Transcript Cases of hypertension

Cardiology department
KyungHee University Hospital
Hyunsoo Kim
 C/C: high BP (158/94mmHg
confirmed on several office visits)
 PMHx: dyslipidemia
 Labs: normal renal function, wellcontrolled lipids and well-controlled
diabetes
 Urine micro-albumin mildly elevated.
Blood Pressure
Classification
Systolic blood
pressure
(mm Hg)
Diastolic blood
pressure
(mm Hg)
< 120
< 80
Pre-hypertension
120-139
80-89
Stage 1 hypertension
140-159
90-99
Stage 2 hypertension
> 160
> 100
Normal
Chobanian AV et al. JAMA 2003;289:2560-72.
Chobanian AV et al. JAMA 2003;289:2560-72.
Commissioned by the NHLBI in 2008
Limited to randomized controlled trials (RCTs)
published between 1966 and 2009
Included patients age 18 or older with hypertension
Sample size of 100 patients or more
Results must have included “hard” outcomes
Subsequent search of studies from 2009 to 2013
required samples of 2000 or more patients
James PA et al. JAMA 2014;311:507-20.
3 critical questions for adults with
hypertension
When to start therapy?
 How low should I go?
 What drug do I use?

James PA et al. JAMA 2014;311:507-20.
Action to Control CV Risk in Diabetes (ACCORD)
 Randomized, double-blind trial
 Total 4.733 patients
 Included patients with T2DM and high CV risk
 Randomized to SBP<120 or SBP<140
 Primary outcome of CV death, MI, or stroke
 Results
 Mean
SBP of 119 mm Hg vs. 133 mm Hg
 No significant difference in primary outcome (HR=0.88, p=0.2
)
 Incidence of stroke was lower with intensive treatment (HR 0.
59, p=0.01)
 Significant increase in serious adverse events
The ACCORD Study Group. N Engl J Med 2010;362:1575-85.
thiazide
Beta blocker
Circulation. 2008;117:2706-2715
CAFE study
Ascot-CAFE study
Losartan Intervention for Endpoint reduction
(LIFE) study
 Compared losartan vs. atenolol in pts. with HTN & LVH
 Primary outcome of CV death, MI, or stroke
 Overall 13% RRR with losartan vs. atenolol (p=0.021)
 Driven mainly by 25% reduction in risk of stroke (p=0.0
01)
 Vasodilating beta blocker (Canada guideline)
 BB still recommended for many patients with
comorbid conditions (CHF, CAD, etc.)
Dahloff B et al. Lancet 2002;359:995-1003.
ALLHAT
Randomized, double-blind trial
Enrolled 33,357 patients age 55 or older
Chlorthalidone
Amlodipine
Lisinopril
Doxazosin
(this arm stopped early 2° worse outcomes)
Primary outcome of CHD death or nonfatal MI
No significant difference in primary outcome among
the thiazide, ACEI, or CCB
The ALLHAT Collaborative Research Group. JAMA 2002;288:2981-97.
Free add-on antih
ypertensive agen
ts*
Amlodipine 10 +
benazepril 40 mg
Screening
Randomization
Amlodipine 5 mg +
benazepril 40 mg
Amlodipine 5 mg +
benazepril 20 mg
Benazepril 20 mg +
HCTZ 12.5 mg
Benazepril 40 mg +
HCTZ 12.5 mg
Benazepril 40 mg +
HCTZ 25 mg
Titrated to achieve BP<140/90
mmHg; <130/80 mmHg in patients
with diabetes or renal insufficiency
14 Days
Day 1
Free add-on antihy
pertensive agents
*
Month 1
Month 2
Month 3
Year 5
*Beta blockers; alpha blockers; clonidine; (loop diuretics).
Jamerson KA et al. Am J Hypertens. 2003;16(part2)193A
ACEI / HCTZ
N=5733
CCB / ACEI
mm Hg
N=5713
130mmHg
Difference of 0.7 mmHg p<0.05*
129.3 mmHg
Month
Patients
5731
5709
DBP: 71.1
5387
5377
5206
5154
DBP: 72.8
4999
4980
4804
4831
4285
4286
2520
2594
1045
1075
*Mean values are taken at 30 months F/U
visit
Cumulative event
rate
ACEI / HCTZ
20% Risk
Reduction
650
CCB / ACEI
526
p=0
.0002
Time to 1st CV morbidity/mortality (days)
HR (95% CI): 0.80 (0.72, 0.90)
INTERIM RESULTS Mar 08
In patients <60 years of age, start medications
at blood pressure of >140/90mm Hg and treat to
goal of <140/90mm Hg
In all adult patients with diabetes or chronic kid
ney disease, start medications at blood pressure
of >140/90mm Hg and treat to goal of <140/90m
m Hg
James PA et al. JAMA 2014;311:507-20.
 Step 1
 ACEi or ARB
 CCB (older than 55 and black people)
 Step 2
 ACEi or ARB + CCB
 Step 3
 ensure step 2 treatment is at optimal or best
tolerated doses.
 ACEi or ARB + CCB+ thiazide-like diuretic
 Step 4
 low-dose spironolactone (25 mg once daily)
 Consider higher-dose thiazide-like diuretic
treatment
NICE clinical guideline 2011
 C/C: high BP(145/85mmHg at
several office BP)
 PMHx: dyslipidemia
 EKG: NSR
 CXR: no cardiomegaly
 No abnormal lab findings
Korea hypertension society 2013 guideline
Often present with isolated systolic HTN
More likely to present with comorbidities
Many clinical trials in HTN have excluded these
patients (particularly for those 80 years and old
er)
Elderly are more susceptible to certain adverse
effects (orthostatic hypotension)
HYpertension in the Very Elderly Trial
 Randomized, double-blind trial
 Total 3336 patients
 Included patients aged 80 or older with SBP>160m
mHg
 Randomized to indapamide +/- perindopril or place
bo
 Target BP of 150/80mmHg
 Primary outcome of fatal or nonfatal stroke
Beckett NS et al. N Engl J Med 2008;358:1887-98.
Results
Mean BP at the end of the trial
Indapamide
+/- perindopril - 143/78 mm Hg
Placebo – 158/84 mm Hg
48.0% of indapamide patients achieved goal BP vs.
19.9% of placebo patients (p<0.001)
Outcomes with indapamide +/- perindopril
30% reduction
in stroke (p=0.06)
64% reduction in heart failure (p<0.001)
21% reduction in all-cause mortality (p=0.02)
Beckett NS et al. N Engl J Med 2008;358:1887-98.
Two “treat-to-target” trials in this age group
 Japanese Trial to Assess Optimal SBP (JATOS)
4416
patients aged 65-85 (average age of 74)
Randomized to SBP<140 vs. SBP 140-160
Achieved BP of 136/75 vs. 146/78
No difference in CV events or renal failure (p=0.99)
 VALISH trial
3079 patients aged 70-84 (average age of 76)
Randomized to SBP<140 or SBP 140-149
No
significant reductions in stroke, CV events, or renal fai
lure in 3 years follow up
 Overall event rates were lower than anticipated in
both of these studies
JATOS Study Group. Hypertens Res 2008;31:2115-27.
Ogihara T et al. Hypertension 2010;56:196-202.
In patients >60 years of age, start medications
at blood pressure of >150/90mm Hg and treat to
goal of <150/90mm Hg
In patients >60 years of age, treatment does not
need to be adjusted if achieved blood pressure is
lower than goal and well-tolerated
James PA et al. JAMA 2014;311:507-20.
The opposing arguments:
The Japanese trials had low event rates and may not
represent the risks in other populations
Post hoc analyses suggested benefit of stricter
control on stroke in patients younger than 75 years
and an adverse interaction with stricter control in
patients older than 75 years
Wright JT Jr et al. Ann Intern Med 2014;160:499-504.
Blue - the patients who met the 2003 JNC-7 recommendations
Red - the patients who met the 2014 panel report recommendations
Green - the group who met the 2014 recommendations but not the 2003 recommendations
10-year ASCVD risk of 27.9%
avert approximately 8,000
cardiovascular events over 10 years
The optimal SBP target is less clear with no
data showing benefits of achieving
pressures less than 140mmHg in patients
over 75 years of age, and there is the
possibility of harm.
In healthier and more functional patients
over the age of 75 years, systolic goals
might logically be lower than in the more
commonly encountered 80 year old with
higher burden of disease or with frailty
http://ePrognosis. ucsf.edu
C/C: hypertension evaluation
(160/100mmHg), headache
PMHx: smoking(-)
FHX: father, mother hypertension
EKG: sinus tachycardia 110bpm
CXR: no cardiomegaly
24 hour urine metanephrine: NL
TFT: NL
No hypokalemia, renin aldosterone normal
Abdominal CT: no renal artery stenosis, no
adrenal mass
Final diagnosis: essential hypertension
Treatment: beta blocker (carvediol SR 16mg
qd) considering sinus tachycardia
complain of erectile dysfunction
 Only thiazide diuretics lead clearly
to ED, while some older betablockers also do so, but the sideeffect of ED was very low (3%)
 In fact, the vasodilating nebivolol
may even improve erectile function.
Charalambos et al. European Heart Journal (2013) 34, 2034–2046
Charalambos et al. European Heart Journal (2013) 34, 2034–2046
idiopathic pulmonary hypertension- current only
indication
co-administration of nitrates and other nitric
oxide (NO) donors may result in severe
vasodilation and hypotension.
A strong body of clinical data
 do not increase the risk of non-fatal myocardial
infarction, stroke, or cardiovascular deaths.
 do not exacerbate ischaemia or worsen exercise
tolerance in patients with known CAD who achieve
levels of exercise comparable or greater than that
achieved during sexual intercourse.(MET >5)
Charalambos et al. European Heart Journal (2013) 34, 2034–2046
C/C: OP risk evaluation ( colon
cancer)
PMHx: smoking(+)
FHX: mother hypertension
V/S BP 150/95mmHg
EKG: RBBB
CXR: no cardiomegaly
No abnormal lab findings
•High risk surgery
–eg. intrathoracic, intraabdominal, or
suprainguinal vascular surgery
36
37
Class I
1. Beta-blocker therapy should be used in all patients with LV systolic dysfunction
(EF ≤40%) with HF or prior MI, unless contraindicated. (LOE: A)
(Use should be limited to carvedilol, metoprolol succinate, or bisoprolol, which have
been shown to reduce mortality.)
2. Beta-blocker therapy should be started and continued for 3 years in all patients with
normal LV function who have had MI or ACS. (LOE: B)
Class IIa
1. It is reasonable to continue beta blockers >3 years as chronic therapy in all patients
with normal LV function who have had MI or ACS. (LOE: B)
2. It is reasonable to give beta-blocker therapy in patients with LV systolic dysfunction
(EF ≤ 40%) without HF or prior MI. (LOE: C)
2011 AHA/ACCF guideline update. JACC 2011;58:2432-46
38
C/C: high BP(160/100 mmHg)
P.I: 16 weeks pregnant woman
PMHX: none
U/A: no proteinuria at OBGY clinic
Echo: No Left ventricular
hypertrophy
Blood pressure :average 10 mm Hg below
non-pregnant values by mid gestation.
 marked fall in the peripheral vascular
resistance as a result of active vasodilatation.
Cardiac output :increases about 40% to
maintain blood pressure and to maintain
supply
 A corresponding increase in blood pressure
occurs, approaching normal pre-pregnancy
levels in the third trimester.
Current Pharmaceutical Design, 2007, 13, 2567-2579
Current Pharmaceutical Design, 2007, 13, 2567-2579
 the National High Blood Pressure Education Program
(NHBPEP)
 antihypertensive medication may be safely withheld in women
with a history of chronic hypertension
 start treatment at SBP greater than 150–160 mm Hg and/or
DBP of 100–110 mm Hg, or in the presence of left ventricular
hypertrophy or renal insufficiency
 The 2007 European Society of Hypertension (ESH)
 In the presence of gestational hypertension and preeclampsia,
antihypertensives are indicated for blood pressures of at least
140/90 mm Hg;
 SBP > 170 mm Hg or DBP >110 mm Hg: emmigency Ix.
 the Society of Obstetricians and Gynaecologists of Canada
 SBP <160 or DBP <110 mm Hg
 C/C: high BP(145/85 mmHg)
 PMHx: hyperlipidemia (no
medication due to GI trouble)
 Chronic fatigue, vasomotor
symptoms(flushing, back pain)
 She wants to take hormone
replacement therapy
The effects of HRT on BP are not as clear-cut as
the effects of OCPs
 low dose
many physicians considered hypertension to be
a contraindication to HRT.
 increased angiotensinogen generation and
increased sodium retention.
<Hypertension. 1997;29:268–263 >
 In fact, estrogen preparations (eg, Premarin and
ethinyl estradiol) with a greater ability to stimulate
hepatic synthesis of angiotensinogen
<Circulation. 998;97(13):1234–1238> <Am J Cardiol. 1999;84(3):367–370. >

 The Postmenopausal Estrogen/Progestin
Interventions Trial
 875 normotensive postmenopausal women, aged
45 to 64 years
 At 3 years of follow-up
 no differences in systolic or diastolic BP in any of
the treatment groups compared with that in the
placebo
<JAMA.
1995;273(3):199-208>
A prospective study of 75 hypertensive women
treated with HRT
 failed to demonstrate an increase in BP after
12months of follow-up,
<J Hum Hypertens. 1994;8(7):491-494>.
International Journal of Women’s Health 2014:6
 Womens Health Initiative (WHI) study
 current use of HRT was associated with a
25% greater risk of having hypertension
compared with nonusers of HRT
<Hypertension.2000;36(5):780-789>
 RCT phase of the WHI
 tablet (n = 8506) or placebo (n = 8102).
 only a very small (1 mmHg) increase in
systolic BP in the HRT arm compared with
placebo.
<JAMA.2003;289(20): 2673-2684>
From: Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women: The Women's Health Initiative:
A Randomized Trial
JAMA. 2003;289(20):2673-2684. doi:10.1001/jama.289.20.2673
MHT is the most effective treatment for
vasomotor symptoms
 HRT on CV outcome: neutral
 VTE, Stroke increase but the absolute
risk is rare below age 60 years.
The risk of breast cancer
 The increased risk of breast cancer is
primarily associated with the addition of a
progestogen to estrogen therapy and
related to the duration of use.
CLIMACTERIC 2013;16:203–204
Palocious Maturitas 2006
Currently available data
 HRT is an uncommon cause of worsening
hypertension in postmenopausal women.
 Subtle increases in BP attributable to HRT
might be difficult to detect in women
already receiving treatment for
hypertension, whose BP may fluctuate with
changes in body weight, level of activity,
and diet.
 VTE, Stroke, Breast cancer
 Among the progestins, DRSP appears to
provide the best anti-hypertensive effects.
c/c: general weakness(90/60 mmHg)
PMHx: DM, HTN, ESRD on PD, PCI at
LAD due to NSTEMI
Med: Amlodipine 10mg qd, Carvediol
25mg bid, valsaltan 320mg qd,
indapamide 1.5mg qd, nebivolol
2.5mg
 short term component
within a 24-hour period and measured
by 24-hour ABPM
 long-term component
 BP is recorded in the same patient
between one visit and the next.
Mallamaci et al. Kidney Int 2013
 Arterial stiffness
 older age and high pulse pressure are strictly associated
to higher visit-to-visit systolic BP variability.
< Atherosclerosis 2011;219: 194–199>
 Chronic inflammation
 inflammation is very frequent in CKD patients
 the association between systolic BP variability, albumin
and C-reactive protein was of borderline statistical
significance.
<Hypertens Res 2008; 31: 2137–2146>
 High sympathetic activity
 High sympathetic activity is strongly associated to left
ventricular mass and clinical outcomes both in
predialysis and dialysis .<Curr Hypertens Rep 2013; 15: 95–101>
In CKD patients , in addition to BP lowering,
stabilization of BP should be regarded as a
potentially relevant treatment target in CKD
patients
 calcium antagonists and thiazides reduce BP
variability
analyses in the US Renal Data System
(USRDS)
 β-blockers confer a higher degree of
protection in comparison to calcium channel
blockers and ACE inhibitors in dialysis patients.
<Kidney Int 2002; 62: 1784–1790 > .
Flushing (+), sweating (+) office BP 130/80 mmHg
 VMA (U) 4.5mg/day(1-5)
 Norep (U) 121.8 ug/day(15-80)
 Epine (U) 16.90 ug/day (1.2-20)
 Meta (U) 0.90 mg/day (0.2-1.2)
 Norep (P) 0.21ng/mL(0.07-0.4)
 Epine (P) 0.11 ng/mL(0.04-0.2)
 Adrenal CT: no adrenal mass, no
renal vein stenosis
1. Sudden onset of hypertensive paroxysms
without any identifiable trigger
2. Hypertensive paroxysms associated with
physical symptoms
3. Episodes are not triggered by emotional
distress or panic
4. Absence of biochemical evidence of a
pheochromocytoma
5. Psychosocial analysis invariably reveals a
history of abuse, trauma, or a defensive
personality
Amarinde et al . Advances in Chronic Kidney Disease, 22,2015: pp 218-223
1. Monoamine oxidase inhibitors
(especially with tyrosine ingestion)
2. Tricyclic antidepressants
3. Adrenergic receptor agonists (eg,
decongestants)
4. Psychoactive drugs
5. Amphetamines
6. Dopaminergic medications
7. Ethanol
8. Clonidine withdrawal
C/C: high BP (150/105mmHg)
despite medical therapy
PMHx: none, obesity
HbA1c:7.7, LDL-cholesterol
165mg/dL. TG: 340mg/dL, HDLcholesterol 34 mg/dL
Amlodipine 10mg qd, Carvediol
25mg bid, Valsaltan 160mg qd,
indapamide 1.5mg qd
C/C: high BP (150/100mmHg)
despite medical therapy
PMHx: none, obesity
HbA1c:6.7, LDL-cholesterol
175mg/dL. TG: 164mg/dL, HDLcholesterol 52 mg/dL
Benidipine 8mg qd, nebivolol 10mg
qd, Fimasartan 120mg qd,
indapamide 1.5mg qd
prospective, randomized, sham-controlled, multicenter
clinical trial in patients with resistant HTN across 90 US
medical centres.
Bhatt et al.New Engl JMed 2014;370:1393–401
Spironolactone :not given routinely
office [SBP] >140 mm Hg
mean ambulatory daytime
SBP >135 mm Hg
despite regular intake of maximally
tolerated doses of ≥3
antihypertensive drugs including a
diuretic.
Hypertension. 2014;63:991-999
 1955
 First description of the primary aldosteronism syndrome
 1999
 The Randomized ALdactone Evaluation Study (RALES) trial demonstrates
the role for aldosterone antagonists in chronic severe (NYHA class III/IV)
systolic HF
 2003
 The Eplerenone Post-myocardial infarction Heart failure Efficacy and
Survival Study (EPHESUS) documents the benefit of aldosterone receptor
antagonists in patients with an EF <40% after MI
 2014
 TOPCAT shows moderate effects of spironolactone in heart failure with
reserved ejection fraction because only hospitalization for heart failure
benefited in this population from MR antagonism
 2011
 treatment with MR blockers lowers blood pressure in patients with
hypertension, and particularly in resistant hypertension.
Carlos et al. Circ Res. 2015;116:206-213
Addition of Spironolactone in Patients With Resist
ant Arterial Hypertension (ASPIRANT)
At 8 weeks, the primary end
points, a difference in mean
fall of BP on daytime
ambulatory BP monitoring
(ABPM), between the groups
was -5.4 mm Hg (95%CI -10.0;
-0.8) for systolic BP (P=0.024)
and -1.0 mm Hg (95% CI -4.0;
2.0) for diastolic BP (P=0.358).
Jan Václavík et al. Hypertension. 2011;57:1069-1075









Adrenal steroid
NSAIDs
Sex hormone
Anti-depressant
Decongestant
Cyclosporine
VEGF inhibitor
Erythropoietin
Appetite suppresant