Secondary Hypertension

1. Secondary Hypertension • J. Bradley Gibson, DO, FACC, FACOI • Cardiology Specialists of Dayton • 21st Annual Family Practice Review & Reunion

2. What is the definition of resistant hypertension? • Blood pressure that remains above goal despite maximal doses of ACE inhibitor and Beta Blocker • Blood pressure that is controlled only after maximal doses of 3 different medications • Blood pressure that remains above goal despite adherence to at least 3 optimally dosed medications of different classes, one of which is a diuretic • Blood pressure that remains uncontrolled after an extensive work up for secondary hypertension

3. The most common cause of renal artery stenosis is? • Fibromuscular Dysplasia • Atherosclerosis • Congenital arterial abnormality • Presence of Accessory Renal Artery 3

4. 4

5. Secondary Hypertension • A number of common and uncommon medical conditions may increase blood pressure and lead to secondary hypertension. • In many cases, these causes may coexist with risk factors for primary hypertension and are significant barriers to achieving adequate blood pressure control. • The evaluation of a patient with hypertension depends upon the likely cause and the degree of difficulty in achieving acceptable blood pressure control since many forms of secondary hypertension cause "treatment resistant" hypertension. 5

6. Secondary Hypertension • Patients likely to have essential (idiopathic or primary) hypertension undergo a relatively limited evaluation because extensive laboratory testing is usually of little value. • By contrast, patients who have clinical clues suggesting the possible presence of secondary hypertension should undergo a more extensive evaluation. • If secondary hypertension is present, the most effective treatment strategy often is one that is focused upon the specific mechanism of the hypertension. In addition, some of these disorders can be cured, leading to partial or complete normalization of the blood pressure. 6

7. 7

8. Clues to Secondary Hypertension • Because it is not cost effective to perform a complete evaluation for secondary hypertension in every hypertensive patient, it is important to be aware of the clinical clues that suggest secondary hypertension. • General Clinical Clues to Secondary Hypertension • Severe or resistant hypertension. Resistant hypertension is defined as the persistence of hypertension despite concurrent use of adequate doses of three antihypertensive agents from different classes, including a diuretic. • An acute rise in blood pressure developing in a patient with previously stable values. • Age less than 30 years in non-obese, non-black patients with a negative family history of hypertension and no other risk factors (eg, obesity) for hypertension. • Malignant or accelerated hypertension (eg, patients with severe hypertension and signs of end-organ damage such as retinal hemorrhages or papilledema, heart failure, neurologic disturbance, or acute kidney injury). • Proven age of onset before puberty. • Evidence of Renovascular Hypertension 8

9. 9

10. Causes of Secondary Hypertension 10

11. 11

12. 12

13. Specific Topics to Review • Renovascular Hypertension • Primary Aldosteronism • Sleep Apnea Syndrome • Coarctation of the Aorta • Pheochromocytoma • Medications • Other Endocrine Disorders 13

14. RENOVASCULAR HYPERTENSION • Renovascular hypertension is the most common potentially correctable cause of secondary hypertension. • The incidence varies with the clinical setting. It probably occurs in less than 1 percent of patients with mild hypertension. • By comparison, between 10 and 45 percent of white patients with severe or malignant hypertension have renal artery stenosis. Renal artery stenosis can be detected in many individuals with other manifestations of atherosclerosis, such as coronary artery disease (10 to 14 percent) and peripheral arterial and aortic disease (24 to 35 percent). 14

15. RENOVASCULAR HYPERTENSION • There are a variety of findings associated with a higher likelihood of hypertension being secondary to renovascular disease. 15

16. 16

17. Renal Artery Stenosis • Radiologic testing to confirm the presence of renal artery stenosis may be indicated in patients for whom the history is suggestive (based upon a general assessment of clinical risk factors) and in whom a corrective procedure will be performed if renovascular disease is detected. • RAS is due to atherosclerosis in 70 to 90% of cases and usually involves the ostium and proximal third of the main renal artery and the perirenal aorta. • The remaining 10% or so of RAS is caused by fibromuscular dysplasia, a type of vasculitis that affects one or more layers of the renal artery, usually including the media. • In contrast to atherosclerotic RAS, fibromuscular dysplasia more often affects younger persons,particularly women, and involves the distal two thirds of the renal artery. 17

18. 18

19. 19

20. Renal Artery Stenosis • A workup for RAS should be done only if there is resistant hypertension or if there is worsening renal function, and if there is no contraindication to an invasive procedure (percutaneous renal angioplasty, with or without stenting, or revascu- larization surgery), and if the patient is willing to accept a more aggressive approach. • Useful noninvasive tests for RAS include: radioisotope scanning with ACE inhibition (captopril scintigraphy), Doppler ultrasound, magnetic resonance angiography (MRA), and CT angiography (CTA). • Renal arteriography is the definitive diagnostic test for RAS, revealing in addition the extent of intrarenal and associated aortic vascular disease and the dimensions of the kidneys. 20

21. RAS Treament • The goals of RAS treatment are BP control and preservation of renal function. • BP control can be attempted with medical therapy alone, with percutaneous renal angioplasty (with or without stenting), or surgery. • Control of BP in renovascular hypertension may be achieved in >90% of cases with medical therapy alone, usually with a combination of antihypertensive drugs. All classes of these drugs may be used, but because the hyper- tension is often the result of activation of the RAAS, drugs that inhibit angiotensin II production or block its receptor are particularly effective. • This should be augmented with antiatherosclerotic and antithrombotic measures such as statin therapy, smoking cessation, and aspirin. 21

22. Primary Aldosteronism • Primary aldosteronism (PA), also called Conn’s syndrome, is a hypertensive syndrome that results from increased production of aldosterone and may account for as many as 5 to 15% of all cases of hypertension, and thus appears to be the most prevalent form of secondary hypertension. • Aldosterone excess generally results in suppressed plasma renin activity, metabolic alkalosis, a potassium-losing diathesis, and hypertension, but these findings are variable. • The increase in BP can be severe and resistant to conventional antihypertensive therapy. • It is important to diagnose and treat PA early because these patients may be at higher risk than other hypertensive persons for target- organ damage of the heart and kidney. 22

23. Primary Aldosteronism • The main clinical clue suggestive of primary aldosteronism is otherwise unexplained or easily provoked hypokalemia due to urinary potassium wasting. • Primary aldosteronism should also be suspected in the presence of slight hypernatremia, drug-resistant hypertension, and/or hypertension with an adrenal incidentaloma. • The morning plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) is the screening test of choice for PA. A ratio >20 with a PAC of at least 12 ng/dl should prompt confirmatory testing. • A ratio >70 with a PAC of >15 ng/dl and a PRA <1 ng/ml/h is virtually diagnostic of PA. • The test can be performed in patients taking all antihypertensive medications except spironolactone or eplerenone. 23

24. Primary Aldosteronism • If the screening test is positive, then the next step is an aldosterone suppression test. • The remainder of the diagnostic algorithm is directed toward confirming the existence of aldosterone excess and identifying the responsible lesion. • The two most common causes of PA, aldosterone-producing adenoma and bilateral adrenal hyperplasia, can be distinguished by high-resolution computed tomography (CT) of the adrenal glands. 24

25. 25

26. 26

27. PA Treatment • Spironolactone or eplerenone is the treatment of choice for a nonlateralizing study such as bilateral adrenal hyperplasia or bilateral adenomas. • Patients with atypical features or who fail to respond to aldosterone antagonists may have one of the rarer forms of PA, such as glucocorticoid-remediable aldosteronism or adrenal carcinoma, and should be referred to a specialized center for evaluation and treatment. • Aldosterone-producing adenomas very rarely undergo malignant degeneration 27

28. 28

29. Sleep apnea syndrome • Obstructive sleep apnea (OSA) is characterized by repetitive interruption of ventilation for 10 seconds or more during sleep caused by collapse of the pharyngeal airway, and with associated respiratory effort. • The syndrome of OSA is characterized by snoring, sleep fragmentation, daytime hypersomnolence, and cognitive impairment. • Approximately 50% of patients with OSA are hypertensive, and as many as 30% of hypertensive patients are estimated to have OSA. • The sleep apnea syndrome is most commonly identified in obese men who snore loudly while asleep. 29

30. Sleep apnea syndrome • Recurrent hypoxia induced by sleep apnea triggers sustained increases in peripheral resistance and cardiac out- put, in part secondary to chronic sympathetic activation. • Sleep deprivation in untreated or inadequately treated hypertensive patients may increase sympathetic nervous activity during the night and the following morning, leading to increased BP and heart rate, and increased risk for both target-organ damage and cardiovascular disease events. 30

31. 31

32. OSA Treatment • The mainstay of treatment is weight loss, which may be curative, but is very difficult to achieve. • Behavioral therapy includes: 1) cessation of alcohol and sedative use, 2) avoidance of sleep deprivation, and 3) sleep positioning to avoid the supine position, in which upper airway obstruction occurs most commonly. • A simple and often effective approach is a mandibular advancement splint, a mouth guard designed to hold the mandible slightly down and forward relative to the natural, relaxed position. • Other medical therapies include: 1) treatment of predisposing comorbid conditions and 2) nocturnal continuous positive airway pressure (CPAP). 32

33. OSA Treatment • Surgical approaches include uvulopalatopharyngoplasty and genioglossal/mandibular advancement in adults and tonsillectomy/adenoid- ectomy in children. • There is no evidence that one class of antihypertensive agents is more or less advanta- geous than any other class in patients with sleep apnea. Special attention should be paid to comorbid conditions, and drugs that cause sedation or daytime somnolence should be avoided. • Patients with obstructive sleep apnea often retain sodium and fail to respond optimally to antihypertensive drug therapy. • Correction of the sleep apnea may improve blood pressure control. 33

34. 34

35. Coarctation of the aorta • Coarctation of the aorta is one of the major causes of secondary hypertension in young children but may first be detected in adulthood. • The classic findings are hypertension in the upper extremities, diminished or delayed femoral pulses ("brachial-femoral delay"), and low or unobtainable arterial blood pressure in the lower extremities. • In addition, a prominent "to-and-fro machinery murmur" from the aorta may be heard over the posterior chest. • Diagnosis by echocardiograpy, CT angiogram, or MRI 35

36. 36

37. 37

38. Pheochromocytoma • Pheochromocytoma should be suspected if there are paroxysmal elevations in blood pressure (which may be superimposed upon stable chronic hypertension), particularly if associated with the triad of headache (usually pounding), palpitations, and sweating. • Patients identified with pheochromocytoma are rarely asymptomatic. • In addition, patients with drug-resistant hypertension and those with an adrenal incidentaloma should be evaluated for pheochromocytoma. • The diagnosis of pheochromocytoma is typically made by measurements of urinary and plasma fractionated metanephrines and catecholamines . 38

39. 39

40. Medications that may interfere with diagnosis of Pheochromocytoma 40

41. 41

42. Medications • Oral contraceptives — Oral contraceptives often raise the blood pressure within the normal range but can induce overt hypertension. • Chemotherapeutic agents — A number of chemotherapeutic agents result in secondary hypertension and kidney injury. • NSAIDs (Renal failure, Increases in sodium and water) • Stimulants (eg, cocaine, methylphenidate) • Calcineurin inhibitors (Cyclosporine, Tacrolimus) • Antidepressants (Increasing vasoactive substances) 42

43. 43

44. Endocrine disorders • Cushing's syndrome — Cushing's syndrome (including that due to glucocorticoid administration) is usually suggested by the classic physical findings of cushingoid facies, central obesity, proximal muscle weakness, and ecchymoses. (Increase Salt and Water, Increased volume and cardiac output, increased PVR) • Thyroid Disease • Hyperparathyroidism- hypercalcemia affects vascular reactivity 44

45. 45

46. Summary • It is not cost effective to perform a complete evaluation for secondary hypertension in every hypertensive patient. Thus, it is important to be aware of the clinical clues that suggest secondary hypertension. • Severe or resistant hypertension. Resistant hypertension is defined as the persistence of hypertension despite concurrent use of adequate doses of three antihypertensive agents from different classes, including a diuretic. • An acute rise in blood pressure developing in a patient with previously stable values. • Age less than 30 years in non-obese, non-black patients with a negative family history of hypertension and no other risk factors (eg, obesity) for hypertension. • Malignant or accelerated hypertension (eg, patients with severe hypertension and signs of end-organ damage such as retinal hemorrhages or papilledema, heart failure, neurologic disturbance, or acute kidney injury). • Proven age of onset before puberty. 46

47. Summary • Other causes of secondary hypertension, including primary kidney disease, primary aldosteronism, use of oral contraceptives, pheochromocytoma, Cushing's syndrome, sleep apnea syndrome, and coarctation of the aorta must also be excluded in the appropriate settings 47

48. What is the definition of resistant hypertension? • Blood pressure that remains above goal despite maximal doses of ACE inhibitor and Beta Blocker • Blood pressure that is controlled only after maximal doses of 3 different medications • Blood pressure that remains above goal despite adherence to at least 3 optimally dosed medications of different classes, one of which is a diuretic • Blood pressure that remains uncontrolled after an extensive work up for secondary hypertension

50. The most common cause of renal artery stenosis is? • Fibromuscular Dysplasia • Atherosclerosis • Congenital arterial abnormality • Presence of Accessory Renal Artery 50