Title: The Associations of Fibroblast Growth Factor 23 and Uncarboxylated Matrix Gla Protein With Mortality in Coronary Artery Disease: The Heart and Soul Study
Topic: General Cardiology
Date Posted: 6/3/2010
Author(s): Parker BD, Schurgers LJ, Brandenburg VM, et al.
Citation: Ann Intern Med 2010;152:640-648.
Clinical Trial: No
Study Question: Is there an association between circulating levels of fibroblast growth factor 23 (FGF23), uncarboxylated matrix Gla protein (ucMGP), and fetuin-A with mortality and cardiovascular disease (CVD) events?
Methods: Blood levels of FGF23, ucMGP, and fetuin-A were measured in 833 outpatients with stable coronary artery disease (CAD). Participants were followed for a median of 6 years for mortality and CVD events.
Results: A total of 220 participants died and 182 had CVD events during the study period. Compared with participants with FGF23 levels in the lowest tertile, those in the highest tertile had twofold greater risk for mortality (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.43-3.24) and CVD events (HR, 1.83; CI, 1.15-2.91) after adjustment for traditional CVD risk factors, C-reactive protein levels, and kidney function. The highest ucMGP tertile was associated with lower mortality risk (HR, 0.48; CI, 0.31-0.75) and showed a nonsignificant trend toward lower CVD event risk by tertile analysis (HR, 0.65; CI, 0.40-1.05)—an association that was significant when modeled continuously (p = 0.029). No significant association of fetuin-A with mortality (HR, 0.84; CI, 0.55-1.27) or CVD events (HR, 0.99; CI, 0.64-1.55) was observed.
Conclusions: In outpatients with stable CAD, higher FGF23 and lower ucMGP levels are independently associated with mortality and CVD events.
Perspective: Preclinical and clinical studies have suggested that factors involved in regulating calcium metabolism may affect arterial calcification and progression of vascular disease. This study strongly supports these previous observations with regard to FGF23 and ucMGP, and suggests that processes involved in tissue mineral deposition may serve as therapeutic targets for prevention of CVD. Additional mechanistic and clinical studies are necessary to confirm these intriguing findings. Daniel T. Eitzman, M.D., F.A.C.C.
Title: Association Between Use of Bleeding Avoidance Strategies and Risk of Periprocedural Bleeding Among Patients Undergoing Percutaneous Coronary Intervention
Topic: Interventional Cardiology
Date Posted: 6/1/2010 4:00:00 PM
Author(s): Marso SP, Amin AP, House JA, et al.
Citation: JAMA 2010;303:2156-2164.
Clinical Trial: No
Study Question: What is the association between the use of two bleeding avoidance strategies, vascular closure devices and bivalirudin, and post–percutaneous coronary intervention (PCI) bleeding rates in a nationally representative PCI population?
Methods: This was an analysis of data from 1,522,935 patients undergoing PCI procedures performed at 955 US hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry from January 1, 2004, through September 30, 2008. This registry is jointly sponsored by the American College of Cardiology (ACC) and the Society for Cardiovascular Angiography and Interventions. The primary outcome was periprocedural bleeding.
Results: Bleeding occurred in 30,654 patients (2%). Manual compression, vascular closure devices, bivalirudin, or vascular closure devices plus bivalirudin were used in 35%, 24%, 23%, and 18% of patients, respectively. Bleeding events were reported in 2.8% of patients who received manual compression, compared with 2.1%, 1.6%, and 0.9% of patients receiving vascular closure devices, bivalirudin, and both strategies, respectively (p < 0.001). Bleeding rates differed by preprocedural risk assessed with the NCDR bleeding risk model (low risk, 0.72%; intermediate risk, 1.73%; high risk, 4.69%). In high-risk patients, use of both strategies was associated with lower bleeding rates (manual compression, 6.1%; vascular closure devices, 4.6%; bivalirudin, 3.8%; vascular closure devices plus bivalirudin, 2.3%; p < 0.001). This association persisted following adjustment using a propensity-matched and site-controlled model. Use of both strategies was used least often in high-risk patients (14.4% vs. 21.0% in low-risk patients, p < 0.001).
Conclusions: The authors concluded that vascular closure devices and bivalirudin were associated with significantly lower bleeding rates, particularly among patients at greatest risk for bleeding.
Perspective: In this large, national PCI registry, the use of vascular closure devices and bivalirudin was associated with significantly lower rates of periprocedural bleeding. However, there was an apparent risk-treatment paradox, whereby patients at greatest risk of bleeding were least likely to receive a bleeding avoidance strategy. These findings emphasize the need for additional research to better understand why higher-risk patients are least likely to receive bleeding avoidance strategies but also suggest the need to test interventions to overcome the risk-treatment paradox, such as directing bleeding avoidance strategies to high-risk patients by providing preprocedural estimates of post-PCI bleeding. Quality improvement tools developed by the ACC NCDR are already helping with rapid adoption of bleeding avoidance and other quality initiative strategies by the cardiovascular community. Debabrata Mukherjee, M.D., F.A.C.C.