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 November 16 - 17, 2018 - Dubai, UAE
Diabetes - The new challenge in cardiovascular risk management Lars Rydén Department of Medicine, Solna Karolinska Institutet Stockholm, Sweden Dubai November 16-17, 2018
Diabetes The new challenge in cardiovascular risk manangement ✓ Diabetes and cardiovascular risk ✓ The impact of target-driven management ✓ Residual risk ✓ Closing the gap
Diabetes The new challenge in cardiovascular risk manangement ✓ Diabetes and cardiovascular risk ✓ The impact of target-driven management ✓ Residual risk ✓ Closing the gap
Global mortality attributed to 19 risk factors By country income levels All related to and common in patients with diabetes WHO Global Health Risks 2009
Diabetes and cardiovascular disease Early observations % Prevalence diabetes 21% 60 50 Deadly 40 30 combination! 20 10 Died Died 0 At hospital After one year Reinfarction Mortality within one year Malmberg & Rydén Eur Heart J 9:256, 1988
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.
Diabetes and cardiovascular disease Mortality risk and years of life lost Estimated years of life lost Men due to diabetes 0 Difference in life expectancy 2 • Patients with T2D 4 From Scottish Care Info – Diabetes database Years (95% CI) 6 no = 272,597 • Controls from the population Most deprived ------------- Least deprived Stratified for socioeconomic status no = 2,750 000 0 • Assessed 2 Age specific life expectancy 4 In people 40 – 89 years 6 • Period 2012-2014 Women Midpoint of age Walker et al. Diabetes Care 2018;61:108
Cardiovascular risk factors Relation in people with and without diabetes 10-year CHD mortality/1,000 patient-years 80 80 Diabetes 60 60 No diabetes 40 40 30 30 10 10 5 5 4 5 6 7 110 120 130 140 150 160 Systolic blood pressure (mmHg) Serum cholesterol (mmol/L) CHD, coronary heart disease. 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
Diabetes The new challenge in cardiovascular risk manangement ✓ Diabetes and cardiovascular risk ✓ The impact of target-driven management ✓ Residual risk ✓ Closing the gap
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.
Target-driven management On the importance of lifestyle modification Patients 179 Age (average; years) 62 Diagnosis Type 2 diabetes Instruction to increase physical activity Walking Analyses Time walking/week Follow-up (years) 2 Di Loreto C et al. Diabetes Ca re 2005;28:1295.
Target-driven management On the importance of lifestyle modification Walking hours/week 0 1,5 4 5,5 7,5 12 Body weight, kg - 3.0 + 0.8 + 0.1 - 2.2 - 3.0 - 3.2 + 0.8 + 0.6 + 0.6 + 0.1 - 2.2 - 3.2 Waist circ., cm + 1.0 + 1.0 - 0.9 - 3.8 - 5.5 - 5.5 - 7.1 + 1.0 + 1.0 - 0.9 - 3.8 - 7.1 45 min/day HbA 1c , % - 0.44 - 0.44 - 1.11 - 1.11 - 1.19 - 1.19 + 0.03 + 0.03 - 0.06 - 0.06 - 0.88 - 0.88 Variable HbA 1c ‒ 0.88% RRsys, mmHg - 6.6 - 1.8 - 1.8 - 1.5 - 1.5 - 6.4 - 6.4 - 5.5 - 6.6 - 9.2 - 9.2 - 5.5 RRdia, mmHg - 5.3 - 4.6 - 4.6 - 2.4 - 2.4 - 2.9 - 2.9 - 4.8 - 4.8 - 5.3 - 7.1 - 7.1 Chol, mg/dl - 3.8 - 10.2 - 10.7 - 7.4 - 10.9 - 3.8 - 5.6 - 5.6 - 10.2 - 10.7 - 7.4 - 10.9 LDL-Chol, mg/dl - 6.3 - 6.3 - 4.5 - 4.5 - 7.1 - 7.1 - 3.4 - 3.4 - 5.3 - 5.3 - 7.7 - 7.7 HDL-Chol, mg/dl + 0.1 + 1.1 + 2.9 + 2.9 + 5.6 + 10.4 + 10.4 + 6.3 + 6.3 + 0.1 + 1.1 + 5.6 TG, mg/dl + 3.4 + 3.4 - 48.2 - 48.2 - 55.2 - 55.2 - 57.4 - 57.4 - 68.4 - 68.4 + 2.1 + 2.1 CHD risk % - 4.8 - 4.8 + 0.1 + 0.1 - 0.3 - 0.3 - 2.6 - 2.6 - 3.7 - 3.7 - 4.3 - 4.3 p<0.05 p value refers to change vs basal. CHD, coronary heart disease; Chol, cholesterol; circ, circumference; HDL-Chol, high-density lipoprotein cholesterol; LDL-Chol, low-density lipoprotein cholesterol; RRdia, diastolic blood pressure; RRsys, systolic blood pressure; TG, triglyceride. Di Loreto C et al. Diabetes Care 2005;28:1295.
EUROASPIRE IV Actual management by diabetes state Germany 38% 12% 50% Bosnia Herzegovina 20% 31% 49% Netherlands 44% 14% 42% Finland 54% 13% 33% Poland 62% 9% 29% France 56% 15% 29% Croatia 58% 15% 27% Belgium 61% 14% 26% Cyprus 68% 7% 25% Ukraine 64% 12% 24% Latvia 71% 7% 22% Czech Rep. 72% 7% 22% Bulgaria 74% 6% 21% Serbia 68% 14% 19% Greece 65% 17% 19% Sweden 68% 14% 19% UK 71% 12% 18% Overall activity level Romania 65% 19% 16% (mean proportion of patients) Spain 69% 16% 15% Russian Fed. 62% 24% 14% Slovenia 75% 12% 13% Low activity (62%) Ireland 79% 8% 13% Lithuania 81% 11% 9% Moderate activity (14%) Turkey 96% 9% 5% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% High activity (25%) Proportion of coronary patients reporting low, moderate and high physical activity Gyberg et al Cardiovasc Diabetology 2015; 14:133
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
Multifactorial target-driven management Prognostic importance of different risk factors UKPDS score in the intensive arm of STENO 2 HbA 1c 13% Total cholesterol Lipids 48% 73% SBP HDL 11% cholesterol 25% Smoking 3% HDL, high-density lipoprotein; SBP, systolic blood pressure; UKPDS, United Kingdom Prospective Diabetes Study. Gaede P and Pedersen O. Diabetes . 2004;53 (Suppl 1):S39.
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; CI, confidence interval; yr, year. Rawshani A et al. N Engl J Med 2018;379:633.
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