27.Eylül.2014 saat 12.00-15.00

1. 27.Eylül.2014 saat 12.00-15.00 Hastane Oryantasyon Eğitimi

2. Approach to the patient with hypertensive disorders Prof.GülçinKantarcı, MD Department of Internal Medicine and Nephrology

3. OBJECTIVESHYPERTENSİON At 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.

4. Contents • Hypertensivedisorders • PrimaryHypertension • SecondaryHypertension • Hypertensiveemergencies • Treatment of hypertensivedisorders • Approachtothepatientwithurgent ant emergenthypertensivedisorders

5. References Data bases: http://accessmedicine.com http://www.uptodate.com 1. CurrentMedicalDiagnosisandTreatment, Maxine A. Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. Chapter 11. SystemicHypertension 2. Bates' Guide toPhysicalExamination & HistoryTaking 11th edition, Bickleys LS, Szilagyi PG; Lippincott Williams andWilkins¸ 3. Kumar andClark'sClinicalMedicine, 8th edition; Kumar & Clark, Elsevier 4. AndreoliandCarpenter'sCecil Essentials of Medicine 8th edition, AndreoliandCarpenter, Elsevier 5. SymptomtoDiagnosis: An Evidence-Based Guide, 2e, Scott D. C. Stern, Adam S. Cifu, DianeAltkorn Chapter 20. I Have a PatientwithHypertension. How Do I DeterminetheCause? 6. CURRENT Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson Chapter 43. Hypertension in High-Risk Populations

6. SUGGESTED READING

7. 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.

8. HypertensionGuidelines • JNC 7 2003 • ESC 2007 • NICE 2011 • CHEP 2012 • ESC 2013 • JNC 8 2014

9. Classification of HTJoint National Committee (JNC 7) the average of two or more properly measurereadings 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

10. 2007 European Societies of Hypertension

11. Pathogenesis: Abnormal cardiovascular or renal development • 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 elasticityor 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.

12. Definitionsbaseduponambulatoryandhomereadings • 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 mmHg • the definition of hypertension based upon an average of multiple home readings is the same as for daytime ambulatory blood pressure

13. 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 everyfourdeathsduetohypertension . Turkish Health Ministry, Turkish Health Load Study, 2004 • BP increaseswith 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 havehypertension

14. Prevalance of HT in Turkey HinT, 2008

15. 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

16. 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

17. 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.

18. 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

19. 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.

20. 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.

21. Renin-angiotensin-aldosterone system

22. Defect in natriuresis Intracellularsodiumandcalcium • 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.

23. Blood pressure = cardiacoutput (CO) × total peripheralvascularresistance (TPR) • Inmostpatients, CO is normal orslightlyincreased, and TPR is increased. Thispattern is typical of; • primaryhypertension • hypertensionduetopheochromocytoma • primaryaldosteronism • renovasculardisease • renalparenchymaldisease

24. 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.

25. 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.

26. Secondaryhypertension 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 —

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

28. Clinical findings • Stage III-IV hypertensiveretinopathy • Abdominalbrut • Renalfailure • Findings of peripheralvasculardis. 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.

29. 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.

30. Evaluating renovascular ht • Renovasculardoppler US • Kaptoprilrenogram • MR angiography • BT angiography • RenalArteriography • suspicion is moderate to low, noninvasive angiography using magnetic resonance (MR) or CT are reasonable approaches. • Doppler sonographymay 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

31. MR Angiography Renovasculardoppler US CT Angiography RenalArteriography

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

39. Assess target organ damages •Cardiovascular ■Electrocardiography ■2-Dimensional echocardiography •Cerebrovascular •Eyes •Kidney function ■Estimated GFR ■Proteinuria: microalbuminuria, alb/cr 46

40. Drug-Induced Hypertension: Prescription Medications • Steroids • Estrogens • NSAIDS • Phenylpropanolamines • Cyclosporine/tacrolimus • Erythropoietin • Sibutramine • Methylphenidate • Ergotamine • Ketamine • Desflurane • Carbamazepine • Bromocryptine • Metoclopramide • Antidepressants • Venlafaxine • Buspirone • Clonidine

41. 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 differenttimes of day.

43. Proper Cuff Size: 40% of circumference, 60-70% of length of upper arm • The bladder is long enough to encircle > 80% of the arm,

44. Measurement of BloodPressure • Self monitoring: • Provides information on: • Response to antihypertensive therapy • Improving adherence with therapy • Evaluating white-coat HTN • Home measurement of >135/85 mmHg is generally considered to be hypertension. • Home measurement devices should be checked regularly.

45. 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 onthe device, and diurnal or nocturnal BP pressure recordingsare 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

46. According to JNC 7 guidelines, ABPM is recommended • Suspected WCH in patients with HT and no target organdamage. • Apparent drug resistance (office resistance). • Hypotensive symptoms with antihypertensive medication. • Episodic HT. • Autonomic dysfunction.

47. Management of Hypertensivepatients Goals of treatment  •Reduction of cardiovascular morbidity and mortality •Delayed progression of proteinuric renal disease

48. JNC 8

50. JNC 8