Vulnerable blood in high risk vascular patients: study design and methods.
BACKGROUND
Basic research suggests that rapid increases in circulating inflammatory and hemostatic blood markers may trigger or indicate impending plaque rupture and coronary thrombosis, resulting in acute ischemic heart disease (IHD) events. However, these associations are not established in humans.


RESULTS
The Biomarker Risk Assessment in Vulnerable Outpatients (BRAVO) Study will determine whether levels of inflammatory and hemostatic biomarkers rapidly increase during the weeks prior to an acute IHD event in people with lower extremity peripheral artery disease (PAD). The BRAVO Study will determine whether biomarker levels measured immediately prior to an IHD event are higher than levels not preceding an IHD event; whether participants who experience an IHD event (cases) have higher biomarker levels immediately prior to the event and higher biomarker levels at each time point leading up to the IHD event than participants without an IHD event (controls); and whether case participants have greater increases in biomarkers during the months leading up to the event than controls. BRAVO enrolled 595 patients with PAD, a population at high risk for acute IHD events. After a baseline visit, participants returned every two months for blood collection, underwent an electrocardiogram to identify new silent myocardial infarctions, and were queried about new hospitalizations since their prior study visit. Mortality data were also collected. Participants were followed prospectively for up to three years.


CONCLUSIONS
BRAVO results will provide important information about the pathophysiology of IHD events and may lead to improved therapies for preventing IHD events in high-risk patients.
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States. Electronic address: mdm608@northwestern.edu.
Mary M
MM
McDermott
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
Philip
P
Greenland
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
Kiang
K
Liu
Stanford University, United States.
Lu
L
Tian
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States.
David
D
Green
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States.
Sanjiv J
SJ
Shah
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
Mark
M
Huffman
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
John
J
Wilkins
Department of Surgery, Feinberg School of Medicine, Northwestern University, United States; Jesse Brown Veterans Affairs Hospital, United States.
Melina
M
Kibbe
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
Yihua
Y
Liao
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
Chiang-Ching
CC
Huang
Department of Surgery, University of Chicago Hospitals, United States.
Christopher
C
Skelly
Department of Surgery, Rush Medical Center, United States.
Chad
C
Jacobs
Department of Surgery, Rush Medical Center, United States.
Walter
W
McCarthy
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States.
Amanda
A
Auerbach
Department of Medicine, Feinberg School of Medicine, Northwestern University, United States; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, United States.
Donald
D
Lloyd-Jones
D015415:Biomarkers; D016022:Case-Control Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D035002:Lower Extremity; D017202:Myocardial Ischemia / Q000503:physiopathology*; D058729:Peripheral Arterial Disease / Q000503:physiopathology*; D012107:Research Design; D012307:Risk Factors; D013927:Thrombosis / Q000503:physiopathology*
D015415:Biomarkers; D018836:Inflammation Mediators
Biomarkers; C reactive protein; Coronary events; Intermittent claudication