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Coronary artery disease
Original research article
Association of high-density lipoprotein cholesterol with non-fatal cardiac and non-cardiac events: a CANHEART substudy
  1. Harindra C Wijeysundera1,2,3,
  2. Maria Koh3,
  3. David A Alter3,
  4. Peter C Austin2,3,
  5. Cynthia A Jackevicius2,4,
  6. Jack V Tu1,2,3 and
  7. Dennis T Ko1,2,3
  1. 1 Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
  2. 2 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
  3. 3 Institute for Clinical Evaluative Sciences (ICES), Toronto, Canada
  4. 4 College of Pharmacy, Western University of Health Sciences, Pomona, California, USA
  1. Correspondence to Dr Harindra C Wijeysundera; Harindra.wijeysundera{at}sunnybrook.ca

Abstract

Background Emerging evidence has questioned the role of high-density lipoprotein cholesterol (HDL-C) as an independent and modifiable risk factor for cardiovascular disease. We sought to understand the relationship between HDL-C levels and subsequent non-fatal clinical events.

Methods Individuals without prior cardiovascular disease or cancer were identified. Outcomes of interest were classified as non-fatal cardiovascular, cancer and infectious. Sex-stratified, multivariable, cause-specific Cox proportional hazards models were created. The reference level HDL-C for both women and men was 51–60 mg/dL.

Results Our cohort consisted of 631 762 individuals. For cardiovascular events, there was a consistent inverse relationship, with higher adjusted HRs for the lower HDL-C strata in both men and women. This relationship was also seen in the composite of non-cardiovascular outcomes. In women, the HR in the <30 mg/dL HDL-C category was 2.10 (95% CI 1.66 to 2.57) and 1.86 (95% CI 1.27 to 2.72) for cardiovascular and non-cardiovascular outcomes, respectively; in contrast, in the >90 mg/dL group, it was 0.87 (95% CI 0.74 to 1.02) and 0.81 (95% CI 0.63 to 1.06). For men, HRs were 2.02 (95% CI 1.79 to 2.28) and 1.84 (95% CI 1.47 to 2.31) in the <30 mg/dL HDL-C category for cardiovascular and non-cardiovascular outcomes, respectively, compared with 0.73 (95% CI 0.53 to 1.00) and 1.07 (95% CI 0.67 to 1.70) in the >90 mg/dL group.

Conclusions We found an inverse relationship between HDL-C and a wide spectrum of non-fatal outcomes, suggesting that HDL-C is a heavily confounded factor that may be a marker of poor overall health, rather than an independent and modifiable risk factor.

  • high-density lipoprotein cholesterol
  • non-fatal cardiovascular events
  • non-fatal non-cardiovascular events
  • competing risk models

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2017-000731

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    Footnotes

    • Contributors HCW developed the concept, interpreted the results and drafted the manuscript. MK performed the analyses, interpreted the results and provided critical revision of the manuscript. DAA, PCA, CAJ and JVT interpreted the results and provided critical revision of the manuscript. DTK developed the concept, interpreted the results and provided critical revision of the manuscript. HCW had full access to all data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.

    • Funding The study was supported by the Institute for Clinical Evaluative Sciences (ICES), an operating grant from the Institute of Circulatory and Respiratory Health, Canadian Institutes of Health Research (ICRH–CIHR) Chronic Diseases Team (grant no. TCA 118349), a CIHR Foundation Grant (grant no. FDN-143313), a CIHR Operating Grant (grant no. MOP-111035) and a Canadian Vascular Network (CVN) seed grant. The CVN is supported by grants from the CIHR–ICRH, and the Institute of Aging in partnership with and supported by Hypertension Canada. ICES is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). JVT is supported by a Tier 1 Canada Research Chair in Health Services Research and by an Eaton Scholar Award. HCW is supported by a Distinguished Clinical Scientist Award from the Heart and Stroke Foundation of Canada. DTK is supported by a Mid-Career Personnel Award from the Heart and Stroke Foundation, Ontario Provincial Office. PCA is supported by a Career Investigator Award from the Heart and Stroke Foundation, Ontario Provincial Office.

    • Disclaimer The opinions, results and conclusions reported in this paper are those of the authors and are independent of the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information. However, the analyses, conclusions, opinions and statements expressed herein are those of the authors, and not necessarily those of the Canadian Institute for Health Information.

    • Competing interests None declared.

    • Ethics approval The retrospective cohort study was approved by the Institutional Research Ethics Board at Sunnybrook Health Sciences Centre, Toronto, Ontario.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement There are no additional unpublished data from this study.