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Published on: October 12, 2017
Coronary heart disease risks associated with high levels of HDL cholesterol
John T Wilkins1, Hongyan Ning, Neil J Stone
1Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Insights
High-density lipoprotein cholesterol (HDL-C) shows diminishing returns for coronary heart disease (CHD) risk reduction in men and women. Further reductions in CHD events were not observed with HDL-C levels above 90 mg/dL in men and 75 mg/dL in women.
Area of Science:
- Cardiovascular Research
- Lipid Metabolism
- Epidemiology
Background:
- The relationship between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) is not fully understood at very high HDL-C levels (>80 mg/dL).
- Existing research often lacks data on the upper ranges of HDL-C and their association with cardiovascular events.
Purpose of the Study:
- To investigate the association between very high levels of HDL-C and the risk of CHD events and total mortality.
- To determine if there is a threshold for HDL-C beyond which further cardiovascular protection is not observed.
Main Methods:
- Pooled analysis of data from 6 community-based cohorts, including over 11,515 men and 12,925 women.
- Utilized Cox proportional hazards models with penalized splines for sex-stratified analyses.
- Examined associations across a wide range of HDL-C levels, including those exceeding 80 mg/dL.
Main Results:
- In men, HDL-C showed an inverse linear association with CHD events until HDL-C levels exceeded 90 mg/dL, after which a plateau effect was observed.
- In women, the protective association of HDL-C with CHD events plateaued at levels above 75 mg/dL.
- While unadjusted models suggested increased total mortality risk with very high HDL-C in men, this association was attenuated after adjusting for traditional risk factors.
Conclusions:
- No additional reduction in CHD risk was found for HDL-C levels exceeding 90 mg/dL in men and 75 mg/dL in women.
- These findings suggest a potential upper limit for the cardioprotective benefits of HDL-C.
- Further research may be needed to understand the implications of extremely high HDL-C levels and their impact on mortality.
Background:
The association between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) events is not well described in individuals with very high levels of HDL-C (>80 mg/dL).
Methods And Results:
Using pooled data from 6 community-based cohorts we examined CHD and total mortality risks across a broad range of HDL-C, including values in excess of 80 mg/dL. We used Cox proportional hazards models with penalized splines to assess multivariable, adjusted, sex-stratified associations of HDL-C with the hazard for CHD events and total mortality, using HDL-C 45 mg/dL and 55 mg/dL as the referent in men and women, respectively. Analyses included 11 515 men and 12 925 women yielding 307 245 person-years of follow-up. In men, the association between HDL-C and CHD events was inverse and linear across most HDL-C values; however at HDL-C values >90 mg/dL there was a plateau effect in the pattern of association. In women, the association between HDL-C and CHD events was inverse and linear across lower values of HDL-C, however at HDL-C values >75 mg/dL there were no further reductions in the hazard ratio point estimates for CHD. In unadjusted models there were increased total mortality risks in men with very high HDL-C, however mortality risks observed in participants with very high HDL-C were attenuated after adjustment for traditional risk factors.
Conclusions:
We did not observe further reductions in CHD risk with HDL-C values higher than 90 mg/dL in men and 75 mg/dL in women.
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