1. Macrovascular disease
Section 5 | 2 of 4
Curriculum Module III-7d | Cardiovascular disease
Macrovascular disease is a very serious complication of diabetes and is the most common cause of premature death.
It is very important to recognize 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.
Slides current until 2008

2. Macrovascular disease
Coronary heart disease
Cerebrovascular disease
Peripheral vascular disease
What is an “event”?
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 Section 5, Part 4 of 4.
In order to interpret clinical trial results in this area of diabetes it is necessary to know what is meant by the term “event”.
Most clinical trials discuss “the number of events reduced by an intervention”, therefore an “event” is usually a myocardial infarction (MI), or a stroke, and (but not in this context) angina or claudication.
Slides current until 2008

3. Macrovascular disease
Major cause of increased morbidity and mortality in diabetes
Underlying abnormality: atherosclerosis
Macrovasular disease is the major cause of increased morbidity and mortality in diabetes.
The underlying abnormality is atherosclerosis.
Williams 1999
Slides current until 2008

4. What is atherosclerosis?
Process in which deposits of fatty substances, cholesterol, cellular waste products and calcium build up in the wall of an artery. This build up is called plaque
Plaques can grow large enough to significantly reduce the blood flow through an artery. An acute event occurs when they become fragile and rupture
Plaques that rupture cause blood clots that can block blood flow or break off and travel to another part of the body causing a heart attack and stroke
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 cause difficulty in walking and eventually gangrene.
Slides current until 2008

5. Coronary heart disease
Known risk factors
Age
Gender
Family history
Lipid abnormalities
Hypertension
Smoking
Diabetes
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.
Slides current until 2008

6. Coronary heart disease in diabetes
It is more common and occurs earlier than in people without diabetes
Ethnic differences
Caucasians: more myocardial infarctions
Chinese/Japanese: more strokes
Women lose gender protection
Myocardial infarction is often painless (silent)
Albuminuria increases risk of vascular event
Coronary heart disease occurs much more commonly in people with diabetes than in people without diabetes and occurs at an earlier age.
There are ethnic differences in the rate and types of macrovascular disease. For example, Caucasians tend to have more myocardial infarctions (MI) whereas the Chinese and Japanese are more likely to have strokes.
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.
Laing 1999
Slides current until 2008

7. Coronary heart disease in diabetes
Compared to people without diabetes, people with type 2 diabetes have:
The same risk of heart attack as those who have already had a heart attack
Two- to three-fold higher risk of heart failure
Sudden death occurs:
- 50% more often in men
- 300% more often in women
than in peers without diabetes but of the same age
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-recognized and under-treated condition in diabetes is heart failure (this will be discussed later in the presentation).
Even more frightening statistic is that sudden death occurs 50% more often in men and 300% more often in women than in peers without diabetes of the same age. (Diabetes and cardiovascular disease: Time to Act, International Diabetes Federation, 2001).
Haffner 1998
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8. Myocardial infarction and diabetes
People with diabetes have
poor prognosis even
after adjustments for infarct
size and risk factors.
People with diabetes have a worse prognosis than non-diabetic individuals even after adjustments for infarct size and risk factors.
Slides current until 2008

9. Controlling risk factors
Research shows the benefits of reducing the controllable risk factors for atherosclerosis
Controllable risk factors are:
Dyslipidaemia (especially LDL or "bad" cholesterol)
Smoking and exposure to tobacco smoke
High blood pressure
Diabetes
Obesity
Physical inactivity
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 assisting people with this.
The controllable risk factors are: dyslipidaemia (see Slide 18 for target lipid levels); smoking tobacco and exposure to tobacco smoke; high blood pressure; obesity; physical inactivity; optimum blood glucose levels.
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10. Case discussion
TJ is newly diagnosed with diabetes. He smokes one pack of cigarettes a day and does not do any exercise. His blood pressure is 150/95 and his BMI is 30.
What are his risk factors?
What else should you assess?
How will you approach him regarding his risk factors?
If time allows break the participants into small groups to discuss this case.
After 10 minutes, ask for ideas from the groups.
Slides current until 2008

11. Controlling risk factors
Lifestyle intervention: modify diet, lose weight, exercise, stop smoking, drink a glass of red wine
Lipid-lowering agents
ACE inhibitors
Aspirin
Benefits of glycaemic control?
Lifestyle interventions: people with diabetes who are overweight need to lose about 10% of their body weight and reduce their saturated fat intake. While a lot of cholesterol is made in the liver, blood cholesterol can also be reduced by having a smaller intake of saturated and trans fats. The quality of the diet is essential. Things to consider are reducing total fat intake and replacing saturated and trans fats with monounsaturated fats, as well as increasing the intake of antioxidants and flavonoids. A glass of red wine per day has also been shown to increase HDL. (See Section 2.4 – Nutritional needs of people with type 1 diabetes and type 2 diabetes). 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 intervention in reducing risks. People should be encouraged to take a low dose of aspirin daily unless they have some contraindication such as gastric ulceration.
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. However, recent 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.
NCEP 2005
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12. What dose should be taken? For whom is aspirin recommended?
Use of aspirin
What dose should be taken?
For whom is aspirin recommended?
What are the side effects of aspirin?
What are the contraindications to aspirin?
Is there any other medicine that can be used if aspirin is contraindicated?
Discuss these questions with the participants.
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13. Diabetes Intervention and Complication Study (EDIC)
Metabolic memory
Follow-up of people who participated in the DCCT. The difference in glycaemic control had all but disappeared
A total follow-up of 18 years
Researchers followed up the original DCCT cohort for 18 years. The resulting EDIC study has shown the concept of “metabolic memory”.
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14. Diabetes Intervention and Complication Study (EDIC)
Metabolic memory
Microvascular disease
Macrovascular disease
57% reduction during EDIC follow-up period
Despite the fact that the glycaemic control in both the DCCT intensive and conventional groups converged, people in the original intensive group still had significantly less micro- and macrovascular complications in the 18-year follow-up.
Slides current until 2008

15. United Kingdom Prospective Diabetes Study (UKPDS)30
Myocardial infarction
p=0.052
Conventional 20
Patients with events (%)
Intensive 10 30 30
Microvascular endpoints
p=0.0099
Stroke
p=0.52 20 20
Patients with events (%)
Patients with events (%)
This slide shows the long-term complication outcomes of the UKPDS.
Statistically, there are significant differences between the conventional and intensive arms in microvascular endpoints.
However, there are no statistically significant differences between the groups for MI (p=0.052) or strokes (p=0.52). Therefore, the importance of glycaemic control in reducing macrovascular risk was inconclusive in type 2 diabetes at the time of the study in 1998. 10 10 3 6 9 12 15 3 6 9 12 15
Time from randomisation (years)
Time from randomisation (years)
UKPDS 1998
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16. Post-study monitoring of UKPDS
Metabolic memory: micro- and macrovascular complications
Myocardial infarction p=0.042, RR 0.86 ( )
Microvascular disease P=0.0002, RR 0.72 ( )
However, similar to the DCCT metabolic memory results, the recently published Post Study Monitoring also showed that microvascular disease and myocardial infarction was significantly less common in those of the intensive arm of the UKPDS.
The message from both DCCT and UKPDS is that not only does good control matter but good control at an early stage has significant long-term benefits in reducing both micro- and macrovascular complications.
Slides current until 2008

17. Main predictors of CVD mortality LDL and HDL cholesterol
Dyslipidaemia
Main predictors of CVD mortality
LDL and HDL cholesterol
Lipid profile in type 2 diabetes
raised triglycerides
low HDL
raised small dense LDL particles
The main predictors of cardiovascular disease mortality are LDL and HDL cholesterols.
Raised triglycerides, low HDL and small dense LDL particles are a typical pattern of dyslipidaemia in type 2 diabetes.
Slides current until 2008

18. Lipids IDF – type 2 diabetes LDL <2.5 mmol/L (<95 mg/dl)
Triglyceride <2.3 mmol/L (<200 mg/dl)
HDL cholesterol >1.0 mmol/L (>39 mg/dl)
Canada
Primary target Secondary target
LDL-C </= 2.0 mmol/L TC:HDL-C <4.0 mmol/L
United States
LDL <100 mg/dl
Triglycerides <150 mg/dl
HDL >40 mg/dl
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.
IDF 2005, CDA 2006, ADA 2004
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19. Lipids: clinical trials
Lipid-lowering agents called statins have an established role in both primary and secondary prevention.
A number of clinical trials over the years have shown the role of lipid-lowering agents. The statins or HMG Co A reductase inhibitors have an established role in both primary and secondary prevention.
Another group of drugs called fibrates have been tested in a large multicentre randomized controlled clinical trial known as the FIELD study. The results from this study were disappointing as while fenofibrate therapy was associated with a reduction in total rate of cardiovascular events compared with placebo they did not reduce risk of death. Individuals should be maintained on their statin therapy.
Scandinavian Simvastatin 1994
Slides current until 2008

20. Lipids: side effects of statins
Muscle pain (with or without an increase in muscle enzymes)
Increase of liver enzymes
Rhabdomyolysis:
more common when statins and fibrates are used in combination
Cluster nightmares and sleep disturbance
While statins are generally extremely safe drugs, there are some side effects that you should be aware of so you can warn your patient or alert the doctor.
Statins on rare occasions can cause generalized 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. As a safety precaution, if a person is taking this combination, the doctor should be alerted to this fact. Rhabdomyolysis is the breakdown of muscle.
Some people also report cluster nightmares which can be very disturbing.
Durrington 2000
Slides current until 2008

21. Use of lipid-lowering agents
What lipid-lowering agents are available in your country?
What is common practice in relation to the use of lipid-lowering agents in your country?
Ask for a group discussion on the use of lipid-lowering agents in the participants’ countries.
Slides current until 2008

22. Hypertension in diabetes
Prevalence
Approximately twice that of people without diabetes
More common in men than women before age of fifty
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.
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23. Hypertension in diabetes
Loss of day/night variation in blood pressure
may be a sign of autonomic neuropathy
Type 1: normotensive until renal disease develops
Type 2: hypertensive before sign of renal disease
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.
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24. JNC 7 and ADA recommendations Hypertension blood pressure: ≥140/90mmHg
Target blood pressure goal in diabetes: 130/80mmHg
Many people require three or more drugs to achieve the recommended target
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. However, 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. In reality what is needed is to keep adding antihypertensive agents to the regimen until the target blood pressure is achieved.
ADA 2004, JNC7
Slides current until 2008

25. Reducing hypertension
Decrease salt
ACE inhibitors and ARBs work more effectively
Avoid non-steroidal anti-inflammatory medicines
Reduce alcohol to recommended levels
Stop smoking
Recommendations from the DASH study:
Doing one of the above is equivalent to a 10 mmHg drop or one antihypertensive tablet
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:
Decreasing salt: the ACE inhibitors and ARBs work more effectively if less salt is consumed.
2. 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.
3. Reducing alcohol intake will reduce blood pressure. (See Section 2.4 – Nutritonal needs in people with type 1 diabetes and type 2 diabetes).
4. Not smoking will also reduce blood pressure.
Indeed reducing alcohol or salt can be the equivalent to a 10 mmHg drop in blood pressure or one antihypertensive tablet.
Slides current until 2008

26. Anti-hypertensive medications
ACE-inhibitors (-prils)
A2 Receptor blockers (Atacand, Avapro, Karvea, Micardis, Teveten)
Calcium antagonists (Dihydropyridine: Norvasc, Zanidip, Adalat ; and non-dihydropyridine: Verapamil, Diltiazem)
Diuretics
B-blockers
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.
Slides current until 2008

27. Side effects of anti-hypertensive medications
ACE-inhibitors (hyperkalaemia, cough, angioedema, rise in creatinine)
A2 Receptor blockers (angioedema, rise in creatinine)
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.
As such, it is not surprising that 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.
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.
Lastly, angioedema is an exceedingly rare but potentially fatal side effect of these agents, ACE inhibitors probably more commonly implicated than A1 receptor blockers. Patients should be told to watch out for swelling around the lips, tongue or throat, wheeze and shortness of breath. Should any of these symptoms appear on treatment, the medication should be immediately ceased and the patient asked to present to the nearest hospital.
Slides current until 2008

28. Side effects of anti-hypertensive medications
ACE-inhibitors (hyperkalaemia, cough, angioedema, rise in creatinine)
A2 Receptor blockers (angioedema, rise in creatinine)
Calcium antagonists
Dihydropyridine: fluid retention, flushing, tachycardia
Non-dihydropyridine: fluid retention, constipation, bradycardia
Calcium channel antagonists were previously very widely used, but have fallen out of favour slightly in recent times (especially the dihyropyridines). They are certainly very 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 (eg nifidipine, amlodipine) and the non-dihydropyridines (eg verapamil, diltiazem). The side effect profiles are different for each class.
Dihydropyridines very commonly cause fluid retention and oedema. Sometimes this is so troublesome that cessation of the medication is necessary. 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.
Slides current until 2008

29. Side effects of anti-hypertensive medications
ACE-inhibitors (hyperkalaemia, cough, angioedema, rise in creatinine)
A2 Receptor blockers (angioedema, rise in creatinine)
Calcium antagonists
Dihydropyridine: fluid retention, flushing, tachycardia
Non-dihydropyridine: fluid retention, constipation, bradycardia
Diuretics: dehydration, hypokalaemia, impotence
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.
Slides current until 2008

30. Side effects of anti-hypertensive medications
ACE-inhibitors (hyperkalaemia, cough, angioedema, rise in creatinine)
A2 Receptor blockers (angioedema, rise in creatinine)
Calcium antagonists
Dihydropyridine: fluid retention, flushing, tachycardia
Non-dihydropyridine: fluid retention, constipation, bradycardia
Diuretics: dehydration, hypokalaemia, impotence
B-blockers: asthma, claudication, tiredness, impotence
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.
Slides current until 2008

31. Meta-analysis of BP treatment
Seven sets of overview covering 29 randomized trials (n=162341)
Mean duration of follow-up ranged from 2.0 to 8.4 years, providing data on 700,000 patient years
Overall, for most comparisons between a half and three-quarters of participants remained on their randomly assigned study treatment
A little over half achieved target BP
The study design was a meta-analysis covering 29 trials and hundreds of thousands of patients.
Slides current until 2008

32. Meta-analysis of BP treatment
ACE inhibitors are better than calcium channel blockers in most endpoints, especially in mortality and heart failure
Overall, ACE inhibitors are comparable to beta-blockers and diuretics used in combination. However, calcium channel blockers are again slightly inferior, especially in terms of heart failure
A2 Receptor blockers are especially useful in preventing stroke, heart failure and major cardiovascular events
Lancet 2005;366:
Slides current until 2008

33. Meta-analysis of various anti-hypertensive regimens
Magnitude of blood pressure reduction is the greatest determinant of efficacy in reducing cardiovascular disease
The only exception may be in severe cardiac failure in which calcium antagonist may be inferior
This slide summarizes the previous slides. The most important message here is that the level of blood pressure reduction achieved is more important than the agent used. However, it is still the case that calcium channel blockers should not be used when cardiac failure is present.
Lancet 362 : 1527, 2003
Slides current until 2008

34. What is the recommended blood pressure target in your country?
Hypertension
What is the recommended blood pressure target in your country?
What is the most common approach to treating hypertension in your country?
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
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.
Slides current until 2008

35. Isolated systolic hypertension
Systolic blood pressure increases with age due to stiffening of arterial wall
Several studies (SHEP and Syst-EUR) have shown that treatment of systolic hypertension reduces risk of stroke and cardiovascular events
In the past it was not considered a problem if an older person had a high systolic blood pressure and a low diastolic blood pressure.
However, we now know that this is a serious sign of arterial stiffness associated with an increased risk of a macrovascular event and heart failure. Therefore, it is important to treat isolated systolic hypertension although this can be clinically difficult.
Shep 1991, Birkenhager 2000
Slides current until 2008

36. Sometimes risk factors need to be treated even if they seem normal
A newer concept
Sometimes risk factors need to be treated even if they seem normal
Micro Hope Study
Heart Protection Study
CARDS Study
Recently, a number of landmark studies have shown the importance of treating risk factors even if they are not obviously higher than the conventionally regarded normal range.
The major studies in this area are the Micro HOPE Study, the Heart Protection Study and the CARDS. These studies have provided evidence to intensively treat macrovascular risks of people with diabetes.
Gerstein 2002, Heart Protection 2002, CARDS
Slides current until 2008

37. Heart Protection Study
Large study, over adults (~5000 with diabetes)
Randomized to 40 mg simvastatin or placebo
Findings
25% reduction in first-time ischaemic stroke
Transient ischaemic attacks and carotid endarterectomy or angioplasty also significantly reduced
Reductions by end of second year of treatment
The Heart Protection Study (HPS) was a very large study of more than adults which, for the first time, included a large number of people with diabetes. It also included women and elderly people.
Results showed that treatment with simvastatin 40 mgs reduced the risk of an event by 25 to 30% regardless of whether the person started with a normal, medium or high level of cholesterol.
Slides current until 2008

38. Heart failure in diabetes
Two to three times more common in diabetes
Under-recognized and under-treated
Progressive syndrome
Systolic heart failure (not pumping)
Diastolic heart failure (not relaxing, more common in diabetes)
determined by echocardiography
As mentioned previously heart failure is 2 to 3 times more common in diabetes. It is under-recognized 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.
Slides current until 2008

39. Treatment of heart failure
ACE inhibitor
Beta blocker
Diuretic
Daily weight
Fluid management
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 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.
Slides current until 2008

40. Cerebrovascular disease in diabetes
Strokes occur twice as often in diabetes and hypertension than those with hypertension alone
Transient Ischaemic Attacks (TIAs) occur two to six times more often
Strokes occur twice as often in people with diabetes and hypertension than in those with hypertension alone.
Transient Ischaemic Attacks (TIAs) occur 2 to 6 times more often. Consequently, cerebrovascular disease is a major cause of morbidity and mortality in diabetes.
IDF 2001
Slides current until 2008

41. Cerebrovascular disease
Prevention
Anti-hypertensive therapy
Aspirin therapy
Statin therapy (CARD Study)
ACE inhibitor therapy (Progress Study)
Drug prevention strategies are very similar to those used to prevent coronary heart disease.
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.
Slides current until 2008

42. Summary Macrovascular disease
Major cause of early morbidity and mortality
Aggressive treatment of dyslipidaemia and hypertension
Intensive treatment of modifiable risk factors
lifestyle: increase physical activity
improved diet: reduce total and saturated fat, increase monounsaturated fat, antioxidants and flavonoids
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).
Slides current until 2008
CDA 2003, ADA 2005

43. Review question
Which of the following findings on a lipid profile of a person with diabetes is NOT considered a risk factor? 
a. High levels of triglycerides
b. High levels of HDL cholesterol
c. High levels of LDL cholesterol
d. High total cholesterol-HDL ratio
Slides current until 2008

44. Review question
2. A 40-year old woman with obesity and type 2 diabetes is concerned about heart attacks because of “heart trouble runs in the family”. Which of the following responses would provide accurate information? 
Only men with diabetes need to be concerned about coronary heart disease
Women with diabetes are at a higher risk for heart attacks before menopause than pre-menopausal women who do not have diabetes
If your weight decreases to your target level, your risk of heart attacks will be no greater than a woman who does not have diabetes
When you have diabetes, a family history of heart disease is not an additional risk factor
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45. Review question
3. A man with type 2 diabetes and hypertension has a blood pressure of 162/94 after several months of taking an antihypertensive medication. What is the next step in his treatment? 
To further decrease his fat intake
To perform a stress electrocardiogram
To add an additional antihypertensive drug
To discontinue the present anti-hypertensive medication and try a different one
Slides current until 2008

46. Review question
4. In which of the following persons with diabetes would aspirin be contraindicated as preventive therapy?
An elderly man with type 2 diabetes who has had a thrombotic stroke
A 19-year old woman who has had type 1 diabetes since she was 5 years old
A 50-year old overweight woman with type 2 diabetes who smokes but has no evidence of coronary artery disease
A 38-year old man with type 1 diabetes and evidence of coronary artery disease
Slides current until 2008

47. Answers b c
Slides current until 2008

48. References
Williams G, Pickup JC. Handbook of Diabetes 2nd ed. London: Blackwell Science, 1999.
Laing SP, Swerdlow AJ, Slater SD, Botha JL, Burden AC, et al. The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999; 16:
Larsen J, Brekke M, Sandvik L, Arnesen H, Hanssen KF, et al. Silent Coronary Atheromatosis in Type 1 Diabetic Patients and Its Relation to Long-Term Glycaemic Control. Diabetes 2002; 51:
Diabetes Control and Complications Trial, Epidemiology of Diabetes Interventions and Complications Research Group. Intensive Diabetes Therapy and Carotid Intima-Media Thickness in Type 1 Diabetes Mellitus. N Engl J Med 2003; 348:
UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998; 352:
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease; the Scandinavian Survival Study. Lancet 1994; 344:
Durrington P, Sniderman A. Hyperlipidemia Oxford: Health Press.
US Department of Health and Human Services. The 7th Report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure.(JNC 7) National Institutes of Health, 2003.
American Diabetes Association. Treatment of hypertension in adults with diabetes, Diabetes Care 2004; 27(suppl 1): S80-S82.
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49. References
Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, BHS IV. J Hum Hypertens 2004; 18:
SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug and treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265:
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