Causes of Hypercholesterolemia

772 known to increase LPL synthesis and secretion. An increase of FFAs may enhance accumulation of hepatic lipids, reducing glucose uptake, and decreasing insulin signaling. Untreated, individuals with CS have a higher mortality than those who are cured. While CVD risk appears to be related to the duration of exposure to excess glucocorticoid, there is considerable residual risk in those whose CS is improved or cured. Conclusions: Dyslipidemia associated with glucocorticoid excess is highly atherogenic. Affected individuals have significant CVD risk despite effective treatment. Continued surveillance, effective implementation of lifelong therapeutic lifestyle changes, and when appropriate, medical treatment of residual CVD risk factors are recommended.

Journal of Clinical Lipidology, Vol 11, No 3, June 2017

Clinical Applications of Biomarkers, Lipoprotein Testing

of the study group and 15.6% of the control group. Lp(a) was 99.8 6 55.4 mg/dL (median 93.0 mg/dL) in the study group and 10.1 6 4.4 mg/dL (median 10.0 mg/dL) in the control group. Between groups, there was no difference in PWV (study 4.7 6 0.8 meters/second [median 4.8 meters/ second]; control 4.8 6 1.7 meters/second [median 4.6 meters/second]; p50.83) or cIMT (study 0.47 6 0.05mm [median 0.45mm]; control 0.47 6 0.04mm [median 0.47mm]; p50.61). Conclusions: Despite the presence of elevated Lp(a) and other atherosclerosis-promoting risk factors in this young, cross-sectional study population, there was no evidence of adverse change in the vasculature when compared to those with normal Lp(a). However, continued follow-up of this high-risk group is recommended in view of their known risk for premature cardiovascular disease. Abstract won fifth place Young Investigator Award.

101 Lipoprotein (a) Does Not Adversely Impact Vascular Health in Children with Dyslipidemia

102 Causes of Hypercholesterolemia

Omar Qayum, Geetha Raghuveer, MD, MPH, Chizitam Ibezim, (Kansas City, MO)

Ernst Schaefer, MD, Margaret Diffenderfer, PhD, Michael Mehan, PhD, (Framingham, MA)

Lead Author’s Financial Disclosures: None Study Funding: UMKC Sarah Morrison Student

Lead Author’s Financial Disclosures: Dr. Schaefer

Research Award; Amount: $1280.00; Participant compensation 5 $20 per participant (64 total) Background/Synopsis: Lipoprotein (a) [Lp(a)] accelerates atherosclerosis and is strongly heritable. Elevation of Lp(a) is an independent risk factor for premature cardiovascular disease in adults, but its role in atherosclerotic progression in children is unclear. Objective/Purpose: We conducted a cross-sectional pilot study to determine whether Lp(a) contributes to altered vasculature in children with dyslipidemia. Methods: Children and adolescents aged 9-18 years with dyslipidemia were prospectively recruited from a pediatric preventive cardiology clinic. Each completed a lipid panel and Lp(a) measurement. Participants were separated into either a study (Lp(a) $30mg/dL) or control group (Lp(a) ,30 mg/dL). Pulse wave velocity [PWV], a measure of vascular stiffness, was calculated using a combined oscillometric and tonometric device. Carotid artery intimamedia thickness [cIMT] was measured along the far wall of the right and left common carotid arteries using semiautomated edge detection software. Results: 64 children (32 per group) were recruited: study group (37.5% males, age 15.43 6 2.35 years) and control group (40.6% males, age 13.42 6 1.84 years). Number of vascular risk factors was 3.7 6 1.6 in the study group and 3.4 6 1.3 in the control group. Family history of premature cardiac death was present in 21.9%

is an employee of Boston Heart Diagnostics, Framingham, MA and a professor at Tufts University School of Medicine Study Funding: None Background/Synopsis: Heterozygous familial hypercholesterolemia (FH) has been defined as having a serum low density lipoprotein cholesterol (LDL-C) . 190 mg/dL and has been associated with mutations at the LDLR (LDL receptor), APOB (apolipoprotein B), and PCSK9 (proprotein convertase subtilisin kexin 9) gene loci. However in a recent study of 1,386 subjects with LDL-C values . 190 mg/dL, only 1.7% were noted to have mutations at these three gene loci (Khera A et al. JACC 2016;67:2578-89). Other causes of elevated LDL-C may include the apoE4 genotype, hypothyroidism, sitosterolemia associated with increased cholesterol absorption, familial combined hyperlipidemia associated with increased cholesterol production, and liver disease. Objective/Purpose: Our purpose was to determine the prevalence of other potential causes of hypercholesterolemia in a large data base of subjects that have been well characterized phenotypically. Methods: In a population of 382,971 subjects sampled after an overnight fast, we measured serum total cholesterol, triglycerides, direct LDL-C, HDL-C, TSH, liver enzymes, and apoE genotype. We also measured plasma sterols by gas liquid chromatography/ mass spectrometry after lipid extraction for the determination of concentrations of lathosterol, desmosterol, b-sitosterol, campesterol, and cholestanol.

Abstracts

Results: Our data analysis on 382,971 subjects indicated that 13,966 (3.6%) had LDL-C values . 190 mg/dL (median 206 mg/dL). When compared with subjects having LDL-C values , 190 mg/dL (median 108 mg/dL, n5369,005), those with elevated LDL-C values were significantly (p,0.001) more likely to have an elevated Lp(a) value . 50 mg/dL (46% vs. 23%), carry the apoE3/4 genotype (29.8% vs. 22.7%) or the apoE4/4 genotype (4.3% vs. 2.2%), have a TSH value consistent with hypothyroidism (10.5% vs. 7.3%), have a b-sitosterol value . than the 99th % (5.4% vs. 1.0%, have a lathosterol value . than the 99th % (3.6% vs. 1.0%), and have a liver transaminase value . 120 U/L (0.8% vs. 0.4%). Moreover in high LDL subjects, 233 (about 1%) had b-sitosterol values . 15.0 mg/L, consistent with homozygous or compound heterozygous sitosterolemia. Conclusions: Our data indicate that elevated LDL-C values . 190 mg/dL are significantly associated in order of frequency with elevated Lp(a), apoE4 genotype, hypothyroidism, elevated b-sitosterol levels associated with cholesterol overabsorption, elevated lathosterol levels associated with cholesterol overproduction, and liver disease. Therefore some of these patients have familial sitosterolemia and some have familial combined hyperlipidemia. In our view such factors are important when considering therapy for such patients who have all been recommended for statin therapy. Abstract selected for third oral presentation during abstract session. 103 Trends in Testing for Lipoprotein(a) at an Academic Medical Center Over 13 Years Michael Wilkinson, MD, Andrew Huynh, BS, Rawan AlGhawi, MD, Cuibin Jin, MD, Gary Ma, MD, Samhita Palakodeti, Lawrence Ang, MD, Bruno Cotter, MD, Sotirios Tsimikas, MD, (San Diego, CA)

773

Methods: We reviewed the electronic medical records of patients at UCSD who had an Lp(a) measured at least once between 2003-2016. Because Lp(a) values are genetically determined only the first Lp(a) measurement for each patient was included in our analysis. The presence or absence of coronary artery disease in these patients was not known. We also determined the number of these patients who had at least mild CAVS, defined by peak aortic valve velocity $ 2 m/s. Results: Between 2003-2016, 2769 patients at UCSD had at least one Lp(a) measurement. The frequency of Lp(a) testing was variable and alternated in 3 waves, ranging from 315 patients/year in 2003 to a low of 104 patients/year in 2008, followed by highs of 270 patients/year in 2009 and 409 patients/year in 2015. The prevalence of CAVS among those with an Lp(a) measurement was 175 patients (6.3%). Regardless of CAVS severity, patients with CAVS represented a very low percentage of those tested for Lp(a), ranging from a low of 1 patient in 2008 and 2012 (,1% of all patients tested for Lp(a) each year), to highs of 27, 26, and 22 patients in 2003, 2015, and 2016 (8.6%, 6.4%, and 8.7% of patients tested for Lp(a) each year, respectively) (Figure 1). Conclusions: The prevalence of Lp(a) testing has fluctuated over the last 13 years, likely in response to novel genetic findings in 2009 on the role of Lp(a) in myocardial infarction and in 2013 on the role of Lp(a) in CAVS. With the causal relationship between Lp(a) elevation and risk for CVD and CAVS, as well as Lp(a) lowering trials in progress, it is anticipated that Lp(a) testing will increase and will be tested prospectively. Institutional programs to encourage physician testing for Lp(a) should be adopted with the goal of identifying potential candidates for therapies capable of normalizing Lp(a) levels.

Lead Author’s Financial Disclosures: None Study Funding: None Background/Synopsis: Lipoprotein(a) (Lp(a)) is a genetically-determined, causal risk factor for cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS). Targeted therapies to potently and safely lower Lp(a), such as antisense oligonucleotides (ASOs), are currently under clinical development and can lower Lp(a) .90%. Therefore, it is increasingly important to identify patients with elevated Lp(a) to define CVD and CAVS risk. Objective/Purpose: We sought to examine trends in practice patterns over the past 13 years at the University of California San Diego (UCSD) with regard to Lp(a) testing, including among patients with CAVS.

Figure 1 Total number of patients with a first Lp(a) measurement per year (solid line), and number of patients with a first Lp(a) measurement and at least mild CAVS (defined by peak aortic valve velocity $ 2 m/s) per year (dashed line). Lp(a) 5 lipoprotein(a), CAVS 5 calcific aortic valve stenosis.