Screening and advanced lipid phenotyping in familial hypercholesterolemia: The Very Large Database of Lipids Study-17 (VLDL-17).
BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes.


METHODS
We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels.


RESULTS
Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was -0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population.


CONCLUSIONS
Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a)-C and RLP-C. Future studies are warranted to study these mixed phenotypic groups and determine the role for further risk stratification and treatment algorithms.
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. Electronic address: elliottmiller@jhmi.edu.
P Elliott
PE
Miller
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
Seth S
SS
Martin
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Department of Preventive Cardiology, CGH Medical Center, Sterling, IL, USA; University of Illinois College of Medicine, Peoria, IL, USA.
Peter P
PP
Toth
Lipid Clinic Heart Institute, Preventive Medicine Center Hospital Israelita Albert Einstein, InCor University of São Paulo Medical School Hospital, Sao Paulo, Brazil.
Raul D
RD
Santos
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
Michael J
MJ
Blaha
Center for Prevention & Wellness Research, Baptist Health Medical Group, Miami, FL, USA.
Khurram
K
Nasir
Section of Cardiovascular Research, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX, USA.
Salim S
SS
Virani
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
Wendy S
WS
Post
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
Roger S
RS
Blumenthal
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
Steven R
SR
Jones
D000293:Adolescent; D000328:Adult; D016208:Databases, Factual; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000175:diagnosis*; D008055:Lipids / Q000097:blood*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
D008055:Lipids
Familial hypercholesterolemia; Friedewald equation; Lipid phenotyping; Lipoprotein(a); Low-density lipoprotein cholesterol; Remnant lipoprotein cholesterol; Screening