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A New Look at CHD Risk Factors  Total Cholesterol  LDL-Cholesterol  HDL-Cholesterol  Lipoprotein(a)  Homocysteine  Particle size/density  Lp subclasses.

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Presentation on theme: "A New Look at CHD Risk Factors  Total Cholesterol  LDL-Cholesterol  HDL-Cholesterol  Lipoprotein(a)  Homocysteine  Particle size/density  Lp subclasses."— Presentation transcript:

1 A New Look at CHD Risk Factors  Total Cholesterol  LDL-Cholesterol  HDL-Cholesterol  Lipoprotein(a)  Homocysteine  Particle size/density  Lp subclasses  Triglycerides  Inflammatory factors  Oxidized-LDL (Ox-LDL)  Metabolic syndrome  Prothrombotic factors  Apolipoproteins  Glucose impairment  Subclinical atherosclerotic diseases  Diabetes mellitus  Life-habit risk factors

2 l LDL = TC – (HDL + VLDL) (TG/5 approximates VLDL) (TG/5 approximates VLDL) Recommendation: Not valid with TG > 400 mg/dL l LDL = Lp(a) + IDL + Remnant Lp + LDL l Total Error = Bias + (1.96 x CV Imprecision ) < 12% (ideal: + 4% & CV < 4%) < 12% (ideal: + 4% & CV < 4%) From: Clin Chem 41: (1995) From: Clin Chem 41: (1995) Measure LDL-C More Accurately Friedewald Calculation:

3 Accuracy of LDL-c Calculation Method TriglyceridesPercent Correct Percent Mg/dL(Within + 10%) Incorrect < % 7% % 25% % 39% % 59% > % From: Warnick GR et. al. Clin Chem 36:15-19 (1990)

4 TriglyceridesCorrect LDL-C Incorrect LDL-C mg/dL(Within + 10%) < % 15% % 23% % 41% % 59% Accuracy of LDL-c Calculation Method From: Warnick GR et. al. Clin Chem 36:15-19 (1990)

5 Friedewald Misclassifies Risk Category When Triglycerides > 177 mg/dL Marniemi J et al. Clin Biochem 1995 June; 28: LDL Risk Category

6 Directly Measured LDL Cholesterol When LDL-C Target is < 100 Friedewald Should Not Be Utilized *Scharnagl H et al. Clin Chem Lab Med 2001 May;39(5):

7 Evaluation of Four Homogeneous Direct LDL-C Methods  Study: LDL-C methods from Genzyme, Reference Diagnostics (RD), Roche, and Sigma were evaluated for precision, accuracy, and specificity for LDL in the presence of abnormal lipoproteins.  Results: Precision was < 2% CV for all methods; and correlation to the CDC reference method was r = ; total error was Genzyme = 12.6%, RD = 16.5%, Sigma = 38.3%, Roche = 41.6%.  Conclusion: The methods show nonspecificity toward abnormal lipoproteins, thus compromising accuracy. These direct methods are no better than the Friedewald LDL-C. From: Miller, WG et.al. Clin Chem 48: (2002)

8 1. Ultracentrifugation: Reference method, accuracy based Time-consuming, tedious, technically difficult, costly 2. Electrophoresis: Simultaneous separation of major lipoprotein fractions, can quantitate, visualize some unusual bands Technically difficult to do; unless automated, it can be tedious and time consuming, can be costly Review of LDL-C Methods

9 Review of LDL-C Methods (Cont.) No pretreatment, full automation, improved analytical precision, fasting specimen not required, save on labor cost Can have lack of LDL specificity; inaccuracy because of analytical interferences from TG, bilirubin, IDL-C, Lp-X, VLDL-C, Lp(a), apo E- rich HDL, and/or hemoglobin; can be costly From: Nauck M et. al. Clin Chem 48: (2002) 3. Third Generation Direct Methods: + -

10 HDL-c Testing NCEP Laboratory Goals – Total Error = ≤ 13% (analytical bias +1.9% CV) – TE = Ideal: ≤ 5% and ≤ 4% CV CDC Reference Method: 3 Stage Procedure 1. Ultracentrifuge = remove chylomicron + VLDL 2. Heparin MnCl 2 ppt. = remove apoB lipoprotein 3. Abell-Kendall cholesterol assay on HDL CRMLN Designated Comparison Method – Dextran Sulfate (50,000 DA) ppt. – Abell Kendall cholesterol assay on HDL

11 From: Warnick et. al. Clin Chem 47: (2001)  There are 4 types of homogeneous HDL-C methods: immunologic, PEG, synthetic polymer, enzymatic.  All can be automated & directly measure HDL.  Most have excellent precision (< 3% CV).  Many have CRMLN certification, suggesting that accuracy is possible with proper instrument, reagents, and calibrator.  Specificity and interferences: most are robust and can tolerate TG < 900 mg/dL, but biases can occur with atypical lipoprotein patterns. Homogenous HDL-c Methods

12 1. Ultracentrifugation: Comparison method for accuracy Time-consuming, tedious, technically difficult, costly, can have interference from Lp(a) and others 2. Electrophoresis: Simultaneous separation of major lipoprotein fractions, can quantitate, visualize some atypical bands Technically difficult to do; unless automated, it can be tedious and time consuming, can be costly Review of HDL-c Methods

13 Review of HDL-C Methods (Cont.) No pretreatment, full automation, improved analytical precision (<3% CV), fasting specimen not required, save on labor cost (20% savings) Can have lack of HDL specificity; inaccuracy because of analytical interferences from bilirubin, hemoglobin, high TG (chylomicrons and VLDL-c), Lp(a), apo E-rich HDL, and/or HDL variants (Apo A-I Milano ) From: Nauck M et. al. Clin Chem 48: (2002) 3. Third Generation Direct Methods: + -

14 Completely automated; better precision Better gel/buffer system (high-resolution) Precision control of temperature during electrophoresis Densitometer designed for higher sensitivity Simultaneously measures VLDL-c, LDL-c, HDL-c & Lp(a)-c LDL-c and HDL-c compares well with CDC reference methods Lp(a) compares well with Lp(a) candidate reference method New Approaches to Quantitative Lipoprotein Electrophoresis

15 PoolVLDL-CLDL-CHDL-C mg/dL mg/dL mg/dL B8.1 ± ± ± 1.5 (5.3% CV)(1.3% CV)(3.6% CV) From: Naito HK, et al. Handbook of Lipoprotein Methods. AACC Press, Washington D.C., Pgs (1997) Within-Run with Helena Electrophoretic Method

16 Comparison of Methods: Helena Electrophoresis vs. CDC Reference Method FractionsRegressionr VLDL-Cy= x LDL-Cy= x HDL-Cy= x From: Naito HK, et al. Handbook of Lipoprotein Methods. AACC Press, Washington D.C., Pgs (1997)

17 Comparison of Methods: Helena vs. Ultracentrifugation FractionsRegressionr VLDL-Cy= 0.929x LDL-Cy= 1.006x HDL-Cy= 1.158x Lp(a)y= 0.23x From: Nauck M, et al. Clin Chem 1995; 41:

18  LDL-C calculation method is not dependable when compared to some of the current direct LDL-C methods.  Ultracentrifugation methods for LDL and HDL still remains the gold standard for accuracy.  The 3 rd -generation electrophoresis methods for lipoprotein-C quantitation have several attractive features.  The 3 rd - generation direct or homogenous LDL-C and HDL-C methods have better precision but may suffer from lack of LDL or HDL specificity; thus, accuracy may be compromised. LDL-c and HDL-c Summary

19  The selection of your instrument-reagent-calibrator system for LDL-C or HDL-C determinations should be based on the approved list of the CDC CRMLN certificate of traceability.  Periodic verification of accuracy of LDL-C and HDL-C should be done, particularly if the reagent and/or calibrator lot number changes.  More robust LDL-C and HDL-C methods should be employed that are not affected by interfering substances (i.e., abnormal lipoproteins, hypertrigly- ceridemia) LDL-c and HDL-c Summary (cont)

20 Lipoprotein(a) Chemistry  Structurally resembles LDL  Has a second large polypeptide, Apo(a)  Is polymorphic in size; Molecular weight kDa  Has 10 types of kringle 4, which is the basis of the different isoform size variability

21 Physiology of Lp(a)  Is an acute phase protein. Apo(a) is made by the liver and is assembled with apo B-100 on the hepatocyte surface. Lp(a) catabolism is unclear.  Compete with plasma plasminogen for binding sites, resulting in decreased synthesis of plasmin and inhibition of fibrinolysis  Increases cholesterol deposition in the arterial wall  Enhances foam cell formation  Makes O 2 -free radicals in monocytes  Promotes SMC proliferation  Induces monocyte-chemotactic activity in subendothelial space  Is an acute phase protein. Apo(a) is made by the liver and is assembled with apo B-100 on the hepatocyte surface. Lp(a) catabolism is unclear.  Compete with plasma plasminogen for binding sites, resulting in decreased synthesis of plasmin and inhibition of fibrinolysis  Increases cholesterol deposition in the arterial wall  Enhances foam cell formation  Makes O 2 -free radicals in monocytes  Promotes SMC proliferation  Induces monocyte-chemotactic activity in subendothelial space

22 Physiology of Lp(a) (Cont.)  Mechanism of CAD: Atherogenesis and Thrombogenesis  Emerging Risk Factor for Vascular Disease  Most prospective and retrospective studies suggest an independent association between Lp(a) and presence and extent of CAD, premature CAD, MI, restenosis after balloon angioplasty, and CVD.  There is evidence for a benefit of lowering Lp(a)  Response to Intervention Therapy  Diet and exercise have no effect: (maybe with monounsaturated fats or caloric restriction with weight loss)  Effect of statins are controversal  Niacin and aspirin will lower  Mechanism of CAD: Atherogenesis and Thrombogenesis  Emerging Risk Factor for Vascular Disease  Most prospective and retrospective studies suggest an independent association between Lp(a) and presence and extent of CAD, premature CAD, MI, restenosis after balloon angioplasty, and CVD.  There is evidence for a benefit of lowering Lp(a)  Response to Intervention Therapy  Diet and exercise have no effect: (maybe with monounsaturated fats or caloric restriction with weight loss)  Effect of statins are controversal  Niacin and aspirin will lower

23 Lp(a) and CHD: Meta-analysis of 27 Prospective Studies n The study (n = 5436) with a mean follow-up of 10 years showed that if an individual in the general population is in the upper third at baseline, you are at 70% increased risk for CHD compared to persons at the lower one-third. n The Lp(a) association to CHD risk is significant and is independent of the standard vascular risk factors. From: Danesh J. Circulation 2000; 102: n The study (n = 5436) with a mean follow-up of 10 years showed that if an individual in the general population is in the upper third at baseline, you are at 70% increased risk for CHD compared to persons at the lower one-third. n The Lp(a) association to CHD risk is significant and is independent of the standard vascular risk factors. From: Danesh J. Circulation 2000; 102:

24 n PROCAM Prospective Study: 788 males were followed for 10 yrs; [Lp(a) measured on fresh blood] n The overall risk of a coronary event was 2.7 times higher if Lp(a) was > 20 mg/dL. The risk increased further if there were other risk factors, I.e., LDL-C > 160 mg/dL, HDL-C 140/90 mmHg n CONCLUSION: Lp(a) is an important independent CHD risk factor that aggravates the coronary risk exerted by elevated LDL-C, low HDL-C, hypertension or the combined effects of multiple risk factors (TG, smoking, diabetes, angina pectoris, and family history of MI) n PROCAM Prospective Study: 788 males were followed for 10 yrs; [Lp(a) measured on fresh blood] n The overall risk of a coronary event was 2.7 times higher if Lp(a) was > 20 mg/dL. The risk increased further if there were other risk factors, I.e., LDL-C > 160 mg/dL, HDL-C 140/90 mmHg n CONCLUSION: Lp(a) is an important independent CHD risk factor that aggravates the coronary risk exerted by elevated LDL-C, low HDL-C, hypertension or the combined effects of multiple risk factors (TG, smoking, diabetes, angina pectoris, and family history of MI) Lp(a) Increases CHD Risk In Men With Other Risk Factors From: Am Coll Cardiol 2001:37:

25 Who Should Have an Lp(a) Test Done? n Patients with a normal lipid profile, but have documentation of definite CHD (MI, angina, CABAG, angioplasty, stent implants) n Patients with parents or 1st-degree relatives who died of premature CHD n Patients with known elevation of Lp(a) or parents with elevation of Lp(a) n High-risk African American males n Postmenopausal women n Men with traditional and/or global CHD risk factors; diabetics and patients with renal disease n Patients with a normal lipid profile, but have documentation of definite CHD (MI, angina, CABAG, angioplasty, stent implants) n Patients with parents or 1st-degree relatives who died of premature CHD n Patients with known elevation of Lp(a) or parents with elevation of Lp(a) n High-risk African American males n Postmenopausal women n Men with traditional and/or global CHD risk factors; diabetics and patients with renal disease

26 It All Began with Some Observations by a Clinical Pathologist and a Cardiologist… Let’s prove it!

27 Clinical Studies Retrospective study of 1124 subjects with lipoprotein electrophoresis (including Lp (a)) performed in a 26 month period. Lipoprotein electrophoresis performed only when abnormal lipids where found apriori and/or in cardiac patients with high hsCRP/histamine. These patients are followed to date. Prospective study of CHD compared with healthy subjects matched for age and sex: Distribution according to race and Lp(a).100 patients, (72 w, 28 aa), and 50 healthy subjects. Prospective study of 51 patients with poorly controlled T2DM before and after treatment with infusion with a external insulin pump.

28 Major Diagnosis T2DMCHDCVDOther Caucasians African Amer major groups: Caucasians + (Hispanics) and African Americans were considered for statistics. CHD: coronary heart disease (MI, angina, coronary insufficiency, angioplasty, bypass surgery, restenosis) CVD: cerebrovascular disease (ischemic stroke, TIA, brain infarction) T2DM: Type 2 diabetes mellitus (  nephrotic syndrome) Other: PAD, chronic renal failure

29 Distribution of Lp(a) Cholesterol According to Race Lp(a) < 4.0Lp(a) Lp(a) > 10.1 Caucasians African Amer Hispanics Asians4264 Pakistani+ Indians 3423 Total (%)509 (45.28)194 (17.26)421 (37.45)

30 Distribution of Lipids in the Cohort with Lp(a) > 4.1 Chol > 200TG > 150HDL < 40 # (%) Caucasians 130 (37.8)110 (32.0)86 (25) African Amer. 29 (72.5)14 (35)16 (40) Hispanics 15 (30.6)10 (20.4)14 (8.6) Asians 12 (28.6)8 (19.1)6 (14.3) Pakistani+ Indians 30 (88.2)14 (41.2)2 (5.9)

31 Distribution of Increased Lipoproteins in the Cohort with Lp (a) > 4.1 VLDL > 35LDL > 120HDL < 40BROAD B Caucasians #(%) 48 (23.5)62 (30.4)40 (19.6)34 (16.6) African Amer. #(%) 50 (23.8)71 (33.8)38 (18.1)10 (4.8)

32 Distribution According to Race & Lp(a) (36w, 21aa) Lp(a)CaucasiansAfrican American # (%) 0 – 425(69.4)12(57.1) 4.1 – 104(11.1)4(19.1) > 10.17(19.5)5(23.8)

33 Normal Lp(a) Values CaucasianAfrican American AllMalesFemalesAllMalesFemales Mean SD Median th Percentile % ≥10 mg/dL Min Max N Lp(a) Non-Diseased Population (Caucasian & African American)

34 Lp(a) Stratified by Risk Score Framingham Risk Assessment All≤45 and 67≥8 Mean SD Median th Percentile th Percentile % ≥10 mg/dL Min Max N Diseased Population

35 ROC of Lp(a) Cut-offs vs Clinical Sensitivity & Specificity at Framingham Risk Assessment Cut-off of < Area under the curve = ± Sensitivity (%) 1-Specificity (%)

36 CP Cardiovascular Disease is the Leading Cause of Death in the US CVCancerAccidentPneumoniaAIDS disease Influenza Millions

37 Ischemic Events in the U.S. 1,500,000 heart attacks:500,000 deaths 500,000 strokes:150,000 deaths One third of individuals who experience an ischemic event will die as a result of that event. Many who have an event have no prior symptoms.

38 Prevention of Ischemic Cardiovascular Events is Key!! How do we determine who will have an ischemic event? Risk Factors Age, smoking status, hypertension, diabetes, Cholesterol, HDL. The ATP-III: NCEP –Provide risk factor screening guidelines and treatment guidelines based on risk factor analysis.

39 Cholesterol Screening: NCEP Everyone over 20 years of age –Every 5 years Total Cholesterol HDL cholesterol Triglyceride LDL cholesterol Treatment guidelines based on LDL cholesterol concentration

40 Cholesterol and Cardiovascular Diseases

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42 Prevention of Ischemic Cardiovascular Events is Key!! One-third to one-half of ischemic events occur in individuals with LDL < 130 mg/dL and in current guidelines for primary prevention the target is < 130 mg/dL.

43 Cardiovascular Risk Factors There is a need for additional risk factors. Additional risk factors would improve accuracy of decisions regarding preventative therapies Rader DJ. NEJM. 2000;343:

44 monocyte chemotaxis Oxidized LDL Native LDL slow rapid ICAM VCAM E-selectin O 2 radicals Growth Factors Thrombin smooth muscle cell mitogenesis Homocysteine Tissue factor VWF Vasoconstriction TXA2 Platelet actv. TXA2 12-HETE B-TBG P-selectin Endothelium Endothelin Prostacyclin Nitric oxide ICAM,VCAM ADMA Fibrinolysis D-Dimer PAI-I Plasminogen Coagulation Fibrinogen PF 1+2 TAT TFPI TPP Lipids/Oxidation LDL subclasses Lp (a) F2 isoprostanes OxLDL Paraoxonase Nutrition HCY B12,B6 Folate Vit. C,E, Carotene Inflamm. hsCRP cytokines chlamydia CMV Lp-PLA2Lp-PLA2 LPC, OxFA

45 Emerging Risk Factors Proposed Panel Homocysteine Lipoprotein(a) [Lp(a)] High-sensitivity CRP Fibrinogen Small dense LDL Currently no guidelines for measurement; may guide intensity of risk reduction therapy in selected patients.

46 The NCEP ATP-III panel identified these novel markers and indicated that clinicians may utilize them in selected persons to guide intensity of risk reduction therapy and modulate clinical judgment when making therapeutic decisions. They do not however, identify in which group of patients these markers are best used or how to respond to elevated values. Emerging Risk Factors JAMA 2001:285;

47 Use of Novel Risk Markers Mayo Test Volumes: 2003 –Homocysteine58,000 –hsCRP26,000 –Lp(a)22,000 –LDL subfractions 3,600 –Fibrinogen ?????

48 Mayo Recommendations for use of Extended Risk Marker Panel Increasing risk Acute coronary syndrome CAD and CAD risk equivalents Low risk population Extended Marker Panel 6%-9% 10 year risk >20% 10 year risk 10% - 20% 10 year risk

49 Mayo Recommendations for Use of Extended Risk Marker Panel When to Measure –Use to enhance clinical decision making in persons at intermediate risk for developing an ischemic event as assessed by the Framingham 10 year risk score: 10-20% risk. Provide with Request –Age, gender, smoking status, blood pressure (treated or untreated)

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51 Mayo Recommendations Clinical Response to Elevated Markers Interpretations are provided with every report of the novel risk marker panel. Interpretations are made by doctoral level staff in Laboratory Medicine or in the Mayo Cardiovascular Health Clinic. Interpretations include a description of abnormal values, as well as suggestions for appropriate treatment, given the noted abnormalities. A separate document describing up to date information on the background, interpretation and recommended therapy for abnormalities of each of the risk markers is included with the report.

52 Novel Risk Markers Relation to Angiographic CAD and Events Mean Age 60 ± 11 years, 62% Male 46% patients have none or mild coronary occlusion 54% patients have significant occlusion (>50% stenosis) Median Follow-up: 4 years None Mild 1V 2V 3V Vessel Disease 504 consecutive patients undergoing coronary angiography

53 Patient Demographics Age (yr)60±11 Male (%)62 Hypertension (%)46 BMI (kg/m 2 )29±6 Prior infarction (%)15 Heart failure (%)12 Significant CAD (%)54 ACS (%)34

54 Study Population Indication for coronary angiography – Acute coronary syndrome (34%) – Positive stress test (25%) – Exertional dyspnea (27%) – Other (14%)

55 Aims Other CAD risk Factors –(both traditional and emerging) Acute coronary syndromes Angiographic CAD Clinical outcomes To analyze for associations between novel risk factors including Lp-PLA2 and:

56 Lipoprotein Associated Phospholipase A2 (Lp-PLA2) AKA: Platelet-activating factor acetylhydrolase 50kDa, Ca-insensitive lipase Produced predominantly by macrophages and contributes to foam cell formation > 80% bound to LDL Not responsive to IL-1, IL-6, TNF-alpha. Hydrolyzes oxidized phospholipids

57 Multivariate Logistic Regression Analysis After adjusting for age, gender, smoking history, hypertension, cholesterol, HDL cholesterol, and triglyceride, Lp-PLA2 was no longer was no longer independently predictive of angiographic CAD. CRP was not predictive of CAD in either the univariate or multivariate model. Data Presented at American College of Cardiology Annual Meeting, March 2003.

58 HR For Angiographic CAD: Multivariate VariableHR95% CIP-Value Age < Male Gender – 6.60< Hypertension Smoking Total cholesterol HDL cholesterol Log triglyceride Log CRP Fibrinogen Lp-PLA Lp(a) protein (per 20 mg/dL) Lp(a) cholesterol (per 5 mg/dL)

59 Lp(a) Cholesterol Electrophoresis Helena Laboratories LDLVLDLHDLLp(a) UC Non-UC UC Non-UC UC Non-UC UC Non-UC UC Non-UC Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 UC Lp(a) =6 Non-UC Lp(a) = 8 Lp(a) mass = 125 UC Lp(a) = 8 Non-UC Lp(a) = 19 Lp(a) mass = 131 UC Lp(a) = < 2 Non-UC Lp(a) = < 2 Lp(a) mass = <7 UC Lp(a) = 19 Non-UC Lp(a) = 21 Lp(a) mass = 72 UC Lp(a) = <2 Non-UC Lp(a) = <2 Lp(a) mass = 11 Baudhuin, et.al., Clinical Biochemistry: 2004 Lp(a) cholesterol can be measured in whole serum Verified in samples from 470 subjects

60 Immunologic Lp(a) vs. Lp(a) Cholesterol

61 HR for Events in 425 Non-AMI: Univariate VariableHR95% CI Age – 2.13 Male Gender Hypertension Smoking LDL cholesterol HDL cholesterol Log triglyceride Log CRP Log HCY LDL size Fibrinogen Lp-PLA Lp(a) protein: > 30 mg/dL Lp(a) cholesterol: detectable – 4.03

62 HR For CVD in 425 non-AMI: Multivariate VariableHR95% CI Age Male Gender Hypertension Smoking LDL cholesterol HDL cholesterol Log triglyceride Log CRP Log HCY LDL size Fibrinogen Lp-PLA Lp(a) protein: > 30 mg/dL Lp(a) cholesterol: detectable

63 Lipoprotein (a) Structure Apo (a): -- Sequence homology to plasminogen (genetic variant) -- Size heterogeneity (~ KDa; 3-40 K4-T2 repeats) Kringle (~13 KDa, ~80 AA) Cleavage site by pg activator Plasminogen (pg) Inactive cleavage site H2NH2N HOOC H2NH2N S S K5 K4 T10 T 9 T 8 T 7 T 6 T 5 T 4 T 3 T 2 ApoB-100 T1

64 M 1 S 2 3 S 4 5 S >S4 S4 S3 S1 B Apolipoprotein (a) Isoform Identification by Western Blotting Apo (a) Size Standards: >S4: 35 KIV repeats, >700 kDa S4: 27 KIV, ~700 kDa S3: 23 KIV, ~650 kDa S1: 19 KIV, >Apo B-100 (512kDa) B: 14 KIV,

65 Apolipoprotein (a) Isoforms 23 and and SSS

66 Overview and Conclusions Prevention of Cardiovascular events is Key!!! Know Your Cholesterol, Know Your Risk –Lipid profile in everyone > 20 years of age –Use ATP III guidelines –Determine Framingham Risk Score –Educate Others Novel/Emerging Risk Markers –Primarily in patients at intermediate risk –Guide intensity and type of therapy –Much more work needs to be done

67 Conclusions Lp-PLA2 is emerging as an independent risk marker for cardiovascular events: orally active specific inhibitors make it a potential therapeutic target. Lp(a) cholesterol is a strong marker for angiographic coronary disease as well as cardiovascular events. Differences observed between Lp(a) cholesterol and Immunologic Lp(a) mass assays need to be further investigated, but may be due to dependance of the mass assays on apo(a) isoform size Efforts to standardize Lp(a) methods need to continue.

68 Lipid Profiles Medicare-approved panel –Total Cholesterol, Triglycerides, LDL-c, HDL-c Candidate additional analytes –ApoA, ApoB, IDL, Lp(a), LDL Sub, HDL Sub, RLP

69 Panel Comparison 266 consecutive subjects 45% had desirable TC, TG by NCEP –Of those, 44% had Lp(a) above 55 th percentile –28% had Lp(a) above 75 th percentile 28% had desirable TC, TG, LDL-c, HDL-c – Of those, 49% had Lp(a) above 55 th percentile

70 Lp(a) Correlates None of the following are correlates or predictors of Lp(a) values: –Total cholesterol –LDL-c –HDL-c –TG –Apo A1 –Apo B100

71 Lp(a)/Lp(a)-c and Platelet Function Study of 100 subjects with existing Lp(a) and Lp(a)-c measurements –Lp(a) ranged from <5-231 mg/dL –Lp(a)-c ranged from mg/dL Measured platelet aggregation to collagen/ADP and collagen/EPI by PFA Medication history: 34% on ASA or NSAIDS

72 Results Closure times with either EPI/collagen or ADP/collagen were not decreased as Lp(a) concentrations increased No difference between Lp(a) and Lp(a)-c


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