Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP) and CAP-related mortality in adults. Pneumococcal vaccination (PV) could protect subjects from cardiovascular events by reducing pneumonia severity or even preventing it. We sought to determine the ability of PV to protect from the risk of cardiovascular events.
Methods and results
A comprehensive search of electronic databases was conducted up to March 2014. Cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CI) were included. Eleven studies were included (332,267 participants, mean follow-up 20.1 months). The pooled RRs for cardiovascular events and cardiovascular mortality were 0.86 (95% CI: 0.76–0.97) and 0.92 (95% CI: 0.86–0.98; fixed-effects), respectively, for subjects with PV versus without PV. Protective ability was more prominent in high cardiovascular risk populations and with older age. The protective role of PV was attenuated after 1 year (RR: 0.72; 95% CI: 0.59–0.88 vs RR: 1.03; 95% CI: 0.93–1.14; p = 0.002, for follow-up >1 year vs ≤1 year, respectively). It also increased as the presence of cardiovascular and pulmonary disease increased. Regarding myocardial infarction (MI) and cerebrovascular events, the protective role of PV was statistically significant only in the elderly (RR: 0.90; 95% CI: 0.817–0.999; fixed-effects and RR: 0.86; 95% CI: 0.75–0.99, respectively).
Conclusion
PV is associated with decreased risk of cardiovascular events and mortality. This protective effect increases at older age and in high cardiovascular risk subjects and decreases as the time elapses from PV. PV decreases the risk of MI and cerebrovascular events in the elderly.
Hoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep 2012; 61: 4. National Center for Health Statistics. Centers for Disease Control and Prevention, http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf (accessed 1 January 2014).
2.
CillónizCEwigSPolverinoE. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax2011; 66: 340–346.
3.
WoodheadM. Community-acquired pneumonia in Europe: causative pathogens and resistance patterns. Eur Respir J Suppl2002; 36: 20s–27s.
4.
JacksonMLNeuzilKMThompsonWW. The burden of community-acquired pneumonia in seniors: results of a population-based study. Clin Infect Dis2004; 39: 1642–1650.
5.
FryAMShayDKHolmanRC. Trends in hospitalizations for pneumonia among persons aged 65 years or older in the United States, 1988–2002. JAMA2005; 294: 2712–2719.
6.
Corrales-MedinaVFMusherDMWellsGA. Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality. Circulation2012; 125: 773–781.
7.
Corrales-MedinaVFSuhKNRoseG. Cardiac complications in patients with community-acquired pneumonia: a systematic review and meta-analysis of observational studies. PLoS Med2011; 8: e1001048–e1001048.
8.
Corrales-MedinaVFMusherDMShachkinaS. Acute pneumonia and the cardiovascular system. Lancet2013; 381: 496–505.
9.
VlachopoulosCDimaIAznaouridisK. Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation2005; 112: 2193–2200.
JacksonLAYuOHeckbertSR. Vaccine Safety Datalink Study Group. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Am J Epidemiol2002; 156: 634–640.
12.
TsengHFSlezakJMQuinnVP. Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men. JAMA2010; 303: 1699–1706.
13.
HungIFLeungAYChuDW. Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study. Clin Infect Dis2010; 51: 1007–1016.
14.
GilbertsonDTGuoHArnesonTJ. The association of pneumococcal vaccination with hospitalization and mortality in hemodialysis patients. Nephrol Dial Transplant2011; 26: 2934–2939.
15.
ChanTCHungIFLukJK. Prevention of mortality and pneumonia among nursing home older adults by dual pneumococcal and seasonal influenza vaccination during a pandemic caused by novel pandemic influenza A (H1N1). J Am Med Dir Assoc2012; 13: 698–703.
16.
ChangYCChouYJLiuJY. Additive benefits of pneumococcal and influenza vaccines among elderly persons aged 75 years or older in Taiwan – a representative population-based comparative study. J Infect2012; 65: 231–238.
17.
ZahidMSinglaIGoodCB. Associations between Pneumococcal Vaccination and Adverse Outcomes in Patients with Suspected Acute Coronary Syndrome. Adv Infect Dis2012; 2: 122–134.
18.
JohnstoneJLoebMTeoKK. Ongoing Telmisartan Alone and in combination with Ramipril Global EndPoint Trial (ONTARGET); Telmisartan Randomized Assessment Study in ACE Intolerant subjects with cardiovascular Disease (TRANSCEND) investigators. Influenza vaccination and major adverse vascular events in high-risk patients. Circulation2012; 126: 278–286.
19.
EurichDTJohnstoneJJMinhas-SandhuJK. Pneumococcal vaccination and risk of acute coronary syndromes in patients with pneumonia: population-based cohort study. Heart2012; 98: 1072–1077.
20.
ChenLFChenHPHuangYS. Pneumococcal pneumonia and the risk of stroke: a population-based follow-up study. PLoS One2012; 7: e51452–e51452.
21.
Vila-CorcolesAOchoa-GondarORodriguez-BlancoT. EPIVAC Study Group. Ineffectiveness of pneumococcal vaccination in cardiovascular prevention: the CAPAMIS study. JAMA Intern Med2013; 173: 1918–1920.
22.
Ochoa-GondarOVila-CorcolesARodriguez-BlancoT. EPIVAC Research Group. Evaluating the clinical effectiveness of pneumococcal vaccination in preventing myocardial infarction: the CAPAMIS study, three-year follow-up. Vaccine2014; 32: 252–257.
23.
SmeethLThomasSLHallAJ. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med2004; 351: 2611–2618.
24.
MeyersDGBeahmDDJurisichPD. Influenza and pneumoccocal vaccinations fail to prevent myocardial infarction. Heart Drug2004; 4: 96–100.
25.
LamontagneFGarantMPCarvalhoJC. Pneumococcal vaccination and risk of myocardial infarction. CMAJ2008; 179: 773–777.
26.
SiriwardenaANGwiniSMCouplandCA. Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case-control study. CMAJ2010; 182: 1617–1623.
27.
SiriwardenaANAsgharZCouplandCAC. Influenza and pneumococcal vaccination and risk of stroke or transient ischaemic attack – matched case control study. Vaccine2014; 32: 1354–1361.
28.
FismanDNAbrutynESpaudeKA. Prior pneumococcal vaccination is associated with reduced death, complications, and length of stay among hospitalized adults with community-acquired pneumonia. Clin Infect Dis2006; 42: 1093–1101.
29.
ViasusDGarcia-VidalCManresaF. Risk stratification and prognosis of acute cardiac events in hospitalized adults with community-acquired pneumonia. J Infect2013; 66: 27–33.
30.
Vila-CorcolesAOchoa-GondarORodriguez-BlancoT. 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 Health2012; 12: 222–222.
31.
Vila-CorcolesAHospital-GuardiolaIOchoa-GondarO. Rationale and design of the CAPAMIS study: effectiveness of pneumococcal vaccination against community-acquired pneumonia, acute myocardial infarction and stroke. BMC Public Health2010; 10: 25–25.
32.
HedlundJChristensonBLundberghP. Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in elderly people: a 1-year follow-up. Vaccine2003; 21: 3906–3911.
33.
ChristensonBPauksenKSylvanSP. Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity. Virol J2008; 5: 52–52.
34.
BondTCSpauldingACKrisherJ. Mortality of dialysis patients according to influenza and pneumococcal vaccination status. Am J Kidney Dis2012; 60: 959–965.
35.
Vila-CorcolesAOchoa-GondarORodriguez-BlancoT. EPIVAC Research Group. Evaluating clinical effectiveness of pneumococcal vaccination in preventing stroke: the CAPAMIS Study, 3-Year follow-up. J Stroke Cerebrovasc Dis2014; 23: 1577–1484.
36.
MoberleySHoldenJTathamDP. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev2013; 1: CD000422–CD000422.
37.
HussAScottPStuckAE. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ2009; 180: 48–58.
38.
StroupDFBerlinJAMortonSC. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA2000; 283: 2008–2012.
39.
LiberatiAAltmanDGTetzlaffJ. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med2009; 151: W65–94.
40.
VlachopoulosCVTerentes-PrintziosDGIoakeimidisNK. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes2013; 6: 99–109.
41.
VlachopoulosCAznaouridisKStefanadisC. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol2010; 55: 1318–1327.
42.
VlachopoulosCAznaouridisKO'RourkeMF. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J2010; 31: 1865–1871.
43.
Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses, www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed 1 January 2014).
44.
AtkinsDBestDBrissPA. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ2004; 328: 1490–1490.
45.
HigginsJPThompsonSGDeeksJJ. Measuring inconsistency in meta-analyses. BMJ2003; 327: 557–560.
46.
AltmanDGBlandJM. Interaction revisited: the difference between two estimates. BMJ2003; 326: 219–219.
47.
DuvalSTweedieR. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics2000; 56: 455–463.
48.
BorensteinMHedgesLHigginsJ. Comprehensive Meta Analysis, Version 2. Englewood, NJ: Biostat, 2005.
49.
FedsonDSLissC. Precise answers to the wrong question: prospective clinical trials and the meta-analyses of pneumococcal vaccine in elderly and high-risk adults. Vaccine2004; 22: 927–946.
50.
Vila-CórcolesA. Vaccinate your child and save its grandparents from a heart attack? Current perspectives in antipneumococcal vaccination. J Intern Med2009; 266: 432–444.
GriffinMRZhuYMooreMR. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med2013; 369: 155–163.
53.
MenéndezRSahuquillo-ArceJMReyesS. Cytokine activation patterns and biomarkers are influenced by microorganisms in community-acquired pneumonia. Chest2012; 141: 1537–1545.
54.
MusherDMRuedaAMKakaAS. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis2007; 45: 158–165.
55.
Corrales-MedinaVFSerpaJRuedaAM. Acute bacterial pneumonia is associated with the occurrence of acute coronary syndromes. Medicine (Baltimore)2009; 88: 154–159.
56.
WangCCPengCLWangGJ. Pneumococcal pneumonia and the risk of acute coronary syndrome: a population-based cohort study. Int J Cardiol2013; 168: 4480–4481.
57.
BinderCJHörkköSDewanA. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med2003; 9: 736–743.
58.
Thygesen K, Alpert JS, Jaffe AS, et al. Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Katus HA, Lindahl B, Morrow DA, et al. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020–2035.
59.
Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep2012; 61: 816–819.
60.
PerkJde BackerGGohlkeH. 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). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol2012; 19: 585–667.
61.
YancyCWJessupMBozkurtB. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation2013; 128: e240–327.
62.
HebertKMarzoukaGArcementL. Prevalence of vaccination rates in systolic heart failure: a prospective study of 549 patients by age, race, ethnicity, and sex in a heart failure disease management program. Congest Heart Fail2010; 16: 278–283.
63.
GohlkeH. Is it worth offering cardiovascular disease prevention to the elderly?Eur J Prev Cardiol2013; 20: 121–126.
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