MACROVASCULAR COMPLICATIONS, DYSLIPIDEMIA and HYPERTENSION

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MACROVASCULAR COMPLICATIONS, DYSLIPIDEMIA and
HYPERTENSION

• 2003 Clinical Practice Guidelines
• for the Prevention and Management
• of Diabetes in Canada

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VASCULAR PROTECTION

• Some of the available treatments, such as
  angiotensin converting enzyme (ACE) inhibitors
  and angiotensin receptor II antagonists (ARBs)
  have potential uses in controlling blood pressure
  and reducing the risks for cardiovascular disease
  (CVD) and renal disease.
• The priorities for vascular and renal protection
  should be
• 1. Vascular protection
• 2. Blood pressure control
• 3. Renal protection

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PRIORITIES FOR VASCULAR RENAL PROTECTION
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STRATEGIES FORVASCULAR PROTECTION

• In alphabetical order
• ACE inhibitor
• Antiplatelet therapy (e.g. ASA)
• Blood pressure control
• Glycemic control
• Lifestyle modification
• Lipid control
• Smoking cessation

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DYSLIPIDEMIA

• Diabetes is associated with high risk for
  vascular disease and aggressive lipid management
  is generally necessary. Attention to the full
  lipid profile is required because
  hypertriglyceridemia and low HDL-cholesterol are
  particularly common.
• Patients should be assessed for their risk of a
  vascular event. Most patients with diabetes are
  at high risk. Younger patients with a shorter
  duration of diabetes and without other risk
  factors and without diabetic complications would
  be considered at moderate risk.

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LIPID TARGETS BASED ON RISK OF A VASCULAR EVENT

• Moderate risk younger age with short duration
  of DM, no complications and no other CVD risks.
• TG are not indicated as a target because almost
  all individuals with hyper-triglyceridemia can be
  identified as having an elevated TCHDL-C.
• Optimal TG is lt 1.5 mmol/L. Optimal apo B lt 0.9
  g/L for high-risk individuals, and 1.05 g/L for
  moderate-risk individuals

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TREATMENT OF DYSLIPIDEMIA
When monotherapy plus lifestyle fails to achieve
lipid targets, the addition of a second drug from
another class should be considered.
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DRUGS FOR DYSLIPIDEMIA
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DRUGS FOR DYSLIPIDEMIA
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HYPERTENSION

• Recommended blood pressure (BP) targets are
• lt 130/80 mm Hg
• Values above systolic 130 mm Hg or diastolic 80
  mm Hg are the BP thresholds recommended to
  initiate treatment.
• These values apply regardless of whether
  nephropathy is present.

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HYPERTENSION

• Results of the Hypertension Optimal Treatment
  (HOT) and UKPDS 38 trials provide strong evidence
  for the diastolic target of 80 mm Hg. Both
  trials demonstrated clinically important
  reductions in micro- and macrovascular
  complications and CV death.
• The evidence for a systolic target of 130 mm Hg
  is less strong, and includes 2 prospective cohort
  studies and the ABCD trial.

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HYPERTENSION TREATMENT

• For people with diabetes without nephropathy, any
  one of these is recommended as initial choice (in
  the following order) if BP cannot be controlled
  by lifestyle interventions
• ACE inhibitor
• ARB
• Cardioselective beta-blocker
• Thiazide-like diuretic
• Long-acting CCB
• Clinical trial evidence exists for each of these
  classes of drugs reducing clinically important
  vascular outcomes in people with diabetes.

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HYPERTENSION TREATMENT

• Multiple drugs will often be needed to approach,
  if not meet, the recommended BP targets.
• For example, in the UKPDS, 29 of subjects
  randomized to tight control required at least 3
  antihypertensive drugs by trials end.

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ANTIPLATELET THERAPY

• Platelet dysfunction in diabetes may contribute,
  in part, to the increased risk of CVD morbidity
  and mortality. Patients with diabetes have a
  variety of alterations in platelet function that
  can predispose to increased platelet activation
  and thrombosis.
• ASA appears to be as effective as other
  antiplatelet agents and is the best choice given
  that it is the most widely studied and the most
  economical. The lowest effective dose (80-325
  mg/day) should be used to limit both
  gastrointestinal toxicity and potential adverse
  effects of prostaglandin inhibition on renal
  function or BP control.
• ASA therapy does not increase the risk of
  vitreous hemorrhage in patients with diabetic
  retinopathy.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• The first priority in the prevention of diabetes
  complications should be reduction of
  cardiovascular (CV) risk by vascular protection
  through a comprehensive multifaceted approach (in
  alphabetical order)
• ACE inhibitor and antiplatelet therapy (e.g.
  acetylsalicylic acid ASA) as recommended
• optimize BP and glycemic control
• lifestyle modifications
• optimize lipid control and
• smoking cessation
• Grade D, Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• People with type 1 or type 2 diabetes should be
  encouraged to adopt a healthy lifestyle to lower
  their risk of CVD. This entails adopting healthy
  eating habits, achieving and maintaining a
  healthy weight, engaging in regular physical
  activity, and stopping smoking Grade D,
  Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• A fasting lipid profile (TC, HDL-C, TG and
  calculated LDL-C) should be conducted at the time
  of diagnosis of diabetes and then every 1 to 3
  years as clinically indicated. Apo B can also be
  measured to accurately estimate atherogenic
  particle number. More frequent testing should be
  done if treatment for dyslipidemia is initiated
  Grade D, Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• Most people with type 1 and type 2 diabetes
  should be considered at high risk for vascular
  disease Grade A, Level 1. However, some people
  with type 1 or type 2 diabetes may be considered
  at moderate risk, such as younger patients with
  shorter duration of disease and without
  complications of diabetes and without other risk
  factors Grade A, Level 1.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• Patients with diabetes should be treated to
  achieve the following target lipid goals
• for patients at high risk of a vascular event
• LDL-C lt 2.5 mmol/L and
• TCHDL-C lt 4.0
• for patients at moderate risk of a vascular
  event
• LDL-C lt 3.5 mmol/L and
• TCHDL-C lt 5.0
• Grade D, Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• Although current evidence does not support
  specific targets for apo B or TG, the optimal TG
  level is lt 1.5 mmol/L, and the optimal levels for
  apo B are lt 0.9 g/L for high-risk patients and lt
  1.05 g/L for moderate-risk patients Grade D,
  Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• The following should be considered when choosing
  treatments for patients with dyslipidemia
• In cases where LDL-C is above target, a statin
  should be prescribed Grade A, Level 1A.
• In high-risk patients with TG levels of 1.5 to
  4.5 mmol/L, HDL-C lt 1.0 and LDL-C at
  target, either a statin Grade A, Level 1A or
  fibrate Grade B, Level 2 can be prescribed.
• In patients with marked hypertriglyceridemia (TG
  levels gt 4.5 mmol/L), a fibrate should be
  prescribed Grade D, Consensus.
• When monotherapy fails to achieve lipid targets,
  the addition of a second drug from another class
  should be considered Grade D, Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• Lifestyle interventions to reduce BP, including
  achieving and maintaining a healthy weight, and
  limiting sodium and alcohol intake, should be
  considered Grade D, Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• BP should be measured at every diabetes visit.
  Patients with systolic BP gt 130 mm Hg or
  diastolic BP gt 80 mm Hg should have their BP
  remeasured on a separate visit Grade D,
  Consensus.
• Persons with diabetes should be treated to target
  a systolic BP lt 130 mm Hg Grade C, Level 3 and
  a diastolic BP ? 80 mm Hg Grade A, Level 1A.
  Systolic BP gt 130 mm Hg and diastolic BP gt 80 mm
  Hg are the thresholds recommended to initiate
  treatment Grade D, Consensus.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• For people with diabetes, no diabetic
  nephropathy, and BP levels gt 130 mm Hg and/or gt
  80 mm Hg despite lifestyle modification, any 1 of
  the following drugs is recommended as the initial
  choice of therapy, in the following order Grade
  D, Consensus for the order
• ACE inhibitor Grade A, Level 1A
• ARB Grade A, Level 1A for co-existent left
  ventricular hypertrophy (LVH) Grade B, Level 2
  if LVH is not present
• cardioselective beta blocker Grade B, Level 2
• thiazide-like diuretic Grade A, Level 1A or
• long-acting CCB Grade B, Level 2.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• If BP targets cannot be reached despite the use
  of 1 of the above drug choices as monotherapy,
  use of 1 or more of these or other
  antihypertensive drugs in combination should be
  considered Grade D, Consensus.
• Alpha-adrenergic blocker are not recommended as
  first-line agents for the treatment of
  hypertension in persons with diabetes Grade A,
  Level 1A.

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MACROVASCULAR COMPLICATIONS- RECOMMENDATIONS

• Unless contraindicated, low-dose ASA therapy (80
  to 325 mg/day) is recommended in all patients
  with diabetes with evidence of CVD, as well as
  for those individuals with atherosclerotic risk
  factors that increase their likelihood of CV
  events Grade A, Level 1A.