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Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study.
Tuesday,2022-10-11 21:26 America/Los_Angeles — ecterry
| Title | Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Lemaitre, RN, Jensen, PN, Zeigler, M, Fretts, AM, Umans, JG, Howard, BV, Sitlani, CM, McKnight, B, Gharib, SA, King, IB, Siscovick, DS, Psaty, BM, Sotoodehnia, N, Totah, RA |
| Journal | EBioMedicine |
| Volume | 83 |
| Pagination | 104189 |
| Date Published | 2022 Sep |
| ISSN | 2352-3964 |
| Keywords | Animals, Arachidonic Acids, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Eicosanoids, Humans, Ischemic Stroke, Prospective Studies |
| Abstract | <p><b>BACKGROUND: </b>Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that may impact atherosclerosis, and animal experimental studies suggest EETs protect cardiac function. Plasma EETs are mostly esterified to phospholipids and part of an active pool. To address the limited information about EETs and CVD in humans, we conducted a prospective study of total plasma EETs (free + esterified) and diabetes-related CVD in the Cardiovascular Health Study (CHS).</p><p><b>METHODS: </b>We measured 4 EET species and their metabolites, dihydroxyepoxyeicosatrienoic acids (DHETs), in plasma samples from 892 CHS participants with type 2 diabetes. We determined the association of EETs and DHETs with incident myocardial infarction (MI) and ischemic stroke using Cox regression.</p><p><b>FINDINGS: </b>During follow-up (median 7.5 years), we identified 150 MI and 134 ischemic strokes. In primary, multivariable analyses, elevated levels of each EET species were associated with non-significant lower risk of incident MI (for example, hazard ratio for 1 SD higher 14,15-EET: 0.86, 95% CI: 0.72-1.02; p=0.08). The EETs-MI associations became significant in analyses further adjusted for DHETs (hazard ratio for 1 SD higher 14,15-EET adjusted for 14,15-DHET: 0.76, 95% CI: 0.63-0.91; p=0.004). Elevated EET levels were associated with higher risk of ischemic stroke in primary but not secondary analyses. Three DHET species were associated with higher risk of ischemic stroke in all analyses.</p><p><b>INTERPRETATION: </b>Findings from this prospective study complement the extensive studies in animal models showing EETs protect cardiac function and provide new information in humans. Replication is needed to confirm the associations.</p><p><b>FUNDING: </b>US National Institutes of Health.</p> |
| DOI | 10.1016/j.ebiom.2022.104189 |
| Alternate Journal | EBioMedicine |
| PubMed ID | 35930887 |
| PubMed Central ID | PMC9356248 |
| Grant List | U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL130880 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 HL096706 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States |
ePub date:
22/09