Master Class in Preventive Cardiology. The New MI Phenotype OR. Klas Malmberg MD, PhD, FESC Karolinska Institutet, Stockholm Sweden

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1 Master Class in Preventive Cardiology The New MI Phenotype OR Klas Malmberg MD, PhD, FESC Karolinska Institutet, Stockholm Sweden

2 The New MI Phenotype OR Coronary disease and glucose abnormalities Klas Malmberg MD, PhD, FESC Karolinska Institutet, Stockholm Sweden

3 Disclosure Global Medical Science Leader Hoffman La Roche, Basel

4 Myocardial Infarction in Diabetic Patients % Non-diabetics Diabetics Prevalence Diabetes: 21% Fatal Fatal Hospital One-year Reinfarction one-year Mortality (Malmberg & Rydén, Eur Heart J 9:256, 1988)

5 Early studies on glucose perturbations in patients with myocardial infarction Year Author Remark/ Proportion 1922; 1929 Levine 1931 Cruickshank 1934 Edelmann 1936 Raab & Rabinowitz 1962 Sowton Glucosuria 34 77% 1963 Reaven 1965 Cohen 1966 Wahlberg 1970 Paasikivi 1976 Opie & Stubb

6 Early studies on glucose perturbations in patients with myocardial infarction Year Author Remark/ Proportion 1922; 1929 Levine 1931 Cruickshank 1934 Edelmann 1936 Raab & Rabinowitz 1962 Sowton Glucosuria 34 77% 1963 Reaven 1965 Cohen 1966 Wahlberg 1970 Paasikivi 1976 Opie & Stubb Review: Induced by adrenergic stress?

7 Early studies on glucose perturbations in patients with myocardial infarction Year Author Remark/ Proportion 1922; 1929 Levine 1931 Cruickshank 1934 Edelmann 1936 Raab & Rabinowitz 1962 Sowton Glucosuria 34 77% 1963 Reaven 1965 Cohen 1966 Wahlberg 1970 Paasikivi 1976 Opie & Stubb Review: Induced by adrenergic stress? Is this only due to a stress epiphenomenon The GAMI study

8 GAMI Study design Patients n= 181 MI, no diabetes admission-glucose <11.1 mmol/l Controls n=185 OGTT 75 g glucose in 200 ml water Capillary blood glucose before and 120 min after glucose ingestion

9 OGTT at discharge n = 168 GAMI Results IGT 34% DM 33% NGT 33% Abnormal 67% (Norhammar, Rydén and Malmberg. Lancet. 2002;359:2140)

10 OGTT at discharge n = 168 GAMI Results OGTT at 3 months n = 145 IGT 34% DM 33% IGT 41% DM 25% NGT 33% NGT 34% Abnormal 67% Abnormal 66% (Norhammar, Rydén and Malmberg. Lancet. 2002;359:2140)

11 Patients after 3 months n = 145 GAMI Results Controls n = 185 DM 11% IGT 41% DM 25% IGT 24% NGT 34% NGT 65% Abnormal 66% Abnormal 35% (Bartnik, Malmberg and Rydén. J Intern Med. 2004; 256: 288)

12 Dysglycemia and coronary artery disease Reliability of OGTT in clinical practice OGTT at discharge OGTT at 3 months OGTT after 1 year IGT 34% DM 33% IGT 41% DM DM IGT 25% 25% 40% 25% NGT 33% NGT 34% NGT 35% Abnormal 67% Abnormal 66% Abnormal 65% (Wallander, Malmberg, Rydén et al, Diabetes Care 2008; 31:36)

13 Euro Heart Survey Diabetes and the Heart Study design Database CAD-patients from 110 centres in 25 countries Type of centre: 47% hospital cardiology wards 45% hospital based outpatient clinics 8% outpatient clinics 2-12 weeks per centre February 2003 to January 2004 (Bartnik, Malmberg, Rydén et al Europ Heart J. 2004;25:1880)

14 Euro Heart Survey Diabetes and the Heart Glucose perturbations and coronary artery disease n= % 29% NGT IFG IGT DM (new) 12% 25% 3% DM (known) (Bartnik, Malmberg, Rydén et al Europ Heart J. 2004;25:1880)

15 Euro Heart Survey Diabetes and the Heart Glucose perturbations and coronary artery disease GAMI Euro Heart Survey Diabetes and the Heart China Heart Survey

16 Dysglycemia and coronary artery disease Glucometabolic category by OGTT in patients without known perturbations 31% 34% 18% 45% 27% 36% 35% 37% 37% GAMI 1 n=164 EHS 2 n=1,920 CHS 3 n=2,263 Normoglycaemia Prediabetes Type 2 diabetes (1. Norhammar et al. Lancet. 2002;359:2140 4) (2. Bartnik et al. Eur Heart J. 2004;25: ) (3. Hu et al. Eur Heart J. 2006;27:2573 9)

17 The MI patient now and then Secular trends in the risk factor pattern 50 year old men in Gothenburg Risk factor Smoking (%) 56 Regular phys act (%) 32 Stress Body Mass Index 24.8 Waist circumference (cm) 87 S-Cholesterol (mmol/l) 6.4 S-Triglycerides (mmol/l) 1.3 Blood pressure (mmhg) 138/91 Diabetes (%) 3.6 (Wilhelmsen L et al. J Intern Med 2008;263:636) /85 6.6

18 Metabolic variables in the GAMI trial Patients with AMI and no known diabetes vs. age and sex matched controls Mmol or pmol/l Patients n=145 Controls n=185 *** *** *** 4 2 * *** 0 (Bartnik, Malmberg, Rydén et al J Int Med 2004;256:288)

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20 Incidence rate MI ( )

21 Baseline Characteristics

22 reatment at hospital admission

23 Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic coronary patients: a prospective cohort study Authors: H. Drexel et al, Austria (ESC meeting, 2010) Purpose: We aimed at identifying which lipid factors drive vascular risk in statin treated patients with coronary artery disease (CAD). Methods: We recorded vascular events over a mean period of 7.2 years in 491 consecutive statin-treated patients with angiographically proven stable CAD, covering 3518 patient-years. Results: Factor analysis in the lipid profiles of our patients revealed an HDL-related factor and an LDL-related factor. Concordant with the results for individual lipid parameters, the HDL-related factor (p = 0.001) but not the LDL-related factor (p=0.644) predicted vascular events. Patients with type 2 diabetes (T2DM; n=116) were at a higher vascular risk than nondiabetic subjects and like in the total population the HDL-related factor but not the LDL-related factor predicted vascular risk in diabetic patients. Conclusions: The pattern of low HDL cholesterol, low apolipoprotein A1, small LDL particles, and high triglycerides drives vascular risk in statin-treated coronary patients, particularly in those with T2DM.

24 Report from the FIELD-study Diabetologia 2010;53: Hazard ratios for total CVD events, baseline lipid values N=9795

25 EASD 2010

26 Dysglycemia and coronary artery disease Glucometabolic category by OGTT in patients without known perturbations 31% 18% 27% Why 34% care 45%? 36% 35% 37% 37% GAMI 1 n=164 EHS 2 n=1,920 CHS 3 n=2,263 Normoglycaemia Prediabetes Type 2 diabetes (1. Norhammar et al. Lancet. 2002;359:2140) (2. Bartnik et al. Eur Heart J. 2004;25:1880) (3. Hu et al. Eur Heart J. 2006;27:2573)

27 Probability of event free survival Cardiovascular events in the GAMI trial OGTT at discharge (n= 168) Time to Major Cardiovascular Event 1.0 IGT 34% NGT 33% DM 33% 0.9 Normal Abnormal 67% 0.8 Abnormal two-sided p = Follow-up (months) (Bartnik, Malmberg, Rydén et al Eur Heart J 2004;25:1990)

28 Survival probability Cardiovascular events in the Euro Heart Survey 1.00 Glucometabolic state 0.98 Normal IFG + IGT New DM 0.92 Log rank test p < Follow up time (days) (Lentzen, Malmberg, Rydén et al Europ Heart J 2006; 27:2969)

29 30-day Mortality adj. OD vs %-7.8% p<0.001 NS 10.0%-7.6% p<0.001

30 Event rate (%) DIGAMI 2 Death/reinfarction/stroke Suspect MI + Type 2 diabetes or B-glucose >11 mmol/l Number at risk Group 1 Group 2 Group 3 (Malmberg et al Eur Heart J 2005;26:650) 0 Group 1 vs Group 3 HR = 1.22 ( ) p = Group 1 (insulin+insulin) Group 2 (insulin+conventional) Group 3 (conventional) Years

31 Mortality (%) One year mortality in Time trends in the Swedish CCU-registry Patients <80 years Diabetes Yes No SWEDEHEART 2010

32 The MI patient now and then Secular trends in risk factor pattern; the new phenotype!!!!!!!!! Then Lean, stressed, chain-smoking CEO With hypertension, high LDL-C and STEMI

33 The MI patient now and then Secular trends in risk factor pattern; the new phenotype!!!!!!!!! Then Now Lean, stressed, chain-smoking CEO With hypertension, high LDL-C and STEMI Sedenatary, overweight labourer with the metabolic syndrome (glucose abnormalilities, T2DM, dyslipidemia, insulin resistance) and non-stemi