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Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population‐based prospective study
Author(s) -
Holm H.,
Nägga K.,
Nilsson E. D.,
Ricci F.,
Melander O.,
Hansson O.,
Bachus E.,
Magnusson M.,
Fedorowski A.
Publication year - 2017
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12621
Subject(s) - medicine , dementia , hazard ratio , vascular dementia , prospective cohort study , endothelial dysfunction , proportional hazards model , quartile , population , confidence interval , rotterdam study , biomarker , cohort study , cardiology , disease , biochemistry , chemistry , environmental health
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.