Advertisement

Cardiovascular and autoimmune diseases in females: The role of microvasculature and dysfunctional endothelium

      Highlights

      • There is a relationship between CV burden and SADs.
      • The relationship is mainly due to inflammation and autoimmunity.
      • It is still debated if it is predominant inflammation or autoimmunity.
      • Sex-related studies could give further important support for management of CV damage in SADs.
      • However, nowadays our knowledge is still poor.

      Abstract

      Cardiovascular (CV) diseases are becoming increasingly frequent and associated with a high incidence of CV events, disability and death. It is known that there is a relationship between CV burden and systemic autoimmune diseases (SADs) that is mainly due to inflammation and autoimmunity, but the other mechanisms underlying the high CV risk of SAD patients have not yet been fully clarified.
      The aim of this review article is to discuss some of the specific factors associated with the accelerated atherosclerosis (ATS) characterising SADs (female sex, the microcirculation and the endothelium) in order to highlight the importance of an early diagnosis and the prompt implementation of preventive measures, as well as the possible role of new therapeutic strategies such as vaccine immunomodulation.
      Finally, as the natural history of ATS begins with endothelial injury (a potentially reversible process that is influenced by various factors) and microvascular damage plays a central role in the etiopathogenesis of SADs, it underlines the crucial need for the development of reliable means of detecting sub-clinical abnormalities in the microcirculation, particularly coronary microcirculation dysfunction.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Liu Y.
        • Dalal K.
        • Stollenwerk B.
        The association between health system development and the burden of cardiovascular disease: an analysis of WHO country profiles.
        PLoS One. 2013; 8: e617-618
        • Perk J.
        • De Backer G.
        • Gohlke H.
        • Graham I.
        • Reiner Z.
        • Verschuren M.
        • et al.
        European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the european society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
        Eur. Heart J. 2012; 33: 1635-1701
        • Nichols M.
        • Townsend N.
        • Scarborough P.
        • et al.
        European Cardiovascular Disease Statistics.
        European Heart Network and European Society of Cardiology, Brussels, Belgium2012
        • Ridker P.M.
        • Cook N.R.
        Statins: new American guidelines for prevention of cardiovascular disease.
        Lancet. 2013; 382: 1762-1765
        • Yusuf S.
        • Hawken S.
        • Ounpuu S.
        • et al.
        INTERHEART study investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Clair C.
        • Rigotti N.A.
        • Porneala B.
        • Fox C.S.
        • D'Agostino R.B.
        • Pencina M.J.
        • et al.
        Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes.
        JAMA. 2013; 309: 1014-1021
        • Ray K.K.
        • Kastelein J.J.
        • Boekholdt S.M.
        • Nicholls S.J.
        • Khaw K.T.
        • Ballantyne C.M.
        • et al.
        The ACC/AHA 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: the good the bad and the uncertain: a comparison with ESC/EAS guidelines for the management of dyslipidaemias 2011.
        Eur. Heart J. 2014; 35: 960-968
        • Turiel M.
        • Sarzi-Puttini P.
        • Atzeni F.
        • De Gennaro Colonna V.
        • Gianturco L.
        • Tomasoni L.
        Cardiovascular injury in systemic autoimmune diseases: an update.
        Intern. Emerg. Med. 2011; 6: 99-102
        • van den Oever I.A.
        • van Sijl A.M.
        • Nurmohamed M.T.
        Management of cardiovascular risk in patients with rheumatoid arthritis: evidence and expert opinion.
        Ther. Adv. Musculoskelet. Dis. 2013; 5: 166-181
        • Liao K.P.
        • Soloman D.H.
        Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoid arthritis.
        Rhematology (Oxford). 2013; 52: 45-52
        • Bairey Merz C.N.
        • Regitz-Zagrosek V.
        The case for sex- and gender-specific medicine.
        JAMA Intern. Med. 2014; 174: 1348-1349
      1. Handbook of Systemic Autoimmune Diseases. The Heart in Systemic Autoimmune Diseses. vol. I. Elsevier, 2004
        • Sitia S.
        • Atzeni F.
        • Sarzi-Puttini P.
        • Di Bello V.
        • Tomasoni L.
        • Delfino L.
        • et al.
        Cardiovascular involvement in systemic autoimmune diseases.
        Autoimmun. Rev. 2009; 8: 281-286
        • Hahn B.H.
        • Grossman J.
        • Chen W.
        • McMahon M.
        The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia.
        J. Autoimmun. 2007; 28: 69-75
        • Wolfe F.
        • Rasker J.J.
        • Boers M.
        • Wells G.A.
        • Michaud K.
        Minimal disease activity, remission, and the long-term outcomes of rheumatoid arthritis.
        Arthritis Rheum. 2007; 57: 935-942
        • Hollan I.
        • Meroni P.L.
        • Ahearn J.M.
        • Cohen Tervaert J.W.
        • Curran S.
        • Goodyear C.S.
        • et al.
        Cardiovascular disease in autoimmune rheumatic diseases.
        Autoimmun. Rev. 2013; 12: 1004-1015
        • Wilcox J.N.
        • Scott N.A.
        Potential role of the adventitia in arteritis and atherosclerosis.
        Int. J. Cardiol. 1996; 56: S21-S35
        • Martínez-Valle F.
        • Solans-Laqué R.
        • Bosch-Gil J.
        • Vilardell-Tarrés M.
        Aortic involvement in giant cell arteritis.
        Autoimmun. Rev. 2010; 9: 521-524
        • Shoenfeld Y.
        Infections, vaccines and autoimmunity.
        Lupus. 2009; 18: 1127-1128
        • Turiel M.
        • Gianturco L.
        • Ricci C.
        • Sarzi-Puttini P.
        • Tomasoni L.
        • De Gennaro Colonna V.
        • et al.
        Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross-sectional study.
        Arthritis Care Res. (Hoboken). 2013; 65: 274-280
        • Au K.
        • Singh M.K.
        • Bodukam V.
        • et al.
        Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis.
        Arthritis Rheum. 2011; 63: 2078-2090
        • Atzeni F.
        • Sarzi-Puttini P.
        • Sitia S.
        • Tomasoni L.
        • Gianturco L.
        • Battellino M.
        • et al.
        Coronary flow reserve and asymmetric dimethylarginine levels: new measurements for identifying subclinical atherosclerosis in patients with psoriatic arthritis.
        J. Rheumatol. 2011; 38: 1661-1664
        • Shoenfeld Y.
        • Gerli R.
        • Doria A.
        • Matsuura E.
        • Cerinic M.M.
        • Ronda N.
        • et al.
        Accelerated atherosclerosis in rheumatic autoimmune diseases.
        Circulation. 2005; 112: 3337-3347
        • Van Doornum S.
        • Mc Coll G.
        • Wicks I.P.
        Accelerated atherosclerosis: an extra-articular feature of rheumatoid arthritis.
        Arthritis Rheum. 2002; 46: 862-873
        • Manzi S.
        • Meilahn E.N.
        • Rairie J.E.
        • Conte C.G.
        • Medsger Jr., T.A.
        • Jansen-McWilliams L.
        • et al.
        Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study.
        Am. J. Epidemiol. 1997; 145: 408-415
        • Akram M.R.
        • Handler C.E.
        • Williams M.
        • Carulli M.T.
        • Andron M.
        • Black C.M.
        • et al.
        Angiographically proven coronary artery disease in scleroderma.
        Rheumatol. (Oxford). 2006; 45: 1395-1398
        • Turiel M.
        • Sitia S.
        • Atzeni F.
        • Tomasoni L.
        • Gianturco L.
        • Giuffrida M.
        • et al.
        The heart in rheumatoid arthritis.
        Autoimmun. Rev. 2010; 9: 414-418
        • Turiel M.
        • Atzeni F.
        • Tomasoni L.
        • de Portu S.
        • Delfino L.
        • Bodini B.D.
        • et al.
        Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients.
        Rheumatol. (Oxford). 2009; 48: 834-839
        • Sitia S.
        • Tomasoni L.
        • Atzeni F.
        • Ambrosio G.
        • Cordiano C.
        • Catapano A.
        • et al.
        From endothelial dysfunction to atherosclerosis.
        Autoimmun. Rev. 2010; 9: 830-834
        • Yildiz M.
        Arterial distensibility in chronic inflammatory rheumatic disorders.
        Open Cardiovasc Med. J. 2010; 4: 83-88
        • Shang Q.
        • Tam L.S.
        • Li E.K.
        • et al.
        Increased arterial stiffness correlated with disease activity in systemic lupus erythematosus.
        Lupus. 2008; 17: 1096-1102
        • De Gennaro Colonna V.
        • Bianchi M.
        • Pascale V.
        • et al.
        Asymmetric dimethylarginine (ADMA): an endogenous inhibitor of nitric oxide synthase and a novel cardiovascular risk molecule.
        Med. Sci. Monit. 2009; 15 (RA91-101)
        • Sitia S.
        • Gianturco L.
        • Tomasoni L.
        • et al.
        Role of cardiovascular imaging in systemic autoimmune diseases.
        World J. Cardiol. 2010; 2: 237-242
        • Cortigiani L
        • Rigo F
        • Gherardi S
        • et al.
        Coronary flow reserve during dipyridamole stress echocardiography predicts mortality.
        JACC Cardiovasc. Imaging. 2012; 5: 1079-1085
        • Recio-Mayoral A.
        • Mason J.C.
        • Kaski J.C.
        • et al.
        Chronic inflammation and coronary microvascular dysfunction in patients without risk factors for coronary artery disease.
        Eur. Heart J. 2009; 30: 1837-1843
        • Kerekes G.
        • Soltész P.
        • Nurmohamed M.T.
        • Gonzalez-Gay M.A.
        • Turiel M.
        • Végh E.
        • et al.
        Validated methods for assessment of subclinical atherosclerosis in rheumatology.
        Nat. Rev. Rheumatol. 2012; 8: 224-234
        • Libby P.
        • Ridker P.M.
        • Hansson G.K.
        Progress and challenges in translating the biology of atherosclerosis.
        Nature. 2011; 473: 317-325
        • Choy E.
        • Sattar N.
        Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions.
        Ann. Rheum. Dis. 2009; 68: 460-469
        • Kaptoge S.
        • Di Angelantonio E.
        • Lowe G.
        C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.
        Lancet. 2010; 375: 132-140
        • Libby P.
        Role of inflammation in atherosclerosis associated with rheumatoid arthritis.
        Am. J. Med. 2008; 121: S21-S31
        • Wensley F.
        • Gao P.
        • Burgess S.
        • Kaptoge S.
        • Di Angelantonio E.
        • Shah T.
        • Engert J.C.
        • Clarke R.
        • Davey-Smith G.
        • Nordestgaard B.G.
        • Saleheen D.
        • Samani N.J.
        • Sandhu M.
        • Anand S.
        • Pepys M.B.
        • Smeeth L.
        • Whittaker J.
        • Casas J.P.
        • Thompson S.G.
        • Hingorani A.D.
        • Danesh J.
        C reactive protein coronary heart disease genetics collaboration (CCGC).
        BMJ. 2011; 342: d548
        • Miller A.M.
        • McInnes I.B.
        Cytokines as therapeutic targets to reduce cardiovascular risk in chronic inflammation.
        Curr. Pharm. Des. 2011; 17: 1-8
        • Galkina E.
        • Ley K.
        Immune and inflammatory mechanisms of atherosclerosis.
        Ann. Rev. Immunol. 2009; 27: 165-199
        • Matsuura E.
        • Lopez L.R.
        • Shoenfeld Y.
        • Ames P.R.
        β2-glycoprotein I and oxidative inflammation in early atherogenesis: a progression from innate to adaptive immunity?.
        Autoimmun. Rev. 2012; 11: 873-882
        • Sollberger G.
        • Strittmatter G.E.
        • Garstkiewicz M.
        • Sand J.
        • Beer H.D.
        Caspase-1: the inflammasome and beyond.
        Innate Immun. 2013; 20: 115-125
        • Peters M.J.
        • van Halm V.P.
        • Nurmohamed M.T.
        • Damoiseaux J.
        • Tervaert J.W.
        • Twisk J.W.
        • et al.
        Relations between autoantibodies against oxidized low-density lipoprotein, inflammation, subclinical atherosclerosis, and cardiovascular disease in rheumatoid arthritis.
        J. Rheumatol. 2008; 35: 1495-1499
        • Schiele F.
        • Chopard R.
        Is coronary artery disease different in women?.
        Presse Med. 2014; 43: 796-802
        • Schlager O.
        • Giurgea A.
        • Hammer A.
        • Charwat-Resl S.
        • Margeta C.
        • Mueller M.
        • et al.
        Impact of age and gender on microvascular function.
        Eur. J. Clin. Invest. 2014; 44: 766-774
        • Panazzolo D.G.
        • da Silva L.H.
        • Cyrino F.Z.
        • Sicuro F.L.
        • Kraemer-Aguiar L.G.
        • Bouskela E.
        Gender differences in microcirculation: observation using the hamster cheek pouch.
        Clin. (Sao Paulo). 2013; 68: 1537-1542
        • Vrijenhoek J.E.
        • Den Ruijter H.M.
        • De Borst G.J.
        • de Kleijn D.P.
        • De Vries J.P.
        • Bots M.L.
        • et al.
        Sex is associated with the presence of atherosclerotic plaque hemorrhage and modifies the relation between plaque hemorrhage and cardiovascular outcome.
        Stroke. 2013; 44: 3318-3323
        • Pietrzak A.
        • Czuczwar P.
        • Mosiewicz J.
        • Paszkowski T.
        • Chodorowska G.
        • Bartosinska J.
        • et al.
        Cardiovascular disease in psoriatic post-menopausal women.
        J. Eur. Acad. Dermatol Venereol. 2014 Jul 30; ([Epub ahead of print])https://doi.org/10.1111/jdv.12620
        • Rennert G.
        • Peterburg Y.
        Prevalence of selected chronic diseases in Israel.
        Isr. Med. Assoc. J. 2001; 3: 404-408
        • Bias W.B.
        • Reveille J.D.
        • Beaty T.H.
        • Meyers D.A.
        • Arnett F.C.
        Evidence that autoimmunity in man is a Mendelian dominant trait.
        Am. J. Hum. Genet. 1986; 39: 584-602
        • McCombe P.A.
        • Chalk J.B.
        • Pender M.P.
        Familial occurrence of multiple sclerosis with thyroid disease and systemic lupus erythematosus.
        J. Neurol. Sci. 1990; 97: 163-171
        • Clayton D.G.
        Prediction and interaction in complex disease genetics: experience in type 1 diabetes.
        PLoS Genet. 2009; 5: e1000540
        • Willer C.J.
        • Dyment D.A.
        • Risch N.J.
        • Sadovnick A.D.
        • Ebers G.C.
        Canadian collaborative study group. Twin concordance and sibling recurrence rates in multiple sclerosis.
        Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 12877-12882
        • Kuusisto H.
        • Kaprio J.
        • Kinnunen E.
        • Luukkaala T.
        • Koskenvuo M.
        • Elovaara I.
        Concordance and heritability of multiple sclerosis in Finland: study on a nationwide series of twins.
        Eur. J. Neurol. 2008; 15: 1106-1110
        • Ansar Ahmed S.
        • Penhale W.J.
        • Talal N.
        Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.
        Am. J. Pathol. 1985; 121: 531-551
        • Lu Q.
        The critical importance of epigenetics in autoimmunity.
        J. Autoimmun. 2013; 41: 1-5
        • Bergholm R.
        • Leirisalo-Repo M.
        • Vehkavaara S.
        • Makimattila S.
        • Taskinen M.R.
        • Yki-Jarvinen H.
        Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1637-1641
        • Foster W.
        • Carruthers D.
        • Lip G.Y.
        • Blann A.D.
        Inflammation and microvascular and macrovascular endothelial dysfunction in rheumatoid arthritis: effect of treatment.
        J. Rheumatol. 2010; 37: 711-716
        • Yeboah J.
        • Crouse J.R.
        • Hsu F.C.
        • Burke G.L.
        • Herrington D.M.
        Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the cardiovascular health study.
        Circulation. 2007; 115: 2390-2397
        • Burger D.
        • Touyz R.M.
        Cellular biomarkers of endothelial health: microparticles, endothelial progenitor cells, and circulating endothelial cells.
        J. Am. Soc. Hypertens. 2012; 6: 85-99
        • Galarraga B.
        • Khan F.
        • Kumar P.
        • Pullar T.
        • Belch J.J.
        C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis.
        Rheumatol. (Oxford). 2008; 47: 1780-1784
        • Datta D.
        • Ferrell W.R.
        • Sturrock R.D.
        • Jadhav S.T.
        • Sattar N.
        Inflammatory suppression rapidly attenuates microvascular dysfunction in rheumatoid arthritis.
        Atherosclerosis. 2007; 192: 391-395
        • Nielen M.M.
        • Schaardenburg D.
        • Reesink H.W.
        • Twisk J.W.
        • Stadt R.J.
        • Horst-Bruinsma I.E.
        • et al.
        Increased levels of C-reactive protein in serum from blood donors before the onset of rheumatoid arthritis.
        Arthritis Rheum. 2004; 50: 2423-2427
        • Kerekes G.
        • Szekanecz Z.
        • Dér H.
        • Sándor Z.
        • Lakos G.
        • Muszbek L.
        • et al.
        Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity.
        J. Rheumatol. 2008; 35: 398-406
        • Tomasoni L.
        • Sitia S.
        • Borghi C.
        • Cicero A.F.
        • Ceconi C.
        • Cecaro F.
        • et al.
        Effects of treatment strategy on endothelial function.
        Autoimmun. Rev. 2010; 9: 840-844
        • Crea F.
        • Camici P.G.
        • Bairey Merz C.N.
        Coronary microvascular dysfunction: an update.
        Eur. Heart J. 2014; 35: 1101-1111

      Linked Article

      • Importance of sex and gender in atherosclerosis and cardiovascular disease
        AtherosclerosisVol. 241Issue 1
        • Preview
          In this special issue of the journal, there are papers on bone health and coronary artery calcification, age and sex differences in the effect of parental stroke on the progression of carotid intima-media thickness, macrophage subsets in the adipose tissue by sex and by reproductive age of women, uric acid levels and metabolic syndrome, sex differences in cardiovascular risk factors and disease prevention, severity of stable coronary artery disease and its biomarkers, cardiovascular disease and autoimmune diseases genetics of cardiovascular disease, outcome after CABG; association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease and relationship of uric acid levels to coronary disease.
        • Full-Text
        • PDF
      • Sex matters to the heart: A special issue dedicated to the impact of sex related differences of cardiovascular diseases
        AtherosclerosisVol. 241Issue 1
        • Preview
          Ever since the early 1980s most cardiovascular research has focused on men [1]. This phenomenon has led to the under appreciation of sex-differences in cardiovascular disease (CVD) from an etiological, prognostic, diagnostic and therapeutic perspective. Several initiatives to promote women's health, such as the Women's Health Initiative [2] have been initiated and have changed the practice of cardiovascular disease prevention in women over the past decade. This ultimately led to the first guidelines for cardiovascular disease prevention in women by the American Heart Association in 1999 [3].
        • Full-Text
        • PDF