1. 38ο Πανελλήνιο Επετειακό Καρδιολογικό Συνέδριο 19-21 Οκτωβρίου 2017
Σακχαρώδης διαβήτης και καρδιά
Διερεύνηση του ασυμπτωματικού διαβητικού ασθενή για στεφανιαία νόσο.
Πότε και πώς
Ιωάννης Σκουλαρίγκης, MD, FACC, FESC

2. Conflict of Interest
None
Σύγκρουση συμφερόντων

3. Screening for CAD in asymptomatic diabetic patients:
What tests, or sequence of tests, should be considered?
Exercise treadmill test
Myocardial perfusion imaging/Stress echo
Coronary computed tomography angiography/CAC score
1 and 3
None
Ποιο από τα κατωτέρω ενδείκνυται στην διερεύνηση του ασυμπτωματικού διαβητικού ασθενούς?
Δοκιμασία κόπωσης
Σπινθηρογράφημα μυοκαρδίου/stress echo
Αξονική στεφανιογραφία/CAC score
1 και 3
Κανένα

5. Correct answer:
5. None

6. Asymptomatic coronary artery disease and silent ischemia are frequently observed in diabetic patients.
The prevalence of silent ischemia ranges from 10% to 69% in diabetic patients, compared with 5% to 35% in patients without diabetes.
Almost one-third of myocardial infarctions in patients with diabetes are not associated with chest pain.
The underlying mechanisms explaining the presence of silent ischemia in patients with diabetes include differences in pain threshold sensitivity and autonomic neuropathy.
Symptoms of easy fatigability, atypical thoracic discomfort or exertional dyspnea can sometimes be the only factors suggesting the presence of coronary artery disease.

7. Lancet 2010;375:

8. Treating CV risk factors in DM pts as aggressively as in non-DM pts with prior MI
Our data suggest that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as nondiabetic patients with previous myocardial infarction. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in nondiabetic patients with prior myocardial infarction.
A small subgroup of diabetic patients be considered at moderate risk.
This subgroup includes diabetic patients who are of young age, have short duration of diabetes, have no other risk factors for vascular disease and have no complications of diabetes.

9. CAD Morphology in Diabetes

10. Patterns of CAD in Diabetes
Atherosclerotic coronary lesions of diabetic patients are more extensive than those in nondiabetic populations.
Diabetic atherosclerotic coronary lesions are often associated with negative coronary remodeling —seen as longer stenotic lesions and smaller diameter vessels on coronary angiography.
Diabetes is also be associated with impaired regulation of the microcirculation, which could exacerbate myocardial ischemia and lead to ischemic cardiomyopathy.
Comorbidities such as renal insufficiency and peripheral and cerebral
vascular disease are more prevalent in patients with DM than in those without, and can lead to worse outcomes.
Kip, et al. Circulation 1996;94: 1818–1825
Brener, et al. Circulation 2004; 109: 2290–2295
Briguori, et al. J Am Coll Cardiol 2005; 45: 464–5

12. On availability of diagnostic modalities
The justification for screening asymptomatic patients with DM using noninvasive testing depends primarily:
On whether the detection of coronary artery disease would result in therapeutic strategies that would reduce cardiac morbidity or mortality
On cost effectiveness
On availability of diagnostic modalities
Justification=αιτιολογηση
At the present time, screening for silent ischemia in asymptomatic patients is controversial, mainly because of the absence of evidence of clinical benefit.

13. Screening or No Screening
for CAD in Diabetes?

14. The present data address only the prevalence, severity, and predictors of silent ischemia at the time of enrollment in the DIAD study.

15. SMI= silent myocardial ischemia, The majority of asymptomatic patients with type 2 diabetes demonstrated resolution of ischemia upon repeat stress imaging after 3 years.
Of the initial 522 DIAD patients, 358 had repeat stress imaging (DIAD-2), of whom 71 (20%) had ischemia at enrollment (DIAD-1). Of 287 patients with normal DIAD-1 studies, 259 (90%) remained normal in DIAD-2, whereas 28 (10%) developed new ischemia in DIAD-2. Of the 71 patients with abnormal DIAD-1 studies, 56 (79%) demonstrated resolution of ischemia, whereas 15 (21%) remained abnormal. During this 3-year interval, medical treatment was intensified, with more patients using statins, aspirin, and ACE inhibitors than at baseline. Patients with resolution of ischemia had significantly greater increases in these medications than patients who developed new ischemia (P < 0.04).

19. Non-perfusion abnormalities: Ischemic electrocardiographic changes, transient LV dilation, baseline LV dysfunction.
Figure B shows cardiac events in the screening group, which varied significantly according to the results of stress MPI (log-rank, 14.93; P=.005). Four hundred nine participants (78%) had normal test results and 50 (10%) had small MPI defects. Only 8 (2%) of 409 participants with normal MPI results and 1 (2%) of 50 participants with small MPI defects had hard cardiac events, in contrast to 4 (12.1%) of 33 with moderate or large MPI defects (HR, 6.3; 95 CI, ; P=.001). In addition, 2 (6.7%) of 30 participants with non-perfusion abnormalities had cardiac events (HR, 3.5; 95% CI, ; P=.08). The mean (SD) MPI defect size was 4.1% (6.6%) of left ventricle in participants with cardiac events and 1.4% (2.2%) of left ventricle in participants without events (P=.12). The negative predictive value of having a normal MPI was 98% (401 of 409). The positive predictive value was only 6% (7 of 113) of patients for any MPI abnormality and 12% (4 of 33) of patients for moderate or large MPI defects.

20. The use of statins, angiotensin-converting enzyme inhibitors, antihypertensive and antihyperglycemic medications, and aspirin for primary medical prevention increased significantly from baseline to 5 years later in the study. However, the increased use of these medications was not different in screened and not-screened patients.
The favorable cardiac outcomes among participants in the DIAD study likely reflect, in part, the impact of aggressive, guideline-driven management of cardiac risk factors, which is known to improve outcomes in patients
with type 2 diabetes.

22. MPS done in all pts with CAC >100 AU (n=127) and in some (n=53, randomly selected) with CAC <100 AU.

23. higher incidence of inducible ischemia in patients with higher calcium scores.
Event-free survival during an average follow-up of years by Cox proportional Hazards model. Survival curves according to the extent of coronary calcification (A) and myocardial perfusion abnormalities (B)

24. In a similar fashion, superior predictive value of CAC as compared to FRS as well UKPDS scoring was observed among asymptomatic type 2 diabetic individuals.
ROC analysis comparing the value of Framingham risk function, UKPDS risk engine, and the CAC score for predicting cardiovascular events.

25. FU: median 4 years
The PREDICT Study is a prospective cohort study designed to evaluate coronary artery calcification score (CACS) as a predictor of cardiovascular events in type 2 diabetes (T2DM).
A total of 589 patients with no history of CV disease and with established T2DM had CACS measured. Participants were followed for a median of 4 years and first CHD and stroke events were identified as primary endpoints.
We have shown that CACS is highly predictive of CV endpoints in patients with T2DM with no history of CVD in a prospective study specifically designed to test this possibility. The risk of sustaining an endpoint increased with increasing category of CACS. Furthermore, CACS had greater predictive value for endpoints than a broad range of conventional and novel risk factors, and added to the predictive power of the Framingham or UKPDS risk scores.

26. FU: mean yrs
Standard therapy:
HBA1c <7.0%
LDL-C <100mg/dL
SBP <130mmHg
Aggressive therapy:
HBA1c <6.0%
LDL-C <70mg/dL
SBP <120mmHg

27. Among asymptomatic patients with type 1 or type 2 diabetes, use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization at 4 years. These findings do not support CCTA screening in this population.
Significant improvements in both blood pressure and lipid panel targets were achieved among those recommended for aggressive risk factor reduction, whereas no interval changes occurred with assignment to standard therapy.

28. Screening = No Screening
Why?

29. Intensive therapy: HBA1c <6.5% TChol <175mg/dL TGs <150mg/dl
SBP <130mmHg
DBP <80mmHg
Panel A shows mean (±SE) values for selected risk factors during the interventional part of the study for all patients (solid lines) and during the follow-up period (dashed lines). In the conventional-therapy group, mean values were obtained at baseline, at 3.8 years, at 7.8 years, and at 13.3 years. At these intervals, the total numbers of patients in both study groups were 160, 149, 130, and 93, respectively.

32. Among 2,287 patients with stable angina, many of whom had multivessel or proximal left anterior descending coronary artery disease, intensive medical treatment was as effective as percutaneous intervention combined
with intensive medical treatment in preventing overall mortality or myocardial infarction. Results were similar in the approximate one-third of subjects with diabetes.
Optimal=αριστη

33. As an initial management strategy in patients with SCAD, PCI did not reduce the risk of death, MI, or other major CV events when added to OMT.

34. There was no significant interaction (P<0
There was no significant interaction (P<0.01) between treatment effect and any predefined subgroup variable. Of note, among patients with multivessel CAD, previous MI, and diabetes, the rate of the primary end point was similar for both groups. When subgroup variables were included in a multivariate analysis, the hazard ratio for treatment was essentially unchanged (1.09; 95% CI, 0.90 to 1.33; P = 0.77).

35. Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision.

36. There was no significant difference in rates of survival between the revascularization group and the medical-therapy group (Panel A) and between the insulin-sensitization group and the insulin-provision group (Panel B). The rates of major CV events (death, MI, or stroke) also did not differ significantly between the revascularization group and the medical-therapy group (Panel C) or between the insulin-sensitization group and the insulin-provision group (Panel D).

37. There was no significant difference in rates of survival between the revascularization group and the medical-therapy group among patients who were selected for the PCI stratum (Panel A) or among those who were selected for the CABG stratum (Panel B). The rates of freedom from major CV events (death, MI, or stroke) also did not differ significantly between the revascularization group and the medical-therapy group among patients in the PCI stratum (Panel C), but the rates were significantly better among patients in the revascularization group than in the medical-therapy group within the CABG stratum (Panel D).

39. Conclusions

40. Patients with T2DM without symptoms to suggest CAD, receiving contemporary medical care, and close follow-up have relatively favorable outcomes in the current era.
Routine screening for inducible ischemia in asymptomatic patients with T2DM cannot be advocated for 4 reasons.
Low detecting yield
Low cardiac event rate
No effect on outcome
Expensive
First, the yield of detecting significant inducible ischemia is relatively low.
Second, the overall cardiac event rate is low. Indeed, even our participants with moderate or large defects and the highest event rate would be conventionally assigned to an intermediate risk category.
Third, routine screening does not appear to affect overall outcome.
Finally, routine screening of millions of asymptomatic diabetic patients would be prohibitively expensive.
The potential of routine screening to alter treatment and to prevent cardiac events in persons without clinically apparent CAD is largely unknown.

42. ADA - STANDARDS OF MEDICAL CARE IN DIABETES — 2017
Recommendations for Screening:
In asymptomatic patients, routine screening for coronary artery disease is not recommended as it does not improve outcomes as long as atherosclerotic cardiovascular disease risk factors are treated. (A)
Consider investigations for coronary artery disease in the presence of any of the following:
atypical cardiac symptoms (e.g., unexplained dyspnea, chest discomfort)
signs or symptoms of associated vascular disease including carotid bruits, transient ischemic attack, stroke, claudication, or peripheral arterial disease
electrocardiogram abnormalities (e.g., Q waves). (E)
(A): Clear evidence from well-conducted, generalizable RCTs that are adequately powered
(E): Expert consensus or clinical experience

44. Cardiovascular disease in DM
Highly prevalent (half of all CV deaths)
Represent, at least, one quarter of all referrals for coronary revascularisation
Higher mortality regardless of treatment strategy
More aggressive expression of atherosclerosis:
Early development
Diffuse
Progressive
Restenosis
Thrombosis
Impaired collateralisation

45. Diabetes is accompanied by more extensive atherosclerosis and inadequate compensatory remodeling. Accelerated plaque progression, despite use of medical therapies, supports the need to develop new antiatherosclerotic strategies in diabetic patients.

46. 10-year primary risk of ASCVD (atherosclerotic cardiovascular disease) among patients without pre-existing cardiovascular disease who are between 40 and 79 years of age. Patients are considered to be at "elevated" risk if the Pooled Cohort Equations predicted risk is ≥ 7.5%. In many ways, the Pooled Cohort Equations have been proposed to replace the Framingham Risk 10-year CVD calculation, which was recommended for use in the NCEP ATP III guidelines for high blood cholesterol in adults.
Current guidelines for the treatment of cholesterol to reduce cardiovascular risk recommend that the following four groups of patients will benefit from moderate- or high-intensity statin therapy:
Individuals with clinical ASCVD
Individuals with primary elevations of LDL ≥ 190 mg/dL
Individuals 40 to 75 years of age with diabetes and an LDL 70 to 189 mg/dL without clinical ASCVD
Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL 70 to 189 mg/dL and a 10-year ASCVD risk of 7.5% or higher