Cardiovascular disease and Older Age Underwriting

Mike Fulks, M.D. and Robert L. Stout, Ph.D.

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Life’s tough; you work hard.

If you are lucky, you get old and you die.

Dr. Bob

Changes in our view of cardiovascular disease

• Cholesterol and obstructive disease.• Soft vulnerable vs stable calcified? plaque.• Networks of inflammation, Senescence

and chronic illness.• Genetic regulation of CVD risk.

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normal senescent

youthadaptablity

cytokineschemokines

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• Immune surveillance• Detect• Remove

• Remodel

youth

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What makes older ageunderwriting different?• 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

1975-80 Select and Ultimate male tables,

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Why so different?

• 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.

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Prevalence of diseaseby age

20-39 40-59 60-69 70>0.000

0.050

0.100

0.150

0.200

0.250

0.300

0.350

0.400

0.450

0.500

Self-reported disease

heart disease

high bp

diabetes

PR

EV

AL

EN

CE

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What age is “old“?

• 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!

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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

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CRL research

• 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

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CRL results

• 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

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Specific Findings - Cardiovascular

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Cholesterol/HDL mortality

Excess Risk as a % relative to middle 50% band of values

Chol/HDLFemales

<60Males

<60Female

60+Male

60+

2.1-2.5 - - - +25

3.1-4.6 - - - -

4.7-5.2 +50 - - -

5.3-5.8 +50 - - -

6.5-7 +100 +25 +25 -

>9 +150 +75 +50 +25

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Cholesterol HDL ratio

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Blood Pressure

Systolic BP is a potent predictor of cardiovascular and cerebro-vascular risk

SYSTOLIC BP

  < 130 130 - 134 135 - 139 140 - 149 150+

F 20-59 -25 0 50 100 200

M 20-59 -25 0 50 75 100

All 60+ -25 0 25 75 100

Excess mortality based on insurance exam BP’s

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NT-ProBNP

1-100 (ref)

101-200

201-300

301-1000

1001+

100%

300%

500%

700%

900%

1100%

1300%

1500%

1700%

1900%

Age 60-69

NT-ProBNP

Mo

rtal

ity

Rat

io

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Specific Findings - Kidney• 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+

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Proteinuria

• 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

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Proteinuria contd.

<= 0.10 0.11 - 0.20 0.21 - 1.00 1.01+50%

100%

150%

200%

250%

300%

350%

Mortality excluding diabetes and low eGFR, age 60+

Protein/Creatinine Ratio gram/gram

Mo

rta

lity

Ra

tio

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Specific Findings - Cancer

• PSA?

• CEA

• Age and sex-specific evaluation of a wide range of tests including LFTs, cholesterol, albumin, etc

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PSA for Age 60-69

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PSA for Age 80>

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Prevalence of PSA in the insurance population

PSA LEVEL

<4.0 4-9.9 10-20 >20

50-59 97.5 2.2 0.21 0.05

60-69 92.3 6.8 0.73 0.15

70-79 86.2 11.8 1.55 0.38

80> 82.0 14.3 2.63 1.00

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

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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

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Specific Findings - Dementia

• 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.

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Specific Findings – Frailty and unrecognized conditions

• Albumin

• Total Cholesterol

• Combination of other labs and measurements

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Albumin and mortality

Lower albumin

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T. Cholesterol and Mortality

<133

133

145

155

167

187

100%

110%

120%

130%

140%

150%

160%

170%

180%

Mortality Ratio for males age 60+

Cholesterol level from lowest to average

Mo

rta

lity

ra

tio

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A surprise: Age, Alcohol & Mortality

0

50

100

150

200

250

20-29 30-39 40-49 50-59 60-69

DE

AT

HS

DECADE AGE

DEATHS/1000 APPLICANTS

0-10

10.1-50

50.1-100

>100

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Can testing identify an older age preferred risk?

• “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

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<=-40

-39 to -20

-19 to 0

1 to 40

41 to 100

101 to 125

126 to 150

151 to 175

176 to 250

>250

0%

50%

100%

150%

200%

250%

300%

350%

CRL Applicants Tested 1993 to 2005, Followed to 2010

M 20 to 39M 40 to 49M 50 to 59M 60 to 69M 70 to 79M 80 to 89

Mo

rta

lity

Ra

tio

CRL Scoring

Preferred

Standard Substd

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Summary• 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

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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

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