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{{DevelopmentPhase}}
''Jonas de Jong and Alice Li''
__TOC__
__TOC__
==Preamble==
==Preamble==
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===Treatments to reduce cardiovascular risk===  
===Treatments to reduce cardiovascular risk===  
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
!colspan="3"|Treatment to reduce cardiovascular risk <cite>34</cite>
|-
|bgcolor="#CCCCFF" colspan="3"|'''Lifestyle and comprehensive management'''
|-
!Recommendation
!Class<sup>a</sup>
!Level<sup>b</sup>
|-
|Structured patient education improves metabolic and blood pressure control
!I
!A
|-
|Non-pharmacological life style therapy improves metabolic control
!I
!A
|-
|Self-monitoring improves glycaemic control
!I
!A
|-
|Near normoglycaemic control (''HbA1c &le; 6.5%<sup>c</sup>'')
reduces microvascular complications
reduces macrovascular complications
!I
!A
|-
|Intensified insulin therapy in type 1 diabetes reduces morbidity and mortality
!I
!A
|-
|Early escalation of therapy towards predefined treatment targets improves a composite of morbidity and mortality in type 2 diabetes
!IIa
!B
|-
|Early initiation of insulin should be considered in patients with type 2 diabetes failing glucose target
!IIb
!C
|-
|Metformin is recommended as first line drug in overweight type 2 diabetes
!IIa
!B
|-
|bgcolor="#CCCCFF" colspan="3"|'''<sup>a</sup>Class of recommendation.'''
'''<sup>b</sup>Level of evidence.'''
'''<sup>c</sup>Diabetes Control and Complication Trial-standardized.'''
|}
To reduce the risk of cardiovascular disease, the followings are needed to be considered:  
To reduce the risk of cardiovascular disease, the followings are needed to be considered:  


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===Treatments and outcomes===
===Treatments and outcomes===
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
!Treatment options based on accumulated evidence <cite>34</cite>
|-
|
*Revascularization
*Anti-ischaemic medication
*Anti-platelet agents
*Anti-thrombin agents
*Secondary prevention by means of
**Lifestyle habits including food and physical activity
**Smoking cessation
**Blocking the renin–angiotensin system
**Blood pressure control (target < 140/85 mmHg)<cite>ESCEADS</cite>
**Lipid-lowering medication (target LDL < 1.8 mmol/L or < 70 mg/dL)<cite>ESCEADS</cite>
**Blood glucose control (target HbA1c < 53 mmol/mol or < 7%)
|}
The preventive modalities include doctors counsel exercise, the “diabetes with CAD meal plan” aiming at long-term weight loss, aspirin in doses of 75 to 81 mg/d,<cite>37</cite> (in patients who do not tolerate or have a contra-indication to aspirin, clopidogrel can be used as an alternative antiplatelet agent <cite>38</cite>), antihypertensive therapy and glycemic control.
The preventive modalities include doctors counsel exercise, the “diabetes with CAD meal plan” aiming at long-term weight loss, aspirin in doses of 75 to 81 mg/d,<cite>37</cite> (in patients who do not tolerate or have a contra-indication to aspirin, clopidogrel can be used as an alternative antiplatelet agent <cite>38</cite>), antihypertensive therapy and glycemic control.


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===Treatments and outcomes===  
===Treatments and outcomes===  
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
!colspan="3"|Heart failure and diabetes<cite>34</cite>
|-
|bgcolor="#CCCCFF" colspan="3"|
|-
!Recommendation
!Class<sup>a</sup>
!Level<sup>b</sup>
|-
|ACE-inhibitors are recommended as first-line therapy in diabetic patients with reduced left ventricular dysfunction with or without symptoms of heart failure
!I
!C
|-
|Angiotensin-II receptor blockers have similar effects in heart failure as ACE-inhibitors and can be used as an alternative or even as added treatment to ACE-inhibitors
!I
!C
|-
|Beta blockers (metoprolol, bisoprolol, and carvedilol) are recommended as first-line therapy in diabetic patients with heart failure
!I
!C
|-
|Diuretics, in particular loop diuretics, are important for symptomatic treatment of diabetic patients with fluid overload owing to heart failure
!IIa
!C
|-
|Aldosterone antagonists may be added to ACE-inhibitors, BBs, and diuretics in diabetic patients with severe heart failure
!IIb
!C
|-
|bgcolor="#CCCCFF" colspan="3"|'''<sup>a</sup>Class of recommendation.'''
'''<sup>b</sup>Level of evidence.'''
|}
According to the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) Guidelines,<cite>31</cite> there are very few clinical trials on heart failure treatment specifically for diabetic patients. Information on treatment efficacy of various drugs is therefore based on diabetic subgroups included in various heart failure trials. A disadvantage of this is that the subgroups are not always well defined as regards the diabetic state and treatment. Most data favor a proportionately similar efficacy in patients with and without diabetes. Traditional treatment of heart failure in diabetic patients is based on diuretics, ACE-inhibitors, and Beta-blockades, as outlined in other guidelines.<cite>44</cite> Moreover, it is assumed that meticulous metabolic control should be beneficial in heart failure patients with diabetes.
According to the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) Guidelines,<cite>31</cite> there are very few clinical trials on heart failure treatment specifically for diabetic patients. Information on treatment efficacy of various drugs is therefore based on diabetic subgroups included in various heart failure trials. A disadvantage of this is that the subgroups are not always well defined as regards the diabetic state and treatment. Most data favor a proportionately similar efficacy in patients with and without diabetes. Traditional treatment of heart failure in diabetic patients is based on diuretics, ACE-inhibitors, and Beta-blockades, as outlined in other guidelines.<cite>44</cite> Moreover, it is assumed that meticulous metabolic control should be beneficial in heart failure patients with diabetes.


Diuretics are mandatory for relief of symptoms that are due to fluid overload. These drugs should, however, not be used in excess since they induce neuro-hormonal activation.<cite>44</cite> ACE-inhibitors are beneficial in moderate-to-severe heart failure with and without diabetes, they inhibit angiotensin-converting enzyme, thereby decreasing the tension of blood vessels and blood volume, thus lowering blood pressure. Frequently prescribed ACE inhibitors include perindopril, captopril, enalapril, lisinopril, and ramipril. Hypoglycaemia has been reported following the institution of ACE-inhibitors in patients with diabetes on glucose-lowering treatment.<cite>45</cite> It is therefore recommended to monitor blood glucose carefully in the early phase of the institution of an ACE-inhibitor in such patients. Beta-blockade decreases myocardial free fatty acid exposure, thereby changing that metabolic pathway in type 2 diabetes.<cite>46</cite> The addition of eplerenone, a selective aldosterone blocker, to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.<cite>47</cite>  
Diuretics are mandatory for relief of symptoms that are due to fluid overload. These drugs should, however, not be used in excess since they induce neuro-hormonal activation.<cite>44</cite> ACE-inhibitors are beneficial in moderate-to-severe heart failure with and without diabetes, they inhibit angiotensin-converting enzyme, thereby decreasing the tension of blood vessels and blood volume, thus lowering blood pressure. Frequently prescribed ACE inhibitors include perindopril, captopril, enalapril, lisinopril, and ramipril. Hypoglycaemia has been reported following the institution of ACE-inhibitors in patients with diabetes on glucose-lowering treatment.<cite>45</cite> It is therefore recommended to monitor blood glucose carefully in the early phase of the institution of an ACE-inhibitor in such patients. Beta-blockade decreases myocardial free fatty acid exposure, thereby changing that metabolic pathway in type 2 diabetes.<cite>46</cite> The addition of eplerenone, a selective aldosterone blocker, to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.<cite>47</cite>


==Atrial fibrillation and diabetes==
==Atrial fibrillation and diabetes==
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===Treatments and outcomes===  
===Treatments and outcomes===  
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
!colspan="3"|Arrhythmias: atrial fibrillation and sudden cardiac death<cite>34</cite>
|-
|bgcolor="#CCCCFF" colspan="3"|
|-
!Recommendation
!Class<sup>a</sup>
!Level<sup>b</sup>
|-
|Aspirin and anticoagulant use as recommended for patients with atrial fibrillation should be rigorously applied in diabetic patients with atrial fibrillation to prevent stroke
!I
!C
|-
|Chronic oral anticoagulant therapy in a dose adjusted to achieve a target international normalized ratio (INR) of 2–3 should be considered in all patients with atrial fibrillation and diabetes, unless contraindicated
!IIa
!C
|-
|Control of glycaemia even in the pre-diabetic stage is important to prevent the development of the alterations that predispose to sudden cardiac death
!I
!C
|-
|Microvascular disease and nephropathy are indicators of increased risk of sudden cardiac death in diabetic patients
!IIa
!B
|-
|bgcolor="#CCCCFF" colspan="3"|
'''<sup>a</sup>Class of recommendation.
'''<sup>b</sup>Level of evidence.
|}
Aspirin and anticoagulant use as recommended for patients with atrial fibrillation should be rigorously applied in diabetic patients with atrial fibrillation to prevent heart stroke. Oral anticoagulation is most beneficial for patients at higher risk for stroke, whereas the risks outweigh the benefit in patients at low risk.<cite>50</cite> Thus, quantifying the risk of stroke is crucial for determining which atrial fibrillation patients would benefit most from anticoagulant therapy.
Aspirin and anticoagulant use as recommended for patients with atrial fibrillation should be rigorously applied in diabetic patients with atrial fibrillation to prevent heart stroke. Oral anticoagulation is most beneficial for patients at higher risk for stroke, whereas the risks outweigh the benefit in patients at low risk.<cite>50</cite> Thus, quantifying the risk of stroke is crucial for determining which atrial fibrillation patients would benefit most from anticoagulant therapy.


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===Treatments and outcomes===  
===Treatments and outcomes===  
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
!colspan="3"|Peripheral vascular disease<cite>34</cite>
|-
|bgcolor="#CCCCFF" colspan="3"|
|-
!Recommendation
!Class<sup>a</sup>
!Level<sup>b</sup>
|-
|All patients with type 2 diabetes and CVD are recommended treatment with low-dose aspirin
!IIa
!B
|-
|In diabetic patients with peripheral vascular disease, treatment with clopidogrel or low molecular weight heparin may be considered in certain cases
!IIa
!B
|-
|Patients with critical limb ischaemia should, if possible, undergo revascularization procedures
!I
!B
|-
|An alternative treatment for patients with critical limb ischaemia, not suited for revascularization, is prostacyclin infusion
!I
!A
|-
|bgcolor="#CCCCFF" colspan="3"|
'''<sup>a</sup>Class of recommendation.'''
'''<sup>b</sup>Level of evidence.'''
|}
Peripheral vascular diseases: Preventions are most important strategies, such as regular exercises, the optimization of glycemic control, management of hypertension, smoking cessation, antiplatelet and anti-cholesterol medications like aspirin, clopidogrel and statins.  
Peripheral vascular diseases: Preventions are most important strategies, such as regular exercises, the optimization of glycemic control, management of hypertension, smoking cessation, antiplatelet and anti-cholesterol medications like aspirin, clopidogrel and statins.  


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If anatomically possible, a revascularization procedure should be attempted in all patients with critical limb ischemia,<cite>65</cite> such as an angioplasty or a  bypass grafting can be done on solitary lesions in large arteries like the femoral artery, but the revascularization may not have sustained benefits. A synthetic prostacyclin (Ilomedin, Iloprost) is the only pharmacological agent so far convincingly shown to have significant beneficial effects on ulcer healing and pain relief on patients with critical limb ischemia, which is given intravenously daily for a period of 2–4 weeks.<cite>66</cite>
If anatomically possible, a revascularization procedure should be attempted in all patients with critical limb ischemia,<cite>65</cite> such as an angioplasty or a  bypass grafting can be done on solitary lesions in large arteries like the femoral artery, but the revascularization may not have sustained benefits. A synthetic prostacyclin (Ilomedin, Iloprost) is the only pharmacological agent so far convincingly shown to have significant beneficial effects on ulcer healing and pain relief on patients with critical limb ischemia, which is given intravenously daily for a period of 2–4 weeks.<cite>66</cite>
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
!colspan="3"|Stroke<cite>34</cite>
|-
|bgcolor="#CCCCFF" colspan="3"|
|-
!Recommendation
!Class<sup>a</sup>
!Level<sup>b</sup>
|-
|For stroke prevention, blood pressure lowering is more important than the choice of drug. Inhibition of the renin–angiotensin–aldosterone system may have additional benefits beyond blood pressure lowering ''per se''
|IIa
|B
|-
|Patients with acute stroke and diabetes should be treated according to the same principles as stroke patients without diabetes
|IIa
|C
|-
|bgcolor="#CCCCFF" colspan="3"|
'''<sup>a</sup>Class of recommendation.'''
'''<sup>b</sup>Level of evidence.'''
|}


Cerebrovascular diseases: Stroke prevention should be based on a multifactorial strategy aimed at the treatment of hypertension, hyperlipidemia, microalbuminuria, hyperglycemia and the use of antiplatelet medications. Antiplatelet therapy reduces the incidence of stroke in diabetic patients and is indicated for both primary and secondary prevention.<cite>67</cite> Low dose Aspirin (75–250 mg daily) should be the initial choice, but in case of intolerance, clopidogrel 75 mg once daily should be given.<cite>68</cite> In patients with recurrent stroke, a combination of aspirin and dipyridamol should be a better option.
Cerebrovascular diseases: Stroke prevention should be based on a multifactorial strategy aimed at the treatment of hypertension, hyperlipidemia, microalbuminuria, hyperglycemia and the use of antiplatelet medications. Antiplatelet therapy reduces the incidence of stroke in diabetic patients and is indicated for both primary and secondary prevention.<cite>67</cite> Low dose Aspirin (75–250 mg daily) should be the initial choice, but in case of intolerance, clopidogrel 75 mg once daily should be given.<cite>68</cite> In patients with recurrent stroke, a combination of aspirin and dipyridamol should be a better option.
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#77 [http://www.who.int/mediacentre/factsheets/fs312/en/index.html World Health Organization (''WHO''), an estimated 347 million people world-wide have  diabetes in 2012]
#77 [http://www.who.int/mediacentre/factsheets/fs312/en/index.html World Health Organization (''WHO''), an estimated 347 million people world-wide have  diabetes in 2012]
#78 pmid=16399854
#78 pmid=16399854
#ESCEADS pmid=23996285
</biblio>
</biblio>
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