High-density lipoprotein cholesterol and cause-specific mortality in individuals without prior cardiovascular conditions: the CANHEART Study

Background — The prognostic importance of high-density lipoprotein (HDL) cholesterol as a specific risk factor for cardiovascular disease has been challenged by recent clinical trials and genetic studies.

Objective — To reappraise the association of HDL cholesterol level with cardiovascular and noncardiovascular mortality utilizing a “big data” approach.

Methods — An observation cohort study was conducted using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) dataset, which was created by linking together 17 different individual-level data sources. Individuals between 40 to 105 years old on January 1^st 2008, living in Ontario, Canada, without prior cardiovascular conditions or severe comorbidities, and had an outpatient fasting cholesterol measurement in the year prior to the inception date were included. The primary outcome was cause-specific mortality (cardiovascular, cancer, and other).

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 cholesterol level was 55.2 mg/dL. There were 17,952 deaths during a mean follow-up period of 4.9 ± 0.4 years. The overall all-cause mortality rate was 8.1 per 1000 person-years for men and 6.6 per 1000 person-years for women. Individuals with lower HDL cholesterol levels were more likely to have low incomes, unhealthy lifestyle, higher triglycerides levels, other cardiac risk factors, and medical comorbidities. Lower HDL cholesterol levels were independently associated with higher risk of cardiovascular, cancer, and other mortality compared with individual in the reference ranges of HDL cholesterol levels. In addition, individuals with higher HDL levels (> 70 mg/dL in men, > 90 mg/dL in women) also had increased hazard of non-cardiovascular mortality.

Conclusions — Complex associations exist between HDL cholesterol levels and socio-demographic, lifestyle, comorbidity factors, and mortality. HDL cholesterol level is unlikely to represent a cardiovascular specific risk-factor given similarities in its associations with non-cardiovascular outcomes.