Reducing CV Disease...


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  • Target populations Age to remember is 50 ( assess risk at 45 for men and 55 for women) Then 10 years earlier for those where prevalence of CVD is high and or outcomes unfavourable People with diabetes should have CVD risk assessment from diagnosis. The risk groups in next slide
  • These is a mixed risk factor list for CVD and /or diabetes CVD in a first-degree relative (Father brother) before 55 or (mother sister) before 65. this will often pick up people with a genetic lipid disorder. If not the prior TC/HDL ratio >7 will. Gestational diabetes and PCO as risk factors for diabetes Traditional risk factors (smoking, elevated BP and lipids) Pre-diabetic risk factors have increased prominence with the inclusion of IGT and IFG and truncal obesity (measured by waist circumference)
  • There is no normal or ideal BP level. When BP levels are chosen as targets they should be individualised to each patient and the calculated risk.
  • 4600mg to 2,300mg (200mmol to 100mmol)
  • There is no normal or ideal lipid level. When lipid levels are chosen as targets they should be individualised to each patient and the calculated risk. in secondary prevention aim for these targets. After CABG even lower targets are indicated 2.0 mmol LDL-C
  • Reducing CV Disease...

    1. 1. Reducing Cardiovascular Disease in Type 2 Diabetes
    2. 2. Case 1 <ul><li>51yo Sri Lankan man </li></ul><ul><li>Does not see GP regularly </li></ul><ul><li>Presents with anterior AMI </li></ul><ul><li>Smoker </li></ul><ul><li>FHx premature vascular disease </li></ul><ul><li>No PHx of DM </li></ul><ul><li>Not on any medications </li></ul>
    3. 3. <ul><li>BSL of 17, HbA1C 9.0% </li></ul><ul><li>Creatinine 110 </li></ul><ul><li>Total Cholesterol 6.5 mmol/L </li></ul><ul><li>LDL 4.2 mmol/L </li></ul><ul><li>HDL 0.8 mmol/L </li></ul><ul><li>Triglycerides 3.2 mmol/L </li></ul>
    4. 4. <ul><li>BP 140/85 </li></ul><ul><li>BMI 27 </li></ul><ul><ul><li>Abdominal distribution </li></ul></ul><ul><li>No left ventricular failure </li></ul>
    5. 5. <ul><li>BD insulin on ward </li></ul><ul><li>Continued Novomix 30 on discharge </li></ul><ul><li>Intensive diabetes education </li></ul><ul><li>Dietician review </li></ul><ul><li>Medications on discharge </li></ul><ul><ul><ul><li>Novomix 22units/10units </li></ul></ul></ul><ul><ul><ul><li>Aspirin 150mg daily </li></ul></ul></ul><ul><ul><ul><li>Ramipril 5mg daily </li></ul></ul></ul><ul><ul><ul><li>Metoprolol 25mg BD </li></ul></ul></ul><ul><ul><ul><li>Atorvastatin 40mg daily </li></ul></ul></ul>
    6. 6. <ul><li>1 st review in clinic 14 days post discharge </li></ul><ul><ul><ul><li>No further chest pain </li></ul></ul></ul><ul><ul><ul><li>BSLs under 12 (adjusted by diabetes educator) </li></ul></ul></ul><ul><ul><ul><li>Metformin commenced </li></ul></ul></ul><ul><ul><ul><li>BP 128/70 with no postural drop </li></ul></ul></ul><ul><ul><ul><li>Seen by endocrinologist, diabetic educator, dietician </li></ul></ul></ul><ul><ul><ul><li>Quit smoking </li></ul></ul></ul>
    7. 7. <ul><li>2 nd review 10 weeks post discharge </li></ul><ul><ul><ul><li>BSL all under 10; insulin had been weaned as an outpatient- </li></ul></ul></ul><ul><ul><ul><ul><li>On Metformin 1g BD </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Diamicron MR 60mg mane </li></ul></ul></ul></ul><ul><ul><ul><ul><li>No hypoglycemia </li></ul></ul></ul></ul><ul><ul><ul><li>HbA1C 7.3% </li></ul></ul></ul><ul><ul><ul><li>Repeat lipids </li></ul></ul></ul><ul><ul><ul><ul><li>TC 4.3 </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Triglycerides 1.8 </li></ul></ul></ul></ul><ul><ul><ul><li>Still not smoking </li></ul></ul></ul><ul><li>Follow up with local GP </li></ul>
    8. 8. <ul><li>Many patients like our case example </li></ul><ul><li>Need to optimise opportunity for CV/ diabetes screening to minimise CV risk </li></ul>
    9. 9. Assessment of Risk <ul><li>New Zealand Cardiovascular Risk Calculator </li></ul><ul><li>Useful tool doctors and patients </li></ul><ul><li>Who should be assessed? </li></ul><ul><ul><li>Assess risk in asymptomatic men>45 yo (>35 if risk factors) </li></ul></ul><ul><ul><li>Assess women> 55 yo (45 if risk factors) </li></ul></ul><ul><ul><li>Fasting lipids, glucose and 2 BP measurements good starting point </li></ul></ul>
    10. 10. Who to risk assess Women Men At diagnosis People with diabetes Age 45 Age 35 Those with at higher risk of CVD or developing diabetes Age 45 Age 35 Māori, Pacific people and people from the Indian sub-continent Age 55 Age 45 Asymptomatic people, without other known risk factors
    11. 11. High risk groups for CVD/diabetes screening <ul><li>Family history of premature CVD or diabetes </li></ul><ul><li>PHx gestational diabetes or polycystic ovary syndrome </li></ul><ul><li>Current smoking </li></ul><ul><li>Prior BP > 160/95 or TC:HDL ratio > 7 </li></ul><ul><li>IGT or IFG </li></ul><ul><li>Obesity (BMI > 30) </li></ul><ul><li>Truncal obesity Waist Circ > 100cm men </li></ul><ul><li> or > 90cm women </li></ul>
    12. 12. Absolute 5 yr Risk <ul><li>Very high >20% </li></ul><ul><li>High >15% </li></ul><ul><li>Moderate >10% </li></ul><ul><li>Mild <10% </li></ul><ul><li>The overall goal of therapy is to achieve a 5 year cardiovascular risk of <15% </li></ul>
    13. 13. Very High Risk Patients <ul><li>Clinically “very high risk” </li></ul><ul><ul><li>Risk assumed to be more than 20% </li></ul></ul><ul><ul><ul><li>Previous CV event </li></ul></ul></ul><ul><ul><ul><ul><li>AMI, angina, CABG, TIA, CVA, PVD </li></ul></ul></ul></ul><ul><ul><ul><li>Genetic lipid disorders </li></ul></ul></ul><ul><ul><ul><li>Diabetes with overt nephropathy </li></ul></ul></ul><ul><ul><ul><li>Diabetes with other renal disease </li></ul></ul></ul>
    14. 14. <ul><li>Also move up one category if </li></ul><ul><ul><li>FHx CVD male >55, female>65 </li></ul></ul><ul><ul><li>Ethnicity </li></ul></ul><ul><ul><li>Diabetes and microalbuminuria </li></ul></ul><ul><ul><li>Type 2 DM >10 years </li></ul></ul><ul><ul><li>HbA1C >8.0% </li></ul></ul><ul><ul><li>People with the metabolic syndrome </li></ul></ul>
    15. 15. <ul><li>Significant improvements in long term prognosis </li></ul><ul><ul><li>Smoking cessation </li></ul></ul><ul><ul><li>Treatment of hypertension </li></ul></ul><ul><ul><li>Improvement of lipid profile </li></ul></ul><ul><ul><li>Addition of aspirin </li></ul></ul><ul><ul><li>Weight loss </li></ul></ul>
    16. 16. <ul><li>In our patient </li></ul><ul><ul><li>Very high risk-- >25% </li></ul></ul><ul><li>Even without AMI </li></ul><ul><ul><li>Man>50 </li></ul></ul><ul><ul><li>Smoker </li></ul></ul><ul><ul><li>Diabetic </li></ul></ul><ul><ul><li>TC :HDL >8 </li></ul></ul>
    17. 18. Diabetes Facts <ul><li>Diabetes increases risk of coronary disease 2-fold in men and 4-fold in women </li></ul><ul><li>65-80% of patients with diabetes die of coronary heart disease </li></ul><ul><li>Diabetes is the leading cause of kidney failure </li></ul><ul><li>15% of diabetics will experience foot ulcers </li></ul><ul><li>Diabetes is the most common cause of blindness under 60 </li></ul>
    18. 19. <ul><li>A child born in the US in 2005 has a 48.5% chance of developing diabetes during their lifetime </li></ul>
    19. 20. Classification of Glucose Tolerance Status <ul><li>Plasma glucose (mmol/l) </li></ul>Diabetes  7.0 or  11.1 Impaired Glucose Tolerance  7.0 & 7.8 - 11.0 Impaired Fasting Glucose 6.1 - 6.9 Normal  6.1 &  7.8 Classification Fasting 2-hr
    20. 21. AusDiab <ul><li>Study of 11,247 Australians over age 25 living in 42 randomly selected urban and rural areas </li></ul><ul><li>Aims- </li></ul><ul><ul><ul><li>Estimate prevalence of diabetes and abnormal GT </li></ul></ul></ul><ul><ul><ul><li>Estimate prevalence of related conditions including obesity, HT, lipid abnormalities </li></ul></ul></ul><ul><ul><ul><li>Assess trends in risk factor levels </li></ul></ul></ul>
    21. 22. Estimated Diabetes Cases in Australia: Number of Persons Thousands 0 200 400 600 800 1000 1200 1400 1982 1986 1990 1994 1998 2202 2006 2010 Year a b c d e a. Busselton, 1981 b. NHF, 1983 c. ABS, 1989-90 d. ABS, 1995 e. (Estimate)
    22. 23. Weighted Prevalence (%) of Associated Conditions Stratified by Glucose Tolerance Status <ul><li>Glucose tolerance status </li></ul>Associated condition Diabetes IFG IGT Normal Hypertension* 69.3 43.5 50.1 21.1 Obesity (BMI  30 kg/m²) 44.4 30.1 31.5 15.9 LDL (  3.5 mmol/l) 45.9 59.6 53.0 44.1 HDL (  1.0 mmol/l) 23.1 16.8 11.6 10.6 Triglycerides (  2.0 mmol/l) 42.9 31.4 31.1 16.0 * On treatment, or systolic pressure  140 mm Hg, or diastolic pressure  90 mm Hg
    23. 24. Control of Risk Factors
    24. 25. BP Targets < 120 / 75 Patients with diabetes and overt nephropathy or other renal disease < 130 / 80 Patients with diabetes or CVD < 140 / 85 Patients without clinical CVD Example BP Condition
    25. 26. United Kingdom Prospective Diabetes Study <ul><li>Each 10mmHg decrease in mean systolic blood pressure accompanied by </li></ul><ul><ul><li>12% reduction in risk for any complication related to diabetes </li></ul></ul><ul><ul><li>15% reduction in deaths related to diabetes </li></ul></ul><ul><ul><li>11% reduction in myocardial infarcts </li></ul></ul><ul><ul><li>13% reduction in microvascular complications </li></ul></ul>
    26. 27. Non-Pharmacological Therapies <ul><li>Weight reduction reduces BP independent of sodium intake </li></ul><ul><li> 1 kg loss of weight, 1mmHg decrease in systolic BP </li></ul><ul><li>Na restriction not studied diabetics </li></ul><ul><ul><li>in essential hypertension, a moderate Na intake restriction leads to a 5mmHg decrease in systolic BP and 2-3mmHg decrease in diastolic BP </li></ul></ul><ul><li>30-45 minutes brisk walking most days of week also shown to decrease BP </li></ul>
    27. 28. Pharmacological Therapy <ul><li>Lots of studies, lots of drugs </li></ul><ul><li>Many patients need 3+ drugs </li></ul><ul><li>ACE-inhibitors and ARBs retard development of diabetic nephropathy </li></ul><ul><li>B-blockers benefit in post-AMI patients </li></ul><ul><li>ACE-inhibitors favorable effect on cardiovascular outcome </li></ul><ul><li>Some studies have shown an excess of selected CV deaths in dihydropyridine calcium channel blockers (DCCB) compared with ACE-inhibitors </li></ul><ul><ul><li>Not evident when DCCB used in combination with ACE-inhibitors, B-Blockers, diuretics </li></ul></ul><ul><ul><li>ACE-inhibitors and B-blockers superior to DCCB in preventing CCF and AMI </li></ul></ul><ul><ul><li>Appropriate addition to but not instead of b-blockers or ACE-inhibitors </li></ul></ul>
    28. 29. Lipid Targets < 1.7 mmol/L Triglycerides < 4.5 TC:HDL Ratio > 1 mmol/L HDL-cholesterol < 2.5 mmol/L LDL-cholesterol < 4 mmol/L Total cholesterol Value Lipid fraction
    29. 30. Lipids and Diabetes <ul><li>Most common pattern of dyslipidemia is elevated triglycerides and reduced HDL </li></ul><ul><li>Mean concentration of LDL no different from non-diabetics </li></ul><ul><ul><ul><li>Qualitative differences </li></ul></ul></ul>
    30. 31. Non-Pharmacological Therapy <ul><li>Weight loss and physical activity leads to decreased triglycerides, increased HDL and modest reduction of LDL </li></ul><ul><li>Maximal medical nutritional activity typically reduces LDL cholesterol by 0.4 to 0.65mmol/L </li></ul><ul><li>Interventions to improve glycemia typically lower triglycerides </li></ul>
    31. 32. <ul><li>Plant Sterols </li></ul><ul><ul><li>Similar structure to cholesterol </li></ul></ul><ul><ul><li>Reduce amount of dietary and biliary cholesterol absorbed </li></ul></ul><ul><ul><li>2g/day reduces LDL-C by 10-15% </li></ul></ul><ul><ul><li>Additive to reductions seen through other dietary changes and statins </li></ul></ul><ul><ul><li>No adverse effects seen in trials but long-term studies not done </li></ul></ul><ul><ul><li>Reduce gut caretenoid absorption- do not use in children or pregnancy </li></ul></ul><ul><li>Fish oils </li></ul><ul><ul><li>Decrease triglycerides </li></ul></ul><ul><ul><li>Encourage fish meals twice a week </li></ul></ul><ul><ul><li>if supplements are used 2 g omega-3 PUFA recommended </li></ul></ul>
    32. 33. Characteristics of Statins <ul><li>Simvastatin </li></ul><ul><ul><li>Max dose 80mg day </li></ul></ul><ul><ul><li>Max LDL-C reduction 47% </li></ul></ul><ul><ul><li>Typical LDL reduction 41% </li></ul></ul><ul><ul><li>Trig reduction 18% </li></ul></ul><ul><ul><li>HDL increase 10% </li></ul></ul>
    33. 34. <ul><li>Atorvastatin </li></ul><ul><ul><li>Max dose 80mg </li></ul></ul><ul><ul><li>Max LDL-C reduction 60% </li></ul></ul><ul><ul><li>Typical LDL reduction 50% </li></ul></ul><ul><ul><li>Trig reduction 29% </li></ul></ul><ul><ul><li>HDL increase 6% </li></ul></ul>
    34. 35. <ul><li>Heart Protection Study </li></ul><ul><ul><ul><li>5963 patients over 40, with diabetes and TC>3.5 </li></ul></ul></ul><ul><ul><ul><li>Patients with diabetes assigned simvastatin had a 22% reduction in the event rate for major CV events </li></ul></ul></ul><ul><ul><ul><li>Risk reduction similar across all LDL categories examined, including patients with lower LDL (<3.0) at entry </li></ul></ul></ul>
    35. 36. <ul><li>Intensive Vs Moderate Lipid Lowering After Acute Coronary Syndromes </li></ul><ul><ul><li>Cannon et al, NEJM, 2004 </li></ul></ul><ul><ul><li>4000 patients </li></ul></ul><ul><ul><li>Hospitalised for ACS preceding 10 days </li></ul></ul><ul><ul><li>Compared 40mg pravastatin (moderate Rx) to 80mg atorvastatin (intensive Rx) </li></ul></ul><ul><ul><li>End-point death from any cause, AMI, stroke, angina needing hospitalisation </li></ul></ul><ul><ul><li>Follow up 24 months </li></ul></ul>
    36. 37. <ul><li>Median LDL achieved with pravastatin 2.5mmol/L </li></ul><ul><li>Median LDL with atorvastatin 1.6mmol/L </li></ul><ul><li>Rates primary endpoints at 2 years 26.3% in pravastatin group </li></ul><ul><li>Rates primary endpoints at 2 years 22.4% in atorvastatin group </li></ul><ul><ul><li>16% reduction in hazard ratio in favour of atorvastatin </li></ul></ul>
    37. 38. Elevated Triglycerides <ul><li>Improve glycaemic control aggressively </li></ul><ul><li>Above 4.5mmol/l strong consideration of pharmacological therapy to prevent pancreatitis </li></ul><ul><li>Pharmacotherapy at clinicians judgement with triglycerides between 2.3mmol/l and 4.5mmol/l </li></ul><ul><li>Higher dose statins moderately effective at reducing triglycerides </li></ul><ul><li>Consider addition of fibric acid derivative </li></ul>
    38. 39. HDL <ul><li>Powerful predictor of CV disease in diabetics </li></ul><ul><li>Difficult to raise HDL without pharmacological intervention </li></ul><ul><ul><li>Weight loss, smoking cessation </li></ul></ul><ul><ul><li>Nicotinic acid and fibrates </li></ul></ul><ul><li>Use nicotinic acid with caution in diabetics </li></ul><ul><ul><li>Effect on glycaemic control </li></ul></ul><ul><li>Statins and fibrates/nicotinic acid- </li></ul><ul><ul><li>increase risk of myositis </li></ul></ul><ul><ul><li>Not evaluated in outcome studies for event reduction </li></ul></ul>
    39. 40. <ul><li>Fibrates </li></ul><ul><ul><li>Veteran Affairs High Density Lipoprotein Cholesterol Intervention Trial </li></ul></ul><ul><ul><li>Gemfibrozil associated with 24% decrease in cardiovascular events in diabetics with prior CV disease, low HDL and modestly elevated triglycerides </li></ul></ul>
    40. 41. <ul><li>Changes to therapy should be based on lab follow-up 4-12 weeks after initiating therapy </li></ul><ul><li>Once goals achieved follow up 6-12 months </li></ul>
    41. 42. Ezetimibe <ul><li>Selectively inhibits the absorption of cholesterol at the brush border membrane in the intestinal lumen </li></ul><ul><li>Available on authority if HMG CoA reductase inhibitor contraindicated or adverse effect </li></ul><ul><ul><li>Severe myalgia, myositis (CK 2x ULN) or ALT 3x ULN </li></ul></ul><ul><li>Co-administration with a statin if lipid targets not met </li></ul><ul><li>Appears safe </li></ul><ul><li>No long term data </li></ul>
    42. 43. United Kingdom Prospective Diabetes Study I <ul><li>10 yr follow-up of 3867 newly diagnosed NIDDM </li></ul><ul><li>HbA1c 7.0% compared to 7.9% </li></ul><ul><li>25% reduction in microvascular end-points </li></ul>
    43. 44. Type 2 DM <ul><li>Preprandial BSL of <5.5-6.0 </li></ul><ul><li>2 hour postprandial BSL of <7.8 </li></ul><ul><li>HbA1C <7.0% </li></ul>
    44. 45. Type 2 DM <ul><li>These recommendations from 3 landmark studies- </li></ul><ul><ul><ul><li>Diabetes Control and Complications Trial </li></ul></ul></ul><ul><ul><ul><li>Kumamoto Study </li></ul></ul></ul><ul><ul><ul><li>UKPDS </li></ul></ul></ul><ul><ul><ul><li>These have shown unequivocally that maintaining BSL as close to normal as possible in type 1 and 2 DM decreases microvascular complications </li></ul></ul></ul>
    45. 46. Type 2 DM <ul><li>Diet, exercise and weight loss- the centre of any therapeutic program </li></ul>
    46. 47. Sulphonylureas <ul><li>Available since 1954 </li></ul><ul><li>Compared to placebo- decrease HbA1C of 1-2% </li></ul><ul><li>Of practical concern- </li></ul><ul><ul><ul><li>Weight gain- 2-5 kg </li></ul></ul></ul><ul><ul><ul><li>Hypoglycaemia- especially in elderly, impaired renal function, irregular eating habits </li></ul></ul></ul><ul><ul><ul><li>Optimal dosing of each member of this class varies </li></ul></ul></ul><ul><ul><ul><ul><li>AS A GENERAL RULE GLUCOSE LOWERING EFFECT PLATEAUS AFTER HALF THE MAXIMUM DOSE IS REACHED </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Most agents are metabolised by the liver and cleared by the kidney so use with caution in patients with renal and hepatic disease </li></ul></ul></ul></ul>
    47. 48. Metformin <ul><li>Ability to lower HbA1C similar to SU- 1-2% </li></ul><ul><li>Associated with weight neutrality and much less hypoglycaemia </li></ul><ul><li>GIT complaints in up to 50% </li></ul><ul><li>Minimised with slow dose titration </li></ul><ul><li>Optimal dose in most patients is 2000mg/day </li></ul><ul><li>Risk of lactic acidosis is 1/30,000 patient-years </li></ul><ul><ul><ul><li>Therefore avoid if abnormal Creatinine </li></ul></ul></ul><ul><ul><ul><li>Avoid if severe hepatic dysfunction, CCF, dehydration, alcoholism </li></ul></ul></ul><ul><ul><ul><li>With-hold in virtually any acute illness </li></ul></ul></ul>
    48. 49. Thiazolidinediones <ul><li>Pioglitazone (ACTOS) and Rosiglitazone (AVANDIA) </li></ul><ul><li>Pharmacological ligands for nuclear receptor- peroxisome-proliferator-activated receptor gamma </li></ul><ul><li>Prominent effect is insulin-stimulated glucose uptake in skeletal muscle </li></ul><ul><li>Like metformin, does not cause pancreatic beta cells to produce more insulin </li></ul><ul><li>Decreases in HbA1C similar to SU and metformin </li></ul>
    49. 50. TZD <ul><li>Actions- </li></ul><ul><ul><ul><li>Decrease insulin levels </li></ul></ul></ul><ul><ul><ul><li>Increase HDL, decrease triglycerides </li></ul></ul></ul><ul><li>Adverse effects- </li></ul><ul><ul><li>weight gain </li></ul></ul><ul><ul><ul><ul><li>usually peripheral subcutaneous sites, with reduction in visceral fat depots </li></ul></ul></ul></ul><ul><ul><li>Oedema </li></ul></ul><ul><ul><ul><li>Patients with advanced CCF should not receive TZD </li></ul></ul></ul>
    50. 51. <ul><li>Individualise therapy </li></ul><ul><li>Lifestyle advice </li></ul><ul><li>Call if concerns </li></ul>