Module 205.1 en

Hinweis der Redaktion

1. Macrovascular disease is a very serious complication of diabetes and is the most common cause of premature death. It is very important to recognise that diabetes is much more than a blood glucose disease and to learn about how the macrovascular risk factors that contribute to this increased risk of morbidity and mortality can be identified and reduced.
2. When talking of macrovascular disease, three main areas need to be considered: Coronary heart disease Cerebrovascular disease Peripheral vascular disease (PVD); PVD will not be discussed in this presentation as it is dealt with in Module 5 – 4c.
3. Macrovasular disease is the major cause of morbidity and mortality in diabetes. The underlying abnormality is atherosclerosis. Gerstein HC. (2002). Reduction of cardiovascular events and microvascular complications in diabetes with ACE inhibitor treatment: HOPE and MICRO-HOPE. Diabetes Metab Res Rev., 18(suppl 3), S82-S85.
4. Atherosclerosis comes from the Greek “athero” (gruel or paste) and “sclerosis” (hardness). It is the name of the process in which deposits of fatty substances, cholesterol, cellular waste products, calcium and other substances build up in the inner lining of an artery. This build up is called plaque. It usually affects large and medium-sized arteries.  Plaques can grow large enough to significantly reduce the blood flow through an artery. But most of the damage occurs when plaques become fragile and rupture. Plaques that rupture cause blood clots to form. These can block blood flow or break off and travel to another part of the body. If a coronary artery is blocked, it causes a heart attack. If it blocks a blood vessel that feeds the brain, it causes a stroke. If blood supply to the legs is reduced, it can make walking difficult and increasingly painful and may even result in gangrene.
5. The typical risk factors for macrovascular disease are: 1. Age: as we grow older our risk increases 2. Gender: males are more at risk than females; however, women with diabetes lose their pre-menopausal protection 3. Family history: if a family history of heart attack or stroke is present then the risk is increased; therefore it is very important when talking with people with diabetes that we find out their family history and particularly if there are any members of the family that died at a young age (less than 65 years) of a heart attack or stroke 4. Lipid abnormalities: people with dyslipidaemia are more at risk 5. Hypertension: people with increased blood pressure are at increased risk 6. Smoking: it is particularly dangerous as tobacco smoke greatly increases atherosclerosis in the coronary arteries, the aorta and arteries in the legs 7. Diabetes: by itself it is also an independent factor for increased risk of macrovascular disease 8. Obesity: this is an important aspect of the insulin resistance syndrome which increases the risk of atherosclerosis and CHD Turner R.C., Millns H., Neil H.A., Stratton, I.M., Manley, S.E., Matthews, D.R., Holman, R.R. (1998). Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ, 316,823-828. Fox C.S., Sullivan L., D’Agostino R.B. Sr., Wilson, W.F. (2004). The significant effect of diabetes duration on coronary heart disease mortality: the Framingham Heart Study. Diabetes Care, 27,704-708. Selvin E, Marinopoulos S, Berkenblit G, Brancati, F.L., Powe, N.R., Hill Golden, S. (2004). Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med., 141,421-431. Mann JF, Gerstein HC, Pogue J, Lonn, E., Yusuf, S. (2002). Cardiovascular risk in patients with early renal insufficiency: implications for the use of ACE inhibitors. Am J Cardiovasc Drugs, 2,157-162.
6. AFR = African Region EUR = European Region MENA = Middle East and Northern Africa Region NAC = North American and Caribbean SACA = South and Central America SEA = South East Asia WP = Western Pacific International Diabetes Federation. (2009). IDF Diabetes Atlas. Brussels: International Diabetes Federation
7. Coronary heart disease occurs much more commonly in people with diabetes than in people without diabetes and occurs at an earlier age. As mentioned earlier women with diabetes lose their gender protection. Due to an element of autonomic neuropathy some people with diabetes can have an MI and not know it - they do not feel the pain. This is called a silent MI. Another important factor is that people with diabetes who have an abnormal level of albuminuria are at much higher risk of a macrovascular event than those without albuminuria. They therefore need more intensive macrovascular risk reduction. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. (2008). 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diab 32(suppl 1)
8. Haffner reported that people with type 2 diabetes have the same risk of having a heart attack as people without diabetes who have already had a heart attack. However, this finding is now being debated in the diabetes community. An under-recognised and under-treated condition in diabetes is heart failure (this will be discussed later in the presentation). Haffner S.M., Lehto S., Ronnemaa T., Pyorala, K., Laakso, M. (1998). Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Eng J Med, 339, 229-234.
9. People with diabetes have a worse prognosis than non-diabetic individuals even after adjustments for infarct size and risk factors. When a person with diabetes has an acute coronary event, the short- and long-term outcomes are considerably worse than for the person without diabetes. Malmberg K., Ryden L. (1988). Myocardial infarction in patients with diabetes mellitus. Eur Heart J, 9,259-264. Malmberg K.,Yusuf S., Gerstein H.C., Brown, J., Zhao, F, Hunt, D., et al. (2000). Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry. Circulation, 102,1014-1019.
10. Men and people with a family history of premature cardiovascular disease have an increased risk of atherosclerosis. These risk factors cannot be controlled. However, research has shown the benefits of reducing the controllable risk factors for atherosclerosis. Diabetes health professionals have a very large role to play in empowering people with diabetes to understand this devastating complication and how to modify controllable risk factors through structured education. The controllable risk factors are: dyslipidaemia (see Slide 18 for target lipid levels); smoking tobacco and exposure to tobacco smoke; high blood pressure; central obesity; physical inactivity; optimum blood glucose levels.
11. Notes to the educator: If time allows break the participants into small groups to discuss this case. After 10 minutes, ask for ideas from the groups.
12. Lifestyle interventions: It is known that losing 10% of body weight in those who are overweight improves insulin sensitivity Cholesterol is made in the liver from saturated and trans fats; blood cholesterol can be reduced by limiting intake of saturated and trans fats or replacing saturated and trans fats with monounsaturated fats, as well as increasing the intake of flavonoids Monounsaturated and polyunsaturated fats and omega-3 may increase HDL (see Section 2.2). Nutritional guidelines may have been developed in your country and you may want to look into these. Regular physical activity increases HDL cholesterol in some people. Ideally it should be recommended to do 30 minutes of exercise a day - but we know that this is often unrealistic for some people, particularly if they are very sedentary. A programme beginning with a 5-minute walk a few times a week may be a good place to start. The time and intensity of exercise should gradually increase. Lipid-lowering agents have proven very effective in reducing morbidity and mortality. Results from clinical trials will be discussed later in the presentation. Aspirin has been shown to be a cost-effective in secondary prevention for those with diabetes and a history of CVD. American Diabetes Association. (2010). Clinical Practice Recommendations. Diabetes Care, 33(suppl 1). It should not be used for primary prevention routinely. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. (2008). Clinical Practice Guidelines for the Prevention and management of diabetes in Canada. Can J Diabetes, 32(suppl 1). Interestingly, while the benefits of tight glycaemic control in reducing microvascular complications have been unequivocally shown by the DCCT and UKPDS, the role of glycaemic control is less clear in reducing macrovascular risk. Evidence from the EDIC study (follow-up of DCCT) for type 1 diabetes and from the UKPDS Post Monitoring Study for type 2 diabetes demonstrate a significant relationship between glycaemic control and a risk of macrovascular disease. However other studies do not demonstrate the same relationship.
13. Notes to the educator: Discuss these questions with the participants. ADA recommendation state: Consider 75-162mg/day in people with type 1 or type 2 at increased cardiovascular risk (10 year risk over 10%). This includes most men over 50 and women over 60 years of age who have at least one additional major risk facter (family history of CVD, hypertension, smoking, dyslipidemia or albuminuria). There is not sufficient evidence to recommend aspirin therapy for those younger without additional risk factors. Aspirin should be used as secondary prevention strategy in those with history of CVD. Clopidogrel should be used when there is aspirin allergy.
14. The main predictors of cardiovascular disease mortality are LDL and HDL cholesterols. Raised triglycerides, low HDL and raised small dense LDL particles are a typical pattern of dyslipidaemia in type 2 diabetes.
15. Targets for lipid levels in diabetes are very strict. Every effort should be made to assist a person with diabetes in reaching these targets. This should be done through adapting lifestyle and using statins and/or other lipid therapy. Some countries or regions have their own specific guidelines – find out what guidelines are used in your area. International Diabetes Federation. (2005). Global Guidelines for Type 2 Diabetes. Brussels: International Diabetes Federation. American Diabetes Association. (2010) Clinical Practice Recommendations. Diabetes Care, 33(suppl 1).
16. A number of clinical trials over the years have shown the role of lipid-lowering medicines. The HMG-CoA reductase inhibitors commonly referred to as statins have an established role in both primary and secondary prevention. Collins R., Armitage J., Parish S., Sleigh, P., Peto, R. (2003). Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet, 361, 2005-2016. Colhoun H.M., Betteridge D.J., Durrington P.N., Hitman, G.A., Neil, H.A., Livingston, S.J. (2004). CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet, 364, 685-696.
17. While statins are generally extremely safe medicines, there are some side effects that people should be aware of. Statins can cause generalised muscle pain; this may require cessation of treatment. Statins can also raise the levels of liver enzymes. There is an increased risk of rhabdomyolysis if statins and fibrates are used in combination. Rhabdomyolysis is the breakdown of muscle. Some people also report cluster nightmares which can be very disturbing.
18. Notes to the educator: Ask for a group discussion on the use of lipid-lowering agents in the participants’ countries.
19. Another risk factor for macrovascular disease is hypertension. Hypertension is twice as prevalent in people with diabetes compared to that in people without diabetes. Before the age of fifty, hypertension is more common in men than women. Geiss, I.S., Rolka, D.B., Engelgau, M.M. (2002). Elevated blood pressure among US adults with diabetes. 1988-1994. Am J Prev Med, 22, 42-48. Sowers, J.R., Epstein, M., Frohlich, E.D. (1995). Diabetes, hypertension and cardiovascular disease: an update. Hypertension, 37, 1053-59.
20. Our blood pressure normally varies from day to night, with daytime readings higher than at night. However, people with diabetes lose this variation. Hypertension in people with type 1 diabetes does not usually occur until they have renal disease. In people with type 2 diabetes, hypertension can occur before they have renal disease.
21. The definition of hypertension is when the blood pressure is greater than 140/90 mmHg. However, the target in diabetes is tighter than this and a blood pressure of less than 130/80 mmHg is recommended. Achieving this can be difficult and it is common that three or more anti-hypertensive agents are required. Side effects of medications should be addressed with the person. Common practice is that when the blood pressure is not reduced with one drug, the person is taken off that medication and a new one is tried. This is not recommended. Health care professionals should use combination therapy, instead of replacing one drug with another they should add antihypertensive agents to the regimen until the target blood pressure is achieved.
22. As well as drug therapies there are several other strategies for reducing hypertension. These should be discussed with the people with diabetes who are hypertensive. They include: Use of antihypertensive medications Attain and maintain a healthy weight Decreasing salt (sodium) intake Not smoking (will also reduce blood pressure) Ideally people with diabetes should avoid taking non-steroidal anti-inflammatory medicines on a regular basis; they should replace them with regular paracetamol (acetominophen) and only take the anti-inflammatory drugs when there is exacerbation of arthritis
23. Almost all treatment in modern medicine, whether they are based on pharmacotherapy or not, have adverse reactions and side effects. Treatment of high blood pressure is no exception. This next series of slides will focus on some common side effects of anti-hypertensive medications. The classes of medication covered are outlined in the slide above. What antihypertensive medications are available in your country?
24. The ACE inhibitors and the Angiotensin-2 receptor blockers are very closely related drugs. They act on different parts of the renin-angiotensin system, an important pathway in regulating intra-renal blood flow, fluid and electrolyte balance as well as blood pressure. A dry cough is an annoying, yet common side effect that is specific to ACE inhibitors. Those who suffer severely can be changed to A2 receptor blockers or other antihypertensives. A raised creatinine (a measure of renal function) is an adverse reaction common to both classes of medications. A related side effect is raised potassium, also closely related to kidney function. Diuretics work by causing the kidneys to excrete fluid and electrolytes. Therefore it is not surprising that dehydration, low potassium and other electrolyte disturbances can occur when these agents are used. Impotence may also result from diuretic usage, and may worsen preexisting impotence from diabetes and vascular disease. Beta-blockers were previously contraindicated in diabetes, due to concerns regarding hypo unawareness. However, the UKPDS showed conclusively that beta-blockers are not only safe to use in diabetes, but are very effective in decreasing mortality and morbidity in people with diabetes. However, several contraindications do exist. They should never be used in asthmatics and will worsen claudication due to peripheral vascular disease. They quite commonly cause tiredness and impotence. Lastly, they may also worsen the lipid profile in people. Lastly, angioedema is an exceedingly rare but potentially fatal side effect of these agents, ACE inhibitors probably more commonly implicated than A2 receptor blockers. People with diabetes should be told to watch out for swelling around the lips, tongue or throat, wheezing and shortness of breath. Should any of these symptoms appear on treatment, the medication should be immediately ceased and the person asked to present to the nearest hospital. Calcium channel antagonists are potent anti-hypertensives, but are not as effective at preventing mortality and morbidity as the previous two agents, especially the ACE inhibitors. The calcium channel blockers can roughly be divided into two classes: the dihydropyridines (e.g. nifidipine, amlodipine) and the non-dihydropyridines (e.g. verapamil, diltiazem). The side effect profiles are different for each class. Dihydropyridines very commonly cause fluid retention and oedema. It may be necessary to stop taking the medication. Flushing is moderately common, but rarely severe enough to warrant cessation. Tachycardia can also occur. The non-dihydropyridines can also cause fluid retention, but also constipation. Bradycardia may occur, but is rarely dangerous unless beta-blockers are used concomitantly. Combinations of beta-blockers and non-dihdropyridines should therefore be avoided.
25. American Diabetes Association. (2010). Clinical practice recommendations 2010. Diabetes Care, 33,(Suppl 1). UK Prospective Diabetes Study Group. (1998). Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ, 317, 703-713 Whelton P.K., Barzilay J., Cushman W.C., Davis, B.R., Iiamathi, E., Kostis, J.B., et al. (2005). ALLHAT Collaborative Research Group. Clinical outcomes in antihypertensive treatment of type 2 diabetes, impaired fasting glucose concentration, and normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med, 165,1401-1409.
26. Notes to the educator: If time allows, break the participants into small groups to discuss this activity. After 10 minutes, ask for ideas from the groups. Take this time to review the correct method for taking blood pressure: Importance of the correct cuff size Having the person sit down for 5 minutes Positioning of the arm (at the same level as the heart) Taking two or more readings 2 minutes apart and average them Making sure no caffeine or tobacco are consumed within 30 minutes prior to testing Having the automated meter calibrated at least yearly.
27. As mentioned previously heart failure is 2 to 3 times more common in diabetes. It is under-recognised and under-treated. It is a progressive syndrome. Many people are aware of systolic heart failure, that is when the heart is not pumping adequately. However, diastolic heart failure (when the heart is not relaxing adequately to allow it to fill properly) is more common in diabetes. Echocardiography can help to distinguish between the two types of heart failure.
28. Standard treatment for heart failure consists of: ACE inhibitor Beta blockers Diuretic(s) It is also important for people with heart failure to weigh themselves daily and look for swelling as an increase in weight may be an indication of fluid retention and a sign that the heart failure needs further treatment. Fluid restriction may also be necessary.
29. Drug prevention strategies are very similar to those used to prevent coronary heart disease. The CARDS study results showed a 37% reduction in major CV events when people were started on atorvastatin 10 mg, when their LDL-C was less than 161mg/dl (4.4 mmol/L) and fasting triglycerides were less than 603 mg/dl (6.78 mmol/L). This study was stopped early for efficacy. The Progress Study looked at the effect of an ACE inhibitor alone, an ACE with a diuretic or a placebo to lower blood pressure and prevent vascular events, stroke or death. The annual rate of vascular event was reduced by 26% in people with diabetes on either ACE alone or in combination. Colhoun H.M., Betteridge D.J., Durrington P.N., Hitman, G.A., Neil, H.A., Livingston, S.J. (2004). CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet, 364, 685-696. Van Gijn. (2002) The PROGRESS Trial: preventing strokes by lowering blood pressure in patients with cerebral ischemia. Stroke, 33, 319.
30. In summary, macrovascular disease is a major cause of early morbidity and mortality in people with diabetes. In an attempt to reduce the risk of an event, it is very important to implement aggressive treatment of dyslipidaemia and blood pressure and all other modifiable lifestyle factors (physical activity and diet).