HYPERTENSION IN GERIATRIC POPULATIONHanna Kujawska-DaneckaDepartment of Internal Medicine, Geriatrics and Clinical Toxicology, Medical University of Gdask

Hypertensionone of the in aging diseasesan estimated 6070% of population of persons > 60 years suffers from hypertension

NHANES III Studyin the U.S. the hypertension prevalence in population > 60 years is 65,4%

Gdask Research 1999 (team work conducted by prof. Krupa-Wojciechowska) in a population > 64 years hypertensionamong women 81%, among men 66,1%

NATPOL PLUS Study 2002 (prof. T. Zdrojewski)in a population > 64 years 59%

Forms of hypertension in the elderlyisolated systolic hypertension (IHS): 62,867,4% caused by an age-related increase in arterial stiffness, more common among womensystolic-diastolic hypertension: 27,630,3%diastolic hypertension sporadically

PathophysiologyThe hypertension in elderly patients is a consequence of the aging processes of cardiovascular system, esp. the age-related increase in arterial stiffness.

Changes in arteries

walls stiffeningdecrease in distension abilities and compliance of arteries (esp. elastic arteries, e.g. the aorta)wall thickening of peripheral arterieshigher vascular wall reactivity to vasoconstrictive factors

Mediaincrease in muscular layer thickness (higher proliferation of vessels smooth muscles in the elderly)change of interstitials composition: increase in the amount of dermatan and heparan; hyaluronan decrease (glycosaminoglycans)decrease and degeneration of elastin fibersincrease in collagen deposition and changes in the cross-linking of collagen

structural changes of the endothelium: increased permeability, laminar flow dysfunction, increased lipids depositiondisturbance of the secretion balance between vasoconstrictive and vasodilative factors (cytokines produced during chronic inflammatory processes lead to the impairment of nitric oxide and prostacyclin synthesis in the endothelium; increased synthesis of endothelin and other vasoconstrictive factors)Intima

Telomere hypothesis of cell agingtelomerase deficiencytelomere shorteningfreeradicalshomocysteinevessels stiffening

Other aging processeshigher sympathetic system activity NA muscular layer hypertrophyvessel walls restructuringwith simultaneous decrease in density and sensitivity of beta-receptors and proper functionality of alpha-receptors vasoconstrictive effectdecrease in sensitivity of beta-receptors stimulation of sympathetic system due to physical effort does not cause an evident increase in heart rate and its contractility

disturbance of balance between the sympathetic and parasympathetic systems patients non dippers no physiologic blood pressure decrease during night hours impaired renal function reduced kidney weight, nephrons amount and filtration surface area lower renal flow and glomerular filtrationimpaired sensitivity of baroreceptors (reset to a higher value of blood pressure) due to changes in vessels structure orthostatic hypotonia, higher variability of blood pressure (organic complications!), oversensitivity to vasodilative drugs

Definition or when one should recognize hypertension 140/90 mmHg

Recognition criteria of hypertension are identical in each age group, even in the population > 65 years.In order to recognize hypertension it is essential to take numerous BP measurements. Due to white-coat hypertension, more frequent in the elderly, 24-h ambulatory BP monitoring (ABPM) or multiple home-based BP measurements may also be helpful.

BP values for defining hypertension depending on measurement method (acc. to ESH/ESC 2013/PTNT 2011)

SBPDBPAt doctors14090ABPM13080 day13585 night12070At home13085

White coat - hypertensionsignificant differences in BP values measured at home and at doctors

suspition of hypertension resistant to pharmacological treatment

lack of systemic changes typical for hypertension

accurate BP values in self-control

hypotension in course of pharmacotherapy

The aim of treatmentrecommended BP values are 140/90 150/90 mmHg,- in patients 80. years provided, that they are in good general condition; decreasing BP values under 150/90 mmHg should be very carful achievement of the therapy goal should be stretched over a long period of time (longer than by younger patients), up to several months in some casesit is useful to set some staging posts of the therapy, e.g. reaching the BP values of 160/90 mmHg such symptoms as: ill-being, vertigo, balance disorders, vision disorders (e.g. scotoma), confusion decreasing the dosage or changing the group of antihypertensivesthe higher initial BP values are, the more carefully they should be reduced

Treatment benefitsPatietns under and over 65 years proportionally similar benefit from hypertension treatment (similar reduction of cardiovascular events risk) According to HYVETrial: the antyhypertensive treatment in patients >80 (without serious comorbidities) should be started if SBP is > 160 mmHg and SBP values should not exceed 150 mmHg Due to differencies of general condition of elderly patients the hypertension therapy should be considered indiyidually and dynamics of BP decrease should be always graduall and strictly monitored Trials results suggest, that the antyhypertensive therapy should be started with long-acting thiazide-like diuretic and sequently ACEI.

Treatment benefitsIsolated systolic hypertension

over 50% of cases of hypertension in the elderly (main arteries stiffness)SBP value and pulse pressure are crucial prognostic factors of hypertension complications in the elderlycardiovascular mortality rate is almost three times higher as compared to other hypertension formsfirst-line treatment Calcium antagonists and diuretics

Meta-analysis (SHEP, Syst-Eur, Syst-China, HEP, MRC-2, EWPHE)

14 825 elderly persons with ISH

reduction in:all-cause mortality rate by 14%cardiovascular mortality rate by 20%fatal and non-fatal cardiovascular events rate by 20%stroke rate by 33%

Hypertension is one of the primary factors leading to dementia in the elderly (vasogenic dementia as well as Alzheimers disease)patients with untreated hypertension may develop dementia in advanced ageAlzheimers disease: cerebral microflow disturbance due to persisting increased arterial blood pressure (collagen deposition and thickening of basement membrane of capillaries slowing down the pace of transporting nutritious substances into neurons as well as of elimination of toxic waste productsdementia can be a common consequence of a stroke (hypertension complications); patients with hypertension > 84 years tend to have ten times higher incidence of stroke than patients aged 55-64

Dementia

Dementia (cont.)

Syst-Eur Study: 4700 patients > 60 years, treated for ISH (nitrendipine)

diagnosed dementia by 50% (Alzheimers and vasogenic types)

PROGRESS Study6150 patients with/without hypertension, history data: ischemic stroke or TIA (perindopril /+indapamide);

dementia rate by 34% stroke rate by 28%

When to start treatment?The decision of beginning of treatment should be based on BP values, risk factors, systemic complications and co-morbidities

According to recommendations of ESH/ESC 2013, in elderly the therapy should be started if BP is over 160 mmHg, pharmacotherapy can be also considered (at least in patients < 80 years) also whan BP values are 140-159 mmHg, provided, that antyhypertensive treatment is well tolerated

Risk factors

age: M > 55 yearsF > 65 yearsmale sexsmoking lipid disorders (CH total > 190mg/dl; LDL > 115mg/dl; HDL M < 40mg/dl F < 46mg/dl; TG > 150mg/dl)family history premature cardiovascular complications: M < 55 years F < 65 yearsoverweight (BMI 30kg/m2)fasting glucose 100 mg/dl or impared glucose tolerance in OGTT

abdominal obesity (waist size M > 102 cm; F > 88 cm)

At least 2 risk factors are usually found in the elderly.

Organic complicationsleft ventricle hypertrophy (Sokolov-Lyons criterion > 35 mm and RaVL> 1,1 mV))left ventricle mass index: M 115 F 95 g/m2USG of carotid artery: thickening of intima-media complex 0,9 mm or presence of atheromatous plaqueankle-brachial index (ABI) < 0,9pulse pressure (in the elderly) > 60 mmHgcarotid-femoral pulse wave velocity > 10 m/schronic kidney disease (eGFR 30-60 ml/min/1,73m2) a slight increase of creatinine level: M: 115133 mol/l (1,3-1,5 mg/dl) F: 107124 mol/l (1,2-1,4)Microalbuminuria 30300 mg/day or albumin/creatinine ratio (M 22 mg/g; F 31 mg/g)

Coexisting diseasesDiabetes or metabolic syndromecerebral circulation disturbances (stroke, TIA)heart disease (myocardial infarction, coronary artery disease, PTCA Percutaneous Transluminal Coronary Angioplasty,CABG Coronary Artery Bypass Graft)heart failure renal failureperipheral vascular diseaseadvanced retinopathy (effusions, petechias, papilloedema)

Pretreatment diagnostic procedure

blood cell countrenal profile (creatinine, electrolytes)glucose, uric acid, lipidsurine analysis (proteinuria)ECGorthostatic hypotonia testalternatively TSH thyrotropin (secondary form of hypertension related to hypothyreosis)recommended diagnostic tests: fundus of the eye, chest X-rays, echocardiography, USG of kidneys and carotid arteries, microalbuminuria, Calcium level, Oral Glucose Tolerance Test, ankle-brachial index, carotid-femoral pulse wave velocity, Epworth Sleepiness Scale

Non-pharmacological treatmentNon-pharmacological treatment significantly results in: BP valuereduction in cardiovascular complicationslipid profile improvement hyperinsulinism

sodium intake reduction up to 6 g/day (min. 5-weeks diet necessary for a hypotensive effect) other advantages: LV hypertrophy, proteinuria, calciuria osteoporosis and the risk of calcium nephrolithiasis, an improvement of antyhypertensive treatmentnormalization of body mass the most effective non-pharmacological method of BP reduction, leading to reduction of other risk factors (obesity, hyperinsulinism, hyperlipidemia) These are the two best statistically proved methods of BP reduction, esp. when practiced simultaneously

Non-pharmacological treatment cont.

diet beneficial: fruits (esp. citrus), vegetables, unsaturated fatty acids, esp. omega-3 fatty acids (saltwater fish); Dietary Approaches to Stop Hypertension (DASH)non-beneficial: saturated fatty acids, high intake of proteins and carbohydratesPotassium suplementation 60 mmol/day; additionally it is crucial in the stroke prevention in the elderlyalcohol has a hypertensive effect, however small amounts may be beneficial; by persons of 50-74 years this effect is stronger than in younger populationNotice: in the elderly impaired hepatic metabolism, smaller distribution volume, drugs interactionstobbacco hypertensively i atherogenically

physical effort isotonic exercises: walking, gardening, cycling, swimming; initially 1520 min. 23 times a week, then gradual progress up to 3045 min. most day of a weekmoderate physical effort < 60% of maximum effort(easy breathing, HR = 220 age)

Pharmacological treatmentThere 5 groups of antihypertensive treatment, which may be used in monotherapy as well as in combined therapy and their effect on prognosis is proven

thiazid and thiazid-like diuretics

B-blockers (vasodilatative preffered)

Calcium chanel blockers

ACE inhibitors

AT1 receptors anatagonists

First line treatment the therapeutic decision is based on risk factors, co-morbidities, systemic complication, hypertension type, other drugs taken. In elderly patients the first line treatment are:

diuretic esp. thiazides and thiazide-like (ALLHAT, ADVANCE, HYVET, PATS); in the age group >80 indapamid is recomended Dihydropyridine calcium channel antagonists esp. effective in ISH

NOTICE:diabetesGouthyperkalcemia DIURETICSthiazides loop diureticsPotassium-sparing diuretics(spironolaktone is recommended as 4. line treatment in resistent hypertension)In most clinical studies diuretics form the basis for antihypertensive treatment. Thiazides enhance the hypotensive effect of all primary hypotensive drugs therefore they seem a perfect component of a combined therapy.CHF, RFcontraindications: decompensated RFNOTICE:hyperkalemiaNOTICE:hipokalemia

indapamide reduction of LV hypertophysmaller metabolic influencesmaller hipokalemia

INDICATIONS: ISH, peripheral vascular disease, diabetes, renal failure, CAD, COPD chronic obstructive pulmonary disease ( pulmonary hypertension)

NOTICE: headaches, flush, ankle edema, tachycardia, constipation, CHF exacerbation

CONTRAINDICATIONS: short-acting dihydropyridine derivatives are contraindicated in long-term therapy due to high fluctuations of BP values and adrenergic stimulation ischemia and hypertrophy of LV

chronotropic negativeinotropic negativeNOTICE: CHF, bradycardia, heart blocks (atrioventricular blocks), esp. combined with z -blockers

ACEIhypotensive effecttarget organ effects:endothelium function improvementcoronary circulation and coronary reserve improvementregression of LV hypertrophy and remodelling process pressure in renal glomerule delayed development of nephropathy

esp. effective when combined with drugs increasing activity of renin-angiotensin-aldosterone system (diuretics)

ACEI cont.INDICATIONS: hypertension, CAD (esp. after myocardial infarction), CHF, diabetes, nephropathy (incl. diabetic), after stroke (secondary prevention)

NOTICE: hiperkalemia, orthostatic hypotonia, renal artery stenosis (of the only kidney or bilateral)

Antagonici receptora AT1 (losartan, telmisartan, valsartan, kandesartan)

indication: hypertension + diabetes, LV hypertrophy, chronic kindey disease, after a stroke, they are alternative for ACEI in cases of intolerance due to a cough

Contradictions: renal artery stenosis (of the only kidney or bilateral)

AT1 antagonists may be used in combined antyhypertensive therapy, also with ACEI (additive cardio- and nephro- protective action). However, as ONTARGET study (telmisartan\ ramipril) has shown, dubled blockage of RAA system is very effective in protection of cardiovascular events, is also connected with high prevalence renal complications (hyperkaliemia, renal function deterioration)

Currently this drug group is not regarded as a first-line treatment option in the elderly as a monotherapy of non-complicated hypertension. However, B-blockers are important element of antyhypertensive therapy in cases combined with diabetes, other cardiovascular diseases or cardiovascular complications of hypertension (esp. vasodilatative B-blokers)

INDICATIONS: hypertension + CAD, CHF, heart rhythm disturbances, diabetes, vasorenal hypertension

BETA-BLOCKERSvasodilatativecardioselectivekarwedilolnebiwololceliprololmetoprololbisoprololbetaxolole

NOTICE: COPD, asthma, peripheral vascular disease, severe decompensated CHF, masking hypoglycaemia symptoms, influence on carbohydrate and fat metabolism, bradycardia and heart blocks, sleep disorder and depression(lipophilic drugs: metoprolol, propranolol), metabolism disorder ( HDL, TG, glucose tolerance i insulin sensitivity)

Alpha-blockers (doxazosin)

This drug group can accelerate the development of heart failure(ALLHAT study) currently not used in monotherapy. Use carefully by patients with symptomatic heart failure, after extensive myocardial infarction, and asymptomatic LV function impairment

INDICATIONS: in combined antihypertensive therapy, esp. by coexisting diabetes, renal failure, obliterative atheromatosis, lipid disorders NOTICE: orthostatic hypotonia, vertigo, astenia, headaches, tachycardia

NOTICE: coegxisting benign prostatae hypertophy is not a indication for indywidualization antyhypertensive therapy!

Clinical symptoms of BPH (benign prostatae hypertophy) are present in 30% of men > 65 years, in this same group of elderly 2/3 suffer from hypertension

doxazosine alfa1-adrenolitic non-uroselective, it is a hypertensive drug of 3-4 line treatment in cases of resistent hypertension requiring combined therapy

tamsulozine uroselective alfa1-adrenolitic urologist makes the decision about the treatment, in cases of unsuccesful antyhypertensive treatment tamsulozine may be changed into doxazosine

Antihypertensive therapystart with small doses; dosage increase significantly extended in timecombined therapy (lower risk of side effects, inhibition of compensatory reactions, various mechanisms of action) long-acting drugs are preferred (24-h BP values fluctuations can lead to LV hypertrophy, heart rhythm disturbances and hypotonia; better control of BP values in the early hours of the day, better cooperation with a patient, fewer pills)weaker hepatic metabolism and renal functionhomeostatic mechanisms disturbances (decline of a baroreceptor mechanism orthostatic hypotonia)coexisting diseases (diabetes, CAD, CHF)intake of many different group of drugs (drug interactions, polypragmasy)inform patients accurately about the diseases character and principles of their therapy (good patients compliance)

Therapy failures (reasons)secondary hypertensioncoexisting diseasesdrugs (NSAID, steroids)improper drugs intake (e.g. therapy breaks when BP returns to normal)polypragmasy (incl. improper combinations of antihypertensive drugs)white-coat hypertensiontoo expensive drugs

Orthostatic hypotonia SBP by at least 20 mmHg, often along with DBP by min. 10 mmHg after postural change (from recumbent into standing). We measure BP after a patient has been standing quietly for at least 1 minutes (and then after 3 minutes) particularly common in the elderly with hypertension15 to 20% of community-dwelling and about 50% of institutionalized elderly persons 10% of physically fit and > 50% of infirm persons > 65 years

Pathomechanism HR i stroke volume (beta-adrenergic stimulation)Postural changelower limbs blood hold venous return stroke volume carotid sinus flow(baroreceptors stimulation)

Orthostatic hypotonia effectssudden cerebral circulation decline ( stroke risk)deterioration in coronary circulation (myocardial ischaemia / infarction)injuries, sometimes life-threatening (as a consequence of vertigo, balance disturbances)psychological trauma, anxiety of physical activity, leading to infirmness

symptoms: vertigo, balance disturbances, dizziness, faintness, falls and trauma, vision disorders, TIA, stenocardia, nausea

Predisposing factorsvenous insuficiency (obesity, lower limbs varices, sedentary life style, aging processes in veins walls)disturbances of BP autonomic control (impairment of a baroreceptor mechanism, lesser variability of HR, a reduction in density and sensitivity of beta-receptors, peripheral neuropathy)impaired cerebral circulation and cerebral vessels autoregulationdehydration, low-sodium dietdrugs (diuretics, alfa-blockers, nitrates, anti-Parkinsonic, phenothiazines, tricyclic antidepressants)

Managementslow postural changeraised-waist clothespressure stockings for patients with venous insufficiencycareful implementation and dosage of drugs which can intensify hypotoniaorthostatic hypotonia test after each change of dosage or implementation of a new drugalternatively consider pharmacological treatment (fludrocortisone, caffeine, ephedrine)

SBP by at least 20 mmHg in 2 hours after meal or < 90 mmHg, when initial BP value > 100 mmHg2436% of institutionalized elderly persons often asymptomatic, however can also lead to: vertigo, balance disturbances, faintness and falls, TIA, nausea, stenocardiapathomechanism: blood accumulation in visceral circulation, activity of vasoactive intestinal hormones, impaired baroreceptor mechanism and adrenergic heart responsePostprandial hypotension

every sixth elderly patient with hypertension

Causesrenal diseases (renal artery stenosis, a kidney disorder e.g. polycystic kidney disease, glomerulonephritis, chronic pyelonephritis)endocrine disorder (eg, Cushing's syndrome, hypothyreosis, primary aldosteronism, pheochromocytoma)drugs (steroids, NSAID, B2-agents)alcohol abuse

Secondary hypertension should be always considered in cases of sudden development of hypertension, drug-resistant hypertension and fast increasing renal failure.Secondary hypertension

the most common form of secondary hypertension due to atherosclerosis (among more rare causes: fibromuscular dysplasia of renal arteries, renal artery aneurysm, renal artery embolism, outside pressure)mainly smoking menoften accompanied by symptoms of advanced atherosclerosis of other vessels (coronary, carotid, of lower limbs, significant LV hypertrophy, heart failure

Clinical picture: sudden appearance of hypertension after the age of 60,severe course and treatment resistance fast development of renal failure after applying ACEIintensification of hypokalemia after applying diureticsvascular murmur in epigastric and umbilical regions, as well as other arteriesrecurrent pulmonary oedemaVasorenal hypertension

Diagnosticsabdominal USG and Doppler USG of renal arteriesrenal arteries angiographyspiral CT of renal arteries preferred method

Treatmentpercoutaneous angioplasty results are rather unsatisfactory in the elderly patients with atheromatous renal artery sclerosis, ca. 10% cured, 40% milder course, stent implantation gives better resultssurgery treatment (when changes are very advanced and bilateral) good results: 8090% cured or improved; no studies in the elderly population howevernon-invasive treatment (by patients not qualifying for surgery due to contraindications and poor general condition)

Recommended drugs: Calcium channel blockers, ACEI (caution in cases of bilateral stenosis), diuretics, beta-blockers

Renal parenchymatous hypertensionHistory data: renal disease (impairment of renal sodium excertion intravascular volume, cardiac output, RAA-axis stimulation and sympathetic system)diagnosis: history, urinanalysis (specific weight, proteinuria, erythrocyturia, leucocyturia), renal USGtreatment: restrictions of sodium and proteins intake, ACEI (up to creatinine level of 4 mg/dl), Calcium channel blockers, loop diuretics, imidazoline receptors antagonistsreference values 130/85 mmHg

Hypothyreosisin Andersons studies 35% of patients > 60 years with secondary hypertension (4429 persons with hypertension examined for secondary hypertension)25% of patients with hypothyreosis suffer from hypertensioncause: stimulation of sympathetic system (in elder age the density of beta-receptors decreases while the sensitivity of alpha-receptors increases vasoconstriction and increase of peripheral resistance)hypothyreosis in the elderly is difficult to diagnose only ca. 30% of patients present typical symptomshypothyreosis a great masquerader: usually recognised as depression, dementia, treatment-resistant heart failurediagnostics: THS, fT4, fT3substitutive treatment of hypothyreosis leads to normalization of BP values in ca. 3050% of cases

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