Hormone Replacement Therapy: Friend or Foe?Hormone Replacement Therapy: Friend or Foe?A Retrospective Study for Prospective ResearchA Retrospective Study for Prospective Research

Research Alliance in Math and ScienceComputational Sciences and Engineering, Oak Ridge National Laboratory

Mentor: Kara L. Kruse

http://wiki.ornl.gov/sites/rams/j_gauld

Acknowledgement of contributions to research:Acknowledgement of contributions to research: Oak Ridge National Laboratory: Sara WezenskyOak Ridge National Laboratory: Sara Wezensky University of Tennessee Medical Center: Oscar Grandas, MD, Fernando Aycinena, MD, Melinda Klar, RN.University of Tennessee Medical Center: Oscar Grandas, MD, Fernando Aycinena, MD, Melinda Klar, RN.

Results and ConclusionsResults and Conclusions

Future ResearchFuture Research

Femoropopliteal Bypass and Femoropopliteal Bypass and Intimal HyperplasiaIntimal Hyperplasia

The Research Alliance in Math and Science program is sponsored by the Office of Advanced Scientific Computing Research, U.S. Department of Energy. The work was performed at the Oak Ridge National Laboratory which is managed by UT-Battelle, LLC under Contract No. De-AC05-00OR22725. This work has been authored by a contractor of the U.S. Government, accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes.

What is the problem?What is the problem?

Jillian GauldQueen’s University

• Intimal Hyperplasia (IH) - universal response of an artery to injury

• Procedures such as fem-pop bypass respond with an influx of cells from the media to the intima

• IH causes restenosis, or post-surgical narrowing of the artery, in 1/3 of cases

• Atherosclerosis: hardening of arterial vessels characterized by chronic inflammation and deposition of fatty plaques

• Risk factors include diabetes, smoking, high blood pressure, and obesity

• Treatments include statin drugs, diets, lifestyle changes, and surgical interventions such as angioplasty and femoropopliteal (fem-pop) bypass

The Role of Hormone The Role of Hormone Replacement TherapyReplacement Therapy

• Post-menopausal women on hormone replacement therapy (HRT) have more complications after fem-pop bypass than post-menopausal women without HRT

• This clinical observation contradicts the accepted theory that estrogen has vascular protective effects

What Did I Work On?What Did I Work On?• Determined statistical significance of numerous

medical risk factors in relation to graft patency and intimal hyperplasia

• Used appropriate tests to find correlations between variables, including use of hormone replacement therapy, diabetes, and high blood pressure

• Utilized Kaplan-Meier survival analysis, chi-square test for independence, student’s t-test, mosaic plot, scatter plot matrices

• Used JMP software for statistical analyses

Kaplan-Meier analysis- patients on hormone replacement therapy have on average lower primary patency rates than patients not on HRT

Chi-square test for independence: few significant p-values were found

Reasons- small sample size: 68 patients

Significance found in relationship between mental and mood disorders and graft patency

Current study designed to assist in future prospective studies on HRT and graft patency

Help define parameters for future study: larger sample size, attention to mental and mood disorders

                   

  

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Surv

ivin

g

1 2 3 4 5 6 7 8 9 10

Time (years)

0

1

Survival Plot

Time to event: Time (years)

Censored by Column 2

Censor Code 1

Grouped by Column 4

Frequency counts from Column 3

0

1

Combined

Group

12

34

46

Number

failed

4

13

17

Number

censored

3.85

4.88781

4.72722

Mean

Biased

Biased

Biased

0.60821

0.47873

0.40538

Std Error

Summary

0

1

Combined

Group

3

5

5

Median Time

1

3

3

Lower95%

7

7

5

Upper95%

3

1

1

25% Failures

7

9

9

75% Failures

Quantiles

Log-Rank

Wilcoxon

Test

0.3170

0.4032

ChiSquare

1

1

DF

0.5734

0.5255

Prob>ChiSq

Tests Between Groups

0.0000

1.0000

3.0000

5.0000

7.0000

10.0000

Time (years)

1.0000

0.7500

0.3750

0.3000

0.2000

0.2000

Survival

0.0000

0.2500

0.6250

0.7000

0.8000

0.8000

Failure

0.0000

0.1083

0.1210

0.1178

0.1133

0.1133

SurvStdErr

0

4

6

1

1

0

Number

failed

0

0

1

1

1

1

Number

censored

16

16

12

5

3

1

At Risk

0

0.0000

1.0000

3.0000

5.0000

7.0000

9.0000

10.0000

Time (years)

1.0000

0.7234

0.5532

0.3772

0.2901

0.1451

0.1451

Survival

0.0000

0.2766

0.4468

0.6228

0.7099

0.8549

0.8549

Failure

0.0000

0.0652

0.0725

0.0739

0.0719

0.0693

0.0693

SurvStdErr

0

13

8

7

3

3

0

Number

failed

0

0

4

2

4

2

1

Number

censored

47

47

34

22

13

6

1

At Risk

1

0.0000

1.0000

3.0000

5.0000

7.0000

9.0000

10.0000

Time (years)

1.0000

0.7302

0.5079

0.3574

0.2681

0.1532

0.1532

Survival

0.0000

0.2698

0.4921

0.6426

0.7319

0.8468

0.8468

Failure

0.0000

0.0559

0.0630

0.0629

0.0610

0.0611

0.0611

SurvStdErr

0

17

14

8

4

3

0

Number

failed

0

0

5

3

5

2

2

Number

censored

63

63

46

27

16

7

2

At Risk

Combined

Product-Limit Survival Fit

http://supermarkethq.com/product/1953

Primary Graft Patency Rates

Non-HRT Patients HRT Patients

Mosaic Plot showing patency rates divided by the patients’ use of HRT

Demonstrates lower primary patency rates, and increased assisted patency in HRT patients

%

Restenosis typically occurs in the distal astomosis, where the graft rejoins the artery. The toe, heel, and bed of the distal astomosis are the most common sites for intimal hyperplasia.

Pat

ency

0.00

0.25

0.50

0.75

1.00

no yes

HRT?

primary

primary assisted

secondary

failure

death

Mosaic Plot

HR

T?

no

yes

27

39.71

79.41

52.94

8

11.76

57.14

15.69

5

7.35

71.43

9.80

6

8.82

75.00

11.76

5

7.35

100.00

9.80

7

10.29

20.59

41.18

6

8.82

42.86

35.29

2

2.94

28.57

11.76

2

2.94

25.00

11.76

0

0.00

0.00

0.00

51

75.00

17

25.00

34

50.00

14

20.59

7

10.29

8

11.76

5

7.35

68

Patency

Count

Total %

Col %

Row %

primary primary as

sisted

secondary failure death

Contingency Table

68

N

4

DF

2.7042167

-LogLike

0.0295

RSquare (U)

Likelihood Ratio

Pearson

Test

5.408

4.448

ChiSquare

0.2479

0.3487

Prob>ChiSq

Warning: 20% of cells have expected count less than 5, ChiSquare

suspect.

Tests

Contingency Analysis of Patency By HRT?

Kaplan-Meier analysis: cumulative primary patency rate over a ten year period

Shows lower primary patency rates in HRT patients

Chi-square analysis of mental and mood disorders vs. graft patency

P value= .0178

Statistical AnalysesStatistical Analyses

http://www.irishscientist.ie

Normal Artery Intimal Hyperplasia Present

Lumen

IntimaIntima

Lumen

In healthy vessels, the intima is only about one cell layer thick. When intimal hyperplasia occurs, smooth muscle cells move from the media to the intima. This occludes the lumen, which decreases arterial blood flow.

CountExpected

Primary PrimaryAssisted

Secondary Total

No 2118.3492

37.55556

108.09524

34

Yes 1315.6508

116.44444

56.90476

29

Total 34 14 15 63

University of Tennessee Graduate School of Medicine

http://www.wikipedia.org

http://vasculardiseasemanagement.com/

docs/goresupp.pdf