication
† Median (IQR) shown.
‡ OR compared with no statin use.

47. Patient Reported Data

48. United States: Data from the CASCADE-FH Registry
LDL-C Levels & Treatment Patterns Among Adults with Heterozygous Familial Hypercholesterolemia in the
United States: Data from the CASCADE-FH Registry
BACKUP SLIDES

49. Study Design
‘Untreated’ LDL-C: highest documented values prior to initiation of drug therapy or occasionally when a patient was on a drug holiday
‘Treated’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry among patients on LDL-lowering medication(s)
‘Entry’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry, regardless of treatment status

50. Study Design
More details about analysis?

51. United States: Data from the CASCADE-FH Registry
LDL-C Levels & Treatment Patterns Among Adults with Heterozygous Familial Hypercholesterolemia in the
United States: Data from the CASCADE-FH Registry
Emil M. deGoma, MD
University of Pennsylvania
on behalf of the CASCADE-FH Registry

52. Study Objectives Describe clinical and lipid characteristics
Assess treatment patterns and LDL-C values
Characterize association between patient characteristics and prevalent CHD
Quantify association between patient characteristics and LDL-C goal attainment, treated LDL-C<100 mg/dl or ↓LDL-C>50%

53. FH History Age at FH diagnosis, years, n=1232 47 (31-59)
FH diagnosis before age 30, % 22
Age at initiation of LDL-lowering medication, years, n=677
39 (25-50)
Medication before age 30, % 17
Family history of early MI, %, n=938 45

54. High Prevalence of CHD (US)
Age 57 40 50 45
LDL-C
239
TC 402
224
256
134 -
172
116
*Prevalence of ASCVD. Stone Circ 1974;49:476. Hopkins Am J Cardiol 2001;87:547. Elis Am J Cardiol 2011;108:223.

55. Familial Hypercholesterolemia Foundation
The FH Foundation is a patient-centered nonprofit organization dedicated to education, advocacy, and research of Familial Hypercholesterolemia

56. Cumulative LDL Exposure & CHD
Baum J Clin Lipidol 2014;:542. Adapted from Horton JD, et al. J Lipid Res. 2009; 50 (Suppl):S172-S177.

57. CASCADE FH Registry data to: Evaluate trends in therapy
clinical outcomes
patient reported outcomes
___improve quality of lige, clinical outcomes, show gaps in care, costs in life years and productivity

58. Title Goes Here # of Enrolling Sites: 18 Total Patients Enrolled: 2561
CASCADE FH Registry
# of Enrolling Sites: 18
9 sites in progress
Total Patients Enrolled: 2561
# of Patients Enrolled via Patient Portal: 349
# of Patients Enrolled via Clinical Sites: 2212
R:1415 / P:797
Title Goes Here

59. CASCADE Site Enrollment Numbers

60. Limitations and Next Steps
Limited generalizability based on 11 lipid centers
Increase number of participating centers
Leverage large electronic health databases
Obstacles to optimal treatment remain unclear
Update data fields to capture additional detail
Cross-sectional study design
Prospective follow-up is ongoing
Our analysis of the diagnosis, management, and outcomes of adult FH patients from 11 lipid specialty centers may not be generalizable to the broader US FH population. To our knowledge, the only published study to examine FH patients in a community setting is a 2012 Danish analysis of 502 FH patients identified from the large Copenhagen General Population Study.2 Despite similar median untreated lipid levels, mean ages, and prevalence rates of CHD (Supplementary Table 2), the Danish cohort exhibited higher on-treatment LDL-C levels compared with the CASCADE-FH Registry (182 vs 134 mg/dl). This suggests that our findings restricted to experienced lipid clinics may well underestimate the existing treatment gap in the US. Increasing the number of institutions participating in the CASCADE-FH Registry (as of August 2015, 17 sites are actively enrolling) along with efforts to leverage large electronic health databases to identify patients with FH will yield more generalizable results. The latter approach, which includes the FH Foundation’s FIND (Flag, Identify, Network, Deliver) FH initiative and the Electronic Medical Records and Genomics (eMERGE) Network, may help identify a larger number and more diverse cohort of FH patients.
While our study identified suboptimal use of high-intensity statin or combination therapy, the reasons for not pursuing these treatments, particularly in younger individuals, remain uncertain. Despite universal recommendations for statin therapy in adult FH patients,1, 3, 8, 10 1 out of 4 patients in our study were not taking statins at the time of registry enrollment, largely due to statin intolerance. The high proportion of statin non-users in the CASCADE-FH Registry may reflect referral bias to participating specialty lipid centers.
Because of the cross-sectional nature of our data, associations between various characteristics and prevalent CHD or LDL-C goal attainment are hypothesis-generating and do not establish causality. Finally, despite the high prevalence of CHD at baseline, our data may in fact underestimate the burden of CHD among adults with FH due to survival bias.

61. Results: Diagnostic Criteria
n = 876 US FH Patients
Age (yrs)
53 (17)
Female
57%
BMI (kg/m2)
28(6)
Ethnicity/Race
78% white
6% black
3% Hispanic
12% other
Age at FH diagnosis (yrs)
43 (19)
Prior CHD
38%
Family history of MI
45%
Tendon Xanthomas
18%
Pre-treatment LDL-C (n = 444, mg/dL)
269 (87)
Data shown as mean (SD) unless otherwise indicated
BMI body mass index, FH familial hypercholesterolemia, CHD coronary heart disease, MI myocardial infarction, LDL-C low density lipoprotein-cholesterol

62. CASCADE FH Patient registry:
Diagnostic criteria were divided into non-exclusive categories:
“clinical diagnosis”
MEDPED*
Simon-Broome
DLCN*
other
*MEDPED denotes Make Early Diagnosis, Prevent Early Death; DLCN Dutch Lipid Clinic Network