12 Prevalent causes of HT by age Age groupMain causesneonatesRenal artery / vein thrombosis, congenital renal anomalies, coarctation of aorta< 1 yearCoarctation of aorta, renovascular / renal parenchymal disease1- 6 yearsRenal parenchymal, renovascular disease, coarctation of aorta7-12 yearsRenal parenchymal, renovascular disease, primary hypertensionyearsPrimary hypertension, medication or substance abuse, renal parenchymal disease
13 Clinical approach of a young hypertensive : 4 goals Detection and confirmation of hypertensionDetection of target organ damageIdentification of other risk factors for cardiovascular diseaseDetection of secondary causes of hypertension
14 Detection of hypertension All children > 3 years should have their BP checkedCheck BP for children < 3 years :- congenital heart disease- hematuria, proteinuria, recurrent UTI- family h/o congenital renal disease- evidence of raised intracranial pressure- solid organ/ bone marrow transplant- treatment with drugs known to raise BP- presence of any systemic illness known to raise BP
15 Confirm high blood pressure At least 2 readings, 5 minutes apart; preferably over 2 visitsConfirm elevated reading in contralateral armRule out pseudo hypertensionAll children with BP > 90th percentile by oscillometric method should be confirmed by auscultatory method
18 look for target organ damage Microalbuminuria : urine albumin to urine creatinine ratio of µg/mgEstimated GFR < 60 ml/minUltrasound evidence of arterial wall thickening or atherosclerotic plaque
19 Identification of co morbidities Diabetes : hypertensives are 2.5 times more likely to develop diabetes within next 5 yearsObesity : > 2/3rd of young hypertensives are either overweight or obeseDyslipidemiaSmoking, tobacco useStress
21 Risk factors for secondary hypertension : when to look for other causes? Poor response to therapy (resistant HT)Worsening of control in previously stable hypertensive patientStage 3 hypertension (SBP > 180 or DBP>110)Onset of HT : age < 20 yrs or > 50 yrsSignificant target organ damageAbsence of family history of hypertensionFindings / history / lab point to a secondary cause
22 Younger the patient, greater is the likelihood for a secondary cause Higher the blood pressure elevation, greater is the likelihood for a secondary cause
23 Rule out pseudoresistance Improper BP measurementExcess sodium intakeInadequate diuretic therapyMedicationInadequate dosesDrug actions and interactions:Nonsteroidal antiinflammatory drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptivesOver-the-counter (OTC) drugs and herbal supplementsExcess alcohol intakeIdentifiable causes of HTNJNC 7 Express. JAMA Sep 10; 290(10):1314
24 Secondary hypertension A : Apnea, aldosteronism B : Bruits, bad kidneys (renal parenchymal disease) C : catecholamines, coarctation, cushings D : drugs, diet E : erythropoietin, endocrine disorders
25 Screening history Day time fatigue, sleepiness, snoring : OSA Polyuria, nocturia, cramps, muscle weakness : aldosteronismMultiple vascular risk factors, history of flash pulmonary edema, unexplained renal insufficiency : renal artery stenosisNocturia, hematuria, peripheral edema : renal parenchymal disease
26 Screening history Early onset HT, leg fatigue : aortic coarctation Proximal weakness, weight gain, diabetes : cushings diseaseParoxysmal headache, palpitations, sweating : pheochromocytomaHistory of drug intake, diet patternLethargy, recent weight gain, change in voice : hypothyroidismHeat intolerance, weight loss, palpitations : hyperthyroidism
27 Screening physical examination Large neck sizeMuscle weaknessAbdominal bruitEdema, signs of renal failureDisparity in arm BP, reduced or delayed leg pulsesTruncal obesity, striaeSweaty palms, pallor, tachycardiaSigns of endocrine disorder
28 Routine screening laboratory tests for hypertension : all patients Complete blood countBlood chemistries (sodium, potassium, creatinine, fasting glucose)Fasting lipid profileUrine analysis12 lead electrocardiogram
29 Laboratory work up for 20 HT DIAGNOSISSCREENINGCONFIRMATIONRenal parenchymal diseaseUrine analysis, BUN, creatinine, eGFRUSG, renal biopsyRenovascular diseaseDuplex renal USGMR angio, renal angiogramPrimary aldosteronismSerum potassium, plasma aldosterone/renin ratioCT scan of adrenalsSleep apneaSleep study with oxygen saturationPolysomnography
30 Laboratory work up DIAGNOSIS CONFIRMATION Cushings syndrome SCREENINGCONFIRMATIONCushings syndromePlasma, urine cortisolDexamethasone suppression testPhaeochromo-cytomaSpot urine metanephrineUrine/plasma catecholamines, CT abdomenCoarctation of aortachest x rayCT angiography, angiographyThyroid disorderAcromegalyTSH levelsGrowth hormone levelT3,T4 levels
32 "The Goal is to Get to Goal!” Hypertension-PLUS-Diabetes or Renal Disease< 140/90 mmHg< 130/80 mmHg
33 Lifestyle Modification Approximate SBP Reduction (range)Weight reduction5-20 mmHg/ 10 kg weight lossAdopt DASH eating plan8-14 mmHgDietary sodium reduction2-8 mmHgPhysical activity4-9 mmHgModeration of alcohol consumption2-4 mmHgWeight reduction + DASH is equivalent to 1-2 antihypertensivesJNC 7 Express. JAMA Sep 10; 290(10):1314
34 Impact of a 5 mmHg Reduction Overall ReductionStroke14%Coronary Heart Disease9%All Cause Mortality7%Hypertension 2003;289:
35 Essential hypertension in young Drug of choice in the absence of any compelling Indication : ARB’s or β blockers initiate with ARB’s (A) or β blockers (B) ↓ add CCB (C) or diuretics (D) add C or D accordingly resistant hypertension aldosterone receptor antagonists/α blockers/ clonidine
36 Renal parenchymal disease Most common secondary causeCommon causes : glomerulonephritis, diabetic nephropathyIncreased salt & fluid retention predominantly contribute to resistant HTTreat underlying cause1st choice : ACE-I/ARB + loop diureticGoal of < 130/80 achieved only in < 15%
39 Case selection for revascularization Surgical treatment of RAS does not always correct HTRAS may not contribute to HT in all patientsIdeal case :- renal FFR < 0.8- resistive index (controversial)Success (> 90%) : if fall in BNP is by > 30%
40 Renovascular disease Fibromuscular dysplasia - < 10% of renal artery stenosis- common in young females- affects the distal part of the renal artery- treatment : ACE-I/ARB + loop diureticAngioplasty
41 Renovascular disease Atherosclerotic disease : - 90 % of renal artery stenosis- ostioproximal part of artery involved- treatment : 2 or more drugs are often required: angioplasty + stenting in pts with- resistant HT, recurrent flash pulmonary edema, B/L RAS, U/L RAS in a single functioning kidney, worsening renal parameters
42 Primary aldosteronism Screening is recommended in the following situations :1) unprovoked unexplainable hypokalemia2) hypokalemia induced by diuretics, but resistant to correction3) unexplained resistant hypertension4) family h/o aldosteronism5) adrenal mass in CT or MRI
43 Primary aldosteronism Adrenal adenoma- surgical excision is the treatment of choice- corrects HT in 60% of patientAdrenal hyperplasia- aldosterone antagonist- surgical correction restores normal blood pressure in only 16% of patients
47 Obstructive sleep apnoea Weight lossContinuous positive airway pressureACE-I are the drug of choiceAldosterone antagonists have a specific roleTo look for pulmonary hypertension
48 Cushings syndrome HT is present in 70-90% of patients CV risk is substantially higher because of associated co morbiditiesTreatment- selective excision of the pituitary adenoma ; 70% cure rate- ectopic ACTH secretion : treatment of neoplasm- non surgical patients : metyrapone, ketoconazole
49 Pheochromocytoma α blockers : mainstay of treatment - phenoxybenzamine - prazosinβ blockers : useful in patients without elevated adrenalineResistant cases : add ACE-I, CCBAvoid diuretics
50 Definitive treatment : surgery to remove the tumour Pre-op preparation for 7-14 days : to control BP, deplete catecholamine stores and expand blood volumeMost cases are free of HT by 5 -7 years
51 Coarctation of aorta: indications for treatment SBP difference between upper and lower limb greater than 20 mmHg at restSignificant hypertension or blood pressure response to exercise (more than 2 SD greater than mean)LV dysfunction
52 Coarctation of aorta : choice of treatment Less than 1 yr1 – 10 yrs (35 kg)>35 kg children and adultsNative Co-AsurgeryInsufficient dataStentingRecurrent Co-AAngioplastyCareful follow up for residual hypertension is essential
55 Prevalence of HBP in different parts of India CityMen (%)Women (%)Jaipur Urban (1995)3033Jaipur Urban (2002)3637Mumbai Urban(1999)4445Mumbai (Executives)2728Thiruvananthapuram Urban (2000)31Haryana (Rural 1999)5Chennai (Urban 2007)23.217.1
57 Hypertension in the Elderly Ten Things You Need to Know:There is a dramatic increase in HTN prevalence with aging; by age 70 yrs, the majority of people have HTNIn older adults, HTN is characterized by an elevated SBP with normal or low DBP, due to age-associated stiffening of large arteries.HTN is a potent risk factor for CVD in the elderly.Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients yrs old with anti-HTN drug therapy though the effect on all-cause mortality has been modest.Although increases in the treatment and control of BP in older hypertensive adults have occurred over the past 2 decades, BP control rates remain suboptimal in the elderly.
58 Ten Things You Need to Know 6. Non-pharmacologic lifestyle measures should be encouraged in older adults, both to retard development of HTN and as adjunctive therapy in those with HTN.Although the specific BP at which antihypertensive therapy should be initiated in the elderly is unclear, a threshold of 140/90 mm Hg in persons yrs and a threshold SBP of 150 mm Hg in people age ≥80 yrs is reasonable.Diuretics, ACEI, angiotensin receptor blockers, calcium antagonists, and beta blockers have all shown benefit on CV outcomes in randomized trials among elderly cohorts: choice is dictated by efficacy, tolerability, comorbidities, and cost.Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated.The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects.
59 Measurement of Blood Pressure JNC VII Guidelines:Measurement of Blood PressureProvides information on response to Rx. May help improve adherence to Rx and evaluate “white-coat” HTNSelf-measurementIndicated for evaluation of “white-coat” HTN. Absence of 10–20% BP decrease during sleep indicates increased CVD riskAmbulatory BP monitoringTwo readings, 5 minutes apart, sitting in chairConfirm elevated reading in contralateral armIn-officeBrief DescriptionMethodJNC VII classification of hypertension is based on a mean of two appropriately performed readings as described above on two separate office visits. Blood pressure is classified as normal (<120/80 mm Hg), pre-hypertension ( /80-89 mm Hg), stage 1 hypertension ( /90-99 mm Hg), or stage 2 hypertension (>160/100 mm Hg).BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension, Rx=TreatmentSource: Chobanian AV et al. JAMA 2003;289:59
60 OSLER’S MANEUVER DIAGNOSIS The Osler's sign of pseudohypertension is an artificially and falsely elevated blood pressure reading obtained through sphygmomanometry due to arteriosclerotic, calcified blood vessels which do not physiologically compress with pressure.Because they do not compress with pressure normally, the blood pressure reading is higher than it truly ought to be.It can indicate pseudohypertension. It is also known as "Osler's maneuver".The sign is named for William Osler.
61 Hypertension in the Elderly 1. There is a dramatic increase in the prevalence of hypertension with aging; by age 70 years, the majority of people have hypertension.
62 High Blood Pressure*: Prevalence Increases with Age National Health and Nutrition Examination Survey (NHANES) III72%66%51%38%Hypertension* Prevalence (%)18%9%The National Health and Nutritional Examination Survey (NHANES) III was a large U.S. survey designed to estimate the prevalence of selected diseases and risk factors. The NHANES III sample was selected from 81 counties between 1988 and The prevalence of hypertension in a representative sample from NHANES III demonstrates that approximately 25% of the U.S. adult population has hypertension and its prevalence increases steadily with advancing age.3%18-2930-3940-4950-5960-6970-7980+Age*Hypertension defined as blood pressure >140/90 mmHg or treatmentSource: JNC-VI. Arch Intern Med 1997;157:62
63 National Health and Nutrition Examination Survey (NHANES) High Blood Pressure*: Prevalence Increases with AgeNational Health and Nutrition Examination Survey (NHANES)0.010.020.030.040.050.060.070.080.090.020-3435-4445-5455-6465-7475+Percent of PopulationMenWomenThe prevalence of hypertension increases with advancing age in men and women alike. Prior to age 55, hypertension is more prevalent in men. After age 55, hypertension is more prevalent in women.*High blood pressure defined as blood pressure 140/90 mmHg or treatmentSource: NHANES: , Source: NCHS and NHLBI
64 High Blood Pressure*: Prevalence in U.S. Adults National Health and Nutrition Examination Survey (NHANES)4540353025Prevalence of Hypertension*201510This slide shows the NHANES hypertension data by sex, race, and ethnicity. Comparison of data from 1988 to 1994 with that from 1999 to 2000 demonstrates that the rate of hypertension increased during this period. Increases were seen in all subpopulations studied: non-Hispanic black men and women, non-Hispanic white men and women, and Mexican-American men and women. The only group in which the increase was significant was non-Hispanic white women.Overall: The incidence of hypertension is increasing in the U.S.5Mexican- AmericanNon-Hispanic WhiteNon-Hispanic BlackFMAllF=Female, M=Male*High blood pressure defined as blood pressure >140/90 mmHg or treatmentSource: Fields LE et al. Hypertension 2004;44:64
65 Lifetime Risk* Starting at Age 55-65 Years High Blood Pressure:Lifetime Risk* Starting at Age YearsFramingham Heart StudyMenWomenRisk of hypertension (%)A total of 1,298 participants from the Framingham Heart Study that were between 55 and 65 years of age and free of hypertension at baseline ( ) were included in the study cohort. Data from long-term follow-up indicates that the lifetime risk of developing hypertension is about 90 percent. The residual life-time risk for developing hypertension (depicted above) was estimated for participants who reached the age of 65 free of hypertension.Years*Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHgSource: Vasan RS, et al. JAMA 2002; 287:
66 Change in Blood Pressure Levels in the United States Over Time National Health and Nutrition Examination Survey (NHANES)Blood pressure age-adjusted percentageThe prevalence of favorable blood pressure status (using only systolic and diastolic blood pressures) for 4 NHANES periods is shown here. The age-adjusted estimates for the 4 time periods were 21.6%, 28.8%, 48.9%, and 43.7%, respectively.Source: Ford, E. S. et al. Figure 2b, Circulation 2009;120: Reprinted with permission.
67 Mean Blood Pressure According to Age, Sex and Ethnic Group in U. S Mean Blood Pressure According to Age, Sex and Ethnic Group in U.S. Adults Chobanian N Engl J Med. 2007;357:789-96
68 SYSTOLIC HYPERTENSION-INDIA ISHCURES 52 MOHAN ET AL JAPI 2007
69 Hypertension in the Elderly 2. In older adults, hypertension is characterized by an elevated systolic blood pressure (BP) with normal or low diastolic BP, due to age-associated stiffening of the large arteries.
70 Joint Influences of SBP and Pulse Pressure on Coronary Heart Disease Adapted from Franklin Circulation 1999;100:354-60
71 Pathophysiology of Hypertension in the Elderly Multiple changes occur in arterial media with aging, including reduced elastin content with increases in non-distensible collagen and calcium (e.g. arterial stiffening).Age-associated arterial stiffening results in a gradual increase in systolic BP and a decrease in diastolic BP.Flow-mediated arterial dilation, primarily mediated by endothelium-derived nitric oxide, declines markedly with aging.Neurohormonal profile of older hypertensive adults characterized by increased plasma norepinephrine, low renin, and low aldosterone levels.Many so-called “normal aging changes” in arterial structure and function are blunted/absent in populations not chronically exposed to high sodium/high calorie diets, low physical activity levels, and high rates of obesity.
72 Conceptual Framework for CV Adaptations to Arterial Stiffening Occurring with Aging CBF indicates coronary blood flow; DBP, diastolic blood pressure; EF, ejection fraction; LA, left atrial; LV, left ventricular; SBP, systolic blood pressure; ↑, increased; and ↓, decreased.
73 Hypertension in the Elderly 3. Hypertension is a potent risk factor for cardiovascular (CV) disease in the elderly.
74 Coronary Heart Disease Rates by SBP and Age Adapted from Lewington et al. Lancet. 2002; 360:120 mm Hg140 mm Hg160 mm Hg180 mm Hg256128Coronary Heart DiseaseMortality6432168For every 20 mm Hg systolic or 10 mm Hg diastolic increase in BP, there is a doubling of mortality from both ischemic heart disease and stroke.Data from observational studies involving more than 1million individuals have indicated that death from both ischemic heart disease and stroke increases progressively and log linearly from BP levels as low as 115 mm Hg systolic and 75 mm Hg diastolic upward. The increased risks are present in all age groups ranging from 40 to 89 years old.42150-5960-6970-7980-8940-49Age
75 Hypertension as a Risk Factor in the Elderly In older adults, hypertension (HTN) is the most prevalent modifiable CV risk factor: antecedent HTN is estimated in:~70% of patients with incident myocardial infarctions~77% of patients with incident strokes~74% with chronic heart failure~90% with acute aortic syndrome30% to 40% with atrial fibrillationHTN is also a major risk factor for conditions directly influencing CV risk in the elderly:DiabetesMetabolic syndromeChronic kidney diseaseThe number of deaths attributable to HTN in the U.S. rose 56% between 1995 and 2005, largely reflecting the increasing number of older Americans and high prevalence of HTN in the elderly.
76 Hypertension in the Elderly 4. Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients years old with anti-hypertensive drug therapy though the effect on all-cause mortality has been modest. In HYVET, antihypertensive therapy reduced all-cause mortality in people ≥80 years old by 21%.
77 Randomized Hypertension in the Very Elderly Trial (HYVET) In 3,845 patients ≥80 years old with SBP ≥160 mm Hg, at 1.8-year follow-up, those randomized to indapamide vs placebo had:30% nonsignificant decrease in fatal/nonfatal stroke39% significant decrease in fatal stroke21% significant decrease in all-cause mortality23% insignificant decrease in CV death64% significant decrease in heart failureHYVET: Treatment of hypertension in patients 80 years of age or older.N Engl J Med. 2008;358:
78 Hypertension in the Elderly 5. Although increases in the treatment and control of BP in older hypertensive adults have occurred over the past 2 decades, BP control rates remain suboptimal in the elderly.
79 Extent of Awareness, Treatment and Control of High Blood Pressure by Age NHANES: 2005-2006
80 Frequency of Untreated Hypertension According to Subtype and Age Chobanian N Engl J Med. 2007;357:789-96
81 Hypertension in the Elderly 6. Non-pharmacologic lifestyle measures should be encouraged in older adults, both to retard development of hypertension and as adjunctive therapy in those with hypertension.
82 Non-Pharmacologic Lifestyle Measures Shown Beneficial in Elderly Hypertensive Subjects Regular physical activitySodium restrictionWeight controlSmoking cessationAvoidance of excessive alcohol intake
83 Hypertension in the Elderly Although the specific BP at which antihypertensive therapy should be initiated in the elderly is unclear, a threshold of 140/90 mm Hg in persons years and a threshold systolic BP of 150 mm Hg in people age 80 years and older is reasonable.
84 Risk of Adverse Outcomes Among Elderly CAD Patients by Age and BP Denardo et al. Am J Med 123: , 2010BP nadirs indicate BP’s with lowest hazard ratio at each age.
85 Hypertension in the Elderly Diuretics, ACE-inhibitors, angiotensin receptor blockers, calcium antagonists, and beta blockers have all shown benefit on CV outcomes in randomized trials among elderly cohorts.The choice of specific agents is dictated by efficacy, tolerability, presence of specific comorbidities, and cost.
86 Compelling Indications for Drug Classes JNC VII Guidelines:Compelling Indications for Drug ClassesClinical-Trial BasisCompelling IndicationALLHAT, HOPE, ANBP2, LIFE, CONVINCEHigh CAD RiskACC/AHA Post-MI Guidelines, BHAT, SAVE, Capricorn, EPHESUSPost-MIMERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALESInitial Therapy OptionsDiuretic, BB, ACE-I, CCBBB, ACE-I, Aldo ANTDiuretic, BB, ACE-I, ARB, Aldo ANTHeart FailureDiabetes MellitusDiuretic, BB, ACE-I, ARB, CCBNKF-ADA Guideline, UKPDS, ALLHATChronic Kidney DiseaseCompelling indications refer to treatments that have demonstrated efficacy for a particular patient population in large randomized controlled trials.ACE-I, ARBNKF Guidelines, Captopril Trial, RENAAL, IDNT, REIN, AASKRecurrent Stroke PreventionDiuretic, ACE-IPROGRESSACE-I=Angiotensin converting enzyme inhibitor, Aldo ANT=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial infarctionSource: Chobanian AV et al. JAMA 2003;289:86
87 Antihypertensive Treatment-Related Side Effects The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects such as:Electrolyte disturbancesRenal dysfunctionExcessive orthostatic BP decline
88 Hypertension in the Elderly Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated.
89 Physiologic Changes with Aging: Potential to Influence Antihypertensive Drug Pharmacokinetics Absorption and distribution of antihypertensive drugs are unpredictable in the elderly
90 Half life of most antihypertensive drugs is increased in the elderly Physiologic Changes with Aging: Potential to Influence Antihypertensive Drug PharmacokineticsContinuedHalf life of most antihypertensive drugs is increased in the elderly
91 Percent of Elderly People in Outcomes Trials Taking ≥Two Antihypertensive Medications (mean SBP achieved)(Mean SBP achieved)
93 Blood Pressure Lowering Therapy Evidence: Primary Prevention Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study9,193 high-risk hypertensive* patients with LVH randomized to losartan (100 mg) or atenolol (100 mg) for 5 yearsAn ARB provides greater efficacy in patients with LVH1612AtenololProportion with CV death, MI, or stroke (%)8Losartan413% RRR, P=0.021In the LIFE trial, treatment with once daily losartan (compared to atenolol) in adults with essential hypertension and electrocardiographic evidence of left ventricular hypertrophy resulted in a significant decrease in the primary composite endpoint of death, MI, or stroke without a significant blood pressure difference between the two arms. This difference was driven predominantly by a statistically significant decrease in stroke, with no statistically significant difference in death from cardiovascular disease and myocardial infarction. There were also fewer new cases of diabetes mellitus in the losartan arm.Overall: In the LIFE trial, an ARB was more effective than a beta blocker in reducing CV risk in hypertensive patients with evidence of LVH.612182430364248546066Study MonthARB=Angiotensin receptor blocker, CV=Cardiovascular, DBP=Diastolic blood pressure, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, SBP=Systolic blood pressure*Defined by SBP= mmHg or DBP= mmHgSource: Dahlöf B et al. Lancet 2002;359: Adapted with permission.93
94 Blood Pressure Lowering Therapy Evidence: Primary Prevention Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA)19,342 high-risk hypertensive patients with 3 additional CV risk factors randomized to amlodipine (10 mg) & perindopril (8 mg) or atenolol (100 mg) & bendroflumethiazide (2.5 mg) for 5.5 yearsBoth BP lowering regimens provide similar efficacy6Atenolol-based regimen4Nonfatal MI and fatal CHD (%)Amlodipine-based regimen2RRR = 10%, P =The goal of the ASCOT-BPLA study was to compare two antihypertensive regimens, one the combination of a diuretic and beta-blocker and the other the combination of a calcium channel blocker and ACE inhibitor, in patients with hypertension and at least 3 additional cardiovascular risk factors. The primary end point (by an intention to treat analysis) was the incidence of non-fatal myocardial infarction (including silent myocardial infarction) and fatal coronary heart disease.The study was stopped prematurely after 5.5 years of median follow-up. There was no statistically significant difference between the two treatment regimens with respect to the primary end point, nor the incidence of fatal and non-fatal stroke, total cardiovascular events and procedures, and all-cause mortality. Among patients receiving the calcium channel blocker and ACE inhibitor regimen, however, there was a lower incidence of diabetes mellitus.123456Time since randomization (years)BP=Blood pressure, CV=Cardiovascular, CHD=Coronary heart disease, MI=Myocardial infarctionSource: Dahlöf B et al. Figure 3, Lancet 2005;366:Adapted with permission.94
95 Blood Pressure Lowering Therapy Evidence: Primary Prevention Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA)Amlodipine-based rate/1000 patient yearsAtenolol-based rate/1000 patient yearsAmlodipine-based betterAtenolol-based better<0.05<0.01<0.00010.001<0.001NSSecondary endpointsNonfatal MI + fatal CHDTotal coronary endpointTotal CV events/proceduresAll-cause mortalityCV mortalityFatal/nonfatal strokeFatal/nonfatal HFPIn the ASCOT-BPLA study, the amlodopine-based regimen did appear more efficacious in lowering several secondary endpoints including nonfatal MI plus fatal CHD (silent myocardial infarctions were excluded in this analysis), total coronary endpoints, total CV events and procedures, all-cause mortality, cardiovascular mortality, and fatal and nonfatal stroke. There was no difference in fatal and nonfatal heart failure.0.500.701.001.452.00An amlodopine-based regimen appears to reduce the rate of other CV eventsCHD=Coronary heart disease, CV=Cardiovascular, HF=Heart failure, MI=Myocardial infarctionSource: Dahlöf B et al. Figure 4, Lancet 2005;366: Reprinted with permission.
96 Blood Pressure Lowering Therapy Evidence: Primary Prevention Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH)11,506 high-risk hypertensive patients randomized to benazepril (40 mg) and amlodipine (10 mg) or benazepril (40 mg) and HCTZ (25 mg) for 36 months*An amlodipine-based regimen provides greater benefit0.160.140.120.100.080.060.040.020.00Composite of CV death, MI, stroke, hospitalization for angina, sudden cardiac arrest, and coronary revascularization (%)Benazepril/HCTZBenazepril/AmlodipineThe ACCOMPLISH trial sought to evaluate the effect of two antihypertensive treatment regimens (one the combination of benazepril and HCTZ and the other the combination of benazepril and amlodipine) in high-risk hypertensive patients. The trial was stopped early (pre-specified stopping rule) because the blood pressure regimen of benazepril/amlodipine showed superiority to benazepril/HCTZ in reducing the primary endpoint of CV death, myocardial infarction, hospitalization for angina, sudden cardiac arrest, and coronary revascularization. For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio for benazaepril/amlodipine was 0.79 (95% CI, 0.67 to 0.92; P=0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group.20% RRR, HR=0.80, P=0.0002Time to first cardiovascular event (days)*The study was prematurely stoppedSource: Jamerson K et al. NEJM 2008;359:
97 Blood Pressure Lowering Therapy Evidence: Primary Prevention Hypertension in the Very Elderly (HYVET) Trial3,845 patients >80 years with SBP >160 mm Hg randomized to treatment to indapamide (1.5 mg) and perindopril (2-4 mg if needed) vs. placebo for 2 yearsBlood pressure control in patients >80 years of age provides benefitRate/1000 patient years (%)P=0.06P=0.05P=0.02P<0.001(Primary end point)The HYVET trial enrolled 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more. Patients were randomly assigned to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting–enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.At 2 years, 25.8%, 23.9%, and 49.5% of patients in the active-treatment group were receiving indapamide alone, indapamide and perindopril (2 mg), and indapamide and perindopril (4 mg), respectively; 14.2%, 13.4%, and 71.8% of patients in the placebo group, respectively, were receiving the corresponding placebos.At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], –1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, –1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were also reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).CV=Cardiovascular, CVA=StrokeSource: Beckett NS et al. NEJM 2008;358:
98 Blood Pressure Lowering Therapy Evidence: Secondary Prevention International Verapamil-Trandolapril Study (INVEST)22,576 patients with HTN and CAD randomized to a BP lowering strategy with verapamil SR (240 mg) or atenolol (50 mg) for 2.7 yearsBoth a CAS and NCAS provide similar efficacy6121824364854426030Calcium antagonist strategy (CAS)*Non-calcium antagonist strategy (NCAS)*Incidence of death, MI, or strokeRR=0.98, P=0.57The goal of the INVEST study was to compare morbidity and mortality in a randomized, open label, blinded end point study of patients with hypertension and coronary artery disease treated with a calcium antagonist strategy (CAS) or a non–calcium antagonist strategy (NCAS). The CAS consisted of sustained release verapamil and the NCAS consisted of atenolol. By the end of the study, approximately half of the patients in each group were also taking trandolapril and hydrochlorothiazide to achieve blood pressure goals according to JNC VI. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment.The primary outcome was first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke. At 24 months, there were no statistical differences between the treatment strategies and the primary outcome. A total of 72% of CAS and 71% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. Overall, the treatment strategy of verapamil-trandolapril was as clinically effective as the atenolol-hydrochlorothiazide strategy in hypertensive patients with coronary artery disease.Overall: In CAD patients with hypertension, multiple agents will likely be needed to control BP. Starting with a calcium channel blocker versus a beta blocker does not impact the composite event rate of death, MI and stroke.MonthsBP=Blood pressure, HTN=Hypertension, MI=Myocardial infarction*Trandolapril (up to 4 mg) was added in those with diabetes mellitus, chronic kidney disease, or heart failureSource: Pepine CJ et al. JAMA 2003;290:98
99 Hypertension in the Elderly The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects.
100 Target Blood Pressure Goals in the Elderly Although the optimal BP treatment goal in the elderly has not been determined, a therapeutic target of <140/90 mm Hg in persons aged years and a SBP of mm Hg, if tolerated, in persons aged ≥80 years is reasonable.
101 Hypertension in the Elderly Summary and ConclusionsVery highly prevalentMajor, treatable risk factor for CV diseaseTypically, SBP elevation with low DBP (“stiff arteries”)Many comorbidities make management challengingLife style modification useful, even with drug therapyBegin with low drug doses and titrate drugs slowlyFor those ≥80 years, mm Hg is acceptable SBP goal
102 HBP in elderly- takeaways 1.Confirm BP- Serial readings2.Secondary causes – Renal Artery Stenosis3.Postural BP4.Pseudohypertension – osler’s maneuver5.Systolic/ Diastolic / Combined/ increased PP6.To rule out AR in increased PP7.ISH – Diuretics8.Increased PP – ACEI / Calcium Blockers (Small dose)9.Low dose – gradual increase10.Comorbidities/ Co existing drug / electrolyte problems