1. JNC 7 blood pressure classification in adults aged ≥18 years BP Classification SBP (mm HG) DBP (mm HG) Normal<120and<80 Prehypertension120-139or80-89 Stage 1 hypertension 140-159or90-99 Stage 2 hypertension  160 or  100 National Heart, Lung, and Blood Institute. JNC 7 Express. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 2003.

2. JNC 7 hypertension treatment algorithm Not at goal blood pressure (<140/90 mm HG) (<130/80 mm HG for those with diabetes or chronic kidney disease) Initial drug choices Drug(s) for 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 mm HG) 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 mm HG) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.0 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. National Heart, Lung, and Blood Institute. JNC 7 Express. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 2003.

3. Definition of hypertension subtypes 1.National Heart, Lung, and Blood Institute. JNC 7 Express. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 2003. 2.Pickering TG, et al. Hypertension. 2002;40:795-796. 3.Staessen JA, et al. Blood Press Monit. 2001;6:355-370. True Hypertension Definition 1 >140/90 mm HG by clinic measurement >130/80 mm HG by home or ambulatory measurement White-Coat Hypertension Synonym Isolated office hypertension 2 Definition Hypertensive by clinic (office) measurement and normotensive by home and ambulatory measurement 3 Masked Hypertension Synonyms White-coat normotension; reverse white-coat hypertension; undetected ambulatory hypertension 2 Definition Normotensive by clinic measurement and hypertensive by home and ambulatory measurement 1

4. Recommendations for clinical use of ambulatory blood pressure monitoring: US guidelines Suspected white-coat hypertension Drug-resistant hypertension Hypotensive symptoms with medications Episodic hypertension Autonomic dysfunction National Heart, Lung, and Blood Institute. JNC 7 Express. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 2003.

5. Use of ambulatory blood pressure in hypertension management Adapted from White WB. N Engl J Med. 2003;348:2377-2378. 24-hour B P <130/80 mm HG 24 hour BP ≥ 130/80 mm HG Change antihypertensive therapy to improve control (target <130/80 mm HG) Maintain present therapy Follow up with an ABPM every two years Follow up with ABPM every 2 years TREATED Office blood pressure >140/90 mm HG in low-risk patients (no target organ disease) >130/80 mm HG in high-risk patients (target organ disease, diabetes) Self-monitored BP <130/80 mm HG Self-monitored BP ≥ 130/80 mm HG Perform ambulatory BP monitoring 24-hour BP <130/80 mm HG 24-hour BP ≥ 130/80 mm HG Initiate antihypertensive therapy Follow up with non-drug therapy on a 6-12 month basis Repeat ambulatory BP measurement every 1-2 years Perform ambulatory blood-pressure monitoring

6. Clinical conclusions: The usefulness of ABPM Accounts for BP variations over time Diagnosis of white-coat hypertension and masked hypertension Allows for evaluation of consistency of drug effect over dosing periods  24 hours More reproducible than clinic BP Mancia G, et al. J Hypertens. 1997;15(Suppl 2):S43-S50.

7. ACE inhibitors 1 Angiotensin-receptor blockers 1 Angiotensin I Renin Impaired release of renin due to NSAIDs, beta-blockers, cyclosporine, tacrolimus, diabetes, or advanced age Proximal tubule Glomerular capsule Juxtaglomerular cells Afferent arteriole Distal convoluted tubule Angiotensin II Angiotensin receptor Adrenal gland Impaired aldosterone metabolism due to adrenal disease, heparin, or ketoconazole Aldosterone Aldosterone- receptor blockers: spironolactone and eplerenone 4 Collecting duct Apical membrane Aldosterone Aldosterone- receptor Collecting duct Collecting duct (principal cell) K+ Na+ Na- K- Lumen Sodium-channel blockers: amiloride, triamterene, trimethoprim, and pentamidine  BP 3 Renin inhibitors 2 1. Palmer BF. N Engl J Med. 2004;351:585-592. 2. Maibaum J, et al. Expert Opin Ther Patients. 2003;13:589-603. 3. Ooi S-YS, et al. Prescriber. 2004;5:33-46. 4. Givertz MM. Circulation. 2005;111:1012-1018. Potential targets for therapeutic intervention on kidney function

8. ACE Renin ACE Angiotensinogen ANG I ANG II AT 1 Receptor Bradykinin Frag ments ACE-independent ANG II Formation Unger T. Am J Cardiol. 2002;89(suppl):3A-10A. Vascular Endothelium AT 2 Receptor ARB Angiotensin receptor blockers (ARBs): Mechanism of action

9. End-stage heart disease Heart failure ACE inhibition Angiotensin receptor blockade GISSI-3 ISIS-4 AIRE SAVE SOLVD-Prevention TRACE CHARM-Preserved OPTIMAAL VALIANT SOLVD-Treat CHARM-Added CHARM-Alternative ELITE II Val-HeFT CONSENSUS HOPE EUROPA ALLHAT ANBP2 ASCOT INVEST LIFE VALUE Studies investigating effects of RAAS manipulation on CV disease outcomes Adapted from: Dzau V, et al. Am Heart J. 1991;121:1244-1263. Ventricular dilation Remodeling LV Dysfunction Arrhythmia Myocardial Infarction Coronary thrombosis Myocardial ischemia CAD Athero- sclerosis LVH Hypertension