To examine dose–response associations between HDL-C levels and mortality from the 10 leading global causes of death, highlighting HDL-C's clinical relevance.
Key Findings:
U-shaped associations were found between HDL-C and death risk from ischemic heart disease, lower respiratory infections, lung cancers, diabetes mellitus, and kidney disease, indicating both low and high levels increase risk.
Optimal HDL-C levels for lowest death risk were 58–74 mg/dL for females and 50–60 mg/dL for males.
J-shaped curves were observed for chronic obstructive pulmonary disease and liver disease, with lowest death risk at 30–50 mg/dL.
Stroke and Alzheimer’s disease/dementias showed sex-specific patterns in death risk related to HDL-C levels.
Extremely high HDL-C levels were associated with increased risk of death across several causes.
Interpretation:
HDL-C is non-linearly and sex-specifically associated with the top 10 global causes of death, indicating that both low and high HDL-C levels confer increased risk through different mechanisms, with implications for clinical practice.
Limitations:
The study is observational and cannot establish causation, which may introduce biases.
Data is limited to UK Biobank participants, which may not be generalizable to other populations.
Conclusion:
The findings emphasize the importance of evaluating HDL functionality rather than just quantity in future research and clinical care, highlighting the need for further studies.
