Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Special Issue: Current evidence and perspectives for hypertension management in Asia
  • Published:

Remnant cholesterol and risk of incident hypertension: a population-based prospective cohort study

Hypertension Research volume 47, pages 1157–1166 (2024)Cite this article

A Comment to this article was published on 05 March 2024

Abstract

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17–1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23–1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03–1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brouwers S, Sudano I, Kokubo Y, Sulaica EM. Arterial hypertension. Lancet. 2021;398:249–61.

    Article  CAS  PubMed  Google Scholar 

  3. Lawes CM, Vander Hoorn S, Rodgers A. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371:1513–8.

    Article  PubMed  Google Scholar 

  4. Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan MJ, et al. National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5·4 million participants. Lancet. 2011;377:568–77.

    Article  PubMed  Google Scholar 

  5. Wang TJ, Gona P, Larson MG, Levy D, Benjamin EJ, Tofler GH, et al. Multiple biomarkers and the risk of incident hypertension. Hypertension. 2007;49:432–8.

    Article  CAS  PubMed  Google Scholar 

  6. Halperin RO, Sesso HD, Ma J, Buring JE, Stampfer MJ, Gaziano JM. Dyslipidemia and the risk of incident hypertension in men. Hypertension. 2006;47:45–50.

    Article  CAS  PubMed  Google Scholar 

  7. Otsuka T, Takada H, Nishiyama Y, Kodani E, Saiki Y, Kato K, et al. Dyslipidemia and the risk of developing hypertension in a working-age male population. J Am Heart Assoc. 2016;5:e003053.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.

    Article  CAS  PubMed  Google Scholar 

  9. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38:2459–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Quispe R, Martin SS, Michos ED, Lamba I, Blumenthal RS, Saeed A, et al. Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: A primary prevention study. Eur Heart J. 2021;42:4324–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Langsted A, Madsen CM, Nordestgaard BG. Contribution of remnant cholesterol to cardiovascular risk. J Intern Med. 2020;288:116–27.

    Article  CAS  PubMed  Google Scholar 

  12. Varbo A, Nordestgaard BG. Remnant cholesterol and triglyceride-rich lipoproteins in atherosclerosis progression and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2016;36:2133–5.

    Article  CAS  PubMed  Google Scholar 

  13. Hao QY, Gao JW, Yuan ZM, Gao M, Wang JF, Schiele F, et al. Remnant cholesterol and the risk of coronary artery calcium progression: Insights from the CARDIA and MESA study. Circ Cardiovasc Imaging. 2022;15:e014116.

    Article  PubMed  Google Scholar 

  14. Castañer O, Pintó X, Subirana I, Amor AJ, Ros E, Hernáez Á, et al. Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease. J Am Coll Cardiol. 2020;76:2712–24.

    Article  PubMed  Google Scholar 

  15. Wang J, Sun Q, An Y, Liu J, Leng S, Wang G. The association of remnant cholesterol (RC) and interaction between RC and diabetes on the subsequent risk of hypertension. Front Endocrinol. 2022;13:951635.

    Article  Google Scholar 

  16. Li K, Fan F, Zheng B, Jia J, Liu B, Liu J, et al. Associations between remnant lipoprotein cholesterol and central systolic blood pressure in a Chinese community-based population: A cross-sectional study. Lipids Health Dis. 2021;20:60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kasahara A, Adachi H, Hirai Y, Enomoto M, Fukami A, Yoshikawa K, et al. High level of plasma remnant-like particle cholesterol may predispose to development of hypertension in normotensive subjects. Am J Hypertens. 2013;26:793–8.

    Article  CAS  PubMed  Google Scholar 

  18. Chen MM, Huang X, Xu C, Song XH, Liu YM, Yao D, et al. High remnant cholesterol level potentiates the development of hypertension. Front Endocrinol (Lausanne). 2022;13:830347.

    Article  PubMed  Google Scholar 

  19. Bernelot Moens SJ, Verweij SL, Schnitzler JG, Stiekema LCA, Bos M, Langsted A, et al. Remnant cholesterol elicits arterial wall inflammation and a multilevel cellular immune response in humans. Arterioscler Thromb Vasc Biol. 2017;37:969–75.

    Article  CAS  PubMed  Google Scholar 

  20. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Elliott P, Peakman TC. The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine. Int J Epidemiol. 2008;37:234–44.

    Article  PubMed  Google Scholar 

  22. Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61:427–36.

    Article  CAS  PubMed  Google Scholar 

  23. Varbo A, Benn M, Smith GD, Timpson NJ, Tybjaerg-Hansen A, Nordestgaard BG. Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease. Circ Res. 2015;116:665–73.

    Article  CAS  PubMed  Google Scholar 

  24. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.

    Article  PubMed  Google Scholar 

  25. Elliott P, Stamler J, Nichols R, Dyer AR, Stamler R, Kesteloot H, et al. Intersalt revisited: further analyses of 24 h sodium excretion and blood pressure within and across populations. Intersalt Cooperative Research Group. BMJ. 1996;312:1249–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Thadhani R, Camargo CA Jr., Stampfer MJ, Curhan GC, Willett WC, Rimm EB. Prospective study of moderate alcohol consumption and risk of hypertension in young women. Arch Intern Med. 2002;162:569–74.

    Article  PubMed  Google Scholar 

  27. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr., et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–52.

    Article  CAS  PubMed  Google Scholar 

  28. Wang NY, Young JH, Meoni LA, Ford DE, Erlinger TP, Klag MJ. Blood pressure change and risk of hypertension associated with parental hypertension: the Johns Hopkins Precursors Study. Arch Intern Med. 2008;168:643–8.

    Article  PubMed  Google Scholar 

  29. Leggio M, Lombardi M, Caldarone E, Severi P, D’Emidio S, Armeni M, et al. The relationship between obesity and hypertension: An updated comprehensive overview on vicious twins. Hypertens Res. 2017;40:947–63.

    Article  PubMed  Google Scholar 

  30. Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. Hypertension. Nat Rev Dis Prim. 2018;4:18014.

    Article  PubMed  Google Scholar 

  31. Zhao YC, Zhao GJ, Chen Z, She ZG, Cai J, Li H. Nonalcoholic fatty liver disease: An emerging driver of hypertension. Hypertension. 2020;75:275–84.

    Article  CAS  PubMed  Google Scholar 

  32. Matsubara K, Yamamoto Y, Sonoyama K, Igawa G, Furuse M, Yatsuhashi T, et al. Current status of lipid management of hypertensive patients. Hypertens Res. 2003;26:699–704.

    Article  CAS  PubMed  Google Scholar 

  33. Park C, Fang J, Hawkins NA, Wang G. Comorbidity status and annual total medical expenditures in U.S. hypertensive adults. Am J Prev Med. 2017;53:S172–S81.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Machlin SR, Soni A. Health care expenditures for adults with multiple treated chronic conditions: Estimates from the Medical Expenditure Panel Survey, 2009. Prev Chronic Dis. 2013;10:E63.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Garg PR, Salam K, Saraswathy KN. Nonhigh-density lipoprotein cholesterol: A better marker of risk for hypertension than the low-density lipoprotein cholesterol. Int J Stroke. 2014;9:E33.

    Article  PubMed  Google Scholar 

  36. Lu K, Ding R, Wang L, Wu S, Chen J, Hu D. Association between prevalence of hypertension and components of metabolic syndrome: The data from Kailuan community. Clin Exp Hypertens. 2015;37:303–7.

    Article  CAS  PubMed  Google Scholar 

  37. Lin YH, Liu YH, Wu DW, Su HM, Chen SC. Dyslipidemia increases the risk of incident hypertension in a large Taiwanese population follow-up study. Nutrients. 2022;14:3277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Varbo A, Benn M, Tybjærg-Hansen A, Nordestgaard BG. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 2013;128:1298–309.

    Article  CAS  PubMed  Google Scholar 

  39. Zhang K, Jiang Y, Wang Y, Suo C, Xu K, Zhu Z, et al. Associations of arterial stiffness and carotid atherosclerosis with cerebral small vessel disease in a rural community-based population. J Atheroscler Thromb. 2020;27:922–33.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Xing Y, Rainey WE, Apolzan JW, Francone OL, Harris RB, Bollag WB. Adrenal cell aldosterone production is stimulated by very-low-density lipoprotein (VLDL). Endocrinology. 2012;153:721–31.

    Article  CAS  PubMed  Google Scholar 

  41. Saha S, Bornstein SR, Graessler J, Kopprasch S. Very-low-density lipoprotein mediates transcriptional regulation of aldosterone synthase in human adrenocortical cells through multiple signaling pathways. Cell Tissue Res. 2012;348:71–80.

    Article  CAS  PubMed  Google Scholar 

  42. Huh JH, Roh E, Lee SJ, Ihm SH, Han KD, Kang JG. Remnant cholesterol is an independent predictor of type 2 diabetes: A nationwide population-based cohort study. Diabetes Care. 2022;46:305–12.

    Article  Google Scholar 

  43. Hu X, Liu Q, Guo X, Wang W, Yu B, Liang B, et al. The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus. Cardiovasc Diabetol. 2022;21:117.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Quispe R, Martin SS, Jones SR. Triglycerides to high-density lipoprotein-cholesterol ratio, glycemic control and cardiovascular risk in obese patients with type 2 diabetes. Curr Opin Endocrinol Diabetes Obes. 2016;23:150–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to express our gratitude to the investigators, staff, and participants of the UK Biobank study for their valuable contributions to this research.

Funding

Funding

This work was supported by grants from the National Natural Science Foundation of China (82170457, 82371573, 82200306); Guangdong Basic and Applied Basic Research Foundation (2023A1515011730, 2022A1515011920, 2021A1515111092).

Author information

Author notes

  1. These authors contributed equally: Da-Chuan Guo, Jing-Wei Gao, Xiang Wang, Zhi-Teng Chen

Authors and Affiliations

  1. Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Da-Chuan Guo, Jing-Wei Gao, Zhi-Teng Chen, Qing-Yuan Gao, Yang-Xin Chen, Jing-Feng Wang, Pin-Ming Liu & Hai-Feng Zhang

  2. Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Xiang Wang

Authors
  1. Da-Chuan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jing-Wei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi-Teng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing-Yuan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yang-Xin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jing-Feng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pin-Ming Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hai-Feng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Pin-Ming Liu or Hai-Feng Zhang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, DC., Gao, JW., Wang, X. et al. Remnant cholesterol and risk of incident hypertension: a population-based prospective cohort study. Hypertens Res 47, 1157–1166 (2024). https://doi.org/10.1038/s41440-023-01558-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-023-01558-7

Keywords

This article is cited by

Search

Advanced search

Quick links