Heart, Lung and Circulation

Syndrome ‘Z’: A Predictor of Angiographic Severity of Coronary Artery Disease in Patients of Acute Coronary Syndrome


      Owing to the growing evidence that the pathophysiology of obstructive sleep apnoea (OSA) and metabolic syndrome (MS) overlap considerably and both adversely impact cardiovascular health, we hypothesised that the presence of OSA with MS additively and adversely affect the severity of coronary artery disease (CAD). Exploration and understanding of this may have direct implications for the development of targeted, preventive strategies for CAD. Thus, this prospective study was aimed to determine the prevalence of ‘Syndrome Z’ in patients of MS who present with an acute coronary event and to correlate it with the angiographic severity of CAD in these patients.


      The present study was a single centre, cross sectional study conducted in a university teaching hospital. In a span of 6 months, 922 patients with acute coronary syndromes (ACS) were screened for the study. Among these, 861 patients had no evidence of MS. The remaining 61 patients who were diagnosed to have MS were then subjected to an overnight sleep study. Only 58 had good sleep data so were included for further analysis. Angiographic parameters in terms of number of vessels involved and culprit lesions were noted and correlated with presence and absence of OSA and also with its severity based on the Apnoea/Hypopnoea Index (AHI).


      The prevalence of OSA positivity in patients with MS who presented with ACS was 34.5% (n = 20). Most of the patients in the OSA negative group (78.9%, n = 30) had disease limited to only one vessel while in the OSA positive group only a minority (15%, n = 3) of patients had their disease limited to a single vessel (p = 0.001). The number of lesions in the culprit vessel was also significantly less in the OSA negative group compared to the OSA positive group. While in the OSA negative group 68.4% (n = 26) patients had a solitary lesion, followed by two and three lesions in 15.8% (n = 6) of the patients each, multiple lesions were more common in OSA positive patients, involving 80% of cases (45.0%, n = 9 with two lesions; 35.0%, n = 7 with three lesions; only 20%, n = 4 had a solitary lesion).


      Prevalence of ‘Syndrome Z’ is high in patients having MS presenting with ACS and it correlates with the angiographic severity of CAD.


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        • Wilcox I.
        • McNamara S.G.
        • Collins F.L.
        • Grunstein R.R.
        • Sullivan C.E.
        “Syndrome Z”: the interaction of sleep apnoea, vascular risk factors and heart disease.
        Thorax. 1998; 53 Suppl 3: S25-S28
        • Reaven G.M.
        Role of insulin resistance in human disease (syndrome X): an expanded definition.
        Annu Rev Med. 1993; 44: 121-131
        • Third report of the National Cholesterol Education Program (NCEP)
        Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report.
        Circulation. 2002; 106: 3143-3421
        • Kapur V.K.
        • Auckley D.H.
        • Chowdhuri S.
        • Kuhlmann D.C.
        • Mehra R.
        • Ramar K.
        • et al.
        Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American academy of sleep medicine clinical practice guideline.
        J Clin Sleep Med. 2017; 13: 479-504
        • Budhiraja R.
        • Budhiraja P.
        • Quan S.F.
        Sleep-disordered breathing and cardiovascular disorders.
        Respir Care. 2010; 55 (discussion 1330–1332): 1322-1332
        • Lee C.-H.
        • Sethi R.
        • Li R.
        • Ho H.-H.
        • Hein T.
        • Jim M.-H.
        • et al.
        Obstructive sleep apnea and cardiovascular events after percutaneous coronary intervention.
        Circulation. 2016; 133: 2008-2017
        • Koo C.-Y.
        • de la Torre A.S.
        • Loo G.
        • Torre M.S.
        • Zhang J.
        • Duran-Cantolla J.
        • et al.
        Effects of ethnicity on the prevalence of obstructive sleep apnoea in patients with acute coronary syndrome: a pooled analysis of the ISAACC trial and sleep and stent study.
        Heart Lung Circ. 2017; 26: 486-494
        • Lam J.C.M.
        • Mak J.C.W.
        • Ip M.S.M.
        Obesity, obstructive sleep apnoea and metabolic syndrome.
        Respirol Carlton Vic. 2012; 17: 223-236
        • Mertens I.
        • Van Gaal L.F.
        New International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment panel III (NCEP-ATPIII) criteria and the involvement of hemostasis and fibrinolysis in the metabolic syndrome.
        J Thromb Haemost. 2006; 4: 1164-1166
        • Sharma S.K.
        • Reddy E.V.
        • Sharma A.
        • Kadhiravan T.
        • Mishra H.K.
        • Sreenivas V.
        • et al.
        Prevalence and risk factors of syndrome Z in urban Indians.
        Sleep Med. 2010; 11: 562-568
        • Sharma S.K.
        • Sreenivas V.
        Are metabolic syndrome, obstructive sleep apnoea & syndrome Z sequential?—a hypothesis.
        Indian J Med Res. 2010; 131: 455-458
        • Nakashima H.
        • Kurobe M.
        • Minami K.
        • Furudono S.
        • Uchida Y.
        • Amenomori K.
        • et al.
        Effects of moderate-to-severe obstructive sleep apnea on the clinical manifestations of plaque vulnerability and the progression of coronary atherosclerosis in patients with acute coronary syndrome.
        Eur Heart J Acute Cardiovasc Care. 2015; 4: 75-84
        • Lee C.-H.
        • Khoo S.-M.
        • Tai B.-C.
        • Chong E.Y.
        • Lau C.
        • Than Y.
        • et al.
        Obstructive sleep apnea in patients admitted for acute myocardial infarction. Prevalence, predictors, and effect on microvascular perfusion.
        Chest. 2009; 135: 1488-1495
        • Venkateswaran S.
        • Shankar P.
        The prevalence of syndrome Z (the interaction of obstructive sleep apnoea with the metabolic syndrome) in a teaching hospital in Singapore.
        Postgrad Med J. 2007; 83: 329-331
        • Young T.
        • Palta M.
        • Dempsey J.
        • Skatrud J.
        • Weber S.
        • Badr S.
        The occurrence of sleep-disordered breathing among middle-aged adults.
        N Engl J Med. 1993; 328: 1230-1235
        • Perk J.
        • De Backer G.
        • Gohlke H.
        • Graham I.
        • Reiner Z.
        • Verschuren M.
        • et al.
        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
        • Javadi H.R.
        • Jalilolghadr S.
        • Yazdi Z.
        • Rezaie Majd Z.
        Correlation between obstructive sleep apnea syndrome and cardiac disease severity.
        Cardiovasc Psychiatry Neurol. 2014; 2014631380
        • Hiestand D.M.
        • Britz P.
        • Goldman M.
        • Phillips B.
        Prevalence of symptoms and risk of sleep apnea in the US population: results from the national sleep foundation sleep in America 2005 poll.
        Chest. 2006; 130: 780-786
        • De Torres-Alba F.
        • Gemma D.
        • Armada-Romero E.
        • Rey-Blas J.R.
        • López-de-Sá E.
        • López-Sendon J.L.
        Obstructive sleep apnea and coronary artery disease: from pathophysiology to clinical implications.
        Pulm Med. 2013; 2013: 1-9
        • Koo C.Y.
        • Drager L.F.
        • Sethi R.
        • Ho H.-H.
        • Hein T.
        • Jim M.-H.
        • et al.
        Obstructive sleep apnea and diabetes independently add to cardiovascular risk after coronary revascularization.
        Diabetes Care. 2018; 41: e12-e14
        • Miri R.
        • Sajjadieh A.
        • Parsamahjoob M.
        • Hajibaratali B.
        • Shekarchizadeh M.
        • Kolahi A.A.
        • et al.
        Relationship between metabolic syndrome and angiographic severity of coronary artery disease.
        ARYA Atheroscler. 2016; 12: 220-225
        • Yavuz B.
        • Kabakci G.
        • Aksoy H.
        • Tulumen E.
        • Deveci O.S.
        • Aytemir K.
        • et al.
        Determining the relationship between metabolic syndrome score and angiographic severity of coronary artery disease.
        Int J Clin Pract. 2008; 62: 717-722
        • Kim J.-Y.
        • Mun H.-S.
        • Lee B.K.
        • Yoon S.B.
        • Choi E.-Y.
        • Min P.-K.
        • et al.
        Impact of metabolic syndrome and its individual components on the presence and severity of angiographic coronary artery disease.
        Yonsei Med J. 2010; 51: 676-682
        • Arias M.A.
        • García-Río F.
        • Alonso-Fernández A.
        • Mediano O.
        • Martínez I.
        • Villamor J.
        Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men.
        Circulation. 2005; 112: 375-383
        • Sun H.
        • Shi J.
        • Li M.
        • Chen X.
        Impact of continuous positive airway pressure treatment on left ventricular ejection fraction in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.
        PloS One. 2013; 8e62298