Top

BMC Geriatrics

Published in:

Open Access 01-12-2023 | Cerebral Small Vessel Disease | Research

Excessive salt intake accelerates the progression of cerebral small vessel disease in older adults

Authors: Di Liu, Qin Zhang, Shasha Xing, Fang Wei, Ke Li, Yingxin Zhao, Hua Zhang, Gary Gong, Yuqi Guo, Zhendong Liu

Published in: BMC Geriatrics | Issue 1/2023

Abstract

Background

It is unclear whether excessive salt intake accelerates the progression of cerebral small vessel disease (CSVD). The major objective of this study was to investigate the harmful effect of excessive salt intake on the progression of CSVD in older individuals.

Methods

Between May 2007 and November 2010, 423 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Salt intake was estimated using 24-hour urine collection for 7 consecutive days at baseline. Participants were classified into low, mild, moderate and high groups according to the salt intake estimation. CSVD including white matter hyperintensities (WMHs), lacunes, microbleeds and an enlarged perivascular space (EPVS) were determined using brain magnetic resonance imaging.

Results

During an average of five years of follow-up, the WMH volume and WMH-to-intracranial ratio were increased in the four groups. However, the increasing trends in the WMH volume and WMH-to-intracranial ratio were significantly faster in the higher salt intake groups compared with the lower salt intake groups (P_adjusted < 0.001). The cumulative hazard ratios of new-incident WMHs (defined as those with Fazekas scale scores ≥ 2), new-incident lacunes, microbleeds or an EPVS, as well as composites of CSVD, were respectively 2.47, 2.50, 3.33, 2.70 and 2.89 for the mild group; 3.72, 3.74, 4.66, 4.01 and 4.49 for the moderate group; and 7.39, 5.82, 7.00, 6.40 and 6.61 for the high group, compared with the low group after adjustment for confounders (P_adjusted < 0.001). The risk of new-incident WMHs, lacunes, microbleeds or an EPVS, and composites of CSVD was significantly increased with each 1-standard-deviation increment in salt intake (P_adjusted < 0.001).

Conclusion

Our data indicates that excessive salt intake is an important and independent contributor to the progression of CVSD in older adults.

Cannistraro RJ, Badi M, Eidelman BH, Dickson DW, Middlebrooks EH, Meschia JF. CNS small vessel disease a clinical review. Neurology. 2019;92(24):1146–56. https://doi.org/10.1212/wnl.0000000000007654.CrossRefPubMedPubMedCentral

Guo YQ, Li YP, Liu XK, Cui Y, Zhao YX, Sun SW, et al. Assessing the effectiveness of statin therapy for alleviating cerebral small vessel disease progression in people ≥ 75years of age. BMC Geriatr. 2020;20(1):292. https://doi.org/10.1186/s12877-020-01682-w.CrossRefPubMedPubMedCentral

Bordes C, Sargurupremraj M, Mishra A, Debette S. Genetics of common cerebral small vessel disease. Nat Rev Neurol. 2022;18(2):84–101. https://doi.org/10.1038/s41582-021-00592-8.CrossRefPubMed

Zhang H, Cui Y, Zhao YX, Dong YL, Wang J, Duan DD, et al. Association of circadian rhythm of blood pressure and cerebral small vessel disease in community-based elderly population. J Gerontol A Biol Sci Med Sci. 2019;74(8):1322–30. https://doi.org/10.1093/gerona/gly212.CrossRefPubMed

Cui Y, Zhang H, Zhao YX, Sun SW, Chai Q, Gong G, et al. Home-measured orthostatic hypotension associated with cerebral small vessel disease in a community-based older population. Hypertens Res. 2020;43(8):798–807. https://doi.org/10.1038/s41440-020-0429-x.CrossRefPubMed

Li Y, Huang Z, Jin C, Xing AJ, Liu YS, Huangfu CM, et al. Longitudinal change of perceived salt intake and stroke risk in a chinese population. Stroke. 2018;49(6):1332–9. https://doi.org/10.1161/STROKEAHA.117.020277.CrossRefPubMedPubMedCentral

Wang Z, Chen Q, Chen JJ, Yang N, Zheng K. Risk factors of cerebral small vessel disease: a systematic review and meta-analysis. Med (Baltim). 2021;100(51):e28229. https://doi.org/10.1097/MD.0000000000028229.CrossRef

Kraft P, Schuhmann MK, Garz C, Jandke S, Urlaub D, Mencl S, et al. Hypercholesterolemia induced cerebral small vessel disease. PLoS ONE. 2017;12(8):e0182822. https://doi.org/10.1371/journal.pone.0182822.CrossRefPubMedPubMedCentral

Duan DD, Dong YL, Zhang H, Zhao YX, Diao YT, Cui Y, et al. Empty-nest-related psychological distress is associated with progression of brain white matter lesions and cognitive impairment in the elderly. Sci Rep. 2017;7:43816. https://doi.org/10.1038/srep43816.CrossRefPubMedPubMedCentral

10.

Makin SDJ, Mubki GF, Doubal FN, Shuler K, Staals J, Dennis MS, et al. Small vessel disease and dietary salt intake: cross-sectional study and systematic review. J Stroke Cerebrovasc Dis. 2017;26(12):3020–8. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.004.CrossRefPubMedPubMedCentral

11.

Sala-Vila A, Arenaza-Urquijo EM, Sanchez-Benavides G, Suarez-Calvet M, Mila-Aloma M, Grau-Rivera O, et al. DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease. Am J Clin Nutr. 2021;113(6):1627–35. https://doi.org/10.1093/ajcn/nqab016.CrossRefPubMedPubMedCentral

12.

Patel Y, Joseph J. Sodium intake and heart failure. Int J Mol Sci. 2020;21(24):9474. https://doi.org/10.3390/ijms21249474.CrossRefPubMedPubMedCentral

13.

Li K, Song H, Wei F, Liu D, Zhao Y, Yin H, et al. High salt intake damages myocardial viability and induces cardiac remodeling via chronic inflammation in the elderly. Front Cardiovasc Med. 2022;9:952691. https://doi.org/10.3389/fcvm.2022.952691.CrossRefPubMedPubMedCentral

14.

13Afshin A, Sur PJ, Fay KA, Cornaby L, Ferrara G, Salama JS, et al. Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the global burden of Disease Study 2017. Lancet. 2019;393(10184):1958–72. https://doi.org/10.1016/S0140-6736(19)30041-8.

15.

Gao P, You M, Li L, Zhang Q, Fang X, Wei X, et al. Salt-induced hepatic inflammatory memory contributes to cardiovascular damage through epigenetic modulation of SIRT3. Circulation. 2022;145(5):375–91. https://doi.org/10.1161/CIRCULATIONAHA.121.055600.CrossRefPubMed

16.

Campbell NRC, He FJ, Tan M, Cappuccio FP, Neal B, Woodward M, et al. The international consortium for quality research on dietary sodium/salt (TRUE) position statement on the use of 24-hour, spot, and short duration (< 24 hours) timed urine collections to assess dietary sodium intake. J Clin Hypertens (Greenwich). 2019;21(6):700–9. https://doi.org/10.1111/jch.13551.CrossRefPubMed

17.

Liu W, Xing S, Wei F, Yao Y, Zhang H, Li YC, et al. Excessive dietary salt intake exacerbates cognitive impairment progression and increases dementia risk in older adults. J Am Med Dir Assoc. 2023;24(1):125–129e4. https://doi.org/10.1016/j.jamda.2022.10.001.CrossRefPubMed

18.

Ji TT, Zhao YX, Wang J, Cui Y, Duan DD, Chai Q, et al. Effect of low-dose statins and apolipoprotein e genotype on cerebral small vessel disease in older hypertensive patients: a subgroup analysis of a randomized clinical trial. J Am Med Dir Assoc. 2018;19(11):995–1002. https://doi.org/10.1016/j.jamda.2018.05.025.CrossRefPubMed

19.

Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–38. https://doi.org/10.1016/S1474-4422(13)70124-8.CrossRefPubMedPubMedCentral

20.

Wang SS, Lay S, Yu HN, Shen SR. Dietary guidelines for chinese residents (2016): comments and comparisons. J Zhejiang Univ Sci B. 2016;17(9):649–56. https://doi.org/10.1631/jzus.B1600341.CrossRefPubMedPubMedCentral

21.

Ghaznawi R, Geerlings MI, Jaarsma-Coes MG, Zwartbol MHT, Kuijf HJ, van der Graaf Y, et al. The association between lacunes and white matter hyperintensity features on MRI: the SMART-MR study. J Cereb Blood Flow Metab. 2019;39(12):2486–96. https://doi.org/10.1177/0271678X18800463.CrossRefPubMed

22.

Gyanwali B, Vrooman H, Venketasubramanian N, Wong TY, Cheng CY, Chen C, et al. Cerebral small vessel disease and enlarged perivascular spaces-data from memory clinic and population-based settings. Front Neurol. 2019;10:669. https://doi.org/10.3389/fneur.2019.00669.CrossRefPubMedPubMedCentral

23.

Balestrieri A, Lucatelli P, Suri HS, Montisci R, Suri JS, Wintermark M, et al. Volume of white matter hyperintensities, and cerebral micro-bleeds. J Stroke Cerebrovasc Dis. 2021;30(8):105905. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.10590521.CrossRefPubMed

24.

Brown IJ, Tzoulaki I, Candeias V, Elliott P. Salt intakes around the world: implications for public health. Int J Epidemiol. 2009;38(3):791–813. https://doi.org/10.1093/ije/dyp139.CrossRefPubMed

25.

Yuan YK, Miao Y, Ren TF, Huang F, Qian LP, Chen XJ, et al. High salt activates p97 to reduce host antiviral immunity by restricting viperin induction. EMBO Rep. 2022;23(1):e53466. https://doi.org/10.15252/embr.202153466.CrossRefPubMed

26.

Heye AK, Thrippleton MJ, Chappell FM, Hernandez MDV, Armitage PA, Makin SD, et al. Blood pressure and sodium: Association with MRI markers in cerebral small vessel disease. J Cereb Blood Flow Metab. 2016;36(1):264–74. https://doi.org/10.1038/jcbfm.2015.64.CrossRefPubMedPubMedCentral

27.

Bailey EL, McBride MW, McClure JD, Beattie W, Graham D, Dominiczak AF, et al. Effects of dietary salt on gene and protein expression in brain tissue of a model of sporadic small vessel disease. Clin Sci (Lond). 2018;132(12):1315–28. https://doi.org/10.1042/CS20171572.CrossRefPubMed

28.

Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, et al. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018;21(2):240–9. https://doi.org/10.1038/s41593-017-0059-z.CrossRefPubMedPubMedCentral

29.

Hu L, Zhu SP, Peng XP, Li KL, Peng WJ, Zhong Y, et al. High salt elicits brain inflammation and cognitive dysfunction, accompanied by alternations in the gut microbiota and decreased SCFA production. J Alzheimers Dis. 2020;77(2):629–40. https://doi.org/10.3233/JAD-200035.CrossRefPubMed

30.

Dominguez LJ, Veronese N, Vernuccio L, Catanese G, Inzerillo F, Salemi G, et al. Nutrition, Physical Activity, and other Lifestyle factors in the Prevention of Cognitive decline and Dementia. Nutrients. 2021;13(11):4080. https://doi.org/10.3390/nu13114080.CrossRefPubMedPubMedCentral

31.

Szadkowski D, Jörgensen A, Essing HG, Schaller KH. Creatinine elimination rate as reference value for analysis of urine samples. I. Effect of daily urine volume and circadian rhythm on creatinine excretion. Z Klin Chem Klin Biochem. 1970;8(5):529–33.PubMed

32.

Arsang-Jang S, Mansourian M, Mohammadifard N, Khosravi A, Oveis-Gharan S, Nouri F, et al. Temporal trend analysis of stroke and salt intake: a 15-year population-based study. Nutr Neurosci. 2021;24(5):384–94. https://doi.org/10.1080/1028415X.2019.1638665.CrossRefPubMed

33.

Tsirimiagkou C, Karatzi K, Argyris A, Basdeki ED, Kaloudi P, Yannakoulia M, et al. Dietary sodium and cardiovascular morbidity/mortality: a brief commentary on the ‘J-shape hypothesis’. J Hypertens. 2021;39(12):2335–43. https://doi.org/10.1097/HJH.0000000000002953.CrossRefPubMed

34.

Zhang Z, Liao H, Zhang X, Meng Q, Shi R, Feng J, et al. Associations of urinary sodium excretion with central hemodynamics and changes in vascular structure and function at high altitude. J Clin Hypertens (Greenwich). 2021;23(10):1907–14. https://doi.org/10.1111/jch.14356.CrossRefPubMed

35.

Wuopio J, Orho-Melander M, Ärnlöv J, Nowak C. Estimated salt intake and risk of atrial fibrillation in a prospective community-based cohort. J Intern Med. 2021;289(5):700–8. https://doi.org/10.1111/joim.13194.CrossRefPubMed

36.

Rust P, Ekmekcioglu C. Impact of salt intake on the pathogenesis and treatment of hypertension. Adv Exp Med Biol. 2017;956:61–84. https://doi.org/10.1007/5584-2016-147.CrossRefPubMed

37.

Mok V, Srikanth V, Xiong YY, Phan TG, Moran C, Chu SG, et al. Race-ethnicity and cerebral small vessel disease - comparison between chinese and white populations. Int J Stroke. 2014;9:36–42. https://doi.org/10.1111/ijs.12270.CrossRefPubMed

38.

Castello JP, Pasi M, Abramson JR, Rodriguez-Torres A, Marini S, Demel S, et al. Contribution of racial and ethnic differences in cerebral small vessel disease subtype and burden to risk of cerebral hemorrhage recurrence. Neurology. 2021;96(20):e2469–80. https://doi.org/10.1212/WNL.0000000000011932.CrossRefPubMedPubMedCentral

Title: Excessive salt intake accelerates the progression of cerebral small vessel disease in older adults
Authors: Di Liu
Qin Zhang
Shasha Xing
Fang Wei
Ke Li
Yingxin Zhao
Hua Zhang
Gary Gong
Yuqi Guo
Zhendong Liu
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Cerebral Small Vessel Disease
Published in: BMC Geriatrics / Issue 1/2023
Electronic ISSN: 1471-2318
DOI: https://doi.org/10.1186/s12877-023-03877-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Association of serum uric acid and fasting plasma glucose with cognitive function: a cross-sectional study

The factors associated with cognitive function among community-dwelling older adults in Taiwan

What are the factors affecting older adults’ experience of unmet healthcare needs amid the COVID-19 pandemic in Korea?

Factors associated with weight loss by age among community-dwelling older people

Implication of different frailty criteria in older people with atrial fibrillation: a prospective cohort study

Association between medication literacy and medication adherence and the mediating effect of self-efficacy in older people with multimorbidity

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials