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Hypertension & Diabetes Mellitus in the Elderly รศ. นพ. ประเสริฐ อัสสันตชัย เวชศาสตร์ผู้สูงอายุ ภาควิชาเวชศาสตร์ ป้องกันและสังคม คณะแพทยศาสตร์ศิริราชพยาบาล.

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งานนำเสนอเรื่อง: "Hypertension & Diabetes Mellitus in the Elderly รศ. นพ. ประเสริฐ อัสสันตชัย เวชศาสตร์ผู้สูงอายุ ภาควิชาเวชศาสตร์ ป้องกันและสังคม คณะแพทยศาสตร์ศิริราชพยาบาล."— ใบสำเนางานนำเสนอ:

1 Hypertension & Diabetes Mellitus in the Elderly รศ. นพ. ประเสริฐ อัสสันตชัย เวชศาสตร์ผู้สูงอายุ ภาควิชาเวชศาสตร์ ป้องกันและสังคม คณะแพทยศาสตร์ศิริราชพยาบาล

2 Prevalence of chronic diseases among the Thai elderly Health System Research Institute 1998 age group > 90 Knee arthralgia Low back pain Hypertension Vision problem Diabetes mellitus Ischemic heart dis Stroke Dementia

3 Conditions related to hypertension in the Thai elderly Health System Research Institute 1999 HT (%) Normal (%) p value Dementia4.12.8< 0.05 Long term disability < Barthel Activity of daily living < 0.05

4 Chronic diseases influenced long term disability Health System Research Institute 1998 Odds ratioAR * Pop.AR ** Accident Stroke Eye disease Knee pain Hypertension * AR: attributable risk, ** Pop.AR : population attributable risk

5 Mortality rate of diseases among the Thai Elderly (per 10 5 ) Health Policy and Planning Institute yr.> 75 yr. rateYLL * rateYLL * Circulatory dis Cancer Diabetes mellitus COPD GI diseases YLL : year of life lost – number of years lost due to premature death

6 Localised myocardial infarction Atherosclerosis: A Worldwide Challenge for the 21st Century “ Cardiovascular disease accounts for 14.8 million deaths per year worldwide ”. W.H.O. report 1998 Atherosclerotic plaque rupture

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8 Atherothrombosis: Main Cause of Major Ischemic (Vascular) Events Atherothrombosis is characterized by a sudden (unpredictable) atherosclerotic plaque disruption (rupture or erosion) leading to platelet activation and thrombus formation Atherothrombosis is the underlying condition that results in events leading to myocardial infarction, ischemic stroke, and vascular death Plaque rupture 1 Plaque erosion 2 1. Falk E et al. Circulation 1995; 92: 657 – Arbustini E et al. Heart 1999; 82: 269 – 272

9 Increasing Worldwide * Prevalence of Atherothrombotic Manifestations 1 *Projected populations of people aged over 50 years, and estimated prevalence of myocardial infarction and ischemic stroke cumulated in 14 countries: Belgium, Canada, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, UK, USA 1. Guillot F, Moulard O. Circulation 1998; 98(abstr suppl 1): Populations aged > 50 year old million (  5.1% since 1997) million (  13.9% since 1997) Myocardial infarction Ischemic stroke Prevalence * million (  12.8% since 1997) 10.7 million (  32.7% since 1997) 7.1 million (  11.8% since 1997) 8.4 million (  31.6% since 1997)

10 Atherothrombosis * is the Leading Cause of Death Worldwide †1 52% 5% 12% 14% 19% 24% Atherothrombosis* Cancer Infectious Disease Pulmonary disease Violent death AIDS Mortality (%) *Cardiovascular disease, ischemic heart disease and cerebrovascular disease † Worldwide defined as Member States by WHO Region (African, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific). 1. World Health Organization. The World Health Report Geneva: WHO; 2001.

11 Atherothrombosis Will Remain the Leading Cause of Disease Burden Note:Disease burden is measured in disability-adjusted life years (DALYs), a measure that combines the impact on health of years lost due to premature death and years lived with a disability. One DALY is equivalent to one lost year of healthy life 1. Murray and Lopez. Global Burden of Disease Study Murray and Lopez. Global Burden of Disease Study The ten leading causes of disease burden in developed countries 1990 – 2020 Self-inflicted Injuries 10 Stomach cancer COPD 9Colon and rectal cancers Dementia and other CNS disorders 8 Congenital anomalies Osteoarthritis 7Lower respiratory infections Alcohol use 6 Conditions during perinatal Road traffic accidents 5 Self-inflicted injuries Trachea bronchus & lung cancers 4 Bronchus and lung cancers Unipolar major depression 3Road traffic accidents Cerebrovascular disease 2 Ischemic heart disease disease or injury 2 Rank order1990 disease or injury 1

12 Distribution of systolic pressure with age

13 Distribution of diastolic pressure with age

14 Distribution of systolic pressure with age among Thai elderly P. Assantachai. Comprehensive study of the Thai elderly. Mahidol Fund 2000 central north south northeast

15 Hypertension in the Elderly What should be concerned before diagnosis ? Why do they need treatment ? When is the best time of intervention ? What is precaution before starting treatment ? How many forms of management ? What is the most appropriate drug of choice ? How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ?

16 Special Characteristics in Geriatrics RAMPS  Reduced body reserve  Atypical presentation  Multiple pathology  Polypharmacy  Social adversity

17 What should be concerned before diagnosis of hypertension in the elderly ? Variability: white-coat (labile) hypertension Pseudohypertension: Osler manoeuvre ISH : exclude aortic insufficiency, severe anemia, hyperthyroidism, arteriovenous fistula, fever. Secondary hypertension: renal artery stenosis Associated disease : DM, dyslipidemia Personal factors : salt intake, obesity, exercise, smoking, drinking

18 White-coat vs. Sustained Hypertension in the Elderly Kario K, et al. J Am Coll Cardiol 2001;38: cases followed up 42 months: 147 (normal), 236 (white-coat), 575 (HT) Stroke occurrence: Normal: 3 (2.0%) White-coat : 5 (2.1%) HT : 54 (9.4%) Incidence of stroke : in white-coat hypertension = in normotensives = ¼ risk in sustained hypertension.

19 Isolated Systolic Hypertension-Why?

20 Secondary hypertension in the elderly Early diagnosis of HT before 30 yrs.old without family history Recent worsening of blood pressure + premature target organ damage Resistant to treatment Recent poor control without obvious reason ARF after ACEI or ARB

21 Hypertension in the Elderly What should be concerned before diagnosis ? Why do they need treatment ? When is the best time of intervention ? What is precaution before starting treatment ? How many forms of management ? What is the most appropriate drug of choice ? How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ?

22 Mulrow et al. Hypertension in the elderly. JAMA 1994, p Aust EWPHE STOP SHEP MRCOA-beta Summary yr NNT Why do they need treatment?__ 3 stages of clinical trials of hypertension in the elderly

23 Second stage of antihypertensive trial in the elderly การศึกษาโดยใช้ยาในกลุ่ม calcium channel blocker ในช่วงปี ค. ศ ได้แก่ การศึกษา STONE ( ใช้ยา nifedipine), SYST- CHINA ( ใช้ยา nitrendipine), HOT ( ใช้ยา felodipine ) และ PREVENT ( ใช้ยา amlodipine) พบว่าสามารถลดอุบัติการณ์ของโรคระบบหัวใจและ หลอดเลือดได้ถึงร้อยละ

24 Third stage of antihypertensive trial in the elderly การศึกษาโดยใช้ยาในกลุ่ม angiotensin converting enzyme inhibitor และกลุ่ม angiotensin receptor blocker (ARB) ในช่วงปี ค. ศ.2000 ถึงปัจจุบัน การศึกษา HOPE ที่ใช้ยา ramipril พบว่าสามารถลดอัตรา ตายจากโรคระบบหัวใจและหลอดเลือดได้อย่างมีนัยสำคัญ (relative risk 0.74) การศึกษา PROGRESS ที่ใช้ยา perindopril ร่วมกับ indapamide ในผู้ป่วยที่มีประวัติโรคหลอดเลือดสมอง พบว่าลดความเสี่ยงต่อการเกิดโรคหลอดเลือดสมองซ้ำได้ อย่างมีนัยสำคัญ การศึกษา SCOPE ใช้ยา candesartan ซึ่งไม่ลดอุบัติการณ์ ของโรคหลักในระบบหัวใจและหลอดเลือด แต่ลด อุบัติการณ์ของ non-fatal stroke ได้อย่างมีนัยสำคัญราว ร้อยละ 28

25 Hypertension in the Elderly What should be concerned before diagnosis ? Why do they need treatment ? When is the best time of intervention ? What is precaution before starting treatment ? How many forms of management ? What is the most appropriate drug of choice ? How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ?

26 When is the best time of intervention? How many forms of management? _Nonpharmacological salt intake In general: every  Na 100 mmol   SP 4-5 mmHg  DP 2 mmHg In elderly: every  Na 100 mmol   SP 10 mmHg In elderly with 95 percentile of BP : every  Na 100 mmol   SP 15 mmHg Law MR, et al. Br Med J 1991; 312:

27 How many forms of management? _Nonpharmacological Obesity Among the Thai elderly: Hypertensive cases   BMI,  subcutaneous fat,  percent body fat ประเสริฐ อัสสันตชัย โครงการศึกษาวิจัยครบวงจรเรื่องผู้สูงอายุ ไทย ม. มหิดล INTERSALT study  BW 10 kg.   SP 3 mmHg Dyer et al. J Hum Hypertension 1989; 3: 299.

28 How many forms of management? _Nonpharmacological Exercise Regular exercise decrease blood pressure 1.in general : 3 / 3 mmHg 2.in mild hypertensives : 6 / 7 mmHg 3.in overt hypertensives : 10 / 8 mmHg Fagard RH J Hypertension 1993; 11(Suppl.5) : S47-52.

29 Hypertension in the Elderly What should be concerned before diagnosis ? Why do they need treatment ? When is the best time of intervention ? What is precaution before starting treatment ? How many forms of management ? What is the most appropriate drug of choice ? How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ?

30 What are precautions before starting antihypertensive treatment? High prevalence of postural hypotension High prevalence of multiple pathology Polypharmacy Poor drug compliance due to inadequate knowledge Heterogeneity among the elderly

31 Hypertension in the Elderly What should be concerned before diagnosis ? Why do they need treatment ? When is the best time of intervention ? What is precaution before starting treatment ? How many forms of management ? What is the most appropriate drug of choice ? How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ?

32 diureticBBCCBACEIARBAldo. Antago AFB DM CRF CVD MI CHF BPH osteoporo sis PAD  COPD 

33 General Guidelines in Prescription for the Elderly Complete and correct diagnosis Non-pharmacological treatment first Well known pharmacokinetics and pharmacodynamics in the elderly Start low go slow Avoid polypharmacy Friendly to use New symptom may be the warning sign Check compliance regularly

34 Hypertension in the Elderly What should be concerned before diagnosis ? Why do they need treatment ? When is the best time of intervention ? What is precaution before starting treatment ? How many forms of management ? What is the most appropriate drug of choice ? How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ?

35 Study of INDANA Group Gueyffier F, et al. Lancet 1999; 353: Retrospective meta-analysis study 1670 cases aged > 80 years old 874 treated cases: 57 strokes, 34 deaths 796 controls : 77 strokes, 28 deaths Conclusion: treatment prevented 34% strokes (95% CI:8-52) major cardiovascular events ↓22% ไม่ลดอัตราตายเนื่องจากโรคในระบบหัวใจและ หลอดเลือด กลับมีอัตราตายเพิ่มขึ้นร้อยละ 14 จาก ทุกสาเหตุรวมกันในกลุ่มที่ได้รับการรักษาอย่างไม่มี นัยสำคัญทางสถิติ

36 How far should blood pressure be lowered? Is it the same between the young old elderly and the very old elderly ? Rationale A 5-year retrospective study in Finland in 561 older people aged > 85 yrs,mortality was greatest among lowest BP, and lowest among SP > 160, DP > 90 mmHg. Mattila et al. Br Med J 1988; 296: A study in California, a paradoxical increase in survival was found in men aged > 75 yrs with increasing DP. Langer et al. Br Med J 1989; 298:

37 80 years old milestone !! Antihypertensive treatment in < 80 years old :  stroke 25 – 40%  cardiac events 13 – 27%  all cardiovascular events 17 – 40% Antihypertensive treatment in > 80 years old ??

38 The Hypertension in the Very Elderly Trial (HYVET) Bulpitt CJ et al. J Hypertension 2003;21: submitted for entry = cases assigned to groups excluded 89 cases: SBP 109 antihypertensives treatment age<80 mental test score < 7 creatinine > 150 μmol/l

39 The Hypertension in the Very Elderly Trial (HYVET) Diuretic n = 426 ACE inhibitor n = 431 No treatment n = 426 died n = 30 lost n = 9 complete 386 pilot trail : March 1994 – June 1998 died n = 27 lost n = 7 complete = 397 died n = 22 lost n = 8 complete = 394

40 Treatment better Control better (RR=1.307, p=0.34) (RR=1.143, p=0.65) (RR=1.227, p=0.42) Double-blind trials (meta-analysis) (RR=1.14, p =0.05) All trails (meta-analysis) (RR=1.06, p =0.30) Total mortality HYVET-Pilot (diuretic) HYVET-Pilot (ACE) HYVET-Pilot (all active)

41 Treatment better Control better Total mortality Double-blind trials (meta-analysis) (RR=1.14, P=0.05) All trails (meta-analysis) (RR=1.06, P=0.30) HYVET-Pilot (diuretic) HYVET-Pilot (ACE) HYVET-Pilot (all active) (RR=1.307, P=0.34) (RR=1.143, P=0.65) (RR=1.227, P=0.42) Cardiovascular death Double-blind trials (meta-analysis) (RR=1.11, P=0.42) All trails (meta-analysis) (RR=1.01, P=0.93) HYVET-Pilot (diuretic) HYVET-Pilot (ACE) HYVET-Pilot (all active) (RR=1.166, P=0.62) (RR=1.087, P=0.79) (RR=1.127, P=0.66) Stroke events Double-blind trials (meta-analysis) All trails (meta-analysis) (RR=0.67, P=0.010) HYVET-Pilot (diuretic) HYVET-Pilot (ACE) HYVET-Pilot (all active) (RR=0.471, P=0.02) (RR=0.629, P=0.21) (RR=0.313, P=0.01) (RR=0.64, P=0.01)

42 HYVET-Pilot study_CONCLUSION Treatment of 1000 patients for 1 year may reduce stroke events by 19 (9 non-fatal), but may be associated with 20 extra non-stroke deaths. Each stroke saved by antiHT treatment, there was one non-stroke death.

43 HYVET_main clinical trial International trial 3,845 cases aged > 80 with SP mmHg. Indapamide SR or placebo Add-on : ACEI (perindopril mg/d.) Target BP 150 / 80 mmHg. Results:  all stroke (RR 0.59, p 0.009), relative risk reduction - 41%  all death from any cause (RR 0.76, p 0.007), relative risk reduction – 24%

44 Quality of life in Syst-Eur Trial Fletcher AE, et al. J Hypertension 2002; 20: Isolated systolic hypertension in older people 4695 cases aged > 60 yrs, SP & DP >95 mmHg. Double-blind RCT, nitrendipine+enalapril+HCTZ Target sitting SP<150 (at least 20 mmHg reduction from baseline) followed for 2 yrs. Result: 42% ↓strokes (p<.003), 26%↓cardiac events (p<.03) Quality of life:Sickness Impact Profile(SIP), Brief Assessment Index (BAI) Conclusion: active treatment was associated with some small adverse impacts on quality of life.

45 การศึกษาที่ติดตามผู้ที่มีอายุ 80 ปีขึ้นไปที่เป็นโรค ความดันเลือดสูงและได้รับยาลดความดันเลือดเป็น เวลา 5 ปี พบว่าในบรรดาผู้ที่มีระดับความดันเลือด อยู่ในเกณฑ์ที่ควบคุมได้ ผู้ที่มีระดับความดันเลือด ต่ำกว่าจะมีอัตราการรอดชีวิตที่ 5 ปี (5-year survival rate) น้อยกว่า ผู้ที่มีระดับความดันเลือดสูง กว่า Oates DJ, et al. Blood pressure and survival in the oldest old. J Am Geriatr Soc 2007 ; 55 : 383-8

46 จากการศึกษา SHEP พบว่าในกลุ่มผู้ที่มีระดับความ ดันเลือดปกติหลังได้รับการรักษา ถ้า DP ลดลงไป อีก 5 มม. ปรอทจากค่าเฉลี่ย 77 มม. ปรอท จะมี ความเสี่ยงต่อการเกิดโรคในระบบหัวใจและหลอด เลือดเพิ่มขึ้นถึงร้อยละ ปรากฏการณ์นี้ เรียกว่า J – curve ซึ่งพบใน DP มากกว่าจาก SP Somes GW, et al. The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med 1999 ; 159 : Cruickshank JM, et al. Benefits and potential harm of lowering high blood pressure. Lancet 1987; 1 :

47 Endocrine Changes in Aging _ Diabetes mellitus Physiologic changes Clinical correlation impaired glucose tolerance ↑ DM ↑ BS 5.3 mg%/10yrs after 30 years old ↑ serum insulin metabolic syndrome ↓ DHEA ↓ libido ↓free testosterone ↓ T3 sick euthyroid syndrome ↑ PTH interpretation & ↓Ca ↓ vitamin D by skin ↓ Ca absorption ↑ serum homocysteine ↑ atherosclerosis

48 Natural History of Type 2 Diabetes Glucose Relative to normal Post-prandial glucose Fasting glucose Insulin resistance Insulin level Years At risk for diabetes Beta-cell dysfunction 250 R.M. Bergenstal, International Diabetes Center mg/dL (%)

49 Changes in blood glucose levels with age Postprandial Fasting Elahi D, et al. Eur J Clin Nutr 2000; 54: S112-S120.

50 Diabetes mellitus Symptoms of DM + random blood glucose > 200 mg/dl. (8 hours) Fasting plasma glucose > 126 mg/dl Two-hour plasma glucose > 200 mg/dl NB: repeat testing on a different day

51 Diabetes mellitus Ideal goals for glycemic control normalgoalaction Preprandial 140 glucose HbA1c(%) 8

52 Diabetes Mellitus One of the most common non-communicable diseases Fourth leading cause of death in most developed countries More than 194 million people with diabetes worldwide Incidence of diabetes is increasing – estimated to rise to 333 million by 2025 To more than double in Africa, the Eastern Mediterranean and Middle East, and South-East Asia To rise by 50% in North America, 20% in Europe, 85% in South and Central Americas and 75% in the Western Pacific International Diabetes Federation website

53 The Chronic Complications of Diabetes Mellitus Macrovascular complications: Cardiovascular disease Leading cause of diabetes related deaths (increases mortality and stroke by 2 to 4 times) Microvascular complications: Retinopathy Leading cause of adult blindness Nephropathy Accounts for 44% of new cases of ESRD Neuropathy 60-70% of patients with diabetes have nervous system damage National Diabetes Statistics US 2000

54 Malmberg K et al. Circulation 2000;102: Patients with Diabetes at Similar Risk to No Diabetes with CVD: OASIS Months of follow-up Event rate (Total mortality) diabetes plus CVD (n=1448) RR 2.88 no diabetes/no CVD (n=2796) RR 1.0 no diabetes plus CVD (n=3503) RR 1.71 diabetes plus no CVD (n=569) RR 1.99 RR relative reduction

55 Survival Post-MI in Men and Women With and Without Diabetes Sprafka JM et al. Diabetes Care. 1991;14: n= Months Post-MI Men Women Survival, % Diabetes No diabetes n=228 n=1628n=568 Months Post-MI

56 Metabolic syndrome 1.Abdominal obesity (waist circumference > 90 cm. in men and > 80 cm.in women) 2.2 of 4 of the followings:  Triglyceride > 150  HDL < 40 in men, < 50 in women  Hypertension : BP > 130 / 85  Fasting blood glucose > 100 or DM case

57 NCEP ATP III: The Metabolic Syndrome <40 mg/dL (1.0 mmol/L) <50 mg/dL (1.3 mmol/L) Men Women >102 cm (>40 in) >88 cm (>35 in) Men Women  110 mg/dL (6.0 mmol/L) Fasting glucose  130/  85 mm Hg Blood pressure HDL-C  150 mg/dL (1.7 mmol/L) TG Abdominal obesity (Waist circumference) Defining LevelRisk Factor Recommends a diagnosis when 3 of these risk factors are present NCEP, Adult Treatment Panel III, JAMA 2001:285;

58 IDF Consensus Definition of the Metabolic Syndrome The new IDF definition is: Central obesity : waist circumference  94 cm for Europid men 80 for Europid women, with ethnicity specific values for other groups (for South Asians: > 90 cm. for men, > 80 cm. for women) Plus any two of the following four factors: raised TG level: 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality reduced HDL-C: <40 mg/dL (1.03 mmol/L) in males and <50 mg/dL (1.29 mmol/L) in females or specific treatment for this lipid abnormality raised blood pressure: 130/85 mmHg or treatment of previously diagnosed hypertension raised fasting plasma glucose (FPG) 100 mg/dL (5.6 mmol/L) or previously diagnosed type 2 diabetes IDF Consensus Worldwide Definition of the Metabolic Syndrome.

59 Risk of Major CHD Event Associated with High Insulin Levels in Men without Diabetes Q1 to Q5 = quintiles of area under the curve (AUC) insulin (Q1=lowest quintile; Q5=highest quintile). Years Proportion with a major CHD event Log rank: Overall P =.001 Q5 vs. Q1 P <.001 Q1 Q2 Q3 Q4 Q5 Pyörälä M et al. Circulation 1998;98:398–404.

60 ประเด็นการแนะนำอาหารสำหรับผู้ป่วย สูงอายุที่เป็นโรคเบาหวาน ปัญหาเศรษฐานะ ปัญหาการเดิน - ทำให้การออกไปจ่ายตลาดเอง ลดลง สูญเสียทักษะในการประกอบอาหารได้เอง โดยเฉพาะชายหม้าย นิสัยการรับประทานที่ติดตัวมานาน สูญเสียความสามารถทางสมอง - ทำให้ไม่สามารถ ปฏิบัติตามคำแนะนำได้ สูญเสียความสามารถในการรับรสอาหาร ภาวะท้องผูก

61 Thank You for Your Attention


ดาวน์โหลด ppt Hypertension & Diabetes Mellitus in the Elderly รศ. นพ. ประเสริฐ อัสสันตชัย เวชศาสตร์ผู้สูงอายุ ภาควิชาเวชศาสตร์ ป้องกันและสังคม คณะแพทยศาสตร์ศิริราชพยาบาล.

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