Macrovascular Complications of Diabetes Flashcards
What does the “metabolic syndrome”
mean for diabetes management?
Multifaceted condition characterized by a constellation of metabolic abnormalities (abdominal obesity, dyslipidemia, elevated blood glucose,
hypertension)
– People with the “metabolic syndrome” have a significantly higher risk of cardiovascular disease compared to those without
Metabolic Syndrome
and Cardiovascular Event Risk
Ppl with some definition of Metabolic syndrome
Multiple risk factors, at risk of CV event
– Look for other elements of the metabolic syndrome in your patients with type 2 diabetes
• Blood pressure, cholesterol profile, waist circumference
– Presence of multiple elements of the metabolic syndrome significantly increases the risk of developing type 2 diabetes
Elements used in this definition of the metabolic syndrome:
High Blood
Pressure, High Lipid Levels, Proteinuria, High BMI, and High Uric Acid Level
The more risk factors you have, the higher likelihood you have developing diabetes over time
Macrovascular Complications
Cardiovascular Disease
• Diabetes confers a cardiovascular event risk equivalent to aging approximately 15 years*
– Vascular age rather than chronological age
• Diabetes is a powerful catalyst for vascular inflammation, accelerating vascular age and significantly increasing risk of cardiovascular events (MI
or stroke) and complications (heart failure, death)
• Blood pressure, cholesterol profile, blood glucose
– Low-to-normal levels = similar risk as general population
– Elevated levels = vascular age accelerates more rapidly than chronological age
45 yrs old, diabetes
Vascular structure of 60 yrs old
Recommendations for Surveillance
historical approach and disadvantages
Historical approach (diabetes considered a cardiovascular risk equivalent) – Models used to predict 10-year risk of cardiovascular event • Framingham Risk Score and UKPDS Risk Engine (see next slide)
• Disadvantages to the historical approach
– Unknown how ‘responsive’ the risk estimate is once an intervention is started
• e.g, what happens after hypertension is treated and reaches target?
– Unable to discriminate between high- and low-risk groups, especially in younger
people
• e.g., a 45 year old male with hypertension, non-smoker, normal cholesterol profile = 7% (very likely an underestimate)
– Add type 2 diabetes =
compare framingham risk vs UKPDS
Framingham Risk Score – Sex – Age – Total Cholesterol or LDL – HDL – Systolic Blood Pressure – Smoking – Diabetes (yes/no)
UKPDS risk engine - Sex – Age at diabetes diagnosis – Total Cholesterol – HDL – Systolic Blood Pressure – Smoking – Diabetes Duration – A1c – Atrial fibrillation – Ethnicity
Recommendations for Surveillance…
Vascular Protection
• Comprehensive, treatment target driven strategy to reduce the risk
of cardiovascular events
– Early detection and persistent follow-up to achieve and maintain
treatment targets and healthy lifestyle goals
– Strong clinical trial evidence demonstrates a multifaceted approach will
significantly reduce risk of cardiovascular events
• General principles…
– Check blood pressure at every clinic visit
– Check lipid panel every 1 to 3 years
– Follow the ABCDES3 of Diabetes Care
Need to keep it simple
Hypertension, diabetes –> check annualy
name the ABCDES3 of diabetes care
A • A1C – optimal glycemic control (usually ≤7%) (within every 6 months every year)
B • BP – optimal blood pressure control (<130/80)
C • Cholesterol – LDL <2.0 mmol/L or >50% reduction
D • Drugs to protect the heart
A – ACEi or ARB │ S – Statin │ A – ASA if indicated │SGLT2i/GLP-1 RA
with demonstrated CV benefit if type 2 DM with CVD and A1C not at target
E • Exercise / Healthy Eating
S • Screening for complications
S • Smoking cessation
S • Self-management, stress and other barriers
Global Comments on Intensive Glycemic Control
• Weak evidence overall that intensive glycemic control will reduce the risk of microvascular and
macrovascular complications from diabetes
• Makes sense from a pathophysiologic perspective
• There is a chronic, progressive loss of blood glucose control in type 2 diabetes associated with
deterioration of beta cell function … ongoing follow-up and monitoring is critical
• Reducing blood glucose levels rapidly (i.e., 1-1.5% absolute drop in A1c within 6 months) in people
with established type 2 diabetes (i.e., 8-10 year history) can increase the risk of all-cause and
cardiovascular-related mortality (ACCORD)
• Intensive glycemic control will increase the risk of hypoglycemic events
– Patient education is critical
• Glucose control alone (a ‘glucocentric’ approach to diabetes management) will not be enough!
Recommendations for bp
• Target: < 130/80 mm Hg
• Initial agent:
– Microalbuminuria, kidney disease, or other cardiovascular risk factors in addition to
hypertension and diabetes… ACE inhibitor or ARB
– All others, choices listed alphabetically: ACE inhibitor, ARB, dihydropyridine CCBs,
thiazide/thiazide-like diuretics
• Combination therapy with 2-3 antihypertensive drugs is often required to
achieve treatment targets (see next slide)
– When adding to ACE inhibitor therapy, a dihydropyridine CCB is preferable to a
thiazide/thiazide-like diuretic
Cholesterol Management Guidelines
Check the lipid profile every 1 to 3 years, depending on overall cardiovascular risk of the individual
• Statin therapy should be used to reduce cardiovascular risk in people with diabetes and…
– Established cardiovascular disease (secondary prevention)
– ≥40 years old
– <40 years old plus one of the following: diabetes >15 years and age >30; microvascular complications; “other risk factors” according to Canadian Cardiovascular Society Guidelines (e.g., Framingham Risk Score ≥10% and LDL ≥3.5 mmol/L)
• Treatment target: LDL < 2.0 mmol/L or 50% reduction from baseline
ACE &/or ARB
Recommending for heart or neal protection: use as long as you have a heart or kidney
Randomized controlled trial data consistently demonstrates benefit
– Ramipril 10 mg daily lowers risk of major cardiovascular events
• HOPE
• Micro-HOPE (people with diabetes ≥55 years old, with one other cardiovascular risk factor)
– Perindopril 8 mg daily had similar benefit in subgroup of people with diabetes (though difference was not statistically significant)
• EUROPA
– Telmisartan 80 mg daily had similar benefit as ramipril 10 mg daily in people with diabetes
• ONTARGET
• Unclear if benefit is related to blood pressure reduction or inhibition of the renin-angiotensin-aldosterone system
– Benefits observed in HOPE and EUROPA were independent of hypertension status and blood pressure change
• RECOMMENDATION: ACE or ARB at doses with demonstrated vascular protection should be used to reduce cardiovascular risk in people with diabetes plus…
Clinical Cardiovascular Disease
Age ≥55 years with additional cardiovascular risk factors or end organ damage
Microvascular complications
Antiplatelet Therapy – Rationale
Platelets have a central role in development of atherothrombosis
• People with diabetes have a variety of alterations to platelet function
– Increased turnover
– Enhanced aggregation
– Increased thromboxane synthesis
• HOWEVER*
– High on-treatment platelet reactivity (HTPR) – sometimes referred to as “aspirin
resistance” – is more likely to occur in people with diabetes compared to people
without diabetes
– Using >100 mg aspirin daily may reduce the likelihood of HTPR in people with diabetes
Antiplatelet Therapy:
Diabetes Canada Recommendations
Primary Prevention?
– Aspirin should NOT be routinely used
– Aspirin MAY be used in the presence of multiple cardiovascular risk factors
• Secondary Prevention?
– Low-dose (81-162 mg daily) should be used in people with established
cardiovascular disease
– Clopidogrel 75 mg daily MAY be used in people unable to tolerate aspirin
ASCEND Tria
15,480 adults with diabetes but no evidence of cardiovascular
disease
• Randomized to 100mg enteric-coated aspirin or matching placebo
• Main Results (mean follow-up 7.4 years):
– Any Serious Vascular Event or Revascularization RR: 0.88 (0.80-0.97)
• Number Needed to TREAT = 91
– Any Serious Bleeding Event RR: 1.29 (1.09-1.52)
• Number Needed to HARM = 112
Showed signifcant benefit
Cost of serious bleeding event
