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Up date on hypertension Doc. dr Amra Macić - Džanković Two or more drugs/combination therapy are usually needed to reach the target BP (below 140/90mmHg, but not below 120mmHg) It has been proven that : ACE inhibitors cardiovascular protective and ARB nephroprotective Blocade of the renin-angiotensin system seems to be an appropriate choice even though there is no concensus on the “drug of choice” for all patients An important risk factor of hypertension and stroke in later adult life of women Starting treatment/ 140/90mmHg in women with gestational hypertension, subclinical organ damage or symptoms and 150/95mmHg in other circumstances The drugs od choice: methyldopa, labetalol, calcium antagonists (proven efficiency), β - blokers. Strictly contraindicated: ACEi, angiotensin II antagonists and RI, diuretic therapy (in pre-eclampsia) BP >170/110 mmHg considered as an emergency and treated hospitaly with i.v. labetalol or p.o. methyldopa (hydralazine is no longer the drug of choice!) Bromocriptin may induce hypertension Antihypertensive drugs are present in very low concentrations in breast-milk,except propranolol and nifedipine which conc are similar in maternal plasma A target BP is <130/80mmHg and at least <120/80mmHg when proteinuria is >1g/24h. The most frequent combination is ACEI, ARB or RI with diuretics; a calcium antagonist or a β – blocker can be added. β – blocker should be used carefully in type 1 diabetic patients and avoided in patients with severe peripheral vascular disease! If GFR<15ml/min the doses of ACEi and RI should be reduced, but this is not necessary with ARB. Addition of selective vitamin D receptor activation in pts with RAAS inhibition lowers residual albuminuria especially in diabetic nephropathy Lifestyle modifications,target systolic BP is <140 mmHg,in very elderly <150 mmHg(more than 80 y) Second line is drugs-diuretics,especially long acting dihidropyridine-type calcium antagonists and RAAS inhibitors LV hypertrophy is independent risk factor for cardiovascular disease just as microalbuminuria Effective constant antihypertensive treatment may determine regression and normalisation od LV hypertrophy Regression is rapidly using some classes of antihypertensive agents-ACE i,ARB and CCB Superiority of ARB versus beta-blockers in reducing LV mass Defined when a terapeutic plan consisting of lifestyle measures and at least three drugs (including diuretic) at a correct doses, failed to lower BP to goal levels It is important to exclude: the white-coat effect, pseudohypertension and non-compliance with treatment The treatment of resistant hypertension includes: the elimination of exogenous factors and the use of the maximum tolerated doses of combined antihypertensive agents – ACEI or ARBs, a calciumchannel blocker, a long-acting thiazide diuretic and a low dose spironolactone Indometacine and other NSAIDs may counteract the antihypertensive effect of thiazide diuretics, β – blockers, ACEI and AT1-receptor antagonists by sodium and fluid retention and decreased formation of vasodilatory prostaglandins The low-dose acetylsalicylic acid does not interfere with the antihypertensive activity of ACEI and other classes of antihypertensive drugs. The combination of i.v. verapamil and β-blocker can cause AV block!, attention!!! Verapamil, amiodarone or quinidine can im pare renal excretion and consequently rise the plasma concentration of digoxin Thiazide diuretics may decelerate renal elimination of lithium salts and reinforce their toxicity Hypertension treatment studies COMET SEVERE SOLVD II CONSENSUS I AIRE CIBIS-1 CAPRICORN NETWORK TRACE MDC CIBIS-2 SOLVD I VALIANT ATLAS SMILE MOCHA ACHEIVE ISIS-4 RALES MERIT-HF MILD Approximately 50% of hypertensive patients can be satisfactorily controlled with a single drug; the rest require two or even more agents The combination therapy is avocated for: isolated systolic hypertension, accelerated hypertension and patients that need the prevention of target organ damage (diabetic, nephropathy) Also fixed dose combinations have been enriched by very low dose combinations and may now be considered as a first-line therapy! The use of fixed combination can improve patient compliance Both ventricular and atrial forms of arrhythmia are common comorbidity with hypertension Arrhythmogenic factors are: LVH, myocardial ischaemia, impared LV function, sympathetic irritability Treatment is on case-by-case basis with objective criteria in sight -blockers and amiodarone are the drugs of choice in ventricular arrhythmia while ACEI and ARBs may directly reduce the chance of reccurence of atrial arrhythmia Any potassium imbalance must be corrected! Antithrombotic therapy is essential in patients with atrial arrhythmia (prevention of systemic embolism!) BP should be at least 140/90mmHg or even slightly lower, as in diabetic patients which can be achieved by all antihypertensive agents The most accepted drugs for increasing claudication distance: naftidrofuryl and cilostazol. ACEI seeems to have, besides of their BP lowering properties, more favourable effect on claudication distance and risk The new β blocking agents with vasodilator capacities (in ex. nebivolol) may even improve the walking distance and help in improving the prognosis It is desirable to avoid β -blockers in patients with critical limb ischaemia... The treatment of hypertension in heart failure may depend on the type: systolic vs. dyastolic dysfunction... Target BP is not clearly defined, but values of SBP between 110 and 130mmHg are associated with an increased benefit. Drugs of choice: ACEI, ARBs, diuretics, β-blockers and aldosterone receptor antagonists In preventing development of heart failure diuretics and βblockers are comparable with ACEI and they are all more effective than calcium antagonists; ARBs seems to be the best option for diabetic hypertensive patients with heart failure or those with renal disease. Result of: penile atherosclerotic disease due to high BP levels or certain antihypertensive drugs or combination of both Duration and severity of hypertension are positively correlated with degree of sexual dysfunction Sexual dysfunction may be used as an early diagnostic indicator for asymptomatic coronary artery disease Concomitant use of of phosphodiesterase-5 inhibitors with all classes of antihypertensive agents is not only safe but provides additional benefit. Family studies has shown BP to be highly heritable The genetic dissection of BP and HTN has been one of the most challenging of all the polygenic traits influenced by multiple genetic and enviromental factors... ?? Renin-angiotensin system blockers are superior to other antihypertensive agents in reducing urinary albumin excretion especially in patients with high range of BP Statins (in ex. atorvastatin) can ameliorate the course of renal function in type 2 diabetic patients If albuminuria persist inspite of high dose therapy (ACEI+statins), administration of metformine or other glucose-lowering agents should be considered Agressive treatment of hypertension may postpone or prevent development and reccurence of AF and reduce thromboembolic complications so that the focus should be on primary prevention of AF. AF reccurence was reduced significantly after treatment with RAS-blockade (ACEI or ARBs) compared with treatment with calcium-channels blockers, despite a similar BP lowering effect. Possible explanation is that angiotensin II is an important mechanism involved in electrical and structural remodeling of the heart produced by AF itself. Sleep deprivation seems to be associated with systemic inflammation, oxidative stress and endothelial dysfunction – all conditions favouring the appearance of hypertension. The relationship is age and gender dependent; hypertension is more prevalent in women and adolescents with short sleep duration than in men and eldery. The nocturnal sympathetic over activity limits obligatory nocturnal BP fall; hypertensive subjects in whom the nocturnal BP fall is blunted are in the higher risk of developing target organ damage and cardiovascular morbi-mortality Pre-existing hypertension + sleep disturbances increased severity of hypertension and limited treatment efficacy Uric acid (UA), the major metabolite of purine nucleotides, is not an inert molecule but possesses biological activity. UA plays a dual role: antioxidant (one of the most important in plasma; helps maintain integrity and function of vacular cells in oxidative stress) and deleterious – prooxidant activity (promoting endothelial dysfunction and proliferation of vascular smooth muscle cells). UA is recognised risk factor for hypertension (hyperuricaemia precedes the onset of hypertension), CVD and CKD, may act as a link between metabolic syndrome and associated nephropathy. Reduction of elevated serum UA levels may reverse hypertension in adolescents with new onset and delay progression of renal disfunction in patients with CKD. Cardio-ankle vascular index (CAVI) is used for evaluation of early arterial damage and it is a clinically useful index for the progression of vascular damage. CAVI is calculated using following parameters: systolic blood pressure, diastolic blood pressure, PWV - pulse wave velocity, blood density and constants. CAVI is positively correlated with age, BP, uric acid, glomerular filtration rate, CHD risk score It is suggested that CAVI is a stable parameter (demonstrated good reproducibility and is not affected by the BP during measurement) in comparison to PWV even though those are both non-invasive methods for assesment of arterial stiffness.