Very high levels of HDL-C tied to higher mortality risk in CAD patients: JAMA

USA: A new study published in the Journal of American Medical Association- Cardiology suggests that extremely high HDL-C levels are related to an increased risk of death in those with coronary artery disease (CAD).

Previous research has linked greater levels of high-density lipoprotein cholesterol (HDL-C) to a decreased risk of cardiovascular disease. However, new findings in the general population reveal that very high HDL-C concentrations are associated with an increased risk of poor outcomes. Chang Liu and colleagues undertook this study to evaluate the relationship between extremely high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease, as well as the correlation of known HDL-C genotypes with high HDL-C level outcomes.

This multicenter, prospective cohort research recruited individuals with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB) from 2006 to the present in the UK and from 2003 to the present in Atlanta, Georgia. Patients who did not have verified CAD were ruled out of the research. Data analyses were carried out between May 10, 2020, and April 28, 2021. The primary outcome of this research was death from any cause, while the secondary outcome was death from cardiovascular disease.

The key findings of this study were as follows:

1. The study comprised 14 478 people from the UKB and 5467 participants from the EmCAB.

2. A U-shaped connection with outcomes was seen across a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, with greater risk in those with both low and extremely high HDL-C levels compared to those with intermediate values.

3. After controlling for confounding variables, very high HDL-C levels were linked with a higher risk of all-cause and cardiovascular mortality in the UKB compared to those with HDL-C levels in the range of 40 to 60 mg/dL.

4. These findings were confirmed in the EmCAB.

5. After adjusting for the HDL-C genetic risk score inside the UKB, these correlations remained.

6. Sensitivity studies revealed that men in the UKB had a greater risk of all-cause death in the extremely high HDL-C group than women.

In conclusion, higher HDL-C levels were related to a higher risk of all-cause and cardiovascular death in CAD populations compared to those with normal HDL-C levels, a finding that has previously only been documented in persons without known CAD. These findings have a significant therapeutic impact on risk prediction.

Reference:

Liu C, Dhindsa D, Almuwaqqat Z, et al. Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations. JAMA Cardiol. Published online May 18, 2022. doi:10.1001/jamacardio.2022.0912