Management of Hypertension

2015 Georgia Chapter ACP Scientific Meeting

John J. White, MD FASN

Disclosures

• Co-I NHLBI

– “Stress Related Mechanisms of Hypertension”

• Co-I NIDDK

– “Red Blood Cell Pathology in Hemodialysis”

Goals & Objectives

At the end of presentation, learners should be able to:

• Describe the basic epidemiology and importance of hypertension

• Discuss current evidence-based management guidelines including limitations

• Apply evidence-based guidelines into practice

• Give High Value Care to their patients

ARS Q1. Which of the following is associated with the highest Global Burden of Disease?

A. Air Pollution

B. Low Child Birthweight

C. HIV

D. Hypertension

E. Smoking

A. B. C. D. E.

1% 0%

15%

82%

1%

Murray CJ, Lopez AD. N Engl J Med 2013;369:448-457.

Global DALYs Attributable to the 25 Leading Risk Factors in 1990 and 2010.

Murray CJ, Lopez AD. N Engl J Med 2013;369:448-457.

Global DALYs Attributable to the 25 Leading Risk Factors in 1990 and 2010.

CV Mortality Risk Doubles with

Each 20/10 mm Hg BP Increment*

Lancet. 2002; 60:1903-1913. JNC VII. JAMA. 2003.

CV

mortality

risk

SBP/DBP (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

Every Millimeter of Blood Pressure

Reduction Counts

= +

Each

10

-14 m

m H

g

Each

5-6

mm

Hg

17%

33%

40%

SBP DBP CHD CV Events Stroke

J HTN 1999;17:151-183

Hypertension Statistics 2013

• Prevalence: 74,500,000 (1:3)

• Controlled ~ 50% (JAMA 2010;303:2043)

• Resistant HTN ~ 30%

• $ 46 Billion/yr

• Mortality data 2013

• HTN contributed to 360,000 deaths

• 1,000/day

www.CDC.gov

• R14.3 Flatulence causing injury

• V97.33XD Sucked into jet engine, sub encounter

• V91.07XA Burn due to water-skis on fire, initial encounter

• W61.62XD Stuck by duck, sub encounter

• W22.02XD Walked into lamppost, sub encounter

• Z631 Problems in relationship with in-laws

ICD-10 Codes

Accurate Diagnosis Requires Correct Measurement

• Office BP inaccurate

• White coat HTN – 15-30% of patients

• Masked HTN – 10% of patients

• US Preventive Services Task Force 2015 – Proposes out-of-office BP measurements (ABPM

or standardized home BP measurements) to confirm office findings

BP Measurement: Key Techniques

• Although home blood pressure monitors are usually not reimbursed by insurers, their relatively low cost (usually less than $100) and reasonable accuracy have made them attractive components to the management of hypertension.

High Value Care MKSAP® 16

Lifestyle Modifications

to Manage Hypertension

Modification Recommendation SBP Reduction

Weight

reduction

Maintain normal body weight

(BMI, 18.5-24.9)

5-20 mm Hg/10-kg

weight loss

Adopt DASH

eating plan

Consume a diet rich in fruits,

vegetables, and low-fat dairy

products with a reduced

content of saturated and total

fat

8-14 mm Hg

Dietary sodium

reduction

Reduce dietary sodium intake

to no more than 100 mEq/L (2.4

g sodium or 6 g sodium

chloride)

2-8 mm Hg

JAMA 2003; 289:2560-2572.

Lifestyle Modifications

to Manage Hypertension

Modification Recommendation

SBP Reduction

Physical Activity Engage in regular aerobic

physical activity such as brisk

walking (at least 30 min/d)

4-9 mm Hg

Moderation of

Alcohol

Consumption

Limit consumption to no more

than 2 drinks/d in most men

and no more than 1 drink/d in

women and lighter-weight

persons

2-4 mm Hg

JAMA 2003; 289:2560-2572.

High Value Care MKSAP® 16

• Lifestyle modifications, including weight loss, reduction of dietary sodium intake, aerobic physical activity of at least 30 minutes a day at least three times a week, and a reduction in alcohol consumption, are a relatively cost-effective way to reduce high blood pressure.

Level of Evidence for Alternative Tx

Hypertension 2013;61:1360

JAMA 2014;311:507

Recommendation #1

• 1. “General population” >= 60 years, initiate treatment to lower BP at >= 150/90 mmHg

• If treatment for high BP results in lower SBP (i.e. < 140 mmHg) and treatment is well-tolerated and without adverse effects on health or quality of life, treatments does not need to be adjusted

Recommendation #2/3

• 2. “General Population” < 60 years, initiate treatment to lower BP at DBP > 90 mmHg

• 3. “General Population” < 60 years, initiate treatment to lower SBP < 140 mmHg

The Elderly

• HTN as high as 60 to 80%

• ISH = BP > 160/90

• CV events increases with increased SBP & PP – Problem of J curve

• SHEP trial

• Syst-Eur trial

• MRC trial

• HYVET

HYVET

• 3845 pts > 80 (84) BP 173/91

• Indapamide (+perindopril) vs placebo

• BP target 150/80

– 143/78 vs 158/84

• Stroke (12.4 vs 17.7% p < 0.06)

• Fatal stroke (6.5 vs 10.7%)

• Death (47.2 vs 59.6%)

Recommendation #4/5

• 4. Population with CKD initiate and treat to lower BP at 140/90 mmHg

• 5. Population with diabetes initiate and treat to lower BP at 140/90 mmHg

BP and Mortality in US Veterans with CKD

SBP 130-160 & Diastolic BP 70-90 associated with lowest mortality risk

Ann Intern Med 2013;159;233

JAMA Intern Med 2014 epub

Strict vs Conventional BP Control in CKD Associate with Worse Survival

ESRD

• Up to 85% with HTN

• Dialysis BP misleading

– Post SBP may reflect interdialytic BP

– Home BP > 150 more accurate

– Best prognosis SBP 125-145

• Targets controversial

– Mortality increases < 110 and > 180

Pre-SBP < 140 Frequency % HR [95% CI]

None 18.4 1.0

0-25% 41.9 1.20 [1.09-1.32]

25-75% 21.5 1.40 [1.26-1.54]

>75% 18.2 1.90 [1.73-2.10]

J Am Soc Nephrol 2007;18:2377

KDOQI Guidelines Pre-SBP < 140

N = 13,792

Recommendation #6,7,8

• 6. General non-black population (including diabetes)– initial treatment should include a thiazide diuretic, calcium channel blocker, ACE-inhibitor, or ARB

• 7. General black population (including diabetes) – initial treatment should include a thiazide diuretic or calcium channel blocker

• 8. Population with CKD, initial or add-on therapy should include and ACEI or ARB to improve kidney outcomes regardless of race or diabetes.

Proportion of US Adults Affected by the 2014 Hypertension Guideline

JAMA 2014;311:1424

Cost-Effectiveness of HTN Therapy According to 2014 Guidelines

NEJM 2015;372:447

Comparison of HTN Guidelines 2011-2014 NICE’11 ESH/ESC ’13 ASH/ISH ’14 AHA/ACC/

CDC ’13 JNC 8

Definition >140/90 >140/90 >140/90 >140/90 NA

Start Tx >160/100 >140/90 >140/90 >140/90 <60 y >140/90 >60 y >150/90

Β-blockers No Yes No No No

Diuretic CLTD Indapamide

Thiazides,CLTD, Indapamide

Thiazides,CLTD, Indapamide

Thiazides Thiazides,CLTD, Indapamide

Start 2 Drugs NA Marked HTN >160/100 >160/100 >160/100

BP targets <140/90 >80 y <150/90

<140/90 <150 systolic in fragile elderly

<140/90 >80 y <150/90

Consider <130/80 if tolerated

<140/90 <60 y <140/90 >60 y <150/90

DM/CKD* NA <140/85 <140/90 <140/90 <140/90

*KDIGO ‘12 – BP < 130/80 with proteinuria; ADA ‘13 - BP < 140/80, consider < 130

Beta-blockers

• Use after MI or rate control with afib

• SHOULD NOT BE 1st line drug for BP control

– ?higher risk of CVA in smokers

– ?higher risk of CAD and all CV events

– ?higher risk of mortality with atenolol

– Impaired glucose tolerance

• Vasodilating beta-blockers carvedilol and nebivolol probably OK

• R46.0 Very low level personal hygeine

• R46.1 Bizarre personal appearance

• T505x6A Underdosing of appetite depressants, initial encounter

• W56.22XA Struck by orca, initial encounter

• W55.41XA Bitten by pig, initial encounter

• W60.XXXS Contact with Sharp Leaves

ICD-10 Codes cont.

Hypertension 2009;54:375

Hypertension 2009;54:375

Δ20/10 mmHg

Efficacy of BP Meds

Wh

ite

Bla

ck

BMJ 2008;17:336:1121-23

BMJ 2009;338:b1665

BMJ 2009;338:b1665

ALLHAT

• 41,000 participants BP 146/84

• CLTD vs amlodipine vs lisinopril vs doxasosin – Doxasosin arm d/c’d re: CHF

• Mean f/u 4.9 years

• BP similar though slightly lower CLTD

• No difference in primary end point

• CLTD lower rate of CHF

• CLTD less CVD events compared to lisinopril

Thiazide vs Thiazide Like Diuretics

• Thiazides

– HCTZ, chlorothiazide, trichlormethiazide, bendrofluazide

• Thiazide-Like

– indapamide, chlorthalidone, metolazone

• Longer half-life

• Better 24 hour BP

• Experiments reduce platelet aggregation and vascular permeability

Meta-Analysis Highlights Superiority of Thiazide-Like Diuretics

12%RR 21%RR

Hypertension 2015;65:1033

• W56.52 Struck by other fish

• Y92241 Hurt at the library

• Y92146 Hurt at swimming pool of prison as the place of occurrence

• Y92.022 Bathroom in mobile home as place of injury

• W5803XA Crushed by alligator, initial encounter

ICD-10 Codes Cont.

Systemic Based Strategies Improve Hypertension Control Rates

• Kaiser Permanente Southern California

– Comprehensive hypertension program in 2000

– Captured hypertensive members using hypertension registry

– Standardized blood pressure measurements

– Drafted & disseminated a treatment algorithm

– Multidisciplinary approach utilizing medical assistants, nurses, and pharmacists

Marked Improvement in BP Control Rates Over Short Period of Time!

ARS Q2. 52 yo WF in follow-up for continued adjustment of BP meds. She has stable CAD and quit smoking 4 years ago. You started lisinopril two visits ago. Last visit, you increased lisinopril to 40 mg daily. BMI is 23.2 kg/m2. BP is 151/86 mmHg.

ARS Q2. Which of the following is the most appropriate next step in treating this patient’s hypertension?

60%

15%

1%

23%

0% A. Increase lisinopril to 80 mg daily (max dose)

B. Add hydrochlorothiazide

C. Discontinue lisinopril and start metoprolol

D. Add amlodipine

E. Add chlorthalidone

ACCOMPLISH trial

• 11,506 patients, 97% on 2+ drugs, BP 145/80

• Benazepril/Amlodipine vs Amlodipine/HCTZ

• DSMB stopped at 3 years

• CV composite end point

– 9.6 vs 11.8% HR 0.8

• Doubling SCr

– 2.0 vs 3.7%

Confirm Treatment Resistance

Identify & Reverse Lifestyle Factors

Exclude Pseudoresistance

Discontinue Interfering Substances

Screen for Secondary HTN

Pharmacological Treatment

Refer to Specialist

AHA Guidelines Resistant HTN

Hypertension 2008;51:1403

Low-Dose Spironolactone in Resistant Hypertension

-24

-10

-28

-13

-25

-12

-22

-10

-22

-9

-30

-25

-20

-15

-10

-5

0

Ouzan

2002

Mahmud

2005

Nishizaka

2003

Chapman

2007

Lane

2007

Meta-Analysis: Aldosterone antagonists for RHTN (2640 pts)

• 3 RCTs

– 135 pts

• 10 Observational Studies

– 2208 pts

• Mean BP – 17/4

– SBP – 16.5 (CI -3 to -30)

• Mean BP – 20/9

– SBP – 19.7 (CI -16 to -23)

• Mild increase(s)

– S Creatinine

– S Potassium J Hum Hypertens 2015;29:159

ARS Q3. A 52 yo WM with hypertension, diabetes, and OSA presents for routine follow-up. His medications are metformin, lisinopril, amlodipine, simvastatin, and HCTZ. BP is 136/82 BMI 34.5. PE and labs are otherwise unremarkable, last HbA1c 7.1%

ARS Q3. Which of the following should be considered to decrease CV risk?

33%

24%

24%

16%

4%A. Discontinue metformin and start insulin glargine

0.25U/kg B. Discontinue lisinopril and add carvedilol

C. Change lisinopril dosing to bedtime

D. Change simvastatin to atorvastatin

E. Refer for bariatric surgery

Timing of Blood Pressure Dosing

• Biology of humans is rhythmic over 24 h

• BP exhibits 24 h variation

– Circadian rhythms

• Neural, endocrine, endothelial, ANS, RAAS

– Cyclical Day-Night Alterations in Behavior

• Physical activity, mental stress, posture, environment

• Net effect

– Higher BP during day, Dip in BP at night

Hypertens Res 2012;35:695

Hypertension 2008;51:69-76

Circadian Dosing

MAPEC Study

• RCT 2156 HTN patients

• All meds AM vs ≥ 1 PM

• ABPM

• F/U 5.6 years

• Better BP control

• Inc Dipping Pattern

• Reduced CV Events

Chronobiol Int 2010;27:1629

Circadian Dosing RHTN

• RCT 776 patients

– RHTN

– 61 yoa

• All meds AM vs ≥ 1 PM

• 48 hr ABPM

• Mean f/u 5.4 yrs

• HR 0.38 (102 v 41 events)

• Night SBP 121 vs 113

• Control ABP 46% vs 61% Chronobiol Int 2013;30:340

Chronotherapy in Other Diseases

JASN 2011;22:2313

661 CKD patients

Composite of death, MI, CP, PCI, CHF, PAD, CVA was 1/3 of controls HR 0.31 (0.21-0.46)

448 DM type 2 patients

CV related death, MI, and CVA reduced to ¼ of controls HR 0.25 (0.10-0.61)

Diabetes Care 2011;34:1270

Effect on Sleep-time Relative BP Decline

Drug Class Awakening Rx Bedtime Rx

ACE-Is ↓ ↑

ARBs = ↑

CCBs = =

Doxazosin ↓ =

Carvedilol = ↑

Nebivolol ↓ =

ARS Q4. 39 yo AAF presents for eval after worksite screening examination found elevated blood pressure. She is asymptomatic and takes no medications. Serial BP measurements in office and at home average 155/96. Physical examination is normal. CBC, electrolytes, FLP, glucose, urinalysis, ECG are all normal.

ARS Q4. Which one of the following is most appropriate for management?

A. Plasma metanephrines

B. Renal Doppler US of kidneys to assess size and blood flow

C. 2D echocardiography

D. Plasma aldosterone and renin activity

E. No further diagnostic testing

A. B. C. D. E.

2%

11%

77%

11%

0%

• Only consider evaluating for secondary causes of hypertension when there is onset at a young age, no family history, no risk factors, rapid onset of significant hypertension, abrupt change in blood pressure in a patient with previously good control, or a concomitant endocrine abnormality.

MKSAP 16®: High Value Care

Secondary Causes of Resistant HTN

Common

CKD

Hyperaldosteronism

Sleep Apnea

Renal Artery Stenosis

Uncommon

Pheochromocytoma

Cushing’s disease

Hyperparathyroidism

Aortic coarctation

Intracranial tumor

Clinical Nephrology 2013

Primary Aldosteronism is Common

Horm Met Res 2012;44:157

16%

20%

4.3%

9.5%

• Best screening test aldosterone-renin ratio (ARR) • Many drugs effect results

– No DRIs or aldo antagonists – Sertraline & escitalopram

• Inc renin (marked) + inc aldo (slight) = net reduction in ARR

• High ARR – PA 30 to 50%

• Considerations – Further work-up with possible surgery – Trial of MRA without screening – Avoid $ biochemical and imaging tests – Avoid invasive adrenal vein sampling and surgery

Update: Diagnosis of PA

Creation iliac AVF lowers BP?

• SPRINT HTN Trial

• Open-label RCT 9361 pts age 50+ with SBP > 130 & one additional CV risk factor

• Intensive SBP < 120 vs Conventional SBP < 140

• DSMB Stopped Early – Decreased CVEs 30%

– Decreased Death 25%

Results Achieved with Cheap Generics

• There is wide variability in the cost of antihypertensive medications; newer and more expensive agents have not been shown to be significantly safer or more effective than many older, well-established medications that are available in generic form.

• Fixed combinations of antihypertensive medications offer less dosing flexibility and are often substantially more expensive than prescribing the component medications independently.

MKSAP 16®: High Value Care

• V0490XA Hit by a Mack Truck

• W22.01 Walked into wall, initial encounter

• Z621 Parental overprotection

• V96.00XS Unspecified balloon accident injuring occupant, sequela

• T63.442S Toxic effect of venom of bees, intentional self harm

ICD-10 Codes cont.

Evaluation

Please take < 90 seconds to evaluate this session.

Time permitting, speaker will take questions following evaluation.

Responses are not displayed and are important in maintaining high quality education.

The overall performance of the speaker:

1. Poor

2. Fair

3. Average

4. Good

5. Excellent

1. 2. 3. 4. 5.

0% 0%

76%

23%

1%

How well were the learning objectives met?

1. Poor

2. Fair

3. Average

4. Good

5. Excellent

PoorFa

ir

Avera

geGood

Excelle

nt

0% 0%

76%

22%

1%

Did speaker present a balanced view of therapeutic options?

1. Yes

2. No

3. N/A

YesNo

N/A

100%

0%0%

How useful will this session be in your practice?

1. Poor

2. Fair

3. Average

4. Good

5. Excellent

PoorFa

ir

Avera

geGood

Excelle

nt

0% 0%

66%

34%

0%

As a result of this program, do you intend to change your patient care?

1. Yes

2. No

YesNo

8%

92%

Thank you!