1 / 53

Clinical aspects of managing the cardiovascular risk in diabetes Dr SH Song MD FRCP

Clinical aspects of managing the cardiovascular risk in diabetes Dr SH Song MD FRCP Consultant Diabetologist Northern General Hospital Sheffield. Increased CHD in type 1 diabetes. Laing at al Diabetologia 2003; 46: 760-5. STENO-2 Evidence - Intensive multifactorial intervention are

trang
Download Presentation

Clinical aspects of managing the cardiovascular risk in diabetes Dr SH Song MD FRCP

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

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

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

  3. STENO-2 Evidence - Intensive multifactorial intervention are effective in reducing CVD events in type 2 DM 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 • Behaviour modification (weight, diet, smoking cessation) • Pharmacological intervention aimed at diabetes, hypertension, • lipids along with aspirinand ACE-I

  4. JBS2 guidelines 2005 • Treatment targets for patients with diabetes: • HbA1c6.5% • BP <130/80 mmHg (<125/75 in T1DM with micro-albuminuria) • TC <4.0 mmol/L • LDL-C <2.0 mmol/L • Preferred values but not targets: • HDL-C <1.0 mmol/L in men (<1.2 mmol/L in women) are associated with an increased risk of cardiovascular disease • Non-HDL-C <3.0 mmol/L • TG <1.7 mmol/L • “A statin should be recommended for all patients aged >40 years with either Type 1 or 2 diabetes” Joint British Societies’ Guidelines on Prevention of Cardiovascular Disease in Clinical Practice 2005

  5. Glycaemic control

  6. Glycaemic control and CVD events

  7. Effect of reducing HbA1c: UKPDS 1% reduction in HbA1c significantly reduced the risk of diabetes-related complications Any diabetes-related endpoint† Diabetes-related deaths Amputationor death from PVD Microvascular complications Myocardial infarction Stroke Reductionin risk(%) **-12% *-14% *-21% *-21% *-37% *-43% UKPDS, United Kingdom Prospective Diabetes Study PVD, peripheral vascular disease Median follow up = 10 years, n = 3642 for relative risk analysis†Primary endpoint; *p<0.0001; **p=0.035 Stratton et al. BMJ 2000; 321: 405–412

  8. UKPDS found that metformin reduces risk of macrovascular complications 50 P=0.017 45 P=0.010 40 P=0.011 P=0.0023 35 P=0.02 30 % risk reduction 25 20 15 10 5 0 Macrovascular Myocardial Diabetes All cause Any related diabetes infarction mortality death related outcome UKPDS 34. Lancet 1998;352:854–865

  9. ?Glitazone reduce CVD events End-point: all-cause mortality, non-fatal MI, stroke Relative RR 16%, p=0.027

  10. Post-hoc analysis

  11. Effects of Pioglitazone inpatients with or without a history of stroke — an analysis of PROactive Robert G.Wilcox; Marie-Germaine Bousser; John Betteridge; Guntram Schernthaner; Valdis Pirags; Stuart Kupfer ; John Dormandy

  12. Summary: In T2DM with CVD, pioglitazone reduced risk of recurrent fatal/nonfatal MI by 28% and ACS by 37% In T2DM with previous stroke, pioglitazone reduced risk of recurrent fatal/nonfatal stroke by 47% In T2DM without previous stroke, pioglitazone has no effect on reducing the risk of first stroke

  13. Blood pressure

  14. Blood Pressure and CVD:Framingham Heart Study MEN WOMEN 174 No Glucose Intolerance Glucose Intolerance No Glucose Intolerance Glucose Intolerance 119 113 90 Age-adjusted CV Event Rate/1,000 Age-adjusted CV Event Rate/1,000 77 74 59 56 50 48 38 36 31 24 23 15 105 135 165 195 105 135 165 195 Systolic BP (mmHg) Systolic BP (mmHg) Kannel WB, et al. Am Heart J. 1991;121:1268-1273.

  15. Relative Risk of Stroke and of CHD Increases with Increasing DBP Stroke and usual DBP Coronary Hearth Disease and usual DBP (in 5 categories defined by baseline DBP) (in 5 categories defined by baseline DBP) 7 prospective observational studies: 843 events 9 prospective observational studies: 4856 events 4.00 4.00 2.00 2.00 1.00 1.00 Relative Risk of Stroke Relative Risk 0.50 0.50 0.25 0.25 1 2 3 4 5 1 2 3 4 5 Baseline Baseline DBP category DBP category 76 84 91 98 105 mm Hg 76 84 91 98 105 mm Hg Approximate mean usual DBP Approximate mean usual DBP MacMahon S et al. Lancet 1990;335:765-774

  16. Preventing cardiovascular complicationsUKPDS: benefits of reducing blood pressure Diabetes-related and all-cause mortality Micro -vascular disease Any diabetes-related endpoint Retinopathy progression Vision deterioration Heart failure Stroke 0 -24 -25 -32 p = 0.0046 -34 -37 % Risk reduction associated with tighter blood pressure control* p = 0.019 p = 0.0038 -44 p = 0.0092 -47 p = 0.013 -50 -56 p = 0.0036 p = 0.0043 -75 *Tight control vs less tight control = 144/82 mmHg vs 154/87 mmHg UK Prospective Diabetes Study Group. BMJ 1998; 317: 703–713.

  17. Major Outcomes of the Hypertension Optimal Treatment (HOT) Trial: Diabetes Subgroup Diastolic Target p<0.005 90 mmHg (N=501) 85 mmHg (N=501) 80 mmHg (N=499) Events/1000 Pt-Years p<0.016 p<0.045 Major CV Events MI CV Mortality Hansson L, et al. Lancet. 1998;351: 1755-1762.

  18. BP Treatment Threshold

  19. BP Targets

  20. Updated UK NICE Guidelines for the Treatment of Newly Diagnosed Hypertension <55 years 55 years or black at any age ACEI (or ARB*) CCB or thiazide-type diuretic Step 1 ACEI (or ARB*) + CCB or ACEI (or ARB*) + thiazide diuretic Step 2 ACEI (or ARB*) + CCB + diuretic Step 3 Add further diuretic therapy, α-blocker, or β-blocker. Consider seeking specialist advice Step 4 *If ACE inhibitor (ACEI)not tolerated http://www.nice.org.uk/download.aspx?o=CG034fullguideline.Accessed June 2006

  21. Principles behind latest BP guideline in the UK • Monotherapy inadequate • Underscores the need for at least 2 drugs • Provides rational for drug selection based on ethnicity and age • Not restrictive or prescriptive & offers therapeutic choice

  22. Lipid

  23. Spectrum of CHD Risk – to guide lipid-lowering strategy Should we treat low HDL? •  HDL-C • TG + • Glucose intolerance • Abdominal obesity •  BP LDL-C Metabolic Syndrome Achieving low LDL/total cholesterol target evidence how to achieve it? Lipid-lowering guidelines (JBS-2, NICE type 1 DM) and young diabetics ?role of metabolic syndrome Expert Panel. JAMA 2001;285:2486-2497.

  24. Diabetic dyslipidaemia low HDL (<1.03 mmol/l male) (<1.29 mmol/l female) raised triglyceride (>1.7 mmol/l) Emphasis on treating total cholesterol HDL and triglyceride – no evidence

  25. Statin • potent agent in lowering total/LDL cholesterol • consistently demonstrated importance of lowering LDL/total • cholesterol to reduce CVD events • agent of choice for lipid-lowering Rx I guidelines • important component of multi-factorial diabetes management • ‘easier’ component to achieve target • tot chol 70-75% BP 50%, HbA1c 15% (STENO-2) • recent trials showed ‘lower the better’ (HPS, TNT, PROVE-IT)

  26. Reduction in 1 mmol/l LDL leads to 20-25% reduction in CVD events (major coronary events, coronary revascularisation and ischaemic stroke) Target total/LDL cholesterol - ‘the lower the better’ Statin meta-analysis Lancet 2005

  27. Lower cholesterol target – strategies to achieve it (1) Use more potent statin

  28. ‘Rule of 6’

  29. Lower cholesterol target – strategies to achieve it (2) Switching to more potent statin Most guidelines – simvastatin (1st) and atorvastatin (2nd) Statin choice if these statins fail to achieve cholesterol target MERCURY II Initital Rx: Switched to: % reduction in LDL Atorvastatin 10 Rosuvastatin 10 17 Atorvastatin 20 Rosuvastatin 20 16 Simvastatin 20 Rosuvastatin 10 18 Simvastatin 40 Rosuvastatin 20 27 Ballantyne CM et al. Am Heart J 2006: 151; 975

  30. Lower cholesterol target – strategies to achieve it (3) Adding fibrate, nicotinic acid and ezetimibe to statin LDLTGHDL Statin + fibrate -28% -41% +22% Statin + niaspan (1g) -8% -24% +24 Statin + niaspan (2g) -23% -30% +27% Statin + ezetimibe -20% -11% +1.7% Fibrate and nicotinic acid – LDL, TG, HDL Ezetimibe - LDL

  31. 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

  32. Framingham equation under-estimate CHD risk in diabetes up to 50% Predicted Observed UKPDS CHD event (%/yr) 1.6 2.7 (Diabetes) WOSCOPS CHD event (%/yr) 1.9 1.8 (Non-diabetes) (Yeo et al Diabet Med 2001; 18: 341-44) Cardiff CHD event Male 8.3 19 (Diabetes) (% / 4 yrs) Female 7.5 17 Stevens et al Diabet Med 2005; 22: 228

  33. 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 male female JBS 19 17.3 UKPDS 24.9 16.5 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. UKPDS risk engine better 15% threshold Framingham calculator better

  34. 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 can’t be calculated by current • methods.

  35. Forms the basis for degree of aggressiveness with lipid Rx

  36. Young T2DM patients

  37. 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

  38. 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 SH Song, CA Hardisty. Practical Diabetes International 2007;24: 20-24

  39. 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

  40. Sheffield experience (2) High prevalence of metabolic syndrome in T2DM regardless of age ~70% <40 yrs and ~90% >40 yrs IDF ATP <40 40-49 50-59 60-69 >70 Average WC ~113 cm or 44 inches (male and female) <40 40-49 50-59 60-69 >70 SH Song. Presented at EASD Copenhagen 2006

  41. Joint British Societies–2 guideline (Dec 2005) Recommendation for statin in diabetes:

  42. 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

More Related