27.Eylül.2014 saat 12.00-15.00

Hastane Oryantasyon Eğitimi

Approach to the patient with hypertensive disorders

Prof.Gülçin Kantarcı, MDDepartment of

Internal Medicine andNephrology

OBJECTIVESHYPERTENSİONAt the end of this lecture the students

Knowledge:

1.Has a good understanding the diagnosis and the differential diagnosis of hypertensive disorders, renovascular hypertension and ischemic renal diseases with their emergent treatment requirements and methods.

2.Has knowledge about diagnosis methods of hypertensive disorders, renovascular hypertension and ischemic renal diseases. (Laboratory tests, screening tests, other invasive and non-invasive medical procedures)

3.Explain the pathophysiology of hypertensive disorders.

Skills:

4. Can name the possible diagnosis and make a differential diagnosis of hypertensive disorders, renovascular hypertension and ischemic renal diseases.

5.Can use the diagnosis methods for hypertensive disorders, renovascular hypertension and ischemic renal diseases economically and properly. (Laboratory tests, screening tests, other invasive and non-invasive medical procedures)

6.Can interpret the result of these tests correctly.

7. Can choose between emergent and non-emergent situations, and give emergent treatment for diseases.

8. Arrange the initial treatments and provide appropriate conditions until the patient is sent to specialist.

Attitudes:

9. Take preventive measures against end-organ damage of hypertension

10 Presents a worthy thought, attitude and behaviour appropriate for a physician in patient communication.

Contents

1. Hypertensive disorders 2. Primary Hypertension3. Secondary Hypertension4. Hypertensive emergencies 5. Treatment of hypertensive disorders6. Approach to the patient with urgent ant

emergent hypertensive disorders

References

Data bases: http://accessmedicine.com http://www.uptodate.com1. Current Medical Diagnosis and Treatment, Maxine A. Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. Chapter 11. Systemic Hypertension2. Bates' Guide to Physical Examination & History Taking 11th edition, Bickleys LS, Szilagyi PG; Lippincott Williams and Wilkins¸ 3. Kumar and Clark's Clinical Medicine, 8th edition; Kumar & Clark, Elsevier4. Andreoli and Carpenter's Cecil Essentials of Medicine 8th edition, Andreoli and Carpenter, Elsevier5. Symptom to Diagnosis: An Evidence-Based Guide, 2e, Scott D. C. Stern, Adam S. Cifu, Diane Altkorn Chapter 20. I Have a Patient with Hypertension. How Do I Determine the Cause?6. CURRENT Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson Chapter 43. Hypertension in High-Risk Populations

SUGGESTED READING

Goldman's Cecile Medicine 24th edition Elsevier Goldman L, Schafer AI

Case files Internal Medicine 5th edition Mc Graw Hill LANGE Toy Patlan

The Cleveland Clinic Intensive Review of Internal Medicine 5th edition

Lippincott Williams and Wilkins Stoller JK, Michota FA, Mandell BF

Definition: HT is the pressure exerted by circulating blood

upon the walls of blood vessels, and is one of the principal vital signs (arterial pressure of the systemic circulation).

During each heartbeat, blood pressure varies between a maximum (systolic) and a minimum (diastolic) pressure.

Correct measurement and interpretation of the blood pressure (BP) is essential in the diagnosis and management of hypertension.

Hypertension Guidelines

JNC 7 2003 ESC 2007 NICE 2011 CHEP 2012 ESC 2013 JNC 8 2014

Classification of HTJoint National Committee (JNC 7)

the average of two or more properly measure readings

at each of two or more visits after an initial screen

Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg

Prehypertension: systolic 120-139 mmHg or diastolic 80-89 mmHg

Hypertension:  Stage 1: systolic 140-159 mmHg or diastolic

90-99 mmHg Stage 2: systolic ≥ 160 or diastolic ≥ 100

mmHg

2007 European Societies of Hypertension

• The normal cardiovascular system develops so that elasticity of the great arteries is matched to the resistance in the periphery to optimize large vessel pressure waves. In this way, myocardial oxygen consumption is minimized and coronary flow maximized.

• Elevated blood pressure later in life could arise from abnormal development of aortic elasticity or reduced development of the microvascular network.

• It has been postulated as the sequence of events in low birth weight infants who have an increased risk of hypertension developing in adulthood. Another hypothesis proposes that the association between low birth weight and hypertension arises from reduced nephron number.

Pathogenesis: Abnormal cardiovascular or renal development

Definitions based upon ambulatory and home readings The diagnosis of hypertension using

ambulatory blood pressure monitoring depends upon the time span over which it is interpreted:

A 24-hour average above 135/85 mmHg Daytime (awake) average above 140/90 mmHg Nighttime (asleep) average above 125/75 mmHgthe definition of hypertension based upon

an average of multiple home readings is the same as for daytime ambulatory blood pressure

epidemiology

The national health and nutrition examination survey (NHANES) conducted from 2005 through 2008 estimated that approximately 29 to 31 percent of adults in the United States have hypertension

One of every four deaths due to hypertension . Turkish Health Ministry, Turkish Health Load Study,

2004 BP increases with age. About 75% of women aged 75 years and over

have hypertension and about 64% of men aged 75 years and over have hypertension

About 2 /3 of people > 65 have hypertension

Prevalance of HT in Turkey

HinT, 2008

Risk Factors Hypertension tends to be both more common and more severe

in blacks. Hypertension in maternal, paternal or both parents Excess sodium intake Excess alcohol intake is associated with the development of

hypertension. Obesity and weight gain. In Turkey 25 % of whole population over weight Over 40 years 15 % excessive obasity

the rise in blood pressure that is commonly observed with aging Physical inactivity Dyslipidemia, independent of obesity fructose may increase hypertension risk , the best data suggest

that it does not raise blood pressure or increase the incidence of hypertension.

Hypertension may be more common among those with certain personality traits, such as hostile attitudes and time urgency/impatience , as well as among those with depression .

Vitamin D deficiency

Etiology

Primary( essential) (85 to 95% of cases) ? The term applied to the hypertensive

patients in which elevated blood pressure results from complex interactions between multiple genetic and environmental factors.

Secondary

Essential hypertension The term applied to the 95% of

hypertensive patients in which elevated blood pressure results from complex interactions between multiple genetic and environmental factors.

The onset is usually between ages 25 and 50 years; it is uncommon before age 20 years.

Essential(Primary) hypertension

The best understood endogenous and environmental determinants of blood pressure include the •sympathetic nervous system •the renin-angiotensin-aldosterone system •the pressure natriuresis •variation in cardiovascular and renal development •intracellular sodium and calcium levels

Sympathetic nervous system hyperactivity

Most apparent in younger persons with hypertension, who may exhibit tachycardia and an elevated cardiac output. However, correlations between plasma catecholamines and blood pressure are poor.

Insensitivity of the baroreflexes may play a role in the genesis of adrenergic hyperactivity, and polymorphisms in some genes have been linked to increased blood pressure responses to stress.

Renin–-angiotensin-Aldosterone system activity

• Renin, a proteolytic enzyme, is secreted by cells surrounding glomerular afferent arterioles (JGA) in response to a number of stimuli, including

• reduced renal perfusion pressure • diminished intravascular volume• circulating catecholamines• increased sympathetic nervous

system activity • increased arteriolar stretch, and

hypokalemia.

Renin-angiotensin-aldosterone system

Defect in natriuresisIntracellular sodium and calcium

According to the classic Guyton hypothesis, increased salt intake triggers an increase in blood pressure that in turn promotes increased natriuresis, thereby bringing blood pressure back toward basal levels.

Salt has long been implicated in the genesis of hypertension, and so-called salt-sensitive hypertension probably arises from a defect in this self-regulating pressure–natriuresis feedback loop.

Intracellular Na+ is elevated in primary (essential) hypertension.

An increase in intracellular Na+ may lead to increased intracellular Ca2+ concentration as a result of facilitated exchange and might explain the increase in vascular smooth muscle tone that is characteristic of established hypertension.

• In most patients, CO is normal or slightly increased, and TPR is increased.

This pattern is typical of; • primary hypertension • hypertension due to pheochromocytoma• primary aldosteronism • renovascular disease• renal parenchymal disease

Blood pressure =

cardiac output (CO) × total peripheral vascular resistance (TPR)

Symptoms and Signs

usually asymptomatic until complications develop in target organs.

Dizziness, flushed facies, headache, fatigue, epistaxis, and nervousness

Severe hypertension can cause severe cardiovascular, neurologic, renal, and retinal symptoms (eg, symptomatic coronary atherosclerosis, HF, hypertensive encephalopathy, renal failure).

A 4th heart sound is one of the earliest signs of hypertensive heart disease.

Secondary hypertension • suspected in patients in whom

hypertension develops at an early age or after the age of 50 years, and in those previously well controlled who become refractory to treatment.

• High BP resistant to three medications is another clue although multiple medications are usually required to control hypertension in persons with diabetes.

Primary renal disease —acute and chronic, glomerular or vascular disorders.

Pheochromocytoma — About ½ of patients with pheochromocytoma have paroxysmal hypertension, most of the rest have what appears to be essential hypertension.

Primary hyperaldosteronism —should be suspected in any patient with the triad of hypertension, unexplained hypokalemia, and metabolic alkalosis.

Genetic causes - Glucocorticoid remediable aldosteronism, Liddle syndrome

Renovascular disease — Renovascular disease is an important correctable cause of secondary hypertension. The frequency with which it occurs is variable.

Cushing's syndrome — Moderate diastolic hypertension is a major cause of morbidity and death in patients with Cushing's syndrome.

Other endocrine disorders — Hypertension may be induced by both hypothyroidism, hyperthyroidism, and hyperparathyroidism.

Sleep apnea syndrome — Disordered breathing during sleep appears to be an independent risk factor for awake systemic hypertension.

Coarctation of the aorta — Coarctation of the aorta is one of the major causes of hypertension in young children

Oral contraceptives —

Secondary hypertension

Renovascular disease Atheromatos diseases (70-80%) Fibromuscular displazia (20-25%) Dis.Aorta Anev. Renal arterial trombozis Abdominal trauma Neurofibromatosis Takayasu arteritis

Clinical findings Stage III-IV hypertensive retinopathy Abdominal brut Renal failure Findings of peripheral vascular dis. Heart- left ventricular hypertrophy.- Aortic insufficiency may be auscultated in up to 5% of patients, and

hemodynamically insignificant aortic insufficiency can be detected by Doppler echocardiography in 10–20%.

- A presystolic (S4) gallop due to decreased compliance of the left ventricle is quite common in patients in sinus rhythm .

Pulses-Radial-femoral delay suggests coarctation of the aorta; loss of peripheral pulses occurs due to atherosclerosis, less commonly aortic

dissection, and rarely Takayasu arteritis, all of which can involve the renal arteries.

Renal vascular hypertension should be suspected

if the documented onset is before age 20 or after age 50 years,

hypertension is resistant to three or more drugs, if there are epigastric or renal artery bruits, if there is atherosclerotic disease of the aorta or

peripheral arteries (15–25% of patients with symptomatic lower limb atherosclerotic vascular disease have renal artery stenosis),

if there is an abrupt increase (> 25%) in the level of serum creatinine after administration of ACE inhibitors, or

if episodes of pulmonary edema are associated with abrupt surges in blood pressure.

Evaluating renovascular ht Renovascular doppler US Kaptopril renogram MR angiography BT angiography Renal Arteriography

suspicion is moderate to low, noninvasive angiography using magnetic resonance (MR) or CT are reasonable approaches.

Doppler sonography may play an increasing role in detection of renal artery stenosis,

Gadolinium, a contrast agent used in MR angiography, is contraindicated in patients with an estimated glomerular filtration rate (GFR) of < 30 mL/min because it might precipitate nephrogenic systemic fibrosis in patients with advanced kidney disease

Renovascular doppler US

CT Angiography

MR Angiography

Renal Arteriography

Other causes of secondary hypertension

Hypertension has also been associated with hypercalcemia, acromegaly, hyperthyroidism, hypothyroidism, baroreceptor denervation, compression of the rostral ventrolateral medulla, and increased intracranial pressure.

A number of medications may cause or exacerbate hypertension—most importantly cyclosporine, tacrolimus, angiogenesis inhibitors, erythrocyte stimulating agents such as erythropoietin, decongestants, and NSAIDs; cocaine and alcohol should also be considered.

Complications of Untreated Hypertension

HYPERTENSIVE CARDIOVASCULAR DISEASE•Left ventricular hypertrophy is associated with incremental cardiovascular risk in association with heart failure (through systolic or diastolic dysfunction), ventricular arrhythmias, myocardial ischemia, and sudden death•The occurrence of heart failure is reduced by 50% with antihypertensive therapy.

HYPERTENSIVE CEREBROVASCULAR DISEASE AND DEMENTIA

Hypertension is the major predisposing cause of hemorrhagic and ischemic stroke. Cerebrovascular complications are more closely correlated with systolic than diastolic blood pressure.

The incidence of these complications is markedly reduced by antihypertensive therapy.

HT is associated with a higher incidence of subsequent dementia of both vascular and Alzheimer types.

Effective blood pressure control may reduce the risk of development of cognitive dysfunction later in life, but once cerebral small vessel disease is established, low blood pressure might exacerbate this problem.

HYPERTENSIVE KIDNEY DISEASE

Chronic hypertension leads to nephrosclerosis. Aggressive blood pressure control, to 130/80 mm Hg or lower, slows the progression of all forms of chronic kidney disease, especially when proteinuria is present.

AORTIC DISSECTION&ATHEROSCLEROTIC COMPLICATIONS

Hypertension is a contributing factor in many patients with dissection of the aorta.

Most of the hypertensive patients die of complications of atherosclerosis, but antihypertensive therapy seems to have a lesser impact on atherosclerotic complications compared with the other effects of treatment outlined before.

46

Assess target organ damages

 •Cardiovascular ■Electrocardiography■2-Dimensional echocardiography•Cerebrovascular•Eyes•Kidney function ■Estimated GFR■Proteinuria: microalbuminuria, alb/cr

Drug-Induced Hypertension: Prescription Medications

• Steroids• Estrogens• NSAIDS• Phenylpropanolamines• Cyclosporine/

tacrolimus• Erythropoietin• Sibutramine• Methylphenidate• Ergotamine

• Ketamine• Desflurane• Carbamazepine• Bromocryptine• Metoclopramide• Antidepressants

– Venlafaxine• Buspirone• Clonidine

Measurement of Blood Pressure

Office monitoring:•Patient should be seated quietly for 5 minutes in a chair feet on the floor, and arm supported at heart level. •Appropriate-sized cuff should be used to ensure accuracy. •At least two measurements should be made at different times of day.

• Proper Cuff Size: 40% of circumference, 60-70% of length of upper arm

• The bladder is long enough to encircle > 80% of the arm,

Measurement of Blood Pressure

Self monitoring: Provides information on:

1. Response to antihypertensive therapy2. Improving adherence with therapy 3. Evaluating white-coat HTN

Home measurement of >135/85 mmHg is generally considered to be hypertension.

Home measurement devices should be checked regularly.

Ambulatory blood pressure monitoring

• is determined using a device worn by the patient that takes BP measurements over a 24 to 48 hour period, usually every 15 to 20 minutes during the daytime and every 30 to 60 minutes during sleep. Measurements are recorded on the device, and diurnal or nocturnal BP pressure recordings are evaluated by computer.

The diagnosis of hypertension using ambulatory blood pressure monitoring :

• A 24-hour average above 135/85 mmHg• Daytime (awake) average above 140/90 mmHg• Nighttime (asleep) average above 125/75 mmHg

According to JNC 7 guidelines, ABPM is recommended

• Suspected WCH in patients with HT and no target organ damage.

• Apparent drug resistance (office resistance).• Hypotensive symptoms with antihypertensive

medication.• Episodic HT.• Autonomic dysfunction.

Management of Hypertensive patients

Goals of treatment •Reduction of cardiovascular morbidity and mortality

•Delayed progression of proteinuric renal disease

JNC 8

JNC 8

Nonpharmacologic theraphy Recommended for all individuals

• Weight loss and exercise• Smoking cessation• Diet: Increased fruits and vegetables,

decreased salt, limited alcohol, increased potassium intake

• a reduction in salt intake of 6 g/day through the fall in blood pressure that would occur would cause

24% reduction in stroke 18% reduction in coronary heart disease

mortality.

Pharmacologic therapy

DIURETICS:in uncomplicated hypertensive thiazide diuretic (ALLHAT) a maximum of 25 mg/day This regimen is associated with a low rate of

metabolic complications, such as hypokalemia, glucose intolerance, and hyperuricemia)

they lower urinary calcium excretion, beneficial in patients with hypercalciuria and recurrent calcium stones and in those with osteoporosis.

Side effects: Hypokalemia (which increases digitalis

toxicity), hyperuricemia, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, hypercalcemia, sexual dysfunction in men, weakness, rash

Loop Diuretics

• Typically only beneficial in patients with resistant HTN and evidence of fluid overload; effective if CrCl <30 ml/min

• MUST be dosed at least twice daily (Lasix = Lasts six hours)

Aldosteron antagonists

Can provide as much as 25 mmHg BP reduction on top of 4 drug regimen in resistant hypertension

Monitor SCr and K

ACEI:Major additional role for reducing BP and cardiovascular risk and proteinuric renal disease, particularly in diabetics

Side effects:A dry, irritating cough is the most common

adverse effect, but angioedema is the most serious and, if it affects the oropharynx, can be fatal.

Angioedema is most common among blacks and smokers. ACE inhibitors may increase serum K and creatinine levels, especially in patients with chronic renal failure and those taking K-sparing diuretics, K supplements, or NSAIDs.

ACE inhibitors are the least likely of the antihypertensives to cause erectile dysfunction. ACE inhibitors are contraindicated during pregnancy.

ANGIOTENSIN II RECEPTOR BLOCKERS: These drugs block angiotensin II receptors and

therefore interfere with the renin-angiotensin system. Angiotensin II receptor blockers and ACE inhibitors are equally effective as antihypertensives.

B-BLOKERS: Slow heart rate and reduce myocardial contractility, thus reducing BP. All β-blockers are similar in antihypertensive efficacy. In patients with diabetes, chronic peripheral arterial disease, or COPD, a cardioselective β-blocker ( acebutolol , atenolol , bisoprolol , metoprolol) may be preferable, although cardioselectivity is only relative and decreases as dose increases.

•Even cardioselective β-blockers are contraindicated in patients with asthma or in patients with COPD with a prominent bronchospastic component

CA CANAL BLOKER: Recent studies confirm benefits with previous coronary disease, however, argue that ARBs may offer greater protection (LIFE trial).*Dihydropyridines ( nifedipine) are potent peripheral vasodilators and reduce BP by decreasing TPR; they sometimes cause reflexive tachycardia. Leg edema*

*The nondihydropyridines (verapamil) slow the heart rate, decrease atrioventricular conduction, and decrease myocardial contractility. These drugs should not be prescribed for patients with 2nd- or 3rd-degree atrioventricular block or with left ventricular failure . Leg edema*

ALPHA2 AGONİSTS: CENTRAL ACTİNG AGENTS

• Mechanism: false neurotransmitters reduce sympathetic outflow reducing sympathetic tone • Clonidine 0.1-0.6 mg PO BID-TID; patch

• Methyldopa, Guanabenz, Guanfacine

• Monitor: HR

• Side effects often limiting: Dry mouth, orthostasis, sedation

• Clonidine patch can be useful in elderly patients with labile blood pressure

ALPHA1 BLOCKERS

• Mechanism: Inhibit peripheral post-synaptic alpha1 receptors causing vasodilation

• Terazosin 1 – 20 mg daily

• Doxazosin 1 – 16 mg daily

• Cause marked orthostatic hypotension, give dose at bedtime

• Consider only combination theraphy

• Can be beneficial in patients with BPH

Choice of Antihypertensive  

Antihypertensives for High-Risk Patients

When to Refer

Referral to a hypertension specialist should be considered in cases of severe, resistant or early/late onset hypertension or when secondary hypertension is suggested by screening.

Hypertensive CrisisDiastolic BP > 120 mmHg

Hypertensive emergency Hypertensive urgency

Acute HT+ Target organ damage Acute HT

JNC 7 2003 ESH-ESC guidelines for the management of arterial hypertension.

NICE Agust. 2011

Approach to the patient with urgent ant emergent hypertensive disorders

Hypertensive emergencies Treatment :

■Oral agents: Difficult to control: Nifedipine, nicardipine, clonidine, labetalol, hydralazine,kaptopril

■Intravenous agents: Nitroprusside, labetalol, enalapril, nicardipine, fenoldopam, nitroglycerin

Situations not considered emergencies: Thrombotic stroke, asymptomatic hypertension, CKD