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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!