Cohort 10year Atherosclerotic Cardiovascular Disease Risk Equations Paul Muntner Lisandro D Colantonio Mary Cushman David C Goff Jr George Howard Virginia J Howard ID: 774857
Download Presentation The PPT/PDF document " Validation of the Pooled " is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Validation of the Pooled Cohort 10-year Atherosclerotic Cardiovascular Disease Risk Equations
Paul Muntner, Lisandro D Colantonio, Mary Cushman, David C Goff Jr., George Howard, Virginia J Howard, Brett Kissela, Emily B Levitan, Donald M. Lloyd-Jones, Monika M Safford University of Alabama at Birmingham, University of Vermont, University of Colorado, University of Cincinnati, Northwestern University.
On behalf of REGARDS and REGARDS-MIThis study was supported by U01 NS041588 (NINDS) and R01 HL080477, K24 HL111154 (NHLBI)
Slide2Disclosures
Drs. Muntner, Howard, Levitan, and Safford have received grant funding from Amgen Inc. for work unrelated to this presentation.
Dr. Muntner has served on an advisory board for Amgen Inc.
Drs. Cushman and Safford have served as consultants for
DiaDexus
.
Slide3Background
In 2013, the American College of Cardiology / American Heart Association (ACC/AHA) published a guideline for the estimation of atherosclerotic cardiovascular disease (ASCVD) risk.This guideline included the development of the Pooled Cohort risk equations for estimating 10-year risk for incident ASCVD. These equations can be used to guide the decision to initiate statins for people 40-79 years without ASCVD or diabetes and with LDL-C of 70 to 189 mg/dL – “clinically relevant population”. Consideration of statin treatment is recommended for adults with a 10-year ASCVD risk ≥ 7.5%
Goff,
J Am
Coll
Cardiol
2013; Stone
, J Am
Coll
Cardiol
2013
Slide4Background
The Pooled Cohort risk equations were developed using data from several studies conducted before 2000. Marked declines in ASCVD incidence have occurred over the past 2 decades.These equations were reported to over-estimate risk in analyses of the Women’s Health Study, Women’s Health Initiative and the Physicians Health Study.Prior analyses: Did not focus on the population for whom the equations may inform a discussion to initiate statins.Did not have surveillance components
Rosamond, Circulation 2012;
Kleindorfer
, Stroke 2010;
Ridker
, Lancet 2013
Slide5Objective
To
evaluate the validity of
the Pooled Cohort risk equations in a contemporary US
population for whom the
equations are intended to inform discussions about initiating
statins.
We assessed
Calibration:
Do the Pooled Cohort risk equations
accurately
estimate
the
observed absolute risk level?
Discrimination:
Are
individuals with higher predicted risk more likely to have
events?
Slide6Methods
We used data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study: Population-based cohort of 30,239 blacks and whites ≥45 years of age residing in 48 contiguous US states and Washington, DCEnrolled between January 2003 and October 2007. All participants provided written informed consent.Primary analyses focused on the “clinically relevant population” Those for whom 10-year ASCVD risk can be used to guide decision-making We excluded participants taking statins, with ASCVD or diabetes, an LDL-C ≥ 190 mg/dL or < 70 mg/dL, and 80 years of age or older.
Howard,
Neuroepidemiology
2005; Safford, JAMA 2012
Slide7Methods – Statistical Methods
We calculated 10-year ASCVD
predicted
risk at
baseline using
the race-sex specific
Pooled Cohort risk
equations.
Participants were stratified by
decile
of 10-year predicted risk.
Calibration
was analyzed
by comparing
observed and predicted
number of ASCVD
events at 5
years:
We used
a modified
Hosmer-Lemeshow
test.
A chi-square >20 or p-value <0.05 indicates poor calibration.
Discrimination
was
analyzed:
We used the
C-index
.
A
C-index
between 0.70 and 0.80 is
good
and ≥0.80
is excellent.
Slide8Pooled Cohort risk equations
S0(t) at 5 years*S0(t) at 10 yearsMean scoreBlack women0.981940.953386.61White women0.988980.9665-29.18Black men0.957260.895419.54White men0.962540.914461.18
* Personal communication (Coady, S).
Goff, et al. Circulation 2013
Individual score calculation is based on:AgeTotal cholesterolHDL cholesterolSystolic blood pressureUse of antihypertensive medicationCurrent smokerDiabetes
HDL: high-density lipoprotein
Slide9Methods – Two sets of outcomes were evaluated
ASCVD outcomes – Non-fatal myocardial infarction, CHD death or non-fatal or fatal stroke.Adjudicated outcomes - Participant were contacted every 6 months and self-reported events were adjudicated. Surveillance outcomes - Medicare claims were searched for myocardial infarction and stroke events:Limited to participants 65 years of age and older.Medicare Part A coverage requiredOutcomes identified using validated algorithms.Outcomes were available through December 31, 2010.
Kiyota
, Am Heart J 2004,
Tirschwell
, Stroke 2002
Slide10Flowchart of participants included in the analysis
†
Defined
by use of
digoxin.
‡
Or non-HDL-C of 100 -
219 mg/
dL
for those without
a valid LDL-C
measurement.
Slide11Baseline characteristics of participants
Clinically relevant population
(n=10,997)
Medicare-linked
population
(n=3,333)
Age (years), mean (SD)
62
(
8)
71
(
4)
Blacks, n (%)
4,132 (
38)
1,095 (
33)
Men, n (%)
4,480 (
41)
1,476 (
44)
Current smoking, n (%)
1,626 (
15)
348 (10)
SBP (mmHg), mean (SD)
124.8 (
16)
128.3 (
16)
Antihypertensive
med,
n (%)
4,134 (
38)
1,491 (
45)
Total-C
(mg/
dL
), mean (SD)
203
(
31)
202
(
31)
HDL-C
(mg/
dL
), mean (SD)
54
(
17)
55
(
17)
The
clinically relevant population included those not taking statins, without ASCVD or diabetes, and with LDL-C 70 to 189 mg/
dL
.
SD: standard deviation; SBP
: systolic blood pressure;
HDL
: high density lipoprotein.
Slide12Calibration – Clinically relevant population
Slide13Results – Calibration and discrimination in the clinically relevant population
Events / person-years
Events in 5-years
5-year incidence
rate
*
Discrimination
Observed
†
Predicted
Observed
†
(
95% CI)
Predicted
C-index
(95% CI)
10-year predicted risk
Clinically relevant
population
0.72
(0.70-0.75)
<5%
28 / 14,816
32
33
1.9 (1.3-2.7)
1.9
5% to <7.5%
32 / 6,866
38
38
4.8 (3.4-6.7)
4.8
7.5% to <10%
34 / 5,853
41
46
6.1 (4.4-8.6)
6.9
≥10%
244 / 19,946
278
350
12.0 (10.6-13.6)
15.1
REGARDS participants without diabetes, with LDL-C 70 to 189 mg/
dL
‡ who were not taking statins are included in this table.
95% CI: 95% confidence interval. HDL-C: high density lipoprotein cholesterol; KM: Kaplan-Meier; LDL-C: low density lipoprotein cholesterol;
REGARDS:
REasons
for Geographic And Racial Differences in Stroke.
* Per 1,000 person-years.
† Kaplan-Meier adjusted.
‡ Or non-HDL-C of 100 - 219 mg/
dL
for those without a valid LDL-C measurement.
Slide14Calibration – REGARDS Medicare-linked population
Slide15Results - Calibration and discrimination for REGARDS Medicare-linked population
Events / person-years
Events in 5-years
5-year incidence
rate*
Discrimination
Observed
†
Predicted
Observed
†
(
95% CI)
Predicted
C-index
(95% CI)
10-year
predicted risk
Medicare linked
participants
0.67
(0.64-0.71)
5% to <7.5%
(Suppressed
)
9
7
5.3 (2.8-10.1)
4.0
7.5% to <10%
(
Suppressed)
15
12
7.9 (4.6-13.5)
6.4
≥10%
212 / 11,754
226
215
17.4 (15.3-19.8)
16.4
REGARDS participants without diabetes, with LDL-C 70 to 189 mg/
dL
‡ who were not taking statins are included in this table.
Suppressed – Medicare data are not presented in these cells due to a small sample size.
95% CI: 95% confidence interval. HDL-C: high density lipoprotein cholesterol; KM: Kaplan-Meier; LDL-C: low density lipoprotein cholesterol;
REGARDS:
REasons
for Geographic And Racial Differences in Stroke.
* Per 1,000 person-years.
† Kaplan-Meier adjusted.
‡ Or non-HDL-C of 100 - 219 mg/
dL
for those without a valid LDL-C measurement.
Slide16Conclusion
In this cohort of US adults for whom statin initiation
may be considered
based on
10-year predicted ASCVD risk:
Observed
and predicted 5-year ASCVD risks were similar indicating that these risk equations were well
calibrated.
Discrimination was moderate/good.
Previous results of over-estimation of ASCVD risk are likely due
to incomplete capture of ASCVD events and inclusion of participants taking statins
.
The current study supports the validity of the Pooled Cohort risk equations to inform clinical management decisions.
Slide17P Muntner and coauthors
Validation of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations
Published online March 29, 2014
Available at www.jama.com and also at mobile.jamanetwork.com
jamanetwork.com