Controversies in hypertension, About Diabetes diabetes and and metabolic Cardiovascular syndrome Risk ESC annual congress August 29, 2011 The target blood pressure in patients with diabetes is <130 mm Hg Pro Lars Rydén Karolinska Institutet Stockholm, Sweden
Diabetes Lars Rydén and the Heart Karolinska Institutet Stockholm Meet the experts Sweden Disclosures August 30 2009 Research grants The Swedish Heart Lung Foundation The Swedish Medical Research Council AFA Insurance Queen Victoria's and King Gustav V Research Fund Karolinska Institutet Stockholm County Council Sanofi-aventis Astrazeneca Hoffman-LaRoche Honoraria for advisory boards, steering committees, lectures DSMB positions (RELY-ABLE; RED-HF) Exec Steering Committees (ACE; ORIGIN; ALECARDIO; REWIND) Lectures by various Swedish organizations Lectures by various commercial companies
The target blood presssure in patients with diabetes is <130 mm Hg Guideline recommendations On the background to these recommendations Epidemiological information Myocardial involvement Blood pressure lowering treatment Conclusion
The target blood presssure in patients with diabetes is <130 mm Hg Guideline recommendations
Guideline recommendations Variable Treatment target (Chobanian et al JAMA 2003; 289: 2560)
Guideline recommendations Variable Treatment target (Graham et al Eur Heart J 2007; 28: 2375)
Guideline recommendations Variable Treatment target (Mancia et al Eur Heart J 2007; 28: 1462)
Guideline recommendations Variable Lifestyle modification Smoking cessation BP Treatment target Structured education Obligatory <130 / 80 mm Hg Renal dysf <125/75 HbA1c (DCCT standard) 6.5% mmol/l mg/dl Venous plasma glucose <6.0 108 Cholesterol <4.5 175 LDL <1.8 70 HDL male >1.0; female >1.2 40; 76 Triglycerides <1.7 150 (Rydén, Standl et al Eur Heart J 2007; 28: 88)
Guideline recommendations Variable Treatment target American Diabetes Association B C Supporting evidence from well-conducted cohort studies Supporting evidence from poorly controlled or uncontrolled trials Conflicting evidence with the weight of evidence supporting the recommendation (ADA Diabetes Care; 34: Suppl 1 January 2011)
The target blood presssure in patients with diabetes is <130 mm Hg Guideline recommendations On the background to these recommendations Epidemiological information
Epidemiological considerations Hypertension and diabetes co-exist too often to be a play of chance Hypertension in patients with diabetes 70 90% Diabetes in patients with hypertension 20 50% (Rydén et al Blood Pressure 2008; 17: 250)
Epidemiological considerations Hypertension and diabetes co-exist too often to be a play of chance People with either hypertension or type 2 diabetes are at an increased risk for premature cardiovascular morbidity/mortality The presence of both conditions increases this risk 2 4 times Blood pressure and hyperglycemia are continuous variables (Rydén et al Blood Pressure 2008; 17: 250)
Hypertension, Diabetes and Cardiovascular Risk About Diabetes and Cardiovascular Risk 10-year CHD mortality/10 000 person years Rate 250 All patients RR=1.9 200 150 Patients with diabetes RR=3.2 RR=2.8 RR=2.0 100 50 RR=4.4 RR=3.4 0 <120 120-139 140-159 160-179 180-199 >200 Systolic blood pressure (mm Hg) (Stamler et al. Diabetes Care. 1993;16:434)
The target blood presssure in patients with diabetes is <130 mm Hg Guideline recommendations On the background to these recommendations Epidemiological information Myocardial involvement
Myocardial involvement in diabetes Possible interactions with high blood pressure Structural abnormalities Myocyte hypertrophy Deposition of PAS-positive glycoproteins Interstitial edema Extracellular matrix accumulation Myocyte loss and interstitial fibrosis Intramyocardial microangiopathy Not specific for patients with diabetes (Shehadeh & Regan Clin Card 1995; 18:301; Hardin Cor Artery Disease 1996; 7:99)
Diabetes mellitus and hypertension Effects on left ventricular structure and function The STRONG Heart Study American Indians n= 4 549 Without diabetes or hypertension 1 025 With diabetes only 642 With hypertension only 614 With diabetes and hypertension 874 Method Echocardiography (Bella et al Am J Card 2001:87;1260)
Diabetes mellitus and hypertension Effects on left ventricular structure and function The STRONG Heart Study % 40 30 20 Proportion with left ventricular hypertrophy Gender specific criteria LV mass/height (g/m 2 ) 19 29 38 10 12 0 No HTN or DM DM HTN HTN and DM (Bella et al Am J Card 2001:87;1260)
Diabetes mellitus and hypertension Effects on left ventricular structure and function The STRONG Heart Study % 16 Proportion with subnormal left ventricular function 18 12 8 4 Stress corrected LV midwall shortening (%) 7 10 11 0 No HTN or DM DM HTN HTN and DM (Bella et al Am J Card 2001:87;1260)
Diabetes mellitus and hypertension Effects on left ventricular structure and function The STRONG Heart Study Conclusions Diabetes associated with increased LV mass independent of and additive to hypertension related to impaired LV systolic function independent of age, gender, BMI and heart rate Insulin resistance a possible common link (Bella et al Am J Card 2001:87;1260)
The target blood presssure in patients with diabetes is <130 mm Hg Guideline recommendations On the background to these recommendations Epidemiological information Myocardial involvement Blood pressure lowering treatment
Antihypertensive treatment in patients with diabetes Overview of different drugs Conclusions These overviews showed that the effect on major cardiovascular events of BP-lowering regimens studied were broadly comparable for patients with and without diabetes (Arch Intern Med 2005:165;1410)
Antihypertensive treatment in patients with diabetes Systolic Hypertension in the Elderly Program (SHEP) Patients 4 149 without & 583 with type 2 diabetes Randomised treatment Chlortalidone + atenolol/reserpine Placebo & any prescription Follow up 5 years Mortality, stroke & MI Trial design (Curb et al JAMA 1996; 276: 1886)
Events no Antihypertensive treatment in patients with diabetes Systolic Hypertension in the Elderly Program (SHEP) Major cardiovascular events during follow up 40 30 Active Placebo 20 10 0 (Curb et al JAMA 1996; 276: 1886) Diabetes No diabetes Saved/1000 101 51
Antihypertensive treatment in patients with diabetes Hypertension Optimal Treatment (HOT) Patients 17 289 without & 1 501 with type 2 diabetes Treatment Felodipine + ACE-inhib or betablocker Target diastolic pressure 80; 85; 90 Follow up 3.8 years (3.3-4.9) Trial design (Hansson et al Lancet 1998; 351:1755I)
Event rate/ 1000 patient years Antihypertensive treatment in patients with diabetes Hypertension Optimal Treatment (HOT) Nonfatal/fatal MI and stroke & all CV events 30 20 10 All patients Patients with diabetes -51% 0 80 85 <90 Diastolic blood pressure (mm Hg) (Hansson et al Lancet 1998; 351:1755I)
Antihypertensive treatment in patients with diabetes UKPDS Trial design Patients 1 148 with type 2 diabetes and hypertension Randomised treatment Tight BP control (758) - mean 144/82 Less tight BP control (390) - mean 154/87 Follow up 8.4 years Diabetes related fatal and non-fatal events (UKPDS 38 Brit Med J 1998; 317: 703)
Antihypertensive treatment in patients with diabetes UKPDS Proportion with any fatal or non-fatal diabetes related end-point Proportion dying of diabetes related causes RR 24%; p=0.0046 RR 32%; p=0.019 (UKPDS 38 Brit Med J 1998; 317: 703)
Antihypertensive treatment in patients with diabetes UKPDS Association between systolic blood pressure and macro- and microvascular complications of type 2 diabetes Lowest risk with systolic BP 120 mm Hg No indication of a threshold (Adler et al Brit Med J 2000; 321: 412)
Antihypertensive treatment in patients with diabetes ADVANCE Patients 11 140 with type 2 diabetes Randomised treatment in addition to ongoing therapy Perindopril + Indapamide Placebo Trial design Follow up 4.3 years Composite major macro- and microvascular events (Patel et al Lancet 2007; 370: 829)
Antihypertensive treatment in patients with diabetes ADVANCE Impact on blood pressure To be noted 5.6 mm Hg (95%CI 5.2-6.0) Entry BP (mm Hg) Mean 145/81 Syst <140 47% Diast <90 41% 2.2 mm Hg (95%CI 2.0-62.4) (Patel et al Lancet 2007; 370: 829)
Cumulative mortality (%) Antihypertensive treatment in patients with diabetes ADVANCE Impact of study drug on all cause mortality HR 0.86 (95%CI 0.75-0.98); p=0.025 Follow up (months) (Patel et al Lancet 2007; 370: 829)
Antihypertensive treatment in patients with diabetes ACCORD Trial design Patients 4 733 with type 2 diabetes Randomised treatment in addition to ongoing therapy Intensive syst BP <120 mm Hg Standard syst BP <140 mm Hg Follow up 4.7 years Composite CV death or non-fatal MI or stroke (ACCORD Study group New Engl J Med 2010; 362: 1575)
Antihypertensive treatment in patients with diabetes ACCORD Blood pressure control (ACCORD Study group New Engl J Med 2010; 362: 1575)
Antihypertensive treatment in patients with diabetes ACCORD Outcome Primary outcome Nonfatal stroke Side effects % Intensive group 3.3 Standard group 1.3 Nonfatal Myocardial Infarction Cardiovascular death Caveats Low event rate No adjudication Open label design Treatment ad hoc (ACCORD Study group New Engl J Med 2010; 362: 1575)
Blood pressure targets by guidelines and CV events Experiences from ONTARGET Trial design Patients 19 631 with CVD or diabetes with end organ damage Randomised treatment in addition to ongoing therapy Telmisartan 80 mg Ramipril 10 mg Combination of the two Follow up 4.6 years Mortality, CV events and hospitalisation for CHF) (Mancia Rydén et al Circulation 2011; In press)
(%) (%) Blood pressure targets by guidelines and CV events Experiences from ONTARGET Baseline SBP 130 mmhg by proportion of visits with BP <130/80 mmhg 20 15 10 5 Proportion of visits BP <130/80 mmhg < 25% 0 8 Death, MI, Stroke or CHF (hosp) Death, MI or Stroke CV death 25 to < 50% 50 to < 75% 4 75% 0 MI CHF (hosp) Stroke (Mancia Rydén et al Circulation 2011; In press)
The target blood presssure in patients with diabetes is <130 mm Hg Guideline recommendations On the background to these recommendations Epidemiological information Myocardial involvement Blood pressure lowering treatment Conclusion
The target blood presssure in patients with diabetes is <130 mm Hg Concluding remarks on blood pressure management in patients with diabetes Check blood pressure regularly Grand conclusion Treat intensively TRUST Combine several drugs THE GUIDELINES Target <130/80 mm Hg and use common sense Individualise the approach
Controversies in hypertension, About Diabetes diabetes and and metabolic Cardiovascular syndrome Risk ESC annual congress August 29, 2011 The target blood pressure in patients with diabetes is <130 mm Hg Rebuttal Lars Rydén Karolinska Institutet Stockholm, Sweden
Multifactorial Intervention in type 2 Diabetes Euro Heart Survey Diabetes and the Heart Patients from all day practice 110 centers in 25 countries n= 4 961 Coronary artery disease with or without diabetes Evidence based medicine The combined use of β-blockade, RAA-inhibition, antiplatelets and statins if not contraindicated One year follow up by management (Anselmino et al Europ J Cardiovasc Prev Rehab 2008;15:216)
Cumulative survival Multifactorial Intervention in type 2 Diabetes Euro Heart Survey Diabetes and the Heart Impact of Evidence Based Medicine (EBM) on 1-year mortality 1,00 0,99 0,98 0,97 0,96 0,95 0,94 0,93 0,92 0,91 0 100 200 300 400 Time of follow up (days) No DM EBM + No DM EBM - DM EBM + DM EBM - (Anselmino et al Europ J Cardiovasc Prev Rehab 2008;15:216)
Multifactorial Intervention in type 2 Diabetes The Steno 2 study Outcome total mortality after 13 years Cumulative incidence of death (%) Numbers at risk Conventional Intensive 70 Number 60 Log-rank of P=0.015 patients needed to treat for 13 years to avoid one... 50 40 30 20 10 Death 5 Cardiovascular death 8 Major cardiovascular event 3 Progression to nephropathy 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Years of follow-up 80 80 80 78 77 75 (Gaede et al New Engl J Med 2008; 358: 580 ) 69 72 63 65 51 62 43 57 30 39 Conventional Intensive
Multifactorial Intervention in type 2 Diabetes Actual contribution of individual risk factors in improving the UKPDS score in STENO 2 intensive arm HbA1c 13% Lipids 73% Total cholesterol 48% SBP 11% HDL cholesterol 25% Smoking 3% (Gaede et al Diabetes 2004; 53: S39)
Patient management in Clinical Practice Euro Heart Survey Diabetes and the Heart Elective consultation 2 854 (58%) Diabetes 860 (30%) No diabetes 1 994 (70%) (Anselmino et al Europ J Cardiovasc Prev Rehab 2007;14:28)
Patient management in Clinical Practice Euro Heart Survey Diabetes and the Heart Variable Target Outside Target Outside n = pat no 98-03 % 2007 % Blood lipids (mmol/l) n=589 Cholesterol <5.0 53 n=532 LDL <3.0 57 n=559 HDL >1.0 37 n=585triglycerides <2.0 39 Blood pressure (mm Hg) n=746 <140/90 27 FP-glucose (mmol/l) n=573 <7.2 54 HbA1c (%) n=397 <7.0 23 (Anselmino et al Europ J Cardiovasc Prev Rehab 2008;15:216)
Euro Heart Survey Diabetes and the Heart Variable Target Outside Target Outside n = pat no 98-03 % 2007 % Blood lipids (mmol/l) n=589 Cholesterol <5.0 53 <4.5 68 n=532 LDL <3.0 57 1.8 93 n=559 HDL A considerable >1.0 37 >1.0 37 n=585triglycerides <2.0 39 1.7 57 Blood pressure (mm (mm Hg) Hg) n=746 <140/90 27 <130/80 56 FP-glucose (mmol/l) n=573 <7.2 54 <6.0 83 HbA1c (%) Patient management in Clinical Practice improvement potential n=397 <7.0 23 <6.5 32 (Anselmino and Rydén. Data on file)
Controversies in hypertension, About Diabetes diabetes and and metabolic Cardiovascular syndrome Risk ESC annual congress August 29, 2011 The target blood pressure in patients with diabetes is <130 mm Hg Thanks for the attention!!!
Diabetes mellitus and hypertension Effects on left ventricular structure and function The STRONG Heart Study Parameter Population No DM/HT DM HT DM+HT American indians n= 4 549 Age (years) 58 8 58 7 62 9 61 8 No diabetes or hypertension 1 025 Females (%) Diabetes only 61 70 58 65 642 BMI Hypertension (kg/m 2 ) only 30 6 32 6 31 6 33 6 614 BPsyst Diabetes (mmhg) and 118 12 Hypertension 120 12 142 21 143 21 874 BPdiast Method (mmhg) 72 8 71 8 79 8 78 11 BP Echocardiography therapy (%) 0 0 62 73 (Bella et al Am J Card 2001:87;1260)
Antihypertensive treatment in patients with diabetes UKPDS Proportion of patients requiring 0, 1, 2 or 3 blood pressure lowering drugs during follow up (UKPDS 38 Brit Med J 1998; 317: 703)
Antihypertensive treatment in patients with diabetes UKPDS Long term follow up after tight BP control Mean BP for patients assigned to tight or less tight control 10 years from the end of the study 1997 Hazard Ratios for any diabetes related end-point 10 years from the end of study 1997 (Holman et al New Engl J Med 2008; 359: 1565)