Original Article| Volume 23, ISSUE 6, P1577-1584, July 2014

Evaluating Clinical Effectiveness of Pneumococcal Vaccination in Preventing Stroke: The CAPAMIS Study, 3-Year Follow-up


      Cerebrovascular benefits using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing ischemic stroke in people older than 60 years.


      We conducted a population-based cohort study involving 27,204 individuals of 60 years or older in Tarragona, Spain, who were prospectively followed from December 01, 2008, until November 30, 2011. Outcomes were neuroimaging-confirmed ischemic stroke, 30-day mortality from stroke, and all-cause death. Pneumococcal vaccination effectiveness was evaluated by Cox regression analyses, estimating hazard ratios (HRs) adjusted for age, sex, comorbidities, and influenza vaccine status.


      Cohort members were followed for a total of 76,033 person-years, of which 29,065 were for vaccinated subjects. Overall, 343 cases of stroke, 45 deaths from stroke, and 2465 all-cause deaths were observed. Pneumococcal vaccination did not alter the risk of stroke (multivariable HR: 1.04; 95% confidence interval [CI]: .83-1.30; P = .752), death from stroke (HR: 1.14; 95% CI: .61-2.13; P = .686), and all-cause death (HR: .97; 95% CI: .89-1.05; P = .448). In analyses focused on people with and without a history of cerebrovascular disease, the PPV23 did not emerge effective in preventing any analyzed event, but influenza vaccine emerged independently associated with a reduced risk of death from stroke (HR: .51; 95% CI: .28-.93; P = .029) and all-cause death (HR: .73; 95% CI: .67-.81; P < .001).


      Our data support that the PPV23 does not provide benefit against ischemic stroke, but it also supports a beneficial effect of influenza vaccine in reducing specific- and all-cause mortality risk in the general population older than 60 years.

      Key Words

      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 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


        • Centers for Disease Control and Prevention (CDC)
        • Advisory Committee on Immunization Practices
        Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23).
        MMWR Morb Mortal Wkly Rep. 2010; 59: 1102-1106
        • Moberley S.
        • Holden J.
        • Tatham D.P.
        • et al.
        Vaccines for preventing pneumococcal infections in adults.
        Cochrane Database Syst Rev. 2013; 1 (review): CD000422
        • Madjid M.
        • Miller C.C.
        • Zarubaev V.V.
        • et al.
        Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34,892 subjects.
        Eur Heart J. 2007; 28: 1205-1210
        • Ramirez J.
        • Aliberti S.
        • Mirsaeidi M.
        • et al.
        Acute myocardial infarction in hospitalized patients with community-acquired pneumonia.
        Clin Infect Dis. 2008; 47: 182-187
        • Madjid M.
        Acute infections, vaccination and prevention of cardiovascular disease.
        CMAJ. 2008; 179: 749-750
        • Madjid M.
        • Musher D.M.
        Preventing myocardial infarction with vaccination: myths and realities.
        JAMA. 2010; 303: 1751-1752
        • Smeeth L.
        • Thomas S.L.
        • Hall A.J.
        • et al.
        Risk of myocardial infarction and stroke after acute infection or vaccination.
        N Engl J Med. 2004; 351: 2611-2618
        • Lamontagne F.
        • Garant M.P.
        • Carvalho J.C.
        • et al.
        Pneumococcal vaccination and risk of myocardial infarction.
        CMAJ. 2008; 179: 773-777
        • Tseng H.F.
        • Slezak J.M.
        • Quinn V.P.
        • et al.
        Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men.
        JAMA. 2010; 303: 1699-1706
        • Eurich D.T.
        • Johnstone J.J.
        • Minhas-Sandhu J.K.
        • et al.
        Pneumococcal vaccination and risk of acute coronary syndromes in patients with pneumonia: population-based cohort study.
        Heart. 2012; 98: 1072-1077
        • Meyers D.G.
        • Beahm D.D.
        • Jurisich P.D.
        • et al.
        Influenza and pneumococcal vaccinations fail to prevent myocardial infarction.
        Heart Drug. 2004; 4: 96-100
        • Hung I.F.
        • Leung A.Y.
        • Chu D.W.
        • et al.
        Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study.
        Clin Infect Dis. 2010; 51: 1007-1016
        • Siriwardena A.N.
        • Gwini S.M.
        • Coupland C.A.
        Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case-control study.
        CMAJ. 2010; 182: 1617-1623
        • Vila-Corcoles A.
        • Hospital-Guardiola I.
        • Ochoa-Gondar O.
        • et al.
        Rationale and design of the CAPAMIS study: effectiveness of pneumococcal vaccination against community-acquired pneumonia, acute myocardial infarction and stroke.
        BMC Public Health. 2010; 10: 25
        • Vila-Corcoles A.
        • Ochoa-Gondar O.
        • Rodriguez-Blanco T.
        • et al.
        • EPIVAC Study Group
        Clinical effectiveness of pneumococcal vaccination against acute myocardial infarction and stroke in people over 60 years: the CAPAMIS study, one-year follow-up.
        BMC Public Health. 2012; 12: 222
        • Vila-Corcoles A.
        • Ochoa-Gondar O.
        • Rodriguez-Blanco T.
        • et al.
        Ineffectiveness of pneumococcal Vaccination in cardiovascular prevention: the CAPAMIS study.
        JAMA Intern Med. 2013; 173: 1918-1920
        • Sacco R.L.
        • Adams R.
        • Albers G.
        • et al.
        • American Heart Association
        • American Stroke Association Council on Stroke
        • Council on Cardiovascular Radiology and Intervention
        • American Academy of Neurology
        Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.
        Stroke. 2006; 37: 577-617
        • D’Agostino Jr., R.B.
        Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group.
        Stat Med. 1998; 17: 2265-2281
        • Brookhart M.A.
        • Schneeweiss S.
        • Rothman K.J.
        • et al.
        Variable selection for propensity score models.
        Am J Epidemiol. 2006; 163: 1149-1156
        • Hosmer D.W.
        • Lemeshow S.
        Applied survival analysis. Regression modeling of time to event data.
        John Wiley & Sons, New York1999
        • Corrales-Medina V.F.
        • Madjid M.
        • Musher D.M.
        Role of acute infection in triggering acute coronary syndromes.
        Lancet Infect Dis. 2010; 10: 83-92
        • Corrales-Medina V.F.
        • Musher D.M.
        • Shachkina S.
        • et al.
        Acute pneumonia and the cardiovascular system.
        Lancet. 2013; 9: 496-505
        • Binder C.J.
        • Hörkkö S.
        • Dewan A.
        • et al.
        Pneumococcal vaccination decreased atherosclerotic lesion formation: molecular mimicry between streptococcus pneumoniae and oxidized LDL.
        Nat Med. 2003; 9: 736-743
        • Heuschmann P.U.
        • Di Carlo A.
        • et al.
        • European Registers of Stroke (EROS) Investigators
        Incidence of stroke in Europe at the beginning of the 21st century.
        Stroke. 2009; 40: 1557-1563
        • Clua-Espuny J.L.
        • Piñol-Moreso J.L.
        • Panisello-Tafalla A.
        • et al.
        Ebrictus study. Functional results, survival, and potential years of life lost after the first stroke.
        Aten Primaria. 2012; 44 ([in Spanish]): 223-231
        • Díaz-Guzmán J.
        • Egido-Herrero J.A.
        • Fuentes B.
        • et al.
        • Proyecto Ictus del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología
        Incidence of strokes in Spain: the Iberictus study. Data from the pilot study.
        Rev Neurol. 2009; 48 ([in Spanish]): 61-65
        • Gurfinkel E.P.
        • de la Fuente R.L.
        Two-year follow-up of the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Registry.
        Tex Heart Inst J. 2004; 31: 28-32
        • Wang C.S.
        • Wang S.T.
        • Lai C.T.
        • et al.
        Impact of influenza vaccination on major cause-specific mortality.
        Vaccine. 2007; 25: 1196-1203
        • Jefferson T.
        • Di Pietrantonj C.
        • Al-Ansary L.A.
        • et al.
        Vaccines for preventing influenza in the elderly.
        Cochrane Database Syst Rev. 2010; : CD004876
        • Vila-Corcoles A.
        • Ochoa-Gondar O.
        Preventing pneumococcal disease in the elderly: recent advances in vaccines and implications for clinical practice.
        Drugs Aging. 2013; 30: 263-276