Abstract
OBJECTIVE The haptoglobin (Hp)2-2 phenotype (~35–40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower trigly-cerides have not reliably prevented cardiovascular disease in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simva-statin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. RESEARCH DESIGN AND METHODS Cox proportional hazards regression models quantified the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n 5 1,795) separately from those without (n 5 3,201). RESULTS Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable adjusted hazard ratio 0.74 [95% CI 0.60–0.90] compared with no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16 [0.87–1.56]; P interaction 5 0.009). Subgroup analy-ses revealed that this protective effect of fenofibrate against CAD events among the non–Hp2-2 phenotype group was pronounced in participants with severe dyslipidemia (P interaction 5 0.01) and in males (P interaction 5 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (P interaction 5 0.002). CONCLUSIONS The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.
| Original language | English |
|---|---|
| Pages (from-to) | 241-250 |
| Number of pages | 10 |
| Journal | Diabetes Care |
| Volume | 45 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2022 |
Bibliographical note
Funding Information:well as the staff and participants of the ACCORD trial. Funding. This study was funded by a Dalhou-sie University Department of Medicine Ad Hoc Operating Grant (Halifax, Nova Scotia, Canada) to L.E.C. and a Nova Scotia Health Research Fund grant (Halifax, Nova Scotia, Canada) to L.E.C. R.A.W. received a Heart and Stroke Foundation of Canada BrightRed Student Research Award. Duality of Interest. A.P.L. is the author of a patent owned by his university regarding use of haptoglobin genotype to predict susceptibility to cardiovascular disease in individuals with diabetes. No other potential conflicts of interest relevant to this article were reported. Author Contributions. R.A.W. and L.E.C. conceived the study idea and design with E.B.R. A.P.L. determined the haptoglobin phenotype in his laboratory while blinded to participant ID and outcome. R.A.W. performed the statistical analyses with guidance from P.A. and with A.S.C. rerunning all analyses in duplicate to confirm all findings. R.A.W. and L.E.C. drafted the manuscript with H.N.G. All authors contributed to additional drafts of the manuscript and approved the submitted version, and each author satisfies the authorship criteria of the International Committee of Medical Journal Editors. L.E.C. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding Information:
This study was funded by a Dalhousie University Department of Medicine Ad Hoc Operating Grant (Halifax, Nova Scotia, Canada) to L.E.C. and a Nova Scotia Health Research Fund grant (Halifax, Nova Scotia, Canada) to L.E.C. R.A.W. received a Heart and Stroke Foundation of Canada BrightRed Stu-dent Research Award.
Publisher Copyright:
© 2021 by the American Diabetes Association.
ASJC Scopus Subject Areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Advanced and Specialised Nursing
PubMed: MeSH publication types
- Clinical Trial
- Journal Article
- Research Support, Non-U.S. Gov't
