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Clinical aspects of managing the cardiovascular risk in diabetes Dr SH Song MD FRCP Consultant Diabetologist Northern General Hospital Sheffield

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Increased CHD in type 1 diabetes Laing at al Diabetologia 2003; 46: 760-5

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STENO-2 Evidence - Intensive multifactorial intervention are effective in reducing CVD events in type 2 DM Behaviour modification (weight, diet, smoking cessation) Pharmacological intervention aimed at diabetes, hypertension, lipids along with aspirin and ACE-I 50% reduction in CVD events, nephropathy, retinopathy and neuropathy Risk reduction 20% higher than single-factor intervention studies (glycaemia, BP, lipid lowering) Important to target all risk factors

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JBS2 guidelines 2005 Treatment targets for patients with diabetes: HbA 1c 6.5% BP 40 years with either Type 1 or 2 diabetes Joint British Societies Guidelines on Prevention of Cardiovascular Disease in Clinical Practice 2005

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Glycaemic control

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Glycaemic control and CVD events

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Effect of reducing HbA 1c : UKPDS 1% reduction in HbA 1c significantly reduced the risk of diabetes-related complications Stratton et al. BMJ 2000; 321: 405412 Microvascular complications Any diabetes- related endpoint Myocardial infarction Amputation or death from PVD Stroke * -37% * -21% * -14% * -43% ** -12% UKPDS, United Kingdom Prospective Diabetes Study PVD, peripheral vascular disease Median follow up = 10 years, n = 3642 for relative risk analysis Primary endpoint; *p

No role for CVD risk calculation table To guide initiation of lipid-lowering treatment in primary prevention Calculates absolute risk of developing CHD (over 10 yrs) introduced when statin cost was expensive (predominantly financial reason) prior to statin trials in diabetes (HPS, CARDS) not evidence-based Purpose: to target high risk individuals to maximise cost-effectiveness to reduce unnecessary treatment in some individuals JBS (1998) and NICE (2002) recommends risk tables statin Rx when >15% (NICE) or >30% (JBS) Available risk calculators:Framingham & UKPDS risk engine

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Framingham equation under-estimate CHD risk in diabetes up to 50% PredictedObserved UKPDSCHD event (%/yr)1.62.7 (Diabetes) WOSCOPSCHD event (%/yr)1.91.8 (Non-diabetes) (Yeo et al Diabet Med 2001; 18: 341-44) CardiffCHD eventMale8.319 (Diabetes)(% / 4 yrs) Female7.517 Stevens et al Diabet Med 2005; 22: 228

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UKPDS risk engine is not a better alternative Comparison between UKPDS risk engine and Framingham equation SH Song et al Diabetic Med 2004; 21: 238-45 Mean CHD risk (over 10 yrs) in type 2 diabetes malefemale JBS1917.3 UKPDS24.916.5 Conclusion: Overall, UKPDS risk engine estimated higher CHD risk score. At high risk (>30%), UKPDS risk engine consistently estimated higher risk score than Framingham equation. At lower risk levels (~15%) where clinical decision to start statin occurs (as per NICE), UKPDS risk engine and Framingham equation equivalent. 15% threshold UKPDS risk engine better Framingham calculator better

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Why under-estimate risk in diabetes? Model based on largely non-DM population (Framingham calculator) Traditional risk factors do not account for excess CHD death in diabetes. Other important factors not included in risk calculation. (ie small dense LDL, microalbuminuria, hypercoagulable state, impaired fibrinolysis, endothelial dysfunction, inflammatory states, insulin resistance etc) Other limitations: No risk calculation method for type 1 diabetes. Young type 2 diabetes increasing and risk cant be calculated by current methods.

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Forms the basis for degree of aggressiveness with lipid Rx

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Young T2DM patients

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Facts: high CVD risk (especially with CVD risk factors) no trial data in this age group (compared to >40yrs HPS/CARDS) increasing number of young T2DM patients

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SH Song, CA Hardisty. Practical Diabetes International 2007;24: 20-24 Sheffield experience Young type 2 diabetes patients: Similar CVD risk profile as older type 2 diabetes patients High prevalence of obesity, hypertension and dyslipidaemia Less likely to be treated with statin and anti-hypertensive agents

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Sheffield experience Tendency to multiple CVD risk factor clustering in young type 2 diabetes patients of similar proportion to older T2DM SH Song, CA Hardisty. Practical Diabetes International 2007;24: 20-24

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High prevalence of metabolic syndrome in T2DM regardless of age ~70% 40 yrs 70 IDF ATP Average WC ~113 cm or 44 inches (male and female) 70 SH Song. Presented at EASD Copenhagen 2006 Sheffield experience (2)

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Recommendation for statin in diabetes: Joint British Societies2 guideline (Dec 2005)

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Effect of intensive lifestyle intervention on CVD risk factors in T2DM Diabetes Care 2007; 30: 1374-83 T2DM 45-74 yrs Intensive lifestyle intervention with diet, physical activity, behaviour modification Aim: to determine effect of intensive lifestyle intervention on CVD outcome

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Diabetes Care 2007; 30: 1374-83 At 1 yr, Intensive life style intervention results improvement in: Glycaemic control BP Lipid profile (HDL, Trig)

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Intensive life style management focusing on dietary and physical activity with community dietitian and Sheffield Active group To achieve coordinated and integrated intervention with diet and exercise T2DM inadequately controlled on oral hypoglycaemic agents Started May 2007 for 2 years

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Conclusions: Intensive management focusing on glycaemic control, BP, lipid, lifestyle Oral hypoglycaemic agents with CVD outcome data metformin, pioglitazone Lowering BP require multiple agents including ACE-I Statin remains first choice for lipid lowering. Additional agents may be needed to further lower cholesterol in some patients Young T2DM have multiple CVD risk factors as older patients Some evidence of lifestyle intervention beneficial effect on CVD risk factors