The relationship of depressive symptoms and subclinical atherosclerosis remains controversial. We performed a systematic review and meta-analysis to evaluate the effect of depressive symptoms on the functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (IMT), pulse wave velocity (PWV) and flow-mediated vasodilation (FMD).
Methods
A systematic literature search was performed electronically. Studies relating IMT, PWV or FMD to depressive symptoms were included. Standard/weighted mean differences (SMD/WMD) and corresponding 95% confidence intervals (95% CIs) were pooled in overall and subgroup analyses (age, sex, depression diagnosis, region, study design, site measured and sample size). Sensitivity analysis and publication bias were also conducted.
Results
Thirty-eight articles involving 5947 patients with depressive symptoms and 34,423 controls without depressive symptoms were included. Compared with controls without depressive symptoms, patients with depressive symptoms showed a significantly thicker IMT (SMD (95% CI) = 0.137 (0.047–0.227), p = 0.003), a higher PWV (SMD (95% CI) = 0.216 (0.139–0.293), p < 0.001) and a lower FMD (WMD (95% CI) = –2.554 (–3.709 to –1.399), p < 0.001). When analyzing subgroups with age and female ratio, all results were still significant (p < 0.05) except IMT and FMD in age < 50 years subgroups (p > 0.05). There was no statistical significance in sensitivity analysis and publication bias (p > 0.05).
Conclusions
Depressive symptoms contributed toward subclinical atherosclerosis, and resulted in impaired functional and structural markers of subclinical atherosclerosis, which holds great promise in early prevention of cardiovascular disease.
ReddyMS. Depression: The disorder and the burden. Indian J Psychol Med2010; 32: 1–2.
2.
RibeiroWSBauerAAndradeMCRet al.Income inequality and mental illness-related morbidity and resilience: A systematic review and meta-analysis. Lancet Psychiatry2017; 4: 554–562.
3.
O'NeilAFisherAJKibbeyKJet al.Depression is a risk factor for incident coronary heart disease in women: An 18-year longitudinal study. J Affect Disord2016; 196: 117–124.
4.
HuffmanJCCelanoCMBeachSRet al.Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol2013; 2013: 695925.
5.
Frasure-SmithNLesperanceF. Recent evidence linking coronary heart disease and depression. Can J Psychiatry2006; 51: 730–737.
6.
LiuYZWangYXJiangCL. Inflammation: The common pathway of stress-related diseases. Front Hum Neurosci2017; 11: 316.
7.
SarandolASarandolEEkerSSet al.Major depressive disorder is accompanied with oxidative stress: Short-term antidepressant treatment does not alter oxidative-antioxidative systems. Hum Psychopharmacol2007; 22: 67–73.
8.
CanMMGulerGGulerEet al.Enhanced platelet reactivity in pediatric depression: An observational study. Blood Coagul Fibrinolysis2015; 26: 731–735.
9.
DomePHalmaiZDobosJet al.Investigation of circulating endothelial progenitor cells and angiogenic and inflammatory cytokines during recovery from an episode of major depression. J Affect Disord2012; 136: 1159–1163.
10.
RozanskiA. Integrating psychologic approaches into the behavioral management of cardiac patients. Psychosom Med2005; 67(Suppl. 1): S67–S73.
11.
RozanskiABlumenthalJAKaplanJ. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation1999; 99: 2192–2217.
12.
BotMChanMKJansenRet al.Serum proteomic profiling of major depressive disorder. Transl Psychiatry2015; 5: e599.
13.
McCafferyJMDuanQLFrasure-SmithNet al.Genetic predictors of depressive symptoms in cardiac patients. Am J Med Genet B Neuropsychiatr Genet2009; 150B: 381–388.
14.
SharmaANda Costa e SilvaBFSoaresJCet al.Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies. J Affect Disord2016; 197: 9–20.
15.
ZhaoMChenLYangJet al.BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction. J Affect Disord2017; 227: 226–235.
16.
WulsinLRSingalBM. Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review. Psychosom Med2003; 65: 201–210.
17.
LesperanceFFrasure-SmithNTalajicMet al.Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction. Circulation2002; 105: 1049–1053.
18.
GoldsteinBIFagioliniAHouckPet al.Cardiovascular disease and hypertension among adults with bipolar I disorder in the United States. Bipolar Disord2009; 11: 657–662.
19.
LiaoXNorataGDPolakJFet al.Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?Eur J Prev Cardiol2016; 23: 1165–1173.
20.
WilleitPThompsonSGAgewallSet al.Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. Eur J Prev Cardiol2016; 23: 194–205.
21.
BotsMLGrobbeeDE. Intima media thickness as a surrogate marker for generalised atherosclerosis. Cardiovasc Drugs Ther2002; 16: 341–351.
22.
MunakataM. Brachial-ankle pulse wave velocity in the measurement of arterial stiffness: Recent evidence and clinical applications. Curr Hypertens Rev2014; 10: 49–57.
23.
XuYAroraRCHiebertBMet al.Non-invasive endothelial function testing and the risk of adverse outcomes: A systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging2014; 15: 736–746.
24.
MercerDALavoieKLDittoBet al.The interaction between anxiety and depressive symptoms on brachial artery reactivity in cardiac patients. Biol Psychol2014; 102: 44–50.
25.
Van SlotenTTMitchellGFSigurdssonSet al.Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: Cross-sectional findings from the AGES-Reykjavik Study. J Psychiatry Neurosci2016; 41: 162–168.
26.
NaritaKMurataTHamadaTet al.Associations between trait anxiety, insulin resistance, and atherosclerosis in the elderly: A pilot cross-sectional study. Psychoneuroendocrinology2008; 33: 305–312.
27.
BohmanHJonssonUvon KnorringALet al.Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders: A pilot study using non-invasive high frequency ultrasound. World J Biol Psychiatry2010; 11: 71–75.
28.
GarciaRGZarrukJGBarreraCet al.Plasma nitrate levels and flow-mediated vasodilation in untreated major depression. Psychosom Med2011; 73: 344–349.
29.
ScuteriAModestinoAFedulloFet al.Depression treatment selectively modifies arterial stiffness in older participants. J Gerontol A Biol Sci Med Sci2013; 68: 719–725.
30.
KimJHKimJWKoYHet al.Coronary endothelial dysfunction associated with a depressive mood in patients with atypical angina but angiographically normal coronary artery. Int J Cardiol2010; 143: 154–157.
31.
Van DoorenFESchramMTSchalkwijkCGet al.Associations of low grade inflammation and endothelial dysfunction with depression – The Maastricht Study. Brain Behav Immun2016; 56: 390–396.
32.
YangEHLermanSLennonRJet al.Relation of depression to coronary endothelial function. Am J Cardiol2007; 99: 1134–1136.
33.
SunDWuYYuanYet al.Is the atherosclerotic process accentuated under conditions of HIV infection, antiretroviral therapy, and protease inhibitor exposure? Meta-analysis of the markers of arterial structure and function. Atherosclerosis2015; 242: 109–116.
34.
DerSimonianRLairdN. Meta-analysis in clinical trials. Control Clin Trials1986; 7: 177–188.
35.
PizziCManzoliLManciniSet al.Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors. Atherosclerosis2010; 212: 292–298.
36.
JonesDJBrombergerJTSutton-TyrrellKet al.Lifetime history of depression and carotid atherosclerosis in middle-aged women. Arch Gen Psychiatry2003; 60: 153–160.
37.
TiemeierHvan DijckWHofmanAet al.Relationship between atherosclerosis and late-life depression: The Rotterdam Study. Arch Gen Psychiatry2004; 61: 369–376.
38.
ChenCSChenCCKuoYTet al.Carotid intima-media thickness in late-onset major depressive disorder. Int J Geriatr Psychiatry2006; 21: 36–42.
39.
FaramawiMFGustatJWildmanRPet al.Relation between depressive symptoms and common carotid artery atherosclerosis in American persons > or = 65 years of age. Am J Cardiol2007; 99: 1610–1613.
40.
SpitzerCVolzkeHBarnowSet al.Association between depression and subclinical carotid atherosclerosis in patients with Type 1 diabetes. Diabet Med2008; 25: 349–354.
41.
KabirAASrinivasanSRSultanaAet al.Association between depression and intima-media thickness of carotid bulb in asymptomatic young adults. Am J Med2009; 122: e1151–e1158.
42.
ParanthamanRGreensteinASBurnsASet al.Vascular function in older adults with depressive disorder. Biol Psychiatry2010; 68: 133–139.
43.
DietzLJMatthewsKA. Depressive symptoms and subclinical markers of cardiovascular disease in adolescents. J Adolesc Health2011; 48: 579–584.
44.
SeldenrijkAvan HoutHPvan MarwijkHWet al.Carotid atherosclerosis in depression and anxiety: associations for age of depression onset. World J Biol Psychiatry2011; 12: 549–558.
45.
ChenGWuYWangTet al.Association between serum endogenous secretory receptor for advanced glycation end products and risk of type 2 diabetes mellitus with combined depression in the Chinese population. Diabetes Technol Ther2012; 14: 936–942.
46.
ViolantiJMCharlesLEGuJKet al.Depressive symptoms and carotid artery intima-media thickness in police officers. Int Arch Occup Environ Health2013; 86: 931–942.
47.
BeutelMEWiltinkJKirschnerYet al.History of depression but not current depression is associated with signs of atherosclerosis: Data from the Gutenberg Health Study. Psychol Med2014; 44: 919–925.
48.
LeeY-HShinM-HChoiJ-Set al.Gender differences in the association between depressive symptoms and carotid atherosclerosis among middle-aged and older Koreans: The Namwon study. J Korean Med Sci2014; 29: 1507–1513.
49.
PoongothaiSPradeepaRIndulekhaKet al.Association of depression with common carotid artery intima media thickness and augmentation index in a large Urban South Indian population – The Chennai Urban Rural Epidemiology Study (CURES – 138). Indian J Endocrinol Metab2015; 19: 136–142.
50.
CamachoAMcClellandRLDelaneyJAet al.Antidepressant use and subclinical measures of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis. J Clin Psychopharmacol2016; 36: 340–346.
51.
DevantierTANorgaardBLPoulsenMKet al.White matter lesions, carotid and coronary atherosclerosis in late-onset depression and healthy controls. Psychosomatics2016; 57: 369–377.
52.
JorgeALertratanakulALeeJet al.Depression and progression of subclinical cardiovascular disease in systemic lupus erythematosus. Arthritis Care Res (Hoboken)2017; 69: 5–11.
53.
RajagopalanSBrookRRubenfireMet al.Abnormal brachial artery flow-mediated vasodilation in young adults with major depression. Am J Cardiol2001; 88: 196–198.
54.
BroadleyAJKorszunAJonesCJet al.Arterial endothelial function is impaired in treated depression. Heart2002; 88: 521–523.
55.
SherwoodAHinderliterALWatkinsLLet al.Impaired endothelial function in coronary heart disease patients with depressive symptomatology. J Am Coll Cardiol2005; 46: 656–659.
56.
MunkPSIsaksenKBronnickKet al.Symptoms of anxiety and depression after percutaneous coronary intervention are associated with decreased heart rate variability, impaired endothelial function and increased inflammation. Int J Cardiol2012; 158: 173–176.
57.
TaylorCBConradAWilhelmFHet al.Psychophysiological and cortisol responses to psychological stress in depressed and nondepressed older men and women with elevated cardiovascular disease risk. Psychosom Med2006; 68: 538–546.
58.
WagnerJATennenHMansoorGAet al.History of major depressive disorder and endothelial function in postmenopausal women. Psychosom Med2006; 68: 80–86.
59.
PizziCManzoliLManciniSet al.Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation, and endothelial function. Eur Heart J2008; 29: 1110–1117.
60.
ChenHYiuKHTseHF. Relationships between vascular dysfunction, circulating endothelial progenitor cells, and psychological status in healthy subjects. Depress Anxiety2011; 28: 719–727.
61.
ZhuoCWangYTianHet al.Impairment of endothelial protection by ischemic postconditioning in patients with major depressive disorder. Can J Physiol Pharmacol2011; 89: 647–653.
62.
MichalMWiltinkJKirschnerYet al.Differential associations of depressive symptom dimensions with cardio-vascular disease in the community: Results from the Gutenberg health study. PLoS One2013; 8: e72014.
63.
Van SlotenTTSchramMTAdriaanseMCet al.Endothelial dysfunction is associated with a greater depressive symptom score in a general elderly population: The Hoorn Study. Psychol Med2014; 44: 1403–1416.
64.
Aydin SunbulESunbulMGulecH. The impact of major depression on heart rate variability and endothelial dysfunction in patients with stable coronary artery disease. Gen Hosp Psychiatry2017; 44: 4–9.
65.
TiemeierHBretelerMMvan PopeleNMet al.Late-life depression is associated with arterial stiffness: A population-based study. J Am Geriatr Soc2003; 51: 1105–1110.
66.
YanartasOSunbulMDurmusEet al.Severity of depression and anxiety symptoms is associated with increased arterial stiffness in depressive disorder patients undergoing psychiatric treatment. Klinik Psikofarmakol Bulteni2016; 26: 287–293.
67.
OulisPKouzoupisAKyrkouKet al.Reversal of increased arterial stiffness in severely depressed women after 6-week antidepressant treatment. J Affect Disord2010; 122: 164–166.
68.
SatohHFujiiSTsutsuiH. Persistent depression is a significant risk factor for the development of arteriosclerosis in middle-aged Japanese male subjects. Hypertens Res2015; 38: 84–88.
69.
HermesdorfMBergerKSzentkiralyiAet al.Reduced fractional anisotropy in patients with major depressive disorder and associations with vascular stiffness. Neuroimage Clin2017; 14: 151–155.
70.
AliSSKhanSAKhosaFet al.Noninvasive assessment of subclinical atherosclerosis in persons with symptoms of depression. Atherosclerosis2017; 264: 92–99.
71.
CooperDCTomfohrLMMilicMSet al.Depressed mood and flow-mediated dilation: A systematic review and meta-analysis. Psychosom Med2011; 73: 360–369.
72.
LombardJH. Depression, psychological stress, vascular dysfunction, and cardiovascular disease: Thinking outside the barrel. J Appl Physiol (1985)2010; 108: 1025–1026.
73.
EschTStefanoGBFricchioneGLet al.Stress in cardiovascular diseases. Med Sci Monit2002; 8: RA93–RA101.
74.
GuHFTangCKYangYZ. Psychological stress, immune response, and atherosclerosis. Atherosclerosis2012; 223: 69–77.
PateMDamarlaVChiDSet al.Endothelial cell biology: Role in the inflammatory response. Adv Clin Chem2010; 52: 109–130.
77.
ChristiansenSBouzinovaEVPalmeRet al.Circadian activity of the hypothalamic-pituitary-adrenal axis is differentially affected in the rat chronic mild stress model of depression. Stress2012; 15: 647–657.
78.
IuchiTAkaikeMMitsuiTet al.Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial dysfunction. Circ Res2003; 92: 81–87.
BouzinovaEVNorregaardRBoedtkjerDMet al.Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression. Psychosom Med2014; 76: 268–276.
81.
GrgicIKaisthaBPHoyerJet al.Endothelial Ca+-activated K + channels in normal and impaired EDHF-dilator responses – relevance to cardiovascular pathologies and drug discovery. Br J Pharmacol2009; 157: 509–526.
EvansJFRagoliaL. Systemic and local ACTH produced during inflammatory states promotes osteochondrogenic mesenchymal cell differentiation contributing to the pathologic progression of calcified atherosclerosis. Med Hypotheses2012; 79: 823–826.
84.
NuttDWilsonSPatersonL. Sleep disorders as core symptoms of depression. Dialogues Clin Neurosci2008; 10: 329–336.
85.
TakaseBAkimaTUehataAet al.Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans. Clin Cardiol2004; 27: 223–227.
86.
AntonSDNewtonRLJrSothernMet al.Association of depression with body mass index, sedentary behavior, and maladaptive eating attitudes and behaviors in 11 to 13-year old children. Eat Weight Disord2006; 11: e102–e108.
87.
DiazKMBoothJN3rdSealsSRet al.Sedentary behavior and subclinical atherosclerosis in African Americans: Cross-sectional analysis of the Jackson heart study. Int J Behav Nutr Phys Act2016; 13: 31.
PizziCCostaGMSantarellaLet al.Depression symptoms and the progression of carotid intima-media thickness: A 5-year follow-up study. Atherosclerosis2014; 233: 530–536.
90.
WagnerJATennenHFinanPHet al.Lifetime history of depression, type 2 diabetes, and endothelial reactivity to acute stress in postmenopausal women. Int J Behav Med2012; 19: 503–511.
91.
GoldsteinBICarnethonMRMatthewsKAet al.Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: A Scientific Statement From the American Heart Association. Circulation2015; 132: 965–986.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
