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Association of high-density lipoprotein cholesterol with non-fatal cardiac and non-cardiac events: a CANHEART
Harindra C Wijeysundera1,2,3, Maria Koh3, David A Alter3
1Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
Insights
High-density lipoprotein cholesterol (HDL-C) levels show an inverse relationship with non-fatal cardiovascular and non-cardiovascular outcomes. This suggests HDL-C may be a marker of overall health rather than an independent risk factor.
Area of Science:
- Cardiovascular Science
- Biochemistry
- Epidemiology
Background:
- Emerging evidence questions the role of high-density lipoprotein cholesterol (HDL-C) as an independent cardiovascular disease risk factor.
- The established view of HDL-C as a modifiable risk factor is being re-evaluated.
- Understanding the precise relationship between HDL-C and clinical events is crucial.
Purpose of the Study:
- To investigate the association between HDL-C levels and subsequent non-fatal clinical events.
- To determine if HDL-C is an independent risk factor or a marker of overall health.
- To analyze sex-specific relationships between HDL-C and various health outcomes.
Main Methods:
- A large cohort of 631,762 individuals without prior cardiovascular disease or cancer was analyzed.
- Sex-stratified, multivariable, cause-specific Cox proportional hazards models were employed.
- Outcomes included non-fatal cardiovascular, cancer, and infectious events, with HDL-C levels categorized for analysis.
Main Results:
- A consistent inverse relationship was observed between lower HDL-C levels and increased risk of cardiovascular events in both men and women.
- This inverse association extended to a composite of non-cardiovascular outcomes.
- Significantly elevated hazard ratios for both cardiovascular and non-cardiovascular outcomes were noted in individuals with HDL-C <30 mg/dL compared to reference levels.
Conclusions:
- HDL-C demonstrates an inverse relationship with a broad spectrum of non-fatal health outcomes.
- Findings suggest HDL-C may be a confounded factor and a marker of underlying poor health.
- The role of HDL-C as an independent and modifiable risk factor warrants further critical assessment.
Background:
Emerging evidence has questioned the role of high-density lipoprotein cholesterol (HDL-C) as an independent and modifiable risk factor for cardiovascular disease. We sought to understand the relationship between HDL-C levels and subsequent non-fatal clinical events.
Methods:
Individuals without prior cardiovascular disease or cancer were identified. Outcomes of interest were classified as non-fatal cardiovascular, cancer and infectious. Sex-stratified, multivariable, cause-specific Cox proportional hazards models were created. The reference level HDL-C for both women and men was 51-60 mg/dL.
Results:
Our cohort consisted of 631 762 individuals. For cardiovascular events, there was a consistent inverse relationship, with higher adjusted HRs for the lower HDL-C strata in both men and women. This relationship was also seen in the composite of non-cardiovascular outcomes. In women, the HR in the <30 mg/dL HDL-C category was 2.10 (95% CI 1.66 to 2.57) and 1.86 (95% CI 1.27 to 2.72) for cardiovascular and non-cardiovascular outcomes, respectively; in contrast, in the >90 mg/dL group, it was 0.87 (95% CI 0.74 to 1.02) and 0.81 (95% CI 0.63 to 1.06). For men, HRs were 2.02 (95% CI 1.79 to 2.28) and 1.84 (95% CI 1.47 to 2.31) in the <30 mg/dL HDL-C category for cardiovascular and non-cardiovascular outcomes, respectively, compared with 0.73 (95% CI 0.53 to 1.00) and 1.07 (95% CI 0.67 to 1.70) in the >90 mg/dL group.
Conclusions:
We found an inverse relationship between HDL-C and a wide spectrum of non-fatal outcomes, suggesting that HDL-C is a heavily confounded factor that may be a marker of poor overall health, rather than an independent and modifiable risk factor.
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