Author + information
- Dennis T. Ko, MD, MSca,b,c,∗ (, )
- David A. Alter, MD, PhDa,b,d,
- Helen Guo, MSca,
- Maria Koh, MSca,
- Geoffrey Lau, BHSc candidatea,
- Peter C. Austin, PhDa,c,
- Gillian L. Booth, MD, MSca,c,e,
- William Hogg, MD, MCIScf,g,
- Cynthia A. Jackevicius, PharmD, MSca,c,h,i,
- Douglas S. Lee, MD, PhDa,c,j,
- Harindra C. Wijeysundera, MD, PhDa,b,c,
- John T. Wilkins, MDk and
- Jack V. Tu, MD, PhDa,b,c
- aInstitute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
- bSchulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- cInstitute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
- dToronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada
- eLi Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
- fOttawa Research Group for Primary Health Care, Bruyère Research Institute, Ottawa, Ontario, Canada
- gDepartment of Family Medicine, University of Ottawa, Ottawa, Ontario, Canada
- hDepartment of Pharmacy, University Health Network, Toronto, Ontario, Canada
- iDepartment of Pharmacy, Western University of Health Sciences, Pomona, California
- jPeter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
- kDivision of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- ↵∗Reprint requests and correspondence:
Dr. Dennis. T. Ko, Institute for Clinical Evaluative Sciences, G106-2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
Background The prognostic importance of high-density lipoprotein cholesterol (HDL-C) as a specific risk factor for cardiovascular (CV) disease has been challenged by recent clinical trials and genetic studies.
Objectives This study sought to reappraise the association of HDL-C level with CV and non-CV mortality using a “big data” approach.
Methods An observational cohort study was conducted using the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) dataset, which was created by linking together 17 different individual-level data sources. People were included if they were between 40 and 105 years old on January 1, 2008, living in Ontario, Canada, without previous CV conditions or severe comorbidities, and had an outpatient fasting cholesterol measurement in the year prior to the inception date. The primary outcome was cause-specific mortality.
Results A total of 631,762 individuals were included. The mean age of our cohort was 57.2 years, 55.4% were women, and mean HDL-C level was 55.2 mg/dl. There were 17,952 deaths during a mean follow-up of 4.9 ± 0.4 years. The overall all-cause mortality rate was 8.1 per 1,000 person-years for men and 6.6 per 1,000 person-years for women. Individuals with lower HDL-C levels were more likely to have low incomes, unhealthy lifestyle, higher triglycerides levels, other cardiac risk factors, and medical comorbidities. Individuals with lower HDL-C levels were independently associated with higher risk of CV, cancer, and other mortality compared with individuals in the reference ranges of HDL-C levels. In addition, individuals with higher HDL levels (>70 mg/dl in men, >90 mg/dl in women) had increased hazard of non-CV mortality.
Conclusions Complex associations exist between HDL-C levels and sociodemographic, lifestyle, comorbidity factors, and mortality. HDL-C level is unlikely to represent a CV-specific risk factor given similarities in its associations with non-CV outcomes.
This study was funded through a Chronic Diseases Team grant (TCA 118349) from the Institute of Circulatory and Respiratory Health-Canadian Institutes of Health Research. This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Parts of this material are based on data and information compiled and provided by the Canadian Institute of Health Information. The design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review, or approval of the manuscript are independent of the funding or participating organizations. No endorsement by any organizations is intended or should be inferred. Dr. Ko is supported by a Clinician Scientist Award from the Heart and Stroke Foundation, Ontario office. Drs. Alter, Austin, and Booth are supported by Career Investigator Awards from the Heart and Stroke Foundation, Ontario office. Dr. Jackevicius has received research grants from Canadian Institutes of Health Research and Heart and Stroke Foundation. Dr. Lee is supported by a Clinician-Scientist Award from Canadian Institutes of Health Research. Dr. Wijeysundera is supported by a Distinguished Clinical Scientist Award from the Heart and Stroke Foundation of Canada. Dr. Tu is supported by a Canada Research Chair in Health Services Research and an Eaton Family Scholar award. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 12, 2016.
- Accepted August 9, 2016.
- The Authors