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. Methods and 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.