Frequency and Determinants of Intracranial Atherosclerotic Stroke in Urban Pakistan


      Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population.


      The Karachi Intracranial Stenosis Study is a case–control study of 313 cases of ischemic stroke secondary to ICAD and 331 controls enrolled from 4 major hospitals in Karachi, Pakistan. Stroke subtype was verified by a vascular neurologist using the Trial of Org 10172 in Acute Stroke Treatment classification. Relationships of conventional and socioeconomic risk factors with ICAD-related strokes are reported by calculating odds ratios (ORs) and their 95% confidence intervals (CIs).


      ICAD was the cause of stroke in 81.1% cases with large-artery atherosclerosis and 19.5% of all stroke events. Along with risk factors like history of hypertension (OR, 3.33; CI, 2.31-4.78), history of diabetes (OR, 2.29; CI, 1.56-3.35), use of tobacco (OR, 1.49; CI, 1.03-2.16), waist-to-hip ratio (OR, 1.58; CI, 1.04-2.41), and family history of stroke (OR, 1.89; CI, 1.21-2.95), other significant social determinants of ICAD strokes were monthly income (OR, 1.59; CI, 1.01-2.51), unemployment (OR, 2.15; CI, 1.21-3.83), and chronic stress (OR, 3.67; CI, 2.13-6.34). These social determinants were independent predictors of the risk of ICAD, in addition to those described in other world populations.


      ICAD accounted for one fifth of all strokes making it the most common ischemic stroke mechanism. In addition to aggressive risk factor control, data also indicated broader holistic efforts on ameliorating inequity, unemployment, and stress reduction to reduce stroke because of ICAD.

      Key Words

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


      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Feigin V.L.
        • Lawes C.M.
        • Bennett D.A.
        • et al.
        Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review.
        Lancet Neurol. 2009; 8: 355-369
        • Asplund K.
        What MONICA told us about stroke.
        Lancet Neurol. 2005; 4: 64-68
        • Bae H.J.
        • Lee J.
        • Park J.M.
        • et al.
        Risk factors of intracranial cerebral atherosclerosis among asymptomatics.
        Cerebrovasc Dis. 2007; 24: 355-360
        • Hartmann A.
        • Rundek T.
        • Mast H.
        • et al.
        Mortality and causes of death after first ischemic stroke: The Northern Manhattan Stroke Study.
        Neurology. 2001; 57: 2000-2005
        • Huang H.W.
        • Guo M.H.
        • Lin R.J.
        • et al.
        Prevalence and risk factors of middle cerebral artery stenosis in asymptomatic residents in Rongqi County, Guangdong.
        Cerebrovasc Dis. 2007; 24: 111-115
        • Kumar G.
        • Kalita J.
        • Kumar B.
        • et al.
        Magnetic resonance angiography findings in patients with ischemic stroke from North India.
        J Stroke Cerebrovasc Dis. 2010; 19: 146-152
        • Lee S.J.
        • Cho S.J.
        • Moon H.S.
        • et al.
        Combined extracranial and intracranial atherosclerosis in Korean patients.
        Arch Neurol. 2003; 60: 1561
        • Leung S.Y.
        • Ng T.H.
        • Yuen S.T.
        • et al.
        Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels.
        Stroke. 1993; 24: 779-786
        • McGarry P.
        • Solberg L.A.
        • Guzman M.A
        • Strong J.P.
        Cerebral atherosclerosis in New Orleans. Comparisons of lesions by age, sex, and race.
        Lab Investig. 1985; 52: 533
        • Sacco R.L.
        • Kargman D.E.
        • Zamanillo M.C.
        Race-ethnic differences in stroke risk factors among hospitalized patients with cerebral infarction The Northern Manhattan Stroke Study.
        Neurology. 1995; 45: 659-663
        • Suwanwela N.C.
        • Chutinetr A.
        Risk factors for atherosclerosis of cervicocerebral arteries: intracranial versus extracranial.
        Neuroepidemiology. 2003; 22: 37-40
        • Wityk R.J.
        • Lehman D.
        • Klag M.
        • et al.
        Race and sex differences in the distribution of cerebral atherosclerosis.
        Stroke. 1996; 27: 1974-1980
        • Jafar T.H.
        Children, obesity, and high blood pressure: Asian populations at high risk.
        Am J Hypertens. 2009; 22: 6-7
        • Kamal A.
        • Itrat A.
        • Murtaza M.
        • et al.
        The burden of stroke and transient ischemic attack in Pakistan: a community-based prevalence study.
        BMC Neurol. 2009; 9: 58
        • Kamal A.K.
        • Taj F.
        • Junaidi B.
        • et al.
        The Karachi Intracranial Stenosis Study (KISS) Protocol: an urban multicenter case-control investigation reporting the clinical, radiologic and biochemical associations of intracranial stenosis in Pakistan.
        BMC Neurol. 2009; 9: 31
        • Adams Jr., H.P.
        • Woolson R.F.
        • Clarke W.R.
        • et al.
        Design of the Trial of Org 10172 in Acute Stroke Treatment (TOAST).
        Control Clin Trials. 1997; 18: 358-377
        • Ay H.
        • Furie K.L.
        • Singhal A.
        • et al.
        An evidence-based causative classification system for acute ischemic stroke.
        Ann Neurol. 2005; 58: 688-697
        • Samuels O.B.
        • Joseph G.J.
        • Lynn M.J.
        • et al.
        A standardized method for measuring intracranial arterial stenosis.
        Am J Neuroradiol. 2000; 21: 643-646
        • Jones W.J.
        • Williams L.S.
        • Meschia J.F.
        Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by neurological history and examination.
        Stroke. 2001; 32: 2232-2236
        • Khan M.
        • Rasheed A.
        • Hashmi S.
        • et al.
        Stroke radiology and distinguishing characteristics of intracranial atherosclerotic disease in native South Asian Pakistanis.
        Int J Stroke. 2012;
      1. World Health Organization, 2008-2013 Action plan for the global strategy for the prevention and control of noncommunicable diseases. 2009. 1–48.

        • Wong K.S.
        • Huang Y.N.
        • Gao S.
        • et al.
        Intracranial stenosis in Chinese patients with acute stroke.
        Neurology. 1998; 50: 812-813
        • Chimowitz M.I.
        • Lynn M.J.
        • Derdeyn C.P.
        • et al.
        • SAMMPRIS Trial Investigators
        Stenting versus aggressive medical therapy for intracranial arterial stenosis.
        N Engl J Med. 2011; 365: 993-1003
        • Turan T.N.
        • Derdeyn C.P.
        • Fiorella D.
        • Chimowitz M.I.
        Treatment of atherosclerotic intracranial arterial stenosis.
        Stroke. 2009; 40: 2257-2261
        • Turan T.N.
        • Chimowitz M.I.
        Treatment of intracranial atherosclerotic stenosis.
        Rev Neurol Dis. 2008; 5: 117-124
        • Jafar T.H.
        Blood pressure, diabetes, and increased dietary salt associated with stroke—results from a community-based study in Pakistan.
        J Hum Hypertension. 2005; 20: 83-85
        • Hashmi S.K.
        • Afridi M.B.
        • Abbas K.
        • et al.
        Factors associated with adherence to anti-hypertensive treatment in Pakistan.
        PLoS One. 2007; 2: e280
        • Saleheen D.
        • Hashmi S.K.
        • Zaidi M.
        • et al.
        Evaluation of therapeutic control in a Pakistani population with hypertension.
        J Eval Clin Pract. 2010; 16: 1081-1084
        • Taj F.
        • Zahid R.
        • Syeda U.E.
        • et al.
        Risk factors of stroke in Pakistan: a dedicated stroke clinic experience.
        Can J Neurologic Sci. 2010; 37: 252-257
        • Farzadfar F.
        • Murray C.J.
        • Gakidou E.
        • et al.
        Effectiveness of diabetes and hypertension management by rural primary health-care workers (Behvarz workers) in Iran: a nationally representative observational study.
        Lancet. 2012; 379: 47-54
        • Jafar T.H.
        • Islam M.
        • Bux R.
        • et al.
        Cost-effectiveness of community-based strategies for blood pressure control in a low-income developing country. Clinical perspective findings from a Cluster-Randomized, Factorial-Controlled Trial.
        Circulation. 2011; 124: 1615-1625
        • Mirza I.
        • Jenkins R.
        Risk factors, prevalence, and treatment of anxiety and depressive disorders in Pakistan: systematic review.
        BMJ. 2004; 328: 794
        • Ngo V.K.
        • Rubinstein A.
        • Ganju V.
        • et al.
        Grand challenges: integrating mental health care into the non-communicable disease agenda.
        PLoS Med. 2013; 10: e1001443
        • Patel V.
        • Belkin G.S.
        • Chockalingam A.
        • et al.
        Grand challenges: integrating mental health services into priority health care platforms.
        PLoS Med. 2013; : e1001448
        • Chimowitz M.I.
        • Lynn M.J.
        • Turan T.N.
        • et al.
        Design of the stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis trial.
        J Stroke Cerebrovasc Dis. 2011; 20: 357-368
        • Moussouttas M.
        • Aguilar L.
        • Fuentes K.
        • et al.
        Cerebrovascular disease among patients from the Indian subcontinent.
        Neurology. 2006; 67: 894-896
        • De Silva D.A.
        • Woon F.P.
        • Lee M.P.
        • et al.
        South Asian patients with ischemic stroke intracranial large arteries are the predominant site of disease.
        Stroke. 2007; 38: 2592-2594
        • Kim Y.D.
        • Choi H.Y.
        • Cho H.J.
        • et al.
        Increasing frequency and burden of cerebral artery atherosclerosis in Korean stroke patients.
        Yonsei Med J. 2010; 51: 318-325
        • Wong K.S.
        • Huang Y.N.
        • Yang H.B.
        • et al.
        A door-to-door survey of intracranial atherosclerosis in Liangbei County, China.
        Neurology. 2007; 68: 2031-2034
        • Mak W.
        • Cheng T.S.
        • Chan K.H.
        • et al.
        A possible explanation for the racial difference in distribution of large-arterial cerebrovascular disease: ancestral European settlers evolved genetic resistance to atherosclerosis, but confined to the intracranial arteries.
        Med Hypotheses. 2005; 65: 637-648
        • Omran A.R.
        The epidemiologic transition: a theory of the epidemiology of population change.
        Milbank Mem Fund Quart. 1971; 49: 509-538
        • Klein I.F.
        • Labreuche J.
        • Lavallée PC.
        • et al.
        Is moderate atherosclerotic stenosis in the middle cerebral artery a cause of or a coincidental finding in ischemic stroke?.
        Cerebrovasc Dis. 2009; 29: 140-145
        • Mazighi M.
        • Labreuche J.
        • Gongora-Rivera F.
        • et al.
        Autopsy prevalence of intracranial atherosclerosis in patients with fatal stroke.
        Stroke. 2008; 39: 1142-1147
      2. World Development Indicators. 2011; Available at: Accessed March 21, 2014.

        • Spence J.D.
        • Hackam D.G.
        Treating arteries instead of risk factors: a paradigm change in management of atherosclerosis.
        Stroke. 2010; 41: 1193-1199