Fibrinogen in South Asians

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Fibrinogen in South Asians
Dr Kirti Kain MD MRCP
Academic Unit of Molecular Vascular
Medicine Leeds University Leeds United Kingdom
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I am a research fellow at Leeds University. My
interest in this field evolved because of my
research on genetic and environmental risk
factors for cerebrovascular disease in South
Asians residing in United Kingdom. I am excited
because my research has lead to a number of novel
findings which are published in respectable
journals. Acknowledgement The project was funded
by Stroke Association UK
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Introduction

• Standardised mortality ratios for 1989-1992 for
  ischaemic heart disease in South Asians (Indians,
  Pakistanis and Bangladeshis) in UK was 141-162 Vs
  100 in Whites

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Introduction

• South Asians have Myocardial infarction 5.5 yrs
  earlier
• Greater no of diseased vessels Vs Whites

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Introduction

• Rate of MI is 4 times in South Asians Vs Whites
• Myocardial damage is greater in South Asians

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Risk Factors

• South Asian men have greater chance of myocardial
  infarction Vs South Asian women.

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Metabolic Risk Factors

• Age adjusted prevalence of hypertension is
  greater in South Asians 26 Vs 13 in Whites and
  risk of hypertension being undetected is higher

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Metabolic Risk Factors

• Prevalence of type 2 diabetes is 3-6 times
  commoner and plasma insulin levels are higher in
  South Asians Vs Whites

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Metabolic Risk Factors

• South Asians have lower BMI but higher waist-hip
  ratio Vs Whites

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Dietary Risk Factors

• South Asians have lower total energy intake
• Higher dietary fibre intake
• Higher polyunsaturated fatty- acid intake Vs
  Whites

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Dietary Risk Factors

• South Asians have lower total cholesterol
• Higher triglycerides and
• Lower high-density lipoprotein cholesterol Vs
  Whites

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Thrombotic Risk factors

• South Asians have increased fibrinogen levels
• Increased plasminogen activator inhibitor -1
  activity
• Lower Factor VII activity Vs Whites

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Fibrinogen in Whites

• Fibrinogen is independent predictor of ischaemic
  vascular disease (stroke and heart disease) in
  Whites

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Fibrinogen in Whites

• 25 of inter-individual variation in circulating
  fibrinogen levels are determined by age, sex,
  type 2 diabetes and hypertension

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Fibrinogen in Whites

• 51 of variation in fibrinogen levels may be
  determined by genetic factors

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Fibrinogen in Whites

• There is relation between fibrinogen and B? Arg
  448Lys, ? -455G/A and A?Thr312Ala polymorphisms

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Fibrinogen in Whites

• In Northwick Park study an increase of 0.6g/l of
  fibrinogen levels was associated with an 84
  increased risk of IHD over ensuing 5 years

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Fibrinogen and ethnicity

• Ethnic groups with lower prevalence of IHD,
  Greenland Inuit and Japanese have lower
  fibrinogen levels Vs Whites

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Fibrinogen and ethnicity

• The Inuit and the Japanese have decreased
  prevalence of ? fibrinogen ? -455A allele which
  might account for the lower levels of plasma
  fibrinogen in them

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Fibrinogen and ethnicity

• Plasma fibrinogen levels probably mirror the
  incidence of atherothrombotic disease in
  different populations.

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Fibrinogen in South Asians

• Fibrinogen levels are higher in females (3.56 Vs
  3.10g/l, p0.0008) Vs males

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Fibrinogen in South Asians

• Fibrinogen levels are higher in South Asian
  smokers (3.87 Vs. 3.19g/l, p0.03) Vs non-smokers

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Fibrinogen in South Asians

• There is no significant association of fibrinogen
  with either hypertension
• or type 2 diabetes

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Fibrinogen in South Asians

• Fibrinogen levels are 0.53g/l higher after
  accounting for the classic risk factors and known
  polymorphisms) Vs Whites

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Fibrinogen in South Asians

• There is no difference in association of
  conventional risk factors and correlates of
  fibrinogen between South Asians Vs Whites

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Fibrinogen in South Asians

• There is evidence of high degree of linkage
  disequilibrium between ?-fibrinogen B?-455G/A and
  B?Arg 448Lys polymorphisms

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Fibrinogen in South Asians

• Fibrinogen levels are high in South Asians
  possessing ?-455A and B?448 Lys alleles and
  magnitude is greater for the ? -455A in the
  linear regression models

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Fibrinogen in South Asians

• There are no differences in genotype distribution
  for A?Thr312Ala, ?-455G/A and B ?Arg448Lys
  polymorphisms between South Asians Vs Whites

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Conclusions

• Elevated fibrinogen levels in South Asians (Vs
  Whites) are determined by sex
• smoking and
• B ?Arg448Lys / ?-455G/A

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Future perspectives

• Fibrinogen levels are influenced by variations in
  health related behaviours
• Energy restriction physical activity lowers
  fibrinogen in adolescents

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Future perspectives

• Effect of diet and exercise on fibrinogen levels
  in South Asians has to be established

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Future perspectives

• Prospective studies in UK and their native
  countries ought to be conducted to elucidate the
  role of elevated fibrinogen in incidence of
  cardiovascular disease.

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Future perspectives

• Studies should be carried out in each South Asian
  subgroup separately because they are a
  heterogeneous population