Underwriting NT-proBNP NEHOUA Fall 2014 Michael Clark, MD FACC DBIM

Agenda: Underwriting NT-proBNP BNP FAQs Case 1: Deciding on BNP thresholds Case 2,3: BNP and co-morbidities Case 4,5: BNP and "offsets" And some other brain teasers….

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BNP – Discovery and development for mortality risk assessment

Year

Findings

Reference

1986

Atrial natriuretic factor in humans

Hypertension (Crozier) 1986

1996

Brain natriuretic factor produced by ventricles

Circ Res (Ogawa) 1991

2002

Breathe Not Properly study

N Eng J Med (Maisel) 2002

2007

BNP in insured applicants

J Insur Med (Illango) 2007

2014

BNP for mortality risk assessment

J Insur Med (Clark) 2014

Source Heart (Bettencourt) 2005

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BNP is elevated by cardiac STRESS…

Prevalence of heart failure (US population)

NHANES (Bui) 2010 Underwriting NT-proBNP NEHOUA Fall 2014

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BNP identifies both systolic and diastolic cardiac dysfunction

Source: barnesjewish.org

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Causes of BNP elevation (besides heart failure!)  Acute coronary syndromes (unstable angina, myocardial infarction)  Atrial fibrillation  Valvular heart disease  Left ventricular hypertrophy/hypertension  Sepsis  Pulmonary embolism/pulmonary hypertension  COPD  Renal dysfunction (NT-proBNP is excreted by the kidneys)

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Case 1: Deciding on BNP thresholds

71 y.o. female  smoker  Normal ECG  Normal TM to early Stage III  Normal echo: EF 60%  NT-proBNP : 228 pg/ml

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Current and future clinical use of BNP

Each clinical indication may require different ranges of "normal"! Source: J Am Coll Cardiol (Maisel) 2012 Underwriting NT-proBNP NEHOUA Fall 2014

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BNP as a screening tool in an asymptomatic population Source: EHJ (Linssen PREVEND cohort) 2010 mean age 49

 Mortality increased at much lower BNP ranges (dotted line)

 Over half of the population were at increased risk (bars) Underwriting NT-proBNP NEHOUA Fall 2014

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Clinical prognostic use of NT-proBNP Source: JACC (Omland PEACE Trial) 2007

Cohort (n= 3761; aged 60-66 years)  stable CAD  Quartile 4 >98 pg/ml (males); > 115 pg/ml (females)

 Low NT-proBNP threshold for adverse prognosis in CAD patients

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Clinical reference ranges (heart failure): BNP vs. NT-proBNP BNP • 400 pg/mL - HF likely • 100-400 pg/mL - Use clinical judgment NT-proBNP • 900 pg/mL – HF likely • Age >75 years, NT-proBNP >1800 – HF likely  Symptomatic patients with dyspnea! Source: Heart (Bettencourt) 2005

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Clinical use of BNP/NT-proBNP: approach and challenges BNP/NT-proBNP measurement is valuable clinically for:  Diagnosis: determining the cause of pulmonary insufficiency in the ER  Prognosis in those at risk: multiple risk factors, known CAD, known CHF BNP/NT-proBNP clinical challenges  Settling on a standard "cut point" value as "normal"  Defining "heart failure"  Monitoring treatment  BNP measurement variability

Underwriting NT-proBNP NEHOUA Fall 2014

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NT-proBNP in an insurance population: distribution NT-proBNP level

% of general population

Source: EHJ (Galasko) 2005

% of insurance cohort Age 55

Age 75

> 200 pg/ml (males)

300 pg/ml (females)

50% of asymptomatic type 2 diabetics Elevated BNP levels are associated with microalbuminuria, nephropathy, and autonomic neuropathy

Source: Circ Res (Poornima) 2006 Underwriting NT-proBNP NEHOUA Fall 2014

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Case 3: More about co-morbidities

72 y.o. male $750,000 Medical history:  Diabetes, controlled  Hypertension, controlled  No other cardiac studies in the file  NT-proBNP: 660 pg/ml

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Agenda: Underwriting NT-proBNP BNP FAQs Case 1: Deciding on BNP thresholds Case 2,3: BNP and co-morbidities Case 4,5: BNP and "offsets" And some other brain teasers….

Underwriting NT-proBNP NEHOUA Fall 2014

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Case 4: BNP and "offsets"

62 y.o. male $1 million  CTA done for family history of CAD  Diffuse CAD  Abnormal calcium score  Normal stress test to Stage 4  Normal echocardiogram  Carotid ultrasound with mild bilateral plaque  BNP: 108 pg/ml

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ECGs: evolution of the underwriting approach ECG finding

Life Re Guide 1993

Life Guide 2013

Change in rating (%)

First degree block

+50

STD

- 33%

Left axis deviation

+50

STD

- 33%

Major ST, T changes

+200

+75/+100

- 50%

Positive treadmill

+250

+100

- 45%

Paroxysmal atrial fibrillation

+100

STD

- 50%

Factors impacting ECG protective value:  Mortality improvement  Age/amount guidelines  Interpretation "flexibility"  Rating "evolution" Underwriting NT-proBNP NEHOUA Fall 2014

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BNP and exercise testing in CAD

355 patients (aged 63 – 75 years) with stable CAD undergoing stress echocardiography

 30% (quartiles I and II) of stable CAD patients will have normal BNP levels but positive exercise tests  >50% of CAD patients with high BNPs will have negative stress tests

Source: Circulation (Bibbins_Domingo) 2003 Underwriting NT-proBNP NEHOUA Fall 2014

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BNP plus calcium scanning  BNP and CAC provide complementary prognostic information  A negative result on either test implies improved survival over situations where both tests are positive  A positive result for both suggests increased risk – Source: EISNER cohort: 2400 asymptomatic adults (mean age 58 – 69 years)

AJC (Shaw) 2009 Underwriting NT-proBNP NEHOUA Fall 2014

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Underwriting BNP: "judgment" factors

Assessment impact

Echo/nuclear results

J Am Coll Cardio (McKie) 2010

ECG/Exercise testing results

Circulation (Bibbins-Domingo) 2003 Am J Cardiol (Mathewkutty) 2013

Coronary imaging results

Coron Artery Dis (Sahinarslan) 2005

Calcium scan results

Am J Cardiol (Shaw) 2009

Classic cardiac risk factors

N Eng J Med (Wang) 2006 J Am Coll Cardiol (Smith) 2010

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Case 4: BNP and "offsets"

62 y.o. male $1 million  CTA done for family history of CAD  Normal stress test to Stage 4  Normal echocardiogram  Carotid ultrasound with mild bilateral plaque  BNP: 108 pg/ml

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Case 5: BNP and "offsets"

71 y.o. male $5 million Inferior MI 5 years ago EF 40%-59% Stress echo: Inferior akinesis but no other changes to Stage 3 exercise NT-proBNP : 2220 ng/ml

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BNP with other insurance testing  In "healthy normal" subgroup (=no cardiovascular risk factors or echo abnormalities) there was no increased risk of death, heart failure, CVA or MI with increased BNP  In stage A/B heart failure subgroup, elevated NT pro-BNP was independently associated with these events, even after adjusting for traditional risk factors

Mayo/Olmstead county community cohort  703 "healthy normal" & 1288 stage A/B heart failure patients  diagnosis based on echo and clinical assessment  All patients underwent labs, ECGs, and treadmills

Analysis: Kenneth Krause, MD Underwriting NT-proBNP NEHOUA Fall 2014

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Sequential testing, 1% prevalence (BNP then TMT favored)

Analysis: Kenneth Krause, MD Underwriting NT-proBNP NEHOUA Fall 2014

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Decision analysis: model to assess value of NTproBNP Conclusions: Separate testing model:  NT-proBNP gave the "most bang for the buck" in low or medium risk patients. (pretest probability of 1%, 5%, 10%)  Treadmills become more protective/cost-effective in higher risk patients (pre-test probability >20%) Sequential model:  Perform NT-proBNP first then do a treadmill if NT-proBNP abnormal  Important: the value of the treadmill suffered in this analysis because of cost as compared to NT-proBNP

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Agenda: Underwriting NT-proBNP BNP FAQs Case 1: Deciding on BNP thresholds Case 2,3: BNP and co-morbidities Case 4,5: BNP and "offsets" And some other brain teasers….

Underwriting NT-proBNP NEHOUA Fall 2014

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Case 6: Any chance?

76 y.o. female applying for $1 million WL  Known "cardiomyopathy" for years  "Walks 2/4 miles almost every day"  ECG: LBBB  NT-proBNP: 5135 pg/ml

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Case 7: Any chance? 63 y.o. male $2 million WL  Anterior MI 2004  2 stents placed at the time of MI:  proximal LAD (90% stenosis) and midLCx (99%)  LV function: "mildly impaired consistent with MI"  ECG: LBBB  Follow-up 2012 (after 4-year absence)  Treadmill: 9 minutes (10 METs). ECG LBBB.  SPECT: "No ischemia". EF 36% "mildly impaired"

 NT-proBNP: 81pg/ml Underwriting NT-proBNP NEHOUA Fall 2014

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BNP – a perspective  BNP rating thresholds should be related to insurance distribution and scaled for age, gender, and possibly build  NT-proBNP measures cardiac stress, so will be elevated in a number of cardiac conditions, including CAD, valvular heart disease, atrial fibrillation, and left ventricular hypertrophy. Unless the NT-proBNP level is extremely high (>1000 ng/ml), our impairment rating should cover the risk of a small/moderate increase with no or only a small additive rating  NT-proBNP is giving us risk information that is different than ECGs, calcium scanning or exercise testing. They can be added together or used as offsets to get to the best risk assessment  Very low BNP levels may be useful as rating "credits", particularly in cases of valvular heart disease or left ventricular hypertrophy of questionable severity  In the final analysis, BNP underwriting requires guidelines…and good judgment! Underwriting NT-proBNP NEHOUA Fall 2014

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Thank you

Underwriting NT-proBNP NEHOUA Fall 2014

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