Deepa M Gopal1, Martin G Larson2, James L Januzzi3, Susan Cheng4, Anahita Ghorbani5, Kai C Wollert6, Tibor Kempf6, Ralph B D'Agostino2, Joseph F Polak7, Vasan S Ramachandran8, Thomas J Wang9, Jennifer E Ho10. 1. Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 2. Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Department of Mathematics and Statistics, Boston University, Boston, MA; 3. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA; 4. Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; 5. Department of Medicine, Mount Auburn Hospital, Boston, MA; 6. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany; 7. Department of Radiology, Tufts Medical Center, Boston, MA; 8. Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Cardiology and Preventive Medicine and. 9. Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Division of Cardiovascular Medicine, Division of Medicine, Vanderbilt University, Nashville, TN. 10. Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA; Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA; jennifer.ho@bmc.org.
Abstract
BACKGROUND: Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described. METHODS: We measured plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995-1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT >1.5 mm), and mean common carotid artery IMT. We carried out multivariable regressions for carotid measurements vs biomarkers using linear and logistic models; P < 0.0056 was deemed statistically significant. RESULTS: Maximal ICA IMT was significantly associated with plasma GDF-15 [β-estimate 0.04 per 1-U increase in log(GDF-15), SE 0.01, P < 0.0001]. Similarly, the odds of having carotid plaque increased 33% [odds ratio 1.33 per 1-U increase in log(GDF-15), 95% CI 1.20-1.48, P < 0.0001]. In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the 3 biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together. CONCLUSIONS: Increased GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted.
BACKGROUND: Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described. METHODS: We measured plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995-1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT >1.5 mm), and mean common carotid artery IMT. We carried out multivariable regressions for carotid measurements vs biomarkers using linear and logistic models; P < 0.0056 was deemed statistically significant. RESULTS: Maximal ICA IMT was significantly associated with plasma GDF-15 [β-estimate 0.04 per 1-U increase in log(GDF-15), SE 0.01, P < 0.0001]. Similarly, the odds of having carotid plaque increased 33% [odds ratio 1.33 per 1-U increase in log(GDF-15), 95% CI 1.20-1.48, P < 0.0001]. In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the 3 biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together. CONCLUSIONS: Increased GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted.
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