Nitric oxide dysregulation in patients with heart failure

The association of depressive symptoms with l-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, and isoprostane

P.M.C. Mommersteeg, R.G. Schoemaker, U.L. Eisel, I.M. Garrelds, C.G. Schalkwijk, W.J. Kop

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Objective: 
Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovascular disease. Because depression is associated with poor HF outcomes, the present study tested the hypothesis that depression is associated with a dysregulated NO pathway in patients with HF.
Methods: 
Serum levels of NO regulation (L-arginine, asymmetric dimethylarginine [ADMA], and symmetric dimethylarginine [SDMA]) and oxidative stress (isoprostane 8-epi prostaglandin F2α) were measured in 104 patients with HF (mean [standard deviation] age = 65.7 [8.4] years, 28% women) at baseline and 12 months. Depressive symptoms were measured using the Beck Depression Inventory. The associations between depressive symptoms with markers of NO regulation were examined with mixed-model analysis, adjusted for age, sex, time of assessment, left ventricular ejection fraction, creatinine, and hypertension.
Results: 
Depressive symptoms were correlated with a lower L-arginine/ADMA ratio (r = −0.22, p = .003) and higher SDMA levels (r = 0.28, p < .001). Associations were similar for somatic depressive symptoms and cognitive-affective symptoms (L-arginine/ADMA ratio: r = −0.20 [p = .009] versus r = −0.19 [p = .013]; ADMA: r = 0.16 [p = .043] versus r = 0.10 [p = .20]; SDMA: r = 0.27 [p < .001] versus r = 0.22 [p = .005], respectively). No associations were found between depressive symptoms and isoprostane. The association between depression and the L-arginine/ADMA ratio remained significant in multivariate adjusted models.
Conclusions: 
Depressive symptoms were associated with markers of NO dysregulation, particularly the L-arginine/ADMA ratio and SDMA, in patients with HF. The lower L-arginine/ADMA ratio indicates less available NO, suggesting that NO-related endothelial dysfunction may play a role in the adverse risk of HF progression associated with depression.
Original languageEnglish
Pages (from-to)292-302
JournalPsychosomatic Medicine
Volume77
Issue number3
DOIs
Publication statusPublished - 2015

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Nitric Oxide
Depression
Affective Symptoms
Dinoprost
Creatinine
Equipment and Supplies
Serum

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@article{8b6182f2dba54db3a9521a987ad1ca21,
title = "Nitric oxide dysregulation in patients with heart failure: The association of depressive symptoms with l-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, and isoprostane",
abstract = "Objective: Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovascular disease. Because depression is associated with poor HF outcomes, the present study tested the hypothesis that depression is associated with a dysregulated NO pathway in patients with HF.Methods: Serum levels of NO regulation (L-arginine, asymmetric dimethylarginine [ADMA], and symmetric dimethylarginine [SDMA]) and oxidative stress (isoprostane 8-epi prostaglandin F2α) were measured in 104 patients with HF (mean [standard deviation] age = 65.7 [8.4] years, 28{\%} women) at baseline and 12 months. Depressive symptoms were measured using the Beck Depression Inventory. The associations between depressive symptoms with markers of NO regulation were examined with mixed-model analysis, adjusted for age, sex, time of assessment, left ventricular ejection fraction, creatinine, and hypertension.Results: Depressive symptoms were correlated with a lower L-arginine/ADMA ratio (r = −0.22, p = .003) and higher SDMA levels (r = 0.28, p < .001). Associations were similar for somatic depressive symptoms and cognitive-affective symptoms (L-arginine/ADMA ratio: r = −0.20 [p = .009] versus r = −0.19 [p = .013]; ADMA: r = 0.16 [p = .043] versus r = 0.10 [p = .20]; SDMA: r = 0.27 [p < .001] versus r = 0.22 [p = .005], respectively). No associations were found between depressive symptoms and isoprostane. The association between depression and the L-arginine/ADMA ratio remained significant in multivariate adjusted models.Conclusions: Depressive symptoms were associated with markers of NO dysregulation, particularly the L-arginine/ADMA ratio and SDMA, in patients with HF. The lower L-arginine/ADMA ratio indicates less available NO, suggesting that NO-related endothelial dysfunction may play a role in the adverse risk of HF progression associated with depression.",
author = "P.M.C. Mommersteeg and R.G. Schoemaker and U.L. Eisel and I.M. Garrelds and C.G. Schalkwijk and W.J. Kop",
year = "2015",
doi = "10.1097/PSY.0000000000000162",
language = "English",
volume = "77",
pages = "292--302",
journal = "Psychosomatic Medicine",
issn = "0033-3174",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

Nitric oxide dysregulation in patients with heart failure : The association of depressive symptoms with l-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, and isoprostane . / Mommersteeg, P.M.C.; Schoemaker, R.G.; Eisel, U.L.; Garrelds, I.M.; Schalkwijk, C.G.; Kop, W.J.

In: Psychosomatic Medicine, Vol. 77, No. 3, 2015, p. 292-302.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Nitric oxide dysregulation in patients with heart failure

T2 - The association of depressive symptoms with l-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, and isoprostane

AU - Mommersteeg, P.M.C.

AU - Schoemaker, R.G.

AU - Eisel, U.L.

AU - Garrelds, I.M.

AU - Schalkwijk, C.G.

AU - Kop, W.J.

PY - 2015

Y1 - 2015

N2 - Objective: Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovascular disease. Because depression is associated with poor HF outcomes, the present study tested the hypothesis that depression is associated with a dysregulated NO pathway in patients with HF.Methods: Serum levels of NO regulation (L-arginine, asymmetric dimethylarginine [ADMA], and symmetric dimethylarginine [SDMA]) and oxidative stress (isoprostane 8-epi prostaglandin F2α) were measured in 104 patients with HF (mean [standard deviation] age = 65.7 [8.4] years, 28% women) at baseline and 12 months. Depressive symptoms were measured using the Beck Depression Inventory. The associations between depressive symptoms with markers of NO regulation were examined with mixed-model analysis, adjusted for age, sex, time of assessment, left ventricular ejection fraction, creatinine, and hypertension.Results: Depressive symptoms were correlated with a lower L-arginine/ADMA ratio (r = −0.22, p = .003) and higher SDMA levels (r = 0.28, p < .001). Associations were similar for somatic depressive symptoms and cognitive-affective symptoms (L-arginine/ADMA ratio: r = −0.20 [p = .009] versus r = −0.19 [p = .013]; ADMA: r = 0.16 [p = .043] versus r = 0.10 [p = .20]; SDMA: r = 0.27 [p < .001] versus r = 0.22 [p = .005], respectively). No associations were found between depressive symptoms and isoprostane. The association between depression and the L-arginine/ADMA ratio remained significant in multivariate adjusted models.Conclusions: Depressive symptoms were associated with markers of NO dysregulation, particularly the L-arginine/ADMA ratio and SDMA, in patients with HF. The lower L-arginine/ADMA ratio indicates less available NO, suggesting that NO-related endothelial dysfunction may play a role in the adverse risk of HF progression associated with depression.

AB - Objective: Nitric oxide (NO) regulation plays a critical role in cardiovascular diseases including heart failure (HF). Markers of NO dysregulation have been found in individuals with depression without cardiovascular disease. Because depression is associated with poor HF outcomes, the present study tested the hypothesis that depression is associated with a dysregulated NO pathway in patients with HF.Methods: Serum levels of NO regulation (L-arginine, asymmetric dimethylarginine [ADMA], and symmetric dimethylarginine [SDMA]) and oxidative stress (isoprostane 8-epi prostaglandin F2α) were measured in 104 patients with HF (mean [standard deviation] age = 65.7 [8.4] years, 28% women) at baseline and 12 months. Depressive symptoms were measured using the Beck Depression Inventory. The associations between depressive symptoms with markers of NO regulation were examined with mixed-model analysis, adjusted for age, sex, time of assessment, left ventricular ejection fraction, creatinine, and hypertension.Results: Depressive symptoms were correlated with a lower L-arginine/ADMA ratio (r = −0.22, p = .003) and higher SDMA levels (r = 0.28, p < .001). Associations were similar for somatic depressive symptoms and cognitive-affective symptoms (L-arginine/ADMA ratio: r = −0.20 [p = .009] versus r = −0.19 [p = .013]; ADMA: r = 0.16 [p = .043] versus r = 0.10 [p = .20]; SDMA: r = 0.27 [p < .001] versus r = 0.22 [p = .005], respectively). No associations were found between depressive symptoms and isoprostane. The association between depression and the L-arginine/ADMA ratio remained significant in multivariate adjusted models.Conclusions: Depressive symptoms were associated with markers of NO dysregulation, particularly the L-arginine/ADMA ratio and SDMA, in patients with HF. The lower L-arginine/ADMA ratio indicates less available NO, suggesting that NO-related endothelial dysfunction may play a role in the adverse risk of HF progression associated with depression.

U2 - 10.1097/PSY.0000000000000162

DO - 10.1097/PSY.0000000000000162

M3 - Article

VL - 77

SP - 292

EP - 302

JO - Psychosomatic Medicine

JF - Psychosomatic Medicine

SN - 0033-3174

IS - 3

ER -