Pneumoniaand Cardiac Disease

Is pneumonia the egg?

Grant WatererMBBS PhD MBA FRACP FCCP MRCP

Professor of Medicine, University of Western AustraliaProfessor of Medicine, Northwestern University, Chicago

Conflicts of interest

• Advisory boards + speaking for AstraZeneca, GlaxoSmithKline, Menarini– Relevant to any discussions around ICS + pneumonia

Am J Respir Crit Care Med 2015

Is it really pneumonia?308 Patients presenting to ED with Clinical Features of pneumonia

CXR

Clinician Diagnosis

188 Pneumonia - YES 120 Pneumonia - NO

CT CT

132 Pneumonia - YES56 Pneumonia - NO

40 Pneumonia - YES80 Pneumonia - NO

Acute outcomes in pneumonia

Mortensen et al Arch Intern Med 2002Mortensen et al Arch Intern Med 2004

Acute RTI’s increase risk of AMI in short term

Meier et al Lancet 1998

Acute RTI’s increase risk of AMI in short term

0

1

2

3

4

5

6

1‐3 Days 4‐7 Days 8‐14 Days 15‐28 Days 29‐91 Days

Smeeth et al N Engl J Med 2004

OR fo

r AMI

Increase risk of cardiac events in acute pneumococcal CAP

Musher et al Clin Infect Dis 2007

EVENT NUMBER of EVENTS

Myocardial infarction 7.1%

New arrhythmia 4.6%

New CHF 7.6%

Total patients with Cardiac Event 19.4%

170 consecutive patients with pneumococcal pneumonia

Increase risk of AMI in acute CAP

Ramirez et al Clin Infect Dis 2008

Risk of AMI or Stroke post AECOPD

0

0.5

1

1.5

2

2.5

1‐5 days 6‐10 days 11‐15 days 16‐49 days

IHDStokeRe

lative

Risk

Donaldson et al Chest 2010

N=28847

New cardiac events and especially AMI are common in pneumonia

Arrhythmias are also common

• Soto‐Gomez et al Am J Med 2013• CAP in 32,689 patients from US VA system• 12% had a new cardiac arrhythmia documented within in 90‐days of admission

• Mostly AF

Soto-Gomez et al Am J Med 2013

Is arrhythmia an effect of macrolides?

Mortensen et al JAMA 201473,690 patients from the VA database with pneumonia

Mortensen et al JAMA 2014

73,690 patients from the VA database with pneumonia

Pathogenesis?

Short term risk of AMI

• Inflammation induces a procoagulant state– More likely to thrombosis a critically narrowed vessel

• Inflammation destablizes atheromatousplaques– More likely to have acute plaque rupture

• Pneumonia increases heart rate and myocardial oxygen consumption– Decreased diastolic filling time– More vulnerable myocardium

Cangemi et al JACC 201431 AMI in 278 patients with CAP

Platelet activation predicts AMI in patients with pneumonia (SIXTUS trial)

Brown et al Am J Respir Crit Care Med 2015; PLoS Pathog 2014

Treatment/prevention options?

Aspirin?

• Oz et al Coron Art Dis 2013• 108 pts with pneumonia• Randomised controlled trial 300mg aspirin per day for 1 month

• 91 (aspirin) vs 94 (control)• Highly selective troponin + ECG• 1 AMI vs 10 AMI p=0.015

Estimated survival during hospitalization of the aspirin group, compared to the nonaspirin group, using Kaplan–Meier survival analysis.

Falcone M et al. J Am Heart Assoc 2015;4:e001595

© 2015 Falcone M et al.

Prospective Observational study of 1005 patients 60yo+

Other anti‐platelets?

• Gross et al J Thromb Thromblysis 2013– 400,000 patients from Kentucky Medicare Database– 15,000 on clopidogrel– 2,908 pneumonias– OR for mortality 0.63

• Storey et al Platelets 2014– 18,421 patients in PLATO ticagrelor vs clopidogrel– Pneumonia events equivalent– Pneumonia deaths 7 vs 23 p=0.003

Other medications?

Wu et al PLOSOne 2014

Drug Odds Ratio 95%CI

Beta‐blocker 1.01 0.91‐1.13

Statin 1.10 0.99‐1.20

ACE Inhibitor 1.02 0.93‐1.12

ARBs 1.013 0.82‐1.28

Risk of Cardiac Adverse event in 21,985 patients with pneumoniafrom the US VA database

Pneumonia and acute CVD events?

• Under recognised• Under treated• Aspirin probably mandatory unless clear C.I.• Dose of aspirin probably 300mg for at least a month

• Possible other anti‐platelet therapy may be more efficacious – await TCAP results

Long‐term cardiac outcomes

Current Paradigm

• Patient gets pneumonia

• We treat the patient

• The patient gets better

• Discharge the patient satisfied we did our job

Mortality due to CAPInpatient mortality

Mortality in the subsequent2 years

0 200 400 600 800 1000

Days post discharge

1.0

0.9

0.8

0.7

0.6

0.5

45-64 yr

65-75 yr

> 75 yr

18-44yr

Long term survival after pneumoniaBrancati et al Lancet 1993;342:30-33

Koivula et al 1999

112 patients with CAP

Finland4167 60yo+

Vergis et al Arch Int Med 2001110 cases110 Age + ADL matched controlsNursing home population

Kaplan et al Arch Intern Med 2003

• Medicare database of Americans aged 65+• 159,000 CAP and 794,000 hospitalised controls• One year mortality 33.6% vs 24.9% (p<0.001)• vs population controls standardised 1‐year mortality 2.69

• Excess mortality unexplained

Mortensen et al Clin Infect Dis 2003

5‐year survival vs population control statistics

One or more co‐morbiditiesNo co‐morbidities

Age Group

18-40 +

41-60 ■

61-80 ○

81+ ▲

Age Group

18-40 +

41-60 ■

61-80 ○

81+ ▲

Waterer et al Am J Respir Crit Care Med 2005

14%20%

0 200 400 600 800 1000 1200 1400 1600 0 200 400 600 800 1000 1200 1400 1600

Days post discharge

Survi

val (P

ropo

rtion)

0

0.1

0.2

0

.3

0.4

0

.5

0.6

0.7

0.

8 0

.9

1.0

3‐year Mortality vs Expected Mortality in patients with no comorbidites

Age Group

AbsoluteDifference

Relative Difference

18-40 years

1.1% 3.0

41-60 years

9.6% 6.6

61-80 years

8.0% 2.0

Cangemi et al Am J Cardiol 2015

Cangemi et al Am J Cardiol 2015

Pneumonia and subsequent IHD• Corales‐Medina et al JAMA 2015• 5888 pts in Cardiovascular heart Study

– Aged 65+– 1989‐1994

• 15792 in the Atherosclerosis risk in communities study– Aged 45‐64– 1987‐1989

• All pneumonias matched to 2 controls• 10‐year follow up• Risk of IHD adjusted for cardiac risk factors + comorbidities

Pneumonia and Stroke/AMI

1

1.5

2

2.5

3

3.5

4

4.5

5

5.5

6

0‐30 31‐90 91‐365

Time post discharge (days)

OR fo

r new

onse

t IHD

or st

roke

Corales-Medina et al JAMA 2015

CHS (n=5888)ARIC (n=15792)

Corrales-Medina et al JAMA 2015

Pneumonia and new onset heart failure

• Corales‐Medina et al Am Heart J 2015• 5613 pts in Cardiovascular heart Study• Aged 65+• 665 cases of pneumonia

Pneumonia and new onset heart failure

1

3

5

7

9

11

13

31‐90 91‐180 181‐365 1‐5 years

Time post discharge (days)

OR fo

r new

onse

t hea

rt fai

lure

Corales-Medina et al Am Heart J 2015

How do we mitigate the risk?• We don’t know

• Assess all cardiovascular risk factors at time of admission and follow up

• Aspirin unless contraindicated– Probably 300mg for first month

• Statin unless contraindicated?? How long??

• Exercise?

Can we tease out high risk patient groups?

Higher risk groups

• Older• Existing CVS risk factors• Pneumococcal disease• Bacteremia• ?

Yende et al Am J Respir Crit Care Med 2008

Recovery in Exercise Tolerance post CAP

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

19yo32yo64yo

Weeks after discharge

% of

6 mo

nth ac

tivity

Conclusion

• CVS events are much more common in both acute pneumonia and in the 1‐year after recovery than we have realised

• This needs immediate attention• You need to change your approach to pneumonia and especially post pneumonia care

• I give aspirin 300mg unless contraindicated• Research!!