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A dose–response meta-analysis to evaluate the relationship between high-density lipoprotein cholesterol and all-cause and cardiovascular disease mortality

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Abstract

Purpose

Previous studies have not fully described the relationship between high-density lipoprotein cholesterol (HDL-C) and death risks from all cause and cardiovascular disease (CVD). This study quantitatively evaluates HDL-C–mortality associations.

Methods

Embase and PubMed databases were searched for relevant articles published up to 1 June 2019. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). We used restricted cubic splines to model the dose–response association.

Results

We identified 32 prospective cohort studies including 369,904 participants and 33,473 total deaths (9426 CVD deaths). Compared to the lowest HDL-C levels, all cause and CVD mortality risks were reduced by 18% (RR 0.82; 95% CI, 0.73–0.93) and 36% (0.64, 0.46–0.89), respectively, for the highest HDL-C levels. All cause and CVD mortality risks were reduced by 15% (0.85, 0.79–0.92) and 23% (0.77, 0.69–0.87), respectively, with each 1 mmol/L increment of HDL-C. We found evidence of nonlinear and negative dose–response associations of HDL-C with all cause and CVD mortality (Pnonlinearity < 0.001), and the lowest death risks from all cause and CVD were observed at approximately 1.34 and 1.55 mmol/L, respectively.

Conclusion

HDL-C is inversely associated with all cause and CVD mortality risks under approximately 2.05 and 2.33 mmol/L, respectively. Optimal doses require investigation via clinical practice or high-quality research.

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Availability of data and materials

The data and materials of this study are available from the corresponding author upon reasonable request.

Code availability

The code of software application is available from the corresponding author upon reasonable request.

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Funding

This study was supported by the National Key R&D Program of China (NO. 2017YFC0907301) and the Science and Technology Plan Project of Guizhou Province, China (NO. QKHPTRC[2018]5403).

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Authors and Affiliations

  1. School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Dongqing Road, Guian New Area, Guiyang, 550025, Guizhou, People’s Republic of China

    L. Liu, X. Zhang, J. Zhang, S. Zhan, L. Zhang, Z. Xu, C. Zhang & F. Hong

  2. College of Public Health, Zhengzhou University, Zhengzhou, 450000, People’s Republic of China

    M. Han, R. Qie & Q. Li

  3. Center for Diseases Control and Prevention of Yunyan District, Guiyang, 550004, People’s Republic of China

    X. Zhang

  4. Guiyang Center for Diseases Control and Prevention, Guiyang, 550001, People’s Republic of China

    J. Zhang

  5. Guizhou Provincial Hospital of Maternal and Child Health Care, Guiyang, 550004, People’s Republic of China

    S. Zhan

Authors
  1. L. Liu
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  2. M. Han
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  3. R. Qie
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  4. Q. Li
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  8. L. Zhang
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  10. C. Zhang
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  11. F. Hong
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Contributions

LL conceived, designed and performed the work; LL and MH screened and evaluated studies; LL and MH extracted the data; LL, MH, RQ, QL, and XZ analyzed the data; LL wrote the manuscript; JZ, SZ, LZ, ZX, CZ, and FH revised the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy. As the corresponding author, FH takes responsibility for the contents of the article.

Corresponding author

Correspondence to F. Hong.

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The authors declare that they have no competing interests.

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As this meta-analysis is performed based on the published studies, no ethical approval was required.

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Not applicable.

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As this meta-analysis is performed based on the published studies, no patient safety consideration was required.

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Liu, L., Han, M., Qie, R. et al. A dose–response meta-analysis to evaluate the relationship between high-density lipoprotein cholesterol and all-cause and cardiovascular disease mortality. J Endocrinol Invest 45, 551–562 (2022). https://doi.org/10.1007/s40618-021-01690-6

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  • DOI: https://doi.org/10.1007/s40618-021-01690-6

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