hypertension- classics trobaugh
TRANSCRIPT
HypertensionDerinda Trobaugh, PGY3
Disclaimer
Objectives
• Touch on history of hypertension as a pathologic entity• Measurements, early treatments, early research
• 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
History of Hypertension
Lithograph showing the leeching of a patient, date unknown.National Library of Medicine, Bethesda, Maryland
History of Hypertension
• 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
Measurement of HTN
• No way to measure prior to 1700s• Physicians could estimate by feeling pulse
Measurement of HTN
• 1733 – Reverend Stephen Hales measured the intra-arterial BP of a horse
“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…”
• 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
Haemotachometer
• 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
• 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
• 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
“Essential” HTN
• 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
HTN and mortality
• First groups to begin paying attention to HTN: Insurance companies
Actuarial Societies of America
• 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
1939
1979
1979
• 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
• 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…
Despite the evidence…
• 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.
• 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
Last piece
• 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
• 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
• 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
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
Comparisons
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
JNC 7
JNC 7 guidelines
• 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 8
This is not your momma’s JNC
Dr. Paul A James, lead author
• "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."
JNC 8
JNC 8 – Evidence Review
• 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:• Overall mortality, CVD mortality, CKD mortality
• MI, CHF, hospitalization for HF, CVA
• Coronary or other revascularization
• ESRD
JNC 8
• 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
Recommendation 1
• 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
Evidence
• 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
• 2 trials (JATOS and VALISH) showing no difference in higher and lower SBP goals in older adults• 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
The minority speaks out…
The minority speaks out…
• 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
Recommendation 2
• 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
Evidence
• 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
Recommendation 3
• 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
Evidence
• Not a lot
Evidence
• 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
Recommendation 4
• 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
Evidence
• REIN-2• 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
Recommendation 5
• Patients with diabetes• Treatment initiation at 140/90, goal 140/90
• Expert Opinion – Grade E
Evidence
• 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)
Recommendation 6
• 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
Evidence
• 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
Comparison of anti-hypertensives
• 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 anti-hypertensives
• 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
What happened to the BB?
• 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
Recommendation 7
• 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
Evidence
• 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 African-Americans
Recommendation 8
• 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 first-line
• If black with CKD without proteinuria, less clear
• Moderate Recommendation – Grade B
Recommendation 9
• 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
Limitations
• 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
ASH/ISH HTN Guidelines 2014
This is not the end…
Controversy
• “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
• Booth J. A short history of blood pressure measurement. Proc R Soc Med. 1977 Nov;70(11):793-9.
• Brenner BM, Cooper ME, de Zeeuw D, et al; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869.
• Cundiff, David, MD. "A Call to Retract the JNC-8 Hypertension Guidelines." KevinMD.com. N.p., n.d. Web. 21 Jan. 2014.
• Esunge, PM. From blood pressure to hypertension: the history of research. J R Soc Med. 1991 October; 84(10): 621.
• James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; DOI:10.1001/jama.2013.284427.
• Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure; a cooperative study. JAMA. 1977;237:255–261.
• Joint National Committee: The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413-24462.
• Kotchen, Theodore A. Historical Trends and Milestones in Hypertension Research: A Model of the Process of Translational Research. Hypertension. 2011;58:522-538
• Lewis EJ, Hunsicker LG, Bain RP, Rohde RD; The Collaborative Study Group. The effect of angiotensin- onverting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329(20):1456-1462.
• Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: What are the right goals and purposes? JAMA 2014; DOI:10.1001/jama.2013.284430.
• Report on the “1979 Build and Blood Pressure Study” Supplementary Observations, 1982 . Society of Actuaries and Association of Life Insurance Medical Directors of America; 1982. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2572.
• Roguin A. Scipione Riva-Rocci and the men behind the mercury sphygmomanometer. Int J Clin Pract. 2006 Jan; 60(1):73-9.
• Sox HC. Assessing the trustworthiness of the guideline for management of high blood pressure in adults. JAMA 2014; DOI:10.1001/jama.2013.284429.
• The 1984 Joint National Committee. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1984;144:1045-1057.
• The 1988 Joint National Committee. The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988;148: 1023-1038.
• The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1980 Expert of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1980;141:1280-1285.
• The Joint National Committee. "The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V)." Archives of Internal Medicine 153.2 (1993): 154-83.
• Weber, Michael A., Ernesto L. Schiffrin, William B. White, Samuel Mann, et al. "Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension and the International Society of Hypertension." Journal of Hypertension 32.1 (2014): 3-15.
• Wood, Shelley. "JNC 8 at Last! Guidelines Ease Up on BP Thresholds, Drug Choices." Medscape. N.p., n.d. Web. 21 Jan. 2014.
• Wright, J. T., L. J. Fine, and D. T. Lackland. "Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150 Mm Hg in Patients Aged 60 Years or Older: The Minority View." Annals of Internal Medicine. N.p., 14 Jan. 2014. Web. 17 Jan. 2014.