Cardiovascular disease and Older Age Underwriting

1. Cardiovascular disease and Older Age Underwriting Mike Fulks, M.D. and Robert L. Stout, Ph.D. Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

2. Life’s tough; you work hard. If you are lucky, you get old and you die. Dr. Bob

3. Changes in our view of cardiovascular disease Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL Cholesterol and obstructive disease. Soft vulnerable vs stable calcified? plaque. Networks of inflammation, Senescence and chronic illness. Genetic regulation of CVD risk.

4. Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

5. Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

6. What makes older ageunderwriting different? 1975-80 Select and Ultimate male tables, • Initial (first year) underwriting impact on mortality is much greater at older age • 81% reduction in (select) risk at age 72 • 63% reduction in (select) risk at age 32 • BUT Ultimate (at 16 years) impact is much smaller at older age • 19% mortality reduction at age 72 • 35% mortality reduction at age 32 Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

7. Why so different? Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • The young have risk factors for future disease rather than current and more behavioral risk leading to traumatic death • The older ages already have current diseases that need detection and much more limited risk of traumatic death.

8. Prevalence of diseaseby age Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

9. What age is “old“? Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • Based on current industry Select and Ultimate data, that transition is around age 60 • Based on CRL research on laboratory studies, BP and build mortality we come to the same conclusion- age 60 • If you are going to have a different approach is terms of testing or handling based on age- do it at age 60, not age 65 or 70!

10. Major Mortal diseases of old age. • Vascular and Renal disease • Heart, especially early heart failure (not presence of CAD) • Stroke, including unrecognized events accounting for a portion of dementia • Cancer, pre-diagnosis • Now as common a cause of mortality as Heart • Cognitive impairment and Dementia • Non-vascular and Vascular • Frailty Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

11. CRL research Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • 10’s of millions of applicant records including all laboratory studies • Duration of follow-up to 15 years • Include BP and Ht/Wt for past 9 years • Able to link those records with the Social Security Death Master File to obtain all-cause mortality

12. CRL results Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL Generated an ongoing series of articles in JIM and OTR as well as other reports on the actual impact of test results on mortality in an age- and sex-specific manner These results supplemented by other recent published works from clinical and general population studies

13. Specific Findings - Cardiovascular Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

14. Cholesterol/HDL mortality Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

15. Cholesterol HDL ratio Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

16. Blood Pressure Excess mortality based on insurance exam BP’s Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL Systolic BP is a potent predictor of cardiovascular and cerebro-vascular risk

17. NT-ProBNP Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

18. Specific Findings - Kidney Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • Value of creatinine, eGFR and cystatin C • Cystain C is good reflex marker when serum creatinine is high. • Must stratify eGFR, creatinine and cystatin C by age as eGFR falls normally the other two increase with aging • When age and proteinuria are properly accounted for, eGFR minimally predictive except at very low values. • Those eGFR values are in the 40s for 70+

19. Proteinuria Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL Mild proteinuria has 50% increase in CV disease and mortality, while heavy has >100% increase. In contrast, eGFR from >60 ml/min compared to <50 ml/min had minimal impact (Hemmelgarn BR. JAMA 2010;303:423-429.) CRL research also shows proteinuria as measured by the protein/creatinine ratio is a potent risk predictor at much lower levels than previously recognized

20. Proteinuria contd. Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

21. Specific Findings - Cancer Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • PSA? • CEA • Age and sex-specific evaluation of a wide range of tests including LFTs, cholesterol, albumin, etc

22. PSA for Age 60-69 Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

23. PSA for Age 80> Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

24. Prevalence of PSA in the insurance population The USPSTF draft statement says: “This recommendation applies to men in the U.S. population that do not have symptoms that are highly suspicious for prostate cancer, regardless of age, race, or family history.” U.S. Preventive Services Task Force October 2011 Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

25. CEA for Older Age • How predictive ages 60+ for NS • CEA 5 to 9.9 rel. risk = 200 to 250% • CEA 10+ = 550 to 1000% • How Common age 60-69 for NS • CEA 5 to 9.9 = 3% • CEA 10+ = 0.5% • How much risk avoided if take action at 10? • Eliminate 3.2% of early deaths but only 0.4% of applicants Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

26. Specific Findings - Dementia Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • Alzheimer’s disease is responsible for over half of dementia but ischemic disease affects 60-90% of those with Alzheimer’s with major infarctions present in 1/3 (Querfurth HW, NEJM 2010;362:329) • DM and BP associated with AD risk, the rest less certain (Duron E. Vasc Health Risk Manag 2008;4:363) • Vascular dementia accounts for a significant minority of dementia cases. However, lab testing likely only provides limited value here.

27. Specific Findings – Frailty and unrecognized conditions Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL Albumin Total Cholesterol Combination of other labs and measurements

28. Albumin and mortality Lower albumin Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

29. T. Cholesterol and Mortality Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

30. A surprise: Age, Alcohol & Mortality Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

31. Can testing identify an older age preferred risk? Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL • “Yes”, as we will show on the next slide. • Need to use all lab, BP and build as well as including any special testing (NT-ProBNP, Hemoglobin) • No magic single test • Age and sex-specific use of lab based on actual mortality, not “normal” ranges

32. CRL Scoring Preferred Standard Substd Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL

33. Summary Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL Older age begins at 60 Lab panel can predict older age risk but must be used with age-specific risk-based ranges Some additional testing such as NT-ProBNP improves risk discrimination Using a combined scoring approach most successful especially for preferred risks

34. Thank you! Clinical Reference Laboratory now generates a certificate of attendance for our seminars. If you would like to receive one please forward your email address to arnoldl@crlcorp.com Copy write Clinical Reference Laboratory 2011 May not be reproduced in any form without the written permission of CRL