Transcript soung_htn
Hypertension:
Case Studies
Michael Soung, MD, FACP
Virginia Mason Medical Center
General Internal Medicine
JNC 8?
Current NHLBI guideline in development:
JNC 8 (Hypertension)
ATP IV (Cholesterol)
Obesity 2
“Integrated Cardiovascular Risk Reduction Guideline”
Why the delay?
Intensified focus on evidence-based recommendations
IOM 2011 reports on systematic reviews and guideline
development
http://www.nhlbi.nih.gov/guidelines/ -- Accessed Oct 2012
JNC 8?
3 clinical questions:
When
to initiate drug treatment?
How low should BP be lowered?
How do you get there?
http://www.ahdbonline.com/node/1009 -- Accessed Oct 2012
Question #1
60 yo man w/ PMH HTN, hyperlipidemia,
smoking. Meds include lisinopril 40mg qAM,
HCTZ 25mg qAM, amlodipine 10mg qAM.
Average bp 145/90.
Which of the following is the next best step in
management?
A) Add losartan 25mg daily
B) Increase HCTZ to 50mg daily
C) Increase Lisinopril to 80mg daily
D) Switch lisinopril dosing to bedtime
E) No change in medications
MAPEC study
2156 patients w/ untreated or resistant HTN (not
well-controlled w/ ≥ 3 anti-HTsives)
Intervention:
Untreated: monotherapy -- morning vs. bedtime
Resistant: (Replace 1 drug and take all BP meds in
morning) vs. (Shift ≥ 1 BP med to bedtime dosing)
Primary composite CV outcome at 5.6y:
Bedtime dosing: RR 0.39 (0.29-0.51)
16 fewer CV events per 1000 patient-years
2 fewer deaths per 1000 patient-years
Chronobiol Int 2010;27:1629-1651
MAPEC study
Chronobiol Int 2010;27:1629-1651
MAPEC study
Single-center (Spain), open-label, choice of
meds left up to providers, use of ambulatory BP
monitoring
No difference in clinic BPs or awake ambulatory
BP monitoring
Lower sleep-time ambulatory BP monitoring
Similar results in DM and CKD subgroup
analyses
Ann Intern Med 2012;156:JC6-8
Answer: D
Chronobiol Int 2010;27:1629-1651
Diabetes Care 2011;34:1270-1276
J Am Soc Nephrol 2011;22:2313-21
J Fam Pract 2012;61:153-155
Question #2
52
yo man, initial clinic visit. Long history
of inconsistently treated HTN. No current
meds. Average BP over the last 6 months:
150/85. Trace LE edema on exam.
Serum creatinine 3.1 (eGFR 21). Cr 3 months
ago was 2.9. K 4.5
Urine albumin/creatinine ratio = 600 mg/g.
Fasting glucose 98, HbA1c = 5.4%.
Renal Ultrasound: medical renal disease, no
hydronephrosis.
Question #2
Which
of the following is the most
appropriate anti-hypertensive?
A) Hydrochlorothiazide
B) Benazepril
C) Diltiazem
D) Amlodipine
E) Metoprolol
HTN and Chronic Kidney Disease
JNC
7: urinalysis in patients w/ HTN
(consider urinary albumin)
NKF
K/DOQI guidelines:
Assess for proteinuria in patients with CKD
Proteinuria is strong predictor of both CKD
progression and cardiovascular disease
Proteinuria as a target of therapy
JAMA 2003;289:2560-2572
Am J Kidney Dis 2004;43:S1-S290
HTN and Chronic Kidney Disease
ACE
inhibitors for nondiabetic CKD:
Meta-analysis of 11 RCTs
RR 0.70 (13.2% vs 20.5%) for renal outcomes
(doubling of serum Cr or ESRD)
Strongest benefit if proteinuria >0.5 g/ day
No
major differences between individual
ACE-inhibitors and ARBs
Ann Intern Med 2001;135:73-87
Am J Kidney Dis 2004;43:S1-S290
HTN and Chronic Kidney Disease
What about advanced CKD?
Largely excluded from earlier ACE-I trials
ACE-I in advanced, nondiabetic, proteinuric CKD
224 patients, serum Cr 3.1-5.0 mg/dL, Uprot > 0.3g/d
Benazepril 20mg daily, 3.4 year f/u
Primary outcome: doubling of Cr, ESRD, death
RR 0.57 (41% vs 60%) for benazepril group
***Started low (10mg), checked weekly labs (Cr, K)***
ACE-I: check Cr and K in 1-2 wks
Up to 30-35% increase in serum Cr is okay
(beneficial), unless hyperkalemia (> 5.6) develops
Answer: B
NEJM 2006;354:131-140
Arch Intern Med 2000;160:685-693
Question #3
66yo woman w/ PMH HTN, CKD w/ proteinuria.
Meds include lisinopril 40mg daily and
amlodipine 10mg daily. Average BP 150/90. No
S3, lungs clear, trace BLE edema on exam.
Serum Cr 1.2, Urine alb/Cr ratio: 1400 mg/g.
Which of the following is the most appropriate
anti-hypertensive?
A) Metoprolol
B) Hydralazine
C) Losartan
D) Hydrochlorothiazide
E) Doxazosin
ACE-inhibitors plus ARBs
ONTARGET (NEJM 2008;358:1547-59 / Lancet 2008;372:547-53.)
Ramipril vs telmisartan vs dual-therapy
25,620 pts w/ CVD or high-risk DM
No improvement in primary CV outcome
Improved urinary albumin
Worsened major renal outcomes (~1% ARI)
VALIANT (NEJM 2003;349:1893-906)
Captopril vs valsartan vs dual-therapy
14,808 pts w/ recent MI c/b CHF
No difference in mortality or CV outcomes
1-3% ARI in drug discontinuation (hypotension, renal)
ACE-inhibitors plus ARBs
CHARM-Added
(Lancet 2003;362:767-71)
Candesartan vs placebo
2548 pts w/ CHF on ACE-inhibitors
4.8% ARR in CV death or CHF hospitalization
7% ARI in drug discontinuation
Val-HeFT (NEJM 2001;345:167-75)
Valsartan vs placebo
5010 pts w/ CHF (93% on ACE-inhibitors)
4.4% ARR in CHF hospitalization (mortality unchanged)
2.2% ARI in drug discontinuation
Worse outcome if already on both ACE-I and β-blocker
ACE-inhibitors plus ARBs
Meta-analysis
Worsened renal function: RR 2.17
Hyperkalemia: RR 4.87
Symptomatic Hypotension: RR 1.50
Meta-analysis
of dual-therapy in CHF:
of dual-therapy in proteinuria
No difference in mortality or CV events
Hypotension: RR 2.21
Arch Intern Med 2007;167:1930-1936
Nephrol Dial Transplant 2011;26:2827-2847
ACE-inhibitors plus ARBs
Pros:
Improves albuminuria and blood pressure
Possible benefit in heart failure
Cons:
May worsen hard renal outcomes
More hyperkalemia
More symptomatic hypotension
Generally avoid dual-therapy w/ ACE-I and ARB
HTN and Chronic Kidney Disease
Diuretics
recommended in CKD and HTN
NKF K/DOQI Grade A recommendation for
most pts w/ CKD and HTN
Thiazides if GFR ≥ 30 mL/min
Loop diuretics if GFR < 30 mL/min
Combination for volume overload / edema
Non-dihydropyridine
calcium-channel
blockers also reduce proteinuria
Answer: D
Am J Kidney Dis 2004;43:S1-S290
Question #4
67 yo woman w/ PMH of DM II, HTN, and
hyperlipidemia, on metformin 1000mg BID,
lisinopril 10mg daily, and atorvastatin 20mg
daily. Average BP:135/85. HbA1c 7.8%, Cr 0.9,
Urine alb/cr ratio 16 mg/g.
What of the following is the most appropriate
next step in her blood pressure management?
A) Add diltiazem
B) Add amlodipine
C) Add hydrochlorothiazide
D) Increase the dose of lisinopril
E) No change in blood pressure meds
Blood pressure targets in diabetes
JNC 7:
Goal blood pressure < 140/90
Exceptions:
Diabetes Mellitus
Chronic Kidney Disease
goal blood pressure < 130/80
JAMA 2003;289:2560-2572
Blood pressure targets in diabetes
ACCORD
BP trial
4733 pts w/ high-risk DM, HbA1c ≥ 7.5%
SBP goals of <120 vs <140 mmHg
SBPs achieved: 119 vs 133.5 mmHg
No change in primary CV outcome at 4.7y
• reduction in CVA: 0.32% vs 0.53%
SBP <120: ↑ serious adverse events (ARI 2%)
No difference for microvascular outcomes
NEJM 2010;362:1575-85
Kidney Int 2012;81:586-594
Blood pressure targets in diabetes
2011 meta-analysis (broad inclusion):
13 RCTs, 37,736 pts, BP <135 vs <140
No difference in overall macro/microvacular outcomes
↓ mortality by 10% (BP 130-135), ↓ CVA by 17%
↑ serious adverse effects by 20%
2012 meta-analysis (strict inclusion):
5 RCTs, 7312 pts, DBP <75-80 vs <90, + ACCORD
No difference in mortality or MI
↓ CVA by 35% (1% ARI)
Answer: E
Circulation 2011;123:2799-2810
Arch Intern Med 2012;172:1296-1303
Blood pressure targets in CKD?
JNC
7 & NKF K/DOQI: < 130/80
Extrapolated from recommendations for
other high-risk groups (e.g. diabetes)
Annals 2011 systematic review:
3 RCTs, 2272 patients
No clear benefit from lower BP targets
Possible benefit in proteinuric patients
Await SPRINT (2018) and HALT-PKD (2013)
Am J Kidney Dis 2004;43:S1-S290
Ann Intern Med 2011;154:541-548
Question #5
62 yo man w/ long history of HTN on max doses
of lisinopril, hydrochlorothiazide, and amlodipine.
Average bp: 155/95. No JVD, lungs clear, no LE
edema. Serum electrolytes, glucose, creatinine,
EKG normal. Negative secondary HTN workup.
Which of the following is the most appropriate
next step in management?
A) Hydralazine
B) Metoprolol
C) Spironolactone
D) Doxazosin
E) Clonidine
Resistant Hypertension
= failure to reach goal BP w/ full doses of
appropriate 3-drug regimen including a diuretic
Multiple
potential causes
Secondary HTN (e.g. 1° hyperaldo, RAS)
Improper measurement (e.g. cuff too small)
Nonadherence, inadequate doses
Drug-induced: NSAIDs, decongestants,
OCPs, steroids, cocaine, amphetamines
Excessive alcohol use, obesity
JAMA 2003;289:2560-2572
Resistant Hypertension
ASCOT-BPLA
Uncontrolled, nonrandomized ASCOT cohort
1411 pts who received spironolactone as fourth-line
anti-hypertensive
Exclusions: hyperaldosteronism or receipt for another
indication (CHF, liver failure)
Median dose = 25mg
Mean bp reduction: 22 / 10 mmHg
Dosing: 12.5 - 50mg daily
Side effects: gynecomastia (6%), hyperkalemia
(monitor closely!)
Answer: C
Hypertension 2007;49:839-845
Question #6
85 yo woman w/ PMH HTN and chronic stable
angina on ASA and metoprolol. No CP, SOB,
edema, HAs, lightheadedness. Healthy diet,
regular exercise. Average BP: 165/85. HR 60, nl
CV exam, no edema. Cr 0.9, K 4.2, UA neg.
Which of the following is the most appropriate
next step in management?
A) Add indapamide
B) Add lisinopril
C) Add amlodipine
D) Increase metoprolol dose
E) No change in blood pressure meds
HTN in the very elderly
Few
patients >80yo included in previous
HTN trials
JNC 7 recommends same management
for elderly (but w/ lower initial drug doses)
Previous meta-analysis of HTN treatment
in pts >80yo suggested reduced CVA risk
but trend towards increase mortality
JAMA 2003;289:2560-2572
NEJM 2008;358:1887-98
HTN in the very elderly
HTN
in the Very Elderly Trial (HYVET)
3845 healthy pts, age 80+, SBP ≥ 160 mmHg
Indapamide +/- perindopril vs placebo
Target blood pressure: 150/80
2y f/u: 48% of Rx group reached target (vs
20% placebo); mean difference 16/6 mmHg
CVA: 5.3 fewer per 1000 pt-yrs
Death (any cause): 12.4 fewer per 1000 pt-yrs
Fewer serious adverse events in Rx group
NEJM 2008;358:1887-98
HTN in the very elderly
2010
Cochrane review on anti-HTsive
drug treatment in the very elderly:
CV mortality / morbidity: RR 0.75 (0.65-0.87)
Total mortality: RR 1.01 (0.90-1.13)
Withdrawals due to adverse effects: RR 1.71
(1.45-2.00)
Answer: A
Cochrane Database of Systematic Reviews 2010
Question #7
63 yo man w/ PMH of HTN, CHF, asthma, gout.
Meds include lisinopril, fluticasone / salmeterol
INH, allopurinol. Average BP 145/90, HR 68,
lungs are clear, no S3, trace BLE edema, a few
gouty tophi.
Which of the following is the most appropriate
anti-hypertensive?
A) Diltiazem
B) Amlodipine
C) Doxazosin
D) Hydrochlorothiazide
E) Metoprolol
Βeta-blockers and lung disease
Cochrane reviews on cardioselective beta-blockers in:
COPD:
22 RCTs in pts w/ COPD
No change in FEV1 or symptoms
No change in response to β2-agonists
Reversible airway disease (asthma/COPD):
29 RCTs in pts w/ reversible airway disease
No change in FEV1 or symptoms
No change in response to β2-agonists
Cochrane Database of Systematic Reviews 2008
Anti-HTsives in systolic heart failure
Drugs
Who?
ACE-I/ARB
All
↓ mortality?
↓ morbidity?
Carvedilol /
All
metoprolol ER
Aldosterone
Class III or
antagonists
IV
Diuretics
Class II - IV
Hydralazine /
Nitrates
ACE-I/ARB
intolerant
Answer: E
Ann Intern Med 2010;152:ITC61-15
Question #8
37 yo woman w/ 5-year history of HTN comes
for pre-pregnancy counseling. Stopped her OCP
and lisinopril 3 weeks ago. Average BP since:
160/90. No edema on exam, serum electrolytes,
Cr, UA all normal.
Which of the following is the most appropriate
next step in management?
A) Hydrochlorothiazide
B) Losartan
C) Labetalol
D) Atenolol
E) No medication
Chronic Hypertension in Pregnancy
Prevalence in U.S.: 3% and rising
↑ risk for preeclampsia, placental abruption, fetal
growth restriction, preterm birth, C-section
Treatment reduces risk for severe HTN (but not the
above outcomes)
BP typically falls late 1st trimester, rises to prepregnacy values during 3rd trimester
Cochrane: insufficient evidence to determine
appropriate BP targets in pregnancy
Recommendations for starting therapy range from
>150-180/100-110, variable targets
NEJM 2011;365:439-46
Cochrane Database of Systematic Reviews 2011
Chronic Hypertension in Pregnancy
First-line:
Second-line:
Methyldopa: longest safety record, somnolence limits
tolerability
Labetalol: better tolerated, good safety data
• (Atenolol: fetal-growth restriction)
Long-acting CCBs: less safety data but appears safe
Diuretics: previously considered unsafe but review of
9 RCTs no difference in pregnancy outcomes
Contraindicated:
ACE-I / ARBs: teratogenic, oligohydramnios
Answer: C
NEJM 2011;365:439-46
Question #9
72 yo woman w/ PMH of HTN, atrial fibrillation
(EF 60%), and hyperlipidemia. Medications
include HCTZ 25mg daily, digoxin 0.125mg
daily, warfarin 5mg daily, and simvastatin 40mg
daily. Average BP 135/85, HR 90-110.
Which of the following is the most appropriate
next step in management?
A) Start metoprolol
B) Start diltiazem
C) Start amiodarone
D) Start amlodipine
E) Increase digoxin dose
Atrial Fibrillation management
2006 ACC/AHA/ESC Guidelines:
Recommended
equally for rate control:
Beta-blockers
Nondihydropyridine calcium channel blockers
Digoxin:
Slows HR at rest, but not w/ exercise, in Afib
Not generally recommended for monotherapy
Circulation 2006; 114:700-752
Drug interactions
SEARCH
trial
Simvastatin 20mg vs 80mg w/ hx of MI
Non-significant 6% RRR in CV events
80mg dose: ↑↑ myopathy
• Excess rate: 4/1000 in 1st year, 1/1000 thereafter
Increased risk in women and elderly
Risk doubled w/ calcium channel blocker
(particularly diltiazem)
Lancet 2010;376:1658–1669
www.fda.gov/Drugs/DrugSafety/ucm256581.htm
Drug interactions
2011 FDA simvastatin warning:
Do not exceed 10mg simvastatin daily with:
Diltiazem, Verapamil
Do not exceed 20mg simvastatin daily with:
Amlodipine, Amiodarone
2012 FDA lovastatin warning:
Do not exceed 20mg lovastatin daily with:
Diltiazem, Verapamil
Answer: A
www.fda.gov/Drugs/DrugSafety/ucm256581.htm
www.fda.gov/Drugs/DrugSafety/ucm283137.htm
www.fda.gov/Drugs/DrugSafety/ucm293101.htm
Question #10
50 yo man w/ hx of difficult-to-control HTN and
recurrent headaches. Average BP 165/95 on
HCTZ 25mg daily, felodipine 10mg daily,
metoprolol 100mg BID, and lisinopril 40mg daily.
Taking all meds as prescribed, no supplements,
checking BPs appropriately. On exam, he is
obese, HR 80, funduscopic exam shows AV
nicking, trace leg edema. Labs show K 3.0 and
Cr 1.0 prior to starting lisinopril. Since then,
stable K 3.2 and Cr 1.3. UA trace protein.
Question #10
Which
of the following is the most
appropriate test?
A) Sleep study
B) Serum aldosterone / renin ratio
C) Plasma free metanephrines
D) MRA of renal arteries
E) 24-hour urinary cortisol
Secondary Hypertension
Consider
workup if:
Severe or resistant hypertension
New-onset HTN at age <25
Malignant HTN
Signs / symptoms of a specific secondary
cause
Rule out other causes of resistant HTN (see
previous slide; e.g. med nonadherence , other
meds, improper measurement, etc)
Ann Intern Med 2008;149:ITC61-16
JAMA 2003;289:2560-2572
UpToDate 2011
Secondary Hypertension
(By ascending age:)
Coarctation of the aorta:
Children, young adults
>20mmHg difference between arm & leg SBP
Diminished / delayed femoral pulses
Initial test: Echocardiogram
Fibromuscular dysplasia (Renal artery stenosis):
Young adults, typically women
Acute, >30-35% increase in serum Cr w/ ACE-I / ARB
Renal bruits
Initial test: CTA, MRA, Duplex U/S of renal arteries
Am Fam Physician 2010;82:1471-1478
UpToDate 2011
Secondary Hypertension
Pheochromocytoma:
Rare. Middle-aged adults
Paroxysms of elevated BPs, esp w/ HA, palpitations,
sweats, flushing
Initial test: plasma free metanephrines
Cushing’s Syndrome:
Middle-aged adults (depending on cause)
Moon facies, buffalo hump, central obesity, dark
abdominal striae
Initial test: 24-hour urine cortisol, late-night salivary
cortisol, low-dose dexamethasone suppresion test
Am Fam Physician 2010;82:1471-1478
UpToDate 2011
Secondary Hypertension
Primary
hyperaldosteronism:
Middle-aged adults
Hypokalemia (though >1/2 are normokalemic)
Common: 6% of pts w/ HTN
Initial test: serum aldosterone / renin ratio
Obstructive
Sleep Apnea:
Middle-aged (and younger) adults
Snoring, apneic events, daytime somnolence
Initial test: sleep study
Am Fam Physician 2010;82:1471-1478
UpToDate 2011
Secondary Hypertension
Renal artery stenosis (atherosclerotic)
Older, vascular disease
Acute, >30-35% increase in serum Cr w/ ACE-I / ARB
Renal bruits
Initial test: CTA, MRA, Duplex U/S of renal arteries
Medical management as effective as
revascularization without clear indications
Other causes:
Thyroid dysfunction
1° hyperPTH
Renal parenchymal disease
Answer: B
Am Fam Physician 2010;82:1471-1478
UpToDate 2011
Question #11
42 yo man w/ new diagnosis of HTN, average
BP 145/90 after intensive lifestyle improvements.
Normal serum electrolytes and creatinine, UA
negative, EKG wnl. Otherwise healthy.
Which of the following is the most appropriate
next step in management?
A) Lisinopril
B) Chlorthalidone
C) Amlodipine
D) Hydrochlorothiazide
E) Atenolol
F) No medication, continued monitoring
Initial Therapy in HTN
JNC 7: Thiazide diuretics for most patients
Hydrochlorothiazide = most common
But not widely used in studies at current doses
HCTZ 12.5-25mg: weaker reduction in BP vs all
other drug classes
No CV morbidity or mortality outcomes data at
low doses (except in combo w/ triamterene or
amiloride)
JAMA 2003;289:2560-2572
J Am Coll Cardiol 2011;57:590-600
Hypertension 2009;54:951-953
Cochrane Database of Systematic Reviews 2009
Initial Therapy in HTN
Some recommend chlorthalidone:
Longer half life, 1.5-2x as potent (vs HCTZ)
(12.5mg chlorthalidone ≈ 25mg HCTZ)
Used in ALLHAT, SHEP
2012 network meta-analysis of CTD vs HCTZ:
greater CV benefit w/ similar BP reduction
Caveats:
Less available (few combo pills, higher cost)
No 12.5mg dose (need to halve a 25mg pill)
More hypokalemia
Hypertension 2009;54:951-953
Hypertension 2011;57:689;694
Hypertension 2012;59:1110-1117
Initial Therapy in HTN
BMJ 2009 meta-analysis:
All classes similar efficacy for reducing CHD events
and CVA
Beta-blockers extra protection first few years post-MI
CCBs slight advantage for CVA prevention
Cochrane 2009 meta-analysis:
Low-dose thiazides (HCTZ <50mg/day, chlorthalidone
<50mg/day): strongest evidence
ACE-I: similar benefit, less evidence
CCBs: insufficient evidence
β-blockers (atenolol) and high-dose thiazides: inferior
BMJ 2009;338:b1665
Cochrane Database of Systematic Reviews 2009
Initial Therapy in HTN
ACCOMPLISH
trial:
11,506 pt w/ high-risk HTN
Benazepril plus (amlodipine or HCTZ)
Target BP <140/90 (<130/80 for DM or CKD)
Similar BPs achieved
Primary composite CV outcome at 3y:
• Benazepril-amlodipine: 9.6%
• Benazepril-hydrochlorothiazide: 11.8%
NEJM 2008;359:2417-2428
Initial Therapy(?) in HTN
Cochrane 2012: mild hypertension
BP 140-159 / 90-99, primary prevention
4 RCTs, 8912 patients, 4-5y f/u
No change in mortality, CHD, CVA, CV events
9% ARI of withdrawals due to adverse effects
Caveats:
Low event rates, mostly driven by a single trial
(MRC), half on propranolol-based Rx
Wide confidence intervals
Long enough follow-up?
Cochrane Database Syst Rev 2012;8 :CD006742
Anti-HTsives in normotension
JAMA
Anti-HTsives in normotensive patients w/ CVD
25 RCTs, 64,000 patients
↓ mortality, CVA, MI, CHF, total CVD events
Eur
2011 meta-analysis:
Heart J 2012 meta-analysis:
ACE-I or ARB in normotensive patients w/
CVD or CVD risk factors
13 RCTs, 80,000 patients
↓ composite CV endpoint, CV mortality
JAMA 2011;305:913-922
Eur Heart J 2012;33:505-514
Initial Therapy in HTN
Sigh…
Consider overall CV risk when managing mild HTN
Really push lifestyle changes
My current approach to meds:
1st line: Lisinopril, HCTZ/triam, or chlorthalidone
(depending on potassium level), or no med if low risk
Still using lisinopril-HCTZ due to low cost and
convenience -- dosing qhs or BID
Amlodipine before beta-blockers
JNC 8??
Answer: A, B, C, D, F?
Take home points
Dose ≥1 BP med at bedtime
Use ACE-inhibitors for proteinuric CKD (even
with very high Cr)
Avoid combining ACE-I & ARB
No benefit from tight BP control in DM (or CKD?)
Add spironolactone for resistant HTN
Treat systolic HTN in octogenarians (with
caution)
Take home points
Beta-blockers okay with chronic asthma & COPD
Use labetolol in pregnancy
Avoid CCBs with ≥10-20mg of simvastatin or
lovastatin (or switch statins)
Watch for clues suggesting secondary causes of
HTN (hypoK & hyperaldo)
First-line Rx: variety of reasonable options
Not atenolol
Consider chlorthalidone over HCTZ
No clear benefit from meds in low-risk mild HTN