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Transcript of Am 8.45 meagher
Hypertension Management in Women: What’s Different?
Emma A. Meagher, MDAssociate Professor, Medicine and Pharmacology
University of Pennsylvania
Conflict of Interest Disclosure
Emma A. Meagher, MD has no conflicts to disclose
Death
s, t
housa
nds
520
500
480
460
440
420
400
Years
1979
1985 1990 1995 2000 2005
Females
Males
Rosamond W et al. Circulation. 2007:115.
United States: 1979–2004
CVD Mortality in Women Has NOT Decreased at the Same Rate as in Men
AHA. 2008 Heart and Stroke Statistical Update. 2010.
Hypertension: The Silent Disorder
• Prevalence– 55 million people in the United States have
hypertension• of these, 31.6% do not know they have it
• Causes– In 9 of 10 individuals with hypertension the etiology
unknown• Detection
– measuring blood pressure is the only way to detect hypertension
Control of Hypertension Low in Women
Hajjar et al. JAMA. 2003;290:199–206.
Control*Treatment
Awareness
III (Phase 1 1988–1991)
III (Phase 2 1991–1994)
1999–2000
Wom
en,
%
About Half Are Treated; About a Quarter Are Controlled
75.1 73.6 71.262.060.060.1
29.627.429.1
0
10
20
30
40
50
60
70
80
*Percentage of hypertensive patients controlled.
Lloyd-Jones DM et al. Hypertension 2000;36:594-599.
SBP and DBP levels of all 1959 subjects with hypertension, treated and untreated, are represented.
SBP is a Major Factor in the Lack of BP Control in the Community
Uncontrolled SBP/DBP
Uncontrolled DBP
140
20
40
60
80
100
120
80 100 120 140 160 180 200 220
SBP (mm Hg)
3.7%
13.4%
53.9%29.0%
DB
P
(mm
Hg)
Hypertensive Subjects Examined in the Framingham Heart Study Between 1990 and 1995
Controlled SBP/DBP
Uncontrolled SBP
Gain ≥25
Gain 20.0–24.9
Gain 1.0–19.9
Hypertension Increases With Weight Gain in Women
Nurses’ Health Study: Hypertension† According to Weight Change
Huang Z et al. Ann Intern Med. 1998;128:81–88. Ogden C et al. JAMA. 2006;295(13):1549-55.
Overweight=BMI ≥25 kg/m2; obese=BMI ≥30 kg/m2; extreme obesity=BMI ≥40 kg/m2
*Adjusted for age, BMI at age 18 years, height, family history of myocardial infarction, parity, oral contraceptive use, menopausal status, postmenopausal use of hormones, and smoking. †>140/90 mmHg.
Loss 5.0–9.9
Loss 2.1–4.9
Loss ≥10
Change ≤2.1
Gain 2.1–4.9
7
6
5
4
3
2
1
0Gain 5.0–9.9
Weight Change After 18 Years, kg
Age <45
Age 45–54
Age ≥55
Overweight: 61.8%Obese: 33.2%Extreme Obesity: 6.9%
Weight Status in WomenNHANES data: 2002–2004
Mult
ivari
ate
RR
*
BP Rises After Menopause—Risk of Hypertension Triples
Staessen JA et al. J Hum Hypertens. 1997;11:507–514.
Changes in SBP From Baseline to Follow-up (Mean 5.2 Years)
6
5
4
3
2
1
0
–1
–2
–3
–1.9
0.4 3.3
†
0.23.8
*
–0.1
*P≤0.05.†P=0.07.Baseline SBP: Pre=121.4 ± 1.3 mmHg; Peri=122.0 ± 1.8 mmHg; Post=126.5 ± 1.7 mmHg; Controls: men matched by age and BMI.
Women ControlsPremenopausal (n=166)
Δ F
rom
Base
line
SB
P,
mm
Hg
Postmenopausal (n=105)
Perimenopausal (n=44)
Menopause Increases Salt-sensitivityIncreases in Salt Intake Lead to Increases in Blood Pressure in Postmenopausal Women
Oparil S, Miller AP. J Clin Hypertens (Greenwich). 2005;7:300–309.
24-hour Mean Blood Pressure, mmHg
Salt
Inta
ke
(U N
a
V,
mm
ol/d) Follicular
LutealContraceptiveMenopause
70 80 90 100 110
250
200
150
100
50
0
Estrogen Is a Potent VasodilatorInterruption of Estrogen in Postmenopausal Hypertension
Estrogen relax vascular smooth muscle by increasing NO levels and decreasing vasoconstriction by acting as a calcium antagonist
Schwertz DW et al. Heart Lung. 2001;30:401–426.Orshal JM et al. Am J Physiol Regul Integr Comp Physiol. 2004;286:R233–R249.
vessel
Endothelial CellL-citrulline L-arginine
No NOS
↑CA2+ VSMCGTPNo
cGMPprotein kinase
acetylcholine
ContractionCatecholamineRelaxationPGI2
Impact of High-Normal BP on CV Risk
JNC 7Classification of Blood Pressure for Adults Aged 18 Years or Older
BP Classification Systolic BP Diastolic BP
Normal <120 And <80
Prehypertension 120-139 Or 80-89
Stage 1 Hypertension 140-159 Or 90-99
Stage 2 Hypertension ≥160 Or ≥100
Chobanian AV, et al. JAMA 2003;289:2560-72
Goals of Hypertensive Management
• Maintenance of normal BP (avoidance of stroke, CHF)
• Cardioprotection (primary/secondary prevention)
• Renoprotection
• Quality of life (cost, avoidance of side effects)
• Non-interference with concurrent diseases/treatments
How Low Should Blood Pressure Be Lowered?
Condition BP Target
Uncomplicated HTN <140/90 mm Hg
HTN + Diabetes <130/80 mm Hg
HTN + Chronic Renal Disease <130/80 mm Hg
JNC 71: Blood Pressure Goals
1. Chobanian AV et al. Hypertension. 2003;42:1206-1252. 2. Rosendorff C et al. Circulation. 2007;115:2761-2788.
AHA2: Blood Pressure GoalsCondition Target
Uncomplicated HTN <140/90 mm Hg
HTN + High Risk of CAD* <130/80 mm Hg
HTN + Angina <130/80 mm Hg
*Diabetes mellitus, chronic kidney disease, known CAD or CAD equivalent, or 10-year Framingham risk score ≥10%.
JNC=Joint National Committee; HTN=hypertension; AHA=American Heart Association; CAD=coronary artery disease.
Lifestyle Modifications to Prevent and Manage Hypertension
Avoid tobacco
(JNC VII)
Reduce weight Moderate consumption of:• alcohol • sodium• saturated fat• cholesterol
Increase physical activity
Maintain adequate intake of dietary:• potassium• calcium • magnesium
A DASH Towards Cardiovascular Health
• DASH* Diet is recommended by JNC 7 for all patients with, or at risk of, hypertension
• Diet adherence is low and declining
– Only about 20% of people with hypertension follow the diet;
DASH Diet Provides Greater BP ReductionsThan Control Diet
-15
-10
-5
0
mm
Hg
Chobanian AV et al. Hypertension. 2003;42:1206-1252. Mitka M. JAMA. 2007;298(2):164-5.Appel LJ et al. Hypertension. 2006;47:296-308.
.
*DASH=Dietary Approaches to Stop Hypertension, a study that showed a diet rich in fruits, vegetables, grains, low-fat dairy products, and low in fat, cholesterol, and sodium lowered systolic and diastolic blood pressures
-11.4
-5.5
Systolic
Diastolic
Limited Efficacy of Monotherapy A Reason for Poor BP Control
HCTZ, hydrochlorothiazide.*Response = DBP <90 mm Hg at the end of the titration period and <95 mm Hg at the end of 1 year of therapy.Materson BJ et al. N Engl J Med. 1993;328:914-921.
59
Diltiazem
Responserate*(%)
0
10
20
30
40
50
60
51
Atenolol
50
Clonidine
46
HCTZ
42
Captopril
42
Prazosin
Advantages of Combination Therapy• Increased efficacy
– Important as lower BP goals require more drug therapy
• Decreased toxicity – Avoid dose dependent side effects– One drug offset side effects of another drug– Improved compliance– Reduced cost of global health care costs
• Reduced cost to patient (in form of co-pays)• Target organ protection
– Reduction in proteinuria, preservation of GFR?– Regression of LVH?
Recommendations Regarding Initial Use of Combination Therapy
JNC 7 >20/10 mm Hg above goal
ISHIB >15/10 mm Hg above goal
ESH >20/10 mm Hg above goal OR high cardiovascular risk
AHA SBP ≥160 mm Hg or DBP ≥100 mm Hg irrespective of the BP goals (Stage 2 Hypertension)
ASH >20/10 mm Hg above goal pressure of <130/80 mm Hg for diabetics
NKF SBP >20 mm Hg above goal according to the stage of CKD and CVD risk
Chobanian AV, et al. Hypertension. 2003;42:1206–1252. Douglas JG, et al. Arch Intern Med. 2003;163: 525-541. American Journal of Kidney Diseases. 2004;43(Suppl 1):S55-S230. Mancia G, et al. J Hypertens. 2007;25:1105–1187. Rosendorff C, et al. Circulation. 2007;115;2761-2788. Bakris GL and Sowers JR. J Clin Hypertens. 2008;10:707-713. K/DOQI. Am J Kidney Dis. 2004;43 (Suppl1):s65-230.
JNC 7=Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; ISHIB=International Society on Hypertension in Blacks; ESH=European Society of Hypertension; AHA=American Heart Association; ASH=American Society of Hypertension; NKF =National Kidney Foundation
JNC 7
Management of Blood Pressure for Adults Without Compelling Conditions
BP Classification Initial Drug Therapy Recommendation
PrehypertensionLifestyle modification only
Stage 1 HypertensionThiazide-type diuretics for most;
ACE inhibitor, ARB, b-Blocker, CCB, or combination
Stage 2 Hypertension2-Drug combination for most (usually
thiazide-type diuretic and ACE inhibitor, ARB, b-Blocker, or CCB)
Chobanian AV, et al. JAMA 2003;289:2560-72
The 7th report of the Joint National Committee: Compelling Indications
Compelling Indications Diuretic βB ACEI ARB CCA AA
Heart Failure √ √ √ √
Post-MI √ √ √
High CAD risk √ √ √ √
Diabetes √ √ √ √
Chronic kidney disease √ √
Recurrent stroke prevention √ √
AA=Aldosterone AntagonistBB=Beta BlockerCCB=Calcium Channel Blocker
Chobanian AV, et al. JAMA. 2003;289(19):2560-2572.
BP = X
P V R R V R
S V R
S trokeV o l H R
C O
Pathophysiology of BP
Antihypertensive Drug Therapy
Directvasodilators
ACEinhibitors-blockers
ARBs Renin inhibitors
Ganglion blockers
Central 2 agonistsCCAs -non DHPs
-blockers
Thiazidesdiuretics
CCAs - DHPs
1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2001 2007
Perceived Improvements in TolerabilityHighly effective
SBP control
ETAs*VPIs*
*Not currently available for clinical use
Rational Use of Antihypertensive DrugsIn Combination
Less effective
Diuretics Beta Blockers
ACEIs ARBs
CCAs
1-Receptor Blockers
Particularly effective
Adapted from Chalmers J. Clin Exp Hypertens. 1993;15:1299–1313.
• t-PA•Cathepsin G•Tonin
Angiotensinogen
Ang I
Renin X DRI
Ang II
CAGECathepsin GChymase
• Antiproliferation• NO Release• Differentiation• Vasodilation
• Hypertrophy/proliferation• Vasoconstriction• Aldosterone release• Antidiuretic hormone release
AT1 receptor AT2 receptorARB site of action
ACEI site of action
ACE
Renin Angiotensin System
de Gasparo M et al. Hypertension. Pathophysiology, Diagnosis, and Management. 2nd ed. New York, NY: Raven Press; 1995:1695–1720. Dzau VJ. J Hypertens. 1989;7:933-936.
Indications and contraindications for major classes of antihypertensive drugs
Drug Indications Contraindications
Diuretics Elderly Gout
Beta-blockers MI, Angina Asthma, Heart blockHeart failure Heart failure
ACE inhibitors HF, Type 1 Pregnancy,DM nephropathy Renovascular disease
Ca2+ antagonists Isolated systolic HTN Short acting in pts with IHDAngina
Alpha-blockers Prostatism Urinary incontinence
AT1 blockers ACE cough Pregnancy,Heart failure Renovascular disease
Case #1• 55 yr old African American Female with hx of HTN for 10 yrs
• CV risk factors include diabetes, obesity and fibromyalgia
• Meds: Simvastatin 40 mg for elevated cholesterol
• FHx: father CKD at 50 and died @ 67 of MI
• Exam: BP 150/92, HR 74, RR 16
• BMI 28.9, waist circumference 37 inches
• CV exam within normal limits
• ECG sinus, HR 70, LVH by volatge criteria
• eGFR 48 mL/min/1.73m2
• Glucose 128, HbA1c 6.8%
• HDL-C 44 mg/dL, LDL-C 112 mg/dL, TG 220 mg/dL
Case #2• 75 yr old Caucasian woman with 20yr history of HTN,
mild urinary incontinence, former smoker
▪ Exam:▪ BP 168/70, HR 68, RR 12, ▪ BMI 25, waist circumference 30”, weight 140 lbs▪ Lungs trace bilateral end expiratory wheezes▪ ECG WNL NSR 68, no chamber enlargement
▪ Labs▪ Urine negative for protein, blood or sediment▪ Fasting blood sugar 82 mg/dL▪ HDL-C 61mg/dL, TG 118 mg/dL, LDL-C 87 mg/dL▪ Bun/Cr 24/0.8, eGFR 66.5 mL/1.73m2
Many Providers Not Motivated to Initiate or Change Treatment
87%79%
72%
55%
0%
20%
40%
60%
80%
100%
150-159 160-169 170-179 ≥180
Percentage of Visits Without Medication Intensification1
1. Adapted from Andrade et al. Am J Manag Care. 2004;10:481-486. 2. Chobanian AV et al. Hypertension 2003;42;1206-1252.
Baseline SBP (mm Hg)
Failure to titrate or combine medications and to reinforce lifestyle modifications despite knowing that the patient is not at goal BP represents clinical inertia that must be overcome.- JNC 72
Retrospective Analysis
Retrospective Study
For your confidential information only
What Is Therapeutic Inertia?
Overestimation of care provided
Use of “soft” reasons to avoid intensifying therapy
Lack of education, training, and practice organizations on:
– The benefits of treating to therapeutic targets
– The practical complexity and need for polypharmacy in treating to target
– The need to structure routine practice to facilitate identification of therapeutic problems
The failure of health care providers to initiate or intensify
therapy when indicated
Causes:
Phillips LS et al. Ann Intern Med. 2001;135:825–834.
CVD Mortality Trends for Males and Females: US 1979–2002
American Heart Association. Heart Disease and Stroke Statistics — 2005 Update. Dallas, Tex: American Heart Association; 2005. ©2005, American Heart Association.
Years
Males Females
400
440
480
520
0
1979 81 83 85 87 89 91 93 95 97 99 01 02
Dea
ths
(tho
usan
ds)
NCEP I NCEP II NCEP III
NCEP = National Cholesterol Education Program.