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  • 08/06/10 JNC VI: BP Classification According to JNC VI, optimal BP is defined as <130/85 mm Hg, and high-normal BP is defined as an SBP of 130–139 mm Hg or a DBP of 85–89 mm Hg. Hypertension of stages I, II, and III is defined as an SBP of 140–159, 160–179, and  180 mm Hg, respectively, or a DBP of 90–99, 100–109, and  110 mm Hg, respectively. 1 Reference 1. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2446. Slide 11
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  • 08/06/10 Slide 8 Multiple Risk Factor Intervention Trial (MRFIT): Effect of BP on CHD- Related Mortality After an average of 12 years of follow-up, 6,327 deaths from coronary heart disease (CHD) occurred among the 316,099 men screened for entry into the Multiple Risk Factor Intervention Trial (MRFIT). 1 As the graph on this slide shows, the age-adjusted CHD death rate per 10,000 person-years was associated with increasing DBP above 70 mm Hg and increasing SBP above 110 mm Hg, with the greatest increases associated with rises in SBP. SBP was a stronger predictor of CHD death than DBP. SBP is the risk factor, DBP adds nothing to risk, and wide pulse pressure, even in young men, is the problem. Reference 1. Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Arch Intern Med . 1992;152:56-64.
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  • 08/06/10 More than one risk factor for CHD is often present in an individual. When risk factors coexist, their combined effect is often much greater than their individual effects. Thus, the patient with severe hypercholesterolemia and no other risk factors may be at a lower risk than the patient with a combination of risk factors, such as hypertension, moderately elevated lipid levels, and smoking. Reference Kannel WB, Neaton JD, Wentworth D, et al. Overall and coronary heart mortality rates in relation to major risk factors in 325,348 men screened for the MRFIT. Am Heart J. 1986;112:825-836.
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  • 08/06/10 Components of CVD Risk Stratification in Hypertensive Patients Major risk factors for cardiovascular disease (CVD) risk are smoking, dyslipidemia, diabetes, age > 60 years, gender (men and postmenopausal women), and family history of CVD. The risk for CVD in hypertensive patients is determined not only by the level of blood pressure but also by the presence or absence of target organ damage, such as heart disease (left ventricular hypertrophy, angina or prior myocardial infarction, prior coronary revascularization, heart failure), stroke or transient ischemic attack, nephropathy, peripheral arterial disease, or retinopathy. Risk factors and clinical disease independently modify the risk for subsequent cardiovascular disease. Identifying risk factors and clinical disease should be routinely attempted during office visits. 1 Reference 1. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2446. Slide 12
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  • 08/06/10 This slide shows the association of age with blood pressure control. Increasing age was associated with poorer rates of SBP control and overall control, whereas it was associated with improved rates of control to DBP goal.
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Hypertension and Cardiovascular Disease ( Presentation Transcript

  • 1. Blood Pressure & CV Disease Stanley S. Franklin, MD University of California, Irvine
  • 2.  
  • 3. Korotkoff, 1905
  • 4. Agenda: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP
  • 5. Agenda: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP
  • 6. Prevalence of Cardiovascular Disease 10 20 30 40 50 60 High BP CAD CHF Stroke Other 50,000,000 12,200,000 4,600,000 4,400,000 2,800,000 Prevalence (millions) BP=blood pressure, CAD=coronary artery disease, CHF=congestive heart failure Estimated Number of Persons With Cardiovascular Disease in the US American Heart Association ® . 2000 Heart and Stroke Statistical Update. 1999. (24%)
  • 7. JNC VI BP Classification Category Optimal Normal High-normal Hypertension stage 1 stage 2 stage 3 Systolic  120  130 130–139 140–159 160–179  180 and and or or or or Diastolic  80  85 85–89 90–99 100–109  110 BP (mm Hg) Adapted from JNC VI. Arch Intern Med . 1997;157:2413-2446.
  • 8. 4-Year Progression To Hypertension: The Framingham Heart Study (<120/80 mm Hg) (130/85 mm Hg) (130-139/85-89 mm Hg) Vasan, et al. Lancet 2001;358:1682-86 Participants age 36 and older
  • 9. 4-Year Progression To Hypertension: The Framingham Heart Study Vasan, et al. Lancet 2001;358:1682-86 Participants age 65 and older (<120/80 mm Hg) (130/85 mm Hg) (130-139/85-89 mm Hg)
  • 10. Vasan, et al, JAMA 2002;287:1003-1010.
  • 11. How Does ABPM Work?
    • Monitor programmed to take BP measurements repeatedly over 24 hours
    • Patients go about normal activities
    • Report shows variation in BP over time
    Burt VL et al. Prevalence of hypertension in the US adult population: Results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-313.
  • 12. What Is the ‘Normal’ 24-Hour, Awake, and Sleep Blood Pressure?
    • Recommendations of ASH (1996) and O’Brien & Staessen (1999)
      • Daytime <135/85 probably normal, >140/90 probably abnormal
      • Nighttime <120/70 probably normal, >125/75 probably abnormal
      • 24 hour <130/80 probably normal, >135/85 probably abnormal
  • 13. 135/85 140/90 Clinic Pressure Ambulatory Pressure Clinic BP versus ABP ? Sustained Hypertension White Coat Hypertension True Normotension Masked Hypertension
  • 14. Men, Age (y) Women, Age (y) Pulse pressure Pulse pressure SBP & DBP by Age & Race/Ethnicity &Gender (US Population  Age 18 Years, NHANES III) Burt VI, et al. Hypertension . 1995;25:305-313. 18-29 30-39 40-49 50-59 60-69 70-79 80+ 0 70 80 110 130 150 18-29 30-39 40-49 50-59 60-69 70-79 80+ 0 70 80 110 130 150 0 70 80 110 130 150 0 70 80 110 130 150 DBP (mm Hg) SBP (mm Hg) DBP (mm Hg) SBP (mm Hg) DBP (mm Hg) SBP (mm Hg) DBP (mm Hg) SBP (mm Hg) Non-Hispanic Black Non-Hispanic White Mexican American
  • 15. Age Distribution of Hypertensives in US Population (NHANES III and the 1991 Census) 3.7 9.5 13 21.3 23.7 19.2 9.6 Hypertensives Within Age Group (%) Franklin SS. J Hypertension. 1999;17(suppl 5):S29-S36. Age Groups (y) 47.4 million hypertensives 26.0% of US population 26% 74% 0 5 10 15 20 25 30 18-29 30-39 40-49 50-59 60-69 70-79 80+
  • 16. <40 40-49 50-59 60-69 70-79 80+ Age (y) 17% 16% 16% 20% 20% 11% Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by Age Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874 . Frequency of hypertension subtypes in all untreated hypertensives (%) ISH (SBP  140 mm Hg and DBP <90 mm Hg) SDH (SBP  140 mm Hg and DBP  90 mm Hg) IDH (SBP <140 mm Hg and DBP  90 mm Hg) 0 20 40 60 80 100
  • 17. Mortality According to Blood Pressure in Men Age 50–69 Actuarial Society of America: Blood Pressure Study 1939 DBP (mm Hg) SBP (mm Hg) 68–82 83–87 88–92 93–97 98–102 98–127 128–137 138–147 148–157 158–167 0 50 100 150 200 250 Mortality Ratio (%)
  • 18. Risk Pyramid: SBP and CHD Mortality for Men Screened in MRFIT Adapted from Stamler J et al. Arch Intern Med . 1993;153:598-615. Hypertension Control. WHO Technical Reports Series, 1996. No. 862. SBP (mm Hg) Excess CHD deaths (%) Men (%)  180 7.2 0.9 170-179 6.8 1.2 160-169 10.1 2.7 150-159 19.5 6.2 140-149 23.4 12.8 130-139 20.7 22.8 120-129 9.9 28.4 110-119 1.3 19.0 <110 0.0 6.1 High BP
  • 19. Blood Pressure and Risk for Coronary Heart Disease in Men Based on 30 year follow-up of Framingham Heart Study Subjects free of CHD at base line but not adjusted for other risk factors.
  • 20. Multiple Risk Factor Intervention Trial* (MRFIT) ( Effect of BP on CHD Mortality Rate) * Men aged 35-57 years followed for a mean of 12 years Neaton and Wentworth, Arch Intern Med . 1992;152:56. DBP (mm Hg) SBP (mm Hg)  100 90-99 80-89 75-79 70-74 <70 <120 120-139 140-159  160
  • 21. Pulse Pressure
    • Increase in pulse pressure (PP) indicates greater stiffness in large conduit arteries, primarily the thoracic aorta.
    • PP , therefore, is a surrogate measure of dynamic, cyclic stress during systole.
    • PP may be a better marker of increased CV risk than either systolic BP or diastolic BP alone in older persons.
    PP = SBP – DBP
  • 22.  
  • 23. Agenda: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP
  • 24. Seven Countries Study: Absolute Risks of Death from CHD Van Den Hoogen et al . NEJM. 2000; 342 (1): 3. 0 20 40 60 80 100 120 140 110 120 130 140 150 160 170 Systolic Blood Pressure (mm Hg) Mortality from CHD (no./10,000 person-yr) U.S. N. Europe Mediterranean S. Europe Inland S. Europe Serbia Japan
  • 25. Estimated CHD Rate Over 10 Years According to Risk Factors 0 10 20 30 40 50 60 70 SBP (mm Hg) 120 160 160 160 160 160 160 Cholesterol (mg/dL) 220 220 259 259 259 259 259 HDL (mg/dL) 50 50 50 35 35 35 35 Diabetes - - - - + + + Smoking - - - - - + + LVH by ECG - - - - - - + Framingham Heart Study Estimated 10-year CHD rate (%) Adapted from Kannel. JAMA 1996;275:1571. Men Women
  • 26. Levels of risk associated with smoking, hypertension, and hypercholesterolemia Adapted from Kannel WB, et al. Am Heart J. 1986;12:825-836. Smoking Serum total cholesterol level (>240 mg/dL) Hypertension (DBP >90 mm Hg) x2.5 x7 x11 x6 x3 x3 x3
  • 27. Risk Factor Clustering with Hypertension None One Two Three 5% 0% 10% 15% 20% 25% 30% Men Women 17 % 19% 26 % 27% 25 % 24% 22% 20% 8% 12 % Four or more Risk factor clustering with hypertension, ages 18-74 years. Framingham offspring. Kannel WB. Am J Hypertens . 2000. % of risk factors Number of risk factors
  • 28. Metabolic Syndrome: A Cluster of Abnormalities
    • (1) Hypertension (or Hi-Norm)
    • (2) Decreased HDL-C
    • (3) Increased triglycerides
    • (Small dense LDL-C
    • and ↑ Apo B)
    • ( Insulin resistance &
    • Hyperinsulinemia)
    • (4) Impaired glucose tolerance
    • (Diabetes)
    • (5) Abdominal obesity
    Adapted from Reaven GM. Clinical Diabetes 1994;12:32-36.
  • 29. Agenda: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP
  • 30. Components of CVD Risk Stratification in Hypertensive Patients Adapted from JNC VI. Arch Intern Med . 1997;157:2413-2446.
    • Major Risk Factors
    • Smoking
    • Dyslipidemia
    • Diabetes
    • Age  60 years
    • Gender (men and postmenopausal women)
    • Family Hx of early CVD
    • (W <65 yrs, M<55 yrs)
    • Target Organ Damage /Clinical CVD
    • Heart diseases
      • LVH
      • Angina or prior MI
      • Prior coronary revascularization
      • CHF
    • Stroke or TIA
    • Proteinuria, Nephropathy:  S CR
    • Peripheral arterial disease
    • Retinopathy
  • 31. JNC VI: BP Risk Stratification
    • Risk Group A
      • No CV risk factors
      • No diabetes, target-organ damage, or clinical CVD
    • Risk Group B
      • At least one other risk factor: age >60, male gender or postmenopausal status, dyslipidemia, smoking, +FH
      • (No diabetes, target-organ damage, or clinical CVD)
    • Risk Group C
      • Diabetes or target-organ damage or clinical CVD with or without other risk factors
    JNC VI. Arch Intern Med 1997;157:2413.
  • 32. JNC VI: Treatment Strategies by Risk Stratification
    • Risk Groups
    • BP stage (mm Hg) A B C
    • High-norma l Lifestyle Lifestyle Drug therapy * † (130-139/85-89) modification modification
    • Stage 1 Lifestyle Lifestyle Drug therapy * (140-159/90-99 ) modification modification (up to 12 mo) (up to 6 mo) ‡
    • Stages 2+ Drug therapy * Drug therapy * Drug therapy * (≥160/≥100)
    * Lifestyle modification should be adjunctive for all patients starting pharmacologic therapy. † For patients with heart failure, renal insufficiency, or diabetes. ‡ For patients with multiple risk factors, drug therapy should be considered in addition to lifestyle modification. Adapted from JNC VI. Arch Intern Med 1997;157:2413.
  • 33.  
  • 34.
    • Intervention
    • Exercise
    • Weight reduction
    • Alcohol intake reduction
    • Sodium intake reduction
    • DASH diet
    Lifestyle Interventions for Prevention or Treatment of Hypertension
    • Blood Pressure Effect
    • 5-10 mm Hg ( > 30 min > 3x/wk)
    • 1-2 mm Hg/Kg 
    • 1 mm Hg/drink/d 
    • 1-3 mm Hg/40 mmol/d 
    • 3-10 mm Hg 
    Adapted from Cushman et al. Endocrine Practice 1997;3:106 & Sacks, et al. NEJM 2001;334:3
  • 35. JNC VI Lifestyle Treatment Measures
    • Nonpharmacologic treatments are used for:
    •  Lowering blood pressure
    • Reducing need for antihypertensive agents
    • Minimizing associated risk factors
    •  Primary prevention of hypertension
  • 36. Agenda: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP
  • 37. “ Hypertension may be an important compensatory mechanism which should not be tampered with, even if it were certain that we could control it.” Paul Dudley White, Textbook of Cardiology, 1931
  • 38.  
  • 39. The evidence pyramid © G Reboldi, 2001 Randomized controlled double-blind trials Animal, in vitro & cell models Editorials, reviews, &quot;expert&quot; opinions Case reports Case series & Cross-sectional studies Case-control studies Cohort studies RCT DB RCT Randomized controlled trials M E T A - A N A L Y S E S Clinical studies Non-randomized trials
  • 40. Hypertension Intervention Trials: 1959-1970
  • 41.
    • Stroke: - 38% (95% CI 31-45%)
    • Ischemic heart disease: - 16% (95% CI 8-23%)
    • Cardiovascular death: - 21% (95% CI 13-28%)
      • Source: meta-analysis of 17 RCTs (diuretics &  B therapy)
      • Average DBP reduction: 5-6 mmHg .
    Antihypertensive treatment: Relative benefit for mild HTN (DBP 90-104 mmHg) Collins R, Peto R. In: Swales JD. Textbook of Hypertension, Oxford, UK, 1994
  • 42. “ Antihypertensive a gent s produce no obvious benefit in patients over 65” Fry J, Lancet 1974 “ Hypertensive drugs should probably not be given (in the elderly) unless the blood pressure is more than 200/110 mm Hg.” Editorial, Br Med J, 1978
  • 43. SHEP Trial: Design
    • N: 4736; 43% male
    • Age: > 60 (mean age = 71 y)
    • BP: SBP 160-219 and DBP <90
    • Design: Placebo control, double blind
    • Active Rx: Chlorthalidone (atenolol as step 2)
    • SBP difference: 12 mm Hg
    • Duration: 4.5 years
    JAMA 1991;265:3255
  • 44. SHEP Trial: Design
    • N: 4736; 43% male
    • Age: > 60 (mean age = 71 y)
    • BP: SBP 160-219 and DBP <90
    • Design: Placebo control, double blind
    • Active Rx: Chlorthalidone (atenolol as step 2)
    • SBP difference: 12 mm Hg
    • Duration: 4.5 years
    JAMA 1991;265:3255
  • 45. SHEP Trial: Cardiovascular Disease Endpoints JAMA 1991;265:3255
  • 46.
    • All-cause death: - 10% (95% CI -1  21%)
    • Cardiovascular death: - 16% (95% CI 2  25%)
    • Coronary events: - 23% (95% CI 5  36%)
    • Stroke: - 30% (95% CI 12  48%)
      • Source: meta-analysis of 7 RCTs (most placebo-controlled)
      • n=13299, age 60+ years (average SBP reduction 10 mm Hg)
    Treating isolated systolic hypertension in the elderly : Relative benefit Staessen JA, et al. Lancet 2000; 355: 865-872
  • 47. Meta-analysis of 5 Randomized Controlled Trials in Very Old People (Age > 80 Years) n=1,670 p=.014 p=ns p=.01 p=ns Gueyffier F, et al. Lancet 1999;353:793-6
  • 48. death CVD death Relative risk (95% CI) treatment better Endpoint no treatment better Long-term benefits of antihypertensive treatment Secular trends in the Framingham Heart Study Sytkowski PA, et al. Circulation 1996;93:697-703 0 0.5 1 1.5
  • 49.
    • Trial duration is <10 years; treatment benefits should be considered in the very long term (decades).
    • Drop-in effect (subjects under placebo are given active drug) and drop-out effect (drop-outs in the active treatment group.
    • Subjects included in the trials are generally healthier than those treated in the clinical practice (selection of low-risk subjects).
    • Secondary end-points & subgroup analyses difficult to interperet.
    Trials & meta-analyses: What we do not know ( ...and maybe will never know )
  • 50. Are “new” antihypertensive drugs more effective than “old” ones in preventing the complications of hypertension ?
  • 51. Study Year N Follow-up Age Primary (years) (years) End-points ( N / O ) UKPDS 1998 758 8.4 56.4 259 / 170 CAPPP * 1999 10985 6.1 52.4 363 / 335 STOP 2 1999 6614 5.0 76.0 438 / 221 INSIGHT 2000 6321 2.9 65.0 200 / 182 NORDIL 2000 10881 1 3.3 60.5 403 / 400 * proper randomization? Randomized Controlled Trials: “ New”: ACEI, CCB,  B vs .“Old” Diuretic,  B
  • 52. UKPDS 39 captopril atenolol diabetes-related event CAPPP captopril diur/  -blockers MI + stroke + CV death STOP 2 CCB/ACEI diur/  -blockers MI + stroke + CV death INSIGHT nifedipine diur + amiloride MI + stroke + CHD death + CHF NORDIL diltiazem diur/  -blockers MI + stroke + CV death
    • Randomized trials comparing (as primary endpoint) the effect of different drug classes on CV morbidity and mortality
    Benefits of antihypertensive therapy: &quot;new&quot; vs &quot;old&quot; drugs Primary endpoint Relative risk (95% CI) &quot;new&quot; better &quot;old&quot; better 0.5 1 1.5
  • 53.
    •  =0.05
    • Power to detect a 15% between-group difference in event occurrence
    Size (of the study) does matter! 200 400 600 800 1000 Power, % 50 60 70 80 90 100 Number of events per treatment group
  • 54. Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356: 1955-1964 A Prospectively Planned Meta-analysis of Antihypertensive Treatment Trials
    • To minimize selection bias, studies selected:
      • before hypothesis were formulated
      • before outcomes were established
      • before results were known
    • CCB superior to placebo : strokes & CV deaths
    • ACE-I superior to placebo : strokes, CHD, CV deaths
  • 55. * CCB 1251 /11685 1234 /11769 diur/  -blockers † ACE-I 1018 /8097 1004 /8064 diur/  -blockers ‡ ACE-I 559 /2440 619 /2431 CCB Benefits of antihypertensive therapy Major cardiovascular events * 99% of the events were from the INSIGHT, STOP-2 and NORDIL studies † identical results after excluding CAPPP ‡ 94% of the events were from the STOP-2 study Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356: 1955-1964 0.5 1 1.5
  • 56. “ Old” & “new” antihypertensive drugs: Where do we stand?
    • The efficacy of different antihypertensive therapies in preventing CV complications was compared directly in 6 randomized studies
    • No significant difference among the different drug classes in:
      • combined primary end-points
      • all-cause & cardiovascular mortality
      • cardiovascular morbidity
    • CCB versus ACE-I : better for stroke prevention & worse for CHD prevention (vs ACE-1 )
  • 57. Are antihypertensive drugs that block the renin-angiotensin system more specific in preventing cardiovascular complications, i.e. is it the BP, the agent, or both ?
  • 58. HOPE Study Hypertension Outcomes Prevention Evaluation (Cause-Specific Class C Disease)
    • n=9297 patients with CVD , or diabetes and  1 additional risk factor
    • ramipril vs placebo  ; baseline BP 139/79 mmHg, 47% hypertensive
    •  stroke (-31 %),  CHD (-19%),  mortality (-15%),  diabetes (-32%)
    HOPE Study investigators. N Engl J Med 2000; 342: 145-153  Add-on placebo after treating hypertension with non-renin-AII drugs
  • 59. Agenda: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP
  • 60. CV events BP
  • 61. Special Recommendations for Therapeutic Goal Blood Pressure
    • For class A & B patients , treatment goal = SBP < 140 mm Hg &
    • DBP < 90 mm Hg (Should it be <150-160/<90 mmHg?)
    • For high-risk class C patients, treatment goal =
    •  DM: <130/85 mm Hg (<140/85 from trials)
      •  CRI: <125/75 mm Hg (if > 1 gm U protein / 24h)
  • 62. Approximately 50 Million Americans Have Hypertension American Heart Association, February 1999. Uncontrolled 72.6% Controlled 27.4% 13.7 million 36 million
  • 63. Treated hypertensive subjects with BP <140/90 mmHg 28% 22% USA Canada UK 6% 24% 27% 25% Belgium Italy France <140/90 mmHg  140/90 mmHg 9% 2% India Zaire 3% 10% China Egypt
  • 64. Hypertension Control by Age Group Cross-sectional analysis among 1189 treated hypertensive subjects from Framingham Lloyd-Jones Hypertension 2000;36:594
  • 65. Why is ISH so Difficult to Treat to Goal?
      • 1. Focus on DBP rather than SBP goal
    • 2. Fear of reaching excessively low DBP
    • 3. Failure to lower goal in high-risk subjects
    • 4.Truly resistant systolic hypertension
    • 5. Failure to use a diuretic
    • 6. Failure to use poly-pharmacy
  • 66. Rationale for Combination Drug Therapy in Hypertension
    • Necessary for Good Control:
    •  All resistant, severe, or secondary hypertension
    • Approx. 2/3 of mild/ moderate hypertension
    • Almost all class C patients , esp. DM, CRI
    • Maximizes Efficacy:
    • Supplementary mechanisms of action
    • Blockade of contra regulatory mechanisms
    • Minimizes Side Effects:
    • Lower doses of each drug
    •  May antagonize adverse pharm. actions of other drug
  • 67. Number of Medications to Achieve Goal BP in 5 Trials of DM &/or Renal Disease Bakris. J Clin Hypertens 1999;1:141-7
  • 68. Recommendations for Improving Outcomes
    • Physician
    •  Establish treatment goals
    •  Maintain adherence
    •  Minimize side effects
    • Patient
    •  Self-Monitor BP
    •  Keep diary of BP therapy
    •  Make life-style changes
  • 69. Summary: BP & CV Disease  BP as an independent risk factor for CV disease  Interaction of BP with other CV risk factors  JNC VI guidelines for determining risk & therapy  Hypertension intervention trials: what do they tell us?  Therapeutic strategies for successful goal BP