Clinical Evaluation and Nonlipid Treatment of Coronary Artery Disease in the Diabetic Patient Richard Nesto, MD
Prevalence of Asymptomatic CAD in Diabetes Mellitus
Koistinen MJ. BMJ 1990;301:92-95.
Type 2 Type 1 Controls
Naka M et al. Am Heart J 1992;123:46-53.
Type 2 Controls
MiSAD Group. Am J Cardiol 1997;79:134-139.
Type 2
Rutter MK et al. Am J Cardiol 1999;83:27-31.
Type 2 w microalb Type 2 w/o microalb
Le A et al. Am J Kidney Dis 1994;24:65-71.
Type 1 Renal Transplant
Holley JL et al. Am J Med 1991;90:563-570.
Type 1 & 2 Renal Transplant
n = 64 n = 72 n = 80
n = 142 n = 149
n = 925
n = 43 n = 43
Positive ETT
Positive Angiography
(thal201)
36% 24% 9%
31% 30%
12.1%
65% 40%
58%
55%
9% 11% 9%
12.1% 5.3%
6.4%
— —
35%
43%
Indications for Cardiac Testing in Diabetic Patients
Typical or atypical cardiac symptoms
Resting ECG suggestive of ischemia or infarction
Peripheral or carotid occlusive arterial disease
Sedentary lifestyle or plan to begin a vigorous exercise program
Two or more of the risk factors listed below
- Total cholesterol >240 mg/dL, LDL cholesterol >160 mg/dL, or HDL cholesterol <35 mg/dL
- Blood pressure >140/90 mmHg
- Smoking
- Family history of premature CAD
- Positive micro/macroalbuminuria
Factors Limiting Accuracy of Noninvasive "Stress" Tests for CAD
Hypertensive Cardiomyopathy
Diabetic Cardiomyopathy
Autonomic Cardiomyopathy
Renal Insufficiency
Microvascular Dysfunction
Benefits of Early Detection of CAD
Implement more aggressive CHD prevention regimen
Initiate anti-ischemic medications
Identify patients who would benefit from revascularization
Educate patients to recognize coronary symptoms
Kannel WB et al. Am Heart J 1991;121:1268-1273.
Blood Pressure and CVD: Framingham Heart Study
Age-adjusted CV Event Rate/1,000
Systolic BP (mmHg)
105
135
165
195
Systolic BP (mmHg)
105
135
165
195
Age-adjusted CV Event Rate/1,000
24
50
38
77
59
119
90
174
15
31
23
48
36
74
56
113
No Glucose Intolerance
Glucose Intolerance
No Glucose Intolerance
Glucose Intolerance
MEN
WOMEN
UKPDS Group. Lancet 1998;352:837-853.
Effect of Glycemic Control in the UK Prospective Diabetes Study (UKPDS)
Any diabetes related*
MI
Stroke
PVD
Microvascular
40.9
14.7
5.6
1.1
8.6
46
17.4
5
1.6
11.4
0.029
0.052
0.52
0.15
0.0099
11
16
–
–
25
(rate/1000 pt yrs)
* Combined microvascular and macrovascular events
Intensive
% Decrease
(rate/1000 pt yrs)
P
Conventional
Endpoints
Reasons for Death in UKPDS Intensive Treatment Arm: 10-Year Follow-up
UKPDS Group. Lancet 1998;352:837-853.
47%
8.7%
24%
15%
3.3%
2.5%
MI or SD
Cancer
Stroke
Other
Renal
Accidents, PVD, Hypo- & Hyperglycemia
UKPDS Group. BMJ 1998;317:703-713.
Effect of Blood Pressure Control in the UKPDS Tight vs. Less Tight Control
Any diabetes-related endpoint
Diabetes-related deaths
Heart failure
Stroke
Myocardial infarction
Microvascular disease
Tight Control
1,148 Type 2 patients
Average BP lowered to 144/82 mmHg (controls: 154/87); 9-year follow-up
24
32
56
44
21
37
Risk Reduction (%)
P value
0.0046
0.019
0.0043
0.013
NS
0.0092
UKPDS: ACE Inhibitor vs. Beta-blocker for HTN Aggregate Clinical Endpoints
0.5
1
2
Relative Risk & 95% CI
Any diabetes-related endpoint
Diabetes-related deaths
All-cause mortality Myocardial infarction
Stroke
Microvascular
1.10
1.27
1.14 1.20
1.12
1.29
0.43
0.28
0.44 0.35
0.74
0.30
p
RR
UKPDS Group. BMJ 1998;317:713-720.
Favors ACE inhibitor
Favors Beta blocker
Placebo
Events / 1000 Pt-Years
Systolic Hypertension in Europe (Syst-Eur) Trial: Effect of Systolic BP Control on All Cardiovascular Events at 2 Years
Tuomilehto J et al. NEJM 1999;340: 677-684.
N=492; P=0.002
Active Rx
57.6
22.0
62%
Risk Reduction
N=4,203; P=0.02
31.4
23.5
Placebo
Active Rx
25%
Risk Reduction
Diabetic Patients
Nondiabetic Patients
Major CV Events
MI
Events / 1000 Pt-Years
Major Outcomes of the Hypertension Optimal Treatment (HOT) Trial: Diabetes Subgroup
Hansson L et al. Lancet 1998;351: 1755-1762.
CV Mortality
<90 mmHg (N=501)
<85 mmHg (N=501)
<80 mmHg (N=499)
Diastolic Target
p<0.045
p<0.016
p<0.005
<90
Events / 1000 Pt-Years
HOT Trial:Cardiovascular Events in Diabetics and Nondiabetics—Effect of Diastolic Target at 4 Years
Hansson L et al. Lancet 1998;351: 1755-1762.
Diabetic Patients n=1,501; p=0.016
<85
<80
<90
<85
<80
Nondiabetic Patients n=18,790; p=NS
24.4
18.6
11.9
9.9
10.0
9.3
48%
Risk Reduction
Completed Clinical Trials with Antihypertensive Agents in Diabetes
SHEP = Systolic Hypertension in the Elderly Program; GISSI = Grupo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico; Syst-Eur = Systolic Hypertension in Europe; HOT = Hypertension Optimal Treatment; CAPPP = Captopril Prevention Project
Curb JD et al. JAMA 1996;276:1886-1892; Zuanetti G et al. Circulation 1997;96:4239-4245; Staessen JA et al. Am J Cardiol 1998;82:20R-22R; Hansson L et al. Lancet 1998;351:1755-1762;UK Prospective Diabetes Study Group. BMJ 1998;317:703-713; Hansson L et al. Lancet 1999;353:611-616.
SHEP
GISSI-3
Syst-Eur
HOT
UKPDS
CAPPP
Results on CVD
Diabetic/Total
Trial
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