Infection and cardiovascular disease

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Infection and cardiovascular disease

• Shah Ebrahim
• NCDEU

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Overview

• Global burden of disease
• Chronic infection and atherosclerosis
• Hepatitis B and cardiovascular disease
• Acute diarrhoea and blood pressure

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Ten leading causes of death by income group, 2001
Lopez et al Lancet 20063671747-1757
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Risk factors and global burden of mortality
Lopez et al Lancet 20063671747-1757
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Disease burden to specific risk factors
East Asia Pacific
Europe Central Asia
Latin America Caribbean
Middle East North Africa
South Asia
Sub-Saharan Africa
High income countries
Lopez et al Lancet 20063671747-1757
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Infection, inflammation and atherosclerosis

• C. pneumoniae, H. pylori, Porphyromonas
  gingivalis, Cytomegalovirus, Herpes simplex
  virus, Hepatitis A, B, and C virus linked with an
  increased risk of cardiovascular diseases
• Proinflammatory effects of infection increased
  CRP, cytokines

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(No Transcript)
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Acute respiratory infection and myocardial
infarction
Influenza vaccination
Age-adjusted incidence ratios
Baseline period
Smeeth et al, NEJM 20043512611-2618
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Hepatitis B and CVD

• Intracellular pathogen, causes systemic effects
  and immune responses, chronic phase
• Serological markers reflecting the presence and
  status of infection
• Thrombosis of small portal and hepatic veins in
  chronic viral hepatitis
• Is HBV infection associated with CVD?

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Hazard ratios for CVDs by HBsAg seropositivity
Korean National Health Service Study, 1986-2001
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HRs for CVDs by HBsAg seropositivity status and
liver function
Haem. stroke
Ischaemic stroke
Myocardial inf.
Korean National Health Service Study, 1986-2001
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HBsAg seropositivity and coagulation markers
Korean National Health Service Study, 1986-2001
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Where next with this?

• Case-control studies in developing countries with
  high prevalence of HBV
• Examine effects of Hepatitis B immunisation
  programmes on CVD risk

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Global burden of hypertension (160/95)
Kearney et al, Lancet 2005365217-223
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Life course exposures and blood pressure
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Dietary sodium Alcohol Adult obesity
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Dietary sodium Childhood obesity
Sensitive periods baroreceptor setting, sodium
retension
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Catch up growth Infant feeding
Critical periods renal development
Intra-uterine growth Genetic variants
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Mean difference in systolic BP for breast fed and
bottle fed infants
1.4 mmHg, 95 CI 2.2, 0.6
Martin, R. et al. Am. J. Epidemiol. 2005 16115-26
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Long-term follow up of an RCT of salt restriction
in infancy
Geleijnse et al, Hypertension. 199729913-917
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Acute diarrhoea and blood pressure

• Severe diarrhoea leads to dehydration which
  results in salt and water retention
• If occurring at sensitive period (infancy) may
  result in developmental plasticity
• Survival advantage in ability to retain salt and
  water in face of dehydration
• High sodium environment, high salt retention
  phenotype high blood pressure

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Acute diarrhoea and blood pressure possible
explanations
Diarrhoea episodes, severity, timing
Raised blood pressure
SEP crowding, water supply, sanitation, health
care
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Direct evaluation ALSPAC
Davey Smith, Leary, Ness JECH 200660142-143
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Indirect evaluation
Climatic factors hot and dry summers
Raised blood pressure in adult life
Increased risk of acute diarrhoea dehydration
in infancy
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Climate and diarrhoea, Peru
Checkley et al, Lancet 2000 355442-450
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Lawlor D et al. J Epidemiol Comm Health 2003
57134-140
 
   
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Approach

• Mean outdoor temperature rainfall data for
  July-Sept for 1st, 2nd, 3rd year of life for each
  women obtained (1919-1940)
• Dinamap BP measurements aged 60-79 in 3964 (97)
  women matched to climatic data (born abroad, no
  place of birth recorded, inadequate BP measure)

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Climatic factors, SEP and leg length
Lawlor et al, AJE 2006163608-14
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Associations with systolic BP and climate
Per SD 33.9mm summer rainfall
Per SD 1.3oC summer temp.
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Hot and dry (women in hottest quarter and driest
quarter, n532) and systolic BP
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Interpretation

• Climate factors not associated with SEP, BMI ?
  good instrument for making unconfounded
  assessment
• Supports hypothesis of dehydration in infancy and
  raised blood pressure in adult life

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What next?

• Ecological studies in developing countries using
  climatic data
• Direct assessment of frequency/severity of
  diarrhoeal illness and blood pressure in
  adolescence/adulthood in developing countries
• Long-term follow up of oral rehydration trials,
  infant feeding trials with measurement of CVD
  risk factors

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Infection and CVD risk

• Antibiotics for secondary prevention do not work
  (see Anderson J. NEJM 200535216)
• Understanding mechanisms by which acute and
  chronic infections may affect development of
  atheroma
• Examine relationships between acute infection and
  markers of endothelial function at different ages
  
• Examine effects of population STD antibiotic
  treatment on endothelial function