4. What types of lesions cause
MI ?
Falk E, et al. Circulation. 1995;92:657-671.
100
80
60
40
20
0
14%
18%
68%
All four
studies
50%-70%<50% >70%
100
60
40
20
0
Ambrose
1988
Little
1988
Nobuyoshi
1991
Giroud
1992
Coronarystenosis(%)
Coronary stenosis severity prior to MI
80
5. What types of lesions cause
MI ?
Falk E, et al. Circulation. 1995;92:657-671.
100
80
60
40
20
0
14%
18%
68%
All four
studies
50%-70%<50% >70%
100
60
40
20
0
Ambrose
1988
Little
1988
Nobuyoshi
1991
Giroud
1992
Coronarystenosis(%)
Coronary stenosis severity prior to MI
80
5
10. Years after DM Diagnosis
≤ 2 3-5 6-9 10-14 15+
15%
21%
24%
29%
48%
Harris, S et al.; Type 2 Diabetes and Associated Complications in Primary Care in
Canada: The Impact of Duration of Disease on Morbidity Load. CDA 2003.
Duration of T2DM and CVD
10
11. Duration of DM - CV Mortality
0
0.5
1
1.5
2
2.5
3
3.5
4
< 5 6 to 10 11 to 15 16 to 25 26 +
Duration of Diabetes (years)
p for trend <0.001
Cho, et al. J Am Coll Card 2002:40:954.
RelativeRisk
11
12. Life Expectancy with Diabetes
Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.
0
10
20
30
40
50
60
70
80
90
Men Women
Years
DM
No DM
0
200
400
600
800
1000
1200
1400
1600
Mortality rate/100,000
Diabetes
No Diabetes
12
13. Cardiovascular Disease and
T2DM
Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.
0%
5%
10%
15%
20%
Hypertension Heart Disease
PrevalenceofCVDisease
Diabetes
No Diabetes
13
14. Clinical Outcome for Diabetes
4-year Follow-up
0
2
4
6
8
10
12
14
CV Death MI Stroke Dialysis
%
HOPE / MICRO-HOPE. Lancet 2000;355:253.
14
15. ACS and Diabetes – Up to 1
Year%ofpatients
1.8
3.9
7.
1
8.9 7.9
14.4 14.1
21.3
P<0.0001
P=0.035
P<0.0001
P<0.0001
0
5
10
15
20
25
In-Hospital
Mortality
Non-fatal MI 1-y All-Cause
Mortality
1-y
Mortality/MI
N = 3429
N = 1149
No Diabetes
Diabetes
Yan R, et al. Can J Cardiol 2003;19(suppl A):260A.
15
17. Predictors of CV Risk in DM
Age; But Gender looses its power
MAU (Microalbuminuria)
W/H Ratio (Abdominal Obesity)
LP(a) (Lipoprotein small ‘a’)
LDL Cholesterol
Not the Glycemic levels !!
17
18. DM = CAD - Because
• CVD is responsible for 60 - 75% of mortality in T2DM
• CVD is 4 times more prevalent in diabetes; CADI is more
• CVD prevalence increases with age, so is T2DM
• CVD in DM is often severe, silent, poor prognosis and fatal
• Diabetes ↑ mortality, 50% pre adm / recurrent MI and ACS
• Diabetes erases the protection conferred to women
• At diagnosis of T2DM, most patients have evidence of CVD
• Abnormal Glucose tolerance is a strong CV Risk factor
18
30. • Elevated total TG
• Reduced HDL
• Small, dense LDL
• ↑ HDL 3 and ↓ HDL1 and HDL 2
• LDL is not usually high
• Postprandial Hyper lipemia
Dyslipidemia in DM and IRS
30
38. IR and TG Increase
Olefsky JM et al. Am J Med. 1974;57:551-560.
Insulin Response to Oral Glucose
625
500
400
300
200
100
100 200 300 400 500 600
PlasmaTG(mg/dL)
r = 0.73
P < 0.0001
38
39. DM, IRS and HDL
HDL-C(mg/dL)
Reaven GM. In: Le Roith D et al., eds. Diabetes Mellitus.1996:509-519.
Non-obese
Hyperinsulinemic
Normoinsulinemic
Obese
P < 0.005
39
P < 0.005
40. • Accumulation of chylomicron remnants
• Accumulation of VLDL remnants
• Generation of small, dense LDL
• Association with low HDL
• Increased coagulability
• PAI-1, and factor VIIc
• Activation of prothrombin to thrombin
Effects of TG on CV Risk
40
41. • Increased susceptibility to oxidation
• Increased vascular permeability
• Conformational change in Apo B
• ↓ Affinity for LDL receptor (↓ clearance)
• Association with insulin resistance syndrome
• Association with high TG and low HDL
Small Dense LDL and CHD
Potential Atherogenic Mechanisms
Austin MA et al. Curr Opin Lipidol 1996;7:167-171.
41
51. A A1c (Hb A1c)
B Blood pressure (goal)
C Cholesterol (all
lipids)
51
52. Ticking Clock of T2DM
1. Micro-vascular (DR, DKD, DPN, DAN)
At the onset of hyperglycemia
Control of hyperglycemia essential
The A1c target of less than 7 must (A)
2. Macro-vascular (CAD, CVD, PVD)
At the onset of insulin resistance
Blood pressure goal of 130/80 (B)
Control of lipid abnormalities (C)
52
54. Goals inT2DM for VP
Risk Factor Goal or Target
Glycemia Hb A1c < 6.5%
Blood Pressure < 130/80 mm Hg
LDL target < 100 mg%; better < 70
HDL target > 40 men, > 50 women
TG target < 150 mg%
BMI < 25 kg/m2
Physical activity At least 5 days - 2 km/day
ADA, CDA, IDF, WWD
54
55. From Blood Sugar to Blood Vessel
ACEi (Ramipril) Vasoprotective, anti HT, ↓ ED
ASA (75 to 150 mg%) Anti inflamm., Anti Platelet
Statin (Powerful, full) ↓ LDL, TG, Corrects ED, Inflam
BP Goal Vascular damage, LVH, CVA
Glycemic control ↓ Micro vascular ? Macrovascular
Physical activity ED, ↓ Inflammation, ↑ HDL
Diet and TLC ↓ TG, LDL, Glycemia, Weight
Smoking cessation ↓ ED and Inflammation
55
56. ACEi in T2DM - VP
• Antihypertensive, vasoprotective, antithrombotic, and
anti-inflammatory properties – Inevitable in DM
• Reduce CV events, Reduce atherosclerosis
• Reduce renal disease which is a strong CV risk factor
• Metabolically ‘friendly’ drugs that prevent rises in glucose
& prevent diabetes
• Well-tolerated with few side effects
56
58. • Total CHO to be reduced < 50% of calories
• Saturated fat must reduced to< 7% of calories
• MUFA and PUFA up to 15% of calories
• Protein in take to be increased – 25% of cal.
• Dietary fiber > 20 g/day -Soy protein, Fenugreek
• Vegetables, Nuts and fruits must every day
MNT and Dyslipidemia
58
59. If all lipid values are normal
1. Lifestyle interventions (TLC)
MNT, Physical Activity, Weight and Waist reduction
2. Statin in a minimum dose of 10 mg o.d
3. Follow up every one year by full lipid profile
4. All Indians must be tested for LP(a) and
If > 30 mg% - Niacin SR 350 to 500 mg started
Priorities for Treatment
59
60. LDL cholesterol lowering – First priority
1. Lifestyle interventions (TLC)
2. Drugs - First choice – Statin with or without
3. Cholesterol absorption inhibitors (EZ)
4. Second choice – Niacin and Fibrate
5. Add on – BAR (Bile acid binding resins)
Priorities for Treatment
60
61. Priorities for Treatment
HDL cholesterol raising – Second priority
1. Lifestyle interventions
2. First choice - Niacin ( doses <2 g/day)
3. Preferably short acting Niacin
4. Fibrates are second choice
61
62. Priorities for Treatment
Triglyceride lowering – Third priority
1. First choice: Lifestyle interventions
2. Glycemic control is the best Rx for ↓TG
3. Fibrates
4. Niacin
5. High dose statins (if LDL is also high )
62
63. Priorities for Treatment
Triglyceride Lowering (continued)
• In case of severe hyper triglyceridemia (> 1000
mg), severe fat restriction (< 10 % of calories ) in
addition to pharmacological therapy is necessary to
reduce the risk of pancreatitis and lipemia effects
63
64. Priorities for Treatment
Combined Dyslipidemia
1. First choice: Glycemic control + Statin
2. Glycemic control+ Statin + Fibrate
3. Glycemic control+ Statin + Niacin
64
65. Drug Rx. – Effect on Lipoproteins
Pharmacological Agents LDL HDL TG
Statins (HMG CoA Reductase In)
Fibrates (PPAR- γ Activators)
BAR (Bile Acid Sequestering
Resins)
Niacin (Plain or SR)
ADA. Diabetes Care 2003;26 (suppl 1):S 83-S 86
65
66. Drugs for Dyslipidemia
Statins
• Rosuvastati
n
• Atorvastati
n
• Simvastatin
• Lovastatin
• Pravastatin
• Cervistatin
Fibric Acid
• Fenofibrate
• Gemfibrozil
• Benzafibrat
e
• Clofibrate
• Ciprofibrat
e
• Clofibride
Niacin
• Neasyn SR
• Neasyn
• Nialip
• Neaspan
66
67. Treatment of LDL
High LDL
Therapeutic Lifestyle Change
Add on drug - EZ , Niacin, BAR
Therapy of Choice: Statin
Drug Therapy
67
68. Treatment of HDL
Low HDL
Therapeutic Lifestyle Change
Add on drug - Finofibrate
Therapy of Choice : Niacin
Drug Therapy
68
69. Treatment of TG
High TG
Therapeutic Lifestyle Change
Add on drug – Statin, Niacin
Therapy of Choice : Fibrate
Drug Therapy
69
79. Screening
In adults, a screening lipid profile
is reasonable at the time of first
diagnosis, at the initial medical
evaluation, and/or at age 40 years
and periodically (e.g., every 1–2
years) thereafter.
80. Lipid profile testing
Cholesterol laboratory testing may
be helpful in monitoring adherence
to therapy, but may not be needed
once the patient is stable on
therapy.
81. Treatment recommendations
• Treatment not aimed towards achieving LDL-C
target goals
• Rather, the type of treatment (high vs moderate
intensity) should be based on risk profile of
patient
• Do not agree with the use of ‘Risk calculator’ of
ACC/AHA 2013 guidelines for DM patients
since diabetes itself confers increased risk for
CVD
83. Combination Therapy
• Combination therapy (statin/ fibrate and statin/niacin) has
not been shown to provide additional cardiovascular
benefit above statin therapy alone and is not generally
recommended.
• Combination therapy (statin and fibrate) may be efficacious
for treatment for LDL cholesterol, HDL cholesterol, and
triglycerides, but this combination is associated with an
increased risk for abnormal transaminase levels, myositis,
or rhabdomyolysis.
• The risk of rhabdomyolysis is more common with higher
doses of statins and with renal insufficiency
84. Statins and diabetes
• There is an increased risk of incident diabetes
with statin use which may be limited to those
with diabetes risk factors. These patients may
benefit from diabetes screening when on statin
therapy.
• However, CV event rate reduction far
outweighed the risk of DM, Even for patients
with highest risk of diabetes
90. Anti HT Drugs and Lipids
Anti hypertensive agents On Lipids
ACEi and ARBS (Excellent)
CCBs (Neutral on lipids)
Diuretics (Unfavourable)
Blockers (Very unfavourable)
Blockers (Mildly unfavourable)
90
91. Glycemic goal alone is not adequate at all
CAD must be prevented at all costs
The A, B, C of Diabetes must be addressed
Statins in full dose Fibrate or Niacin
All T2DM must receive drugs/advise on
ACEi/ARB, ASA, Statin, TLC, PA, ↓ Weight
To Reiterate
91