Lars Ryden, MD Stockholm, Sweden Cardio Diabetes Master Class - PowerPoint PPT Presentation

Session: Diabetes & Cardiovascular Disease: How do they relate? Diabetes: The new challenge in cardiovascular risk management Lars Ryden, MD Stockholm, Sweden Cardio Diabetes Master Class February 22-23, 2019 - Barcelona, Spain

Diabetes The new challenge in cardiovascular risk management Lars Rydén Department of Medicine, Solna Karolinska Institutet Stockholm, Sweden Barcelona February 22, 2019

Lars Rydén Declaration of interest Advisory Board AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly Speaker Lexington, MSD, Novo Nordisk, Sanofi Research Support Swedish Heart-Lung Foundation, Swedish Diabetes Foundation, Karolinska Institutet, Family E Persson ´ s Foundation, Private Foundations, Stockholm County Council, Swedish Medical Assembly, Amgen, Bayer, Boehringer Ingelheim, MSD, Novo Nordisk

Diabetes and myocardial infarction A deadly combination % Prevalence diabetes 21% 60 50 40 An early observation 30 ! - three decades ago 20 10 Died Died 0 At hospital After one year Reinfarction Mortality within one year Malmberg & Rydén Eur Heart J 9:256, 1988

Cardiovascular risk management in type 2 diabetes A paradigm shift ✓ On diabetes and cardiovascular risk ✓ The impact of target-driven management ✓ Residual risk ✓ How can we close the gap? ✓ Future necessity – a preventive approach

Diabetes and cardiovascular disease Mortality risk and years of life lost Mortality risk Estimated years of life lost due to diabetes with vs. without diabetes Vascular causes (n=820,900) Other causes Men Women 3 7 7 (diabetes vs no diabetes) Hazard ratio [95% CI] 6 6 Years of life lost Years of life lost 5 5 2 4 4 3 3 1 2 2 1 1 0 0 0 040 50 60 70 80 90 0 40 50 60 70 80 90 CV death All-cause Age (years) Age (years) mortality CI, confidence interval; CV, cardiovascular. Rao Kondapally Seshasai S et al. N Engl J Med 2011;364:829.

Perspective on reasons behind mortality Number due to diabetes, HIV/AIDS, Tbc and malaria International Diabetes Federation. IDF Diabetes Atlas – 7th Edition 2015. http://www.diabetesatlas.org. Accessed October 21, 2016.

Mortality in diabetes Causes around the world (Morrish et al Diabetologia 2001; 44:S14) Cardiovascular deaths in type 2 diabetes = 52% Cardiovascular deaths in type 2 diabetes = 52% IHD CVA Other Morrish NJ et al. Diabetologia . 2001;44 suppl 2:S14

Factors threatening global health With a focus on diabetes WHO Global Health Risks 2009 . http:// http://www.who.int/healthinfo/global_burden_disease/global_health_risks/ IDF Diabetes Atlas – 7th Edition 2015. http://www.diabetesatlas.org. Accessed October 2017.

Mortality (no) attributed to 19 risk factors By country income levels All related to and common in patients with Diabetes and/or Cardiovascular disease WHO Global Health Risks 2009

DALYs lost (%) attributed to 19 risk factors By country and income level All related to and common in patients with Diabetes and/or Cardiovascular disease WHO Global Health Risks 2009

Cardiovascular risk factor increase In people with and without diabetes 10-year CHD mortality/1,000 patient-years Diabetes 80 80 60 60 40 40 No diabetes 30 30 10 10 5 5 4 5 6 7 110 120 130 140 150 160 Systolic blood pressure (mmHg) Serum cholesterol (mmol/L) Stamler J et al. Diabetes Care 1993;16:434.

Diabetes and cardiovascular risk factors Multifactorial pattern 100% Have dysglycaemia 90% Are overweight or obese 70% Have dyslipidaemia 66% Have arterial hypertension Libby P and Plutzky J. Circulation 2002;106:2760; Bays HE et al. Int J Clin Practice 2007;61:737 Jacobs MJ et al. Diabetes Res Clin Pract 2005;70:263.

Diabetes and cardiovascular risk Principles for management Multifactorial Multifactorial CAUSE INTERVENTION

Cardiovascular risk management in type 2 diabetes A paradigm shift ✓ On diabetes and cardiovascular risk ✓ The impact of target-driven management ✓ Residual risk ✓ How can we close the gap? ✓ Future necessity – a preventive approach

Target-driven management European guidelines Antiplatelet therapy Glycaemic control (HbA 1c ) Patients with CVD In general <7.0% ASA 75 – 160 mg/day Individual basis <6.5% – 6.9% Best practice Blood pressure control Lipid control (LDL-C) <140/85 mmHg Very high risk <1.8 mmol/L High risk <2.5 mmol/L or – 50% Nephropathy: SBP <130 mmHg Lifestyle modification ASA, acetylsalicylic acid; CVD, cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure. Rydén L et al. Eur Heart J 2013;34:3035.

Importance of risk factor control in type 2 diabetes Trial data - the STENO 2 study Survival free from heart failure or myocardial infarction Intensive therapy Conventional therapy Patients Diabetes + microalbuminuria Treatment Intensive n=80 Conventional n=80 Trial design PROBE 7.8 years Observational +13.4 years . Oellgaard et al. Diabetologia 2018; 61:1724

Importance of risk factor control in type 2 diabetes Population data - Swedish National Diabetes Register • Patients with T2D From Swedish National Diabetes Register (no = 271,174) • Controls from the population Matched for age, sex and county (no = 1,355,870) • Assessed According to age and risk-factor control HbA 1c , blood pressure,, albuminuria, smoking & LDL-cholesterol • Follow-up Median 5.7 years • Trends in Death, AMI, stroke and heart failure hospitalisation AMI, acute myocardial infarction; LDL, low-density lipoprotein. Rawshani A et al. N Engl J Med 2018;379:633.

Importance of risk factor control in type 2 diabetes From the Swedish National Diabetes Register Excess mortality in relation to range of risk factor control Adj Hazard Ratio 1 2 3 4 6 8 Adj Hazard Ratio 1 2 3 4 6 8 AMI, acute myocardial infarction; LDL, low-density lipoprotein. Rawshani A et al. N Engl J Med 2018;379:633.

Importance of risk factor control in type 2 diabetes Population data - Swedish National Diabetes Register Excess AMI in relation to range Excess stroke in relation to Mortality MI Stroke Heart failure of risk factor control range of risk factor control Control ≥80 yr Reference Reference Reference Reference ≥65 to <80 yr Reference Reference Reference Reference ≥55 to <65 yr Reference Reference Reference Reference <55 yr Reference Reference Reference Reference No risk factors ≥80 yr 0.99 [0.84; 1.17] 0.72 [0.49; 1.07] 0.95 [0.74; 1.22] 1.12 [0.89; 1.41] Conclusion ≥65 to <80 yr 1.01 [0.92; 1.12] 0.80 [0.69; 0.93] 0.90 [0.76; 1.06] 1.42 [1.28; 1.58] ≥55 to <65 yr 1.15 [1.00; 1.34] 0.93 [0.73; 1.18] 0.94 [0.72; 1.23] 1.61 [1.31; 1.97] <55 yr 1.29 [0.94; 1.77] 0.91 [0.62; 1.35] 1.22 [0.70; 2.13] 2.40 [1.63; 3.54] 1 risk factor ≥80 yr 0.94 [0.88; 1.00] 1.05 [0.93; 1.19] 1.06 [0.95; 1.18] 1.17 [1.08; 1.27] Considerable risk reduction with ≥65 to <80 yr 1.05 [1.02; 1.09] 1.05 [0.97; 1.14] 1.11 [1.04; 1.18] 1.46 [1.39; 1.53] ≥55 to <65 yr 1.23 [1.16; 1.31] 1.14 [1.04; 1.25] 1.27 [1.14; 1.41] 1.80 [1.63; 1.98] <55 yr 1.56 [1.34; 1.81] 1.46 [1.26; 1.69] 1.55 [1.23; 1.95] 2.37 [1.99; 2.82] 2 risk factors ≥80 yr 0.99 [0.94; 1.04] 1.38 [1.27; 1.49] 1.13 [1.04; 1.24] 1.23 [1.15; 1.32] combined risk-factor control ≥65 to <80 yr 1.17 [1.13; 1.20] 1.44 [1.39; 1.50] 1.32 [1.26; 1.38] 1.62 [1.56; 1.68] ≥55 to <65 yr 1.32 [1.27; 1.38] 1.54 [1.44; 1.65] 1.59 [1.50; 1.69] 2.11 [1.98; 2.26] <55 yr 1.68 [1.56; 1.80] 2.08 [1.90; 2.27] 2.04 [1.76; 2.36] 2.71 [2.40; 3.05] 3 risk factors ≥80 yr 1.13 [1.06; 1.21] 1.78 [1.60; 1.98] 1.35 [1.21; 1.51] 1.42 [1.31; 1.54] ≥65 to <80 yr 1.46 [1.42; 1.50] 2.11 [2.02; 2.20] 1.73 [1.65; 1.82] 2.01 [1.92; 2.10] ≥55 to <65 yr 1.63 [1.55; 1.71] 2.16 [2.02; 2.31] 2.13 [2.01; 2.27] 2.82 [2.63; 3.02] <55 yr 2.21 [2.05; 2.37] 3.02 [2.80; 3.27] 2.78 [2.46; 3.16] 3.93 [3.50; 4.42] 4 risk factors ≥80 yr 1.47 [1.28; 1.70] 2.32 [1.78; 3.01] 1.54 [1.12; 2.11] 1.81 [1.42; 2.30] ≥65 to <80 yr 2.10 [1.96; 2.26] 2.87 [2.62; 3.14] 2.31 [2.09; 2.55] 2.88 [2.64; 3.14] ≥55 to <65 yr 2.53 [2.37; 2.70] 3.32 [3.02; 3.66] 2.66 [2.30; 3.08] 3.85 [3.47; 4.26] <55 yr 2.80 [2.51; 3.13] 4.56 [4.01; 5.18] 3.34 [2.72; 4.10] 5.70 [4.84; 6.71] 5 risk factors ≥80 yr 1.39 [0.51; 3.80] 3.19 [1.23; 8.28] 2.65 [0.96; 7.30] 2.76 [0.82; 9.25] ≥65 to <80 yr 3.10 [2.53; 3.80] 4.60 [3.37; 6.29] 3.54 [2.36; 5.31] 3.93 [2.75; 5.60] ≥55 to <65 yr 3.88 [3.07; 4.92] 4.84 [3.78; 6.21] 2.79 [1.88; 4.14] 6.54 [4.85; 8.81] <55 yr 4.99 [3.43; 7.27] 7.69 [5.02; 11.77] 6.23 [3.22; 12.05] 11.35 [7.16; 18.01] 0 2 4 6 8 0 5 10 0 5 10 15 0 5 10 15 20 Rawshani A et al. N Engl J Med 2018;379:633. Hazard ratio [95% CI]

Cardiovascular risk management in type 2 diabetes A paradigm shift ✓ On diabetes and cardiovascular risk ✓ The impact of target-driven management ✓ Residual risk ✓ How can we close the gap? ✓ Future necessity – a preventive approach

Residual risk after myocardial infarction One-year mortality in Sweden 1995 - 2016 x 35 Diabetes 1988 30 25 x 1-year mortality (%) 20 15 10 No diabetes 5 0 Swedeheart annual report 2017