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 19TH ED

6. • In children and adolescents:
Systolic and/or diastolic blood pressure
consistently >95th percentile for age, sex, and
height.
• Blood pressures between the 90th and 95th
percentiles are considered pre hypertensive.
HARRISON 19TH 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 19TH 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 2ND 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 19TH 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 19TH 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.

28. Causes
 Atherosclerotic
 Fibromuscular dysplasia
 Renal vasculitis
 Coarctation of the aorta with renal ischemia
 Aortitis with renal ischemia
 Cholesterol emboli
 Compression of this vessel by nearby tumors.

29. 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

30. Pathophysiology

32. Clinical features
Clues for Renovascular hypertension.
• Evidence of atherosclerotic vascular disease.
• Severe or refractory hypertension.
• Recent loss of hypertension control or recent
onset of moderately severe hypertension.
• Unexplained deterioration of renal function
• Deterioration of renal function associated
with an ACE inhibitor.

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

41. 2017
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH
/ASPC/NMA/PCNA Guideline for
the Prevention, Detection, Evaluation, and

42. 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

43. 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.

44. • 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)

45. ENDOCRINE

47. 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 19TH ED

48. 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 18TH ED

49. Clinical features
BRAUNWALDS HEART DISEASE

50. 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.

51. • 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

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

53. INVESTIGATIONS

54. 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 19TH ED

55. 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 19TH ED

56. 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.

57. 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.

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

59. • 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 19TH ED

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

63. 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 19TH ED

64. Etiology
• Exogenous Glucocorticoid-MCC
• ACTH independent
• ACTH dependent

65. HARRISON 19TH 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

70. 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.

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

73. 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.

74. 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.

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

76. 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

77. 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)

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

79. 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 19TH ED

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

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

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

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

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

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

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

92. 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

93. 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.

94. 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.

95. 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

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

97. 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 19TH ED

98. 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.

99. • 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.

100. 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 19TH ED

101. 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.

102. • 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.

103. 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.

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

105. • 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.

107. Drugs and Toxins

108. 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

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

110. APPROACH TO PATIENT WITH
HYPERTENSION

111. .

113. PHYSICAL EXAMINATION:
1) 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.

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

118. TREATMENT
1) Lifestyle interventions.
2) Pharmacologic therapy.

120. 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.

121. 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.

122. 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

123. AHA/ACC 2017 BP GOAL

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

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

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

132. • 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

134. • 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

135. • 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.

136. • 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.

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

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

142. THANK YOU