1. L’Ipertensione Arteriosa nel Paziente Diabetico: Nuovi Target Terapeutici Dr. Vittorio Emanuele Scalea 16.5.09

2. Linee Guida JNC 7. 2003. WHO. 2003. BHS. 2004. ESH/ESC. 2007. Australian Heart F.2008.

3. U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) National Heart, Lung, and Blood Institute National High Blood Pressure Education Program

4.  For persons over age 50, SBP is a more important than DBP as CVD risk factor.  Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range.  Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN.  Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD. New Features and Key Messages

5. Blood Pressure Classification Normal<120and<80 Prehypertension 120 – 139 or 80 – 89 Stage 1 Hypertension 140 – 159 or 90 – 99 Stage 2 Hypertension >160or>100 BP Classification SBP mmHg DBP mmHg

6. CVD Risk  HTN prevalence ~ 50 million people in the United States.  The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors.  Each increment of 20/10 mmHg doubles the risk of CVD across the entire BP range starting from 115/75 mmHg.  Prehypertension signals the need for increased education to reduce BP in order to prevent hypertension.

7. Benefits of Lowering BP Average Percent Reduction Stroke incidence 35–40% Myocardial infarction 20–25% Heart failure50%

8. Benefits of Lowering BP In stage 1 HTN and additional CVD risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

9. BP Control Rates Trends in awareness, treatment, and control of high blood pressure in adults ages 18–74 National Health and Nutrition Examination Survey, Percent II 1976–80 II (Phase 1) 1988–91 II (Phase 2) 1991–941999–2000 Awareness51736870 Treatment31555459 Control10292734 Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

10. Patient Evaluation Evaluation of patients with documented HTN has three objectives: 1.Assess lifestyle and identify other CV risk factors or concomitant disorders that affects prognosis and guides treatment. DIABETE? 2.Reveal identifiable causes of high BP. 3.Assess the presence or absence of target organ damage and CVD.

11. CVD Risk Factors  Hypertension*  Cigarette smoking  Obesity* (BMI >30 kg/m 2 )  Physical inactivity  Dyslipidemia*  Diabetes mellitus*  Microalbuminuria or estimated GFR <60 ml/min  Age (older than 55 for men, 65 for women)  Family history of premature CVD (men under age 55 or women under age 65) *Components of the metabolic syndrome.

12. Goals of Therapy  Reduce CVD and renal morbidity and mortality.  Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.  Achieve SBP goal especially in persons >50 years of age.

13. Algorithm for Treatment of Hypertension Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. With Compelling Indications Lifestyle Modifications Stage 2 Hypertension (SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Without Compelling Indications Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

14. WHO 2003

19. BHS Guidelines for the management of hypertension BHS IV, 2004 and Update of the NICE Hypertension Guideline, 2006 Guidelines for management of hypertension: report of the fourth Working Party of the British Hypertension Society, 2004 BHS IV B Williams et al: J Hum Hyp (2004); 18: 139-185. www.nice.org.uk/CG034NICEguideline www.bhsoc.org

20. BHS classification of blood pressure levels

22. Suggested target blood pressures during antihypertensive treatment. Systolic and diastolic blood pressures should both be attained, e.g. <140/85 mmHg means less than 140 mmHg for systolic blood pressure and less than 85 mmHg for diastolic blood pressure Clinic BP (mmHg) No diabetesDiabetes Optimal treated BP pressure<140/85<130/80 Audit Standard<150/90<140/80 Audit standard reflects the minimum recommended levels of blood pressure control. Despite best practice, the Audit Standard will not be achievable in all treated hypertensives. For ambulatory (mean daytime) or home blood pressure monitoring - reducing these targets by ~10/5 is recommended.

24. 2007 Guidelines for the Management of Arterial Hypertension Journal of Hypertension 2007;25:1105-1187 European Society of Hypertension European Society of Cardiology

25. <90and≥140Isolated Systolic Hypertension ≥110and/or≥180Grade 3 Hypertension 100-109and/or 160-179Grade 2 Hypertension 90-99and/or 140-159Grade 1 Hypertension 85-89and/or 130-139High Normal 80-84and/or120-129Normal <80and<120Optimal DiastolicSystolicCategory Definitions and Classification of Blood Pressure Levels (mmHg)

26. Stratification of CV risk in four categories Blood pressure (mmHg) Other risk factors, OD or disease Normal SBP 120-129 or DBP 80-84 High normal SBP 130-139 or DBP 85-89 Grade 1 HT SBP 140-159 or DBP 90-99 Grade 2 HT SBP 160-179 or DBP 100-109 Grade 3 HT SBP ≥180 or DBP ≥110 No other risk factors Average risk Average risk Low added risk Moderate added risk High added risk 1-2 risk factors Low added risk Low added risk Moderate added risk Very high added risk 3 or more risk factors, MS, OD or diabetes Moderate added risk High added risk Very high added risk Established CV or renal disease Very high added risk SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non-fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.

27. Factors influencing Prognosis Risk FactorsSubclinical Organ Damage Systolic and diastolic BP levelsElectrocardiographic LVH (Sokolow-Lyon >38 mm; Cornell >2440 mm*ms) or Levels of pulse pressure (in the elderly)Echocardiographic LVH (LVMI M≥ 125g/m ², W ≥110 g/m ² ) Age (M>55 years; W>65 years)Carotid wall thickening (IMT >0.9 mm) or plaque SmokingCarotid-femoral pulse wave velocity >12 m/sec Dyslipidaemia TC>5.0 mmol/l (190 mg/dL) or LDL-C >3.0 mmol/l (115 mg/dL) or HDL-C:M <1.0 mmol/l (40 mg/dL), W <1.2 mmol/l (46 mg/dL) or TG >1.7 mmol/l (150 mg/dL) Slight increase in plasma creatinine: M: 115-133 μmol/l (1.3-1.5 mg/dL); W: 107-124 μmol/l (1.2-1.4 mg/dL) Fasting plasma glucose 5.6-6.9 mmol/L (102-125 mg/dL) Low estimated glomerular filtration rate (<60 ml/min/1.73 m ² ) or creatinine clearance (<60 ml/min) Abnormal glucose tolerance testAnkle/Brachial BP index <0.9 Abdominal obesity (Waist circumference >102cm (M), 88cm (W)) Microalbuminuria 30-300 mg/24h or albumin-creatinine ratio: ≥22 (M), or ≥31 (W) mg/g creatinine Family history of premature CV disease (M at age <55 years, W at age <65 years)

28. Factors influencing Prognosis Diabetes MellitusEstablished CV or renal disease Fasting plasma ≥7.0 mmol/l (126 mg/dL) on repeated measurement, or Cerebrovascular disease: ischaemic stroke; cerebral haemorrhage; transient ischaemic attack Postload plasma glucose >11.0 mmol/l (198 mg/dL) Heart disease: myocardial infarction; angina; coronary revascularization; heart failure Renal disease: diabetic nephropathy; renal impairment (serum creatinine M >133, W >124 mmol/l); proteinuria (>300 mg/24 h) Peripheral artery disease Advanced retinopathy: haemorrhages or exudates, papilloedema

29. High/ Very High Risk Subjects BP ≥180 mmHg systolic and/or ≥110 mmHg diastolic Systolic BP >160 mmHg with low diastolic BP (<70 mmHg) Diabetes mellitus Metabolic syndrome ≥3 cardiovascular risk factors

30. SBPDBP Office or Clinic 14090 24-hour125-13080 Day130-13585 Night12070 Home130-13585 Blood Pressure Thresholds (mmHg) for Definition of Hypertension with Different Types of Measurement

31. Initiation of antihypertensive treatment Other risk factors, OD or disease Normal SBP 120-129 or DBP 80-84 High normal SBP 130-139 or DBP 85-89 Grade 1 HT SBP 140-159 or DBP 90-99 Grade 2 HT SBP 160-179 or DBP 100-109 Grade 3 HT SBP ≥180 or DBP ≥110 No other risk factors No BP intervention Lifestyle changes for several months then drug treatment if BP uncontrolled Lifestyle changes for several weeks then drug treatment if BP uncontrolled Lifestyle changes + immediate drug treatment 1-2 risk factorsLifestyle changes Lifestyle changes for several weeks then drug treatment if BP uncontrolled Lifestyle changes + immediate drug treatment 3 or more risk factors, MS, OD or diabetes Lifestyle changes Lifestyle changes and consider drug treatment Lifestyle changes + drug treatment Lifestyle changes + immediate drug treatment DiabetesLifestyle changes Lifestyle changes + drug treatment Established CV or renal disease Lifestyle changes + immediate drug treatment

32. Goals of Treatment In hypertensive patients, the primary goal of treatment is to achieve maximum reduction in the long-term total risk of cardiovascular disease This requires treatment of the raised BP per se as well as of all associated reversible risk factors BP should be reduces to at least below 140/90 mmHg (systolic/diastolic) and to lower values, if tolerated, in all hypertensive patients

33. Goals of Treatment Target BP should be at least <130/80 mmHg in diabetics and in high or very high risk patients, such as those with associated clinical conditions (stroke, myocardial infarction, renal dysfunction, proteinuria) Despite use of combination treatment, reducing SBP to <140 mmHg may be difficult and more so if the target is a reduction to <130 mmHg. Additional difficulties should be expected in elderly and diabetic patients and, in general, in patients with CV damage In order to more easily achieve goal BP, antihypertensive treatment should be initiated before significant cardiovascular damage develops

34. Monotherapy versus combination strategies Choose between If goal BP not achieved Previous agent at full dose Switch to different agent at low dose Previous combination at full dose Add a third drug at low dose Two-to three-drug combination at full dose Full dose monotherapy Two-three drug combination at full doses Mild BP elevation Low/moderate CV risk Conventional BP target Marked BP elevation High/very CV high risk Lower BP target Single agent at low doseTwo-drug combination at low dose

35. Thiazide diuretics ACE inhibitors β-blockers Angiotensin receptor antagonists Calcium antagonists α- blockers The preferred combinations in the general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled intervention trials Possible combinations between some classes of antihypertensive drugs

36. Antihypertensive Treatment in Diabetics Where applicable, intense non-pharmacological measures should be encouraged in all diabetic patients, with particular attention to weight loss and reduction of salt intake in type 2 diabetes Goal BP should be <130/80 mmHg and antihypertensive drug treatment may be started already when BP is in the high normal range To lower BP, all effective and well tolerated drugs can be used. A combination of two or more drugs is frequently needed Available evidence indicates that lowering BP also exerts a protective effect on appearance and progression of renal damage. Some additional protection can be obtained by the use of a blocker of the renin angiotensin system (either an angiotensin receptor antagonist or an ACE inhibitor)

37. Antihypertensive Treatment in Diabetics A blocker of the renin-angiotensin system should be a regular component of combination treatment and the one preferred when monotherapy is sufficient Microalbuminuria should prompt the use of antihypertensive drug treatment also when initial BP is in the high normal range. Blockers of the renin-angiotensin system have a pronounced antiproteinuric effect and their use should be preferred Treatment strategies should consider an intervention against all cardiovascular risk factors, including a statin Because of the greater change of postural hypotension, BP should also be measured in the erect measure

38. The Metabolic Syndrome The metabolic syndrome is characterized by the variable combination of visceral obesity and alterations in glucose metabolism, lipid metabolism and BP. It has a high prevalence in the middle age and elderly population Subjects with the metabolic syndrome also have a higher prevalence of microalbuminuria, left ventricular hypertrophy and arterial stiffness than those without the metabolic syndrome. Their cardiovascular risk is high and the chance of developing diabetes markedly increased In patients with a metabolic syndrome diagnostic procedures should include a more in-depth assessment of subclinical organ damage. Measuring ambulatory and home BP is also desirable

39. Treatment of Associated Risk Factors Lipid Lowering Agents All hypertensive patients with established cardiovascular disease or with type 2 diabetes should be considered for statin therapy aiming at serum total and LDL cholesterol levels of, respectively, <4.5 mmol/L (175 mg/dL) and <2.5 mmol/L (100 mg/dL) and lower, if possible Hypertensive patients without overt cardiovascular disease but with high cardiovascular risk ( ≥20% risk of events in 10 years) should also be considered for statin treatment even if their baseline total and LDL serum cholesterol levels are not elevated

40. Treatment of Associated Risk Factors Antiplatelet Therapy Antiplatelet therapy, in particular low-dose aspirin, should be prescribed to hypertensive patients with previous cardiovascular events, provided that there is no excessive risk of bleeding Low-dose aspirin should also be considered in hypertensive patients without a history of cardiovascular disease if older that 50 years, with a moderate increase in serum creatinine or with a high cardiovascular risk. In all these conditions, the benefit-to-risk ratio of this intervention (reduction in myocardial infraction greater than the risk of bleeding) has been proven favourable To minimize the risk of haemorrhagic stroke, antiplatelet treatment should be started after achievement of BP control

41. Treatment of Associated Risk Factors Glycaemic Control Effective glycaemic control is of great importance in patients with hypertension and diabetes In these patients dietary and drug treatment of diabetes should aim at lowering plasma fasting glucose to values ≤6 mmol/L (108 mg/dL) and at glycated haemoglobin of <6.5%

42. CONCLUSIONE Il Diabete espone ad elevato rischio CHD …

43. CVD Risk Factors  Hypertension*  Cigarette smoking  Obesity* (BMI >30 kg/m 2 )  Physical inactivity  Dyslipidemia*  Diabetes mellitus*  Microalbuminuria or estimated GFR <60 ml/min  Age (older than 55 for men, 65 for women)  Family history of premature CVD (men under age 55 or women under age 65) *Components of the metabolic syndrome.

45. High/ Very High Risk Subjects BP ≥180 mmHg systolic and/or ≥110 mmHg diastolic Systolic BP >160 mmHg with low diastolic BP (<70 mmHg) Diabetes mellitus Metabolic syndrome ≥3 cardiovascular risk factors

46. Goals

47. Goals of Therapy  Reduce CVD and renal morbidity and mortality.  Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.  Achieve SBP goal especially in persons >50 years of age.

48. Suggested target blood pressures during antihypertensive treatment. Systolic and diastolic blood pressures should both be attained, e.g. <140/85 mmHg means less than 140 mmHg for systolic blood pressure and less than 85 mmHg for diastolic blood pressure Clinic BP (mmHg) No diabetesDiabetes Optimal treated BP pressure<140/85<130/80 Audit Standard<150/90<140/80 Audit standard reflects the minimum recommended levels of blood pressure control. Despite best practice, the Audit Standard will not be achievable in all treated hypertensives. For ambulatory (mean daytime) or home blood pressure monitoring - reducing these targets by ~10/5 is recommended.

49. Goals of Treatment Target BP should be at least <130/80 mmHg in diabetics and in high or very high risk patients, such as those with associated clinical conditions (stroke, myocardial infarction, renal dysfunction, proteinuria) Despite use of combination treatment, reducing SBP to <140 mmHg may be difficult and more so if the target is a reduction to <130 mmHg. Additional difficulties should be expected in elderly and diabetic patients and, in general, in patients with CV damage In order to more easily achieve goal BP, antihypertensive treatment should be initiated before significant cardiovascular damage develops

50. CONCLUSIONE PZ Diabetico = PA <130/80 mmHg

51. PRAIA A MARE Vista da Ospedale 4 Agosto 2006 Ore 06:30 am GRAZIE