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Hypertension & Diabetes Mellitus in the Elderly

Hypertension & Diabetes Mellitus in the Elderly. รศ.นพ. ประเสริฐ อัสสันตชัย เวชศาสตร์ผู้สูงอายุ ภาควิชาเวชศาสตร์ป้องกันและสังคม คณะแพทยศาสตร์ศิริราชพยาบาล. Prevalence of chronic diseases among the Thai elderly Health System Research Institute 1998.

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Hypertension & Diabetes Mellitus in the Elderly

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

  2. Prevalence of chronic diseases among the Thai elderlyHealth System Research Institute 1998

  3. Conditions related to hypertension in the Thai elderlyHealth System Research Institute 1999

  4. Chronic diseases influenced long term disabilityHealth System Research Institute 1998 * AR: attributable risk , ** Pop.AR : population attributable risk

  5. Mortality rate of diseases among the Thai Elderly (per 105)Health Policy and Planning Institute 2000 YLL : year of life lost – number of years lost due to premature death

  6. 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 Localised myocardial infarction

  7. 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 erosion2 Plaque rupture1 1. Falk E et al. Circulation 1995; 92: 657–71. 2. Arbustini E et al. Heart 1999; 82: 269–272

  8. Increasing Worldwide* Prevalence of Atherothrombotic Manifestations1 Prevalence*2000 2005 205.0 million (5.1% since 1997) 222.2 million (13.9% since 1997) Populations aged > 50 year old 9.1 million (12.8% since 1997) 10.7 million (32.7% since 1997) Myocardial infarction 7.1 million (11.8% since 1997) 8.4 million (31.6% since 1997) Ischemic stroke *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): 1421.

  9. Atherothrombosis* is the Leading Cause of Death Worldwide†1 Atherothrombosis* 52% Cancer 24% Infectious Disease 19% Pulmonary disease 14% 12% Violent death AIDS 5% 0 10 20 30 40 50 60 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 2001. Geneva: WHO; 2001.

  10. Atherothrombosis Will Remain the Leading Cause of Disease Burden The ten leading causes of disease burden in developed countries 1990–2020 2020 disease or injury2 1990 disease or injury1 Rank order Ischemic heart disease Ischemic heart disease 1 Cerebrovascular disease Cerebrovascular disease 2 Unipolar major depression Road traffic accidents 3 Trachea bronchus & lung cancers Bronchus and lung cancers 4 Road traffic accidents Self-inflicted injuries 5 Alcohol use 6 Conditions during perinatal Osteoarthritis Lower respiratory infections 7 Dementia and other CNS disorders Congenital anomalies 8 COPD Colon and rectal cancers 9 Self-inflicted Injuries Stomach cancer 10 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. 1996 2. Murray and Lopez. Global Burden of Disease Study. 1997

  11. Distribution of systolic pressure with age

  12. Distribution of diastolic pressure with age

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

  14. 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 ?

  15. Special Characteristics in Geriatrics RAMPS • Reduced body reserve • Atypical presentation • Multiple pathology • Polypharmacy • Social adversity

  16. 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

  17. White-coat vs. Sustained Hypertension in the ElderlyKario K, et al. J Am Coll Cardiol 2001;38: 238-45. • 958 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.

  18. Isolated Systolic Hypertension-Why?

  19. 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

  20. 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 ?

  21. Why do they need treatment?__ 3 stages of clinical trials of hypertension in the elderly Mulrow et al. Hypertension in the elderly. JAMA 1994, p.1932-8. 5-yr NNT Aust EWPHE 16 14 37 52 STOP SHEP MRCOA-beta Summary

  22. Second stage of antihypertensive trial in the elderly • การศึกษาโดยใช้ยาในกลุ่ม calcium channel blocker ในช่วงปี ค.ศ. 1996 - 2000 ได้แก่ การศึกษา STONE (ใช้ยา nifedipine), SYST-CHINA (ใช้ยา nitrendipine), HOT (ใช้ยา felodipine ) และ PREVENT (ใช้ยา amlodipine) • พบว่าสามารถลดอุบัติการณ์ของโรคระบบหัวใจและหลอดเลือดได้ถึงร้อยละ 37 - 60

  23. Third stage of antihypertensive trial in the elderly • การศึกษาโดยใช้ยาในกลุ่ม angiotensin converting enzyme inhibitor และกลุ่มangiotensin receptor blocker (ARB) ในช่วงปี ค.ศ.2000 ถึงปัจจุบัน • การศึกษา HOPE ที่ใช้ยา ramipril พบว่าสามารถลดอัตราตายจากโรคระบบหัวใจและหลอดเลือดได้อย่างมีนัยสำคัญ (relative risk 0.74) • การศึกษา PROGRESS ที่ใช้ยา perindopril ร่วมกับ indapamide ในผู้ป่วยที่มีประวัติโรคหลอดเลือดสมอง พบว่าลดความเสี่ยงต่อการเกิดโรคหลอดเลือดสมองซ้ำได้อย่างมีนัยสำคัญ • การศึกษา SCOPE ใช้ยา candesartan ซึ่งไม่ลดอุบัติการณ์ของโรคหลักในระบบหัวใจและหลอดเลือด แต่ลดอุบัติการณ์ของ non-fatal stroke ได้อย่างมีนัยสำคัญราวร้อยละ 28

  24. 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 ?

  25. 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: 811-5.

  26. How many forms of management? _Nonpharmacological • Obesity • Among the Thai elderly: Hypertensive cases   BMI,  subcutaneous fat,  percentbody fat ประเสริฐ อัสสันตชัย โครงการศึกษาวิจัยครบวงจรเรื่องผู้สูงอายุไทย ม.มหิดล 2542. • INTERSALT study  BW 10 kg.   SP 3 mmHg Dyer et al. J Hum Hypertension 1989; 3: 299.

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

  28. 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 ?

  29. 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

  30. 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 ?

  31. 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

  32. 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 ?

  33. Study of INDANA GroupGueyffier F, et al. Lancet 1999; 353:793-6. • 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% • ไม่ลดอัตราตายเนื่องจากโรคในระบบหัวใจและหลอดเลือด กลับมีอัตราตายเพิ่มขึ้นร้อยละ 14 จากทุกสาเหตุรวมกันในกลุ่มที่ได้รับการรักษาอย่างไม่มีนัยสำคัญทางสถิติ

  34. 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; 296:887-9. • 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; 298:1356-8.

  35. 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??

  36. The Hypertension in the Very Elderly Trial (HYVET) Bulpitt CJ et al. J Hypertension 2003;21:2409-17. submitted for entry = 1372 • excluded 89 cases: • SBP< 160, DBP<90 & >109 • antihypertensives treatment • age<80 • mental test score < 7 • creatinine > 150 μmol/l 1283 cases assigned to groups

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

  38. Treatment better Control better 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 Total mortality Double-blind trials (meta-analysis) (RR=1.14, p =0.05) All trails (meta-analysis) (RR=1.06, p =0.30) (RR=1.307, p=0.34) HYVET-Pilot (diuretic) (RR=1.143, p=0.65) HYVET-Pilot (ACE) (RR=1.227, p=0.42) HYVET-Pilot (all active)

  39. Control better Treatment better 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 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=0.64, P=0.01) (RR=0.313, P=0.01) (RR=0.629, P=0.21) (RR=0.471, P=0.02)

  40. 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.

  41. HYVET_main clinical trial • International trial • 3,845 cases aged > 80 with SP 160-199 mmHg. • Indapamide SR or placebo • Add-on : ACEI (perindopril 2 - 4 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%

  42. Quality of life in Syst-Eur TrialFletcher AE, et al. J Hypertension 2002; 20: 2069-79. • Isolated systolic hypertension in older people • 4695 cases aged > 60 yrs, SP 160-219 & 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.

  43. การศึกษาที่ติดตามผู้ที่มีอายุ 80 ปีขึ้นไปที่เป็นโรคความดันเลือดสูงและได้รับยาลดความดันเลือดเป็นเวลา 5 ปี พบว่าในบรรดาผู้ที่มีระดับความดันเลือดอยู่ในเกณฑ์ที่ควบคุมได้ ผู้ที่มีระดับความดันเลือดต่ำกว่าจะมีอัตราการรอดชีวิตที่ 5 ปี (5-year survival rate) น้อยกว่า ผู้ที่มีระดับความดันเลือดสูงกว่า Oates DJ, et al. Blood pressure and survival in the oldest old. J Am Geriatr Soc 2007 ; 55 : 383-8

  44. จากการศึกษา SHEP พบว่าในกลุ่มผู้ที่มีระดับความดันเลือดปกติหลังได้รับการรักษา ถ้า DP ลดลงไปอีก 5 มม.ปรอทจากค่าเฉลี่ย 77 มม.ปรอท จะมีความเสี่ยงต่อการเกิดโรคในระบบหัวใจและหลอดเลือดเพิ่มขึ้นถึงร้อยละ 11 - 14 ปรากฏการณ์นี้เรียกว่า 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 :2004-9. Cruickshank JM, et al. Benefits and potential harm of lowering high blood pressure. Lancet 1987; 1 : 581-4.

  45. Endocrine Changes in Aging _ Diabetes mellitus Physiologic changesClinical 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

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

  47. 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

  48. Diabetes mellitus Ideal goals for glycemic control normal goal action • Preprandial <100 80-120 <80, >140 glucose • HbA1c(%) < 6 < 7 > 8

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