Hypertension 2020 Chris Rembold MD Preventive Cardiology - - PDF document

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Hypertension 2020 Chris Rembold MD Preventive Cardiology - - PDF document

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1/28/2020 Hypertension 2020 Chris Rembold MD Preventive Cardiology Cardiovascular Division Hypertension 1 1/28/2020 Ischemic heart death is predicted by AGE > BP, total cholesterol, and HDL 61 trials with 900,000 patients; Lancet

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Hypertension 2020

Chris Rembold MD Preventive Cardiology Cardiovascular Division

Hypertension

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Ischemic heart death is predicted by AGE > BP, total cholesterol, and HDL

61 trials with 900,000 patients; Lancet 360:1903, 2002 & 370:1829, 2007

Systolic BP Total Cholesterol HDL

4.5 is 174 8 is 310 1 is 39 2 is 77

Stroke is predicted by AGE > BP, not by total cholesterol or HDL

61 trials with 900,000 patients; Lancet 360:1903, 2002 & 370:1829, 2007

Systolic BP Total Cholesterol HDL

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The Pathophysiology of Hypertension

How Low should we treat BP ? Observational data

130-139/ 85- 89 120-129/ 80- 84 <120/<80 mmHg

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SPRINT NEJM (2015)

  • 9361 people SBP >130 no diabetes for 3.3 y
  • Randomized SBP goal 120 vs 140
  • Achieved 121/69 vs 136/76 on 2.8 vs 1.8 meds
  • Primary: MI, ACS, CVA, CHF, CV death
  • Surprisingly, no effect on stroke, reduced mortality

Parachute Trial BMJ 2018; 363:k5094

  • Do clinical trials always show the correct

result?

  • 92 people randomized to jumping from an

airplane with a parachute or an empty backpack

  • Parachute use did not significantly reduce

death or major injury (0% for parachute or 0% for empty backpack, p>0.9)

  • This is the first and only trial testing benefit
  • f a parachute, there was no benefit.
  • Go back and read the methods
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SPRINT NEJM (2015)

  • Lets go back and read the methods
  • Nothing helpful in main paper, keep looking
  • The previously published methods paper reveals that

BP was measured with an automated BP machine that measured and averaged BP when there was no clinician in the room

  • This automated BP machine finds SBP values 5-13

points lower than cuff BP

  • So Sprint aggressive rx 121/69 is cuff SBP 126-134
  • & Sprint less aggressive 136/76 is cuff SBP 141-149
  • Prior trials suggest goal ~130 with cuff, so Sprint

actually adds little to prior knowledge

  • Serious adverse events (hypotension, syncope,

electrolyte anomaly, acute kidney injury, and injurious falls) sorted by pulse pressure

  • Higher pulse pressure and more aggressive BP Rx

associated with more adverse events

SPRINT PP (Krishnaswami, AJM 131:1220. 2018)

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  • On treatment DBP < 56 at any visit was associated

with higher MI, ACS, CVA, CHF, or death

  • Occurred in both aggressive and regular BP treatment

groups

SPRINT DBP (Lee, AJM 131:1228, 2018) INVEST AIM 144:884, 2006

  • 22576 patients with CAD and HBP
  • Rx atenolol ± HCTz vs. verapamil ± trandolapril
  • No difference in outcomes between Rx groups
  • DBP <70 associated with more MI

– Blood flow to heart occurs during diastole

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  • Combined Sprint and

Accord data

  • Resistant HBP is use

4+ meds or BP >130/80 on 3 meds

  • Most benefit in

Resistant Hypertension

SPRINT & ACCORD Resistant HBP

(Smith, AJM 131:1463, 2018)

How to decide who needs more and less BP treatment ?

  • Resistant needs more BP control
  • Use pulse pressure ?
  • Get more data (fundoscopy, albumin

creatinine ratio, 24 hour BP monitor)

– Normal BP (low office, low home) – White Coat (high office, low home) – Hypertension (high office, high home) – Masked (low office, high home)

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Masked HT or Sustained HT worse than White coat HBP or normal BP

  • 7295 people with ISH (DBP < 90) followed 10.6 years, 655 CV events
  • Sustained HT = cuff >140, amb>135 Masked = cuff <140, amb>135

White coat HT = cuff >140, amb<135 Normal BP = cuff <140, amb<135

  • Hypertension 59:564, 2012

BP dipping (BP fall at night)

Cuspidi et al. J Clin HBP 19:713, 2017

  • 2900 dippers

(nocturnal fall 10-20%)

– Low risk

  • 2712 nondippers

(nocturnal fall 0-10%)

– Intermediate risk

  • 696 reverse dipper

(nocturnal BP rise)

– Highest risk

  • Extreme dipper

(nocturnal fall >20%)

– Also low risk Day 121/75 Night 108/68 Nonfatal and fatal CV events

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Hansen Nocturnal BP Hypertension 57:2, 2011

  • 9,641 people in 8 studies
  • Mortality and CV events (CV death, MI, revasc, CHF,

CVA) adjusted for sex, age, BMI, smoking, TC, HxCVD, DM, BP meds

  • Nighttime BP & not dipping more associated w mortality

more c

IDACO JAMA 322:4019 2019

  • 11135 people followed 13.8 y (Europe, Asia, SA)
  • BP Office 132/80, automated office 135/82
  • 24 h 123/73, Day 130/79, Night 113/64, Dip 13%
  • Nighttime BP predicted mortality, D&N predict CVAs
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HYGIA EurHeartJ 2019

  • 19084 hypertensive Galicians (Spain) for 6.3 y
  • Age 61, 56% female, 23% DM, 15% smoker, 10%

CAD, creatinine 1.06, albumin creatinine ratio 6

  • HBP is SBP >135/85 awake or >120/70 asleep
  • BP Office 149/86, Wake 136/81, Sleep 123/70
  • Average 1.8 meds:

– Monotherapy ARBorACEI 69% CCB (amlodipine) 13% – Dual ARBorACEI/HCTz 43% ARBorACEI/CCB 26% – Triple ARBorACEI/HCTz/CCB 69% – ARB 53% HCTz 43% CCB 34% ACEI 24% BB 22%

HYGIA EurHeartJ 2019 #2

  • 19084 hypertensive Galicia (Spain) for 6.3 y
  • Randomized: all BP meds Awakening vs. Bedtime

– If GLACOMA, excluded, NO BEDTIME BP MEDs

  • Awakening

Bedtime

  • Number meds

1.8 1.7 *

  • Office BP

143/82 140/81 *

  • Waking BP

130/77 129/76 NS

  • Asleep BP

118/66 115/65 *

  • Dipping

13% 15% *

  • Creatinine

1.16 1.06 *

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HYGIA EurHeartJ 2019 #3

  • Raw numbers not in paper, but to get OR 0.55, Bed

n=643 vs AM n=1109, p = 2E-30 (p of p >99.99%)

HYGIA #4 EurHeartJ 2019

  • Bedtime dosing of BP

meds clearly better than AM dosing

  • Benefit more if no prior

BP rx and no prior CV event (right)

  • No difference in adverse

events

  • IF GLACOMA, NO

BEDTIME BP MEDs

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24 hour BP monitoring #1

  • 73 M on Benicar 40 Metoprolol 100 Office 164/86
  • Mean Day 127/65 Night 115/59 with White Coat
  • No further Rx needed

24 hour BP monitoring #2

  • 59 F on no BP meds Office BP 152/90
  • Mean Day 130/89 Night 128/81 (no dipping)
  • White coat (high office) but Nocturnal HBP, Rx
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24 hour BP monitoring #3

  • 57 F on no meds Office BP 146/86
  • Mean Day 156/96 Night 157/94 – mild office HBP

but Masked severe HBP with reverse dipping – Rx

24 hour BP monitoring #4

  • 55 M DMx20y A1c 12 on Lisinopril 2.5 Office BP

98/66 sitting 72/50 standing with presyncope

  • Mean Day 99/67 night 116/80 – Rx orthostasis
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Which BP agent ?

  • 50+ trials in mostly in moderate-severe HBP
  • Thiazides better than placebo (MRC, SHEP, lots)
  • Thiazides better than β blockers (MRC)
  • ARB better than β blockers (LIFE)
  • ACEI better dihydropyridine (StopHBP2, Insight)
  • In DM, ACEI better dihydropyridine (ABCD, FACET)
  • In CRI, ACEI orARB better than no (many, Renaal, Idnt)
  • In CRI, ACEI better than dihydropyridine or βB (AASK)
  • In mild hypertension, thiazides = ACEI = amlodipine

and all three better than α blockers

  • In moderate hypertension, thiazides=ACEI/ARB >other

Beta blocker inferior to ACEI, ARB, CCB, and diuretics

  • Ettehad Lancet 387:957, 2015
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LEGEND Lancet 2019 (Suchard)

  • 4,893,591 patients with new onset of and new

single agent treatment for hypertension

  • From OHDSI global network of 6 claim and 3

EMR databases with data from 1996-2018

  • Corrected for treatment bias (eg ACEI in DM)
  • Thiazides (mostly HCTz) 861k

17%

  • ACEI (mostly lisinopril) 2373k

48%

  • ARB (mostly losartan) 752k

16%

  • dCCB (mostly amlodipine) 799k

15%

  • ndCCB (mostly diltiazem) 139k

3%

LEGEND Lancet 2019 (Suchard)

  • ARB vs Thiazide: ARB more hyperkalemia, Thiazide

more hypokalemia and hyponatremia – overall SIMILAR

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LEGEND Lancet 2019 (Suchard)

  • ACEi vs Thiazide: ACEi had more mortality, diarrhea,

GI bleed, AKI, high K, hypotension, angioedema cough

LEGEND Lancet 2019 (Suchard)

  • Dihydropyridine vs Thiazide: DHP more mortality,

dementia, CRI, ESRD, high K, neutropenia, low platelets thrombocytopenia

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LEGEND Lancet 2019 (Suchard)

  • Diltiazem/Verapamil vs Thiazide: more mortality, low HR,

TIA, dementia, GI bleed, AKI, ESRD, high K, hypotension

Summary of BP treatment

  • Best agents are THIAZIDEs and ARBs

– Second agents ACEi or dihydropyridine

  • Bedtime dosing (except GLACOMA)
  • Consider 24 hour monitoring to Rx

Nocturnal BP (goal <120/70)

  • β blockers and α blockers clearly inferior
  • Do not use ACEI and ARB (ONTARGET)

– combination no benefit & more adverse effects

  • Dihydropridines ok as 3rd line, less effective
  • n outcomes if DM or CRI
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Prior CVA or TIA

PROGRESS - Lancet 358:1033, 2001

6105 patients with prior CVA or TIA (mean BP 147/86) for 4.0 years Randomization (blind): Perindopril 4mg +/- Indapamide vs. placebo ACEI lowered BP 5/3 mmHg; ACEI+thiazide lowered BP 12/5 mmHg Treatment better NNT RRR Stroke 27 ( 20 to 45)** 27** Fatal/Disabling 50 ( 32 to 148)** 23** Ischemic 41 ( 28 to 99)** 23** Hemmorhagic 82 ( 62 to 168)** 50** ACEI only 157 ( 34 to -45) 5 ACEI+thiazide 16 ( 13 to 23)** 41** MI 76 ( 47 to 341)** 25** Total Mortality 240 ( 55 to -83) 4

MOSES Stroke 36:1218, 2005

  • 1405 Stroke patients with HBP, carotids <70% sten.
  • 34% monotherapy, 30% 2 drugs, 36% >2 drugs
  • Randomized Eprosartan vs. Nitrendipine Odds Ratio
  • BP on Rx

137/81 136/80

  • MI CV death

4.95% 6.62% 0.75 (0.55-1.02)

  • CVA

6.56% 8.78 0.75 (0.58-0.97)*

  • All Events

13.25% 16.71% 0.79 (0.66-0.96)*

  • MESSAGE, if prior CVA or TIA,

ACEI or ARB and thiazide

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BP and Lipids predict Dementia

BMJ 322:1447, 2001

1443 Finns with BP and Lipid tests in the 1970s followed 21 years Blood pressure RR for Alzheimers Normal SBP < 140 1.0 (reference) Borderline SBP 140-160 1.8 (0.9 to 3.7) High SBP > 160 2.3 (1.0 to 5.0) ** Total Cholesterol Normal TC < 6.5 1.0 (reference) High TC > 6.5 2.7 (1.4 to 5.4) ** (adjusted for age & BMI)

Dementia Prevention in HBP Trials

  • PROGRESS Trial – 6105 pts with CVA/TIA
  • ACEI/HCTz  Dementia 23% (CI 0-41%) *

– 106 vs. 136 cases, most benefit if recurrent CVA – JAMA 163, 1069, 2003

  • Syst-Eur Trial – 2902 pts with Systolic HBP
  • SBP  7 mmHg  Dementia 55% (CI 16-76%) *

– 21 vs. 43 cases, age at onset 79 – ArchIntMed 162, 2046, 2002

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NHANES Survey 1995

  • 24% of Americans had High Blood Pressure
  • Of those with High Blood Pressure

– 47% were on NO medications – 28% were Treated but not controlled – 25% were Treated AND CONTROLLED

Non Drug Therapy

  • Diet – Dash diet lowers BP 8/5 mmHg
  • Weight – loss 10 kg lowers BP 10/10 mmHg
  • Salt – reduction helps when on Rx
  • Isotonic exercise
  • Smoking cessation
  • Alcohol
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I have lived temperately, eating little animal food…so much as a condiment for the vegetables, which constitute my principal diet.

  • Thomas Jefferson to Dr. Vine Utley, 1819

Alcohol in French Soldiers in WWI

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Alcohol consumption and CV events

Romelsjo, BMJ 319:821, 1999

  • 49,618 Swedish military conscripts x 25 years
  • Compared to nondrinkers, 30g alcohol / day
  • Reduced MI 39%
  • Increased total mortality 53%
  • Increased stroke by 130%

CPAP in Sleep Apnea lowers BP

Becker, et al. – Circ 107:68, 2002

  • 32 patients with mod-severe obstructive

sleep apnea randomized to effective vs. subtherapeutic CPAP

  • Effective CPAP  apnea/hypopnea by 95%

and  mean BP by 9.9+11.4 mmHg

  • Subtherapeutic CPAP  apnea/hypopnea by

50% and  mean BP by 0.6+9.5 mmHg

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Inadequate Response to BP Therapy

  • Noncompliance
  • Associated medical conditions
  • Secondary hypertension (RAS, aldo)
  • Volume overload (medication induced)
  • Pseudo hypertension
  • Inconvenient Dosing
  • Drug Interactions (NSAIA)

The Joint Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Int Med. 1993;153:154-183

Summary of BP treatment

  • Best agents are THIAZIDEs and ARBs

– Second agents ACEi or dihydropyridine

  • Bedtime dosing (except GLACOMA)
  • Consider 24 hour monitoring to Rx

Nocturnal BP (goal <120/70)

  • β blockers and α blockers clearly inferior
  • Do not use ACEI and ARB (ONTARGET)

– combination no benefit & more adverse effects

  • Dihydropridines ok as 3rd line, less effective
  • n outcomes if DM or CRI