CoChat
Sign Up
Cited by 78Blood Pressure and Hypertension StudiesDiabetes, Cardiovascular Risks, and LipoproteinsLipoproteins and Cardiovascular Health

High Remnant Cholesterol Level Potentiates the Development of Hypertension

Open access
Chen, Ming-Ming, Huang, Xuewei, Xu, Chengsheng, Song, Xiao-Hui, Liu, Ye-Mao, Yao, Dongai, Lu, Huiming, Wang, Gang +14 more·2022·Frontiers in Endocrinology
DOI 10.3389/fendo.2022.830347PMC PMC8863865
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Emerging evidence suggests an association between remnant cholesterol (RC) and vascular damage and hypertension. However, this association has not been explored in a large-scale population in China, and a temporal relationship between RC and hypertension also needs to be investigated. Methods: We conducted a retrospective cross-sectional study in 2,199,366 individuals and a longitudinal study in 24,252 individuals with repeated measurements of lipid profile and blood pressure in at least a 3-year follow-up. The logistic model was used to explore the association between lipid components and hypertension in the cross-sectional analysis. The Cox model was used to analyze the association between high RC (HRC) at baseline and the subsequent incidence of hypertension or the association between hypertension at baseline and incidence of HRC. The cross-lagged panel model was applied to analyze the temporal relationship between RC and hypertension. Results: RC level as a continuous variable had the highest correlation with hypertension among lipid profiles, including RC, low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides, with an odds ratio of 1.59 (95% confidence interval: 1.58–1.59). In the longitudinal cohort, HRC at baseline was associated with incident hypertension. We further explored the temporal relationship between RC and hypertension using the cross-lagged analysis, and the results showed that RC increase preceded the development of hypertension, rather than vice versa. Conclusions: RC had an unexpected high correlation with the prevalence and incidence of hypertension. Moreover, RC increase might precede the development of hypertension, suggesting the potential role of RC in the development of hypertension.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fendo.2022.830347

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 51

  1. [1]Kopin L Lowenstein C. Dyslipidemia. Ann Intern Med (2017) 167: ITC81– 96. doi: 10.7326/AITC201712050 29204622 · DOI
  2. [2]Grundy SM. Metabolic Syndrome Update. Trends Cardiovasc Med (2016) 26: 364–73. doi: 10.1016/j.tcm.2015.10.004 26654259 · DOI · Paper page
  3. [3]Hong KN Fuster V Rosenson RS Rosendorff C Bhatt DL. How Low to Go With Glucose, Cholesterol, and Blood Pressure in Primary Prevention of CVD. J Am Coll Cardiol (2017) 70: 2171–85. doi: 10.1016/j.jacc.2017.09.001 29050566 · DOI
  4. [4]Si XB Liu W. Relationship Between Blood Lipid and Arterial Stiffness in Hypertension. Clin Invest Med (2019) 42: E47–55. doi: 10.25011/cim.v42i3.33092 31563160 · DOI
  5. [5]Zhan B Huang X Wang J Qin X Zhang J Cao J. Association Between Lipid Profiles and Arterial Stiffness in Chinese Patients With Hypertension: Insights From the CSPPT. Angiology (2019) 70: 515–22. doi: 10.1177/0003319718823341 30651004 · DOI
  6. [6]Pavlovska I Kunzova S Jakubik J Hruskova J Skladana M Rivas-Serna IM. Associations Between High Triglycerides and Arterial Stiffness in a Population-Based Sample: Kardiovize Brno 2030 Study. Lipids Health Dis (2020) 19: 170. doi: 10.1186/s12944-020-01345-0 32669093 PMC7362636 · DOI
  7. [7]Wu S Jin C Li S Zheng X Zhang X Cui L. Aging, Arterial Stiffness, and Blood Pressure Association in Chinese Adults. Hypertension (2019) 73: 893–9. doi: 10.1161/HYPERTENSIONAHA.118.12396 30776974 · DOI
  8. [8]Borghi C Urso R Cicero AF. Renin-Angiotensin System at the Crossroad of Hypertension and Hypercholesterolemia. Nutr Metab Cardiovasc Dis (2017) 27: 115–20. doi: 10.1016/j.numecd.2016.07.013 27745933 · DOI
  9. [9]Ivanovic B Tadic M. Hypercholesterolemia and Hypertension: Two Sides of the Same Coin. Am J Cardiovasc Drugs (2015) 15: 403–14. doi: 10.1007/s40256-015-0128-1 26062915 · DOI
  10. [10]Wiggenhauser LM Kroll J. Vascular Damage in Obesity and Diabetes: Highlighting Links Between Endothelial Dysfunction and Metabolic Disease in Zebrafish and Man. Curr Vasc Pharmacol (2019) 17: 476–90. doi: 10.2174/1570161116666181031101413 30378499 · DOI
  11. [11]Langsted A Madsen CM Nordestgaard BG. Contribution of Remnant Cholesterol to Cardiovascular Risk. J Intern Med (2020) 288: 116–27. doi: 10.1111/joim.13059 32181933 · DOI
  12. [14]Varbo A Benn M Tybjaerg-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. doi: 10.1161/CIRCULATIONAHA.113.003008 23926208 · DOI · Paper page
  13. [15]Bernelot Moens SJ Verweij SL Schnitzler JG Stiekema LCA Bos M Langsted A. Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans. Arterioscler Thromb Vasc Biol (2017) 37: 969–75. doi: 10.1161/ATVBAHA.116.308834 28336558 · DOI
  14. [16]Li K Fan F Zheng B Jia J Liu B Liu J. 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. doi: 10.1186/s12944-021-01490-0 34174876 PMC8235613 · DOI
  15. [17]Xu J Qu P Du X Xiang Q Guo L Zhu L. Change in Postprandial Level of Remnant Cholesterol After a Daily Breakfast in Chinese Patients With Hypertension. Front Cardiovasc Med (2021) 8: 685385. doi: 10.3389/fcvm.2021.685385 34212015 PMC8239280 · DOI
  16. [18]Kasahara A Adachi H Hirai Y Enomoto M Fukami A Yoshikawa K. High Level of Plasma Remnant-Like Particle Cholesterol may Predispose to Development of Hypertension in Normotensive Subjects. Am J Hypertens (2013) 26: 793–8. doi: 10.1093/ajh/hpt011 23403840 · DOI
  17. [19]Wang Z Chen Z Zhang L Wang X Hao G Zhang Z. Status of Hypertension in China: Results From the China Hypertension Survey, 2012-2015. Circulation (2018) 137: 2344–56. doi: 10.1161/CIRCULATIONAHA.117.032380 29449338 · DOI · Paper page
  18. [20]Chinese Sciety of Laboratory Medicine. Recommendations for Clinical Lipid Determination (2004). 2004 National Smposium on Lipid Analysis and Clinical Application & Collection of Papers From the 7th National Lipoprotein Conference. p. 91–5.
  19. [21]Zhang P Su Q Ye X Guan P Chen C Hang Y. Trends in LDL-C and Non-HDL-C Levels With Age. Aging Dis (2020) 11: 1046–57. doi: 10.14336/AD.2019.1025 PMC7505266 33014521 · DOI
  20. [22]Joint Committee for Guideline, Revision. 2018. Chinese Guidelines for Prevention and Treatment of Hypertension-A report of the Revision Committee of Chinese Guidelines for Prevention and Treatment of Hypertension. J Geriatr Cardiol (2019) 16: 182– 241. doi: 10.11909/j.issn.1671-5411.2019.03.014 31080465 PMC6500570 · DOI
  21. [23]Nordestgaard BG Langsted A Mora S Kolovou G Baum H Bruckert E. Fasting is Not Routinely Required for Determination of a Lipid Profile: Clinical and Laboratory Implications Including Flagging at Desirable Concentration Cut-Points-a Joint Consensus Statement From the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J (2016) 37: 1944–58. doi: 10.1093/eurheartj/ehw152 PMC4929379 27122601 · DOI · Paper page
  22. [24]Joint Committee Issued Chinese Guideline for the Management of Dyslipidemia in Adults. Chinese Guideline for the Management of Dyslipidemia in Adults. Zhonghua Xin Xue Guan Bing Za Zhi (2016) 44: 833–53. doi: 10.3760/cma.j.issn.0253-3758.2016.10.005 27903370 · DOI
  23. [25]American Diabetes A Executive Summary: Standards of Medical Care in Diabetes–2014. Diabetes Care (2014) 37(Suppl 1): S5– 13. doi: 10.2337/dc14-S005 24357214 · DOI
  24. [26]Cheng X Liu YM Li H Zhang X Lei F Qin JJ. Metformin is Associated With Higher Incidence of Acidosis, But Not Mortality, in Individuals With COVID-19 and Pre-Existing Type 2 Diabetes. Cell Metab (2020) 32: 537– 47.e3. doi: 10.1016/j.cmet.2020.08.013 32861268 PMC7439986 · DOI
  25. [27]Zhou H Guo ZR Yu LG Hu XS Xu BH Liu HB. Evidence on the Applicability of the ATPIII, IDF and CDS Metabolic Syndrome Diagnostic Criteria to Identify CVD and T2DM in the Chinese Population From a 6.3-Year Cohort Study in Mid-Eastern China. Diabetes Res Clin Pract (2010) 90: 319–25. doi: 10.1016/j.diabres.2010.09.001 20934770 · DOI
  26. [28]Song QB Zhao Y Liu YQ Zhang J Xin SJ Dong GH. Sex Difference in the Prevalence of Metabolic Syndrome and Cardiovascular-Related Risk Factors in Urban Adults From 33 Communities of China: The CHPSNE Study. Diabetes Vasc Dis Res (2015) 12: 189–98. doi: 10.1177/1479164114562410 25670848 · DOI
  27. [29]Park YS Park SH Lee SS Kim DY Shin YM Lee W. Biopsy-Proven Nonsteatotic Liver in Adults: Estimation of Reference Range for Difference in Attenuation Between the Liver and the Spleen at Nonenhanced CT. Radiology (2011) 258: 760–6. doi: 10.1148/radiol.10101233 21212369 · DOI
  28. [30]Saverymuttu SH Joseph AE Maxwell JD. Ultrasound Scanning in the Detection of Hepatic Fibrosis and Steatosis. Br Med J (Clin Res Ed) (1986) 292: 13–5. doi: 10.1136/bmj.292.6512.13 PMC1338970 3080046 · DOI
  29. [31]Waljee AK Mukherjee A Singal AG Zhang Y Warren J Balis U. Comparison of Imputation Methods for Missing Laboratory Data in Medicine. BMJ Open (2013) 3: e002847. doi: 10.1136/bmjopen-2013-002847 PMC3733317 23906948 · DOI
  30. [32]Chen Z Chen J Zhou J Lei F Zhou F Qin JJ. A Risk Score Based on Baseline Risk Factors for Predicting Mortality in COVID-19 Patients. Curr Med Res Opin (2021) 37: 917–27. doi: 10.1080/03007995.2021.1904862 PMC8054492 33729889 · DOI
  31. [34]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. doi: 10.1161/HYPERTENSIONAHA.119.13419 31865799 · DOI
  32. [35]Bai L Li H. Innate Immune Regulatory Networks in Hepatic Lipid Metabolism. J Mol Med (Berl) (2019) 97: 593– 604. doi: 10.1007/s00109-019-01765-1 30891617 · DOI
  33. [37]Varbo A Nordestgaard BG. Directly Measured vs. Calculated Remnant Cholesterol Identifies Additional Overlooked Individuals in the General Population at Higher Risk of Myocardial Infarction. Eur Heart J (2021) 42: 4833–43. doi: 10.1093/eurheartj/ehab293 34023898 · DOI
  34. [38]Fogacci F Norata GD Toth PP Arca M Cicero AFG. Efficacy and Safety of Volanesorsen (ISIS 304801): The Evidence From Phase 2 and 3 Clinical Trials. Curr Atheroscler Rep (2020) 22: 18. doi: 10.1007/s11883-020-00836-w 32458077 · DOI
  35. [39]Golomb BA Dimsdale JE White HL Ritchie JB Criqui MH. Reduction in Blood Pressure With Statins: Results From the UCSD Statin Study, a Randomized Trial. Arch Intern Med (2008) 168: 721–7. doi: 10.1001/archinte.168.7.721 PMC4285458 18413554 · DOI
  36. [40]Quispe R Martin SS Michos ED Lamba I Blumenthal RS Saeed A. Remnant Cholesterol Predicts Cardiovascular Disease Beyond LDL and ApoB: A Primary Prevention Study. Eur Heart J (2021) 42: 4324–32. doi: 10.1093/eurheartj/ehab432 PMC8572557 34293083 · DOI · Paper page
  37. [41]Wong ND Zhao Y Quek RGW Blumenthal RS Budoff MJ Cushman M. Residual Atherosclerotic Cardiovascular Disease Risk in Statin-Treated Adults: The Multi-Ethnic Study of Atherosclerosis. J Clin Lipidol (2017) 11: 1223–33. doi: 10.1016/j.jacl.2017.06.015 PMC6394854 28754224 · DOI
  38. [42]Vallejo-Vaz AJ Fayyad R Boekholdt SM Hovingh GK Kastelein JJ Melamed S. Triglyceride-Rich Lipoprotein Cholesterol and Risk of Cardiovascular Events Among Patients Receiving Statin Therapy in the TNT Trial. Circulation (2018) 138: 770–81. doi: 10.1161/CIRCULATIONAHA.117.032318 29618599 · DOI · Paper page
  39. [43]Roever L. Pitavastatin Versus Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients With Dyslipidemias. Clin Ther (2016) 38: 1250–1. doi: 10.1016/j.clinthera.2016.03.019 27041404 · DOI
  40. [44]Nakamura T Takano H Umetani K Kawabata K Obata JE Kitta Y. Remnant Lipoproteinemia is a Risk Factor for Endothelial Vasomotor Dysfunction and Coronary Artery Disease in Metabolic Syndrome. Atherosclerosis (2005) 181: 321–7. doi: 10.1016/j.atherosclerosis.2005.01.012 16039286 · DOI · Paper page
  41. [45]Bautista LE. Blood Pressure-Lowering Effects of Statins: Who Benefits? J Hypertens (2009) 27: 1478–84. doi: 10.1097/HJH.0b013e32832b1e78 19365283 · DOI
  42. [46]Heart Protection Study Collaborative G Jonathan E Derrick B Emma L Sarah P John D. C-Reactive Protein Concentration and the Vascular Benefits of Statin Therapy: An Analysis of 20,536 Patients in the Heart Protection Study. Lancet (2011) 377: 469–76. doi: 10.1016/S0140-6736(10)62174-5 PMC3042687 21277016 · DOI
  43. [47]Zheng XY Liu L. Remnant-Like Lipoprotein Particles Impair Endothelial Function: Direct and Indirect Effects on Nitric Oxide Synthase. J Lipid Res (2007) 48: 1673–80. doi: 10.1194/jlr.R700001-JLR200 17496332 · DOI
  44. [48]Dinh QN Drummond GR Sobey CG Chrissobolis S. Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension. BioMed Res Int (2014) 2014: 406960. doi: 10.1155/2014/406960 25136585 PMC4124649 · DOI
  45. [49]Guzik TJ Touyz RM. Oxidative Stress, Inflammation, and Vascular Aging in Hypertension. Hypertension (2017) 70: 660–7. doi: 10.1161/HYPERTENSIONAHA.117.07802 28784646 · DOI
  46. [50]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. doi: 10.1007/s00441-012-1346-3 22331364 · DOI
  47. [51]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. doi: 10.1210/en.2011-1752 PMC3275386 22186415 · DOI
  48. [52]Chan DC Watts GF Barrett PH O'Neill FH Redgrave TG Thompson GR. Relationships Between Cholesterol Homoeostasis and Triacylglycerol-Rich Lipoprotein Remnant Metabolism in the Metabolic Syndrome. Clin Sci (Lond) (2003) 104: 383–8. doi: 10.1042/cs1040383 12653682 · DOI
  49. [53]Ohnishi H Saitoh S Takagi S Ohata J Isobe T Kikuchi Y. Relationship Between Insulin-Resistance and Remnant-Like Particle Cholesterol. Atherosclerosis (2002) 164: 167–70. doi: 10.1016/S0021-9150(02)00057-6 12119206 · DOI
  50. [54]Twickler TB Dallinga-Thie GM Cohn JS Chapman MJ. Elevated Remnant-Like Particle Cholesterol Concentration: A Characteristic Feature of the Atherogenic Lipoprotein Phenotype. Circulation (2004) 109: 1918–25. doi: 10.1161/01.CIR.0000125278.58527.F3 15117861 · DOI · Paper page
  51. [55]da Silva AA do Carmo JM Li X Wang Z Mouton AJ Hall JE. Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited. Can J Cardiol (2020) 36: 671–82. doi: 10.1016/j.cjca.2020.02.066 PMC7219403 32389340 · DOI

Cited by

Sorted by citations

Authors
Chen, M.-M., Huang, X., Xu, C., Song, X.-H., Liu, Y.-M., Yao, D., Lu, H., Wang, G., Zhang, G.-L., Chen, Z., Sun, T., Yang, C., Lei, F., Qin, J.-J., Ji, Y.-X., Zhang, P., Zhang, X.-J., Zhu, L., Cai, J., Wan, F., She, Z.-G., & Li, H.
Affiliations
  • Renmin Hospital of Wuhan University (CN)
  • Huanggang Central Hospital (CN)
  • Wuhan University (CN)
  • Zhongnan Hospital of Wuhan University (CN)
  • General Hospital of Central Theater Command (CN)
  • The Central Hospital of Xiao gan (CN)
  • Central South University (CN)
Corresponding author
  • Wan, Feng
  • She, Zhi-Gang
  • Li, Hongliang
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2022-02-09
Volume
13
Issue
3
Pages
830347-830347
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2022.830347
PMC
PMC8863865
OpenAlex
W35222285
Cited by
78
References
4
Citations by year
2026: 6 · 2025: 19 · 2024: 15 · 2023: 16 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 5
FWCI
9.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Problemi dell'informazione
Funders
  • National Natural Science Foundation of China (81770053, 82170595, 81970070, 81970364, 82000299, 81970011, 82170455, 82170436, 81870171, 2018BEC473)
  • Wuhan University (TFJH2018006)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
remnant cholesterol, hypertension, hypertension incidence, temporal relations, lipid profile, non-HDL cholesterol, triglycerides, LDL cholesterol, total cholesterol, vascular injury, Chinese population
MeSH terms
Adult, Blood Pressure, Cholesterol, Cross-Sectional Studies, Female, Humans, Hypertension, Lipoproteins, Longitudinal Studies, Male, Middle Aged, Retrospective Studies, Triglycerides

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review