Approach to secondary hypertension in young patients

1. APPROACH TO SECONDARY
HYPERTENSION IN YOUNG
PATIENTS

2. Classification of Hypertension
• The Eight Report of the Joint National Committee
Alabama pharmacy ASSOCIATION 8 | Summer 2015: Continuing EDUCATION

3. Risk factors for Hypertension in Young Patients
• Physical inactivity
• Family history
• Diabetes
• Obesity
• Tobacco products & alcohol
• Drugs- Amphetamine, Cocaine
• Psychosocial risk factors, higher time urgency, impatience, and hostility in
young adults aged 18– 30 year
• In one study, 20-35 year age group, having exaggerated response to
exercise towards SBP & DBP
JAMA 2003;290(16):2138–2148.
Am J Hypertens. 1994;7:234–241.

4. Epidemiology (18-39 year age group)
• The prevalence of hypertension (age adjusted) among US adults ≥ 18
years of age is estimated to be 28.6%, based on National Health and
Nutrition Examination Survey (NHANES) data
• Among adolescents and young adults (18 – 39 years old) the incidence is
>10%
• Worryingly, there has been a startling increase, with the prevalence
approximately doubling in this age group within a decade3
Circulation. 2014;129: e28–e292
HSRC Press, 2014
Medical Research Council South Africa, 2011.

5. Clinical Presentation of Hypertension
• Most young patients are asymptomatic and diagnosed during screening or
when presenting with an unrelated condition
• May present with symptom of raised blood pressure is Headache i.e.,
“Hypertensive headache” occurs in the morning and is localized to the
occipital region generally occurs only in patients with severe hypertension
• A minority present with a hypertensive emergency (heart failure, renal
failure or malignant hypertension etc.)

6. Secondary Hypertension
• • Secondary hypertension is a type of hypertension with an underlying
identifiable and potentially correctable cause
• • Hypertension due to underlying etiology affects approximately 10% of
young hypertensives
• • The probability of secondary hypertension is inversely proportional to the
age of the patient (i.e. higher in a school-going child, but lower in a young
adult)
• • Secondary hypertension is curable with appropriate treatment
Pediatr Cardiol 2012;33(7):1013-1020.

7. Clinical features of Secondary Hypertension

8. Causes of Secondary
Hypertension

9. Most Common Causes of Secondary Hypertension by
Age
Am Fam Physician 2010 Dec 15; 82(12):
1471-8.

10. Signs and Symptoms That Suggest Specific Causes of
Secondary Hypertension
Am Fam Physician 2010 Dec 15;82(12):1471-8.

11. Signs and Symptoms That Suggest Specific Causes of
Secondary Hypertension
Am Fam Physician 2010 Dec 15;82(12):1471-8.

12. GeneralApproach to the Patient
• Proper history including patient’s diet, habits & family history
• Physical examination
• Investigation: Oriented towards
• To detect risk factors
• To detect etiology of hypertension
• To detect target organ damage
The majority(>90%) of young patients will have primary hypertension, while
only a minority (<10%) will have secondary hypertension. it is not
recommended an extensive workup for all newly diagnosed young
hypertensives, as has been the practice in the past.

13. Evaluation for
Suspected
Secondary
Hypertension

14. Accuracy of Diagnostic
Tests for Causes of
Secondary Hypertension

15. Detection of Secondary forms of Hypertension
Features of secondary Hypertension
• Poor response to therapy (resistant hypertension)
• Worsening of control in previously stable hypertensive patient
• SBP > 180 mm Hg or DBP >110 mm Hg
• Onset of hypertension in persons younger than age 30 or older than age 55
• Significant hypertensive target organ damage
• Lack of family history of hypertension

16. Renal & renovascular hypertension
Most common causes in young:
• Renal parenchymal disease(acute/chronic)
• Fibromuscular dysplasia
• Takayasu’s artritis
• Renin-Secreting Tumors

17. Approach to renal / renovascular hypertension
• History:
• Abrupt onset of hypertension <30 years or >50 years of age
• Severe or resistant hypertension (≥3 drugs)
• Symptoms of atherosclerotic disease elsewhere
• Negative family history of hypertension
• Smoker
• Worsening renal function after renin-angiotensin inhibition i.e., increase in S. creatinine
level by ≥30%
• Recurrent “flash” pulmonary edema
• Physical Examination Findings:
• Abdominal bruits
• Other bruits
• Advanced fundal changes
Hypertension Canada CHEP Guidelines for the Management of Hypertension 2016

18. Approach to renal / renovascular hypertension
• Laboratory Findings:
• Raised serum creatinine level
• Low serum K+ & Na+ level
• Raised plasma renin level
• Proteinuria, usually moderate
• Secondary aldosteronism
• USG-Unilateral small (atrophic) kidney size
• Special tests for renovascular hypertension:
• Renal vein renin ratio (>1.5affacted/contralateral)
• Captopril enhanced radioisotope renal scan
• Doppler sonography
• Magnetic resonance angiography
• CT- angiography (for those with normal renal function)
Hypertension Canada CHEP Guidelines for the Management of Hypertension 2016

19. Renal CT angiogram with 3D reconstruction
Severe prox. Atherosclerotic stenosis of the Rt.
renal artery and mild stenosis of the left renal
artery
Classic “string-of-beads” lesion of
fibromuscular dysplasia

20. Fibromuscular Dysplasia, before and after PTRA

21. Atherosclerotic RAS before and after
stenting

22. Takayasu’s arteritis: Indian studies

23. Study at PGI Chandigarh
• 205 patients with hypertension ere shown to have renovascular aetiology
over 16 yrs .
• Of these –
• 125 (61%) - Takayasu’s arteritis
• 58 (28.3%) – Fibromuscular dysplasia
• 16 (7.8%) – Atherisclerosis
• 5 (2.4%) – Polyarteritis nodosa and
• 1 (0.5%) – Renal artery aneurysm
Q J Med. 1992;85:833-43.

24. Study at PGI Chandigarh
• Among the TA patients, males were affected as commonly as females
• The mean age – 26.8 ± 8.6 years (range 5 -52)
• Type I – arteritis in 9 (7.2%)
• Type II – 40 (32%) patients and
• Type III – 76 (60.8%) patients
• The abdominal aorta was involved in 117 (93.3%) patients
Q J Med. 1992;85:833-43.

25. Seth GS Medical College and KEM Hospital, Parel, Mumbai
• Medical records of 54 patients with RVH showed
• Aortoartertis – 44 (81.5%)
• Atherosclerotic disease 7 (31.5%) and
• Fibromusculaar dysplasia 3 (5.6%) as etiologies of RVH
32nd Annual Conference of Indian Society of Nephrology September, 2001

26. Mineralocorticoid-Induced Hypertension
• Primary aldosteronism:
• Aldosterone-producing adenoma
• Unilateral/Bilateral adrenal hyperplasia
• Glucocorticoid-remediable aldosteronism
• Cortisol Excess:
• Cushing syndrome
• Deoxycorticosterone Excess:
• Deoxycorticosterone-secreting tumors
• Congenital adrenal hyperplasia
• 11β-Hydroxylase deficiency
• 17α-Hydroxylase deficiency

27. Hyperaldosteron induced hypertension
• Clinical feature:
• Hypertensive patients with spontaneous hypokalemia (K+ <3.5 mmol/L) or marked diuretic-
induced hypokalemia (K+ <3.0 mmol/L)
• Screening for hyperaldosteronism:
• Serum K+ and HCO3- & serum Na+ and Mg2+
• Plasma aldosteron/plasma renin activity
• Oral salt loading suppression test
• Adrenal vein sampling

28. Subtype evaluation of Primary aldosteronism
• Adrenal CT scan
• Adrenal venous sampling
• Posture stimulation test

29. Adrenal CT scan
a. CT scan showing a9-mm left adrenal aldosterone producing adenoma (arrow)
b. left adrenocortical carcinoma

30. Adrenal venous sampling
AVS is the gold standard test to differentiate unilateral from bilateral disease
in PA.

31. SUBTYPE TESTING, AND TREATMENT OF PA

32. Cortisole excess hypertension
• Clinical feature:
• Suspected in hypertensive patients with truncal obesity, wide purple striae, thin skin,
muscle weakness, and osteoporosis (80%)
• If left untreated, it can cause marked LVH and congestive heart failure
• The secretion of mineralocorticoids can increase along with cortisol, which itself is a potent
activator of the mineralocorticoid receptor
• Screening:
• Measurement of free cortisol in a 24-hour urine sample
• Dexamethasone suppression test
• Determination of late-night salivary cortisol

33. Approach for diagnosis Cushing’s syndrome
Steps of work up Cushing’s syndrome
• Cushing's syndrome?
• Clinical suspicion
• ACTH-dependent or independent
• Laboratory confirmation
• Determining the source of the ACTH
• Localization

35. Deoxycorticosteron excess hypertension
• If hypertension with pseudohermaphroditism/virilisation/musculinization
• Screening for hyperaldosteronism:
• Serum K+ and HCO3- & serum Na+
• Plasma aldosteron/plasma renin activity

37. Catecholamine related hypertension
• Patients with hypertension(paroxysmal) and multiple symptoms suggestive
of catecholamine excess (e.g., Headaches, palpitations, sweating, panic
attacks and pallor)
Sudden paroxysms used to occur in :
• Stress: anesthesia, angiography, parturition
• Pharmacologic provocation: Histamine, Nicotine,
• Caffeine, ß-blockers, TCA,MAO inhibitors
• Manipulation of tumors: abdominal palpation, urination

38. Screening :
• Serum Metanephrine testing highest sensitivity (96%) lower specificity
(85%)
• 24 Hr Urinary metanephrin/Normetanephrin sensitivity(87.5%),sp(99.7%)
• localization of Pheochromocytomas or Paragangliomas
• Magnetic resonance imaging
• Computed tomography (if MRI unavailable)
• I131 Metaiodobenzylguanidine (MIBG) scintigraphy

39. Vascular causes of hypertension
• Most common cause of hypertension is coarctation of aorta in children and
≈8 times more common in boys
• Typically diagnosed around 5 years age with the onset of HTN or a cardiac
murmur, rarely, mild cases of coarctation have occurred in adults
• Discrepancies between bilateral brachial, or brachial and femoral blood
pressures
• Screening & diagnosis:
• Chest radiography:- In younger patients, may be nonspecific, in adults the classic
“three”sign or rib notching may be evident
• Barium swallow:- Show “Reverse 3” sign
• Transthoracic echocardiography
• Magnetic resonance imaging

40. Red arrows - rib notching caused by the dilated intercostal arteries
Yellow arrow - the aortic knob,
Blue arrow - the actual coarctation and
Green arrow - the poststenotic dilation of the descending aorta

41. Hormone related hypertension
• Half of patients with various hormonal disturbances have hypertension:
• Hypothyroidism
• Hyperparathyroidism
• Acromegaly
• Hypercalcemia
• Thyroid hormone affects cardiac output and systemic vascular resistance,
which in turn affect BP
• Hypothyroidism can cause an elevation in DBP
• Hyperthyroidism may cause isolated elevation of SBP(wide P.P.)

42. Treatment of hypertension in young
A. Non pharmacological:
Lifestyle changes:
• Weight reduction and diet modification
• Eliminating refined carbohydrate, reducing saturated fat intake
• Salt intake must be reduced, Avoidance of junk food
• Fresh fruit and vegetables in the diet should be encouraged
• Exercise programme or joining an organised sports programme
• Alcohol use needs to be moderated and tobacco product use discontinued

46. B. Pharmacological:
• Considered in the following situations:-
• Severe hypertension
• After failure of lifestyle therapy
• Patients with target-organ damage
• Secondary causes of hypertension

47. Thiaazide Diuretics
Generic Name Dose (mg/day)
Chlorthalidone 12.5-25 mg
Hydrochlorothiazide 12.5-50 mg
Indapamide 1.25-2.5 mg
Metolazone 2.5-5 mg
First Line Treatments

48. First Line Treatments
• Other newer agents utilized for HTN treatment include angiotensin-
converting enzyme (ACE) inhibitors and angiotensin II receptor blockers
(ARBs)
ACE Inhibitor ARBs
Benazepril Azilsartan
Captopril Candesartan
Enalapril Eprosartan
Fosinopril Irbesartan
Lisinopril Losartan
Moexipril Olmesartan
Perindopril Telmisartan

49. Second Line Treatments
• Other medications utilized for the treatment include beta-blockers,
aldosterone antagonists, alpha-blockers, and direct renin inhibitors
• To name a few –
• Atenolol
• Bisoprolol
• Betaxolol
• Spironolactone
• Eplerenone
• Guanfacine
• Methyldopa
• Doxazosin
• Minoxidil

50. Summary - Screening and confirmatory tests for
evaluating young hypertension

52. Take Home Message
• First to identify the actual hypertensive patients
• Take proper history for symptoms, life style, habits and family history & other
risk factor
• Complete physical examination from head to toe and order to run basic lab
tests
• Extensive workup in all newly diagnosed young hypertensive in search of sec.
cause not recommended always*
• If no evidence of sec. hypertension start early treatment, non -
pharmacological/ pharmacological otherwise treat the cause
• Maintain target blood pressure <140/90 mmHg
• Council for treatment adherence