Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial
BACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high‐risk coronary atherosclerotic plaque (HRP). Blood‐based biomarkers that associate with imaging‐defined HRP and predict M...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.026662 |
| _version_ | 1797905032306229248 |
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| author | Robert W. McGarrah Maros Ferencik Stephanie N. Giamberardino Udo Hoffmann Borek Foldyna Julia Karady Geoffrey S. Ginsburg William E. Kraus Pamela S. Douglas Svati H. Shah |
| author_facet | Robert W. McGarrah Maros Ferencik Stephanie N. Giamberardino Udo Hoffmann Borek Foldyna Julia Karady Geoffrey S. Ginsburg William E. Kraus Pamela S. Douglas Svati H. Shah |
| author_sort | Robert W. McGarrah |
| collection | DOAJ |
| description | BACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high‐risk coronary atherosclerotic plaque (HRP). Blood‐based biomarkers that associate with imaging‐defined HRP and predict MACE are lacking. METHODS AND RESULTS Nuclear magnetic resonance–based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP‐associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high‐density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56–0.85]; P<0.001) and medium HDL (OR, 0.84 [95% CI, 0.72–0.98]; P=0.028) and HDL size (OR, 0.82 [95% CI, 0.69–0.96]; P=0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P=0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88–0.94]; P<0.001). CONCLUSIONS Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT01174550 |
| first_indexed | 2024-04-10T09:58:38Z |
| format | Article |
| id | doaj.art-2fbbbca0406f44a5a75a6fcc5d5be5ae |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T09:58:38Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2fbbbca0406f44a5a75a6fcc5d5be5ae2023-02-16T10:55:33ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-01-0112110.1161/JAHA.122.026662Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical TrialRobert W. McGarrah0Maros Ferencik1Stephanie N. Giamberardino2Udo Hoffmann3Borek Foldyna4Julia Karady5Geoffrey S. Ginsburg6William E. Kraus7Pamela S. Douglas8Svati H. Shah9Division of Cardiology, Department of Medicine Duke University School of Medicine Durham NCKnight Cardiovascular Institute Oregon Health and Science University Portland ORDuke Molecular Physiology Institute Duke University School of Medicine Durham NCCardiovascular Imaging Research Center Harvard Medical School–Massachusetts General Hospital Boston MACardiovascular Imaging Research Center Harvard Medical School–Massachusetts General Hospital Boston MACardiovascular Imaging Research Center Harvard Medical School–Massachusetts General Hospital Boston MADuke Center for Applied Genomics & Precision Medicine Duke University School of Medicine Durham NCDivision of Cardiology, Department of Medicine Duke University School of Medicine Durham NCDivision of Cardiology, Department of Medicine Duke University School of Medicine Durham NCDivision of Cardiology, Department of Medicine Duke University School of Medicine Durham NCBACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high‐risk coronary atherosclerotic plaque (HRP). Blood‐based biomarkers that associate with imaging‐defined HRP and predict MACE are lacking. METHODS AND RESULTS Nuclear magnetic resonance–based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP‐associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high‐density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56–0.85]; P<0.001) and medium HDL (OR, 0.84 [95% CI, 0.72–0.98]; P=0.028) and HDL size (OR, 0.82 [95% CI, 0.69–0.96]; P=0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P=0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88–0.94]; P<0.001). CONCLUSIONS Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT01174550https://www.ahajournals.org/doi/10.1161/JAHA.122.026662atherosclerotic plaquebiomarkerscirculating lipoproteinscomputed tomography angiography |
| spellingShingle | Robert W. McGarrah Maros Ferencik Stephanie N. Giamberardino Udo Hoffmann Borek Foldyna Julia Karady Geoffrey S. Ginsburg William E. Kraus Pamela S. Douglas Svati H. Shah Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atherosclerotic plaque biomarkers circulating lipoproteins computed tomography angiography |
| title | Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial |
| title_full | Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial |
| title_fullStr | Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial |
| title_full_unstemmed | Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial |
| title_short | Lipoprotein Subclasses Associated With High‐Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial |
| title_sort | lipoprotein subclasses associated with high risk coronary atherosclerotic plaque insights from the promise clinical trial |
| topic | atherosclerotic plaque biomarkers circulating lipoproteins computed tomography angiography |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.026662 |
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