Optimizing risk assessment of total cardiovascular risk What are the tools? Lars Rydén Professor Karolinska Institutet Stockholm, Sweden

Cardiovascular Disease Prevention (CVD) Three Strategies for CVD Prevention Population High Risk Secondary Primary Population distribution of cardiovascular (CV) risk Proportion Low risk: Covering most of those falling ill High risk: Covering a few at high risk falling ill 10-year risk WHO Technical Report Series 678, Geneva, 1982

Impact of CVD: Prevention vs Treatment 0-10 Smoking Blood pressure Proportionate reduction -20-30 -40-50 -60 Observed Mortality Enhanced by therapeutic success Cholesterol Predicted by the three factors combined -70 1975 1980 1985 1990 Vartiainen et al. BMJ 1994;309:445

Impact of CVD: Prevention vs Treatment Treatment and Prevention: Estimated Reduction of Coronary Heart Disease (CHD) Mortality The Netherlands Scotland, UK Finland Ireland England & Wales 0 50 100 % Treatment Prevention Unexplained Bots 1996; Capewell 1999; Unal 2004; Laatikainen 2005

European Guidelines for CVD Prevention vs Treatment 1994 First Joint Task Force recommendations 1998 Second Joint Task Force recommendations 2003 Third Joint Task Force guidelines 2007 Fourth Joint Task Force guidelines

Assessment of CV Risk Classic and Emerging Methods ID of (vulnerable) plaques MR/MSCRT Case history Length/weight Blood pressure 12-lead ECG Stress test Lab examinations Lipids Glucose ECG, echocardiogram.

The Concept of Total Risk Assessment Cornerstone in European Guidelines for CVD Prevention Since 1994 CVD is multifactorial in origin Risk factors interact synergistically Physicians see people, not isolated risk factors Pyörälä K et al. Atherosclerosis. 1994;110:121-161.

CVD Risk Continuum 10-year CHD mortality (per/10 3 ) Rate Relative Risk (RR) for CVD mortality WHO border for diabetes 80 60 40 30 10 Diabetic Nondiabetic RR 3.0 2.5 2.0 1.5 5 4 5 6 7 Serum cholesterol (mmol/l) 1.0 4 6 8 10 2-h plasma glucose (mmol/l) 12 Stamler et al. Diabetes Care. 1993;16:434-444. Coutinho et al. Diabetes Care.1999;22:233-240.

Consider Total CV Risk CVD Risk Continuum Family history Metabolic syndrome Ethnicity Obesity DM Prediabetes Age and sex Smoking Hyper- lipidemia Hypertension Physical inactivity Need for prevention of CVD

A Need to Adapt Prevention to Total Individual Cardiovascular Risk Randomized trials show that statins cause a RR reduction of 30% (applied to 2 different risk patterns) Total CV risk 10 years Variable 1 10 Adj RR (%) 0.3 3 NNT (n) 333 33

Assessment of Total CV Risk General rule Total CV risk is high or very high in subjects with: Established CVD DM Markedly elevated single risk factors - Total cholesterol 8 mmol/l, LDL cholesterol 6 mmol/l -SBP 180 mm Hg and/or DBP 110 mm Hg Pronounced family history of CVD at young age In all other subjects, total CV risk should be estimated with a risk score model. LDL, low-density lipoprotein; SBP, systolic blood pressure; DBP, diastolic BP. De Backer et al. Eur Heart J. 2003;24:1601-1610.

Assessment of Total CV Risk Framingham Heart Disease Risk Calculator Kannel WB, McGee D, Gordon T A general cardiovascular risk profile: the Framingham Study Am J Cardiol.1976;38:46

Assessment of Total CV Risk Framingham Heart Disease Risk Calculator Step 1: Age Years Points 20-34 9 35-39 4 40-44 0 45-49 3 50-54 6 55-59 8 60-64 10 65-69 11 70-74 12 75-79 13 Step 2: Total Cholesterol TC Points (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 0 200-239 7 5 3 1 0 240-279 9 6 4 2 1 >280 11 8 5 3 1 Step 5: Smoking Status Points at Age 20-39 40-49 50-59 60-69 70-79 Nonsmoker 0 0 0 0 0 Smoker 8 5 3 1 1 Characteristics A rather small US population for fatal/nonfatal CHD includes: Sex and age Total & HDL cholesterol Smoking Systolic blood pressure Step 3: HDL-C HDL-C (mg/dl) Points >60 1 50-59 0 40-49 1 <40 2 Step 6: Adding Points Category: Points Age Total-C HDL-C SBP Smoking status Point Total: HDL, high-density lipoprotein. NCEP guidelines. JAMA. 2001;285:2486-2497. Step 4: Systolic Blood Pressure SBP Points mm Hg Untreated Treated <120 0 0 120-129 0 1 130-139 1 2 140-159 1 2 >160 2 3 Step 7: CHD Risk Point Total 10-Year Risk <0 <1% 0 1% 1 1% 2 1% 3 1% 4 1% 5 2% 6 2% 7 3% 8 4% 9 5% 10 6% 11 8% 12 10% 13 12% 14 16% 15 20% 16 25% >17 >30%

Assessment of Total CV Risk Framingham Heart Disease Risk Calculator: Online Access http://www.nhlbi.nih.gov Highest risk: >20% or a history of heart disease or DM High risk: 10%-20% and 2 risk factors Moderate risk: <10% and 2 risk factors Low risk: 1 risk factor

Assessment of Total CV Risk Systematic Coronary Risk Evaluation (SCORE) European Cohort Studies (n = 12) Some with multiple sub-studies Mainly population based Some figures: About 250,000 people Follow-up 3 million person years Cardiovascular fatalities >7000 Conroy et al. Eur Heart J. 2003;24:987-1003.

Assessment of Total CV Risk Systematic Coronary Risk Evaluation (SCORE) 10-year risk of fatal CVD in population at high risk 10-year risk of fatal CVD in populations at low risk A 10-year risk of CVD death >5% considered as a high or at least increased risk Conroy et al. Eur Heart J. 2003;24:987-1003.

Assessment of Total CV Risk Systematic Coronary Risk Evaluation (SCORE) Indication of RR 55-year-old male in a low-risk population Conroy et al. Eur Heart J. 2003;24:987-1003.

Assessment of Total CV Risk Prospective Cardiovascular Münster Risk Calculator (PROCAM) Observed CV events and 10-year risk for coronary events according to the PROCAM risk calculator Observed events per 100 subjects Calculated 10-year coronary event risk 50 Morbidity/mortality N = 20,000 1979-1985 16-65 years 40 30 20 10 0 High risk = 10-year event rate >20% Corresponds to a PROCAM score = 53 40 30 20 10 0 Assmann G et al. Eur Heart J. 2005;26:2120-2126.

Assessment of Total CV Risk Prospective Cardiovascular Münster Risk Calculator (PROCAM) www.chd-taskforce.com Characteristics include: Sex Age LDL & HDL cholesterol Triglycerides Smoking DM Family history Assmann G et al. Eur Heart J. 2005;26:2081-2082.

Diabetes, Prediabetes and Cardiovascular Risk Volume 28 Number 1 January 2007 Rydén L et al. Eur Heart J. 2007;28:88-136. http://www.escardio.org/knowledge/guidelines/guidelines_list.htm

Type 2 diabetes and coronary heart disease 7-Year Incidence of Fatal/Nonfatal MI (East West Study) 7-Year Incidence Rate of MI 50 45 40 35 30 25 20 15 10 5 0 MI = myocardial infarction *These patients had no prior MI at baseline. Nondiabetic Diabetic n = 1373 n = 1059 P <.001 P <.001 4% No prior MI* 19% 20% MI No prior MI* 45% MI Haffner SM et al. N Engl J Med. 1998;339:229-234.

Diabetes, Prediabetes and Cardiovascular risk Prediabetes 3.2 DM 4.2 RR for CAD 5 4 3 2 Men 1.8 Women 2.6 1 0 Chicago NHANES Metaanalysis NHS N = 117,629 CAD, coronary artery disease; NHANES, National Health and Nutrition Examination Survey; NHS, Nurses Health Study. Lee WL et al. Diabetes Care. 2000;23:962-968; Hu et al. Diabetes Care. 2002;25:1129-1134.

Diagnostic Criteria for DM, IFG, and IGT Fasting Glucose (mmol/l) 6.9 5.6 8.5 7.5 6.5 5.5 4.5 IFG Normal glucose IFG + IGT IGT 7.8 11.1 2-h Postload Glucose (mmol/l) DM 3.5 2.5 4.5 6.5 8.5 10.5 12.5 14.5 IFG = Impaired fasting glucose IGT = Impaired glucose tolerance American Diabetes Association. Diabetes Care. 2003;26(suppl 1):S5-S20.

Prevalence of Diabetes and Prediabetes in Patients with Coronary Artery Disease Patients with CAD 31% 32% Known DM New DM IGT 12% 3% 22% NGR Isolated IFG Euro Heart Survey Diabetes and the Heart IGT, impaired glucose tolerance; IFG, impaired fasting glucose; NGR, normal glucose regulation. Bartnik et al. Eur Heart J. 2004;25:1880.

Assessment of the Risk for Diabetes FINDRISC Finnish Diabetes Risk Score (FINDRISC) to address 10-year risk of type 2 DM (T2DM) in adults Available at: www.diabetes.fi/english

Assessment of Total Cardiovascular Risk Risk Engine According to United Kingdom Prospective Diabetes Study (UKPDS) For Diabetic Patients Available at: www.dtu.ox.ac.uk/index.php?maindoc=/riskengine/

Conclusions Prevention of CVD should be based on total CV risk rather than be split on primary and secondary prevention CVD Risk Continuum Risk calculators, such as the SCORE and UKPDS, help in Ethnicity assessing total CV Family risk Age and sex history Obesity DM is an independent risk factor for CVD Metabolic DM Smoking syndrome Prediabetes The risk of CV events increases dramatically with concomitant risk factors Hyper- lipidemia Hypertension Physical inactivity Need for prevention of cardiovascular disease

Assessment of Total Cardiovascular Risk Risk Engine According to United Kingdom Prospective Diabetes Study (UKPDS) Case example

Patient 1 Background 1 Background 45-year-old sedentary, nonsmoking female No family history of heart disease T2DM for approximately 4 years No signs of CVD Lifestyle counseling ( eat less, walk more ) for the past 2 years HbA1c 7.8% and metformin HCl was added Examinations Weight 78 kg (172 lb), height 165 cm (5 5 ) Body mass index (BMI) 28.6 kg/m 2 (obese: 30 kg/m 2 ) Blood pressure (BP) 125/80 mm Hg

Patient 1 Background 2 Laboratory findings HbA1c 7.8% F-plasma glucose 7.8 mmol/l (139 mg/dl) S-creatinine 102 mmol/l (1.2 mg/dl) Total cholesterol 4.8 mmol/l (185 mg/dl) Triglycerides 1.5 mmol/l (135 mg/dl) HDL cholesterol 0.9 mmol/l (38 mg/dl) LDL cholesterol 2.7 mmol/l (105 mg/dl) Current medications (mg/day) Metformin 1000 Aspirin 81 Atorvastatin 10

Patient 1 Question 1 How does this patient s history of DM affect her risk of future CV events? 1. Decreases 2. Increases 3. Will not affect her CV risk 4. I am uncertain

Patient 1 Question 2 This patient has DM but minimal additional CHD risk factors. What would you estimate the risk for myocardial infarction (MI) in the next 10 years according to the PROCAM risk calculator? 1. 0-5 % 2. 6-10 % 3. 11-15 % 4. 16-20 % 5. >21%

Optimizing risk assessment of total cardiovascular risk What are the tools? Thanks for the attention!!