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Biomarkers of microvascular endothelial dysfunction predict incident dementia : a population-based prospective study

Holm, Hannes LU ; Nägga, K LU ; Nilsson, E D LU ; Ricci, F; Melander, O LU ; Hansson, Oskar LU ; Bachus, E LU ; Magnusson, Martin LU and Fedorowski, A LU (2017) In Journal of Internal Medicine 282(1). p.94-101
Abstract

BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults.

METHODS: A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83... (More)

BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults.

METHODS: A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis.

RESULTS: Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P < 0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L(-1) vs. Q1, 22-77 pmol L(-1) : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L(-1) (Q3-Q4, 68-432 pmol L(-1) vs. Q1-Q2,4-68 pmol L(-1) ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors.

CONCLUSIONS: Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Internal Medicine
volume
282
issue
1
pages
94 - 101
publisher
Wiley-Blackwell
external identifiers
  • scopus:85018419236
  • wos:000403441800008
ISSN
1365-2796
DOI
10.1111/joim.12621
language
English
LU publication?
yes
id
4ed7953e-2e0c-4073-b5f8-665eda5f9489
date added to LUP
2017-05-12 14:49:58
date last changed
2017-09-18 11:35:47
@article{4ed7953e-2e0c-4073-b5f8-665eda5f9489,
  abstract     = {<p>BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults.</p><p>METHODS: A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis.</p><p>RESULTS: Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P &lt; 0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L(-1) vs. Q1, 22-77 pmol L(-1) : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L(-1) (Q3-Q4, 68-432 pmol L(-1) vs. Q1-Q2,4-68 pmol L(-1) ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors.</p><p>CONCLUSIONS: Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.</p>},
  author       = {Holm, Hannes and Nägga, K and Nilsson, E D and Ricci, F and Melander, O and Hansson, Oskar and Bachus, E and Magnusson, Martin and Fedorowski, A},
  issn         = {1365-2796},
  language     = {eng},
  month        = {05},
  number       = {1},
  pages        = {94--101},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Internal Medicine},
  title        = {Biomarkers of microvascular endothelial dysfunction predict incident dementia : a population-based prospective study},
  url          = {http://dx.doi.org/10.1111/joim.12621},
  volume       = {282},
  year         = {2017},
}