Age . 55(n 5 196)

Age # 55(n 5 65) P-Value

Age 72.5 46.3 ,0.0001Male Gender 90 (45.9) 33 (51.0) 0.50CAD 53 (27.0) 11 (16.9) 0.14

Abstracts 303

3. Identifying prevalence of various physical exam findingsin patients with dysbetalipoproteinemia

Methods: We analyzed serum lipid markers, apolipopro-tein E genotype, electrophoretic data, physical findings, andatherosclerotic vascular events from 4458 patients that werereferred to the lipid clinic of the Clinical Research Instituteof Montreal. 252 patients were classified as dysbetalipo-proteinemic based on the E2/E2 genotype and cholesterol-enriched VLDL content.

Results: Using strict definition of dysbetalipoproteine-mia, smoking and age were identified as being the strongestpredictors of cardiovascular disease in our patient popula-tion. Serum markers, hypertension, and Body Mass Indexdid not show a significant difference. Female genderbecame another predictor after stratifying for smoking.Age onset of cardiovascular disease was 54. Broad betaband was present in 38% and 46% of dysbetalipoproteine-mic patients, and those who also had a cardiovascular eventrespectively. Broad beta band alone was able to detect 30%dysbetalipoproteinemic patient, whereas VLDL-C/TG ratio(.0.69) only detected 13%. Synergistically, they had adetection rate of 58%. 61% of dysbetalipoproteinemicpatients had at least one clinical finding on physicalexam. ROC curve analysis showed that VLDL-C/TG ratioof .0.71 would be the ideal cut-off with 73% sensitivityand 69% specificity. Striata palmaris, arcus cornialis, andtuberoeruptive xanthoma accounted for 23%, 13% and 9%as the most common hyperlipidemic signs.

Conclusion: Smoking and age are two strongest pre-dictors of cardiovascular disease in dysbetalipoproteinemia.Detection of broad beta band with electrophoresis issuperior to VLDL-C ratio as a diagnostic test. The cut-offof VLDL-C/TG of .0.71 was found to have most areaunder the curve. Most importantly, since the age onset ofcardiovascular disease in dysbetalipoproteinemia is similarto that in familial hypercholesterolemia, it is of crucial tomake early diagnosis and to initiate treatment in dysbeta-lipoproteinemic patients.

Hypertension 168 (85.7) 41 (63.1) ,0.001Hyperlipidemia 100 (51.0) 21 (32.3) 0.01Previous Stroke 45 (23.0) 11 (16.9) 0.39Diabetes 69 (35.2) 15 (23.1) 0.10Heart Failure 25 (12.8) 9 (13.8) 0.99BMI 28.54 ± 0.94 30.55 ± 1.82 0.04Systolic BloodPressure

147.34 6 3.73 144.45 6 7.41 0.24

Diastolic BloodPressure

75.61 ± 2.46 81.65 ± 3.72 0.01

Creatinine 1.54 6 0.20 1.39 6 0.50 0.58TC (mg/dL) 154.62 ± 6.34 176.72 ± 12.74 ,0.01LDL (mg/dL) 93.05 ± 5.47 110.13 ± 9.65 ,0.01HDL (mg/dL) 42.63 6 2.31 40.03 6 3.37 0.25TG (mg/dL) 118.65 ± 9.97 176.72 ± 12.74 ,0.0001nHDL (mg/dL) 111.99 ± 5.98 137.31 ± 13.35 ,0.001

Comparison of Risk Factors

Comparison of cardiovascular risk factors and lipid profiles between

younger and older cohorts

110

Comparison of Lipid Profiles and BMI by Age Groups inAcute Ischemic Stroke*

Demetrios Doukas, DO, Mauro Montevecchi, MD, MSCI,Michael Schneck, MD, John Barron, MD, PhD, BinhAn Phan, MD, (Maywood, IL)

Lead Author’s Financial Disclosures: NoneStudy Funding: NoneBackground/Synopsis: Hyperlipidemia (HL) is a wellknown risk factor for cardiovascular disease, includingstroke. We sought to examine the lipid profiles for patientsdiagnosed with acute ischemic stroke and compare thembased on age.

Objective/Purpose: Compare lipid profiles of patientswith ischemic stroke and determine whether older cohorts(age .55) had significantly different lipid profiles orelevated body mass index (BMI) compared to youngercohorts (age # 55).

Methods: We screened a total of 2334 patients from2008-2012 who had a stroke code called during theirhospitalization. We narrowed our evaluation to patientsadmitted from January 1, 2011 to December 31, 2011. Thestudy population included all patients over age 18 admittedto our institution with the diagnosis of ischemic cerebro-vascular accident (CVA). All patients had radiologicalevidence of acute ischemia.

Results: A total of 261 patients were analyzed anddivided into 2 age groups: .55 (n 5 196) or # 55 (n 565). There was no statistically significant difference be-tween groups for gender, history of coronary disease,previous CVA, diagnosis of diabetes, prior heart failure,serum creatinine level, or systolic blood pressure (p .0.05). There was a significant difference between groupswhen assessing hypertension (85.7% vs 63.1%, p ,0.001),diagnosis or treatment of hyperlipidemia (51.0% vs 32.3%,p50.01), and diastolic blood pressure (75.61 vs 81.65mmHg, p50.01). Total cholesterol (TC), low densitylipoprotein (LDL), triglycerides (TG), non-high densitylipoprotein (nHDL), and body mass index (BMI) were allsignificantly higher in the age # 55 group compared to theage.55 group (TC 176.72 vs 154.62 mg/dL, p,0.01; LDL110.13 vs 93.05 mg/dL, p,0.01; TG 176.72 vs 118.65mg/dL, p ,0.001; nHDL 137.31 vs 111.99 mg/dL,

304 Journal of Clinical Lipidology, Vol 8, No 3, June 2014

p,0.001; and BMI 30.55 vs 28.54 kg/m2, p50.04). A priordiagnosis or current treatment for hyperlipidemia was notcorrelated with cholesterol levels when analyzed by groupsseparately or as an entire cohort. HDL levels were notdifferent between the two age groups.

Conclusion: In our analysis of CVA patients, lipidprofiles showed increased levels of atherogenic cholesterolwith elevated TC, LDL, TG, and non-HDL independent ofcurrent lipid treatment and higher BMI levels in ouryounger #55 cohort. This raises the question of whetherischemic CVA etiology and risk are driven more byatherogenic risk factors in younger populations, whichmay have important treatment implications.

Figure 1 Kaplan-Meir curves depicting the age of onset of pre-mature CHD in females (A) and males (B). Premature CHD isdefined as the diagnosis of CHD at ages # 55 yrs in males or# 65 yrs in females. Each step down represents the occurrenceof the patient’s CHD diagnosis. Symbols represent censored ob-servations. Cox proportional hazard models were used forcomparing risk of premature CHD and censoring age at 55 yearsfor males and 65 years for females.

Genetics, Gene Therapy and Atherosclerosis

111

Effects of Apolipoprotein E Polymorphism on PlasmaLipoprotein (a) Levels and Cardiovascular Outcomes inFamilial Hypercholesterolemia*

Michael Chen, MD, Jean Davignon, MD, Alexis Baass,MD, (Montreal, QC)

Lead Author’s Financial Disclosures: NoneStudy Funding: NoneBackground/Synopsis: Familial hypercholesterolemia(FH) is a genetic disorder caused by defects in low-densitylipoprotein (LDL) receptor genes. Its phenotype is charac-terized by high LDL cholesterol levels, and increasedatherosclerotic cardiovascular disease (CVD). However,effects of apolipoprotein E (apo E) genotype in lipoprotein(a) concentrations and cardiovascular outcome have notbeen clearly established.

Objective/Purpose: We sought to identify the impli-cation of apo E genotype for plasma lipoprotein (a) levelsand cardiovascular outcomes in FH patients.

Methods: 942 patients were selected from a large cohortof patients referred to the lipid clinic of the ClinicalResearch Institute of Montreal. All selected patient had atleast one LDL receptor mutation by genetic testing. Allpatients were assigned to three groups according to theirapo E genotypes E2 (n5112 for E2/2 and E2/3); E3(n5582 for E3/3); and E4 (n5248 for E3/4 and E4/4).

Results: 8 different LDL receptor mutations were identi-fied with 10-kb deletion accounting for 70% of all mutations.CVDwas present in 334 patients (35%). Sex, age, body massindex, smoking status, high blood pressure, total cholesterollevel, and high-density lipoprotein cholesterol level did notdiffer among apolipoprotein E genotypes. Low-densitylipoprotein cholesterol level was significantly lower in apoE2 genotype (mean56.51mmol/L) than in apo E3 (mean-57.03mmol/L) and in apo E4 genotype (mean57.06mmol/L). Triglyceride level was 16% higher in apo E2 genotype

(mean51.98) than the other two groups. Median levels ofplasma Lp (a) was 13.5mg/dl. Plasma Lp (a) level was lowestin apo E4 genotype (median510mg/dl), followed by apo E2genotype (median513.5mg/dl), and highest in apo E3genotype (median517mg/dl). However, age of onset ofCVD and incidents of CVD did show any differences amongapo E genotypes.

Conclusion: Our investigation shows that apo E2 geno-type is associated with lower LDL cholesterol level in FHpatients. The data also imply that difference in plasma Lp(a)levels in patients with LDL receptor gene mutations are, atleast partly, modulated by apolipoprotein E polymorphismpossibly through changes in LDL cholesterol metabolism.

112

Familial Hypercholesterolemia: A Role for GeneticScreening in Women†*

Zahid Ahmad, MD, Beverley Adams-Huet, MS, Xilong Li,MS, Abhimanyu Garg, MD, (Dallas, TX)

Lead Author’s Financial Disclosures: Dr. Ahmadparticipates in educational talks for Sanofi-Aventis andGenzyme; and advisory board meetings for AegerionPharmaceuticals.

Study Funding: YesFunding Sources: Grants from Department of InternalMedicine at UT Southwestern, National Institutes of Health(NIH) HL020948, and NIH K23 HL114884.

Background/Synopsis: Mutations in LDL receptor(LDLR), apolipoprotein B-100 (APOB), and proproteinconvertase subtilisin-like kexin type 9 (PCSK9) causefamilial hypercholesterolemia (FH), characterized byelevated LDL-cholesterol (LDL-C), xanthomas, and pre-mature coronary heart disease (CHD). However, 20-60%of adult FH patients lack an identifiable genetic cause,and the benefit of routine genetic screening remainsunclear.