Very high HDL-C levels associated with risk of cardiovascular death

By Samar Mahmoud, MS
Published January 27, 2022

Key Takeaways

  • This prospective cohort study found that very high high-density lipoprotein cholesterol (HDL-C) levels are associated with a heightened risk of all-cause mortality and cardiovascular death in men, but not in women, without coronary artery disease. 

  • The results from this study challenge the idea that there is a simple inverse relationship between HDL-C levels and cardiovascular disease and suggests that both low and extremely high HDL-C levels lead to an increased risk of adverse outcomes.

Increased levels of HDL-C have previously been associated with reduced cardiovascular risk.

Why This Study Matters

Recent studies, using general population cohorts, have shown that very high levels of HDL-C are associated with an increased risk of adverse events. To further investigate the relationship between high HDL-C levels and adverse events, this study sought to evaluate the gender-specific association between very high HDL-C levels and cardiovascular outcomes.

Study Design

The study consisted of 415,416 participants without coronary artery disease enrolled in the United Kingdom Biobank. The median follow-up period was 9 years. 

Investigators defined high HDL-C levels as being >80mg/100 ml.  The primary outcomes of the study were all-cause death and cardiovascular death. 

Results and Conclusions

After adjustment for multiple variables, such as age and smoking status, a high HDL-C level was associated with an increased risk of all-cause mortality and cardiovascular death, with a hazard ratio of 1.11 and 1.24, respectively. 

Investigators also performed a gender-stratified analysis to determine if a high HDL-C level was associated with adverse outcomes in both men and women. However, high HDL-C levels were associated with increased risks of cardiovascular death and all-cause death in men, but not in women.

Researchers reported a hazard ratio of 1.79 for all-cause death and 1.92 for cardiovascular death in men and a hazard ratio of 0.97 for all-cause death and 1.04 for cardiovascular death in women. 

Related Research

Consider these findings from similar research studies:

  • Extreme high levels of HDL-C place both men and women at increased risk of all-cause mortality (Source). 

  • High HDL-C levels were not associated with an increased risk of death, MI, and stroke in the general population (Source).

Original Source 

Liu C, Dhindsa D, Almuwaqqat Z, Sun YV, Quyyumi AA. Very high high-density lipoprotein cholesterol levels and cardiovascular mortality. The American Journal of Cardiology. Published online January 2022:S0002914921011875.

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