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High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular
Dennis T Ko1, David A Alter2, Helen Guo3
1Institute 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.
Insights
High-density lipoprotein cholesterol (HDL-C) levels are linked to cardiovascular and non-cardiovascular mortality. Lower HDL-C is associated with increased mortality risk, while very high HDL-C may also increase non-cardiovascular mortality risk.
Area of Science:
- Cardiovascular Medicine
- Epidemiology
- Biochemistry
Background:
- The role of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular disease risk factor is increasingly debated.
- Recent clinical trials and genetic studies have challenged its prognostic importance.
Purpose of the Study:
- To re-evaluate the association between HDL-C levels and both cardiovascular (CV) and non-CV mortality.
- To utilize a "big data" approach for a comprehensive analysis.
Main Methods:
- An observational cohort study using the CANHEART dataset, linking 17 data sources.
- Inclusion criteria: 40-105 years old, Ontario residents, no prior CV disease or severe comorbidities, with prior fasting cholesterol measurement.
- Primary outcome: cause-specific mortality.
Main Results:
- 631,762 individuals analyzed; mean follow-up 4.9 years.
- Lower HDL-C levels associated with adverse sociodemographic, lifestyle, and comorbidity factors.
- Lower HDL-C independently linked to higher risk of CV, cancer, and other mortality.
- Higher HDL-C levels (>70 mg/dl men, >90 mg/dl women) associated with increased non-CV mortality hazard.
Conclusions:
- HDL-C exhibits complex associations with mortality, influenced by various factors.
- HDL-C is unlikely to be a CV-specific risk factor due to similar associations with non-CV outcomes.
- Both low and very high HDL-C levels may indicate increased mortality risk.
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.
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