1. Meredith Cook Mercer COPHS August,2012

2. Total Cholesterol HDL Could CVD prediction be improved by also assessing additional lipid-related markers (replacing or adding these levels) Total Cholesterol : HDL ratio Non-HDL (Total Cholesterol-HDL) Apolipoprotein B Apolipoprotein A-I Lipoprotein (a) Lipoprotein-associated phospholipase A 2

3. To determine whether REPLACING information on total cholesterol and HDL with various lipid parameters improves prediction CVD To determine whether ADDITIONAL information on apoB and A-I, lipo(a), or lipo-associated PLA 2 improves CVD risk prediction

4. Baseline Characteristics Total cholesterol HDL Age Sex Smoking status Diabetes BP TG Apo-B Apo-A-I Lipo (a) Lipo-associated PLA 2

5. No selection based on whether or not patient had previous CVD (defined in each study at the initial examination) Recorded cause-specific mortality, vascular morbidity, or both during follow-up >1 year follow-up Fatal outcomes determined based on death certificates Direct measure of LDL, BMI, family history of CVD, and socioeconomic factors were only available in certain subsets of participants, therefore this data was not included in the main analysis.

6. Primary outcome – first onset CVD (defined as fatal or nonfatal CHD event or stroke) Clinical Modeling Assumed sequential screening Assumed statin allocation would reduce CVD risk by 20% in people without a history of CVD Assumed a policy of statin allocation per Adult Treatment Panel III guidelines

7. Individual records for 165,544 patients withOUT baseline CVD in 37 prospective cohort studies (1968-2007) Up to 15,126 fatal and non-fatal CVD outcomes (10,132 CHD and 4,994 strokes) recorded during a median of 10.4 years (range 7.6-10.4 years)

8. REPLACEMENT with other lipid-related markers Did NOT improve risk discrimination or reclassification Ex: replacement of total cholesterol and HDL with apoB and apoA-I significantly WORSENED risk discrimination (p<0.001) and risk classification (p=0.01) No improvement in risk discrimination with baseline characteristics or with CHD/stroke

9. ADDITION of lipid-related markers None of these lipid-related markers significantly improved CVD risk classification ApoB, apoA-I, and lipo(a) could improved CVD prediction more in patients with higher total cholesterol or in patients initially classified at 10%-<20% predicted 10-year risk (p<0.001) Addition of apoB and apoA-I improved CVD risk discrimination in men (p=0.01), patients using BP meds (p<0.005), and patients with lower HDL (p=0.022)

10. ADDITION of lipid-related markers Addition of apoB and apoA-I significantly improved risk discrimination for CHD (p<0.001), but not for stroke (p=0.30) Addition of lipo(a) or lipo-associated PLA 2 did not show improved risk discrimination for CHD

11. Clinical Modeling 100,000 adults >40 years old 15,436 people 10%-<20% 10-year predicted CVD risk 13,622 remained after excluding those recommended for statin treatment by Adult Treatment Panel III guidelines Assessment of lipo(a) reclassified 555 patients (4.1%) to 20% or greater predicted risk (86 of these were expected to have CVD event within 10 years) Assessment of lipo-associated PLA2 reclassified 365 patients (2.7%) to 20% or greater predicted risk (72 of these were expected to have CVD event within 10 years)

12. REPLACEMENT of total cholesterol and HDL with apoB and apoA-I significantly WORSENED risk discrimination (clinically relevant to patients with DM and elevated TG levels) ADDITION of various lipid-related markers resulted in a slight potential for improvement in CVD prediction Clinical benefits have yet to be established

13. Analysis does not include etiological and therapeutic questions Reclassification analyses are sensitive to choice of follow-up interval and clinical risk categories Clinical models could have over- estimated potential benefits because not all patients eligible for statin therapy actually took them

14. Lipid-Related Markers and Cardiovascular Disease Prediction. JAMA, June 20, 2012. Vol 307, No 23, p 2499- 2506.