for Health Care Providers
This chapter does not address hypertensive emergency or urgency in detail.
Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.
- Hypertension is an independent, reversible risk factor for cardiovascular, cerebrovascular, and renal disease that is underdiagnosed and undertreated.
- HIV-infected patients have a high prevalence of hypertension and other cardiovascular risk factors.
- In most cases, the treatment of hypertension should start with lifestyle modification and a thiazide diuretic. Other antihypertensive drugs may be useful, depending on the patient's additional comorbidities.
Rationale for Detecting and Treating High Blood Pressure
- Elevated blood pressure (BP) is an independent risk factor for myocardial infarction (MI), stroke, heart failure, and kidney disease.
- The relationship between BP and these disease events is continuous; the risk of cardiovascular disease doubles for every 20 mmHg increase in systolic BP or 10 mmHg increase in diastolic BP. This effect applies across the spectrum of BP, from normal to severely elevated.
- In clinical trials, treatment of hypertension is associated with substantial reductions in the incidence of MI, stroke, and heart failure.
- "Prehypertension" (as defined in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC 7], see Table 1) confers an increased risk of developing hypertension and often warrants therapeutic intervention. Because the short-term pharmaceutical treatment of prehypertension has not been shown to forestall the development of hypertension, some experts have questioned the benefit of labeling patients with this diagnosis.
- Although hypertension can be controlled for most patients by a combination of lifestyle changes and pharmaceutical therapy, hypertension remains poorly controlled for many patients.
Veterans with HIV*
Special Considerations regarding Hypertension and ART
Although a relationship between ART and other components of the metabolic syndrome, such as hyperlipidemia and elevated blood glucose, has been established, it is not clear whether HIV or specific ARVs are independent risk factors for hypertension.
Some early studies suggested a link between PI-based ART and elevated BP. More recent and larger studies, including the D:A:D study, found that this relationship was accounted for by other factors, such as age, race, and, in particular, increases in BMI that occurred after initiation of ARVs. Another study suggests a link between the duration of ART and BP. Prolonged ART, defined as 2-5 years in duration, was independently associated with development of hypertension in the MACS study, whereas ART of <2 years in duration was not.
Treatment Goals (see Table 1)
Current VA recommendations are to lower BP to a target of <140/90 (<140/80 for patients with diabetes) to reduce the risk of cardiovascular events and other end-organ damage.
JNC 7 and the American Heart Association (AHA) recommend a target BP of <130/80 for patients with:
- Chronic kidney disease (CKD)
- Although an optimal screening interval has not been defined, the current VA/DoD guidelines recommend annual BP screening. JNC 7 recommends screening for hypertension every 2 years for patients with BP <130/85, and more frequently for patients with BP >130/85.
- Checking BP at all clinic visits should be encouraged.
How to Measure Blood Pressure in the Office
- The patient should be seated in a chair for 5 minutes, feet on the floor, with arm at heart level.
- The patient should not have smoked, had caffeine, or exercised within 30 minutes before BP measurement.
- Cuff bladder should encircle ≥80% of arm.
- The average of at least 2 measurements per office visit should be recorded.
- The diagnosis of prehypertension or hypertension (see Table 1 below) is based on the presence of an elevated BP taken on at least 2 office visits over a 2-month period. For Stage 2 hypertension, evaluation or referral should be performed within 1 month of the initial measurement.
|Blood Pressure (mmHg)||Classification||Treatment (associated tables in bold)|
|* Comorbidities include diabetes, CAD, peripheral vascular disease, cerebrovascular disease, heart failure, or renal disease defined as a reduced GFR (CrCl <60 mL/min/1.75 m2) or albuminuria (>300 mg/dL).
# The JNC 7 Report recommends a target BP of <130/80 for patients with diabetes or CKD. AHA 2007 guidelines also recommend a target BP of <130/80 for patients withknown CAD, or CAD equivalents (carotid or peripheral arterial disease, abdominal aortic aneurysm), or 10-year Framingham Risk Score ≥10%.
Adapted from VA/DoD Clinical Practice Guideline Working Group. Management of Hypertension in Primary Care. Washington, D.C.: Department of Veterans Affairs, Office of Quality and Performance; 2004.
Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72.
Rosendorff C, Black HR, Cannon CP, et al. Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease: A Scientific Statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007 May 29;115(21):2761-88.
|Stage 1 hypertension|
|Stage 2 hypertension|
Office Evaluation of the Hypertensive Patient
Specific findings of end-organ damage or cardiovascular comorbidities should guide the choice or intensity of therapy and prompt possible additional workup. The basic evaluation of the hypertensive patient, adapted from the JNC 7, is shown below. Although <5% of patients have secondary hypertension, clinicians should be alert to possible underlying causes such as Cushing syndrome or sleep apnea. Workup of secondary hypertension is addressed in VA/DoD guidelines.
Evaluation of Hypertensive Patients for End-Organ Damage and Treatable Comorbidities
- All hypertensive patients should be encouraged to attempt lifestyle modification.
- Whenever possible, tobacco use should be addressed (see Smoking Cessation).
Lifestyle Modifications Shown to Reduce Blood Pressure
|Area to Modify||Goals||Anticipated SBP Reduction|
|Adapted from Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72.|
|Weight||5-20 mmHg per 10 kg weight loss|
- Many patients will require pharmacologic therapy.
- Considerations in choosing antihypertensive medication:
- Thiazide diuretics have been shown to prevent cardiovascular events related to hypertension and are recommended as first-line therapy for most patients. For patients with renal or cardiovascular comorbidity, other agents may offer additional benefit (see below and Table 2).
- ACEIs, ARBs, BBs, and long-acting CCBs also have been shown to reduce the cardiovascular complications of hypertension.
- In the absence of known coronary disease or congestive heart failure, BBs are not recommended for first-line treatment of HTN, given their association with insulin intolerance and increased risk of stroke, particularly among smokers.
- Many patients require 2 agents for sufficient control. Add a second agent if upward titration of the initial agent does not adequately control BP.
- Patients with Stage 2 hypertension generally should be started on 2 drugs. One study has shown the combination of an ACEI + a dihydropyridine CCB to be associated with decreased mortality and cardiovascular events compared with an ACEI + a thiazide; however, many experts include a thiazide in first-line therapy.
- Patients with renal or cardiovascular comorbidities may gain particular benefit from specific types of antihypertensive drugs. See below and Table 2).
- Many antihypertensive drugs that are commonly prescribed together are marketed as single-tablet FDCs. These can be useful if the patient tolerates the same dosage of each drug given separately.
- Whenever possible, use medications that can be given once daily to promote adherence.
Classes of Antihypertensives Favored in the Setting of Specific Comorbidities
* Not recommended as monotherapy for HTN, and may worsen glucose homeostasis|
Adapted from Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72.
|High risk of CAD||x||x||x||x|
|Prevention of recurrent stroke||x||x|
Evaluation of Treatment Response
- Home BP monitoring can provide extremely useful information on BP control; BP cuffs for home use can be ordered through the local Prosthetics Service. Devices with a memory function are preferable to patient recall or diary-keeping.
- Patients should be seen within 1 month after initiating therapy to assess efficacy, adherence, and toxicity. (Patients requiring blood tests, those at high risk of end-organ damage, and those at risk of postural hypotension should be seen earlier.)
- If BP is controlled to the target range, adequacy of control should be reevaluated at least every 3-6 months.
- If BP is not controlled:
- Explore adherence to regimen and educate patients about the importance of controlling hypertension.
- Be alert to use of concomitant medications that may increase BP (eg, NSAIDs, decongestants, erythropoietin, cyclosporine) and to substance use (eg, alcohol, methamphetamine, cocaine).
- Consider titration of initial drug regimen (usually doubling of dosage; see Table 2).
- Add an agent from a second class. Agents shown to decrease morbidity and mortality are preferred (ACEI, ARB, BB, long-acting CCB, thiazide).
- Consider joint care management with a clinical pharmacist.
When to Refer
|Hypertension Clinic, Cardiology, or Renal|
- Dosages listed here are for hypertension only. Many of these agents (eg, ACEIs) have additional indications, such as for congestive heart failure, for which lower dosages may be appropriate.
- "Divided" means "1/X of the daily dosage, given X times per day." Therefore, "100 mg daily, divided BID" means 50 mg BID. It does not mean 100 mg BID.
- Drugs listed are representative of their respective classes only; other drugs within each class are also used, and specific dosing information should be followed.
|Generic Drug Name||Usual Starting Dosage/Dosage Titration||Comments/Drug Interactions|
|Chlorthalidone||Start at 12.5-25 mg QD; may increase up to 50 mg QD; dosages >50 mg carry risk of hypokalemia without added benefit|
|Hydrochlorothiazide (HCTZ)||Start at 12.5-25 mg QD; may increase up to 50 mg QD (dosages >25 mg carry risk of hypokalemia with limited added benefit)|
|Atenolol||Start at 25-50 mg QD or divided BID; maximum 100 mg per day||ATV may ↑ atenolol concentrations; no dosage adjustment appears to be necessary.|
|Metoprolol||Start at 50 mg BID; maximum 225 mg BID||CYP 2D6 substrate; PIs may ↑ metoprolol levels.|
|Metoprolol Extended Release||Start at 50-100 mg QD; maximum 400 mg QD||CYP 2D6 substrate; PIs may ↑ metoprolol levels.|
|Propranolol||Start at 20 mg BID; maximum 640 mg per day in divided doses|
|Propranolol Extended Release||Start at 60 mg QD; maximum 640 mg QD||Extended-release formulation cannot be substituted for immediate-release form on a mg per mg basis; may require dosage change.|
|Carvedilol||Start at 6.25 mg BID; titrate slowly; usual dosage: 12.5-50 mg/day, divided BID||CYP 2D6 substrate; PIs may ↑ carvedilol levels.|
|Labetalol||Usual dosage: 200-800 mg/day, divided BID||IV form useful in hypertensive emergencies.|
|Benazepril||Start at 10 mg QD; maximum 80 mg per day; usual dosage: 20-40 mg QD or divided BID; may need BID dosing for continuous BP control||Start at 5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.|
|Fosinopril||Start at 10 mg QD; maximum 80 mg per day, but no additional effect over 40 mg per day; usual dosage: 10-40 mg QD or divided BID; BID dosing may be needed for continuous BP control||Start at 5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.|
|Lisinopril||Start at 10 mg QD; maximum 80 mg QD but no additional effect over 40 mg per day; usual dosage: 20-40 mg QD||Start at 2.5-5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.|
|Ramipril||Start at 2.5 mg QD; maximum 20 mg QD; usual dosage: 2.5-20 mg QD or divided BID; may need BID dosing for continuous BP control||Start at 1.25 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.|
|Angiotensin Receptor Blockers (ARBs)|
|Candesartan||Usual starting dosage: 16 mg QD, may be divided BID; maximum 32 mg per day||Start at lower dosage in patients with moderate or worse hepatic impairment, volume depletion.|
|Irbesartan||Start at 150 mg QD; maximum 300 mg QD||Start at 75 mg QD for patients with volume depletion.|
|Losartan||Start at 50 mg QD; maximum 100 mg QD or divided BID||Start at 25 mg QD for patients with volume depletion or hepatic insufficiency.|
|Telmisartan||Usual starting dosage: 40 mg QD; maximum 80 mg QD||Start at 20 mg QD in elderly, patients with hepatic impairment or volume depletion; monitor closely.|
|Valsartan||Start at 80 mg QD; maximum 320 mg QD|
|Calcium Channel Blockers (CCBs)|
|Amlodipine||Start at 2.5 mg QD; maximum 10 mg daily||See Cons above.|
|Diltiazem Sustained Release||Start at 60 mg BID; maximum 360 mg per day in divided doses|
|Diltiazem Extended Release||Start at 120 mg QD; maximum 540 mg QD|
|Nifedipine Extended Release||Start at 30 mg QD; maximum 120 mg QD|
|Verapamil Sustained Release||Start at 120 mg QD; maximum 480 mg per day, but divide BID if using >240 mg per day||Immediate-release formulation is not recommended for treatment of hypertension.|
|Verapamil Extended Release||Immediate-release formulation is not recommended for treatment of hypertension.|
|Potassium-Sparing Diuretics and Aldosterone Antagonists|
|Spironolactone||Usual dosage is 50 mg to 100 mg QD or divided BID|
|Triamterene||Start at 100 mg BID; maximum daily dosage is 300 mg||Monitor for hyperkalemia; check K+ 1 week after starting triamterene.|
|Direct Vasodilators and Anti-Adrenergic Agents|
|Clonidine||Possible adverse effects include bradycardia, sedation. Risk of rebound hypertension upon discontinuation: taper over course of 7 days.|
|Hydralazine||Start at 25 mg BID; increase by 10-25 mg/dose to effective dosage; may divide effective daily dosage BID; maximum 200 mg per day in divided doses||Possible adverse effects include lupus-like syndrome, requiring discontinuation (increased risk at higher dosages). May cause reflex tachycardia; use with caution in patients with CAD.|
|Doxazosin||Start at 1 mg QHS; maximum 16 mg per day||Not a first-line agent. Possible adverse effects include risk of CHF, dizziness, postural hypotension, drowsiness, and syncope; all more likely if doxazosin is given with other vasodilators, including PDE-5 inhibitors. Risk of syncope with initial dosages; start at lowest dose QHS. If drug is interrupted, restart at 1 mg QHS dosing.|
|Prazosin||Start at 1 mg BID or TID; usual maintenance dosage 20 mg/day divided BID or TID; maximum 40 mg divided BID or TID||Not a first-line agent. Possible adverse effects include risk of CHF, dizziness, postural hypotension, drowsiness, and syncope; all more likely if prazosin is given with other vasodilators, including PDE-5 inhibitors. Risk of syncope with initial dosages; start at lowest dose QHS. If drug is interrupted, restart at 1 mg QHS.|
|Terazosin||Start at 1 mg QHS; usual daily dosage 1-5 mg QD or divided BID; maximum 20 mg per day||Not a first-line agent. Possible adverse effects include risk of CHF, dizziness, postural hypotension, drowsiness, and syncope; all more likely if terazosin is given with other vasodilators, including PDE-5 inhibitors. Risk of syncope with initial dosages; start at lowest dosage QHS. If drug is interrupted, restart at 1 mg QHS dosing.|
- Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72.
- Crane HM, Van Rompaey SE, Kitahata MM. Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy. AIDS. 2006 Apr 24;20(7):1019-26.
- Friis-Møller N, Weber R, Reiss P, et al. Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy. Results from the DAD study. AIDS. 2003 May 23;17(8):1179-93.
- Jamerson K, Weber MA, Bakris GL, et al; ACCOMPLISH Trial Investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008 Dec 4;359(23):2417-28.
- Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005 Oct 29-Nov 4;366(9496):1545-53.
- Rosendorff C, Black HR, Cannon CP, et al; American Heart Association Council for High Blood Pressure Research; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention. Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease: A Scientific Statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention.. Circulation. 2007 May 29;115(21):2761-88.
- Seaberg EC, Muñoz A, Lu M, et al. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS. 2005 Jun 10;19(9):953-60.
- VA/DoD Clinical Practice Guideline Working Group. Management of Hypertension in Primary Care. Washington, D.C.: Department of Veterans Affairs, Office of Quality and Performance; 2004.