Management of Management of HypertensionHypertension

Laura Fitzpatrick, MD, MPHLaura Fitzpatrick, MD, MPH

Intern AcademicsIntern Academics

Friday the 13Friday the 13thth, August 2004, August 2004

BackgroundBackground

The JNC VII guidelines are issued The JNC VII guidelines are issued periodically from the National Heart, periodically from the National Heart, Lung, and Blood Institute. (NHLBI)Lung, and Blood Institute. (NHLBI)

Many new observational studies and Many new observational studies and clinical trials since JNC VI in 1997.clinical trials since JNC VI in 1997.

JNC VII published in 2003: express JNC VII published in 2003: express format in format in JAMAJAMA, full report in , full report in Hypertension. Hypertension.

What are the differences What are the differences between JNC VI and JNC VII?between JNC VI and JNC VII?

A new category added called “pre-A new category added called “pre-hypertension”; this combines normal hypertension”; this combines normal and borderline.and borderline.

Previous stage 2 and 3 were Previous stage 2 and 3 were combined.combined.

Lower threshhold for starting Lower threshhold for starting therapy.therapy.

Blood pressure classificationsBlood pressure classifications

BP BP classclass

SBPSBP DBPDBP LifestylLifestyle e ChangeChangess

Initial Initial Drug Drug therapytherapy

NormalNormal <120<120 <80<80 EncourageEncourage NoneNone

Pre-HTNPre-HTN 120-139120-139 80-8980-89 YesYes No drug if No drug if no DM/CKDno DM/CKD

Stage 1Stage 1 140-159140-159 90-9990-99 YesYes Thiazides Thiazides first-linefirst-line

Stage 2Stage 2 >=160>=160 >=100>=100 YesYes 2-drug 2-drug combinatiocombination for mostn for most

BP increases with ageBP increases with age

How does one measure BP?How does one measure BP?

Auscultatory methodAuscultatory methodPerson seated at least 5 min with Person seated at least 5 min with

feet on the floor, arms supported at feet on the floor, arms supported at heart level.heart level.

Use a cuff bladder that encircles at Use a cuff bladder that encircles at least 80% of the arm to ensure least 80% of the arm to ensure accuracy.accuracy.

What are the target organs of What are the target organs of injury?injury?

Cardiac: LVH, angina, CAD, CHFCardiac: LVH, angina, CAD, CHFNeuro: CVA/TIANeuro: CVA/TIARenal: CKDRenal: CKDPVDPVDRetinopathyRetinopathy

What components of history are What components of history are important in a newly diagnosed important in a newly diagnosed

pt?pt?h/o smokingh/o smokingh/o hyperlipidemiah/o hyperlipidemiaphysical activityphysical activityh/o diabetesh/o diabetesage age family history of premature CAD family history of premature CAD

defined as males < 55 and females < defined as males < 55 and females < 6565

What PE components should be What PE components should be performed in a newly diagnosed performed in a newly diagnosed

pt?pt? checking BP in both armschecking BP in both arms examination of the optic fundiexamination of the optic fundi documenting the BMIdocumenting the BMI listening for carotid, abdominal, and femoral listening for carotid, abdominal, and femoral

bruitsbruits palpating the thyroidpalpating the thyroid detailed cardiac/pulmonary examdetailed cardiac/pulmonary exam assessing for enlarged kidneys on abdominal assessing for enlarged kidneys on abdominal

examexam documenting peripheral pulsesdocumenting peripheral pulses neurologic examneurologic exam

What labs should we obtain?What labs should we obtain?

EKGEKG U/AU/A glucoseglucose hematocrithematocrit K+K+ creatininecreatinine CalciumCalcium Lipid profileLipid profile optional: albumin/creatinine ratio or urinary optional: albumin/creatinine ratio or urinary

albumin excretionalbumin excretion

What is the goal BP in patients What is the goal BP in patients with hypertension?with hypertension?

Goal is <140/90Goal is <140/90 In patients with DM or CKD, goal is In patients with DM or CKD, goal is

<130/80<130/80 In patients with >1g proteinuria, the In patients with >1g proteinuria, the

goal is <125/75goal is <125/75

When do you follow up?When do you follow up?

Why these goals?Why these goals?

HOT (Hypertension Optimal HOT (Hypertension Optimal Treatment) Trial.Treatment) Trial.

The National Kidney Foundation The National Kidney Foundation (NKF) Kidney Disease Outcome (NKF) Kidney Disease Outcome Quality Initiative (Quality Initiative (K/DOQIK/DOQI) clinical ) clinical practice guidelines.practice guidelines.

ADA recommendationsADA recommendations

Hypertension Optimal Treatment Hypertension Optimal Treatment Trial (HOT)Trial (HOT)

Goal was to determine the optimal level of BP to Goal was to determine the optimal level of BP to reduce CV morbidity/ mortality. ? J-curve existence.reduce CV morbidity/ mortality. ? J-curve existence.

Randomized 19,000 pts with HTN (mean 170/105 Randomized 19,000 pts with HTN (mean 170/105 mm Hg) to 3 different goal diastolic bp arms: <= mm Hg) to 3 different goal diastolic bp arms: <= 90, <= 85, <= 80 mm Hg.90, <= 85, <= 80 mm Hg.

Felodipine 5 mg was given as baseline therapy, Felodipine 5 mg was given as baseline therapy, with addition of other agents according to a 5-step with addition of other agents according to a 5-step regimen.regimen.

Half were randomized to receive aspirin.Half were randomized to receive aspirin.

Hypertension Optimal Treatment Hypertension Optimal Treatment Trial (HOT)Trial (HOT)

DBP was reduced to 85.2, 83.2, and DBP was reduced to 85.2, 83.2, and 81.1 mm Hg.81.1 mm Hg.

Outcomes: CV events, MI, CVA, CV Outcomes: CV events, MI, CVA, CV mortality, total mortality.mortality, total mortality.

No significant differences among the No significant differences among the 3 arms with respect to any outcome.3 arms with respect to any outcome.

Hypertension Optimal Treatment Hypertension Optimal Treatment Trial (HOT)Trial (HOT)

Trial did not prove/ disprove the J-curve.Trial did not prove/ disprove the J-curve.

Lower bp further did not appear to enhance Lower bp further did not appear to enhance risk.risk.

ASA 75 mg significantly reduced MI and CV ASA 75 mg significantly reduced MI and CV events (by 15%).events (by 15%).

Lancet 1998 Jun 13;351(9118):1755-Lancet 1998 Jun 13;351(9118):1755-62 62

What are the lifestyle What are the lifestyle modifications suggested by the modifications suggested by the

JNC VII?JNC VII? weight loss to BMI 18-24 (decrease of 5-20 mm weight loss to BMI 18-24 (decrease of 5-20 mm

Hg for every 10 kg wt. loss)Hg for every 10 kg wt. loss)

DASH diet rich in potassium and calcium (lead DASH diet rich in potassium and calcium (lead to 8-14 mm Hg reduction in SBP)to 8-14 mm Hg reduction in SBP)

limit Na intake (a 2.4 g Na diet lead to 2-8 mm limit Na intake (a 2.4 g Na diet lead to 2-8 mm Hg reduction in SBP)Hg reduction in SBP)

physical activity at least 30 min/day 7 days a physical activity at least 30 min/day 7 days a week (lead to 4-9 mg Hg reduction in BP)week (lead to 4-9 mg Hg reduction in BP)

limit etoh intakelimit etoh intake

What are the different classes of What are the different classes of BP lowering medications BP lowering medications

available? available? ThiazidesThiazides Other diuretics (loop, K+ - sparing)Other diuretics (loop, K+ - sparing) Beta-blockersBeta-blockers Combined alpha and beta- blockers (carvedilol, Combined alpha and beta- blockers (carvedilol,

labetalol)labetalol) ACE inhibitorsACE inhibitors Angiotensin-receptor blockersAngiotensin-receptor blockers CCB’s (non-dihydropyridine) – verapamil, diltCCB’s (non-dihydropyridine) – verapamil, dilt CCB’s (dihydropyridines) – amlodipine, felodipineCCB’s (dihydropyridines) – amlodipine, felodipine Central-acting agentsCentral-acting agents Direct vasodilatorsDirect vasodilators

What to use whenWhat to use whenIschemic heart Ischemic heart diseasedisease

Beta-blockers and ACE-I’sBeta-blockers and ACE-I’s

CHFCHF ACE-inhibitors, beta-ACE-inhibitors, beta-blockers, aldosterone blockers, aldosterone antagonistsantagonists

Diabetes Diabetes MellitusMellitus

ACE-I’s/ ARB’s first choice, ACE-I’s/ ARB’s first choice, slow the progression of slow the progression of diabetic nephropathydiabetic nephropathy

CKDCKD Consider ACE-I/ ARB; can Consider ACE-I/ ARB; can tolerate up to increase of tolerate up to increase of 35% Cr or until 35% Cr or until hyperkalemia.hyperkalemia.

Cerebrovasc. Cerebrovasc. diseasedisease

Combination of ACE-I/ TD Combination of ACE-I/ TD can decrease recurrencecan decrease recurrence

PregnancyPregnancy Methyldopa, b-blocker Methyldopa, b-blocker (not atenolol) and direct (not atenolol) and direct vasodilators; avoid vasodilators; avoid ACE/ARB’sACE/ARB’s

What to use whenWhat to use when

Congestive Heart FailureCongestive Heart Failure

SOLVD (1991) SOLVD (1991) randomized pts with CHF-EF<35% to randomized pts with CHF-EF<35% to

enalapril vs. placebo and followed for 41 enalapril vs. placebo and followed for 41 months.months.

16% risk reduction in mortality (p=.0036)16% risk reduction in mortality (p=.0036)26% risk reduction for hospitalization 26% risk reduction for hospitalization

(p<.0001)(p<.0001)XSOLVD showed that this gap narrowed XSOLVD showed that this gap narrowed

over time.over time.N Engl J Med 1991 Aug N Engl J Med 1991 Aug

1;325(5):293-302 1;325(5):293-302

Congestive Heart FailureCongestive Heart Failure

MERIT-HF (1999)MERIT-HF (1999)

~4000 patients with class II-IV CHF and ~4000 patients with class II-IV CHF and EF<40% randomized to metoprolol XL/CR vs. EF<40% randomized to metoprolol XL/CR vs. placebo. Followed for ~1 yr.placebo. Followed for ~1 yr.

All-cause mortality lowered with metoprolol All-cause mortality lowered with metoprolol (RR=0.66) (RR=0.66)

Also decreased sudden deaths, deaths from Also decreased sudden deaths, deaths from worsening heart failure, and hospitalization.worsening heart failure, and hospitalization.

Study terminated prematurely.Study terminated prematurely.

Lancet 1999 Jun Lancet 1999 Jun 12;353(9169):2001-7 12;353(9169):2001-7

Congestive Heart FailureCongestive Heart Failure

United States Carvedilol Heart Failure United States Carvedilol Heart Failure Program (NEJM, 1996)Program (NEJM, 1996)

1100 pts already receiving dig, diuretics, ACE 1100 pts already receiving dig, diuretics, ACE randomized to carvedilol vs. placebo.randomized to carvedilol vs. placebo.

Decreased total mortalityDecreased total mortality Decreased hospitalizationsDecreased hospitalizations Increased event-free survivalIncreased event-free survival Study terminated prematurelyStudy terminated prematurely

N Engl J Med 1996 May N Engl J Med 1996 May 23;334(21):1349-55 23;334(21):1349-55

Ischemic Heart DiseaseIschemic Heart Disease

SAVE trial (1992)SAVE trial (1992)

2231 patients with EF<40% but no overt 2231 patients with EF<40% but no overt HF signs/symptoms, 3-16 days post-MI HF signs/symptoms, 3-16 days post-MI randomized to placebo vs. captopril.randomized to placebo vs. captopril.

All-cause mortality decreased 19% All-cause mortality decreased 19% (P=.019)(P=.019)

Major CV events decreased 21%Major CV events decreased 21%Recurrent MI decreased 25%Recurrent MI decreased 25%

N Engl J Med 1992 Sep N Engl J Med 1992 Sep 3;327(10):669-77 3;327(10):669-77

Cerebrovascular DiseaseCerebrovascular Disease

SHEP (Systolic HTN in the Elderly, SHEP (Systolic HTN in the Elderly, 1991)1991)4736 pts 60 yrs and over with isolated 4736 pts 60 yrs and over with isolated

systolic HTN (mean 170/77) randomized to systolic HTN (mean 170/77) randomized to chlorthalidone vs. placebo. Atenolol added, chlorthalidone vs. placebo. Atenolol added, if needed, to achieve a goal reduction of 20 if needed, to achieve a goal reduction of 20 mmHg.mmHg.

Primary outcome: CVA; Secondary: CV Primary outcome: CVA; Secondary: CV M/M, all-cause mortality, QOL measures. M/M, all-cause mortality, QOL measures.

JAMA 1991 Jun JAMA 1991 Jun 26;265(24):3255-64 26;265(24):3255-64

SHEP trialSHEP trial

OutcomesOutcomesRisk of stroke significantly lower in the Risk of stroke significantly lower in the

treatment group. (RR=0.64; p=.0003)treatment group. (RR=0.64; p=.0003)Risk of CV events was reduced, but NS.Risk of CV events was reduced, but NS.

High-risk for coronary diseaseHigh-risk for coronary disease

LIFE (2002)LIFE (2002)

Randomly assigned 9193 pts with severe HTN and Randomly assigned 9193 pts with severe HTN and EKG evidence LVH to losartan vs. atenolol.EKG evidence LVH to losartan vs. atenolol.

Outcomes were death, MI or stroke.Outcomes were death, MI or stroke.

RR of primary composite endpoint was 0.87 RR of primary composite endpoint was 0.87 (p=.021)(p=.021)

Decreased stroke RR=0.75 (p=.001)Decreased stroke RR=0.75 (p=.001)

Lancet 2002 Mar 23;359(9311):995-Lancet 2002 Mar 23;359(9311):995-1003 1003

LIFE trialLIFE trial

LIFE trialLIFE trial

High-risk for coronary diseaseHigh-risk for coronary disease

HOPE (2000)HOPE (2000)9451 high-risk pts without acute MI, HF or LV 9451 high-risk pts without acute MI, HF or LV

dysfunction. dysfunction. High-risk: either evidence of vascular disease High-risk: either evidence of vascular disease

OR diabetes + another CV RF.OR diabetes + another CV RF.Pts randomly assigned to ramipril vs. Pts randomly assigned to ramipril vs.

placebo.placebo.Endpoints were CV death, MI, or CVAEndpoints were CV death, MI, or CVA

N Engl J Med 2000 Jan 20;342(3):145-N Engl J Med 2000 Jan 20;342(3):145-53 53

HOPE trialHOPE trial

Study terminated after a 4.5 year Study terminated after a 4.5 year follow-up when it showed the follow-up when it showed the following:following:

Reduction in primary endpoint Reduction in primary endpoint (RR=0.78)(RR=0.78)

Reduction in nonfatal MI (RRR=23%)Reduction in nonfatal MI (RRR=23%)Reduction in Stroke (RR=0.68)Reduction in Stroke (RR=0.68)

HOPE trialHOPE trial

ALLHATALLHAT

A RCT of high-risk pts with HTN, designed to A RCT of high-risk pts with HTN, designed to determine if occurrence of fatal CHD or nonfatal determine if occurrence of fatal CHD or nonfatal MI is lower with a CCB, ACE-I, alpha-blocker vs. MI is lower with a CCB, ACE-I, alpha-blocker vs. thiazide diuretic.thiazide diuretic.

Secondary outcomes included all-cause mortality, Secondary outcomes included all-cause mortality, CVA, and CVD events.CVA, and CVD events.

A subtrial included moderately hyperlipidemic A subtrial included moderately hyperlipidemic patients randomized to pravastatin vs. placebo to patients randomized to pravastatin vs. placebo to determine differences in mortality. determine differences in mortality.

ALLHATALLHAT

42,000 patients >55 years (men and 42,000 patients >55 years (men and women) with stage 1 or 2 HTN and >=1 women) with stage 1 or 2 HTN and >=1 additional CVD risk factor.additional CVD risk factor.

Randomized to 4 arms: tx with amlodipine, Randomized to 4 arms: tx with amlodipine, chlorthalidone, lisinopril or doxazosin. chlorthalidone, lisinopril or doxazosin. Goal: <140/90Goal: <140/90

Doxazosin arm discontinued due to higher Doxazosin arm discontinued due to higher rates of CVD and CHF.rates of CVD and CHF.

ALLHATALLHAT

Patient population was diversePatient population was diverseMean age: 67 yearsMean age: 67 years36% had diabetes36% had diabetes47% female47% female35% black 35% black 19% Hispanic19% Hispanic

Populations virtually identical at Populations virtually identical at baselinebaseline

ALLHAT resultsALLHAT results

ALLHAT resultsALLHAT results

No significant difference among the 3 arms No significant difference among the 3 arms with respect to the primary outcome.with respect to the primary outcome.

The amlodipine group had a 38% higher risk The amlodipine group had a 38% higher risk of CHF compared with chlorthalidone group. of CHF compared with chlorthalidone group. (p<.001)(p<.001)

Lisinopril group had a 15% higher risk of CVA Lisinopril group had a 15% higher risk of CVA (p=.02), a 10% higher risk of combined CVD (p=.02), a 10% higher risk of combined CVD (p<.001); 19% higher risk of HF.(p<.001); 19% higher risk of HF.

The efficacy of chlorthalidone compared to The efficacy of chlorthalidone compared to lisinopril was higher in blacks than in whites. lisinopril was higher in blacks than in whites.

Secondary HTNSecondary HTN

What are the identifiable causes What are the identifiable causes of HTN?of HTN?

chronic kidney diseasechronic kidney disease aortic coarctation aortic coarctation cushing syndrome/ chronic steroid therapycushing syndrome/ chronic steroid therapy drug-related (ex. Cocaine, amphetamines, drug-related (ex. Cocaine, amphetamines,

decongestants)decongestants) PheochromocytomaPheochromocytoma primary aldosteronismprimary aldosteronism renovascular hypertensionrenovascular hypertension sleep apneasleep apnea thyroid/ parathyroid diseasethyroid/ parathyroid disease

When is a workup of secondary When is a workup of secondary HTN appropriate?HTN appropriate?

In patients whose history, PE, severity In patients whose history, PE, severity of HTN or initial labs suggest of HTN or initial labs suggest secondary causessecondary causes

BP responds poorly to drug therapyBP responds poorly to drug therapy BP begins to increase without BP begins to increase without

explanation after being well-controlledexplanation after being well-controlled Onset of HTN is suddenOnset of HTN is sudden

CasesCases A 54 y.o. WF with PMH of HTN, fibromyalgia, recently diagnosed A 54 y.o. WF with PMH of HTN, fibromyalgia, recently diagnosed

type 2 DM presents for her regular diabetes visit. Baseline EKG type 2 DM presents for her regular diabetes visit. Baseline EKG shows no abnormalities, and urinary dipstick showed trace shows no abnormalities, and urinary dipstick showed trace proteinuria. Her bp is 147/92, and her current regimen consists of proteinuria. Her bp is 147/92, and her current regimen consists of HCTZ 12.5 mg daily and atenolol 50 mg daily. HCTZ 12.5 mg daily and atenolol 50 mg daily. (1) What is her goal bp?(1) What is her goal bp? (2) What is the next step in the management of her bp?(2) What is the next step in the management of her bp? (3) What agents would you consider if the EKG had shown (3) What agents would you consider if the EKG had shown

evidence of LVH?evidence of LVH? (4) You place her on ramipril, and her creatinine bumps from (4) You place her on ramipril, and her creatinine bumps from

its baseline of 1.2 to 1.5, where it stabilizes. Do you stop the its baseline of 1.2 to 1.5, where it stabilizes. Do you stop the ACE-I?ACE-I?

AnswersAnswers (1) What is her goal bp? 130/ 80 in a patient with DM. Her trace (1) What is her goal bp? 130/ 80 in a patient with DM. Her trace

proteinuria is not likely to exceed 1g/day, but if it did, her goal would proteinuria is not likely to exceed 1g/day, but if it did, her goal would be 125/ 75 mm Hg.be 125/ 75 mm Hg.

(2) What is the next step in the management of her bp? Add another (2) What is the next step in the management of her bp? Add another agent. You could titrate up one of her existing medications, however, agent. You could titrate up one of her existing medications, however, given her proteinuria you should consider the addition of an ACE-I or given her proteinuria you should consider the addition of an ACE-I or ARB. ARB.

(3) What agents would you consider if the EKG had shown evidence of (3) What agents would you consider if the EKG had shown evidence of LVH? You could consider an ARB (or ACE-I). The LIFE trial compared LVH? You could consider an ARB (or ACE-I). The LIFE trial compared losartan and atenolol in hypertensive patients with LVH; losartan was losartan and atenolol in hypertensive patients with LVH; losartan was superior, mainly due to its reduction of stroke risk.superior, mainly due to its reduction of stroke risk.

(4) Serum creatinine should be carefully monitored with ACE-I (4) Serum creatinine should be carefully monitored with ACE-I initiation, but creatinine increases up to 35% are acceptable. Increases initiation, but creatinine increases up to 35% are acceptable. Increases over 20% may be a clue to the presence of renal artery stenosis.over 20% may be a clue to the presence of renal artery stenosis.

CasesCases

A 48 y.o. WM presents to your office with no significant PMH. His A 48 y.o. WM presents to your office with no significant PMH. His bp is 168/92. This has been confirmed on two other separate bp is 168/92. This has been confirmed on two other separate occasions. He is on no meds at present. He has no DM, no known occasions. He is on no meds at present. He has no DM, no known heart disease, no history of CVA/ TIA. His family history is heart disease, no history of CVA/ TIA. His family history is unremarkable. He does not smoke, and drinks minimal alcohol. unremarkable. He does not smoke, and drinks minimal alcohol.

(1) What class of hypertension does he have?(1) What class of hypertension does he have?

(2) How would you manage his blood pressure? (2) How would you manage his blood pressure?

(3) What labs would you order now?(3) What labs would you order now?

AnswersAnswers

(1) What class of hypertension does he have? He has stage 2 (1) What class of hypertension does he have? He has stage 2 hypertension, as his systolic value places him in that category.hypertension, as his systolic value places him in that category.

(2) How would you manage his blood pressure? Start 2 agents. (2) How would you manage his blood pressure? Start 2 agents. HCTZ would be a good choice for one of the agents. HCTZ would be a good choice for one of the agents.

(3) What labs would you order now? 12-lead EKG, fasting lipid (3) What labs would you order now? 12-lead EKG, fasting lipid panel, glucose, serum Cr and U/A. A Hct and electrolytes may be panel, glucose, serum Cr and U/A. A Hct and electrolytes may be helpful. helpful.

CasesCases A 87 y.o. AAM has never visited a physician in his life and comes A 87 y.o. AAM has never visited a physician in his life and comes

to see you. His bp is 180/75. He states he has never had any to see you. His bp is 180/75. He states he has never had any health problems. Your workup of target end-organ damage, along health problems. Your workup of target end-organ damage, along with all bloodwork, is completely negative.with all bloodwork, is completely negative. (1) Would you start 1 or 2 agents?(1) Would you start 1 or 2 agents? (2) What would be the first agent you would choose and why?(2) What would be the first agent you would choose and why?

AnswersAnswers (1) Would you start 1 or 2 agents? Although he falls under the (1) Would you start 1 or 2 agents? Although he falls under the

category of stage 2 HTN (and therefore needs to be started on category of stage 2 HTN (and therefore needs to be started on 2 agents), given his advanced age (and likely decreased 2 agents), given his advanced age (and likely decreased metabolism), you could consider starting 1 agent, then metabolism), you could consider starting 1 agent, then bringing him back soon (within 2-4 weeks) to start a second bringing him back soon (within 2-4 weeks) to start a second agent. Ultimately, he will very likely need 2 agents. agent. Ultimately, he will very likely need 2 agents.

(2) What agent(s) would you choose and why? According to (2) What agent(s) would you choose and why? According to the SHEP trial, elderly patients with isolated systolic HTN had a the SHEP trial, elderly patients with isolated systolic HTN had a significant decrease in stroke risk when patient were placed on significant decrease in stroke risk when patient were placed on chlorthalidone. You could therefore consider a thiazide diuretic chlorthalidone. You could therefore consider a thiazide diuretic as initial therapy.as initial therapy.