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Subclinical macro and microvascular disease is differently associated with depressive symptoms in men and women: Findings from the SABRE population-based study.

ABSTRACT: BACKGROUND AND AIMS:Mechanisms underlying the association between cardiovascular disease (CVD) and depression are unknown, and sex differences understudied. We investigated associations between a comprehensive set of measures of macro and microvascular disease and depressive symptoms in older men and women. METHODS:We performed cross-sectional analyses of the SABRE (Southall And Brent REvisited) population-based study. Participants (1396) attended clinic between 2008 and 2011 for assessment of subclinical macrovascular (carotid ultrasound, echocardiography, cerebral magnetic resonance imaging) and microvascular (retinopathy, nephropathy) disease, and depression. RESULTS:Mean age of 1396 participants was 69.5 years, and 76.2% were male. The median (interquartile range) of depression score was 1 [0, 2] for men and 1 [0, 3] for women. All measures of subclinical macro and microvascular disease were adversely associated with depressive symptoms, even when known CVD was excluded. Physical activity partly explained some of these relationships. The association between left atrial dimension index (LADI), a measure of chronic elevated left ventricular filling pressure, and depressive symptoms was stronger in women (regression coefficient 0.23 [95% CI 0.11, 0.35]) than men (0.07 [-0.01, 0.15]), p for interaction 0.06, on multivariable adjustment. CONCLUSIONS:Subclinical macro and microvascular disease is associated with depressive symptoms, even in the absence of established CVD. These were in part accounted for by physical activity. We observed stronger association between LADI and depressive symptoms in women than in men. The beneficial role of physical activity in abrogating the association between subclinical CVD and depression warrants further investigation.

SUBMITTER: Wang J

PROVIDER: S-EPMC7594642 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Subclinical macro and microvascular disease is differently associated with depressive symptoms in men and women: Findings from the SABRE population-based study.

Wang Jingyi J Tillin Therese T Hughes Alun D AD Richards Marcus M Sattar Naveed N Park Chloe C Chaturvedi Nish N

Atherosclerosis 20200913

<h4>Background and aims</h4>Mechanisms underlying the association between cardiovascular disease (CVD) and depression are unknown, and sex differences understudied. We investigated associations between a comprehensive set of measures of macro and microvascular disease and depressive symptoms in older men and women.<h4>Methods</h4>We performed cross-sectional analyses of the SABRE (Southall And Brent REvisited) population-based study. Participants (1396) attended clinic between 2008 and 2011 for ...[more]

PMID: 32971394

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Project description:ObjectiveTo estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms.MethodsWe conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression.ResultsTwo hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5-15] vs 10 [5-17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31-1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3-11] vs 6 [3-12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results.ConclusionsThis study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.

Project description:RATIONALE:In rodent models of depression, oxidative stress-induced reductions in NO bioavailability contribute to impaired endothelium-dependent dilation. Endothelial dysfunction is evident in major depressive disorder (MDD); however, the molecular mediators remain undefined. OBJECTIVE:We sought to translate preclinical findings to humans by testing the role of oxidative stress in mediating microvascular endothelial dysfunction, including potential modulatory influences of sex, in MDD. METHODS AND RESULTS:Twenty-four treatment-naive, otherwise healthy, young adults with MDD (14 women; 18-23 years) and 20 healthy adults (10 women; 19-30 years) participated. Red blood cell flux (laser Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine, alone and in combination with an NO synthase inhibitor (L-NAME), a superoxide scavenger (Tempol), and an NADPH oxidase inhibitor (apocynin), as well as during perfusion of the endothelium-independent agonist sodium nitroprusside. Tissue oxidative stress markers (eg, nitrotyrosine abundance, superoxide production) were also quantified. Endothelium-dependent dilation was blunted in MDD and mediated by reductions in NO-dependent dilation. Endothelium-independent dilation was likewise attenuated in MDD. In MDD, there were no sex differences in either NO-mediated endothelium-dependent dilation or endothelium-independent dilation. Acute scavenging of superoxide or inhibition of NADPH oxidase improved NO-dependent dilation in MDD. Expression and activity of oxidative stress markers were increased in MDD. In a subset of adults with MDD treated with a selective serotonin reuptake inhibitor for their depressive symptoms and in remission (n=8; 7 women; 19-37 years), NO-mediated endothelium-dependent dilation was preserved, but endothelium-independent dilation was impaired, compared with healthy adults. CONCLUSIONS:Oxidative stress-induced reductions in NO-dependent dilation, as well as alterations in vascular smooth muscle function, directly contribute to microvascular dysfunction in MDD. Strategies targeting vascular oxidative stress may be viable therapeutic options for improving NO-mediated endothelial function and reducing cardiovascular risk in MDD.

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Subclinical macro and microvascular disease is differently associated with depressive symptoms in men and women: Findings from the SABRE population-based study.

Publications

Subclinical macro and microvascular disease is differently associated with depressive symptoms in men and women: Findings from the SABRE population-based study.

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