LongTerm Prognosis Associated with Coronary Calcification

1
Long-Term Prognosis Associated with Coronary
Calcification
Matthew J. Budoff, MD, Leslee J. Shaw, PhD, Sandy
T. Liu, Steven R. Weinstein, Tristen P.
Mosler, Philip H. Tseng, Ferdinand R.
Flores, Tracy Q. Callister, MD, Paolo Raggi, MD,
Daniel S. Berman, MD Published in JACC May 8,
2007
2
Background

• Primary prevention interventions are often
  focused on patients who are classified as
  intermediate-risk or high-risk.
• Stratification into risk groups is helpful but
  can be imprecise when large proportions of
  patients are considered to be at intermediate
  risk.
• Intermediate-risk patients receive cholesterol
  therapy that can range from no therapy to a
  low-density lipoprotein target lt100 mg/dl.

Budoff, et al. JACC 2007 49 1860-70
3
Background

• More effective assessment of coronary heart
  disease (CHD) risk might improve the outcome,
  cost-effectiveness, and safety of primary
  prevention efforts.
• This study aimed to develop risk-adjusted
  multivariable models that include risk factors
  and coronary artery calcium (CAC) scores measured
  with electron-beam tomography (EBT) in
  asymptomatic patients for the prediction of
  all-cause mortality.

Budoff, et al. JACC 2007 49 1860-70
4
Study Design
A cohort of 25,253 consecutive, asymptomatic
individuals referred by their primary physician
for CAC scanning to assess cardiovascular risk
CAC scanning
CAC Score 0 44
CAC Score 1-10 14
CAC Score 11-100 20
CAC Score 101-400 13
CAC Score 401-1000 6
CAC Score gt1000 4
6.8 3 yrs. follow-up
Assessment of all-cause mortality
Budoff, et al. JACC 2007 49 1860-70
5
Clinical Characteristics

• Of the 25,253 patients, the average age was 56
  11 years with more than half being male and
  having a family history of premature coronary
  artery disease (CAD).
• The prevalence of cardiac risk factors was as
  follows family history of premature CAD (58),
  hypercholesterolemia (18), hypertension (15),
  smoking (9), and diabetes (4).

Budoff, et al. JACC 2007 49 1860-70
6
Clinical Characteristics

• In the overall cohort, the average CAC score was
  146 443.
• In subsets with more extensive CAC scores,
  patients were older and had more frequent cardiac
  risk factors. Nearly one-half of the patients
  with CAC scores 1000 were male (plt0.0001),
  hypertensive (plt0.0001), hyperlipidemic
  (plt0.0001), or had a family history of premature
  CAD (p0.052).

Budoff, et al. JACC 2007 49 1860-70
7
Cumulative Survival by Coronary Calcium Score
0 (n11,044)
1.00
1-10 (n3,567)
11-100 (n5,032)
0.95
101-299 (n2,616)
0.90
300-399 (n561)
Cumulative Survival
400-699 (n955)
0.85
700-999 (n514)
0.80
0.75
1,000 (n964)
0.70
0.0
2.0
4.0
6.0
8.0
10.0
12.0
Time to Follow-up (Years)
?21363, plt0.0001 for variable overall and for
each category subset.
Budoff, et al. JACC 2007 49 1860-70
8
Cumulative Survival by the Coronary Calcium
Extent in the Number of Vascular Territories
1.00
0 Vessel (n24,340)
0.95
0.90
1 Vessel (n596)
Cumulative Survival
0.85
2 Vessel (n143)
0.80
3 Vessel (n28)
0.75
Left Main (n146)
0.70
0.0
2.0
4.0
6.0
8.0
10.0
12.0
Time to Follow-up (Years)
Budoff, et al. JACC 2007 49 1860-70
?2251, plt0.0001
9
Cumulative Survival in Patients with No
Significant Calcium Score but with CAC Scores in
the Range of 11-100
1.00
0 Vessel (n19,302)
1 Vessel (n2,563)
0.95
2 Vessel (n1,432)
Cumulative Survival
0.90
3 Vessel (n848)
0.85
3 Vessel LM (n195)
0.80
0.00
2.00
4.00
6.00
8.00
10.00
12.00
Time to Follow-up (Years)
?2182, plt0.0001 for the variable and for each
category subset.
Budoff, et al. JACC 2007 49 1860-70
10
5-year and 12-year Survival from 2 EBT Centers
Nashville and Los Angeles
Survival rate ()
CAC Score
Budoff, et al. JACC 2007 49 1860-70
11
Receiver Operating Characteristics Curves Noting
the Incremental Value of the Total Agatston
Scores Over and Above the Total Number of
Clinical Risk Factors as well as Age.
5a. Incremental Value of Agatston Score over the
Total Number of Cardiac Risk Factors
5b. Incremental Value of Agatston Score over the
Age
1.0
1.0
0.813 (0.794-0.832)
0.813 (0.794-0.832)
0.8
0.8
0.6
0.6
Sensitivity
0.771 (0.750-0.793)
0.611 (0.585-0.637)
0.4
0.4
0.2
0.2
plt0.0001
plt0.0001
0.0
0.0
0.0
0.2
0.4
0.6
0.8
1.0
0.0
0.2
0.4
0.6
0.8
1.0
1 - Specificity
1 - Specificity
ROC analysis for other indivduals risk factors
were less from 0.586 for sex, 0.440 for family
history, 0.573 for smoking, 0.577 fpr diabetes,
0.518 for ethnicity, 0.484 for hyperlipidemia,
and 0.562 for hypertension.
Budoff, et al. JACC 2007 49 1860-70
12
Limitations

• The majority of patients in this study that were
  referred for calcium scanning had cardiac risk
  factors and, therefore, are not representative of
  the general population.
• There was incomplete information related to
  cardiovascular risk factors, because these
  measures were taken by survey rather than being
  measured.
• Information on subsequent therapy after calcium
  scanning is unknown. It was previously
  demonstrated that patients with higher calcium
  burdens are more likely to maintain statin
  therapy over 3-5 years. Therefore, higher
  calcium scores are confounded by improved
  anti-athersoclerotic therapies that would
  possible lower cardiovascular mortality.
• Also, the National Death Index data do not
  include the cause of death. Therefore, this
  studys models include mortality possibly
  unrelated to athersoclerotic disease.

Budoff, et al. JACC 2007 49 1860-70
13
Summary

• This large observational data series shows the
  CAC provides independent incremental information
  in addition to traditional risk factors in the
  prediction of all-cause mortality.
• The results marked a difference in survival at
  6.8 years as the CAC scores increase from 0 to
  gt1,000, which supports the notion that increasing
  coronary atherosclerosis is a strong and
  independent predictor of future cardiac events/
• Furthermore, the study shows that CAC provides
  independent and incremental prognostic
  information in addition to traditional risk
  factors in the prediction of all-cause mortality.

Budoff, et al. JACC 2007 49 1860-70