Fibrinogen in South Asians

Dr Kirti Kain MD MRCP

Academic Unit of Molecular Vascular Medicine

Leeds University

Leeds

United Kingdom

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

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

Introduction

• South Asians have Myocardial infarction 5.5 yrs earlier &

• Greater no of diseased vessels Vs Whites

Introduction

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

• Myocardial damage is greater in South Asians

Risk Factors

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

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

Metabolic Risk Factors

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

Metabolic Risk Factors

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

Dietary Risk Factors

• South Asians have lower total energy intake

• Higher dietary fibre intake

• Higher polyunsaturated fatty- acid intake Vs Whites

Dietary Risk Factors

• South Asians have lower total cholesterol

• Higher triglycerides and

• Lower high-density lipoprotein cholesterol Vs Whites

Thrombotic Risk factors

• South Asians have increased fibrinogen levels

• Increased plasminogen activator inhibitor -1 activity

• Lower Factor VII activity Vs Whites

Fibrinogen in Whites

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

Fibrinogen in Whites

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

Fibrinogen in Whites

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

Fibrinogen in Whites

• There is relation between fibrinogen and B Arg 448Lys, -455G/A and AThr312Ala polymorphisms

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

Fibrinogen and ethnicity

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

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

Fibrinogen and ethnicity

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

Fibrinogen in South Asians

• Fibrinogen levels are higher in females (3.56 Vs 3.10g/l, p=0.0008) Vs males

Fibrinogen in South Asians

• Fibrinogen levels are higher in South Asian smokers (3.87 Vs. 3.19g/l, p=0.03) Vs non-smokers

Fibrinogen in South Asians

• There is no significant association of fibrinogen with either hypertension

• or type 2 diabetes

Fibrinogen in South Asians

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

Fibrinogen in South Asians

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

Fibrinogen in South Asians

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

Fibrinogen in South Asians

• Fibrinogen levels are high in South Asians possessing -455A and B448 Lys alleles and magnitude is greater for the -455A in the linear regression models

Fibrinogen in South Asians

• There are no differences in genotype distribution for AThr312Ala, -455G/A and B Arg448Lys polymorphisms between South Asians Vs Whites

Conclusions• Elevated fibrinogen levels in

South Asians (Vs Whites) are determined by sex

• smoking and

• B Arg448Lys / -455G/A

Future perspectives• Fibrinogen levels are

influenced by variations in health related behaviours

• Energy restriction + physical activity lowers fibrinogen in adolescents

Future perspectives

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

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.

Future perspectives

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