PowerPoint Presentation  Familial Hypercholesterolemia (FH) is a common genetic disease that leads to substantially elevated levels of low- density lipoprotein cholesterol (LDL-C)  The 2013 ACC/AHA guidelines for treatment of Blood Cholesterol to Reduce ASCVD risk in adults denote an LDL-C level > 190 mg/dL (suggestive of FH) as an independent high-risk feature.  Individuals with FH have a 20-fold increase in risk of early cardiovascular disease.  Despite its prevalence, FH remains largely underrecognized: an estimated 1.5 million individuals in the U.S. have FH, yet fewer than 10% have been formally diagnosed.  In 2013, the FH Foundation (a patient-led nonprofit organization) created the CASCADE-FH Registry.  The CASCADE-FH Registry is a national initiative to increase FH awareness, characterize trends in treatment, and monitor clinical and patient-reported outcomes over time.  CASCADE-FH represents a collaboration between The FH Foundation, cardiologists, primary care providers, lipid specialists, and patients with FH. Initial Results from the CASCADE-FH Registry: CAscade SCreening for Awareness and Detection of Familial Hypercholesterolemia Emily C. O'Brien1, Emil M. deGoma2, Patrick M. Moriarty3, MacRae F. Linton4, Michael D. Shapiro5, P. Barton Duell5, Christie M. Ballantyne6, William A. Neal7, Zahid S. Ahmad8, Danielle Duffy9, Lisa C. Hudgins10, Linda C. Hemphill11, James A. Underberg12, Karol E. Watson13, Samuel S. Gidding14, Seth J. Baum15, Katherine Wilemon7, Dave Pickhardt7, Iris Kindt7, Daniel J. Rader2, Matthew T. Roe1, Joshua W. Knowles16 1Duke Clinical Research Institute, Durham, NC; 2University of Pennsylvania, Philadelphia, PA; 3University of Kansas, Kansas City, KS; 4Vanderbilt University, Nashville, TN; 5Oregon Health and Science University, Portland, OR; 6Baylor College of Medicine, Houston, TX; 7FH Foundation, South Pasadena, CA; 8UT Southwestern, Dallas, TX; 9Thomas Jefferson University, Philadelphia, PA; 10Rogosin Institute, New York, NY; 11MGH Heart Center, Boston, MA; 12NYU Langone Medical Center, New York, NY; 13UCLA School of Medicine, Los Angeles, California; 14Nemours DuPont Hospital, Wilmington, DE; 15Preventive Cardiology, Boca Raton, FL; 16Stanford School of Medicine, Stanford, CA  CASCADE-FH uses a multi-pathway enrollment strategy to ensure maximum availability to interested FH patients  Registry participants may enroll in CASCADE-FH by one of two methods: 1) Enrollment by a provider in a specialized lipid clinic 2) Self-enrollment via an interactive online portal for participants meeting pre- specified LDL criteria consistent with FH. Funding/disclosures The CASCADE FH Registry has been supported by Amgen, Astra Zeneca, Regeneron, Sanofi and Aegerion. Contact Emily O’Brien, PhD Medical Instructor Duke Clinical Research Institute Duke Medical Center 2400 Pratt Street Durham, NC 27705 Email: emily.obrien@duke.edu . . Variable Overall (N=1605) Online Portal (N=215; 13.4%) Clinical Sites (N=1390; 86.6%) Median age, years 53.0 52.0 53.0 (IQR) (37.0, 64.0) (41.0, 60.0) (36.0, 65.0) <18 years of age 8.2 --- 10.2 White race, % 81.4 92.7 79.6 Female sex, % 58.7 72.7 56.6 Formal FH diagnosis, % 97.4 80.6 100.0 Family member with FH, % 31.5 46.7 29.2 Prior MI, % 12.4 17.2 11.6 Prior PCI, % 17.0 19.4 16.6 Prior CABG, % 13.8 14.9 13.6 Diabetes 11.5 9.3 11.9 Hypertension 39.6 32.1 40.8 Current Smoker 6.2 3.7 6.6 Historical Highest LDL-C (mg/dL) 249.0 (211.0, 310.0) 290.0 (231.0, 355.0) 245.0 (210.0, 303.0) Current LDL level (mg/dL) 143.0 (107.0, 196.0) 150.0 (118.0, 200.0) 143.0 (107.0, 196.0) The CASCADE FH Registry Background Methods Results Conclusions Data Elements • Demographics • Medical history and laboratory values • Current lipid-lowering therapies • Clinical events (hospitalizations, mortality) • Patient-reported outcomes (QOL, treatment satisfaction) Data Analysis • Baseline characteristics presented as percentages for categorical variables and medians with interquartile ranges (IQRs) for continuous variables PHASE 1 Online patient self- enrollment • Patient-reported information through online portal • Medical release for comparison with clinical data PHASE 2 Retrospective clinical data collection • Deidentified patient data abstracted and entered at each site PHASE 3 Prospective clinical data collection • Longitudinal data collected at 6 month intervals • Information on quality of life, medication changes, and clinical events • The CASCADE-FH Registry represents a collaboration between FH patients and clinical researchers who have partnered to address gaps in knowledge regarding FH screening, identification, and treatment. • CASCADE-FH will evaluate future longitudinal treatment patterns and outcomes in this high risk patient population Abbreviations: MI=myocardial infarction; PCI=percutaneous coronary intervention; CABG=coronary artery bypass graft *High-intensity statins defined as atorvastatin>40 mg or rosuvastatin>20 mg Variable Overall (N=1605) Online Portal (N=215; 13.4%) Clinical Sites (N=1390; 86.6%) Currently treated with statins, % 74.1 73.0 76.0 Currently treated with high- intensity statins*, % 55.8 63.5 54.6 Number of LLT 0 10.8 17.2 9.8 1 33.6 35.4 33.4 2 25.6 8.8 28.1 3+ 30.0 38.6 28.7 Table 1. Baseline Characteristics of the CASCADE-FH Patient Population (September 2013 – February 2015). Table 2. Treatment patterns of the CASCADE-FH Patient Population (September 2013 – February 2015). *Among patients treated with statins Abbreviations: LLT=Lipid lowering therapy Results (continued) 53.7 56.9 34.2 43.1 33.8 58.8 70.9 0 10 20 30 40 50 60 70 80 How FH can negatively affect my health Current medication regimen Available treatment options How FH increases risk of heart disease Where I can go to get more information about FH Your personal risk for events like heart attack and Stroke Why FH screening of family members is important Not satisfied at all 8% Mostly dissatisfied 6% Somewhat dissatisfied 20% Mostly satisfied 30% Highly satisfied 36% I can't stop worrying about it 7% I often worry about it 21% I occasionally worry about it 38% I rarely worry about it 23% I never worry about it 11% Figure 2. How satisfied are you that everything possible is being done to treat your FH?* Figure 3. How often do you worry that you may have a heart attack or die suddenly?* Figure 1. Percent of patients reporting that they “completely understand” the following about FH* % *Online portal patients only