HDL-C and Cause-Specific Mortality: The CANHEART Study

Study Questions:

What is the association of high-density lipoprotein cholesterol (HDL-C) level with cardiovascular (CV) and non-CV mortality utilizing 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 prior 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 the 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. 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.


The authors concluded that HDL-C level is unlikely to represent a CV-specific risk factor given similarities in its associations with non-CV outcomes.


This study reports that lower HDL-C levels were associated with a progressively higher proportion of individuals who were socioeconomically disadvantaged and had less healthy lifestyle behaviors, more cardiac risk factors, and a greater burden of medical comorbidities. Even after adjusting for a comprehensive list of potential confounding factors, the relationship between HDL-C levels and outcomes was not linear. Lower HDL-C levels had increased hazard of both CV and non-CV mortality, and individuals who had very high HDL-C levels also demonstrated increased hazard of non-CV mortality. Overall, these data suggest that HDL-C level is a marker of poor general health and may not be an independent modifiable risk factor specifically for CV disease.

Keywords: Cardiovascular Diseases, Cholesterol, HDL, Comorbidity, Dyslipidemias, Life Style, Metabolic Syndrome, Neoplasms, Primary Prevention, Risk Factors, Social Class, Triglycerides, Vulnerable Populations

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