High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions: The CANHEART Study.
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.



This study sought to reappraise the association of HDL-C level with CV and non-CV mortality using a "big data" approach.



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.



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.



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.
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address: dennis.ko@ices.on.ca.
Dennis T
DT
Ko
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada.
David A
DA
Alter
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Helen
H
Guo
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Maria
M
Koh
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Geoffrey
G
Lau
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.
Peter C
PC
Austin
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
Gillian L
GL
Booth
Ottawa Research Group for Primary Health Care, Bruyère Research Institute, Ottawa, Ontario, Canada; Department of Family Medicine, University of Ottawa, Ottawa, Ontario, Canada.
William
W
Hogg
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacy, University Health Network, Toronto, Ontario, Canada; Department of Pharmacy, Western University of Health Sciences, Pomona, California.
Cynthia A
CA
Jackevicius
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
Douglas S
DS
Lee
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.
Harindra C
HC
Wijeysundera
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
John T
JT
Wilkins
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.
Jack V
JV
Tu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D002423:Cause of Death / Q000639:trends; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
D015415:Biomarkers; D008076:Cholesterol, HDL
cardiac and noncardiac death; epidemiology; outcomes; risk factor; sociodemographic