Secondary hypertension - Etiopathogenesis, Clinical features, Advances in Management

Secondary hypertension - Etiopathogenesis, Clinical features, Advances in Management

1. SECONDARY HYPRTENSION CHAIR PERSON: DR. RAM S KAULGUD Asst. Professor Dept of medicine KIMS STUDENT: DR. RAGHU. G

2. Definition (JNC7) Average of two or more seated blood pressure readings during each of two or more outpatient visits. - SBP ≥ 140 - DBP ≥ 90 Isolated systolic hypertension - SBP ≥140 - DBP <90

3. AHA 2017GUIDELINES DEFINTION- SBP ≥130 DBP ≥80 CIRCULATION NOV 13 2017

4. Definition of HTN ACC 2017 JNC7 JNC8 SBP GENERAL POPULATION ≥130 ≥140 ≥140 AGE >60 YR WITHOUT DM OR CKD ≥150 DBP GENERAL POPULATION ≥80 ≥90 ≥90

5. 24-hr ambulatory blood pressure monitoring(ABPM) Average awake BP ≥135/85 mmHg and asleep BP ≥120/75 mmHg. HARRISON 19 TH ED

6. In children and adolescents: Systolic and/or diastolic blood pressure consistently >95 th percentile for age, sex, and height. Blood pressures between the 90th and 95th percentiles are considered pre hypertensive. HARRISON 19 TH ED

7. JNC 7 HYPERTENSION CLASSIFICATION

8. ACC/AHA 2017 CLASSIFICATION

9. CIRCULATION NOV 13 2017

10. www.clevelandclinicmeded.com

11. White coat hypertension Approximately 15–20% of patients with stage 1 hypertension based on office blood pressures have average ambulatory readings <135/85 mmHg. This phenomenon, so-called white coat hypertension. Individuals with white coat hypertension are at increased risk for developing sustained hypertension. BRAUNWALDS HEART DISEASE

12. Masked Hypertension Approximately 10% to 20% of individuals are found by ABP or home BP monitoring to have BP that is normal during clinic visits but elevated at other times. BRAUNWALDS HEART DISEASE

13. Resistant Hypertension BP that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes. Ideally, 1 of the 3 agents should be a diuretic. Pseudo v/s True Resistant Hypertension. www.clevelandclinicmeded.com

14. HYPERTENSION is broadly divided into two categories Primary Hypertension(Essential) : 80-95% . Secondary Hypertension: 5-20%. HARRISON 19 TH ED

15. PRIMARY HYPERTENSION Primary hypertension tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors.

16. SECONDARY HYPERTENSION Reversible Renal Endocrine Neurogenic Vascular Iatrogenic/toxic Irreversible Renal Monogenic syndromes

17. Epidemiology ETIOLOGY PREVELANCE RENAL PARENCHYMAL DISEASE 2- 5% CHRONIC GN 1.8% RENOVASCULAR HTN 1- 3.3% ENDOCRINE 1% DRUGS AND SUBSTANCE ABUSE <1% VIJAY RAGHAWA RAO 2 ND ED

18. Renal Hypertension

19. RENAL CAUSES a)Renal parenchymal diseases b) Renovascular hypertension.

20. HTN CKD

21. RENAL PARENCHYMAL DISEASES Renal parenchymal disease is the most common cause of secondary hypertension. Responsible for 2% to 5% of cases. Virtually all disorders of the kidney may cause hypertension. HARRISON 19 TH ED

22. Hypertension is present in >80% of patients with chronic renal failure. In general, hypertension is more severe in glomerular diseases than in interstitial diseases. HARRISON 19 TH ED

23. CAUSES Acute and chronic glomerulonephritis Pyelonephritis . Interstitial nephritis. Renal tumors Polycystic kidney disease. Liddles syndrome Gordons syndrome.

24. RENOVASCULAR HYPERTENSION Potentially curable form of hypertension. Most renovascular hypertension develops from partial obstruction of one main renal artery.

25. Epidemiology Common Disease: Incidence General Population 0.1% HTN 0.6 to 3% Ressistant HTN 10-20% Malignant HTN and Renal Insufficiency 30-40% BRENNER AND RECTORS THE KIDNEY

26. Mechanism: In the initial stages activation of the RAS system over time, recruitment of other pressure mechanisms may contribute to elevated arterial pressure.

27. Causes Atherosclerotic F ibromuscular dysplasia Renal vasculitis Coarctation of the aorta with renal ischemia Aortitis with renal ischemia Cholesterol emboli Compression of this vessel by nearby tumors .

28. RENAL ARTERY ATHEROSCLEROSIS FIBROMUSCULAR DYSPLASIA 90% 10% Elderly (>50) Young age(15-50) M> F F:M , 8:1 Proximal 1/3 Distal 2/3 Associated comorbidity Limited comorbidity BRENNER AND RECTORS THE KIDNEY

29. Pathophysiology

30. Clinical features Clues for Renovascular hypertension . E vidence of atherosclerotic vascular disease. S evere or refractory hypertension. R ecent loss of hypertension control or recent onset of moderately severe hypertension. U nexplained deterioration of renal function Deterioration of renal function associated with an ACE inhibitor.

31. BRAUNWALDS HEART DISEASE

32. Renal Artery Obstruction The Dilemma of Diagnosis Is it the cause of hypertension? Is it the cause of renal insufficiency? Will treatment improve either? Will treatment prevent deterioration?

33. Screening And Diagnostic tests for Renal Artery Stenosis Non Invasive Tests of Choice: depends on patient factors/ availability/ expertise. MRA CT Angiogram Duplex Doppler ultrasound . Renal Arteriogram Gold standard.

34. Duplex Doppler Ultrasound Non Invasive, can detect bilateral disease/ recurrent and or re- stenosis . Less useful for FMD and abnormalities in accessory renal arteries . Renal artery velocity >200 or 300cm/sec Highly operator dependant/ time consuming . Measurement of peak systolic velocity 85% sensitive and 92% specific. Williams, GJ, et al. Comparative accuracy of renal duplex sonographic parameters in the diagnosis of renal artery stenosis: paired and unpaired analysis . AJR Am J Roentgenol 2007; 188:798.

35. MRA in Renal Artery Stenosis Mainly for suspected atherosclerotic lesions. Non invasive, good for proximal lesions. MRA is now less often used, as gadolinium contrast has been associated with nephrogenic systemic fibrosis. Caution with GFR <30 ml/min. Nephrogenic systemic Fibrosis: potentially fatal.

36. Spiral CT with CT Angiogram : Non-Invasive, highly accurate, excellent images. Nephrotoxic potential. Better for atherosclerotic lesions, lower sensitivity In FMD ~ 28%.

37. Comparing Non invasive tests

38. Captopril renography with technetium 99mTc mertiatide (99mTc MAG3) Usefull to Assess Differential Renal Blood Flow. Captopril -mediated fall in filtration pressure amplifies differences in renal perfusion. Normal study excludes renovascular hypertension. Limitations-in patients with advanced atherosclerosis or creatinine >2.0 mg/dl.

39. TREATMENT

40. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA /ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults

41. Indications for Revascularization of RA Resistant hypertension Progressive renal insufficiency during treatment of hypertension. Decline in the GFR during therapy with ACE inhibitors or ARBs. Recurrent congestive heart failure in a patient in whom the adequacy of left ventricular function does not explain a cause

42. Factors Favoring Medical Therapy and Surveillance of Renal Artery Disease Controlled blood pressure with stable renal function (e.g., stable renal insufficiency) Stable renal artery stenosis without progression on surveillance studies (e.g., serial duplex ultrasound) Very advanced age and/or limited life expectancy.

43. Extensive comorbidity that make revascularization too risky High risk for or previous experience with atheroembolic disease Other concomitant renal parenchymal diseases that cause progressiv renal dysfunction (e.g., interstitial nephritis, diabetic nephropathy)

44. ENDOCRINE

45. Primary Aldosteronism Very uncommon cause. However, in studies systematically screening all patients with HTN prevalence varies from 5% to 12% of hypertensive individuals. Prevelance is higher pateints with Hypokalemic hypertension. HARRISON 19 TH ED

46. CAUSES OF MINERALOCORTICOID EXCESS PRIMARY HYPERALDOSTERONISM- 99% Adrenal adenoma( conn’s )- 40% Bilateral adrenal hyperplasia- 60% OTHER RARE CAUSES- <1 % Syndrome of apparen mineralocorticoid excess(AME) Cushings syndrome Adrenacartical carcinaoma Congenital adrenal hyperplasia HARRISON 18 TH ED

47. Clinical features BRAUNWALDS HEART DISEASE

48. Clinical features Age- 20 to 40yrs. The clinical hallmark of mineralocorticoid excess is hypokalemic hypertension Serum sodium tends to be normal due to the concurrent fluid retention.

49. Most patients are asymptomatic; however, infrequently, polyuria , polydipsia , paresthesias , or muscle weakness may be present as a consequence of hypokalemic alkalosis. Severe alkalosis contributes to muscle cramps and, in severe cases, can cause tetany

50. Although aldosterone is a salt-retaining hormone, patients with primary aldosteronism rarely have edema .

51. INVESTIGATIONS

52. Hypokalemia Unprovoked hypokalemia : the prevalence of primary aldosteronism approaches 40–50%. Patients on diuretics, serum potassium <3.1 meq /L. However, serum potassium is an insensitive and nonspecific screening test. HARRISON 19 TH ED

53. Plasma Aldosterone Renin ratio(ARR) Usefull screening test. These measurements preferably obtained in ambulatory patients in the morning. A ratio >30:1 in conjunction with a plasma aldosterone concentration >20 ng /dl reportedly has a sensitivity of 90% and a specificity of 91 for an aldosterone -producing adenoma. HARRISON 19 TH ED

54. In a Mayo Clinic series, aldosterone -producing adenoma subsequently was confirmed surgically In >90% of hypertensive patients with a PA/PRA ratio ≥20 and Plasma aldosterone concentration ≥15 ng / dL . HARRISON 19 TH ED

55. Drawbacks of ARR The cutoff for a “high” ratio is laboratory- and assay-dependent. Antihypertensive agents may affect the ratio. Current recommendations are to withdraw aldosterone antagonists for at least 4–6 weeks before obtaining these measurements.

56. Because aldosterone biosynthesis is potassium-dependent, hypokalemia should be corrected with oral potassium supplements prior to screening.

57. A high ratio in the absence of an elevated plasma aldosterone level is considerably less specific for primary aldosteronism . In patients with renal insufficiency, the ratio may also be elevated because of decreased aldosterone clearance.

58. Confirmatory test In patients with an elevated PA/PRA ratio, the diagnosis of primary aldosteronism can be confirmed by demonstrating failure to suppress plasma aldosterone to (<5 ng / dL ) after IV infusion of 2 L of isotonic saline over 4 h.

59. Alternative confirmatory tests include failure to suppress aldosterone (based on test specific criteria) in response to an oral NaCl load, fludrocortisone , or captopril .

60. Imaging High-resolution CT may identify tumors as small as 0.3 cm and is positive for an adrenal tumor 90% of the time. If the CT is not diagnostic, an adenoma may be detected by adrenal scintigraphy with 6 β-[I131] iodomethyl-19- norcholesterol after dexamethasone suppression (0.5 mg every 6 h for 7 days) However, this technique has decreased sensitivity for adenomas <1.5 cm.

61. Bilateral adrenal venous sampling Most accurate means of differentiating unilateral from bilateral forms of primary aldosteronism .

62. The sensitivity and specificity of adrenal venous sampling (95% and 100%, respectively) for detecting unilateral aldosterone hypersecretion are superior to those of adrenal CT. Success rates are 90–96%, and complication rates are <2.5%. HARRISON 19 TH ED

63. ALGORITHM FOR THE DIAGNOSIS AND MANAGENENT OF SUSPECTED MINERALOCORTICOID EXCESS

64. Cushing’s syndrome Excess glucocorticoids of any etiology . Incidence of 1–2 per 100,000 population per year. Hypertension occurs in75-80% of patients. Mechanism: stimulation of mineralocorticoid receptors. HARRISON 19 TH ED

65. Etiology Exogenous Glucocorticoid -MCC ACTH independent ACTH dependent

66. HARRISON 19 TH ED

67. CLINICAL FEATURES Most Specific Nonspecific Spontaneous Bruising Proximal Myopathy Abdominal striae Central obesity w/ extremity wasting Dorsocervical fat pads (“Buffalo Hump” Round facies (“Moon Facies ”) DM HTN Obesity Oligomenorrhea Osteoporosis Depression Insomnia Psychosis Impaired Cognition Hirsutism Fungal Skin Infections Nephrolithiasis Polyuria

68. DIAGNOSIS Exclude exogenous glucocorticoid use. Suspected cases should be tested if there are multiple and progressive features of Cushing’s, particularly features with a potentially higher discriminatory value.

69. ALGORITHM FOR MANAGEMENT OF THE PATIENT WITH SUSPECTED CUSHING’S SYNDROME

70. Ectopic ACTH syndrome Further imaging should include high-resolution, fine-cut CT scanning of the chest and abdomen for scrutiny of the lung, thymus, and pancreas. If no lesions are identified, an MRI of the chest can be considered because carcinoid tumors usually show high signal intensity on T2-weighted images. Furthermore, octreotide scintigraphy can be helpful in some cases because ectopic ACTH-producing tumors often express somatostatin receptors.

71. TREATMENT In ACTH-independent: -Small tumors : minimally invasive surgery -Large tumors /malignant: open surgery In ACTH-dependent: -Endoscopic transsphenoidal approach. -This results in an initial cure rate of 70–80% when performed by a highly experienced surgeon.

72. Long-term follow-.If pituitary disease recurs, there are several options including second surgery, radiotherapy, stereotactic radiosurgery and bilateral adrenalectomy .

73. Medical treatment INDICATIONS Overt Cushing’s (e.g., difficult to control hypokalemic hypertension or acute psychosis) Before surgery. patients with metastasized, glucocorticoid -producing carcinomas . Ectopic ACTH syndrome

74. Antiglucocortiod drugs Metyrapone : starting doses are 500 mg tid . (maximum dose, 6 g) Ketoconazole : 200 mg tid (maximum dose, 1200 mg). Mitotane : In adrenocortical carcinoma, low-dose treatment (500–1000 mg/d)

75. Etomidate : can be used to lower cortisol in severe cases. It is administered by continuous IV infusion in low, nonanesthetic doses

76. Pheochromocytoma These are catecholamine-producing tumors derived from the sympathetic or parasympathetic nervous system. Incidence 2–8 / 1 million per year. ∼0.1% of hypertensive patients harbor a pheochromocytoma . M = F, 3rd to 10th decades of life. HARRISON 19 TH ED

77. World Health Organization (WHO) restricts the term pheochromocytoma to adrenal tumors and applies the term paraganglioma to tumors at all other sites.

78. Etiology Sporadic Familial MEN 2a and 2b- NF1 (Von Recklinghausen's )

79. Other: 1. Tuberous sclerosis 2. Sturge -Weber 3. Ataxia- telangectgasia 4. Carney’s Triad ( Pheo , Gastric Leiomyoma , Pulm chondroma )

80. CLINICAL FEATURES CLASSIC TRIAD. Episodes of palpitation Headache. Profuse sweating. PLUS Hypertension

81. Classically, patients have episodic hypertension, but sustained hypertension is also common. Resistant hypetension .

82. DIAGNOSIS The diagnosis is based on Documentation of catecholamine excess by biochemical testing Localization of the tumor by imaging.

83. Biochemical tests Elevated plasma and urinary levels of catecholamines and metanephrines form the cornerstone of diagnosis.

84. HARRISON 19 TH ED

85. Diagnostic Imaging CT and MRI are similar in sensitivity. T2-weighted MRI with gadolinium contrast is optimal for detecting pheochromocytomas and is somewhat better than CT for imaging extraadrenal pheochromocytomas and paragangliomas

86. MIBG Scan (123I or 131I labelled metaiodobenzylguanidine ) Cases where pheo diagnosed biochemically but no tumor on CT/ MRI MIBG catecholamine precurosr taken up by the tumor .

87. Treatment Complete tumor removal, the ultimate therapeutic goal, can be achieved by partial or total adrenalectomy . Minimally invasive techniques (laparoscopy or retroperitoneoscopy ) have become the standard approaches in pheochromocytoma surgery.

88. Preoperative preparation BP < 160/90 mmHg. α-adrenergic blockers -oral phenoxybenzamine , 0.5–4 mg/kg of body weight -Oral prazosin or intravenous phentolamine Beta blockers (e.g., 10 mg TID/QID) Calcium channel blockers ACEIs

89. Blood pressure can be labile during surgery,. Nitroprusside infusion is useful for intraoperative hypertensive crises, and hypotension usually responds to volume infusion.

90. Obstructive sleep apnea HTN is reported in > 50% of individuals with sleep apnea. Severity of HTN correlates with severity of OSA. HTN due to OSA should be considered in patients with drug resistant HTN and history of snoring. HARRISON 19 TH ED

91. Mechanisms Elevated plasma catecholamine levels. With repeated arterial desaturation during apneas , activation of carotid body chemoreceptors causes dramatic pressor episodes throughout the night and resets the chemoreceptor reflex. Daytime normoxia is misinterpreted as hypoxia, producing sustained reflex sympathetic activation and hypertension even during waking hours.

92. Diagnosis is by polysomnography . Weight loss reduce OSA and Hypertension. With CPAP patients with apparently drug-resistant hypertension may be more responsive to antihypertensive agents.

93. Coarctation of the aorta MC congenital cardiovascular cause of hypertension. Incidence is 1–8 per 1000 live births. It is usually sporadic but occurs in 35% of children with Turner’s syndrome. HARRISON 19 TH ED

94. Clinical features Radio-femoral or Radio-radial delay. Difference BP between Rt and left or UL and LL. A blowing systolic murmur may be heard in the posterior left interscapular areas.

95. Diagnosis may be confirmed by chest x-ray and transesophageal echocardiography. Therapeutic options include surgical repair and balloon angioplasty, with or without placement of an intravascular stent. Even after surgical correction 30% of patients develop subsequent HTN.

96. Hypertension During Pregnancy In about 12% of first pregnancies in previously normotensive women, hypertension appears after 20 weeks (gestational hypertension). In about half of cases , this hypertension will progress to preeclampsia when it is complicated by proteinuria , edema , or hematologic or hepatic abnormalities.

97. which in turn increase the risk of progress to eclampsia , defined by the occurrence of convulsions

98. Women with hypertension predating pregnancy have an even higher incidence of preeclampsia. The diagnosis is based on a rise in pressure of 30/15 mm Hg or more to a level above 140/90 mm Hg.

99. Drugs and Toxins

100. Oral Contraceptive Use The use of estrogen -containing oral contraceptive (OC) pills can cause secondary hypertension in young women. OC use probably causes hypertension by volumeexpansion because estrogens and some synthetic progestogens used in OC pills cause sodium retention.

101. When use of the OC is discontinued, BP falls to normal within 3 to 6 months in about 50% of patients.

102. The use of estrogen -containing OCs should be restricted in women older than 35 years, particularly if they also smoke or are hypertensive or obese.

103. If BP has risen, an alternative contraceptive method should be offered. If OC remains the only acceptable contraceptive method, Drospirenone -containing OC pills are a better alternative. Drospirenone contain a spironolactone -like moiety with mild mineralocorticoid antagonist action.

104. Monogenic Hypertension FEATURE LIDDLE’S SYNDROME GORDON’S SYNDROME INHAERITANCE AUTOSOMAL DOMINANT AUTOSOMAL DOMINANT DEFECT APICAL SODIUM CHANNEL NA- CL CHANNEL OVERACTIVITY CHARCTERSTICS HYPOKALEMIA METABOLIC ALKALO SIS HYPERYTENSION LOW RENIN, LOW ALDOSTERONE HYPERKALEMIA METABOLIC ACIDOSIS HYPERTENSION LOW RENIN, LOW ALDOSTERONE TREATMENT POTASSIUM CHANNEL BLOCKER THIAZIDE DIURETICS

105. OTHER RARE MONOGENIC TYPES Congenital adrenal hyperplasia. - 11β- hydroxylase deficiency - 17α- hydroxylase deficiency -21 hydroxylase deficiency Glucocorticoid -remediable hyperaldosteronism

106. APPROACH TO PATIENT WITH HYPERTENSION

107. .

108. PHYSICAL EXAMINATION: BP should be measured in both arms, if HTN is detected before 30 years BP should be measured in lower limb. 2) Heart rate should be noted and all peripheral pulses should be felt to look for peripheral vascular disease. 3) Neck should be palpated for thyroid swelling.

109. 4) Auscultation for bruits over carotid ,femoral, and renal artery . 5) Fundoscopy . 6 ) Cardiac examination to look for apex , S4 . 7 ) Neurological examination.

110. TREATMENT Lifestyle interventions. 2) P harmacologic therapy.

111. Pharmacologic therapy Lowering SBP by 10-12 mm hg and DBP by 5-6 mm hg confers relative risk reduction of 35-40% for stroke,and 12-16% for CHD within 5yrs of initiation of treatment.

112. SALIENT FEATURES OF JNC 8 Advises higher BP goals and less use of several types of antihypertensives . Control of SBP and DBP with age and comorbidity specific cut offs.

113. INDICATION TO START TREATMENT AND GOALS PATIENT GROUP JNC 8 2014 AHA 2017 JNC 7 2004 1) ≥ 60 YRS ≥ 150/90 2)< 60 YRS ≥ 140/90 ≥ 140/90 ≥140/90 3) DM (ANY AGE) ≥ 140/90 ≥ 130/80 ≥130/80 4) CKD (ANY AGE) ≥ 140/90 ≥ 130/80 ≥130/80 5)HIGH CVD RISK ≥ 130/80

114. AHA/ACC 2017 BP GOAL

115. INDICATION TO START TREATMENT

116. Other guidelines ADA 2013- BP <140/80. KIDIGO- 2012 CKD No Proteinuria - <140/90 CKD with Proteinuria - <130/80

117. The first line of antihypertensives 1) Thiazide diuretics. 2)CCB. 3) ACE inhibitors. 4) ARB.

118. ACC/AHA 2017 GUIDELINES Prevalence ACC/AHA- 45.6% . JNC 7- 31.9%. Antihypertensive medication was recommended ACC/AHA- 36.2% JNC7- 34.3%.

119. Compared with the JNC8 panel member report, an additional 5.1% of US adults were recommended antihypertensive medication according to the 2017 ACC/AHA guideline

120. Those with hypertension defined by the 2017 ACC/AHA guideline but not the JNC7 guideline were younger, had lower total cholesterol, SBP, DBP and 10-year predicted CVD risk levels, and were less likely to have diabetes, reduced eGFR , albuminuria and a history of CVD.

121. Among US adults taking antihypertensive medication, 53.4% had above goal BP according to he 2017 ACC/AHA guideline compared to 39.0% with above goal BP according to the JNC7 guideline. Overall, 28.7% of US adults had BP above goal according to the thresholds in the 2017 ACC/AHA guideline but met the BP goal according to the JNC8 panel member report

122. Also, 14.4% of US adults taking antihypertensive medication had a BP above the goal defined by the 2017 ACC/AHA guideline whereas they would have met the BP goal according to the JNC7 guideline

123. In addition, intensive antihypertensive drug treatment in patients with hypertension to BP goals below those recommended in the JNC7 guideline have been associated with CVD and mortality risk reduction benefits.

124. Nonpharmacological therapy on its own is the recommended treatment for the majority of US adults with SBP/DBP of 130-139/80-89 mm Hg. The 2017 ACC/AHA guideline concluded there is insufficient evidence to support a recommendation for antihypertensive drug treatment in addition to nonpharmacological therapy.

125. However, the diagnosis of hypertension provides an opportunity for healthcare providers and patients to discuss the value of nonpharmacological therapy.

126. Reference Harrison 19 th ed. Williams textbook of Endocrinology. Brenner and Rectors The Kidney 9 th ed Braunwalds Heart Disease 9 th ed JNC 7 and 8 guidelines. ACC/AHA 2017 guidelines on Hypertension. KIDIGO and ADA guidelines.

127. THANK YOU