# A New Look at CHD Risk Factors

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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 Triglycerides Inflammatory factors Oxidized-LDL (Ox-LDL) Metabolic syndrome Prothrombotic factors Apolipoproteins Glucose impairment Subclinical atherosclerotic diseases Diabetes mellitus Life-habit risk factors

Measure LDL-C More Accurately
Friedewald Calculation: l LDL = TC – (HDL + 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 CVImprecision) < 12% (ideal: + 4% & CV < 4%) From: Clin Chem 41: (1995)

Accuracy of LDL-c Calculation Method
Triglycerides Percent Correct Percent Mg/dL (Within + 10%) Incorrect < % % % % % % % % > < 20% > 80% From: Warnick GR et. al. Clin Chem 36:15-19 (1990)

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

Friedewald Misclassifies Risk Category When Triglycerides > 177 mg/dL
Estimating LDL-C is Unreliable When triglycerides (TG) > 400 everyone knows the LDL may be 25% falsely low and you have to order a directly measured LDL. You may not realize that even at relatively modest elevations of TGs when TG > 200 the estimated, or Friedewald LDL is already 10% falsely low or more, at TG > 300 it may be 15%-20% falsely low. What’s more when TG < 100 Friedewald breaks down again and you get a falsely low LDL. In this study by Marnieri of 225 patients whose LDL was measured with the preparative ultracentrifuge, it was found that the Friedewald equation would have put persons in the wrong LDL risk category as much as half the time – this occurred for patients with TG > 177 mg/dl (which is > 2.0 mmol/l). Of course you’re supposed to fast for Friedewald else TG’s go up and the estimated LDL goes down. In my mind we systematically underestimate LDL with Friedewald mainly because so many patients do not really fast. LDL Risk Category Marniemi J et al. Clin Biochem 1995 June; 28:

When LDL-C Target is < 100 Friedewald Should Not Be Utilized
Directly Measured LDL Cholesterol When LDL-C Target is < 100 Friedewald Should Not Be Utilized The third and perhaps most important reason to move immediately to direct LDL measurement in all patients is that Friedewald never intended for us to use his equation on persons’ with low LDL values, I.e. LDL-C < 100 mg/dL. The Friedewald equation is 15% - 19% falsely low in persons whose directly measured LDL is under 100 mg/dL. We are in an era where all CAD patients should have LDL below 100 and it must be measured directly to be accurate. The fact that VAP provides a direct LDL-C, reliable at values below 100, reliable in persons with high or low TGs, and reliable in non-fasting persons - is sufficient reason alone to replace the old lipid panel with the VAP. It’s just a Better Cholesterol Test. When you switch you will notice that your patient’s LDLs suddenly look higher because the Friedewald underestimates LDL. *Scharnagl H et al. Clin Chem Lab Med May;39(5):

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)

Review of LDL-C Methods
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 (Cont.)
3. Third Generation Direct Methods: + 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) -

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 Ultracentrifuge = remove chylomicron + VLDL Heparin MnCl2 ppt. = remove apoB lipoprotein Abell-Kendall cholesterol assay on HDL CRMLN Designated Comparison Method Dextran Sulfate (50,000 DA) ppt. Abell Kendall cholesterol assay on HDL

Homogenous HDL-c Methods
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. From: Warnick et. al. Clin Chem 47: (2001)

Review of HDL-c Methods
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 (Cont.)
3. Third Generation Direct Methods: + 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-IMilano) From: Nauck M et. al. Clin Chem 48: (2002) -

New Approaches to Quantitative Lipoprotein Electrophoresis
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

Within-Run with Helena Electrophoretic Method
Pool VLDL-C LDL-C HDL-C mg/dL mg/dL mg/dL B 8.1 ± ± ± 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)

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

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

LDL-c and HDL-c Summary
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 3rd-generation electrophoresis methods for lipoprotein-C quantitation have several attractive features. The 3rd- 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 (cont)
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)

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

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 O2-free radicals in monocytes Promotes SMC proliferation Induces monocyte-chemotactic activity in subendothelial space

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

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:

Lp(a) Increases CHD Risk In Men With Other Risk Factors
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 < 35 mg/dL, BP > 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) From: Am Coll Cardiol 2001:37:

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

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

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.

Major Diagnosis 2 major groups: Caucasians + (Hispanics) and African Americans were considered for statistics. T2DM CHD CVD Other Caucasians 82 90 20 10 African Amer. 88 84 24 14 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

Distribution of Lp(a) Cholesterol According to Race
Caucasians 344 85 184 African Amer. 40 89 210 Hispanics 49 12 20 Asians 42 6 4 Pakistani+ Indians 34 2 3 Total (%) 509 (45.28) 194 (17.26) 421 (37.45)

Distribution of Lipids in the Cohort with Lp(a) > 4.1
Chol > 200 TG > 150 HDL < 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)

Distribution of Increased Lipoproteins in the Cohort with Lp (a) > 4.1
VLDL > 35 LDL > 120 HDL < 40 BROAD 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)

Distribution According to Race & Lp(a) (36w, 21aa)
Caucasians African American # (%) 0 – 4 25(69.4) 12(57.1) 4.1 – 10 4(11.1) 4(19.1) > 10.1 7(19.5) 5(23.8)

Normal Lp(a) Values Caucasian African American
Lp(a) Non-Diseased Population (Caucasian & African American) Caucasian African American All Males Females Mean 2.6 2.4 2.9 3.4 3.2 3.8 SD 2.8 2.7 3.6 Median 1.9 1.6 2.3 2.2 2.0 95th Percentile 6.2 5.2 6.3 8.6 8.3 % ≥10 mg/dL 98.3 98.8 97.7 97.9 98.2 97.0 Min 0.2 0.4 9.2 Max 11.4 10.9 11.8 11.3 11.5 N 254 146 108 102 56 46

Lp(a) Stratified by Risk Score
Diseased Population Framingham Risk Assessment All ≤4 5 and 6 7 ≥8 Mean 11.1 3.2 6.6 10.9 14.9 SD 8.7 3.4 5.9 8.8 8.0 Median 7.2 1.9 4.4 9.0 10.6 5th Percentile 2.4 1.5 2.3 4.2 5.4 95th Percentile 22.4 9.8 14.8 18.0 26.3 % ≥10 mg/dL 51.6 22.5 59.4 65.2 Min 0.2 0.6 1.6 3.3 Max 24.4 14.6 23.2 28.8 N 530 103 105 195 127

ROC of Lp(a) Cut-offs vs Clinical Sensitivity & Specificity at Framingham Risk Assessment Cut-off of < 4 0.2 2.0 3.9 5.9 8.1 9.9 12.5 15 18.2 20 25 28 40 60 80 100 Area under the curve = ± 0.007 Sensitivity (%) 1-Specificity (%)

Cardiovascular Disease is the Leading Cause of Death in the US
CV Cancer Accident Pneumonia AIDS disease Influenza Millions CP

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.

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.

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

Cholesterol and Cardiovascular Diseases

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.

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:

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-PLA2 Homocysteine Thrombin monocyte chemotaxis ICAM VCAM E-selectin TXA2 Tissue factor VWF Native LDL Growth Factors slow LPC, OxFA O2 radicals Lp-PLA2 smooth muscle cell mitogenesis Vasoconstriction rapid Oxidized LDL

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.

Emerging Risk Factors 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. JAMA 2001:285;

Use of Novel Risk Markers
Mayo Test Volumes: 2003 Homocysteine 58,000 hsCRP 26,000 Lp(a) 22,000 LDL subfractions 3,600 Fibrinogen ?????

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

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)

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.

Novel Risk Markers Relation to Angiographic CAD and Events
504 consecutive patients undergoing coronary angiography Vessel Disease 3V None 2V Mild 1V 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

Patient Demographics Age (yr) 60±11 Male (%) 62 Hypertension (%) 46
BMI (kg/m2) 29±6 Prior infarction (%) 15 Heart failure (%) 12 Significant CAD (%) 54 ACS (%) 34

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

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

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

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.

Variable HR 95% CI P-Value Age <0.0001 Male Gender – 6.60 <0.0001 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)

Lp(a) Cholesterol Electrophoresis Helena Laboratories
LDL VLDL HDL Lp(a) 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 Lp(a) cholesterol can be measured in whole serum Verified in samples from 470 subjects Baudhuin, et.al., Clinical Biochemistry: 2004

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

HR for Events in 425 Non-AMI: Univariate
Variable HR 95% 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

HR For CVD in 425 non-AMI: Multivariate
Variable HR 95% 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

Lipoprotein (a) Structure
Inactive cleavage site H2N HOOC S K5 K4 T10 T 9 T 8 T 7 T 6 T 5 T 4 T 3 T 2 ApoB-100 T1 Kringle (~13 KDa, ~80 AA) 4 3 5 2 1 Cleavage site by pg activator Plasminogen (pg) Apo (a): -- Sequence homology to plasminogen (genetic variant) -- Size heterogeneity (~ KDa; 3-40 K4-T2 repeats)

Apolipoprotein (a) Isoform Identification by Western Blotting
M S S S >S4 S4 S3 S1 B Apo (a) Size Standards: >S4: KIV repeats, >700 kDa S4: KIV, ~700 kDa S3: KIV, ~650 kDa S1: KIV, >Apo B-100 (512kDa) B: KIV, <Apo B-100 1- 5: Patient Serum Samples M: Protein Size Marker, Myosin band (207 kDa)

Apolipoprotein (a) Isoforms
23 and 31 S 12 20 and 27 S 21 16 S

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

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.

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

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

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

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

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