Management of Patients with Hypertension; Defining

the Barriers to Control

David Feldman, MD/PhD, FACC, FAHADirector of Heart Failure and Cardiac

TransplantationThe Ohio State University

Learning Goals Recognize the economic burden of hypertension. Understand that hypertension is an antecedent to

many cardiovascular events. Aggressive screening and management is

required to reach the goals of the evidence-based guidelines.

Recognize some of the most important barriers to overcome in order to improve blood pressure control.

Explore therapeutic combinations that can prevent disease progression and improve morbidity and mortality.

?

Hypertension

Pre-Test Questions

Significance of Hypertension•HTN affects approximately 50 million individuals in the US and 1 billion people worldwide.

• HTN is the most common primary diagnosis in the USA with 35 million office visits per year.

• Framingham Heart Study—Individuals who are normotensive at 55 years of age have a 90% lifetime risk of developing HTN

• Relationship between BP and risk of CVD is continuous, consistent, and independent of other risk factors

• Only 35% of hypertensive patients on treatment are under control.

• For those age 40-70, each increased increment of 20 mmHg in systolic BP or 10 mmHg in diastolic BP doubles the risk of CVD across the entire BP range of 115/75 to 185/115.

JNC 7: U.S. 2004 direct costs = $55.5 Billion If co-morbidities are added (ESRD, CAD, CHF,

DM, CVA) cost is $108 Billion. 30% of adults do not know they have

hypertension. 40% of those who are hypertensive are not on

treatment. 66% of those who are being treated have a BP

greater than 140/90 mmHg.

Benefits of Lowering Blood Pressure

•Anti-HTN Therapy associated with:

• 35 – 40% mean decrease in stroke• 20 – 25% decrease in MI• More than 50% decrease in HF

•Patients with Stage 1 HTN/Additional Risk Factors:

• Achieving a sustained 12 mmHg decrease in systolic BP 10 years will prevent 1 death for every 11 pts treated

•The majority of Patients will require 2 or more anti-HTN drugs.

JNC 7: Treatment Algorithm for Hypertension

SBP=systolic blood pressure; DBP=diastolic blood pressure; ACEI=angiotensin- converting enzyme inhibitor; ARB=angiotensin receptor blocker; BB=-blocker; CCB=calcium channel blocker

JNC 7. May 2003. NIH publication 03-5233.

Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist.

Not at goal blood pressure

Without compelling indications

Stage 1 hypertension(SBP 140–159 or DBP 90–99 mm Hg)Thiazide-type diuretic for most.May consider ACEI, ARB, BB, CCB, or combination.

Stage 2 hypertension(SBP 160 or DBP 100 mm Hg)Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB).

Lifestyle modifications

Not at goal blood pressure (<140/90 mm Hg)(<130/80 mm Hg for those with diabetes or chronic kidney disease)

Initial drug choices

With compelling indications

Drugs for compelling indicationsOther antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB) as needed.

?

JNC 7: The Fine Print

Cracking open the door beyond diuretics for first line in a patient without co-morbid conditions Along with promoting a thiazide diuretic for

Stage 1 HTN, the committee added this surprising sentence: “May consider ACEI, ARB, BB, CCB.”

The ‘Compelling Indication’ Category - JNC put emphasis on evidence showing benefits with specific antihypertensive agents for certain medical conditions. Again, taking a small sidestep from the NHLBI dictum of diuretics first.

Case Presentation-The Executive Physical

Vicki Struthers 36 White Female

Presents for an Executive Physical

PMH Recently returned to work 10

weeks after the birth of first child

Total Cholesterol: 160 mg/dL HDL 66 mg/dL; Low-density lipoprotein (LDL):

120 mg/dL Family History of Diabetes

Mellitus No History of Smoking

*Hypothetical case based on a typical patient expected to present in clinical practice

Vicki Struthers – by the numbers

Tests Ordered Before Your Visit Today

ECG- LBBB,

Labs CR 0.9 mg/dL, NA 135

mmol/L, Glucose 97 mg/dL, HCT 35, TSH 2.1,

Vitals HR 98 bpm, BP 148/91

mm/Hg, BMI 23 No Rx, NKDA

Vicki Struthers –Parasternal Long Axis Echo

What Should We Be Thinking About?

?

Vicki Struthers 12 Years Later

At 1 YR- “I take my medicine”, Structured Exercise program

Law salt, Low fat Diet AT 12 YRS- Running 10Ks,

Daughter in Middle school. Blood Pressure 118/70

WHAT SHOULD WE BE THINKING ABOUT?

Clinical Practice Recommendation

Exercise may be beneficial in lowering Exercise may be beneficial in lowering blood pressure and reducing blood pressure and reducing

cardiovascular risk.cardiovascular risk.

Strength of Evidence:Three reviews of 50 observational studies found the risk of CV disease was lowered in those who were physically active. Conversely, a review of 43 epidemiological studies found that physical inactivity was associated with a doubling of cardiovascular disease.

Key Diet History Questions for Patients with HTN

Do you use a salt shaker?

Do you taste your food before you add salt?

How often do you eat salty foods, such as chips, pretzels,

salted nuts, canned and smoked foods?

Do you read labels for sodium content?

How many servings of fruits and vegetables do you eat everyday?

How often do you eat or drink dairy products? What kind?

How often do you eat out? What kinds of restaurants?

Do you like to drink alcohol? How much?

How often do you exercise, including walking?

?

When the First Drug Doesn’t Work

JNC 7 pushes for rapid progression to combination therapy before fully exploring mono-therapy.

This approach is not an issue for those with Stage 2, but for Stage 1. Different mechanisms may cause HTN in different patients; and heterogeneous mechanisms from multiple class of agents may be necessary.

Alternative approach: if there is a partial response, then increase the dose or add a second agent. If there is no response at all, then try an alternate class. The goal here being to find the simplest way to control BP.

Initial Drug Therapy

BP Classification

SBP* (mm Hg)

DBP* (mm Hg) Lifestyle

Without Compelling Indications

With Compelling Indications

Normal <120 and <80 Encourage

No antihypertensive drug indicated.

Drug(s) for compelling indications.

Prehypertension

120–139or 80–

89Yes

Stage 1 hypertension

140–159or 90–

99Yes

Thiazide-type diuretic for most. May cosider ACEI, ARB, BB, CCB, or combination.

Drug(s) for compelling indications.

Other antihypertensive drugs (diuretic, ACEI, ARB, BB, CCB) as needed.

Stage 2 hypertension

160 or 100 Yes

Two-drug combination for most (usuallythiazide-type diuretic

and ACEI or ARB or BB or CCB).

JNC 7: Classification and Management of Blood Pressure for Adults

JNC 7. May 2003. NIH publication 03-5233.

Case Presentation #2

Nate Biddleson

55 AA male presents for follow-up after his original Executive Physical.

PMH Blood pressure on

presentation 145/95, now 140/90

Non-smoker , no Known CAD

Fasting glucose 142 (repeated from previous visit)

Initial Therapy; Diet modification, Increased exercise, take “some vacation”, and started 25 mg of HCTZ

What Other Risk Stratification Should I Do at this Juncture to

Proactively Assess my Patient?

?

Nate Biddleson 55 AA male presents for

follow-up 6 months after his last appointment

PMH Blood pressure on

presentation 125/75 Fasting glucose 98 Therapy; Salt modification,

Increased exercise, HCTZ 12.5 mg, CCB, ACEI and sulfonourea/metformin combination.

1 2 3 4

ABCD2,3 (132 mm Hg)

AASK1 (134 mm Hg)

High-Risk Hypertensive Patients Require Multiple Agents to Get to Goal

AASK=African-American Study of Kidney Disease and Hypertension; ABCD=Appropriate Blood Pressure Control in Diabetes; ALLHAT=Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trials; HOT=Hypertensive Optimal Treatment; IDNT=Irbesartan Diabetic Nephropathy Trial; RENAAL=Reduction of Endpoints in Non-Insulin Diabetes Mellitus with the Angiotensin II Antagonist Losartin; UKPDS=United Kingdom Prospective Diabetes Study.1Wright JT et al. JAMA. 2002;288:2421-2431. 2Bakris GL. J Clin Hypertens. 1999;1:141-147. 3Estacio RO et al. N Engl J Med. 1998;338:645-652. 4The ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997. 5Hansson L et al. Lancet. 1998;351:1755-1762. 6Lewis EJ et al. N Engl J Med. 2001;345:851-860. 7Bakris GL et al. Arch Intern Med. 2003;163:1555-1565. 8UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.

Number of BP Medications

ALLHAT4 (135 mm Hg)

RENAAL7 (140 mm Hg)

IDNT6 (140 mm Hg)

UKPDS2,8 (144 mm Hg)

HOT2,5 (141 mm Hg)

AchievedSystolic BP

Compelling Indications for Consideration of One Drug Class vs. Another

Heart Failure:

Post- MI:

High CVD risk:

DM:

CRF Cr > 1.5 in men Cr > 1.3 in women

Thiazide/loop, BB, ACEI, ARB, Aldosterone antagonist

BB, ACE, Aldosterone antagonist

Thiazide, BB, ACE, ARB

Thiazide, BB, ACE, ARB, CCB

ACE, ARB. For creatinine 2-3 try loop diuretic

?

High Risk for Developing HFHypertension

CADDiabetes mellitus

Family history of cardiomyopathy

Structural Heart Disease Previous MI

LV systolic dysfunctionAsymptomatic valvular disease

HF with Current or Prior SymptomsKnown structural heart diseaseShortness of breath and fatigue

Reduced exercise tolerance

Refractory End-Stage HF

Marked symptoms at restdespite maximal medical therapy*

ACC/AHA Practice Guidelines

Pyramid Approach to HF Stages

A

B

C

D

Hunt et al., Journal of American College of Cardiology. 2005;38:1116-43

?

Case Number Three

Clark Galloway 42 White Male

Presents for a Executive Physical

Past Medical History (PMH) “Borderline” Hypertension

(HTN) “…too Busy to Exercise” Cholesterol Total: 223 mg/dL High-density lipoprotein

(HDL): 24 mg/dL Parents deceased related to

“some heart failure thing” +TOB (smoker)

*Hypothetical case based on a typical patient expected to present in clinical practice

Clark Galloway – by the numbers Tests Ordered Before Your Visit

Today ECG (electrocardiogram)- normal sinus rhythm

(NSR), No Q wave, normal intervals, No STT Abnormalities

Echocardiogram (Echo) -next slide Labs

Serum Creatinine (SCr) 1.1mg/dL, Sodium (Na) 140 mmol/L, Fasting Glucose 140 mg/dL, Hematocrit (HCT) 44, Thyroid-Stimulating Hormone (TSH) 1.1, Fasting Blood Glucose taken on two separate days 128 mg/DL and 138 mg/DL

Vitals Heart Rate: 82 beats per minute (bpm), Blood

Pressure: 142/86 mmHg, Body Mass Index (BMI): 26

No Prescription Medicine (Rx), No Known Drug Allergies (NKDA)

Clark Galloway –Parasternal Long Axis Echo

Clark Galloway 12 Years Later

At 1 YR- “I was too busy to exercise and I don’t like medicine… I felt fine”

AT 5 YRS- Promoted, gained 15 lbs, and joined a cigar club

AT 8 YRS- First MI, LVD, uncontrolled DM, ED

AT 12 YRS- Next Appt. with you.

?

New Medical Profile

Left Ventricular Ejection Fraction (LVEF) <20%

VO2 MAX 11 BP 108/50 mmHg, HR 95 bpm Shortness of Breath (SOB) at rest, Chest

Pain (CP) 2-3/day, Paroxysmal nocturnal dyspnea (PND)

9 kg weight gain despite two calls to office this wk

High Risk for Developing HFHypertension

CADDiabetes mellitus

Family history of cardiomyopathy

Structural Heart Disease Previous MI

LV systolic dysfunctionAsymptomatic valvular disease

HF with Current or Prior SymptomsKnown structural heart diseaseShortness of breath and fatigue

Reduced exercise tolerance

Refractory End-Stage HF

Marked symptoms at restdespite maximal medical therapy*

ACC/AHA Practice Guidelines

Pyramid Approach to HF Stages

A

B

C

D

Hunt et al., Journal of American College of Cardiology. 2005;38:1116-43

Hypertension in Patients With High-Risk Conditions

~3/4 of adults with diabetes have BP 130/80 mmHg or use prescription medications for HTN1

~2/3 of patients with HF have a past or current history of HTN2

More than 50%–75% of patients with chronic kidney disease have BP >140/90 mmHg3

1. National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics. Bethesda, MD: US Department of Health and Human Services, NIH, 2005. Available at http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm. Accessed Oct. 2006. 2. Hunt SA et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Available at http://www.acc.org/qualityandscience/clinical/guidelines/failure/update/index.pdf. Accessed Oct. 2006. 3. National Kidney Foundation. Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Available at http://www.kidney.org/professionals/KDOQI/guidelines_bp/guide_1.htm. Accessed Oct. 2006.

Chronic Kidney Disease

Goals: 1) Slow deterioration of renal function 2) Prevent CVD

• Often need 3 or more drugs

• Target < 130/80

• Drugs: ACE-Inhibitors/ARBs—Favorable effects on progression

-- Increase in Creatinine of 35% is acceptable

• Advanced Renal Disease:GFR < 30, CR 2.5 – 3.0 mg/dlIncreased dose of loop diuretics usually needed in combo with other drugs

Incidence of Coronary Heart Disease (CHD) Events in Patients With and Without Diabetes

Haffner SM et al. N Engl J Med. 1998;339:229-234.

Events per 100 Person-years

0

10

20

30

40

50

Incid

en

ce D

uri

ng

7-Y

ear

Follow

-up

* (%

)

n=69

18.8

Diabetics with prior MI

n=1,304 n=169 n=890

3.0 0.5 7.8 3.2

3.5

45.0

20.2P<.001

P<.001

Nondiabetics with no prior MI

Nondiabetics with prior MI

Diabetics with no prior MI

*Among 1373 nondiabetic subjects and 1059 diabetic subjects, from a Finnish population-based study.

Causes of Death in Persons With Diabetes, Based on US Studies

0 10 20 30 40 50 60

All Other

Pneumonia/ Influenza

Malignant Neoplasms

Diabetes

CerebrovascularDisease

Cardiac Disease

1990 US death certificates with mention of diabetes, all ages.1990 US death certificates with mention of diabetes, age at death 45 years.

Moss SE et al. Am J Public Health. 1991;81:1158-1162. Ochi JW et al. Diabetes Care. 1985;8:224-229. Kleinman JC et al. Am J Epidemiol.1998;128:389-401. Bender AP et al. Diabetes Care.1986;9:343-350.

Deaths (%)

DIGAMI=Diabetes Insulin-Glucose Infusion in Acute MI.

American Heart Association. Heart and Stroke Statistical—2004 Update. Dallas, TX: AHA; 2003; 2Haffner SM et al. N Engl J Med. 1998;339:229-234; 3Malmberg K et al. Eur Heart J. 1996;17:1337-1344.

The Diabetic Hypertensive Patient Is at Especially High Risk…

For CV disease “Two thirds to three fourths of people with diabetes

mellitus die of some form of heart or blood vessel disease”1

For myocardial infarction (MI) Patients with diabetes without a previous MI have as

high a risk of MI as patients without diabetes with a previous MI2

For congestive heart failure (CHF) In the DIGAMI trial, 66% of total mortality among

patients with diabetes was due to HF3

UKPDS Group. UKPDS 38. BMJ. 1998;317:703-713.

Ris

k R

edu

ctio

n (

%)

UKPDS: Blood Pressure Control Study in Type 2 Diabetes Effect of Intensive BP Lowering on Micro-

and Macrovascular Complications Risk

Benefits of 144/82 vs 154/87

AnyDiabetes-

relatedEndpoint

Diabetes-relatedDeath Retinopathy Stroke HF

24P=.0046

32 P=.019

34 P=.0038

44 P=.013

56 P=.0043

-70

-20

0

-10

-50

-60

-30

-40

MI

21P=.13

RenalFailure

42 P=.29

47 P=.0036

Vision Deterioration

1,148 hypertensive patients with type 2 diabetes were allocated to tight (144/82 mm Hg, n=758) or less tight (154/87 mm Hg, n=390) and followed for a median of 8.4 years.

UKPDS: Benefits of Glycemic vs BP Control With ACEIs or -Blockers

ACEI=Angiotensin-converting enzyme inhibitor. UKPDS Group. BMJ. 1998;317:703-713. Lancet. 1998;352:837-853.

-9

+7

-12-8

-56

-44

-21

-32

0

20

-20

-40

-60

Ris

k o

f E

ven

t (%

)

HF Stroke MI Diabetic Death

Glycemic control

ACEI or b-Blocker

?

?

Causes of Resistant HTN

Improper MeasurementVolume Overload

Excess SodiumVolume retention from Renal DiseaseInadequate Diuretic Therapy

Drug-Induced/Other CausesNoncompliance LicoriceInadequate Doses EphedraInappropriate Combos ma haungNSAIDS; COX 2 inhibitors Bitter OrangeCocaine, amphetamines, other illicits ObesitySympathomimetics (decongestants etc.) EtOHOCPsSteroidsErythropoietinCyclosporine and tacrolimus

• Implement evidence-based care and therapies

• Majority of patients eligible for treatment

• Early benefit of therapy not missed

• Higher persistence rates postdischarge

In-hospital Initiation2,3

Increasing Outpatient

Compliance2,3

AHA/JNC-7 Guidelines1

• Improve quality of care and outcomes

• Clinical trial evidence incorporated into recommendations for patient care

Strategies to Improve Management of Patients With HTN and DM

I IIa IIb III

1. Hunt SA et al. Circulation. 2005;112:1825–1852. 2. Fonarow GC. Rev Cardiovasc Med. 2002;3:S2–S10. 3. Gattis W et al. J Am Coll Cardiol. 2004;43:1534–1541.

Noncompliance

Estimates of noncompliance with medical treatment in general: Noncompliance causes 125,000 deaths a year -

twice the mortality rate from MVAs 30% of hospital admissions for people over the age

of 65 are directly caused by noncompliance. Half of all prescriptions are taken incorrectly,

contributing to prolonged or additional illnesses. Noncompliance increases with the number of meds

and doses per day; at 4 times a day, only 40% get it right.

Additional Patient Challenge in Treatment of HTN: Medication Adherence

Adherence to a drug regimen is an important component of BP control Approximately 50% of patients with poor BP control have

adherence problems (defined by taking <80% of medication) Several drug-related factors can influence medication

adherence, including: Adverse events

Frequency of adverse events has been inversely correlated with adherence rates

Dosing frequency Reduction in dose frequency can lead to improved

adherence

Feldman R et al. Can J Public Health. 1998;89:I-16–I-18.

Improved Adherence Has Been Associated With Improved Outcomes

In the BHAT trial, patients who took 75% of their prescribed β blocker regimen were 2.6 times more likely to die within the first year of follow-up, compared with more compliant patients1

In the COMPASS study, patients treated with oral nitrates had better efficacy with once-daily dosing2

Mean weekly number of chest pain episodes: 94% decrease in once-daily group 30% decrease in twice-daily group (P<.0001 compared to once-

daily group)Beta-Blocker Heart Attack Trial (BHAT): multicenter, randomized, double-blind trial comparing propranolol vs placebo in 3837 patients aged 30–69 years surviving acute MI. Patients 5–21 days post-MI were randomized to propranolol or placebo and were followed for an average of 25 months. Adherence data were available for 2175 patients (1081 randomized to propranolol).

Compliance With Oral Mononitrates in Angina Pectoris Study (COMPASS): open, nonblinded, randomized, parallel-group study in 101 patients aged 40–75 years; compared patient compliance (using electronic measurement) and treatment effectiveness in patients with stable angina pectoris treated with oral nitrates administered once daily vs twice daily.

1. Horwitz R et al. Lancet. 1990;336:542–545. 2. Kardas P et al. Am J Cardiol. 2004;94:213–216.

Clinical Practice Recommendation

Treating hypertension to goal with drugs Treating hypertension to goal with drugs reduces the risk of cardiovascular disease reduces the risk of cardiovascular disease

and death.and death.

Strength of Evidence: A Recommendation; There is robust evidence to recommend a pattern of care.

SUMMARY-CHALLANGE

1. Every patient in my practice will be screened for hypertension.

2. I understand that hypertension is a significant risk factor for cardiovascular disease.

3. Every patient in my practice will be treated to goal to decrease the risk of CV death.

4. My treatment plans will include helping patients comply with lifestyle and medication changes. I will make an extra effort to demonstrate to my patients how important their hypertension is to me and will provide additional time if needed.

Hypertension

Post-Test Questions

?

JNC-7

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Full text available: Hypertension, 2003;42:1206-1252

References

• JNC 7 report: available via NIH (JNC 7 report: available via NIH (Publication 03-5233)

• JAMA 289 (19), May 21 2003 (online)

• Adapted slides from Dr. Omar Khan’s AAFP Adapted slides from Dr. Omar Khan’s AAFP 01/2006 update (online)01/2006 update (online)

• AAFP monograph: #305AAFP monograph: #305

• AHA/ACC Hypertensive GuidelinesAHA/ACC Hypertensive Guidelines

• Weber, MA. The JNC 7 Report: Challenges and Weber, MA. The JNC 7 Report: Challenges and Dilemmas in Writing Guidelines. Dilemmas in Writing Guidelines. J. Clin J. Clin HtnHtn.;5(4):p282, .;5(4):p282, 2003.2003.