Hypertension Management in Women: What’s Different?              Emma A. Meagher, MD Associate Professor, Medicine and Pha...
Conflict of Interest DisclosureEmma A. Meagher, MD has no conflicts to disclose
CVD Mortality in Women Has NOT Decreased at                              the Same Rate as in Men                          ...
Hypertension: The Silent Disorder• Prevalence      –     55 million people in the United States have          hypertension...
Control of Hypertension Low in Women           About Half Are Treated; About a Quarter Are Controlled           80    75.1...
SBP is a Major Factor in the Lack of BP Control                        in the Community                    Hypertensive Su...
Hypertension Increases With                                      Weight Gain in Women                   Nurses’ Health Stu...
BP Rises After Menopause—                             Risk of Hypertension Triples                  Changes in SBP From Ba...
Menopause Increases Salt-sensitivity                           Increases in Salt Intake Lead to Increases in              ...
Estrogen Is a Potent Vasodilator       Interruption of Estrogen in Postmenopausal Hypertension                            ...
Impact of High-Normal BP on CV Risk
JNC 7  Classification of Blood Pressure  for Adults Aged 18 Years or Older              BP Classification              Sys...
Goals of Hypertensive Management•   Maintenance of normal BP (avoidance of stroke, CHF)•   Cardioprotection (primary/secon...
How Low Should Blood Pressure                              Be Lowered?        JNC 71: Blood Pressure Goals        Conditio...
Lifestyle Modifications to            Prevent and Manage HypertensionReduce weight                  Moderate consumption o...
A DASH Towards Cardiovascular Health  • DASH* Diet is recommended by                                        DASH Diet Prov...
Limited Efficacy of Monotherapy                A Reason for Poor BP Control                60          59                 ...
Advantages of Combination Therapy• Increased efficacy   – Important as lower BP goals require more drug therapy• Decreased...
Recommendations Regarding Initial Use                      of Combination Therapy       JNC 7              >20/10 mm Hg ab...
JNC 7  Management of Blood Pressure  for Adults Without Compelling Conditions                                             ...
The 7th report of the Joint National      Committee: Compelling IndicationsCompelling                             Diuretic...
Pathophysiology of BPBP =X     CO              SVR  StrokeVol    HR      PVR      RVR
Antihypertensive Drug Therapy                                                                                    Highly ef...
Rational Use of Antihypertensive Drugs           In CombinationDiuretics                                                  ...
Renin Angiotensin System                                       Angiotensinogen                                            ...
Indications and contraindications for       major classes of antihypertensive drugsDrug                     Indications   ...
Case #1• 55 yr old African American Female with hx of HTN for 10 yrs• CV risk factors include diabetes, obesity and fibrom...
Case #2• 75 yr old Caucasian woman with 20yr history of HTN,  mild urinary incontinence, former smoker▪ Exam:   ▪   BP 168...
Many Providers Not Motivated to Initiate or Change                   Treatment                                         Ret...
What Is Therapeutic Inertia?                                                                     Causes:                  ...
CVD Mortality Trends for                                          Males and Females: US 1979–2002                        5...
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  • ESRD- end stage renal disease
  • Am 8.45 meagher

    1. 1. Hypertension Management in Women: What’s Different? Emma A. Meagher, MD Associate Professor, Medicine and Pharmacology University of Pennsylvania
    2. 2. Conflict of Interest DisclosureEmma A. Meagher, MD has no conflicts to disclose
    3. 3. CVD Mortality in Women Has NOT Decreased at the Same Rate as in Men United States: 1979–2004 520 Females 500Deaths, thousands 480 460 Males 440 420 400 1979 1985 1990 1995 2000 2005 Years Rosamond W et al. Circulation. 2007:115.
    4. 4. 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 hypertensionAHA. 2008 Heart and Stroke Statistical Update. 2010.
    5. 5. Control of Hypertension Low in Women About Half Are Treated; About a Quarter Are Controlled 80 75.1 73.6 71.2 70 62.0 60.1 60.0 60Women, % 50 40 29.1 27.4 29.6 30 20 10 0 III (Phase 1 III (Phase 2 1999–2000 1988–1991) 1991–1994) Awareness Treatment Control**Percentage of hypertensive patients controlled. Hajjar et al. JAMA. 2003;290:199–206.
    6. 6. SBP is a Major Factor in the Lack of BP Control in the Community Hypertensive Subjects Examined in the Framingham Heart Study Between 1990 and 1995 140 Uncontrolled Uncontrolled 13.4% DBP 120 SBP/DBP 3.7% DBP (mm Hg) 100 80 60 40 29.0% 53.9% Uncontrolled Controlled SBP SBP/DBP 20 80 100 120 140 160 180 200 220 SBP (mm Hg) SBP and DBP levels of all 1959 subjects with hypertension, treated and untreated, are represented.Lloyd-Jones DM et al. Hypertension 2000;36:594-599.
    7. 7. Hypertension Increases With Weight Gain in Women Nurses’ Health Study: Hypertension† According to Weight Change 7 Weight Status in Women Age <45 6 NHANES data: 2002–2004 5 Overweight: 61.8% Age 45–54Multivariate RR* 4 Obese: 33.2% Age ≥55 3 Extreme Obesity: 6.9% 2 1 0 Loss Loss Loss Change Gain Gain Gain Gain Gain ≥10 5.0–9.9 2.1–4.9 ≤2.1 2.1–4.9 5.0–9.9 1.0–19.9 20.0–24.9 ≥25 Weight Change After 18 Years, kgOverweight=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. Huang Z et al. Ann Intern Med. 1998;128:81–88. Ogden C et al. JAMA. 2006;295(13):1549-55.
    8. 8. BP Rises After Menopause— Risk of Hypertension Triples Changes in SBP From Baseline to Follow-up (Mean 5.2 Years) Women Controls 6 Premenopausal 5 (n=166) 4 † * Perimenopausal (n=44) 3 Δ From BaselineSBP, Postmenopausal 2 (n=105) 1 –1.9 –0.1 0 0.4 3.3 3.8 0.2 –1 mmHg –2 –3*P≤0.05.†P=0.07.Baseline SBP: Pre=121.4 ± 1.3 mmHg; Peri=122.0 ± 1.8 mmHg; Post=126.5 ± 1.7mmHg; Controls: men matched by age and BMI. Staessen JA et al. J Hum Hypertens. 1997;11:507–514.
    9. 9. Menopause Increases Salt-sensitivity Increases in Salt Intake Lead to Increases in Blood Pressure in Postmenopausal Women 250 Follicular 200 Luteal (U Na V, mmol/d) Contraceptive 150 Menopause Salt Intake 100 50 0 70 80 90 100 110 24-hour Mean Blood Pressure, mmHgOparil S, Miller AP. J Clin Hypertens (Greenwich). 2005;7:300–309.
    10. 10. Estrogen Is a Potent Vasodilator Interruption of Estrogen in Postmenopausal Hypertension vessel L-citrulline L-arginine Endothelial Cell No NOS acetylcholine No GTP cGMP protein kinase ↑CA2+ VSMC PGI2 Relaxation Contraction Catecholamine Estrogen relax vascular smooth muscle by increasing NO levels and decreasing vasoconstriction by acting as a calcium antagonistSchwertz DW et al. Heart Lung. 2001;30:401–426.Orshal JM et al. Am J Physiol Regul Integr Comp Physiol. 2004;286:R233–R249.
    11. 11. Impact of High-Normal BP on CV Risk
    12. 12. JNC 7 Classification 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 ≥100Chobanian AV, et al. JAMA 2003;289:2560-72
    13. 13. 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
    14. 14. How Low Should Blood Pressure Be Lowered? JNC 71: Blood Pressure Goals Condition BP Target Uncomplicated HTN <140/90 mm Hg HTN + Diabetes <130/80 mm Hg HTN + Chronic Renal Disease <130/80 mm Hg AHA2:Blood Pressure Goals Condition 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.1. Chobanian AV et al. Hypertension. 2003;42:1206-1252. 2. Rosendorff C et al. Circulation. 2007;115:2761-2788.
    15. 15. Lifestyle Modifications to Prevent and Manage HypertensionReduce weight Moderate consumption of: • alcohol • sodium • saturated fat • cholesterol Maintain adequate intake of dietary: • potassium • calcium Increase • magnesium physical activity Avoid tobacco(JNC VII)
    16. 16. A DASH Towards Cardiovascular Health • DASH* Diet is recommended by DASH Diet Provides Greater BP JNC 7 for all patients with, or at ReductionsThan Control Diet risk of, hypertension 0 • Diet adherence is low and Diastolic -5 mm Hg declining -5.5 – Only about 20% of people with -10 Systolic hypertension follow the diet; -11.4 -15*DASH=Dietary Approaches to Stop Hypertension, a study that showed a diet rich infruits, vegetables, grains, low-fat dairy products, and low in fat, cholesterol, and sodiumlowered systolic and diastolic blood pressures 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.
    17. 17. Limited Efficacy of Monotherapy A Reason for Poor BP Control 60 59 51 50 50 46 42 42 40 Response rate* 30 (%) 20 10 0 Diltiazem Atenolol Clonidine HCTZ Captopril PrazosinHCTZ, hydrochlorothiazide.*Response = DBP <90 mm Hg at the end of the titration period and <95 mm Hg at the end of 1 year oftherapy.Materson BJ et al. N Engl J Med. 1993;328:914-921.
    18. 18. 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?
    19. 19. 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 SBP ≥160 mm Hg or DBP ≥100 mm Hg irrespective of AHA the BP goals (Stage 2 Hypertension) >20/10 mm Hg above goal pressure of <130/80 mm Hg ASH for diabetics SBP >20 mm Hg above goal according to the stage of CKD and NKF CVD riskJNC 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 FoundationChobanian AV, et al. Hypertension. 2003;42:1206–1252. Douglas JG, et al. Arch Intern Med. 2003;163: 525-541. American Journal of KidneyDiseases. 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.
    20. 20. JNC 7 Management of Blood Pressure for Adults Without Compelling Conditions Initial Drug Therapy BP Classification Recommendation Lifestyle modification only Prehypertension Thiazide-type diuretics for most; Stage 1 Hypertension ACE inhibitor, ARB, -Blocker, CCB, or combination 2-Drug combination for most (usually Stage 2 Hypertension thiazide-type diuretic and ACE inhibitor, ARB, -Blocker, or CCB)Chobanian AV, et al. JAMA 2003;289:2560-72
    21. 21. The 7th report of the Joint National Committee: Compelling IndicationsCompelling Diuretic βB ACEI ARB CCA AAIndicationsHeart Failure √ √ √ √Post-MI √ √ √High CAD risk √ √ √ √Diabetes √ √ √ √Chronic kidney √ √diseaseRecurrent stroke √ √prevention AA=Aldosterone Antagonist BB=Beta Blocker CCB=Calcium Channel BlockerChobanian AV, et al. JAMA. 2003;289(19):2560-2572.
    22. 22. Pathophysiology of BPBP =X CO SVR StrokeVol HR PVR RVR
    23. 23. Antihypertensive Drug Therapy Highly effective Perceived Improvements in Tolerability SBP control1940’s 1950 1957 1960’s 1970’s 1980’s 1990’s 2001 2007 ACE ARBs Renin Direct inhibitors inhibitors vasodilators -blockers Ganglion Thiazides ETAs* blockers diuretics VPIs* Central 2 agonists CCAs -non DHPs CCAs - DHPs -blockers *Not currently available for clinical use
    24. 24. Rational Use of Antihypertensive Drugs In CombinationDiuretics Beta BlockersACEIs CCAsARBs 1-Receptor Blockers Less effective Particularly effective Adapted from Chalmers J. Clin Exp Hypertens. 1993;15:1299–1313.
    25. 25. Renin Angiotensin System Angiotensinogen • t-PA Renin X DRI • Cathepsin G Ang I • Tonin CAGE ACE Cathepsin G Chymase Ang II ACEI site of actionARB site of AT1 receptor AT2 receptoraction • Hypertrophy/proliferation • Antiproliferation • Vasoconstriction • NO Release • Aldosterone release • Differentiation • Antidiuretic hormone release • Vasodilationde 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.
    26. 26. Indications and contraindications for major classes of antihypertensive drugsDrug Indications ContraindicationsDiuretics Elderly GoutBeta-blockers MI, Angina Asthma, Heart blockHeart failure Heart failureACE inhibitors HF, Type 1 Pregnancy, DM nephropathy Renovascular diseaseCa2+ antagonists Isolated systolic HTN Short acting in pts with IHD AnginaAlpha-blockers Prostatism Urinary incontinenceAT1 blockers ACE cough Pregnancy, Heart failure Renovascular disease
    27. 27. 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
    28. 28. 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
    29. 29. Many Providers Not Motivated to Initiate or Change Treatment Retrospective Analysis Percentage of Visits Without Medication Intensification1 100% 80% 87% 79% 60% 72% 55% 40% 20% 0% 150-159 160-169 170-179 ≥180Retrospective Study 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 1. Adapted from Andrade et al. Am J Manag Care. 2004;10:481-486. 2. Chobanian AV et al. Hypertension 2003;42;1206-1252. For your confidential information only
    30. 30. What Is Therapeutic Inertia? Causes:  Overestimation of care provided The failure of  Use of “soft” reasons to avoid health care intensifying therapy providers to  Lack of education, training, and practice initiate or intensify organizations on: therapy when – The benefits of treating to therapeutic targets indicated – The practical complexity and need for polypharmacy in treating to target – The need to structure routine practice to facilitate identification of therapeutic problemsPhillips LS et al. Ann Intern Med. 2001;135:825–834.
    31. 31. CVD Mortality Trends for Males and Females: US 1979–2002 520 Deaths (thousands) 480 Males Females 440 400 0 NCEP I NCEP II NCEP III 1979 81 83 85 87 89 91 93 95 97 99 01 02 YearsNCEP = National Cholesterol Education Program.American Heart Association. Heart Disease and Stroke Statistics — 2005 Update.Dallas, Tex: American Heart Association; 2005. ©2005, American Heart Association.
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