Clinical Practice Guidelines to Management of

HypertensionCombined JNC 7 and JNC 8 Hypertension Guidelines

Gene Pabayos, MD

O 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults O Report From the Panel Members Appointed to the

Eighth Joint National Committee (JNC 8)O The Seventh Report of the Joint National

Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

O 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

HypertensionO Hypertension is the most common

condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately.O JNC8

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Classification of BP for adults 18 years and older. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits

Prehypertension is not a disease category

O high risk of developing hypertensionO not candidates for drug therapyO based on their level of BP and should

be firmly and unambiguously advised to practice lifestyle modification in order to reduce their risk of developing hypertension in the future

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Importance of Systolic Blood Pressure

O The rise in SBP continues throughout lifeO DBP, which rises until approximately age 50, tends

to level off over the next decade, and may remain the same or fall later in life

O Diastolic hypertension predominates before age 50, either alone or in combination with SBP elevation.

O The prevalence of systolic hypertension increases with ageO above 50 years of age, systolic hypertension

represents the most common form of hypertension.O DBP is a more potent cardiovascular risk factor

than SBP until age 50; thereafter, SBP is more important

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Accurate Blood Pressure Measurement in the Office

O Persons should be seated quietly for at least 5 minutes in a chair (rather than on an exam table), with feet on the floor, and arm supported at heart level.

O Caffeine, exercise, and smoking should be avoided for at least 30 minutes prior to measurement.

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Accurate Blood Pressure Measurement in the Office

O Measurement of BP in the standing position is indicated periodically, especially in those at risk for postural hypotension, prior to necessary drug dose or adding a drug, and in those who report symptoms consistent with reduced BP upon standing.

O At least two measurements should be made and the average recorded

Accurate Blood Pressure Measurement in the Office

O An appropriatelysized cuff (cuff bladder encircling at least 80 percent of the arm) should be used to ensure accuracy.

O At least two measurements should be made and the average recorded.

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Self-MeasurementO Self-monitoring of BP at home and workO Practical approach to assess differences

between office and out-of-office BP prior to consideration of ABPM

O For those whose out-of-office BPs are consistently <130/80 mmHg despite an elevated office BP, and who lack evidence of target organ disease

O 24-hour monitoring or drug therapy can be avoided

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Ambulatory Blood Pressure Monitoring (ABPM)

O Provides information about BP during daily activities and sleep

O Prevents white-coat effectO usually lower than clinic readings

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Patient EvaluationO Evaluation of hypertensive patients

has three objectives: 1. to assess lifestyle and identify other

cardiovascular risk factors or concomitant disorders that may affect prognosis and guide treatment

2. to reveal identifiable causes of high BP

3. to assess the presence or absence of target organ damage and CVD

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Laboratory Tests and Other Diagnostic Procedures

O 12-lead electrocardiogramO UrinalysisO blood glucose and hematocritO serum potassiumO creatinine (or the corresponding estimated

glomerular filtration rate [eGFR])O CalciumO lipoprotein profile (after a 9- to 12-hour fast) that

includes: O high-density lipoprotein cholesterol (HDL-C)O low-density lipoprotein cholesterol (LDL-C)O triglycerides

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O Optional tests include:O measurement of urinary albumin

excretion; orO albumin/creatinine ratio (ACR)

O except for those with diabetes or kidney disease where annual measurements should be made

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Identifiable Causes of Hypertension

O Additional diagnostic procedures may be indicated to identify causes of hypertension, particularly in patients whose

1. age, history, physical examination, severity of hypertension, or initial laboratory findings suggest such causes

2. BP responds poorly to drug therapy3. BP begins to increase for uncertain reason

after being well controlled; and4. onset of hypertension is sudden

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Clinical Questions1. In adults with hypertension, does initiating

antihypertensive pharmacologic therapy at specific BP thresholds improve health outcomes?

2. In adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified BP goal lead to improvements in health outcomes?

3. In adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes?

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Treatment goalsJNC 7 JNC 8

O SBP <140 mmHg and DBP <90 mmHg

O For patients with diabetes and renal diseases: SBP <130 mmHg and DBP <80 mmHg

O In patients ≥60 years old: SBP <150 mmHg and DBP <90 mmHg

O In patients <60 years old: SBP <140 mmHg DBP <90 mmHg

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Lifestyle Management Recommendations

O Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy products, poultry, fish, legumes, nontropical vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages and red meats.

a) Adapt this dietary pattern to appropriate calorie requirements, personal and cultural food preferences, and nutrition therapy for other medical conditions (including diabetes mellitus).

b) Achieve this pattern by following plans such as the DASH dietary pattern, the USDA Food Pattern, or the AHA Diet.

Lower sodium intake. a) Consume no more than 2,400 mg of

sodium/day; b) Further reduction of sodium intake to

1,500 mg/day is desirable since it is associated with even greater reduction in BP; and

c) Reduce intake by at least 1,000 mg/day since that will lower BP, even if the desired daily sodium intake is not yet achieved.

O Combine the DASH dietary pattern with lower sodium intake.

Sodium IntakeO In adults aged 25–75 years with BP 120–

159/80–95 mmHg, reducing sodium intake that achieved a mean 24-hour urinary sodium excretion of approximately 2,400 mg/day, relative to approximately 3,300 mg/day, lowers BP by 2/1 mmHg, and reducing sodium intake that achieved a mean 24-hour urinary sodium excretion of approximately 1,500 mg/day lowers BP by 7/3 mmHg.O Strength of evidence: moderate

Sodium IntakeO In adults aged 30–80 with or

without hypertension, counseling to reduce sodium intake by an average of 1,150 mg per day reduces BP by 3–4/1–2 mmHg.O Strength of evidence: high

DASH Dietary Pattern High In Low In

O VegetablesO FruitsO low-fat dairy productsO whole grainsO PoultryO FishO NutsO Diet rich in:

O PotassiumO MagnesiumO CalciumO ProteinO fiber

O sweetsO sugar-sweetened

beveragesO red meats O saturated fatO total fatO cholesterol

DASH DietO When all food was supplied to adults

with blood pressure 120–159/80–95 mmHg and both body weight and sodium intake were kept stable, the DASH dietary pattern, when compared to a typical American diet of the 1990s, lowered blood pressure by 5–6/3 mmHg. O Strength of evidence: high

DASH Variations

1. 10% of total daily energy from carbohydrate with protein

2. replaced the same amount of carbohydrate with unsaturated fat

DASH VariationO In adults with BP of 120–159/80–95 mmHg,

modifying the DASH dietary pattern by replacing 10 percent of calories from carbohydrates with the same amount of either protein or unsaturated fat (8 percent monounsaturated and 2 percent polyunsaturated) lowered systolic BP by 1 mmHg compared to the DASH dietary pattern. Among adults with BP 140–159/90–95 mmHg, these replacements lowered systolic BP by 3 mmHg relative to DASH. O Strength of evidence: moderate

PHYSICAL ACTIVITY O In general, advise adults to engage

in aerobic physical activity to lower BP: 3 to 4 sessions a week, lasting on average 40 minutes per session, and involving moderate-to-vigorous intensity physical activity.

Aerobic exercise training and blood pressure

O Among adult men and women at all BP levels, including hypertensive individuals, aerobic physical activity decreases systolic and diastolic BP, on average, by 2–5 and 1–4 mmHg, respectively. Typical interventions shown to be effective for lowering BP include aerobic physical activity of, on average, at least 12 weeks duration, 3 to 4 sessions per week, lasting on average 40 minutes per session, and involving moderate-to-vigorous intensity physical activity.O Strength: high

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Drug Therapy

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O Thiazide-type diuretics for most

O May consider ACEI, ARB, BB, CCB, or combination

O In the general nonblack population, including those with diabetes, initial antihypertensive: O thiazide-type diureticO CCBO ACEIO ARB

O In the general black population, including those with diabetes, initial antihypertensive:O thiazide-type diureticO CCB

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2014 Evidence-Based Guideline for the Management

of High Blood Pressure in Adults Report From the Panel

Members Appointed to the Eighth Joint National Committee (JNC 8)

Recommendation 1O In the general population aged 60

years, initiate pharmacologic treatment to lower blood pressure (BP) at systolic blood pressure (SBP)150 mmHg or diastolic blood pressure (DBP)90mmHg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg. O Strong Recommendation – Grade A

Corollary Recommendation

O In the general population aged60years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140mmHg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted. O Expert Opinion – Grade E

Recommendation 2O In the general population <60 years,

initiate pharmacologic treatment to lower Bp at DBP 90mmHg and treat to a goal DBP <90mmHg.O For ages 30-59 years

O Strong Recommendation – Grade AO For ages 18-29 years

O Expert Opinion – Grade E

Recommendation 3O In the general population <60 years,

initiate pharmacologic treatment toO Lower BP at SBP 140mmHg and treat

to a goal SBP <140mmHg.O Expert Opinion – Grade E

Recommendation 4O In the population aged 18 years with

chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP 90 mmHg and treat to goal SBP <140mmHg and goal DBP <90mmHg. O Expert Opinion – Grade E

Recommendation 5O In the population aged 18 years with

diabetes, initiate pharmacologic treatment to lower BP at SBP 140mmHg or DBP90mmHg and treat to a goal SBP <140mmHg and goal DBP <90mmHg. O Expert Opinion –Grade E

Recommendation 6O In the general nonblack population,

including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB).O Moderate Recommendation – Grade B

O Each of the 4 drug classes recommended by the panel in recommendation 6 yielded comparable effects on overall mortality and cardiovascular, cerebrovascular, and kidney outcomes, with one exception: heart failure.

O Initial treatment with a thiazide-type diuretic was more effective than a CCB or ACEI and an ACEI was more effective than a CCB in improving heart failure outcomes

O The panel did not recommend β-blockers for the initial treatment of hypertension O in one study use of β-blockers resulted in

a higher rate of the primary composite outcome of cardiovascular death, myocardial infarction, or stroke compared to use of an ARB, a finding that was driven largely by an increase in stroke.

O β-blocker performed similarly to the other drugs

O α-Blockers were not recommended as first-line therapy because in one study initial treatment with an α-blocker resulted in worse cerebrovascular, heart failure, and combined cardiovascular outcomes than initial treatment with a diuretic

O There were no RCTs of good or fair quality comparing the following drug classes to the 4 recommended classes:O dual α1- + β-blocking agents (eg, carvedilol) O vasodilating β-blockers (eg, nebivolol)O central α2-adrenergic agonists (eg, clonidine)O Direct vasodilators (eg, hydralazine)O aldosterone receptor antagonists (eg,

spironolactone)O adrenergic neuronal depleting agents

(reserpine)O loop diuretics (eg, furosemide)

Recommendation 7O In the general black population,

including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic or CCB. O For general black population

O Moderate Recommendation –Grade BO for black patients with diabetes

O Weak Recommendation – Grade C

O In the ALLHAT study, a thiazide-type diuretic was shown to be more effective in improving cerebrovascular, heart failure, and combined cardiovascular outcomes compared to an ACEI in the black patient subgroup, which included large numbers of diabetic and nondiabetic participants

O Although a CCB was less effective than a diuretic in preventing heart failure in the black subgroup of this trial, there were no differences in other outcomes (cerebrovascular, CHD, combined cardiovascular, and kidney outcomes, or overall mortality) between a CCB and a diuretic

O The panel recommended a CCB over an ACEI as first-line therapy in black patients because there was a 51% higher rate (relative risk, 1.51; 95% CI, 1.22-1.86) of stroke in black persons in ALLHAT with the use of an ACEI as initial therapy compared with use of a CCB.

O The ACEI was also less effective in reducing BP in black individuals compared with the CCB

O Therefore, both thiazide-type diuretics and CCBs are recommended as first-line therapy for hypertension in black patients

Recommendation 8O In the population aged18 years with

CKD, initial (or add-on) antihypertensive treatment should include an ACEI or ARB to improve kidney outcomes. This applies to all CKD patients with hypertension regardless of race or diabetes status. O Moderate Recommendation – Grade B

Recommendation 9O The main objective of hypertension treatment

is to attain and maintain goal BP. If goal BP is not reached within a month of treatment, increase the dose of the initial drug or add a second drug from one of the classes in recommendation(thiazide-type diuretic, CCB, ACEI, or ARB).

O The clinician should continue to assess BP and adjust the treatment regimen until goal BP is reached. If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list provided.

Recommendation 9O Do not use an ACEI and an ARB together in the

same patient.O If goal BP cannot be reached using only the drugs

in recommendation because of a contraindication or the need to use more than 3 drugs to reach goal BP, antihypertensive drugs from other classes can be used.

O Referral to a hypertension specialist may be indicated for patients in whom goal BP cannot be attained using the above strategy or for the management of complicated patients for whom additional clinical consultation is needed.

O Expert Opinion – Grade E

JNC 8 Guideline Algorhythm

Categories of Antihypertensives

1. Diuretics2. Sympathoplegic agents3. Direct vasodilators4. Agents that block production or

action of angiotensin

Angiotensin Converting Enzyme Inhibitors (ACEi)O Captopril, Enalapril, LisinoprilO MOA: Blocks Angiotensin converting enzyme

leads to decreased production of angiotensin II (decreased vasoconstriction, and aldosterone secretion), and decreased bradykinin conversion

O ADR: acute renal failure, dry cough, angioedema, fetal hypotension, anuria, renal failure, teratogenic

O Mild ADR: altered sense of taste, allergic skin rashes, and drug fever (10% of patients)

Angiotensin II Receptor Blockers (ARBs)

O Losartan, Valsartan, Candesartan, Eprosartan, Irbesartan

O MOA: blocks receptor sites for Angiotensin II, more selective blocker of angiotensin effects

O ADR: acute renal failure, dry cough (less common), angioedema, fetal hypotension, anuria, renal failure, teratogenic

Beta-BlockersO Atenolol, MetoprololO MOA: inhibiting stimulation of β 1

adrenoceptors such as those in the heart but 50- to 100-fold less potent than propranolol in blocking β 2 receptors

O Metoprolol is extensively metabolized by CYP2D6 with high first pass metabolism

O Atenolol is not extensively metabolized and is excreted primarily in the urine

O ADR: Bradycardia, fatigue, vivid dreams, cold hands

Other Beta BlockersO Non beta selective: PropranololO Beta Blocking and Vasodilating

effects: Labetalol, Carvedilol, Nebivolol

O ADR: Bradycardia, worsened asthma, fatigue, vivid dreams, cold hands

Calcium Channel Blockers (CCB)

O Amlodipine, Diltiazem, NitrendipineO MOA: inhibition of calcium influx into

arterial smooth muscle cells. Have anti-anginal and anti-arrhythmic effect

O ADR: Excessive hypotension, baroreceptor reflex tachycardia

O Interactions: Additive with other vasodilators

Calcium Channel Blocker Types

O Dihydropyridine: amlodipine, felodipine, isradipine, nicardipine, nifedipine, and nisoldipine

O Nondihydropyridine: Verapamil, diltiazem

Thiazide-Type DiureticsO Bendroflumethiazide, Chlorthalidone,

Hydrochlorothiazide, IndapamideO MOA: inhibit NaCl reabsorption at the

DCT blocking Na/Cl transporterO ADR: hypokalemia(most common),

magnesium depletion, impair glucose tolerance, increase uric acid concentrations

Other DiureticsO Loop Diuretics: Furosemide, BumetanideO MOA: inhibit NKCC2, the luminal Na + /K

+ /2Cl − transporter in the TAL of Henle’s loop

O Potassium Sparing: Spironolactone, eplerenone, amiloride, triamterene

O MOA: prevent K + secretion by antagonizing the effects of aldosterone in collecting tubules

Other Anti-hypertensives

Centrally ActingSympathoplegic DrugsO Methyldopa: analog of L-dopa and

is converted to α-methyldopamineO Clonidine: 2-imidazoline derivativeO Guanabenz and guanfacine share

the central α-adrenoceptor–stimulating effects of clonidine

Alpha 1 BlockersO Prazosin, terazosin, and doxazosin

O selectively blocking α 1 receptors in arterioles and venules

O phentolamine and phenoxybenzamineO useful in diagnosis and treatment of

pheochromocytoma

VasodilatorsO Hydralazine

O dilates arterioles but not veinsO Minoxidil

O very efficacious orally active vasodilatorO opening of potassium channels in smooth muscle

membranes by minoxidil sulfateO Sodium nitroprusside

O Parenteral; dilates both arterial and venous vessels

O Diazoxide: parenteralO FenoldopamO Calcium channel blockers

Special Situations in Hypertension Management

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Compelling Indications

O Compelling indications for specific therapy involve high-risk conditions that can be direct sequelae of hypertension (HF, IHD, chronic kidney disease, recurrent stroke) or commonly associated with hypertension (diabetes, high coronary disease risk).

O Therapeutic decisions in such individuals should be directed at both the compelling indication and BP lowering.

Ischemic Heart DiseaseO Lowering both SBP and DBP reduces

ischemia and prevents CVD events in patients with CAD, in part by reducing myocardial oxygen demand.

O Unless contraindicated, pharmacologic therapy should be initiated with a BB

O BBs will lower BP; reduce symptoms of angina; improve mortality; and reduce cardiac output, heart rate, and AV conduction.

O The reduced inotropy and heart rate decrease myocardial oxygen demand.

O Treatment should also include smoking cessation, management of diabetes, lipid lowering, antiplatelet agents, exercise training, and weight reduction in obese patients.

O If angina and BP are not controlled by BB therapy alone, or if BBs are contraindicated (severe reactive airways disease, severe peripheral arterial disease, high-degree AV block, or the sick sinus syndrome)O long-acting dihydropyridine or

nondihydropyridine type CCBs may be used.

O If angina or BP is still not controlled on this two-drug regimen, nitrates can be added, but these should be used with caution in patients taking phosphodiesterase-5 inhibitors such as sildenafil.

Heart FailureO Stage A group (NYHA class I), for those at

high risk for HF but with no demonstrable clinical symptoms or left ventricular dysfunctionO treatment should include fastidious risk-

factor management to control BP, hypercholesterolemia, and hyperglycemia.

O ACEIs - beneficial effects on mortality in patients

O Thiazide-diuretic therapy is useful in preventing disease progression

O Stage B HF (NYHA class I), defined by the presence of reduced left ventricular function (ejection fraction [EF] ≤40 percent) in otherwise asymptomatic individualsO ACEIs and BBs are recommended

O Stage C HF patients (NYHA class II–III)O manifest left ventricular dysfunction

and overt symptomsO ACEIs and BBsO Aldosterone antagonists also may be

of value in this situation.O Loop diuretics are often necessary to

control volume retention

O Patients with stage D HF (NYHA class IV) may require advanced careO inotropic drugsO implantable defibrillatorsO biventricular pacemakersO mechanical-assist devicesO TransplantationO in addition to the treatment described

above for stage C patients.

O HF is a “compelling indication” for the use of ACEI.

O In patients intolerant of ACEIs, ARBs may be used

Diabetes and Hypertension

O Clinical trials with diuretics, ACEIs, BBs, ARBs, and calcium antagonists have a demonstrated benefit in the treatment of hypertension in both type 1 and type 2 diabetics

O In the new guidelines, BB not indicated as first line

Chronic Kidney DiseaseO ACEI or an ARB in combination with a

diuretic (usually loop diuretic)O In the new guidelines, ACEI or ARBs

are indicated

Cerebrovascular Disease

O Diuretic and ACEi

Metabolic SyndromeO constellation of cardiovascular risk

factors related to hypertension, abdominal obesity, dyslipidemia, and insulin resistance

Left Ventricular Hypertrophy

O Several studies suggest that LVH regression is associated with a lower overall CVD risk.

O Weight loss, salt restriction, and BP lowering with most antihypertensive agents produce LVH regression.

Peripheral Arterial Disease

O BBs may cause peripheral vasoconstriction and have the potential to increase the frequency of intermittent claudication in individuals with PAD

O BBs have little effect on walking distance or calf blood flow in patients with intermittent claudication

O BBs can be used in PAD patients, especially if needed for treatment of CAD or HF.

Orthostatic Hypotension

O Diuretics and nitrates may further aggravate OH

O common barrier to intensive BP control

O drug therapy should be adjusted accordingly and appropriate warnings given to patients

Resistant HypertensionO failure to achieve goal BP in patients

who are adhering to full doses of an appropriate three-drug regimen that includes a diuretic

O May be due to:O Improper BP measurementO Inadequate diuretic therapyO Failure to receive adequate medicationsO Drug interactionsO Specific causes

Hypertension in WomenPregnant Women

Treating hypertension during lactation

O all antihypertensive drugs that have been studied are excreted into human breast milk

O mothers with stage 1 hypertension who wish to breast-feed for a few months may withhold medications

O Propranolol and labetalol are preferred if a BB is indicated

O ACEIs and ARBs should be avoided (fetal and neonatal renal effects)

O Diuretics may reduce milk volume and thereby suppress lactation

Hypertension in Children and Adolescents

O elevated BP that persists on repeated measurement at the 95th percentile or greater for age, height, and gender

O Secondary forms of hypertension are more common in children and in individuals with severe hypertension

O Benefits from early lifestyle management

O Same pharmacological treatment

Hypertensive Crises: Emergencies and

Urgencies

Hypertensive urgenciesO severe elevations (>180/120 mmHg)

in BP without progressive target organ dysfunction

O upper levels of stage II hypertension associated with severe headache, shortness of breath, epistaxis, or severe anxiety

Hypertensive Emergencies

O characterized by severe elevations in BP (>180/120 mmHg)

O evidence of impending or progressive target organ dysfunction

O require immediate BP reduction (not necessarily to normal)

Hypertensive Emergencies

O Target organ dysfunctions:O hypertensive encephalopathyO Intracerebral hemorrhageO acute MIO acute left ventricular failure with

pulmonary edemaO unstable anginaO PectorisO dissecting aortic aneurysmO eclampsia

ManagementO Early triage is criticalO Patients with hypertensive

emergencies should be admitted to an intensive care unit for continuous monitoring of BP and parenteral administration of an appropriate agent

ManagementO Hypertensive Emergencies

O reduce mean arterial BP by no more than 25 percent (within minutes to 1 hour)

O Then if stable, to 160/100–110 mmHg within the next 2–6 hours

O Excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia should be avoided

O If well tolerated and the patient is clinically stable, further gradual reductions toward a normal BP within the next 24–48 hours

ManagementO Hypertensive Urgencies

O May benefit from treatment with an oral, short-acting agent such as captopril, labetalol, or clonidine followed by several hours of observation.

Thank you!