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Hypertension Overhaul 2009

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  1. Hypertension Update 2009 Adena Health System 2009 Cardiovascular Symposium October 2009

  2. Key Concepts Hypertension is common Hypertension increases cardiovascular risk Effective treatment confers benefit Lessons from recent clinical trials Compelling indications for certain antihypertensive agents and blood pressure targets 2

  3. Epidemiology • Over 65 million Americans age 20 and older have HTN • Prevalence increases with age • Prevalence of hypertension varies by ethnic group several-fold higher in young African Americans • >60% of Caucasians over 60 • >70% of African American over 60 • Primary Hypertension 95% • Secondary Hypertension 5%

  4. Epidemiology • Level of BP directly correlates with LVH/microalbuminuria • LVH and hypertension: • Strong predictor of sudden death and MI • Microalbuminuria and hypertension: (Persistent urinary albumin excretion of 30-300mg/24hrs) • Increased risk of CVD • Marker for endothelial dysfunction

  5. Mortality Due to CHD per Quartile of Usual SBP USA Japan van den Hoogen et al. N Engl J Med 2000;342:1. 5

  6. Impact of High-Normal BP on the Risk of CV Disease Vasan RS et al. N Engl J Med 2001;345:1291. 6

  7. Relationship Between Hypertension and IHD Mortality Lewington S, et al. Lancet 2002; 360:1903–13

  8. Update Hypertension 2009Main Themes • What level of BP should we achieve? • What does the hypertension workup consist of ? • How should we measure BP? • Future directions……..personalized medicine and home monitoring !

  9. Historical Trends in HTN National Health and Nutrition Examination Survey Trends in awareness, treatment, and control of high blood pressure in adults ages 18-74 1976-1980 51% 31% 10% 1988-1991 73% 55% 29% 1991-1994 68% 54% 27% 1994-2000 70% 59% 34% 2003-2004 75% 65% 33% Awareness Treatment Control SBP < 140 mmHg and DBP < 90 mmHg Adapted from: Hajjar I, et al. JAMA. 2003;290:199-206. Ong KL et al Hypertension 2007: 49;69-75

  10. Effective blood pressure control, regardless of which (or how many) agents are employed, is paramount to reduce CV endpoints Current control rates, even in idealized study populations, is sub-par. On a practical level, whatever potential benefits or drawbacks occur as a result of a specific property of one agent vs. another at equivalent blood pressure levels is drowned out by the adverse events of those that remain uncontrolled At equivalent levels of blood pressure control, newer agents offer a more appealing biochemical profile… the long-term importance of which remains to be seen Lessons Learned from ALLHAT and ASCOT-BPLA on specific antihypertensive agents 10

  11. 18% Factors Contributing to Poor Blood Pressure Control Took no action Increased dose Changed drug Prescribed add-on therapy From: Taylor Nelson Healthcare, Epson, Surrey England - Cardiomonitor 1992 11

  12. Blood Pressure (BP) Classification and Management* Life- Initial Drug Therapy BP SBP, DBP, style Compelling Indications Classification mm Hg*mm Hg* Changes Without With Normal <120 and <80 encourage Pre HYTN 120-139 or 80-89 Yes No Yesa Stage 1 HYTN 140-159 or 90-99 Yes Yesb Yesc Stage 2 HYTN >160 or >100 Yes Yesd Yese SBP=systolic BP, DBP=diastolic BP; HYTN=hypertension, ACEI=Angiotensin-converting enzyme inhibitor, ARB=angiotensin, CCB=calcium channel blocker * Treatment determined by highest BP category a Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mm Hg b Thiazide-type diuretics for most; may consider ACEI, ARB, b-blocker, CCB or combination c Other antihypertensive drugs (diuretics, ACEI, ARB, b-blocker, CCB) as needed d Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or b-blocker of CCB. Initiation of combined therapy should be used cautiously in those at risk for orthostatic hypotension. e Other antihypertensive drugs (diuretics, ACEI, ARB, b-blocker, CCB) as needed. JNC VII. JAMA 2003;289:2560.

  13. What is the optimal target BP level…….normal kidney donors? Rafey et al NKF 2008

  14. Goals of the Hypertensive Evaluation Does the patient have primary or secondary (reversible) hypertension? Is target organ damage present? Are other cardiovascular (CV) risk factors present? 14

  15. JNC 7 Recommendations for Routine Work-up of Hypertensive Patients • Routine Tests • Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR, and calcium • Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and triglycerides • Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio • More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

  16. JNC 7 Recommendations for Routine Work-up of Hypertensive Patients • Routine Tests • Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR, and calcium • Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and triglycerides • Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio • More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

  17. Secondary Causes of Hypertension: Renovascular Disease Clinical Clues Abrupt onset <30 or >55 years of age Refractory to 3-drug regimen Evidence of diffuse vascular disease ARF with ACEI Accelerated retinopathy Epigastric bruit Diagnosis Duplex renal arteries Captopril renography MRA Angiogram Renal vein renin Treatment Angioplasty/stent Surgery Medical treatment 17

  18. Etiologies for Secondary Hypertension Renal Endocrine Renal parenchymal Renal artery stenosis Obstruction PCKD Cushing’s syndrome Adrenogenital syndrome Pheochromocytoma Adrenal and adrenal-like Acromegaly Liddle’s syndrome, Gordon’s syndrome Other Pre-eclampsia Acute intermittent porphyria Thyroid (hyper, hypo) Drugs Hypercalcemia Coarctation of Aorta

  19. Secondary Hypertension Chronic Kidney Disease and hypertension: • Present in more than 80% of patients • Mechanism: Excessive salt retention and increased peripheral resistance • Exacerbates proteinuria • Accelerated progression of CKD • ACEI and ARBs slow progression of CKD

  20. Angioplasty and Stent for Renal Artery Lesions ASTRAL

  21. Cardiovascular Outcomes in Renal Atherosclerotic Lesions CORAL

  22. 23 www.coralclinicaltrial.gov

  23. For persons over age 50, SBP is a more important than DBP as CVD risk factor. Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. Starting at 115/75 mm Hg, CVD risk doubles with each increment of 20/10 mm Hg throughout the BP range. Those with SBP 120–139 mmHg or DBP 80–89 mm Hg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD. New Features and Key Messages JNC VII 24

  24. New Features and Key Messages (Continued) Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes. Certain high-risk conditions are compelling indications for other drug classes. Most patients will require two or more antihypertensive drugs to achieve goal BP. If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic. JNC VII 25

  25. Combination Therapy Needed to Achieve Target SBP Goals Trial/SBP Achieved UKPDS (144 mm Hg) RENAAL (141 mm Hg) ALLHAT (135 mm Hg) IDNT (138 mm Hg) HOT (138 mm Hg) INVEST (133 mm Hg) ABCD (132 mm Hg) MDRD (132 mm Hg) AASK (128 mm Hg) 1 2 3 4 Number of BP meds Updated from Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.

  26. RAS Inhibitor use in Hypertensive Blacks • ACEIs/ARBs should be considered first line in patients (including blacks) with nephropathy (esp. with proteinuria) and or heart failure • Available data suggest that RAS inhibitors are less effective in lowering BP in black hypertensives in the absence of adequate doses of a diuretic or CCB (and in preventing clinical outcomes) • ACEI also carry increased risk of angioedema , esp. in blacks • In the absence of HF or CKD, particularly in Black hypertensives, beta blockers, ACEI,and ARBs(and presently renin inhibitors) should be prescribed only in combination with thiazide-type diuretics or calcium channel blockers

  27. Blood pressure measurement… • Recognize the diagnostic limitations of traditional office blood pressure measurement.. • 24hr ambulatory BP measurement: diagnostic utility and clinical correlations… • Understand the physiology of the arterial waveform, central BP measurement, vascular stiffness indices and pulsology in clinical practice

  28. Center for Blood Pressure DisordersClinical Program: Goals • Accurate BP Measurement • Comprehensive Vascular Evaluation

  29. Reduction of WCE in Clinical Practice 180 – 170 – 160 – 150 – 140 – 130 – 120 – 110 – 100 – 90 – 80 – 0 – 152 140 134 132 Blood Pressure (mmHg) 87 75 80 77 Ambulatory BP BpTRU Family Physician Research Technician n=309 Myers M, et al, Journal of Hypertension 2009 27(2) 280-286

  30. White coat effect Work in progress BpTRU

  31. ComprehensiveEvaluation of Hypertension Nurse/MA Retinal Exam Urine protein Limited Echo BpTRU Sphigmocor ABI TOD Central BP /PWV TOD TOD Peripheral BP PVD Physician Evaluation • Lab Review • Dyslipidemia • Fasting plasma glucose H & P Comprehensive Management Plan Based on Risk Estimates

  32. 24 Hour Ambulatory Blood Pressure Monitoring

  33. HBPM: New Recommendations May 2008

  34. Indications for 24 Hour ABPM Clinical situations in which ABPM may be helpful: • Rule out white-coat HTN • Apparent drug resistance (office resistance) • To better define resistant HTN • Hypotensive symptoms with antihypertensives • Episodic hypertension • Autonomic dysfunction

  35. Dipping Pattern and Decline in GFR • 322 consecutive patients • 137 dippers • 185 nondippers • Follow-up 3.2 yrs • Dippers mean change in GFR 1.3% • Nondippers mean change in GFR 15.9% (P<0.001) Davidson et al Arch Intern Med. 2006;166:846-852

  36. Prevalence of Nocturnal Hypertension in AASK Study

  37. 24 Hour Ambulatory Blood Pressure Monitoring

  38. Measures of Arterial Stiffness • Central Aortic Pressure • Pulse Wave Velocity (PWV) • Augmentation Index (AIx)

  39. QRS- carotid QRS-femoral  time Notch-carotid Notch-femoral  distance Aortic PWV (distance/time) 55 msec 135 msec 80 msec 85 mm 690 mm 605 mm 7.6 m/sec How PWV is measured... 85 mm FEMORAL CAROTID 690 mm 55 msec 135 msec EKG-QRS EKG-QRS Velocity = Distance/Time

  40. APWV measurement (cont.)

  41. Elderly stiff arteries with ISH : Increased PW velocity (12 m/sec) Aortic Stiffening and Early Wave Reflection Young compliant arteries :Normal PW velocity (8 m/sec) Systole Diastole (1) Ventricular-Vascular coupling (2)  coronary blood flow Systole (1) Ventricular-vascular mismatch (2) The reflected wave increases or “augments” central SBP during late systole:

  42. Arterial stiffness measures CBP (central BP) AIX (Augmentation Index) PVW(Pulse wave velocity) SphygmoCor • ? Evidence to change management? • Does depend on accurate peripheral blood pressure measurement eg: BPtru / manual BP • How to incorporate it with out interfering with the work flow?

  43. TOP: Brachial (solid symbols) and derived central aortic (open symbols) systolic blood pressure with time (mean, 95% CI) for patients randomized to receive atenolol ± thiazide- or amlodipine ± perindopril-based therapy.BOTTOM: Systolic blood pressure difference (brachial minus central aortic; mean, 95% CI) with time. For calculation of AUC, see the Data Supplement. Numbers below abscissa represent the number of patients seen at each time point. Time represents the duration from randomization into ASCOT to patient follow-up visit at which tonometry measurement was made in the CAFE study. PP indicates pulse pressure. CAFE Investigators, for ASCOT Investigators. Circulation 2006;113:1213.

  44. CAFÉ Study Results

  45. AIx in CKD vs. non CKD AIx was significantly higher in the non-CKD patients compared to the CKD patients (median AIx 27 % [18, 32] vs. 21 % [14, 29], P = 0.002). AIx was similar in the CKD and non-CKD groups after adjusting for age, gender, height, SBP and eGFR CKD Non-CKD

  46. Linear Regression of AIx by SBP Augmentation Index (%) R = 0.24, P <0.0001 SBP

  47. Linear Regression of AIx by PPP

  48. Future Developments in Hypertension Personal medicine Home BP monitoring

  49. Corin Variants in African-Americans with Hypertension and Heart Disease enzyme enzyme T555I Q568P cell membrane Dries et al. Circulation 2005;112:2403 Wang et al. Circ Res 2008;103:502