1. Hypertension in the Elderly ACCF/AHA 2011 Expert Consensus Document Developed in collaboration with the American Academy of Neurology, Association of Black Cardiologists, American Geriatrics Society, American Society of Hypertension, American Society of Nephrology, American Society for Preventive Cardiology, and the European Society of Hypertension

2. Hypertension in the Elderly Ten Things You Need to Know: 1.There is a dramatic increase in HTN prevalence with aging; by age 70 yrs, the majority of people have HTN 2.In older adults, HTN is characterized by an elevated SBP with normal or low DBP, due to age-associated stiffening of large arteries. 3.HTN is a potent risk factor for CVD in the elderly. 4.Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients 60-79 yrs old with anti-HTN drug therapy though the effect on all- cause mortality has been modest. 5.Although increases in the treatment and control of BP in older hypertensive adults have occurred over the past 2 decades, BP control rates remain suboptimal in the elderly.

3. Ten Things You Need to Know 6. Non-pharmacologic lifestyle measures should be encouraged in older adults, both to retard development of HTN and as adjunctive therapy in those with HTN. 7.Although the specific BP at which antihypertensive therapy should be initiated in the elderly is unclear, a threshold of 140/90 mm Hg in persons 65-79 yrs and a threshold SBP of 150 mm Hg in people age ≥80 yrs is reasonable. 8.Diuretics, ACEI, angiotensin receptor blockers, calcium antagonists, and beta blockers have all shown benefit on CV outcomes in randomized trials among elderly cohorts: choice is dictated by efficacy, tolerability, comorbidities, and cost. 9.Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated. 10.The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects.

4. Hypertension in the Elderly 1. There is a dramatic increase in the prevalence of hypertension with aging; by age 70 years, the majority of people have hypertension.

5. Without treatment, approximately 30% of adults in the U.S. have hypertension (HTN). 1 HTN prevalence increases markedly with age: 2 -by 60 years, ~60% have HTN -by 70 years, ~65% of men and ~75% of women have HTN -most prevalent in older African American women In Framingham Study, HTN eventually developed in >90% of subjects with normal BP at age 55 years. 3 1 Ong Hypertension 2007;49:69-75 2 Burt Hypertension 1995;25:305-313 3 Vasan N Engl J Med 2001;345:1291-1297 Epidemiology of Hypertension and Aging

6. Prevalence of High Blood Pressure in Adults by Age and Sex: NHANES 2005-2006 9 NHLBI.

7. Population Projections by Selected Age Groups and Sex for the United States: (in 1000’s) U.S. Census Bureau, 2008

8. Mean Blood Pressure According to Age, Sex and Ethnic Group in U.S. Adults Chobanian N Engl J Med. 2007;357:789-96

9. Hypertension in the Elderly 2. In older adults, hypertension is characterized by an elevated systolic blood pressure (BP) with normal or low diastolic BP, due to age- associated stiffening of the large arteries.

10. Joint Influences of SBP and Pulse Pressure on Coronary Heart Disease Adapted from Franklin Circulation 1999;100:354-60

11. Pathophysiology of Hypertension in the Elderly Multiple changes occur in arterial media with aging, including reduced elastin content with increases in non-distensible collagen and calcium (e.g. arterial stiffening). Age-associated arterial stiffening results in a gradual increase in systolic BP and a decrease in diastolic BP. Flow-mediated arterial dilation, primarily mediated by endothelium- derived nitric oxide, declines markedly with aging. Neurohormonal profile of older hypertensive adults characterized by increased plasma norepinephrine, low renin, and low aldosterone levels. Many so-called “normal aging changes” in arterial structure and function are blunted/absent in populations not chronically exposed to high sodium/high calorie diets, low physical activity levels, and high rates of obesity.

12. Conceptual Framework for CV Adaptations to Arterial Stiffening Occurring with Aging CBF indicates coronary blood flow; DBP, diastolic blood pressure; EF, ejection fraction; LA, left atrial; LV, left ventricular; SBP, systolic blood pressure; ↑, increased; and ↓, decreased.

13. 3. Hypertension is a potent risk factor for cardiovascular (CV) disease in the elderly. Hypertension in the Elderly

14. Coronary Heart Disease Rates by SBP and Age Adapted from Lewington et al. Lancet. 2002; 360:1903-1913 120 mm Hg 140 mm Hg 160 mm Hg 180 mm Hg Coronary Heart Disease Mortality 256 128 64 32 16 8 4 2 40-49 Age 50-59 60-69 70-79 80-89 1

15. Hypertension as a Risk Factor in the Elderly In older adults, hypertension (HTN) is the most prevalent modifiable CV risk factor: antecedent HTN is estimated in: –~70% of patients with incident myocardial infarctions –~77% of patients with incident strokes –~74% with chronic heart failure –~90% with acute aortic syndrome –30% to 40% with atrial fibrillation HTN is also a major risk factor for conditions directly influencing CV risk in the elderly: –Diabetes –Metabolic syndrome –Chronic kidney disease The number of deaths attributable to HTN in the U.S. rose 56% between 1995 and 2005, largely reflecting the increasing number of older Americans and high prevalence of HTN in the elderly.

16. 4. Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients 60-79 years old with anti- hypertensive drug therapy though the effect on all-cause mortality has been modest. In HYVET, antihypertensive therapy reduced all- cause mortality in people ≥80 years old by 21%. Hypertension in the Elderly

17. Randomized Hypertension in the Very Elderly Trial (HYVET) In 3,845 patients ≥80 years old with SBP ≥160 mm Hg, at 1.8-year follow-up, those randomized to indapamide vs placebo had: –30% nonsignificant decrease in fatal/nonfatal stroke –39% significant decrease in fatal stroke –21% significant decrease in all-cause mortality –23% insignificant decrease in CV death –64% significant decrease in heart failure HYVET: Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-98.

18. 5. Although increases in the treatment and control of BP in older hypertensive adults have occurred over the past 2 decades, BP control rates remain suboptimal in the elderly. Hypertension in the Elderly

19. Extent of Awareness, Treatment and Control of High Blood Pressure by Age NHANES: 2005-2006

20. Frequency of Untreated Hypertension According to Subtype and Age Chobanian N Engl J Med. 2007;357:789-96

21. 6. Non-pharmacologic lifestyle measures should be encouraged in older adults, both to retard development of hypertension and as adjunctive therapy in those with hypertension. Hypertension in the Elderly

22. Non-Pharmacologic Lifestyle Measures Shown Beneficial in Elderly Hypertensive Subjects Regular physical activity Sodium restriction Weight control Smoking cessation Avoidance of excessive alcohol intake

23. 7.Although the specific BP at which antihypertensive therapy should be initiated in the elderly is unclear, a threshold of 140/90 mm Hg in persons 65- 79 years and a threshold systolic BP of 150 mm Hg in people age 80 years and older is reasonable. Hypertension in the Elderly

24. Risk of Adverse Outcomes Among Elderly CAD Patients by Age and BP Denardo et al. Am J Med 123:719-726, 2010 BP nadirs indicate BP’s with lowest hazard ratio at each age.

25. 8.Diuretics, ACE-inhibitors, angiotensin receptor blockers, calcium antagonists, and beta blockers have all shown benefit on CV outcomes in randomized trials among elderly cohorts. The choice of specific agents is dictated by efficacy, tolerability, presence of specific comorbidities, and cost. Hypertension in the Elderly

26. Antihypertensive Treatment-Related Side Effects The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects such as: –Electrolyte disturbances –Renal dysfunction –Excessive orthostatic BP decline

27. 9.Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated. Hypertension in the Elderly

28. Physiologic Changes with Aging: Potential to Influence Antihypertensive Drug Pharmacokinetics Absorption and distribution of antihypertensive drugs are unpredictable in the elderly

29. Physiologic Changes with Aging: Potential to Influence Antihypertensive Drug Pharmacokinetics Continued Half life of most antihypertensive drugs is increased in the elderly

30. Percent of Elderly People in Outcomes Trials Taking ≥Two Antihypertensive Medications (mean SBP achieved) (Mean SBP achieved)

31. 10.The high prevalence of both CV and non- CV comorbidities among the elderly dictates need for great vigilance to avoid treatment- related side effects. Hypertension in the Elderly

32. Target Blood Pressure Goals in the Elderly Although the optimal BP treatment goal in the elderly has not been determined, a therapeutic target of <140/90 mm Hg in persons aged 65-79 years and a SBP of 140-145 mm Hg, if tolerated, in persons aged ≥80 years is reasonable.

33. Stage 1 Hypertension SBP 140-159 mmHg or DBP 90-99 mmHg ACEI, ARB, CA, diuretic, or combination Stage 2 Hypertension SBP ≥160 mmHg or DBP ≥100 mmHg Majority will require ≥2 drugs to reach goal if ≥20 mmHg above target. Initial combinations should be considered. The combination of amlopidine with an RAS blocker may be preferred to a diuretic combination, though either is acceptable. Compelling Indication Heart Failure Post myocardial infarction CAD or High CVD risk Angina Pectoris Aortopathy/Aortic Aneurysm Diabetes Chronic kidney disease Recurrent stroke prevention Early dementia Initial Therapy Options* THIAZ, BB, ACEI, ARB, CA, ALDO ANT BB, ACEI, ALDO ANT, ARB THIAZ, BB, ACEI, CA BB, CA BB, ARB, ACEI, THIAZ, CA ACEI, ARB, CA, THIAZ, BB ACEI, ARB THIAZ, ACEI, ARB, CA Blood pressure control *Combination therapy Principles of Hypertension Treatment in the Elderly Not at Target BP Optimize dosages or add additional drugs until goal BP is achieved. Refer to a clinical hypertension specialist if unable to achieve control. Lifestyle Modifications Initial Drug Choices Not at Target BP With Compelling IndicationsWithout Compelling Indications

34. Hypertension in the Elderly Summary and Conclusions –Very highly prevalent –Major, treatable risk factor for CV disease –Typically, SBP elevation with low DBP (“stiff arteries”) –Many comorbidities make management challenging –Life style modification useful, even with drug therapy –Begin with low drug doses and titrate drugs slowly –For those ≥80 years, 140-145 mm Hg is acceptable SBP goal