Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial
Background High‐density lipoprotein (HDL) cholesterol has inverse association with cardiovascular disease. HDL possesses anti‐inflammatory properties in vitro, but it is unknown whether this may be protective in individuals with inflammation. Methods and Results The functional capacity of HDL to inh...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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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.119.016507 |
| _version_ | 1819175145558769664 |
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| author | Oluremi N. Ajala Olga V. Demler Yanyan Liu Zareen Farukhi Steven J. Adelman Heidi L. Collins Paul M Ridker Daniel J. Rader Robert J. Glynn Samia Mora |
| author_facet | Oluremi N. Ajala Olga V. Demler Yanyan Liu Zareen Farukhi Steven J. Adelman Heidi L. Collins Paul M Ridker Daniel J. Rader Robert J. Glynn Samia Mora |
| author_sort | Oluremi N. Ajala |
| collection | DOAJ |
| description | Background High‐density lipoprotein (HDL) cholesterol has inverse association with cardiovascular disease. HDL possesses anti‐inflammatory properties in vitro, but it is unknown whether this may be protective in individuals with inflammation. Methods and Results The functional capacity of HDL to inhibit oxidation of oxidized low‐density lipoprotein (ie, the HDL inflammatory index; HII) was measured at baseline and 12 months after random allocation to rosuvastatin or placebo in a nested case‐control study of the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Evaluating Rosuvastatin) trial. There were 517 incident cases of cardiovascular disease and all‐cause mortality compared to 517 age‐ and sex‐matched controls. Multivariable conditional logistic regression was used to examine associations of HII with events. Median baseline HII was 0.54 (interquartile range, 0.50–0.59). Twelve months of rosuvastatin decreased HII by a mean of 5.3% (95% CI, −8.9% to −1.7%; P=0.005) versus 1.3% (95% CI, −6.5% to 4.0%; P=0.63) with placebo (P=0.22 for between‐group difference). HII had a nonlinear relationship with incident events. Compared with the reference group (HII 0.5–1.0) with the lowest event rates, participants with baseline HII ≤0.5 had significantly increased risk of cardiovascular disease/mortality (adjusted hazard ratio, 1.53; 95% CI, 1.06–2.21; P=0.02). Furthermore, there was significant (P=0.002) interaction for HDL particle number with HII, such that having more HDL particles was associated with decreased risk only when HDL was anti‐inflammatory. Conclusions In JUPITER participants recruited on the basis of chronic inflammation, HII was associated with incident cardiovascular disease/mortality, with an optimal anti‐inflammatory HII range between 0.5 and 1.0. This nonlinear relationship of anti‐inflammatory HDL function with risk may account in part for the HDL paradox. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00239681. |
| first_indexed | 2024-12-22T20:50:13Z |
| format | Article |
| id | doaj.art-2fd3986e2fd8443c975dfbc846da29ac |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T20:50:13Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2fd3986e2fd8443c975dfbc846da29ac2022-12-21T18:13:07ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-09-0191710.1161/JAHA.119.016507Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical TrialOluremi N. Ajala0Olga V. Demler1Yanyan Liu2Zareen Farukhi3Steven J. Adelman4Heidi L. Collins5Paul M Ridker6Daniel J. Rader7Robert J. Glynn8Samia Mora9Center for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MACenter for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MACenter for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MACenter for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MAVascularStrategies Plymouth PAVascularStrategies Plymouth PACenter for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MADepartment of Genetics University of Pennsylvania Philadelphia PACenter for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MACenter for Lipid Metabolomics and Division of Preventive Medicine Brigham and Women’s Hospital Boston MABackground High‐density lipoprotein (HDL) cholesterol has inverse association with cardiovascular disease. HDL possesses anti‐inflammatory properties in vitro, but it is unknown whether this may be protective in individuals with inflammation. Methods and Results The functional capacity of HDL to inhibit oxidation of oxidized low‐density lipoprotein (ie, the HDL inflammatory index; HII) was measured at baseline and 12 months after random allocation to rosuvastatin or placebo in a nested case‐control study of the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Evaluating Rosuvastatin) trial. There were 517 incident cases of cardiovascular disease and all‐cause mortality compared to 517 age‐ and sex‐matched controls. Multivariable conditional logistic regression was used to examine associations of HII with events. Median baseline HII was 0.54 (interquartile range, 0.50–0.59). Twelve months of rosuvastatin decreased HII by a mean of 5.3% (95% CI, −8.9% to −1.7%; P=0.005) versus 1.3% (95% CI, −6.5% to 4.0%; P=0.63) with placebo (P=0.22 for between‐group difference). HII had a nonlinear relationship with incident events. Compared with the reference group (HII 0.5–1.0) with the lowest event rates, participants with baseline HII ≤0.5 had significantly increased risk of cardiovascular disease/mortality (adjusted hazard ratio, 1.53; 95% CI, 1.06–2.21; P=0.02). Furthermore, there was significant (P=0.002) interaction for HDL particle number with HII, such that having more HDL particles was associated with decreased risk only when HDL was anti‐inflammatory. Conclusions In JUPITER participants recruited on the basis of chronic inflammation, HII was associated with incident cardiovascular disease/mortality, with an optimal anti‐inflammatory HII range between 0.5 and 1.0. This nonlinear relationship of anti‐inflammatory HDL function with risk may account in part for the HDL paradox. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00239681.https://www.ahajournals.org/doi/10.1161/JAHA.119.016507cardiovascular disease risk factorsHDL functionHDL inflammatory indexHDL particle numberhigh‐density lipoprotein |
| spellingShingle | Oluremi N. Ajala Olga V. Demler Yanyan Liu Zareen Farukhi Steven J. Adelman Heidi L. Collins Paul M Ridker Daniel J. Rader Robert J. Glynn Samia Mora Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular disease risk factors HDL function HDL inflammatory index HDL particle number high‐density lipoprotein |
| title | Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial |
| title_full | Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial |
| title_fullStr | Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial |
| title_full_unstemmed | Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial |
| title_short | Anti‐Inflammatory HDL Function, Incident Cardiovascular Events, and Mortality: A Secondary Analysis of the JUPITER Randomized Clinical Trial |
| title_sort | anti inflammatory hdl function incident cardiovascular events and mortality a secondary analysis of the jupiter randomized clinical trial |
| topic | cardiovascular disease risk factors HDL function HDL inflammatory index HDL particle number high‐density lipoprotein |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.119.016507 |
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