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Published in: BMC Geriatrics 1/2024

Open Access 01-12-2024 | Vitamin D Deficiency | Research

Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults

Authors: Chi Zhang, Ju Cui, Shaojie Li, Ji Shen, Xuanmei Luo, Yao Yao, Hong Shi

Published in: BMC Geriatrics | Issue 1/2024

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Abstract

Background

Vitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people.

Methods

3072 older adults (86.07 ± 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012–2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted.

Results

During 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend < 0.05). In combined analyses, the highest all-cause mortality (HR: 2.18, 95% CI: 1.73 ~ 2.56), CVD mortality (HR: 2.30, 95% CI: 1.64 ~ 3.21), and non-CVD mortality (HR: 2.19, 95% CI: 1.79 ~ 2.49) were obtained in participants with both 25(OH)D deficiency (< 50 nmol/L) and high hs-CRP (≥ 3.0 mg/L), respectively. We observed significant additive interactions of 25(OH)D and hs-CRP on all-cause mortality and non-CVD mortality (RERIS>0).

Conclusions

Low 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.
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Literature
1.
go back to reference Krist AH, Davidson KW, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Epling JW Jr., Kubik M, et al. Screening for vitamin D Deficiency in adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(14):1436–42.PubMedCrossRef Krist AH, Davidson KW, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Epling JW Jr., Kubik M, et al. Screening for vitamin D Deficiency in adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(14):1436–42.PubMedCrossRef
2.
go back to reference Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144(Pt):138–45.PubMedCrossRef Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144(Pt):138–45.PubMedCrossRef
3.
go back to reference Jiang Z, Pu R, Li N, Chen C, Li J, Dai W, Wang Y, Hu J, Zhu D, Yu Q et al. High prevalence of vitamin D deficiency in Asia: a systematic review and meta-analysis. Crit Rev Food Sci Nutr 2021:1–10. Jiang Z, Pu R, Li N, Chen C, Li J, Dai W, Wang Y, Hu J, Zhu D, Yu Q et al. High prevalence of vitamin D deficiency in Asia: a systematic review and meta-analysis. Crit Rev Food Sci Nutr 2021:1–10.
4.
go back to reference Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Ann Oncol. 2019;30(5):733–43.PubMedPubMedCentralCrossRef Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Ann Oncol. 2019;30(5):733–43.PubMedPubMedCentralCrossRef
5.
go back to reference Zhang Y, Fang F, Tang J, Jia L, Feng Y, Xu P, Faramand A. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019;366:l4673.PubMedPubMedCentralCrossRef Zhang Y, Fang F, Tang J, Jia L, Feng Y, Xu P, Faramand A. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019;366:l4673.PubMedPubMedCentralCrossRef
6.
go back to reference Pilz S, Grübler M, Gaksch M, Schwetz V, Trummer C, Hartaigh B, Verheyen N, Tomaschitz A, März W. Vitamin D and mortality. Anticancer Res. 2016;36(3):1379–87.PubMed Pilz S, Grübler M, Gaksch M, Schwetz V, Trummer C, Hartaigh B, Verheyen N, Tomaschitz A, März W. Vitamin D and mortality. Anticancer Res. 2016;36(3):1379–87.PubMed
7.
go back to reference Busse B, Bale HA, Zimmermann EA, Panganiban B, Barth HD, Carriero A, Vettorazzi E, Zustin J, Hahn M, Ager JW 3, et al. Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture. Sci Transl Med. 2013;5(193):193ra188.CrossRef Busse B, Bale HA, Zimmermann EA, Panganiban B, Barth HD, Carriero A, Vettorazzi E, Zustin J, Hahn M, Ager JW 3, et al. Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture. Sci Transl Med. 2013;5(193):193ra188.CrossRef
8.
go back to reference Marcos-Pérez D, Sánchez-Flores M, Proietti S, Bonassi S, Costa S, Teixeira JP, Fernández-Tajes J, Pásaro E, Valdiglesias V, Laffon B. Low vitamin D levels and Frailty Status in older adults: a systematic review and Meta-analysis. Nutrients. 2020;12(8):2286.PubMedPubMedCentralCrossRef Marcos-Pérez D, Sánchez-Flores M, Proietti S, Bonassi S, Costa S, Teixeira JP, Fernández-Tajes J, Pásaro E, Valdiglesias V, Laffon B. Low vitamin D levels and Frailty Status in older adults: a systematic review and Meta-analysis. Nutrients. 2020;12(8):2286.PubMedPubMedCentralCrossRef
9.
go back to reference Yang A, Lv Q, Chen F, Wang Y, Liu Y, Shi W, Liu Y, Wang D. The effect of vitamin D on Sarcopenia depends on the level of physical activity in older adults. J Cachexia Sarcopenia Muscle. 2020;11(3):678–89.PubMedPubMedCentralCrossRef Yang A, Lv Q, Chen F, Wang Y, Liu Y, Shi W, Liu Y, Wang D. The effect of vitamin D on Sarcopenia depends on the level of physical activity in older adults. J Cachexia Sarcopenia Muscle. 2020;11(3):678–89.PubMedPubMedCentralCrossRef
10.
go back to reference Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer’s disease: a meta-analysis of dose-response (†). Nutr Neurosci. 2019;22(11):750–9.PubMedCrossRef Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer’s disease: a meta-analysis of dose-response (†). Nutr Neurosci. 2019;22(11):750–9.PubMedCrossRef
11.
go back to reference Sutherland JP, Zhou A, Hyppönen E. Vitamin D Deficiency increases Mortality Risk in the UK Biobank: a nonlinear mendelian randomization study. Ann Intern Med. 2022;175(11):1552–9.PubMedCrossRef Sutherland JP, Zhou A, Hyppönen E. Vitamin D Deficiency increases Mortality Risk in the UK Biobank: a nonlinear mendelian randomization study. Ann Intern Med. 2022;175(11):1552–9.PubMedCrossRef
12.
go back to reference Yue Z, Liang H, Gao X, Qin X, Li H, Xiang N, Liu E. The association between falls and anxiety among elderly Chinese individuals: the mediating roles of functional ability and social participation. J Affect Disord. 2022;301:300–6.PubMedCrossRef Yue Z, Liang H, Gao X, Qin X, Li H, Xiang N, Liu E. The association between falls and anxiety among elderly Chinese individuals: the mediating roles of functional ability and social participation. J Affect Disord. 2022;301:300–6.PubMedCrossRef
13.
go back to reference Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014;2(1):76–89.PubMedCrossRef Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014;2(1):76–89.PubMedCrossRef
15.
go back to reference Beavers DP, Kritchevsky SB, Gill TM, Ambrosius WT, Anton SD, Fielding RA, King AC, Rejeski WJ, Lovato L, McDermott MM, et al. Elevated IL-6 and CRP levels are Associated With Incident Self-reported major mobility disability: a pooled analysis of older adults with slow gait speed. J Gerontol A Biol Sci Med Sci. 2021;76(12):2293–9.PubMedPubMedCentralCrossRef Beavers DP, Kritchevsky SB, Gill TM, Ambrosius WT, Anton SD, Fielding RA, King AC, Rejeski WJ, Lovato L, McDermott MM, et al. Elevated IL-6 and CRP levels are Associated With Incident Self-reported major mobility disability: a pooled analysis of older adults with slow gait speed. J Gerontol A Biol Sci Med Sci. 2021;76(12):2293–9.PubMedPubMedCentralCrossRef
16.
go back to reference Soysal P, Stubbs B, Lucato P, Luchini C, Solmi M, Peluso R, Sergi G, Isik AT, Manzato E, Maggi S, et al. Inflammation and frailty in the elderly: a systematic review and meta-analysis. Ageing Res Rev. 2016;31:1–8.PubMedCrossRef Soysal P, Stubbs B, Lucato P, Luchini C, Solmi M, Peluso R, Sergi G, Isik AT, Manzato E, Maggi S, et al. Inflammation and frailty in the elderly: a systematic review and meta-analysis. Ageing Res Rev. 2016;31:1–8.PubMedCrossRef
17.
go back to reference Li Y, Zhong X, Cheng G, Zhao C, Zhang L, Hong Y, Wan Q, He R, Wang Z. Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: a meta-analysis. Atherosclerosis. 2017;259:75–82.PubMedCrossRef Li Y, Zhong X, Cheng G, Zhao C, Zhang L, Hong Y, Wan Q, He R, Wang Z. Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: a meta-analysis. Atherosclerosis. 2017;259:75–82.PubMedCrossRef
18.
go back to reference Devaraj S, O’Keefe G, Jialal I. Defining the proinflammatory phenotype using high sensitive C-reactive protein levels as the biomarker. J Clin Endocrinol Metabolism. 2005;90(8):4549–54.CrossRef Devaraj S, O’Keefe G, Jialal I. Defining the proinflammatory phenotype using high sensitive C-reactive protein levels as the biomarker. J Clin Endocrinol Metabolism. 2005;90(8):4549–54.CrossRef
19.
go back to reference Zipperer MB, Churilla JR, Stapleton JN, Richardson MR. Joint effect of cognitive function and C-reactive protein on all-cause mortality risk: 1999–2002 NHANES. Ann Epidemiol. 2022;74:111–7.PubMedCrossRef Zipperer MB, Churilla JR, Stapleton JN, Richardson MR. Joint effect of cognitive function and C-reactive protein on all-cause mortality risk: 1999–2002 NHANES. Ann Epidemiol. 2022;74:111–7.PubMedCrossRef
20.
go back to reference Sung KC, Ryu S, Chang Y, Byrne CD, Kim SH. C-reactive protein and risk of cardiovascular and all-cause mortality in 268 803 East asians. Eur Heart J. 2014;35(27):1809–16.PubMedCrossRef Sung KC, Ryu S, Chang Y, Byrne CD, Kim SH. C-reactive protein and risk of cardiovascular and all-cause mortality in 268 803 East asians. Eur Heart J. 2014;35(27):1809–16.PubMedCrossRef
21.
go back to reference Chen PL, Li ZH, Yang HL, Cao ZJ, Cheng X, Zhao F, Zhang XR, Lv YB, Li FR, Zhou YF, et al. Associations between high-sensitivity C-Reactive protein and all-cause Mortality among Oldest-Old in Chinese Longevity areas: A Community-based Cohort Study. Front Public Health. 2022;10:824783.PubMedPubMedCentralCrossRef Chen PL, Li ZH, Yang HL, Cao ZJ, Cheng X, Zhao F, Zhang XR, Lv YB, Li FR, Zhou YF, et al. Associations between high-sensitivity C-Reactive protein and all-cause Mortality among Oldest-Old in Chinese Longevity areas: A Community-based Cohort Study. Front Public Health. 2022;10:824783.PubMedPubMedCentralCrossRef
22.
go back to reference Hu FB. Metabolic profiling of diabetes: from black-box epidemiology to systems epidemiology. Clin Chem. 2011;57(9):1224–6.PubMedCrossRef Hu FB. Metabolic profiling of diabetes: from black-box epidemiology to systems epidemiology. Clin Chem. 2011;57(9):1224–6.PubMedCrossRef
23.
go back to reference Kruit A, Zanen P. The association between vitamin D and C-reactive protein levels in patients with inflammatory and non-inflammatory diseases. Clin Biochem. 2016;49(7):534–7.PubMedCrossRef Kruit A, Zanen P. The association between vitamin D and C-reactive protein levels in patients with inflammatory and non-inflammatory diseases. Clin Biochem. 2016;49(7):534–7.PubMedCrossRef
24.
go back to reference Haussler MR, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh J-C, Jurutka PW. Molecular mechanisms of vitamin D action. Calcif Tissue Int. 2013;92(2):77–98.PubMedCrossRef Haussler MR, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh J-C, Jurutka PW. Molecular mechanisms of vitamin D action. Calcif Tissue Int. 2013;92(2):77–98.PubMedCrossRef
25.
26.
go back to reference Luan Y-y. Yao Y-m: the clinical significance and potential role of C-reactive protein in chronic inflammatory and neurodegenerative diseases. Front Immunol. 2018;9:1302.PubMedPubMedCentralCrossRef Luan Y-y. Yao Y-m: the clinical significance and potential role of C-reactive protein in chronic inflammatory and neurodegenerative diseases. Front Immunol. 2018;9:1302.PubMedPubMedCentralCrossRef
27.
go back to reference Li Q, Dai Z, Cao Y, Wang L. Association of C-reactive protein and vitamin D deficiency with cardiovascular disease: a nationwide cross-sectional study from National Health and Nutrition Examination Survey 2007 to 2008. Clin Cardiol. 2019;42(7):663–9.PubMedPubMedCentralCrossRef Li Q, Dai Z, Cao Y, Wang L. Association of C-reactive protein and vitamin D deficiency with cardiovascular disease: a nationwide cross-sectional study from National Health and Nutrition Examination Survey 2007 to 2008. Clin Cardiol. 2019;42(7):663–9.PubMedPubMedCentralCrossRef
28.
go back to reference Zhu DM, Liu Y, Zhang AG, Chu ZX, Wu Q, Li H, Ge JF, Dong Y, Zhu P. High levels of vitamin D in relation to reduced risk of schizophrenia with elevated C-reactive protein. Psychiatry Res. 2015;228(3):565–70.PubMedCrossRef Zhu DM, Liu Y, Zhang AG, Chu ZX, Wu Q, Li H, Ge JF, Dong Y, Zhu P. High levels of vitamin D in relation to reduced risk of schizophrenia with elevated C-reactive protein. Psychiatry Res. 2015;228(3):565–70.PubMedCrossRef
29.
go back to reference Fassula AS, Gonzalez-Chica D, Giehl MC, Silva DAS, Cembranel F, Moreno YMF. Moderator role of vitamin D concentrations on the association between metabolic syndrome and C-reactive protein among adults. Arch Endocrinol Metab. 2021;64(6):695–703.PubMed Fassula AS, Gonzalez-Chica D, Giehl MC, Silva DAS, Cembranel F, Moreno YMF. Moderator role of vitamin D concentrations on the association between metabolic syndrome and C-reactive protein among adults. Arch Endocrinol Metab. 2021;64(6):695–703.PubMed
30.
go back to reference Zhu C, Walsh C, Zhou L, Zhang X. Latent classification analysis of leisure activities and their impact on ADL, IADL and cognitive ability of older adults based on CLHLS (2008–2018). Int J Environ Res Public Health. 2023;20(2):1546.PubMedPubMedCentralCrossRef Zhu C, Walsh C, Zhou L, Zhang X. Latent classification analysis of leisure activities and their impact on ADL, IADL and cognitive ability of older adults based on CLHLS (2008–2018). Int J Environ Res Public Health. 2023;20(2):1546.PubMedPubMedCentralCrossRef
31.
go back to reference Zeng Y, Feng Q, Gu D, Vaupel JW. Demographics, phenotypic health characteristics and genetic analysis of centenarians in China. Mech Ageing Dev. 2017;165(Pt B):86–97.PubMedCrossRef Zeng Y, Feng Q, Gu D, Vaupel JW. Demographics, phenotypic health characteristics and genetic analysis of centenarians in China. Mech Ageing Dev. 2017;165(Pt B):86–97.PubMedCrossRef
33.
go back to reference Matchar DB, Chei CL, Yin ZX, Koh V, Chakraborty B, Shi XM, Zeng Y. Vitamin D levels and the risk of Cognitive decline in Chinese Elderly people: the Chinese longitudinal healthy longevity survey. J Gerontol A Biol Sci Med Sci. 2016;71(10):1363–8.PubMedPubMedCentralCrossRef Matchar DB, Chei CL, Yin ZX, Koh V, Chakraborty B, Shi XM, Zeng Y. Vitamin D levels and the risk of Cognitive decline in Chinese Elderly people: the Chinese longitudinal healthy longevity survey. J Gerontol A Biol Sci Med Sci. 2016;71(10):1363–8.PubMedPubMedCentralCrossRef
34.
go back to reference Lv YB, Yin ZX, Chei CL, Qian HZ, Kraus VB, Zhang J, Brasher MS, Shi XM, Matchar DB, Zeng Y. Low-density lipoprotein cholesterol was inversely associated with 3-year all-cause mortality among Chinese oldest old: data from the Chinese longitudinal healthy longevity survey. Atherosclerosis. 2015;239(1):137–42.PubMedPubMedCentralCrossRef Lv YB, Yin ZX, Chei CL, Qian HZ, Kraus VB, Zhang J, Brasher MS, Shi XM, Matchar DB, Zeng Y. Low-density lipoprotein cholesterol was inversely associated with 3-year all-cause mortality among Chinese oldest old: data from the Chinese longitudinal healthy longevity survey. Atherosclerosis. 2015;239(1):137–42.PubMedPubMedCentralCrossRef
35.
go back to reference Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.PubMedCrossRef Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.PubMedCrossRef
36.
go back to reference Zhai Y, Shi XM, Fitzgerald SM, Qian HZ, Kraus VB, Sereny M, Hu P, Yin ZX, Xu JW, Zeng Y. High sensitivity C-reactive protein associated with different health predictors in middle-aged and oldest old Chinese. Biomed Environ Sci. 2012;25(3):257–66.PubMedPubMedCentral Zhai Y, Shi XM, Fitzgerald SM, Qian HZ, Kraus VB, Sereny M, Hu P, Yin ZX, Xu JW, Zeng Y. High sensitivity C-reactive protein associated with different health predictors in middle-aged and oldest old Chinese. Biomed Environ Sci. 2012;25(3):257–66.PubMedPubMedCentral
37.
go back to reference Chen C, Liu Y, Cao Z, Yin Z, Zhao F, Lv Y, Liu Z, Mao C, Song S, Liu L, et al. Combined associations of hs-CRP and cognitive function with all-cause mortality among oldest-old adults in Chinese longevity areas: a prospective cohort study. Immun Ageing. 2019;16:30.PubMedPubMedCentralCrossRef Chen C, Liu Y, Cao Z, Yin Z, Zhao F, Lv Y, Liu Z, Mao C, Song S, Liu L, et al. Combined associations of hs-CRP and cognitive function with all-cause mortality among oldest-old adults in Chinese longevity areas: a prospective cohort study. Immun Ageing. 2019;16:30.PubMedPubMedCentralCrossRef
38.
go back to reference Bernabe-Ortiz A, Carrillo-Larco RM, Gilman RH, Smeeth L, Checkley W, Miranda JJ. High-sensitivity C-reactive protein and all-cause mortality in four diverse populations: the CRONICAS Cohort Study. Ann Epidemiol. 2022;67:13–8.PubMedCrossRef Bernabe-Ortiz A, Carrillo-Larco RM, Gilman RH, Smeeth L, Checkley W, Miranda JJ. High-sensitivity C-reactive protein and all-cause mortality in four diverse populations: the CRONICAS Cohort Study. Ann Epidemiol. 2022;67:13–8.PubMedCrossRef
39.
go back to reference Jin X, Xiong S, Ju SY, Zeng Y, Yan LL, Yao Y. Serum 25-Hydroxyvitamin D, Albumin, and Mortality among Chinese older adults: a Population-based Longitudinal Study. J Clin Endocrinol Metab. 2020;105(8):dgaa349.PubMedCrossRef Jin X, Xiong S, Ju SY, Zeng Y, Yan LL, Yao Y. Serum 25-Hydroxyvitamin D, Albumin, and Mortality among Chinese older adults: a Population-based Longitudinal Study. J Clin Endocrinol Metab. 2020;105(8):dgaa349.PubMedCrossRef
40.
go back to reference Wan Z, Guo J, Pan A, Chen C, Liu L, Liu G. Association of serum 25-Hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with diabetes. Diabetes Care. 2021;44(2):350–7.PubMedCrossRef Wan Z, Guo J, Pan A, Chen C, Liu L, Liu G. Association of serum 25-Hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with diabetes. Diabetes Care. 2021;44(2):350–7.PubMedCrossRef
41.
go back to reference Lin SW, Chen W, Fan JH, Dawsey SM, Taylor PR, Qiao YL, Abnet CC. Prospective study of serum 25-hydroxyvitamin D concentration and mortality in a Chinese population. Am J Epidemiol. 2012;176(11):1043–50.PubMedPubMedCentralCrossRef Lin SW, Chen W, Fan JH, Dawsey SM, Taylor PR, Qiao YL, Abnet CC. Prospective study of serum 25-hydroxyvitamin D concentration and mortality in a Chinese population. Am J Epidemiol. 2012;176(11):1043–50.PubMedPubMedCentralCrossRef
42.
go back to reference Lv X, Li W, Ma Y, Chen H, Zeng Y, Yu X, Hofman A, Wang H. Cognitive decline and mortality among community-dwelling Chinese older people. BMC Med. 2019;17(1):63.PubMedPubMedCentralCrossRef Lv X, Li W, Ma Y, Chen H, Zeng Y, Yu X, Hofman A, Wang H. Cognitive decline and mortality among community-dwelling Chinese older people. BMC Med. 2019;17(1):63.PubMedPubMedCentralCrossRef
43.
go back to reference Andersson T, Alfredsson L, Källberg H, Zdravkovic S, Ahlbom A. Calculating measures of biological interaction. Eur J Epidemiol. 2005;20(7):575–9.PubMedCrossRef Andersson T, Alfredsson L, Källberg H, Zdravkovic S, Ahlbom A. Calculating measures of biological interaction. Eur J Epidemiol. 2005;20(7):575–9.PubMedCrossRef
44.
go back to reference Knol MJ, van der Tweel I, Grobbee DE, Numans ME, Geerlings MI. Estimating interaction on an additive scale between continuous determinants in a logistic regression model. Int J Epidemiol. 2007;36(5):1111–8.PubMedCrossRef Knol MJ, van der Tweel I, Grobbee DE, Numans ME, Geerlings MI. Estimating interaction on an additive scale between continuous determinants in a logistic regression model. Int J Epidemiol. 2007;36(5):1111–8.PubMedCrossRef
45.
go back to reference Fan X, Wang J, Song M, Giovannucci EL, Ma H, Jin G, Hu Z, Shen H, Hang D. Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK Biobank. J Clin Endocrinol Metab 2020, 105(10). Fan X, Wang J, Song M, Giovannucci EL, Ma H, Jin G, Hu Z, Shen H, Hang D. Vitamin D status and risk of all-cause and cause-specific mortality in a large cohort: results from the UK Biobank. J Clin Endocrinol Metab 2020, 105(10).
46.
go back to reference Zeng J, Li T, Sun B, Miao X, Wang L, Ma LC, Li N, Gong Y, He Y, Li C, et al. Change of vitamin D status and all-cause mortality among Chinese older adults: a population-based cohort study. BMC Geriatr. 2022;22(1):245.PubMedPubMedCentralCrossRef Zeng J, Li T, Sun B, Miao X, Wang L, Ma LC, Li N, Gong Y, He Y, Li C, et al. Change of vitamin D status and all-cause mortality among Chinese older adults: a population-based cohort study. BMC Geriatr. 2022;22(1):245.PubMedPubMedCentralCrossRef
47.
go back to reference Bikle D, Christakos S. New aspects of vitamin D metabolism and action - addressing the skin as source and target. Nat Rev Endocrinol. 2020;16(4):234–52.PubMedCrossRef Bikle D, Christakos S. New aspects of vitamin D metabolism and action - addressing the skin as source and target. Nat Rev Endocrinol. 2020;16(4):234–52.PubMedCrossRef
48.
go back to reference Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev. 2019;40(4):1109–51.PubMedCrossRef Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P, Munns CF, Lazaretti-Castro M, Giustina A, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev. 2019;40(4):1109–51.PubMedCrossRef
49.
go back to reference Iuliano S, Poon S, Robbins J, Bui M, Wang X, De Groot L, Van Loan M, Zadeh AG, Nguyen T, Seeman E. Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial. BMJ. 2021;375:n2364.PubMedPubMedCentralCrossRef Iuliano S, Poon S, Robbins J, Bui M, Wang X, De Groot L, Van Loan M, Zadeh AG, Nguyen T, Seeman E. Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial. BMJ. 2021;375:n2364.PubMedPubMedCentralCrossRef
51.
go back to reference Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D’s Effect on Immune Function. Nutrients 2020, 12(5). Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D’s Effect on Immune Function. Nutrients 2020, 12(5).
53.
go back to reference Kositsawat J, Kuo C-L, Barry LC, Melzer D, Bandinelli S, Ferrucci L, Wu R, Kuchel GA. Interaction between vitamin D and interleukin 6 on slow gait speed: 6-Year follow-up data of older adults from InCHIANTI. The Journals of Gerontology: Series A. 2019;75(6):1161–6. Kositsawat J, Kuo C-L, Barry LC, Melzer D, Bandinelli S, Ferrucci L, Wu R, Kuchel GA. Interaction between vitamin D and interleukin 6 on slow gait speed: 6-Year follow-up data of older adults from InCHIANTI. The Journals of Gerontology: Series A. 2019;75(6):1161–6.
54.
55.
go back to reference Schnatz PF, Nudy M, O’Sullivan DM, Jiang X, Cline JM, Kaplan JR, Clarkson TB, Appt SE. The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis. Maturitas. 2012;73(2):143–7.PubMedPubMedCentralCrossRef Schnatz PF, Nudy M, O’Sullivan DM, Jiang X, Cline JM, Kaplan JR, Clarkson TB, Appt SE. The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis. Maturitas. 2012;73(2):143–7.PubMedPubMedCentralCrossRef
56.
go back to reference Gunta SS, Thadhani RI, Mak RH. The effect of vitamin D status on risk factors for cardiovascular disease. Nat Rev Nephrol. 2013;9(6):337–47.PubMedCrossRef Gunta SS, Thadhani RI, Mak RH. The effect of vitamin D status on risk factors for cardiovascular disease. Nat Rev Nephrol. 2013;9(6):337–47.PubMedCrossRef
57.
go back to reference Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013;202:100–7.PubMedCrossRef Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013;202:100–7.PubMedCrossRef
58.
go back to reference Ni P, Yu M, Zhang R, Cheng C, He M, Wang H, Chen S, Duan G. Dose-response association between C-reactive protein and risk of all-cause and cause-specific mortality: a systematic review and meta-analysis of cohort studies. Ann Epidemiol. 2020;51:20–27e11.PubMedCrossRef Ni P, Yu M, Zhang R, Cheng C, He M, Wang H, Chen S, Duan G. Dose-response association between C-reactive protein and risk of all-cause and cause-specific mortality: a systematic review and meta-analysis of cohort studies. Ann Epidemiol. 2020;51:20–27e11.PubMedCrossRef
59.
go back to reference Lakoski SG, Cushman M, Palmas W, Blumenthal R, D’Agostino RB Jr., Herrington DM. The relationship between blood pressure and C-reactive protein in the multi-ethnic study of atherosclerosis (MESA). J Am Coll Cardiol. 2005;46(10):1869–74.PubMedCrossRef Lakoski SG, Cushman M, Palmas W, Blumenthal R, D’Agostino RB Jr., Herrington DM. The relationship between blood pressure and C-reactive protein in the multi-ethnic study of atherosclerosis (MESA). J Am Coll Cardiol. 2005;46(10):1869–74.PubMedCrossRef
60.
go back to reference Calabrò P, Golia E, Yeh ET. CRP and the risk of atherosclerotic events. Semin Immunopathol. 2009;31(1):79–94.PubMedCrossRef Calabrò P, Golia E, Yeh ET. CRP and the risk of atherosclerotic events. Semin Immunopathol. 2009;31(1):79–94.PubMedCrossRef
61.
go back to reference Kaura A, Hartley A, Panoulas V, Glampson B, Shah ASV, Davies J, Mulla A, Woods K, Omigie J, Shah AD, et al. Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study. PLoS Med. 2022;19(2):e1003911.PubMedPubMedCentralCrossRef Kaura A, Hartley A, Panoulas V, Glampson B, Shah ASV, Davies J, Mulla A, Woods K, Omigie J, Shah AD, et al. Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study. PLoS Med. 2022;19(2):e1003911.PubMedPubMedCentralCrossRef
62.
go back to reference Liu Y, Zhang C, Jiang L, Xu L, Tian J, Zhao X, Feng X, Wang D, Zhang Y, Sun K, et al. Relationship between high-sensitivity C-Reactive protein and long-term outcomes in Elderly patients with 3-Vessel disease. Angiology. 2022;73(1):60–7.PubMedCrossRef Liu Y, Zhang C, Jiang L, Xu L, Tian J, Zhao X, Feng X, Wang D, Zhang Y, Sun K, et al. Relationship between high-sensitivity C-Reactive protein and long-term outcomes in Elderly patients with 3-Vessel disease. Angiology. 2022;73(1):60–7.PubMedCrossRef
63.
go back to reference Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001;103(13):1813–8.PubMedCrossRef Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001;103(13):1813–8.PubMedCrossRef
64.
go back to reference Wang X, Bao W, Liu J, Ouyang YY, Wang D, Rong S, Xiao X, Shan ZL, Zhang Y, Yao P, et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36(1):166–75.PubMedCrossRef Wang X, Bao W, Liu J, Ouyang YY, Wang D, Rong S, Xiao X, Shan ZL, Zhang Y, Yao P, et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36(1):166–75.PubMedCrossRef
65.
go back to reference Hegazy SH, Thomassen JQ, Rasmussen IJ, Nordestgaard BG, Tybjaerg-Hansen A, Frikke-Schmidt R. C-reactive protein levels and risk of dementia-observational and genetic studies of 111,242 individuals from the general population. Alzheimers Dement. 2022;18(11):2262–71.PubMedPubMedCentralCrossRef Hegazy SH, Thomassen JQ, Rasmussen IJ, Nordestgaard BG, Tybjaerg-Hansen A, Frikke-Schmidt R. C-reactive protein levels and risk of dementia-observational and genetic studies of 111,242 individuals from the general population. Alzheimers Dement. 2022;18(11):2262–71.PubMedPubMedCentralCrossRef
66.
go back to reference Zhu M, Ma Z, Zhang X, Hang D, Yin R, Feng J, Xu L, Shen H. C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and mendelian randomization analysis. BMC Med. 2022;20(1):301.PubMedPubMedCentralCrossRef Zhu M, Ma Z, Zhang X, Hang D, Yin R, Feng J, Xu L, Shen H. C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and mendelian randomization analysis. BMC Med. 2022;20(1):301.PubMedPubMedCentralCrossRef
67.
go back to reference Lee M, Lee K, Kim DW, Cho JS, Kim TS, Kwon J, Kim CJ, Park CS, Kim HY, Yoo KD, et al. Relationship of serial high-sensitivity C-Reactive protein changes to long-term clinical outcomes in stabilised patients after myocardial infarction. Can J Cardiol. 2022;38(1):92–101.PubMedCrossRef Lee M, Lee K, Kim DW, Cho JS, Kim TS, Kwon J, Kim CJ, Park CS, Kim HY, Yoo KD, et al. Relationship of serial high-sensitivity C-Reactive protein changes to long-term clinical outcomes in stabilised patients after myocardial infarction. Can J Cardiol. 2022;38(1):92–101.PubMedCrossRef
68.
go back to reference Sugimoto A, Toyokawa T, Miki Y, Yoshii M, Tamura T, Sakurai K, Kubo N, Tanaka H, Lee S, Muguruma K, et al. Preoperative C-reactive protein to albumin ratio predicts anastomotic leakage after esophagectomy for thoracic esophageal cancer: a single-center retrospective cohort study. BMC Surg. 2021;21(1):348.PubMedPubMedCentralCrossRef Sugimoto A, Toyokawa T, Miki Y, Yoshii M, Tamura T, Sakurai K, Kubo N, Tanaka H, Lee S, Muguruma K, et al. Preoperative C-reactive protein to albumin ratio predicts anastomotic leakage after esophagectomy for thoracic esophageal cancer: a single-center retrospective cohort study. BMC Surg. 2021;21(1):348.PubMedPubMedCentralCrossRef
69.
go back to reference Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012;188(5):2127–35.PubMedCrossRef Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012;188(5):2127–35.PubMedCrossRef
70.
go back to reference Jin D, Zhu DM, Hu HL, Yao MN, Yin WJ, Tao RX, Zhu P. Vitamin D status affects the relationship between lipid profile and high-sensitivity C-reactive protein. Nutr Metab (Lond). 2020;17:57.PubMedCrossRef Jin D, Zhu DM, Hu HL, Yao MN, Yin WJ, Tao RX, Zhu P. Vitamin D status affects the relationship between lipid profile and high-sensitivity C-reactive protein. Nutr Metab (Lond). 2020;17:57.PubMedCrossRef
71.
go back to reference Petermann-Rocha F, Gray SR, Pell JP, Celis-Morales C, Ho FK. Biomarkers Profile of people with Sarcopenia: a cross-sectional analysis from UK Biobank. J Am Med Dir Assoc. 2020;21(12):2017. e2011-2017.e2019.CrossRef Petermann-Rocha F, Gray SR, Pell JP, Celis-Morales C, Ho FK. Biomarkers Profile of people with Sarcopenia: a cross-sectional analysis from UK Biobank. J Am Med Dir Assoc. 2020;21(12):2017. e2011-2017.e2019.CrossRef
73.
go back to reference Custodero C, Mankowski RT, Lee SA, Chen Z, Wu S, Manini TM, Hincapie Echeverri J, Sabbà C, Beavers DP, Cauley JA, et al. Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: a systematic review and meta-analysis. Ageing Res Rev. 2018;46:42–59.PubMedPubMedCentralCrossRef Custodero C, Mankowski RT, Lee SA, Chen Z, Wu S, Manini TM, Hincapie Echeverri J, Sabbà C, Beavers DP, Cauley JA, et al. Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: a systematic review and meta-analysis. Ageing Res Rev. 2018;46:42–59.PubMedPubMedCentralCrossRef
74.
go back to reference Han S, Zhang F, Yu H, Wei J, Xue L, Duan Z, Niu Z. Systemic inflammation accelerates the adverse effects of air pollution on metabolic syndrome: findings from the China health and Retirement Longitudinal Study (CHARLS). Environ Res. 2022;215(Pt 1):114340.PubMedCrossRef Han S, Zhang F, Yu H, Wei J, Xue L, Duan Z, Niu Z. Systemic inflammation accelerates the adverse effects of air pollution on metabolic syndrome: findings from the China health and Retirement Longitudinal Study (CHARLS). Environ Res. 2022;215(Pt 1):114340.PubMedCrossRef
Metadata
Title
Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults
Authors
Chi Zhang
Ju Cui
Shaojie Li
Ji Shen
Xuanmei Luo
Yao Yao
Hong Shi
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2024
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-024-04706-x

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