(SABRE) cohort Therese Tillin Institute of Cardiovascular Science - PowerPoint PPT Presentation

Southall And Brent REvisited (SABRE) cohort Therese Tillin Institute of Cardiovascular Science University College London

….and Brent

Background- mid 1980s A) Higher rates of diabetes, coronary heart disease and stroke in South Asians B) Higher rates of diabetes, hypertensive organ damage and stroke in African Caribbeans, but less coronary heart disease Why? Insulin resistance, body fat distribution and associated cardiometabolic disturbances? McKeigue P, Marmot M et al, Lancet 1985 McKeigue P, Marmot M, BMJ, 1988 Wild S, McKeigue P, BMJ, 1997

Southall and Brent studies baseline methods: 1988-91 • Population based study: age 40-69, 5000 people • Random selection from primary care lists (78%) and local workplaces • 2346 Europeans (76% men). • 1710 Indian Asians(83% men), 801 African Caribbeans (57% men, 92% from Caribbean)- all first generation migrants • Baseline (1988-91): fasting bloods, OGTT, anthropometrics, BP, health and lifestyle questionnaire Subset (African Caribbeans and Europeans): 24 hour ambulatory blood pressure Echocardiography Retinal photography

Southall and Brent baseline study findings (Cross-sectional) South Asians : central obesity, insulin resistant, dyslipidaemic regardless of ethnic sub-group.

Southall and Brent baseline study findings (Cross-sectional) South Asians : central obesity, insulin resistant, dyslipidaemic regardless of ethnic sub-group.  Is insulin resistance the underlying explanation for excess CVD risk?

Southall and Brent baseline study findings (Cross-sectional) African Caribbeans : less central obesity (in men), favourable lipids, but more glucose and less insulin than Europeans. Higher resting BP in African Caribbean women was enough to explain excess stroke, but not in men. More left ventricular structural impairment and adverse remodelling patterns

Southall and Brent baseline study findings (Cross-sectional) African Caribbeans : less central obesity (in men), favourable lipids, but more glucose and less insulin than Europeans. Higher resting BP in African Caribbean women was enough to explain excess stroke, but not in men. More left ventricular structural impairment and adverse remodelling patterns  Is diabetes is different in African Caribbeans? Does this lead to protection from CHD? Why more stroke? (24 hour BP was not the whole story)

20 year mortality and morbidity follow-up (V2) Southall and Brent Revisited (SABRE) • Why more diabetes in both ethnic minorities? • Why more CHD in South Asians? • Why more stroke in both ethnic minorities? • Subclinical circulatory disease? • Risk factor intervention thresholds?

20 year mortality and morbidity follow-up (V2) Southall and Brent Revisited (SABRE) • 2008-2011, age 60-90 • Mortality/ cancer registration • Survivors invited to attend follow-up clinic at St Mary’s Hospital /complete health and lifestyle questionnaire/ consent to primary care medical record review

20 year mortality and morbidity follow-up (V2) Southall and Brent Revisited (SABRE) • 2008-2011, age 60-90 • Mortality/ cancer registration • Survivors invited to attend follow-up clinic at St Mary’s Hospital /complete health and lifestyle questionnaire/ consent to primary care medical record review • Clinic measurements included: – Fasting and OGTT bloods – Anthropometrics – CT: coronary calcium and abdominal and mid-thigh fat depots – MRI: brain- white matter hyperintensities, infarcts, hippocampal and brain volumes – Retinal photography – Cognitive function – 2D and 3D echocardiography – Vascular assessment- central, brachial and ankle BP, pulse wave velocity, carotid IMT

Cumulative incidence of diabetes during 20 years of follow-up Mean age at diagnosis of incident diabetes: Europeans: 67 years South Asians: 62 years African Caribbeans: 68 years a. MEN b. WOMEN .6 .6 .5 .5 .4 .4 Cumulative Incidence Cumulative Incidence .3 .3 .2 .2 .1 .1 0 0 40 50 60 70 80 90 40 50 60 70 80 90 Age Age European South Asian European South Asian African Caribbean African Caribbean Tillin T, Hughes AD, Godsland IF, Whincup P, Forouhi N, Welsh P, Sattar N, McKeigue PM, Chaturvedi N, Diabetes Care 2013

Incidence of diabetes over 20 years of follow-up and baseline BMI, age adjusted 60 40 20 0 20 21 22 23 24 25 26 27 28 29 30 31 Body mass index, kg/m2 European South Asian African Caribbean

Incidence of diabetes over 20 years of follow-up and baseline BMI, age adjusted 60 40 20 0 20 21 22 23 24 25 26 27 28 29 30 31 Body mass index, kg/m2 European South Asian African Caribbean

CHD and stroke incidence: fatal and non-fatal first events, age and sex adjusted Coronary heart disease incidence Stroke incidence .8 .8 .6 .4 .3 .2 .2 .1 0 0 40 50 60 70 80 90 40 50 60 70 80 90 Age Age Europeans South Asians Europeans South Asians African Caribbeans African Caribbeans

Predicting CVD risk over 10 years of follow-up: QRISK2 and Framingham 25 Observed events QRISK2 predicted 20 % risk (95% CI) Framingham predicted 15 10 5 0 European South Asian African European South Asian African men men Caribbean women women Caribbean men women Tillin T, Hughes AD, Whincup P, Mayet J, Sattar N, McKeigue PM, Chaturvedi N, , Heart Jan 2014

Proportion of observed events which occurred in participants identified as high risk (>20%) by Framingham and QRISK2 70 60 50 40 % 30 20 10 0 % of events predicted by Framingham >=20% European South % of events predicted by QRISK2>=20% men African Asian men European South Caribbean women African men Asian Caribbean women women

CHD and stroke incidence: fatal and non-fatal first events Tillin T, Hughes AD, Mayet J, Whincup P, Forouhi N, Sattar N, McKeigue PM, Chaturvedi N, JACC 2013

CHD and stroke incidence: fatal and non-fatal first events P for ethnicity x diabetes interactions for stroke: South Asians vs Europeans: 0.038 African Caribbeans vs Europeans: 0.019 Tillin T, Hughes AD, Mayet J, Whincup P, Forouhi N, Sattar N, McKeigue PM, Chaturvedi N, JACC 2013

SABRE V2: Severe White Brain Matter White matter Infarcts Hyperintensities hyperintensities (severe: 3+) and large infarcts in Europeans and African Caribbeans Shibata D, Tillin T, Beauchamp N, Heasman J, Hughes AD, Park C, Gedroyc W, Chaturvedi N, J Hypertens, 2013

Ethnic differences in cognitive impairment and hippocampal volumes in SABRE 20 year follow-up (mean ±SE) Data are adjusted for age, sex and educational status. *p<0.05 Europeans as comparator **p<0.01 Europeans as comparator § p<=0.01 for ethnicity x diabetes interaction †p=0.058 for ethnicity x diabetes interaction †† p=0.093 for ethnicity x diabetes interaction European South Asian African Caribbean Global cognitive function 0.31± 0.62 -0.23 ± 0.53** -0.25 ± 0.58** (average z score) Diabetes vs no diabetes Odds ratio for lowest 10% of 1.20(0.66, 2.18) 1.86(1.09, 3.17) 2.80(1.24, 6.32) † cognitive function score Hippocampal volume (mm) 7.60±0.04 7.06±0.05** 7.29±0.07** Diabetes vs no diabetes 2.47(1.18, 5.18)** § 1.64(0.63, 4.27 ) †† Odds ratio for lowest 10% of 0.58(0.26, 1.29) hippocampal volume

Ethnic differences in cognitive impairment and hippocampal volumes in SABRE 20 year follow-up (mean ±SE) Data are adjusted for age, sex and educational status. *p<0.05 Europeans as comparator **p<0.01 Europeans as comparator § p<=0.01 for ethnicity x diabetes interaction †p=0.058 for ethnicity x diabetes interaction †† p=0.093 for ethnicity x diabetes interaction European South Asian African Caribbean Global cognitive function 0.31± 0.62 -0.23 ± 0.53** -0.25 ± 0.58** (average z score) Diabetes vs no diabetes Odds ratio for lowest 10% of 1.20(0.66, 2.18) 1.86(1.09, 3.17) 2.80(1.24, 6.32) † cognitive function score Hippocampal volume (mm) 7.60±0.04 7.06±0.05** 7.29±0.07** Diabetes vs no diabetes 2.47(1.18, 5.18)** § 1.64(0.63, 4.27 ) †† Odds ratio for lowest 10% of 0.58(0.26, 1.29) hippocampal volume

Ethnic differences in cognitive impairment and hippocampal volumes in SABRE 20 year follow-up (mean ±SE) Data are adjusted for age, sex and educational status. *p<0.05 Europeans as comparator **p<0.01 Europeans as comparator § p<=0.01 for ethnicity x diabetes interaction †p=0.058 for ethnicity x diabetes interaction †† p=0.093 for ethnicity x diabetes interaction European South Asian African Caribbean Global cognitive function 0.31± 0.62 -0.23 ± 0.53** -0.25 ± 0.58** (average z score) Diabetes vs no diabetes Odds ratio for lowest 10% of 1.20(0.66, 2.18) 1.86(1.09, 3.17) 2.80(1.24, 6.32) † cognitive function score Hippocampal volume (mm) 7.60±0.04 7.06±0.05** 7.29±0.07** Diabetes vs no diabetes 2.47(1.18, 5.18)** § 1.64(0.63, 4.27 ) †† Odds ratio for lowest 10% of 0.58(0.26, 1.29) hippocampal volume