Up date on hypertension

Doc. dr Amra Macić - Džanković

Treatment of hypertension in DM type 2 patients 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 andARB 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

Hypertension in pregnancy 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

Hypertension in chronic renal failure

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

Isolated systolic hypertension

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

Hypertension and LV hypertrophy

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

Resistant hypertension 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 calcium-channel blocker, a long-acting thiazide diuretic and a low dose spironolactone

Interactions antihypertensive agents-other drugs

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 impare 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

CONSENSUS I

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Benefitial combinations of two or more antihypertensive drugs

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

Hypertension and arrhythmias

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!)

Hypertension in patients with peripheral artery disease

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...

Hypertension and heart failure

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 β-blockers 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.

Sexual dysfunction in hypertension

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.

Genetics determinants of hypertensionFamily 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... ??

Microalbuminuria in essential hypertension 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

Hypertension and atrial fibrillation

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.

Hypertension and sleep 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

The role of uric acid in hypertension,cardiovascular events and chronic kidney disease

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.

CAVI measurement 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.

UP DATE ON HYPERTENSION