Brachial flowmediated dilation predicts incident cardiovascular events in older adults: The Cardiova

1
Brachial flow-mediated dilation predicts incident
cardiovascular events in older adults The
Cardiovascular Health Study.

• Joseph Yeboah MD
• John R. Crouse III MD
• Fang-Chi Hsu PhD
• Gregory L. Burke MD MS
• David M. Herrington MD MHS
• Wake Forest University School of Medicine
• ( Circulation 20071152390-7)

2
Endothelial function and FMD

• Vascular endothelium plays a central role in
  regulating
• Vasomotor tone
• Thrombosis
• Platelet adhesion
• Endothelial function is a measure of vascular
  health.
• Brachial flow-mediated dilation(FMD) is a
  validated non-invasive measure of endothelial
  function.

3
Brachial Scanning Procedure
4
(No Transcript)
5
Brachial FMD and CVD

• Brachial FMD has been associated with
  cardiovascular risk factors
• Cardio-protective therapies have been associated
  with improvement of brachial FMD
• Data on the association of brachial FMD and CVD
  events have mixed results.

6
Prior studies of FMD and CVD
FMD
FMD
FMD
FMD
FMD
FMD
7
Limitations in prior studies

• Relatively young participants
• Small sample sizes
• Highly selected participants

8
Cardiovascular Health Study

• NHLBI- funded observational study of risk factors
  for cardiovascular disease in adults 65 years and
  older
• CHS sites
• University of California Davis
• The John Hopkins University
• Wake Forest University School of Medicine
• University of Pittsburg
• Brachial FMD ancillary study started on the tenth
  clinic visit.

9
CHS brachial FMD ancillary cohort
5,888 Adults 65 years
3032 Adults Contacted on tenth visit
130 excluded Mastectomy, Raynauds etc
61 refused to enroll 49 discontinued scan
2791 Adults Brachial FMD ancillary study
5 years of Follow-up
10
Hypothesis

• Endothelial function measured by brachial
  flow-mediated dilation is a predictor of incident
  cardiovascular events in older adults.
• Defined CVD event CHD death, myocardial
  infarction, Stroke, Congestive heart
  failure,CABG, Angioplasty or Claudication
• Five years of follow-up

11
Statistical analysis

• Kaplan-Meier analysis and Log rank tests
• Dichotomized FMD by the median
• Cox proportional hazard analysis ( p 0.20)
• Adjust for confounders age, gender,
  diabetes,hypertension, statin use,smoking, total
  cholesterol,baseline CVD status
• Subgroup analysis based on CVD status at baseline
• Two-tailed p 0.05
• SAS version 9.1(SAS institute Cary, NC).

12
Baseline Characteristics
TABLE 1 Characteristics of subjects at baseline
in the Brachial FMD ancillary study
13
Kaplan-Meier curves of even-freesurvival
rates(N2791)
14
Multivariate predictors of composite outcome
(N2791)
HR0.91
15
Predictive value of FMD for outcomes in
multivariate Cox model
HR0.91
16
Multivariate predictors of compositeoutcome for
the CVD free subset(N2125)
HR0.92
17
Multivariate predictors of composite outcome in
subset with prior CVD (N666)
HR0.84
18
ROC curves of full model (model 1) and full model
without FMD(model 2)
Legend
19
Conclusions

• Brachial FMD is an independent predictor of
  incident cardiovascular events in older adults.
• Brachial FMD added very little to the predictive
  value of traditional cardiovascular risk factors
  for future cardiovascular events.

20
Study Limitations

• Residual confounding
• Smooth muscle dysfunction (endothelial-
  independent vasodilation) not evaluated in this
  cohort
• Study may not apply to younger adults
• New risk markers such CRP, IL-6 not
  measured/included in the multivariate model

21
Future studies

• Studies in younger and more diverse population
  (MESA).
• Identify sex and age-specific normal ranges
• Interventions designed to improve endothelial
  function (clinical trials).
• FMD targeted therapy and CVD outcomes

22
Thank You

• NHLBI
• CHS investigators
• CHS data managers
• CHS participants
• Statistical Support
• Fang-Chi Hsu PhD
• Georgia Saylor

• Mentors
• John R Crouse III MD
• Gregory L Burke MD
• David M Herrington MD