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Hypertension and HIV

for Health Care Providers

Hypertension

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.

Key Points

  • 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.

Background

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 7Link will take you outside the VA website.], 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*

Hypertension: 45%

*Veterans in the VA HIV Clinical Case Registry in care in 2007 who had an ICD-9 code corresponding to this condition

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:

  • Diabetes
  • Chronic kidney disease (CKD)

Evaluation

Screening

  • 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.
Table 1. Definition and Treatment of High Blood Pressure
Blood Pressure (mmHg)ClassificationTreatment (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 reportLink will take you outside the VA website.. 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 PreventionLink will take you outside the VA website.. Circulation. 2007 May 29;115(21):2761-88.
<120/80Normal
  • No treatment indicated.
  • Encourage lifestyle measures as shown under Management.
  • Systolic: 120-139
  • or
  • Diastolic: 80-89
Prehypertension
  • Lifestyle modification and
  • Treat comorbidity,* if present and appropriate.
  • If diabetic, treat to target BP of <140/80.
  • Systolic: 140-159
  • or
  • Diastolic: 90-99
Stage 1 hypertension
  • Goal: BP <140/90 (140/80 if diabetic)
  • Lifestyle modification and
  • Start medication
    • If no comorbidity,* use thiazide (preferred) or angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), beta-blocker (BB), calcium channel blocker (CCB), or fixed-dose combination (FDC) of agents.
    • If comorbidity,* choose from table of disease-specific antihypertensives.
  • Systolic: >159
  • or
  • Diastolic: >99
Stage 2 hypertension
  • Goal: BP <140/90 (140/80 if diabetic)
  • Lifestyle modification and
  • Start 2 medications
    • If no comorbidity,* use thiazide plus ACEI, ARB, BB, or CCB, dosed separately or as an FDC.
    • If comorbidity,* choose from table of disease-specific antihypertensives.
  • Consider gradual BP reduction starting with 1 agent for patients at risk of postural hypotension (eg, elderly).

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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

ComponentEvaluationPossible Findings
History
  • Review of systems
  • Past medical history
  • Health-related behavior
  • Family history
  • Dyspnea, chest pain, edema, polyuria/polydipsia
  • CAD, CHF, diabetes, renal disease
  • Tobacco use, physical activity
  • Early CAD, diabetes
Physical examination
  • Vital signs
  • Ophthalmologic examination
  • Peripheral circulation
  • Cardiac examination
  • Respiratory examination
  • Elevated BMI
  • Arteriovenous nicking, papilledema (hypertensive retinopathy)
  • Diabetic retinopathy
  • Bruits: carotid, abdominal, or femoral (peripheral vascular disease)
  • Decreased peripheral pulses
  • LVH, S3, S4, distended neck veins (hypertrophy, failure)
  • Crackles/wheezes
Studies
  • Electrolytes, BUN, Cr, glucose, Ca2+
  • Fasting lipids
  • Urinalysis
  • ECG
  • Spot urine protein/Cr ratio
  • Decreased renal function, diabetes, hyperaldosteronism
  • Hyperlipidemia
  • Proteinuria, glycosuria, hematuria
  • LVH, CAD

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Management

Initial Management

Lifestyle modification

  • 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 ModifyGoalsAnticipated 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 reportLink will take you outside the VA website.. JAMA. 2003 May 21;289(19):2560-72.
Diet
  • DASH (Dietary Approaches to Stop Hypertension) diet:
    • HIGH in fruit/vegetables, lean protein, low-fat dairy products, nuts, fiber, K+, Mg+ Ca+, whole grains (risk of hyperkalemia in patients with renal disease)
    • LOW in lean red meat, sugars
  • For specific dietary recommendations, including serving sizes and ingredients, see the DHHS DASH diet guide
  • Low sodium diet: ≤2.4 g/day
8-14 mmHg
Exercise
  • >30 minutes of aerobic exercise daily
    • Aerobic activity = brisk walking
4-9 mmHg
Alcohol
  • ≤2 alcoholic drinks/day (men) or ≤1 drink/day (women)
    • 1 drink = 0.4 oz (12 g) of ethanol: 12 oz beer, 5 oz wine, or 1.5 oz 80-proof (40%) liquor
  • See Alcohol Misuse
2-4 mmHg
Weight5-20 mmHg per 10 kg weight loss
Resources

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Medications

  • 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

ComorbidityDiureticBBACEIARBCCBAldosterone Antagonist
* 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 reportLink will take you outside the VA website.. JAMA. 2003 May 21;289(19):2560-72.
CHFxxxxx
Post-MIxxx
High risk of CADxxxx
Diabetesx*xxx
CKDxx
Prevention of recurrent strokexx

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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
  • Failure to achieve target BP after addition of second drug class
  • Workup indicating secondary hypertension
Emergency Department
  • Hypertensive emergency: BP >180/120 complicated by:
    • Hypertensive encephalopathy
    • Intracranial hemorrhage
    • Acute MI or unstable angina
    • Dissecting aortic aneurysm
    • Acute heart failure with pulmonary edema
  • Hypertensive urgency: BP >180/120 without target organ dysfunction. May see:
    • Headache
    • Epistaxis
    • Shortness of breath
    • Severe anxiety

Notes

  • 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.
Table 2. Antihypertensives: Drug Dosing and Interactions with ARVs
Generic Drug NameUsual Starting Dosage/Dosage TitrationComments/Drug Interactions
Thiazide Diuretics
  • Pros: Cardioprotective in ALLHAT study; first-line therapy in JNC 7, VA/DoD guidelines. Thiazide diuretics and CCBs may be more effective than other antihypertensives for African American patients.
  • Cons: Risk of hypokalemia. Monitor electrolytes periodically. Other potential adverse effects include rash, hyperglycemia, sexual dysfunction, and frequent urination. Should not be given to patients with a history of gout, as they may trigger attacks.
ChlorthalidoneStart 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)
Beta-Blockers (BBs)
  • Pros: Useful for patients with concomitant CAD, CHF, previous MI, or those in need of rate control owing to atrial fibrillation or flutter.
  • Cons: May be associated with increased risk of stroke (particularly in smokers) and insulin resistance. When discontinuing, taper over course of 14 days to avoid rebound hypertension, angina, MI, or arrhythmia. May be less effective for patients without CAD, especially elderly patients. Use with caution in patients with reactive airway disease. Potential adverse effects include bradycardia, hypotension, fatigue, and sexual dysfunction.
AtenololStart at 25-50 mg QD or divided BID; maximum 100 mg per dayATV may ↑ atenolol concentrations; no dosage adjustment appears to be necessary.
MetoprololStart at 50 mg BID; maximum 225 mg BIDCYP 2D6 substrate; PIs may ↑ metoprolol levels.
Metoprolol Extended ReleaseStart at 50-100 mg QD; maximum 400 mg QDCYP 2D6 substrate; PIs may ↑ metoprolol levels.
PropranololStart at 20 mg BID; maximum 640 mg per day in divided doses
Propranolol Extended ReleaseStart at 60 mg QD; maximum 640 mg QDExtended-release formulation cannot be substituted for immediate-release form on a mg per mg basis; may require dosage change.
Mixed Alpha-/Beta-Blockers
  • Pros: Useful for patients with known CAD or CHF.
  • Cons: Same as for BBs. Avoid in patients with decompensated heart failure who are dependent on sympathetic stimulation.
CarvedilolStart at 6.25 mg BID; titrate slowly; usual dosage: 12.5-50 mg/day, divided BIDCYP 2D6 substrate; PIs may ↑ carvedilol levels.
LabetalolUsual dosage: 200-800 mg/day, divided BIDIV form useful in hypertensive emergencies.
ACE Inhibitors
  • Pros: Cardioprotective, renal protective.
  • Cons:Avoid during pregnancy; use with caution in patients who are elderly, are fluid depleted, or have renal insufficiency. Risk of hyperkalemia. Check electrolytes 1 week after starting ACEI. Other potential adverse effects include angioedema, cough, renal insufficiency, and sexual dysfunction.
BenazeprilStart 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 controlStart at 5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
FosinoprilStart 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 controlStart at 5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
LisinoprilStart at 10 mg QD; maximum 80 mg QD but no additional effect over 40 mg per day; usual dosage: 20-40 mg QDStart at 2.5-5 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
RamiprilStart 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 controlStart at 1.25 mg QD if patient is elderly, has renal insufficiency, or is taking a diuretic.
Angiotensin Receptor Blockers (ARBs)
  • Pros: Cardioprotective, renal protective.
  • Cons:Avoid during pregnancy; use with caution in patients who are elderly, are fluid depleted, or have renal insufficiency. Risk of hyperkalemia. Other potential adverse effects include angioedema and renal dysfunction.
CandesartanUsual starting dosage: 16 mg QD, may be divided BID; maximum 32 mg per dayStart at lower dosage in patients with moderate or worse hepatic impairment, volume depletion.
IrbesartanStart at 150 mg QD; maximum 300 mg QDStart at 75 mg QD for patients with volume depletion.
LosartanStart at 50 mg QD; maximum 100 mg QD or divided BIDStart at 25 mg QD for patients with volume depletion or hepatic insufficiency.
TelmisartanUsual starting dosage: 40 mg QD; maximum 80 mg QDStart at 20 mg QD in elderly, patients with hepatic impairment or volume depletion; monitor closely.
ValsartanStart at 80 mg QD; maximum 320 mg QD
Calcium Channel Blockers (CCBs)
  • Pros: CCBs and thiazide diuretics may be more effective than other antihypertensives for African American patients.
  • Cons: Metabolism of CCBs is inhibited by PIs; if CCBs must be used with PIs, reduce initial dosage and titrate up while monitoring for side effects (eg, hypotension, conduction block, bradycardia, and peripheral edema). Metabolism of CCBs may be induced by the NNRTIs EFV and NVP, leading to blunted antihypertensive effect.
  • Avoid immediate-release forms. Avoid in patients with CHF.
AmlodipineStart at 2.5 mg QD; maximum 10 mg dailySee Cons above.
Diltiazem Sustained ReleaseStart at 60 mg BID; maximum 360 mg per day in divided doses
Diltiazem Extended ReleaseStart at 120 mg QD; maximum 540 mg QD
Nifedipine Extended ReleaseStart at 30 mg QD; maximum 120 mg QD
Verapamil Sustained ReleaseStart at 120 mg QD; maximum 480 mg per day, but divide BID if using >240 mg per dayImmediate-release formulation is not recommended for treatment of hypertension.
Verapamil Extended Release
  • Covera HS: Start at 180 mg QHS; maximum 480 mg QHS
  • Verelan PM: start at 100 mg QHS; maximum 400 mg QHS
Immediate-release formulation is not recommended for treatment of hypertension.
Potassium-Sparing Diuretics and Aldosterone Antagonists
  • Pros: Indicated in CAD, and CHF with EF <40%, class IV heart failure. May be useful in patients with hypokalemia; often combined with a thiazide diuretic.
  • Cons: May cause hyperkalemia: monitor K+
SpironolactoneUsual dosage is 50 mg to 100 mg QD or divided BID
  • Monitor for hyperkalemia; check K+ 1 week after starting spironolactone.
  • Potential adverse effects include liver toxicity, gynecomastia, and sexual dysfunction.
TriamtereneStart at 100 mg BID; maximum daily dosage is 300 mgMonitor for hyperkalemia; check K+ 1 week after starting triamterene.
Direct Vasodilators and Anti-Adrenergic Agents
  • (Note: Alpha-blockers used for treatment of benign prostatic hypertrophy are not recommended as monotherapy for hypertension; however, these may cause hypotension especially in patients who are taking other antihypertensive medications.)
Clonidine
  • PO: Start at 0.1 mg BID; increase to usual maintenance dosage of 0.2-1.2 mg divided BID to TID; maximum 2.4 mg in divided doses
  • Patch: Start at 0.1 mg/24-hour patch, increasing to desired effect; maximum dosage is 0.6 mg/24-hour patch
Possible adverse effects include bradycardia, sedation. Risk of rebound hypertension upon discontinuation: taper over course of 7 days.
HydralazineStart 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 dosesPossible adverse effects include lupus-like syndrome, requiring discontinuation (increased risk at higher dosages). May cause reflex tachycardia; use with caution in patients with CAD.
DoxazosinStart at 1 mg QHS; maximum 16 mg per dayNot 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.
PrazosinStart at 1 mg BID or TID; usual maintenance dosage 20 mg/day divided BID or TID; maximum 40 mg divided BID or TIDNot 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.
TerazosinStart at 1 mg QHS; usual daily dosage 1-5 mg QD or divided BID; maximum 20 mg per dayNot 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.

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References