1. Hypertension
Derinda Trobaugh, PGY3

2. Disclaimer

3. • Touch on history of hypertension as a pathologic entity
• Measurements, early treatments, early research
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Early papers linking hypertension to increased mortality
Quickly touch on evolution of JNC guidelines
Latest JNC guidelines (JNC 8), evidence behind them
Review
7:17
Objectives

4. History of Hypertension

5. Lithograph showing the
leeching of a patient, date
unknown.
National Library of Medicine,
Bethesda, Maryland

7. • Historical records as far back as 2600 B.C. hold mention
of “hard pulse disease”
• First treatments: Leeching/phlebotomy, acupuncture
• Hippocrates recommended phlebotomy
• 120 AD – cupping of the spine to draw animal spirits
down and out was recommended
History of Hypertension

8. • No way to measure prior to 1700s
• Physicians could estimate by feeling pulse
Measurement of HTN

9. • 1733 – Reverend Stephen Hales measured the intraarterial BP of a horse
Measurement
of HTN

10. “In December I caused a mare to be tied
down alive on her back; she was fourteen
hands high, and about fourteen years of age;
had a fistula of her withers, was neither very
lean nor yet lusty; having laid open the left
crural artery about three inches from her
belly, I inserted into it a brass pipe whose
bore was one sixth of an inch in diameter…
I fixed a glass tube of nearly the same
diameter which was nine feet in length: then
untying the ligature of the artery, the blood
rose in the tube 8 feet 3 inches
perpendicular above the level of the left
ventricle of the heart;… when it was at its
full height it would rise and fall at and after
each pulse 2, 3, or 4 inches…”

11. • 1828 – Poiseuilles measured
BP by cannulating an artery
and attaching a mercury
manometer (a
haemodynamometer)
• Also introduced the unit mm
Hg
• 1847 – Carl Ludwig developed
the kymograph (Greek for
wave writer)
• Same as Poiseuilles’
invention; however, the
manometer was attached to a
slender rod with a brush on the
end which floated on the
mercury and graphed the
measurements

12. Haemotachometer

13. • 1870s - Samuel Siegfried Karl Ritter von Basch
• Rubber bag inflated with
water, tightly drawn
around the neck of a
mercury manometer so
pressure was transmitted
• Bag inflated until pulse
distal to bag ceased;
manometer’s position was
recorded as the SBP
• This method was tested
against cannulation in
dogs and found to
correlate
• 1889 – water was replaced
with air

14. • 1896 – Scipione Riva-Ricci modified sphygmanometer to
closer to the current instrument
• Used brachial artery
• Rubber bag surrounded by a cuff, wrapped around the arm
and inflated with air
• Pressure in the cuff increased until radial pulse could no
longer be palpated
• Pressure then slowly released until
pulse reappeared – this was the SBP
• Initially only measured SBP, later
used strength of pulsations to
determine DBP
• Initially only 5 cm wide; corrected in
1901 by von Recklinghausen to 12 cm

15. • 1905 – N.C. Korotkoff reported on the method of
auscultation of brachial artery, the method which is widely
used today
• Allowed auscultation of diastolic BP as well

16. • 1912 – Sir William Osler
• “In this group of cases it is well to recognize that the extra
pressure is a necessity–as purely a mechanical affair as in
any great irrigation system with old encrusted mains and
weedy channels. Get it out of your heads, if possible, that
the high pressure is the primary feature, and particularly the
feature to treat.”
• Tolerated pressures to 210/100 as benign HTN
“Essential” HTN

17. • First groups to begin paying attention to HTN: Insurance
companies
HTN and mortality

18. • 1925
• Reported that SBP, DBP, and pulse pressure increase with
age
• Conclusions
• Mortality is lower with lower blood pressures
• Mortality increases rapidly with the increase in BP over the
average
Actuarial Societies of
America

19. 1939

20. 1979

21. • Men with SBP 140-159/90-94
• Death rates from CAD and cerebral hemorrhage were 50%
higher than normotensive men
• Men with BP 160/95
• Death rates from CAD and cerebral hemorrhage more than
double
• Death rates from hypertensive heart disease 4 times higher
• Death from kidney disease double
• These effects increased with rise in BP
• When reduced to normotensive
range, these effects disappeared
1979

22. • 1931 – Dr. Paul Dudley White
• “Hypertension may be an important compensatory
mechanism which should not be tampered with, even were
it certain that we could control it.”
• 1931 – Hay in British Medical Journal
• “The greatest danger to a man with high blood pressure lies
in its discovery, because then some fool is certain to try and
reduce it.”
Despite the evidence…

23. • 1946 - Tice’s Practice of Medicine (one of the leading
textbooks of Medicine at the time)
• May not the elevation of systemic blood pressure be a
natural response to guarantee a normal circulation to the
heart, brain and kidneys (“essential” hypertension).
Overzealous attempts to lower the pressure may do no good
and often do harm. Many cases of essential hypertension
not only do not need any treatment but are much better off
without it.
Despite the evidence…

24. • 1965
• Report of the US President’s Commission on Heart Disease,
Cancer, and Stroke recommended a nationwide increase in
screening and treatment of high blood pressure
• Unfortunately, the data for decreasing mortality with
decreased blood pressure really did not exist

25. • 1967, 1970
• Dr. Edward Fries, Veterans Administration Cooperative
Studies
• Both placebo-controlled trials
• Active drug treatment in patients with DBP 90-129 resulted in
lower incidence of stroke, aortic dissection, and malignant
HTN within 2 years
• Treatment primarily with reserpine, chlorothiazide, hydralazine,
and guanethidine
• Followup terminated prematurely
Last piece

26. • 1972
• Secretary of Health, Education and Welfare charged
Director of the National Heart and Lung Institute to develop
a national plan of action
• Result: National High Blood Pressure Education Program
• Created a task force to develop definitions, standards of care
and effective treatment regimens

27. • NHBPEP created the Joint National Committee on Detection,
Evaluation, and Treatment of High Blood Pressure
• Identify segment of population with HTN
• Determine those who could be expected to benefit from
antihypertensive therapy
• Propose appropriate therapeutic regimens

28. Threshold for treatment initiation
Goal BP
JNC 1 & 2
DBP >105, ?90-104
DBP < 90
JNC 3 & 4
DBP > 95, monitor 90-94; SBP > 160 DBP < 90
JNC 5
140/90, ?140/85 in older patients
Same
JNC 6
140/90, 130/85 in DM, CKD
Same
JNC 7
140/90, 130/80 in DM, CKD
Same
Comparisons

29. First line therapy
Second line therapy
Third
Fourth
JNC 1 & 2
Thiazide diuretic
Adrenergic blocker
Vasodilator
Guanethidine sulfate
JNC 3
Thiazide or BB
Adrenergic blocker
Vasodilator
Guanethidine sulfate
JNC 4
Thiazide, BB,
ACEI, or CCB
Different class
Different
class
Different class
JNC 5
Diuretics or BB
Different class
ACEI or
CCB
Different class
JNC 7
Thiazide
Comparisons

30. JNC 7

31. • BP goal
• 140/90 for most patients, 130/80 for patients with DM and CKD
• Thiazide is initial therapy, except for
• Angina – BB or CCB
• ACS – BB, ACEI
• Post-MI – ACEI, BB, Aldo Ant
• CKD – ACEI or ARB
• HF – BB, ACEI; loop and Aldo Ant if end-stage
• DM – Thiazide, BB, ACEI/ARB
• Stroke prevention – Diuretic, ACEI
• African American – Thiazide or CCB
• When BP >20/10 above goal, consider starting with 2 drugs rather
than monotherapy
JNC 7 guidelines

32. JNC 8

33. This is not your
momma’s JNC

34. • "Our goal was to create a very simple document. We
wanted to make the message very simple for physicians:
treat to 150/90 mm Hg in patients over age 60 and 140/90
for everybody else. And we simplified the drug regimen
as well, to say that any of these [four] choices are good,
just get people to goal. Monitor them, track them,
remonitor them. That's a very simple message."
Dr. Paul A James, lead author

35. JNC 8

36. •
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RCT focusing on adults >18 yoa with HTN
Excluded studies with <100 studies
Excluded studies with followup period <1 year
Included studies reporting effects on:
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Overall mortality, CVD mortality, CKD mortality
MI, CHF, hospitalization for HF, CVA
Coronary or other revascularization
ESRD
JNC 8 – Evidence Review

37. • Drafted evidence statements
• Panel reviewed and voted
• 2/3 majority acceptable
• If recommendation based on expert opinion, required 75%
agreement
• Followed Institute of Medicine’s standards for guideline
creation and review
JNC 8

38. • Patients aged 60+
• Treatment threshold and BP goal 150/90+
• Strong Recommendation – Grade A
• If treatment achieves BP <150/90, do not step-down
medication (i.e. if already controlled <140, don’t change
treatment)
• Expert Opinion – Grade E
• Does not apply to high-risk groups such as black persons,
those with CVD including stroke, and those with multiple
risk factors
Recommendation 1

39. • 3 trials (SHEP, Syst-EUR, and HYVET) with SBP goals less than or
equal to 150 mm Hg
• Decrease in cerebrovascular morbidity and mortality
(primary outcome)
• Decreased fatal and nonfatal heart failure (secondary
outcome)
• Decreased coronary heart disease including non-fatal
MI, fatal MI, CHD death, or sudden death (secondary
outcome)
• Goal SBP </= 150 mm Hg in these 3 studies
• Rated as Good evidence
Evidence

40. • 2 trials (JATOS and VALISH) showing no difference in
higher and lower SBP goals in older adults
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Low quality evidence
Trends in both direction
Did not show statistically significant differences in BP goal
<140 vs higher goal; however, no increase in adverse events
• Theory these goals were underpowered
Evidence

41. The minority speaks out…

42. • 2 trials (JATOS and VALISH) showing no increase in
adverse events between higher and lower SBP goal
• FEVER trial
• Did not meet inclusion criteria
• 137 vs 143; significant reduction in CVD, mortality, CAD,
HF
• SPS3 trial
• 137 vs 144; significant reduction in stroke
• 2 meta-analyses with conflicting conclusions
• JNC 8 uses lack of evidence to support higher goal;
minority would use lack of evidence to support lower goal
• Recommended BP goal 150/90 in patients over 80
The minority speaks out…

43. • Patients aged <60, DBP treatment threshold and
treatment goal <90 mm Hg
• For ages 30 through 59 years, Strong Recommendation –
Grade A
• For ages 18 through 29 years, Expert Opinion – Grade E
Recommendation 2

44. • Based on evidence from six trials - EWPHE, HDFP,
Hypertension-Stroke Cooperative, HYVET, MRC and
VA Cooperative
• Treatment threshold DBP > 90 decreased cerebrovascular
morbidity/mortality (High), heart failure (Moderate), overall
mortality (Low)
• Insufficient evidence on CAD related mortality
• One trial (HOT trial) looking at stricter BP goals found
no statistically significant differences
• Trend towards increase in MI with DBP goal <90 compared
with <85
• No trials included patients <30 years of age
Evidence

45. • In the general population younger than 60 years, initiate
pharmacologic treatment to lower BP at SBP of 140 mm
Hg or higher and treat to a goal SBP of lower than
140mmHg.
• Expert Opinion – Grade E
Recommendation 3

46. • Not a lot
Evidence

47. • Cardio-sis, 2009
• SBP <130 vs SBP <140
• Significant difference in coronary revascularization but no
other statistically significant difference
• Limitation: Only about 4 mm Hg in reality separated the
groups
• JATOS and VALISH
• No significant differences
Evidence

48. • Patients >18 years of age with CKD
• Treatment threshold and treatment goal SBP 140 mm Hg
and DBP 90 mm Hg
• Insufficient evidence to recommend lower goal
• Expert Opinion – Grade E
Recommendation 4

49. • REIN-2
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Adults with CKD
Intensive control (<130/80) vs conventional (DBP <90)
No difference in GFR decline
Did not look at mortality, CVD, etc
• AASK and MDRD
• MAP <92 (120/75) vs <107 (140/90)
• No difference
• AASK looked at HF, CAD, overall mortality, MDRD did
not
Evidence

50. • Patients with diabetes
• Treatment initiation at 140/90, goal 140/90
• Expert Opinion – Grade E
Recommendation 5

51. • SHEP, Syst-Eur, UKPDS
• Showed reduction in cardiovascular-related events, stroke and
mortality with SBP goal <150
• ACCORD
• Compared goal SBP <120 to <140
• Intensive treatment group had lower stroke rate (secondary
outcome) but no other differences
• ABCD
• Compared goal DBP <75 to 80-89
• All cause mortality decreased with lower goal
• HOT
• Compared DBP <80, <85, <90
• Decreased CV events; however, diabetes group was a post hoc
subgroup consisting of only 8% of the study (1500 patients)
Evidence

52. • In the general nonblack population, including those with
diabetes, initial antihypertensive treatment should include
a thiazide-type diuretic, calcium channel blocker (CCB),
angiotensin-converting enzyme inhibitor (ACEI), or
angiotensin receptor blocker (ARB).
• Moderate Recommendation – Grade B
• Only included trials as evidence that compared one drug to
another and their effect on health outcomes
Recommendation 6

53. • ALLHAT, INSIGHT, ANBP2
• Showed lower rates of heart failure with diuretics than CCB
or ACEI
• ACEI reduces rates of heart failure
• Diuretic results in worsened hyperglycemia
• Comparisons of other anti-hypertensives gave varying
results but no consistent differences
• Multiple trials showing antihypertensive therapy with
diuretic is similar compared to ACEI, CCB, or alpha
blocker
Evidence

54. • ACEI vs CCB
• ACEI reduces heart failure
• ALLHAT: In African-Americans, ACEI had higher stroke
incidence – also less effective at lowering BP
• STOP-HTN2: Lower rate of MI with ACEI
• ARB vs CCB
• VALUE: More diabetes with CCB, more MI with ARB
• CASE-J: More diabetes with CCB
• MOSES: Did not report
Comparison of antihypertensives

55. • Diuretic vs CCB
• INSIGHT: Fewer MI with diuretics
• Diuretic vs ACEI
• ANBP2: Fewer MI with ACEI
• ALLHAT: Fewer strokes with diuretic
• BB vs diuretic
• MAPHY: Fewer fatal CHD events with BB
Comparison of antihypertensives

56. • BB vs ARB
• LIFE: ARB group less CV death, less new onset DM
• One study
• Review did not include trials including subjects with CHF,
CAD, etc but not HTN
What happened to the
BB?

57. • In black patients, including with DM, initial
antihypertensive treatment should include thiazide or
CCB
• For general black population: Moderate Recommendation
–Grade B
• For black patients with diabetes:Weak Recommendation –
Grade C
Recommendation 7

58. • ALLHAT
• Prespecified subgroup analysis
• Thiazide improves cerebrovascular, HF, and CV outcomes
over ACEI
• CCB less effective than diuretic in HF, but similar in other
outcomes
• CCB fewer strokes than ACEI
• No evidence for other antihypertensives in AfricanAmericans
Evidence

59. • Adults with CKD and HTN should be on an ACEI or
ARB as initial antihypertensive therapy
• Regardless of DM status
• If black with CKD and proteinuria, ACEI or ARB as firstline
• If black with CKD without proteinuria, less clear
• Moderate Recommendation – Grade B
Recommendation 8

60. • The main objective of hypertension treatment is to attain and
maintain goal BP. If goal BP is not reached within a month of
treatment, increase the dose of the initial drug or add a second drug
from one of the classes in recommendation 6 (thiazide-type diuretic,
CCB, ACEI, or ARB). The clinician should continue to assess BP
and adjust the treatment regimen until goal BP is reached. If goal BP
cannot be reached with 2 drugs, add and titrate a third drug from the
list provided. Do not use an ACEI and an ARB together in the same
patient. If goal BP cannot be reached using the drugs in
recommendation 6 because of a contraindication or the need to use
more than 3 drugs to reach goal BP, antihypertensive drugs from
other classes can be used. Referral to a hypertension specialist may
be indicated for patients in whom goal BP cannot be attained using
the above strategy or for the management of complicated patients for
whom additional clinical consultation is needed.
• Expert Opinion – Grade E
Recommendation 9

63. • Very focused review
• Only included RCTs, did not include systematic reviews,
meta-analyses, observational or prospective studies
• Excluded trials including participants with normal BP
• Many recommendations were based on panel members’
knowledge and experience
Limitations

64. ASH/ISH HTN Guidelines 2014

66. This is not the end…

67. Controversy

68. • “While it is likely that there will be considerable controversy in
hypertension treatment for the foreseeable future, several critical
next steps are needed. First, larger RCTs need to compare different
BP thresholds in diverse patient populations...Second, there is an
important need to create a national consensus group to draft an
updated comprehensive practice guideline that would harmonize the
hypertension guideline with other cardiovascular risk guidelines and
recommendations, thereby resulting in a more coherent overall
cardiovascular prevention strategy…Finally, once the right targets
for BP thresholds are determined, patients and physicians need to
work together to consistently achieve these new goals.”
JAMA. Published online December 18, 2013.
doi:10.1001/jama.2013.28443

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