NT-ProBNP – What It Means In Underwriting And How A Normal Value Can Help You!!

1. NT-ProBNP – What It Means In Underwriting And How A Normal Value Can Help You!!

2. N-Terminal Pro Brain-Type Natriuretic Peptide (NT-ProBNP)

3. First discovered in the 1950’s and really began to be studied closely in the1980’s. Insurance laboratories made available as part of SMAC in 2005. • A complex amino acid substance produced within the muscle cells of the heart. • “Stress and strain” on the heart cells increase productions of BNP. • Helps relax the muscle cells of the heart and vessels to lower the workload of the heart. • BNP increases circulation to the kidneys and allows them to unload more salt and fluid from the body.

4. Natriuretic Peptides (NP’s) ANP: Atrial Natriuretic Peptide BNP: The physiologically active portion NT-ProBNP: Inactive but more stable and easier to measure in the laboratory ~ longer half-life, making it more stable for laboratory testing (stable 18 times longer at room temperature). ExamOne Normal Range: <125 pg/ml

5. Used clinically to diagnose and follow up the treatment of congestive heart failure (CHF). But also can be elevated with: • Unstable coronary disease or myocardial infarctions (heart attacks) • Excessive thickening of the heart muscle (hypertrophy) • Cardiac arrhythmias (atrial fibrillation) • Valvular heart disease • Pulmonary hypertension and emboli (blood clots) • Chronic renal failure • Chronic obstructive lung disease (COPD) • CHF From the life insurance standpoint…it also helps predict higher cardiac and all-cause mortality!

6. Lincoln Benefit Life We use NT-ProBNP because it is stable longer for the laboratory and has the same predictive value as BNP. We began screening in August, 2008 at age 65 and older, for face values of $100,000 and above. We offer potential credits for favorable results! We use age-adjusted levels and set the cut offs fairly high to avoid those in the “gray zone”.

7. We review NT-ProBNP results in-depth for our business on a periodic basis: • Prior to initiating NT-ProBNP screening as part of a cost/benefit analysis • Shortly after implementing or screening in August, 2008 • And periodically since

8. Each time the results were very similar: • Over 1/3 of screenings would be eligible for credits if needed! • Less then 10% of screenings require any type of adverse underwriting action based on our current policies. - Approximately half of these already have known ratable cardiac conditions. - Approximately a third of these would require declination. - Average age 75, average face between $800k to $1M • 80% of BNP’s done “for cause” came back in the favorable range! - Average age 55 and face of $3.4M

9. Tests that assess cardiac ventricular function and enlargement, coronary artery status, heart valve function and cardiac rhythms are used to evaluate many of the conditions that BNP screens for: • Echocardiograms • Nuclear stress tests or stress echocardiograms • Coronary angiograms with left ventriculogram • Cardiac CT, MRI and PET scans • Holter monitors If the underwriter has this type of current information available to them for review, it can be very helpful in assessing the significance of an elevated screening BNP level or in cases where the BNP requirement is not available.

10. Fun Facts! • Does the time of collection matter? No, not at all. • Does posture or heart rate at the time of collection significantly affect levels? No. • Is NT-ProBNP affected by any cardiovascular drugs? Yes. ACE inhibitors can raise it and beta-blockers can lower it. • Does NT-ProBNP increase with age? Yes, very gradual until age 65 and over. • Is NT-ProBNP higher in women than men? Yes, minimally, though. • Does NT-ProBNP elevate during an exercise stress test? No. • Is NT-ProBNP affected by weight? Yes, it is generally higher in non-obese as compared to obese individuals. • Is the impact due to weight significant? No.

11. NT- ProBNP ~ How a normal value can HELP You! (Tell me how!) • A favorable NT-ProBNP result may allow an improved offer in those cases where there is a ratable cardiac history . • Excellent point of reference for the underwriter when reviewing cardiac cases where recent cardiac testing has not been completed.

12. REAL LIFE CASES Pertinent case information: • Male age 66 • Quoted Standard • Attorney - Income $200k Medical history: • Per application, only history is rotator cuff surgery • Medications include daily aspirin and Cardizem (note what this is for) These are hypothetical cases developed for discussion purposes only. Any similarities to real cases submitted to Lincoln Benefit Life is coincidental. Underwriting opinions and rating suggestions are based on pertinent factors of each individual case and not necessarily applicable to similar cases.

13. Exam • 6’ 0” 184 pounds BP 122/80, Pulse 70 • Smokes 1 cigar per month while playing golf • Same history on the exam as on the application, but states the Cardizem is taken for prophylaxis • EKG showed atrial fibrillation

14. APS review History of CAD, 1992 coronary spasm with no significant fixed CAD • Mitral annular calcification • Paroxsymal Atrial Fibrillation • Deverticulosis • Stable pulmonary nodules Tentative T2 subject to review of labs.

15. Labs Slide showing NT-ProBNP at 1,332!

16. Recommendation was to decline due to the elevation of the initial NT-ProBNP but was later issued after a repeat NT-ProBNP came back normal.

17. Final case disposition: • Case was issued and placed based on the new NT-ProBNP result without any additional cardiac workup completed. • Applicant died 18 months later from a CVA thought to be related to the atrial fibrillation.

18. Review of key points and lessons of the case: • The NT-ProBNP result will go back to normal, even to levels one might consider to be exceptional, after a cardiac event.

19. Positive Consequence Recent Favorable BNP Case Examples • Case #1: This is a 77 year old male applicant that had an abnormality on this insurance EKG. No history of underlying cardiac disease. A favorable NT-ProBNP level on his insurance lab allowed the underwriter to go from a low substandard offer to a standard offer. • Case #2: This is a 75 year old female applicant who was at a low substandard rating for a history of Parkinson’s disease and mild-moderate obstructive coronary disease. Her screening NT-ProBNP returned favorably and allowed the underwriter to improve the offer. • Case #3: A 69 year old male applicant with a history of glucose intolerance, hypertension and hyperlipidemia. He was potentially low substandard rating but with favorable Healthy Credits considerations, and a favorable NT-ProBNP level he qualified for a Standard offer.

20. QUESTIONS? 2013 Allstate Insurance Company