Hypertension

1. Hypertension Author: Jennifer Kraschnewski MD Editor: Amy Shaheen, MD, Assistant Professor of Clinical Medicine Duke University Medical Center

2. Hypertension: The Silent Killer • Hypertension affects an estimated 50 million individuals in the United States. Data from the Framingham Heart Study suggest that normotensive, 55-year-old patients have a 90% lifetime risk for developing hypertension.[i] • The widespread prevalence should not, however, overshadow the impressiveness of hypertension as an independent risk factor for cardiovascular disease (CVD). Studies have consistently shown that the higher the blood pressure, the greater the risk of heart attack, heart failure, stroke and kidney disease. For example, the risk of CVD doubles in individuals 40-70 years of age for each increment of 20 mmHg SBP or 10 mmHg DBP across the entire BP range (115/75 – 185/115).[ii] Clinical trials have associated antihypertensive therapy with reductions in stroke incidence averaging 35-40%; myocardial infarction, 20-25%; and heart failure, more than 50%.[iii]

3. Defining Hypertension • The classification of BP for adults is provided by JNC VII Guidelines, as adapted in Table 1 below. Determination of proper classification is based on the average of two or more properly measured BP readings on each of two or more office visits. • The classification “prehypertension” is new to the JNC VII Guidelines, introduced to increase education as to the importance of blood pressure control. A staggering 30% of patients with hypertension are unaware of their diagnosis.

4. Classification and management of blood pressure for adults (adapted from JNC VII Guidelines) 1 Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines; the compelling indication is managed in parallel with the BP. Compelling indications include heart failure, postmyocardial infarction, high coronary disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention. 2 Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

5. Measuring Blood Pressure • Indirect auscultation with a mercury or well-calibrated aneroid sphygmomanometer is the pragmatic reference standard. Prior to obtaining a blood pressure reading, patients should be sitting in a chair for at least 5 minutes, with their feet on the floor and their arm supported at heart level. It is important to use an appropriately sized cuff (cuff bladder encircling at least 80% of the arm) to ensure accuracy of the reading.

6. Measuring BP (continued) • Figure 1. Note the proper blood pressure measuring technique used in this figure: • Patient is seated (for a minimum of 5 minutes). • The correct cuff size is used, with the cuff bladder encircling at least 80% of the arm. • The arm is supported at the level of the heart.

7. Measuring BP (continued) • Self-monitoring of BP can be used both for diagnosis and treatment monitoring. When used to diagnose hypertension, a mean self-reported SBP > 135 mmHg or DBP > 85 mmHg should be used. Patients should use a fully automated monitor with an appropriately sized cuff. The first day of readings should be discarded, with the remaining values used to calculate the mean blood pressure. Additionally, home measurement devices should be checked regularly for accuracy. • Ambulatory blood pressure monitoring (ABPM) may be useful in ruling-out “white-coat” hypertension in patients without target organ injury. Blood pressure measurements by ABPM correlate better with target organ injury than office measurements.[i]

8. Evaluating a newly diagnosed patient • Patients meeting the requirements for a diagnosis of hypertension require further evaluation. Particular elements of the history that should be addressed include the following: patient’s age, history of tobacco use, history of hyperlipidemia, physical activity, history of diabetes, and family history of premature CAD (defined as CAD in males < 55 years and females < 65). These elements are important to identify other cardiovascular risk factors or comorbid conditions that may affect prognosis and guide treatment.

9. Major Risk Factors Hypertension* Cigarette smoking Obesity* (BMI > 30) Physical Inactivity Dyslipidemia* Diabetes mellitus Microalbuminuria or estimated GFR < 60mL/min Age (older than 55 for men, 65 for women) Family history of premature CAD (men under age 55 or women under age 65) Target Organ Damage Heart Left Ventricular hypertrophy Angina or prior myocardial infarction Prior coronary revascularization Heart failure Brain Stroke or TIA Chronic kidney disease Peripheral arterial disease Retinopathy Cardiovascular Risk Factors (adapted from the JNC VII Guidelines) *Components of the metabolic syndrome

10. Goals of physical exam and laboratory data • The goals of the physical exam and laboratory data are to both search for identifiable causes of high BP as well as the presence of target organ damage or CVD. The physical examination should include the following components: measuring blood pressure in both arms, documentation of the BMI, examination of the optic fundi, auscultation for carotid, abdominal and femoral bruits, palpating the thyroid, a detailed cardiac and pulmonary exam, palpation for enlarged kidneys, documentation of peripheral pulses and a complete neurologic exam. • Laboratory data that should be obtained include: urinalysis, glucose, hematocrit, potassium, creatinine, calcium, and lipid profile. An EKG should also be obtained. Urinary albumin excretion or an albumin/creatinine ratio is considered optional.

11. Sleep Apnea Chronic steroid use & Cushing’s syndrome Drug-induced or related causes Pheochromocytoma Coarctation of the aorta Primary aldosteronism Thyroid or parathyroid disease Renovascular disease Chronic kidney disease Identifiable causes of hypertension

12. Work-up of Secondary Hypertension • The work-up of secondary hypertension is appropriate in patients whose history, physical examination, severity of hypertension, or initial labs are suggestive of secondary causes. Additionally, work-up may be warranted in patients who have the sudden onset of hypertension, a poor response to drug therapy, or an increase in blood pressure after previously being well-controlled.

13. Goal blood pressure with treatment • The goal for the typical patient with hypertension is a blood pressure of < 140/90 mmHg. Patients with diabetes or chronic kidney disease should strive for a goal of < 130/80 mmHg. In patients with > 1 g of proteinuria, the goal blood pressure is < 125/75 mmHg to prevent further damage.

14. Lifestyle modifications • A major component of both the prevention and treatment of hypertension is adopting a healthy lifestyle. Modifications recommended by the JNC VII Guidelines include: weight reduction in those individuals who are overweight or obese, adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan, dietary sodium reduction, physical activity, and moderation of alcohol consumption. Studies have shown that lifestyle modification, such as adopting a 1600 mg DASH eating plan, has blood pressure lowering effects similar to single drug therapy.[i] • The importance of lifestyle modification in blood pressure control cannot be overstated. These healthy changes may be of particular interest to newly diagnosed patients who do not wish to start medications. Combinations of modifications can easily place a pre-hypertensive or stage I hypertensive patient back into the normal blood pressure range, greatly decreasing their overall risk of complications.

15. Lifestyle modifications to manage hypertension (adapted from the JNC VII Guidelines) * Various amounts of sodium restriction have been studied (see Sacks et al). However, a 2.4 g limit, as recommended by the JNC VII Guidelines, has been proven effective and may be more attainable for some individuals than stricter levels of restriction.

16. Pharmacologic treatment of hypertension • Antihypertensive agents are, for the most part, equally effective in producing an antihypertensive response in 30-50% of cases. However, there is wide inter-patient variability in response, as well as some predictable differences (such as race), which may further define treatment choices. Some of the advantages and disadvantages of the various classes are outlined following in Table 6. Recall that, according to JNC VII Guidelines, thiazide-type diuretics are the first-line therapy for Stage I hypertension. Stage II hypertension typically requires the use of two-drug combination therapy.

17. Pharmacologic treatment of hypertension • Patients with compelling indications (including heart failure, postmyocardial infarction, high coronary disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention) should initiate drugs targeted at the compelling indications. Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines. With drug therapy, the compelling indication is managed in parallel with the BP. Table 5, adapted from the JNC VII Guidelines, exhibits drug recommendations for the different compelling indications.

18. Clinical trial and guideline basis for compelling indications for individual drug classes. (adapted from JNC VII Guidelines)

19. Thiazide-type diuretics • Given the efficacy of these medications, both alone and when used in combination with other antihypertensives, and the lower overall cost, thiazide-type diuretics are recommended as initial therapy for most patients with hypertension. The thiazide diuretics are specifically indicated in black patients, patients with edema or CHF, and as first-line therapy in the elderly. Unfortunately, this class of medication also has multiple adverse metabolic effects, including hypokalemia, hyperuricemia, mild elevations in cholesterol and glucose, and hyperinsulinemia. • Multiple trials have shown the benefits of thiazide-type diuretics in preventing cardiovascular complications of hypertension. In ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial), no significant differences were demonstrated in terms of fatal CHD or non-fatal myocardial infarctions between chlorthalidone, amlodipine or lisinopril. However, chlorthalidone was found to be more effective at reducing the SBP below target than either of the other two drugs.

20. Beta Blockers • Although widely used in the treatment of hypertension, most studies have failed to support the theory that beta blockers are cardioprotective in these patients (as they are following a myocardial infarction). Beta blockers are preferred in patients with resting tachycardia, congestive heart failure due to diastolic dysfunction, migraine headaches, glaucoma, and those with a previous myocardial infarction or angina pectoris. • Side effects of the nonselective and B-1 selective agents include moderate elevation in plasma glucose concentration, increased insulin resistance, reduced HDL cholesterol, and elevated triglycerides. The inhibition of sympathetic activity, which can lead to fatigue, depression, or decreased exercise capacity, has been proposed, although not proven, to decrease quality of life. Beta blockers (except atenolol) can be used in pregnancy.

21. ACE Inhibitors • This class of medications should be used as first-line therapy in patients with the following comorbidities: CHF or asymptomatic LV dysfunction, history of an ST-elevation MI, history of a non-ST elevation MI with an anterior infarct, diabetes, systolic dysfunction, or a history of proteinuric chronic renal failure. Combination therapy with an ARB is recommended in patients with CHF and proteinuric chronic renal failure. ACE inhibitors have been shown to regress left ventricular hypertrophy more rapidly than beta blockers as well as slow the rate of progression of diabetic nephropathy. • ACE inhibitors act synergistically with a thiazide diuretic. By inhibiting the converting enzyme, these medications prevent the increase in renin release due to hypovolemia induced by diuretic therapy, thereby resulting in a more prominent BP reduction. The use of this combination has also been shown to prevent some of the metabolic complications associated with diuretic use, including hypokalemia (by lowering angiotensin II-induced aldosterone release), hyperlipidemia, and hyperuricemia. • Overall, ACE inhibitors have few toxic side effects. Approximately 7% of men and 15-20% of women will suffer from a dry hacking cough secondary to ACE inhibitor use. Other potential complications include angioedema, which can be life threatening, and hyperkalemia. ACE inhibitors should not be used in pregnancy.

22. ARBs • Given the similarities between their mechanisms, it is thought that the indications for and efficacy of ARBS are not different from those with ACE inhibitors. Like ACE inhibitors, ARBs have been shown to regress left ventricular hypertrophy more rapidly than beta blockers and slow the rate of progression of diabetic nephropathy. Certainly, ARBs can be used with confidence as an alterative in patients who are unable to tolerate ACE inhibitors secondary to a cough.

23. Calcium Channel Blockers • The calcium channel blockers (CCBs) can be divided into three major types: the dihyrdropyridines (including nifedipine, amlodipine, and nicardipine), which are potent vasodilators; verapamil, which has cardiac depressant activity; and diltiazem, which has less vasodilator activity than nifedipine and less cardiac depression than verapamil. All three types are equally efficacious in blood pressure control, however, they have different side effect profiles. • Long-acting CCBs have been shown to be particularly effective in older patients or those with a low plasma rennin activity. They have many of the same advantages of ACE inhibitors and have been shown to improve vascular design. Because post-treatment blood pressure is independent of salt intake, CCBs may be particularly useful in patients who are non-compliant with dietary salt restriction.

24. Calcium Channel Blockers (continued) • Due to findings in ALLHAT of increased risk of heart failure on amlodipine (as compared to chlorthalidone), CCBs should not be used as first-line hypertension therapy. However, several patient populations may benefit from calcium channel blocker use, including those with angina, recurrent SVTs (verapamil), Raynaud phenomenon (dihydropyridines), migraine headaches, heart failure due to diastolic dysfunction, and esophageal spasm. Short-acting CCBs should not be used for chronic antihypertensive therapy, due to a greater side effect profile in comparison to the long-acting versions.

25. Follow-up for Patients with Hypertension • Most patients should return to clinic at monthly intervals until their blood pressure goals are reached. Patients with Stage II hypertension should be followed more frequently. Patients with hypertension on a stable regimen and at their goal blood pressure should follow-up every 3-6 months (depending on comorbidities) and have their potassium and creatinine levels checked 1-2 times a year.

26. A comparison of oral anti-hypertensive medications (part 1) *Agent available in long acting formulation

27. A comparison of oral anti-hypertensive medications (part 2) *Agent available in long acting formulation

28. A comparison of oral anti-hypertensive medications (part 3) *Agent available in long acting formulation

29. A comparison of oral anti-hypertensive medications (part 4) *Agent available in long acting formulation

30. A “Jeopardy” style quiz will open in a separate window within the next five seconds. If it doesn’t, click on this link Jeopardy Hypertension Quiz. This file is also include on “Attachment” link in the upper right hand corner of this presentation and in the Course Content tree for this Course in the Learning Management System. Also be sure to complete the course evaluation – Here. This is also included in the Course Content Tree

31. References [i] Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002; 287: 1003-10. [ii] Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in prospective studies. Lancet. 2002; 360: 1903-13. [iii] Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: Results of prospectively designed overviews of randomized trials. Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000; 356: 1955-64. [iv] US Department of Health and Human Service. National Institutes of Health. National Heart, Lung, and Blood Institute. National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. May 2003. [v] Verdecchia P. Prognostic value of ambulatory blood pressure: current evidence and clinical implications. Hypertension. 2000; 35: 844-51. [vi] Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001; 344: 3-10.