Transcript NT-proBNP

WAHLU
Critical
Underwriting
Issues
Betsy Sears
Evolution of Underwriting
1692
Earliest Mortality
Tables Permit
Accurate Pricing
by Age and Sex
1948
1980s
Cotinine Testing
Enables Credible
Non-Smoker
Pools
Framingham Heart
Study Begins
Quantification of
Cardiovascular
Risk
Age and Sex
2000s
Today
Teleunderwriting,
Prescription
History and Other
Data Products
Provide More
Detail
Risk IQ
Offers Data
Analytics and
Decision
Support
HIV Testing
Inaugurates Era
of Routine Blood
Screening
Broadly Defined
Risk Categories
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respective owners. © 2011 Quest Diagnostics Incorporated. All rights reserved.
Individualized
Risk Assessments
New Tests & Trends
 A1c screening
 Risk IQ
 Older Age Testing
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Diabetes
 25.8 M diabetics in U.S. (9% of population)
 18.8 M diagnosed
 24% (7M) undiagnosed
(50% 10 years ago)
 1.9 M new cases 2010
 79 M pre-diabetic
 450,000 people die annually
http://www.cdc.gov/diabetes/faq/research.htm
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CDC
Number (in Millions) of Civilian, Noninstitutionalized Persons
with Diagnosed Diabetes, United States, 1980–2010
Centers for Disease Control and Prevention 2011
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Developments in Hgb A1c
 American Diabetes Association: new
guidelines for diagnosing and treating
diabetes January 2010
 Big change: recommendation that A1c
now be used to diagnose pre-diabetes and
diabetes
 Screen guidelines
Diabetes Care January 2010 33:S11-S61
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Hgb A1c
 Glucose passes freely into and out of red
blood cells and reaches equilibrium
 Glucose binds to hemoglobin
 Hgb A1c gives picture of average serum
glucose over previous 2 to 3 months
(rbcs turn over every 120 days)
 Not affected by glycolysis
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Hgb A1c: Predicting Diabetic Risk
 Prospective 3 year study - VAMC
 1253 outpatients; age 45 – 64
 4.5% (52) diabetes at baseline;
additional 73 by end of third year
 Baseline HbA1c and baseline body
mass index (BMI) were the only
significant predictors of new onset
diabetes
Edelman, MK Olsen, TK Dudley, AC Harris, EZ
Journal of General Internal Medicine, 2004
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EPIC-Norfolk Study A1c
“In men and women A1c concentrations predicted coronary heart,
CV disease, and total mortality…independent of and only
slightly attenuated after adjustment for known risk factors”
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Hgb A1c
 Guidelines suggest: A1c > 6.4% be used to
diagnose diabetes (threshold for retinopathy)
 Studies have shown: A1c 5.7 – 6.4% have
an 88% chance of developing diabetes over
next 6 years
 Those with A1c > 6% should be considered
at very high risk of subsequent diabetes
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A1c Testing
The past:
 Reflex when serum glucose, urine
glucose, fructosamine are elevated
or . . .
 History of Diabetes
Current:
 Screening – Age 40 and up
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ExamOne A1c Summary
 Insurance pilot studies: 8-36% of those
with: normal serum glucose, fructosamine, and
negative urine glucose have elevations of A1c
 21 of top 25 volume companies are doing
some screening with A1c
 Through March 2012 (YTD) – 49% of all
ExamOne bloods had an A1c performed
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A1c Summary
 A1c screening is viable option for identifying
undiagnosed diabetics
 A1c associated with CV events & death
 We are missing significant numbers of
elevations using current reflex criteria
Glucose < 60
29% A1c > 6.1
Glucose 60 – 109 31% A1c > 6.1
Antiselection?
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What If You Could…
 Reduce underwriting requirements such
as APS
 Reduce claims
 More accurately assess risk
 Underwrite with more confidence
Confidential and Proprietary - Do not Copy or Distribute. Quest, Quest Diagnostics, ExamOne, any associated logos, and all associated Quest
Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics. All third party marks - ® and ™ - are the property of their
respective owners. © 2011 Quest Diagnostics Incorporated. All rights reserved.
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Risk IQ: What is it?
 Data analysis tool to help u/w gauge mortality risk
 Millions of applicant lives from 2001 to today
 SS death master file utilized with results to analyze
>144 variables: Multivariate analysis
 Percentile ranking of the mortality risk associated
with an applicant’s specific laboratory and physical
measurement profile
 Each applicant is ranked relative to his or her peers
–Members of the same age and gender group
 Mortality runs from less than half that expected for
low Risk IQs to more than 10x for Risk IQs of 99
0
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99
Confidential – Do not copy or distribute | 17
Contributors to Increased Risk
45-Year-Old Male
Non-Smokers
63-Year-Old Male
Non-Smokers
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Composite Hazard
Risk IQ Hazard by Cause of Death
All Applicants
250
150
100
50
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Confidential and Proprietary - Do not Copy or Distribute. Quest, Quest Diagnostics, ExamOne, any associated logos, and all associated Quest
Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics. All third party marks - ® and ™ - are the property of their
respective owners. © 2011 Quest Diagnostics Incorporated. All rights reserved.
LABORATORY TESTING
for the “mature” age group
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What is “old?”
 1936 - life expectancy was 61; Social
Security Administration used age 65
 2008 - average life expectancy
is 78.7 years
 Calendar vs. biological
www.cdc.gov
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Feisty vs. Frail
There can be a big difference in health and
expected mortality between two elderly
individuals that are the same age
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What starts the downhill trend?
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Atherosclerosis
Anemia
Obesity
Cardiovascular disease
Chronic renal insufficiency
Depression
Cognitive impairment
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Laboratory tests – older age
 Microalbumin
 Serum creatinine
 Serum albumin and cholesterol
 Hemoglobin
 NT-proBNP
 Cystatin C
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Hemoglobin
 The iron-containing oxygen-transport
protein in the red blood cells
 Hemoglobin transports oxygen from the
lungs to the rest of the body, such as to
the muscles, where it releases
the oxygen for cell use
 Purple top - stability
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Prevalence of Anemia
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Anemia
Causes of anemia
 Chronic disease
 Iron deficiency
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Renal insufficiency
Cancer
Inflammatory disorders
Chronic infections
Acute, chronic hepatitis
Myelodysplastic syndrome
Medication, alcohol
Nutritional deficiency
2x risk of physical decline
National Health And Nutrition Examination Survey 2009 (NHANES)
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Anemia
Consequences of anemia in elderly
 Diminished cognitive function
 Increased frailty
 Poor exercise performance
 Risk of developing dementia
 Decreased mobility
 Increased risk of recurrent falls
 Lower bone density and skeletal muscle density
 Increased risk of depression
 Elevated risk of hospitalization and of complications
during hospitalization
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Hemoglobin Study in Elderly
 Compared association of Hgb concentration and
anemia status with subsequent death over time
in elderly
 5,888 individuals age 65 and up
 1989 - 1993
 After 11.2 years of follow-up, lower hemoglobin
concentrations were associated with increased
mortality risk, independent of many potentially
confounding factors
Arch Intern Med. 2005; 165: 2214-2220
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Kaplan-Meier curve of survival over 11.2 years by anemia status
(based on World Health Organization criteria)
Zakai, N. A. et al. Arch Intern Med 2005;165:2214-2220.
Copyright restrictions may apply.
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Anemia in the Elderly
Extremely common problem:
associated with increased mortality
and poorer health-related quality of
life, regardless of underlying cause
of low hemoglobin
2007 - 36M age > 65
2050 - 85M age > 65
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Heart Disease - NT-proBNP
 5.3 million afflicted CHF in U.S. ($40 billion)
 Each year, another 550,000 people
diagnosed for the first time
 Hospital discharges for HF rose from 400,000
in 1979 to 1,084,000 in 2005; increase
of 171 percent (NHDS and NHLBI; AHA computation)
 People age 40 and > have a 1 in 5
chance of developing CHF in their
lifetime;
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Congestive Heart Failure
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Congestive Heart Failure
 CHF and Underwriting
Symptoms Nonspecific
– Shortness of breath
– Swollen feet and ankles
But echocardiograms too expensive and
inconvenient to use routinely
 Clinical CHF – 50% or > mortality at 5 yrs
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Natriuretic Peptides NT-proBNP
 Regulate homeostasis of salt and water
 Cardiac ventricles: ProBNP BNP NT-proBNP
 Dilates blood vessels – reduces fluid load
and pressure on heart
 Elevated by increased Ventricular tension,
CAD, Atrial Fibrillation
 More stable than BNP
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NT-proBNP - Mortality studies
Kragelund Study
 1034 patients –stable angina and angiographicallyconfirmed disease
 9 year follow-up – 288 deaths (28%)
 Significantly lower NT-proBNP levels in survivors
 Independent of hypertension, smoking, high
cholesterol
 By adding NT-proBNP – enhance capacity to identify
high risk individuals
 Normal NT-proBNP values rule out CV disease
Kragelund, C. et al. N Engl J Med 2005;352:666-675
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Overall survival among patients with stable coronary
artery disease with progressive mortality associated
with increasing levels of NT-pro-BNP
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NT-proBNP – Mortality studies
Rancho Bernardo Study
 957 persons, mean age 77, followed for
nearly 7 years
 Subset free of CV disease; elevated
NT-proBNP; mortality
3.5 fold increase
 NT-proBNP turned out to be a superior mortality
marker than troponin T, smoking, diabetes,
fasting blood sugar and all lipid parameters
Journal of the American College of Cardiology. 52(2008):450
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NT-proBNP – Mortality Study
CV Risk Study in Elderly
 2975 community dwelling older adults free of HF
 NT-proBNP measured baseline – then 2 to 3 years
Results:
 NT-proBNP levels in highest quintiles (267.7pg/ml)
independently associated with greater risks of HF
 Inflection point of elevated risk: NT-proBNP 190 pg/ml
Conclusions: NT-proBNP levels independently predict
heart failure and cardiovascular death in older adults.
NT-proBNP levels frequently change over time, and these
fluctuations reflect dynamic changes in cardiovascular risk
J Am Coll Cardiol, 2010; 55:441-450
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NT-proBNP
According to the Journal of the American Medical
Association “elevated levels of NT-ProBNP
predict cardiovascular morbidity and mortality,
independent of other prognostic markers, and
identify at risk individuals even in the absence of
systolic or diastolic dysfunction by
echocardiography”
ExamOne – 15 out of 20 largest clients
screening
125 pg/ml < age 75 - 17% elevated
450 pg/ml age 75 or older - 14% elevated
JAMA. 2007;297(2):169
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OLDER AGE TESTING NT-proBNP
 Consider screening for age > 60 and
higher face amounts
 Order for shortness of breath, swelling
of feet and legs
 Order for known or suspected
Coronary Disease
 Excellent marker for
preferred risk for elderly
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Kidney Disease - ESRD
 Prevalence (2004): 472,099 U.S. residents
were under treatment as of the end of the
calendar year.
 Resulting from these primary diseases:
Diabetes: 172,938
Hypertension: 114,481
Glomerulonephritis: 77,121
Cystic kidney: 21,397
All other: 86,162
 Incidence (2004): 104,364 U.S. residents
were new beneficiaries of treatment
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Kidney Disease - ESRD
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OLDER AGE TESTING
 Creatinine levels underestimate
reduction of kidney function in the
elderly
– Not sensitive to small changes
– Less muscle mass, less creatine and its
metabolite creatinine
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Cystatin C – What is it?
 Protease inhibitor produced by nearly all
human cells; filtered by the glomerulus
 Reabsorbed; broken down by the renal tubule
 Should remain at steady level in blood
 Independent of age, gender, race or lean
muscle mass
 Superior to serum creatinine/GFR
 Indicator of risk of heart failure
and death
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Cystatin C – Morality Study
 Analysis of 4637 participants aged 65 or
older at inception
 Followed for median 7.4 years
 Population was divided into Fifths (Quintiles)
based on laboratory results
 Compare Cystatin C, creatinine and GFR as
predictors for mortality
 Cystatin C – stronger predictor of death and
risk of CV events
NEJM 2005;352:2049-60
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Mortality from All Causes According to Quintile of Measures of Renal Function
Cystatin C categories – nearly linearly associated with risk of death
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Resources
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Ahmed N, et al. Am J Med 2007;120, 748-753. Frailty: An emerging
geriatric syndrome
Arch Intern Med. 2005; 165: 2214-2220
Torpy, Janet M, MD, et al. JAMA, November 8, 2006 – Vol 296, No. 18
McQueen, M.P. Wall Street Journal, March 6, 2007 – D1 Life Insurers
Expand Offerings for the Elderly
Archives of Internal Medicine. Monday 14th November, 2005
AHA at http://www.americanheart.org
Mayo Clin Proc. 2007;82(8):958-966
Manini TM, Everhart JE, Patel KV, et al. JAMA 2006;296:171-179
Weber M, Dill T, Arnold R, et al. Am Heart J 2004;148:612-620
NEJM 2005;352:2049-60
Kragelund, C. et al. N Engl J Med 2005;352:666-675
Izaks, G. J. et al. JAMA 1999;281:1714-1717
Am Fam Physician 2000;62:1565-72
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The end!
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