U-Shaped Association of High-Density Lipoprotein Cholesterol with All-Cause and Cardiovascular Mortality in Hypertensive Population

Abstract

Purpose

Whether the paradox of high-density lipoprotein cholesterol (HDL-C) and elevated mortality risk extends to hypertensive patients is unclear. We aimed to investigate the association between HDL-C and all-cause and cardiovascular disease mortality in adults with hypertension.

Methods

In the National Health and Nutrition Examination Surveys, 11,497 hypertensive participants aged ≥18years old and examined at baseline between 1999 and 2014 were followed up until December 2015. We categorized the HDL-C concentration as ≤30, 31–40, 41–50, 51–60 (reference), 61–70, >70 mg/dL and examined their associations with all-cause and cardiovascular mortality, respectively. Multivariate Cox regression was used to calculated hazard ratio (HR) and 95% confidence interval (CI) for mortality risk.

Results

During follow-up (median: 9.2 ± 3.8 years), 3012 deaths and 713 cardiovascular deaths were observed. In the restrictive cubic curves, associations of HDL-C levels and all-cause and cardiovascular mortality were detected to be U-shaped. After multivariable adjustment, HRs for all-cause mortality were for the lowest HDL-C concentration (≤30 mg/dL) 1.29 (95% CI, 1.07–1.56) and the highest (>70 mg/dL) 1.20 (1.06–1.37), comparing with the reference group. For cardiovascular mortality, HRs were 1.31 (0.83–1.48) and 1.09 (0.83–1.43), respectively. Similar results were obtained in subgroups stratified by age, gender, race, and taking lipid-lowering drugs. The lowest all-cause mortality risk was observed at HDL-C 66 mg/dL (concentration) and 51–60 mg/dL (range).

Conclusion

Both lower and higher HDL-C concentration appeared to be associated with higher mortality in hypertensive population. Further investigation is warranted to clarify the underlying mechanisms.

Keywords:

• all-cause mortality
• high-density lipoprotein cholesterol
• cardiovascular mortality
• hypertension

Acknowledgment

We are grateful to all the participants.

Ethical Statement

Our experimental study was approved by the institutional medical ethical committee the Guangdong General Hospital, Guangzhou, China. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Written informed consents were obtained from all participants.

Disclosure

The authors declare that they have no conflicts of interest for this work.

Additional information

Funding

This work was supported by the Science and Technology Program of Guangzhou (No.201604020143, No.201604020018, No.201604020186, and No.201803040012), the National Key Research and Development Program of China (No.2017YFC1307603, No.2016YFC1301305), and the Key Area R&D Program of Guangdong Province (No.2019B020227005).