1. Approach to a young hypertensive patient - Investigations and diagnosis Dr.

2. Overview  Introduction  General Approach to the Patient  Most Common Causes of Secondary HT by Age Children and Adolescents  (Birth to 18 Years of Age)  Renal parenchymal disease  Coarctation of the aorta Young Adults  (19 to 39 Years of Age)  Takayasu’s arteritis in India (Asia)  Fibromuscular dysplasia  Thyroid dysfunction  Algorithm for initial evaluation of secondary HT  Conclusions

3. Introduction SBP, systolic blood pressure; DBP, diastolic blood pressure Classification of Hypertension: The Seventh Report of the Joint National Committee (JNC VII) NIH Publication No. 04- 5230 August 2004

4. General Approach to the Patient  Confirm that the patient’s blood pressure (BP) has been accurately measured using Correct positioning with an appropriately sized cuff  If white coat hypertension suspected Ambulatory BP monitoring can be useful to rule out Hypertension. 2003;42(6):1206-1252, Am Fam Physician. 2009;79(10):863-869.

5. General Approach to the Patient (Contd)  Important to review The patient’s diet and medication use for other potential causes of HT  Excessive consumption of Sodium, Licorice (Hindi: Jethimadh, Mulhathi), or Alcohol is known to increase BP J Clin Hypertens (Greenwich) 2008;10(7):556-566.HT - hypertension

6. General Approach to the Patient (Contd)  Many drugs affect BP A trial period off of a potentially offending medication may be all that is needed to reduce BP Am Fam Physician 2010 Dec 15;82(12):1471-8.

7. General Approach to the Patient (Contd)  If these potential contributors to hypertension have been excluded and  Concern for secondary hypertension remains, the physician can investigate for potential physiologic causes Am Fam Physician 2010 Dec 15;82(12):1471-8.

8. Most Common Causes of Secondary Hypertension by Age* Am Fam Physician 2010 Dec 15;82(12):1471-8. Must remember that these are not absolute categories; There may be overlap of causes between age groups

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

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

11. Children and Adolescents (Birth to 18 Years of Age)  Renal parenchymal disease  Coarctation of the aorta Am Fam Physician 2010 Dec 15;82(12):1471-8.

12. Renal parenchymal disease  Most common cause of hypertension in preadolescent children In this age group, such renal pathology includes  Glomerulonephritis  Congenital abnormalities and  Reflux nephropathy  Sometimes the resulting hypertension is not apparent until young adulthood, so This etiology should still be considered in the differential diagnosis outside of childhood Am Fam Physician 2010 Dec 15;82(12):1471-8.

13. Renal parenchymal disease (Contd)  Initial evaluation for suspected renal parenchymal disease should include Measurement of blood urea nitrogen and creatinine levels A urinalysis Urine culture and Renal ultrasonography Am Fam Physician 2010 Dec 15;82(12):1471-8.

14. Coarctation of the aorta  The second most common cause of HT in children, and Two to five times more common in boys  Although coarctation may present acutely in the neonate as congestive heart failure, It is typically diagnosed around five years of age with the onset of HT or a cardiac murmur  Rarely, mild cases of coarctation have occurred in adults Am Fam Physician 2010 Dec 15;82(12):1471-8.

15. Coarctation of the aorta (Contd)  Discrepancies between bilateral brachial, or brachial and femoral blood pressures, suggest coarctation  Chest radiography In younger patients, may be nonspecific, whereas In adults the classic “three” sign or rib notching may be evident Am Fam Physician 2010 Dec 15;82(12):1471-8.

16. Coarctation of the aorta (Contd) Close up of upper thorax in a patient with Coarctation of the Aorta. Red arrows - rib notching caused by the dilated intercostal arteries Yellow arrow - the aortic knob, Blue arrow - the actual coarctation and Green arrow -the post- stenotic dilation of the descending aorta

17. Coarctation of the aorta (Contd)  Transthoracic echocardiography Sufficient for diagnosis in children, given their smaller body habitus, and Useful to concurrently evaluate for left ventricular hypertrophy  Magnetic resonance imaging (MRI) is increasingly common and The preferred imaging method in adults Am Fam Physician 2010 Dec 15;82(12):1471-8.

18. Young Adults (19 to 39 Years of Age)  Takayasu’s arteritis in India (Asia)  Thyroid dysfunction  Fibromuscular dysplasia  Renal parenchymal disease

19. Takayasu’s arteritis (TA) Although TA has a worldwide distribution, it is observed frequently in Asia than in North America The most common cause of RVH in  India  China  Korea  Japan and other countries of South East Asia Eur J Vasc Endovasc Surg 2007;33, 578-82 RVH-Renovascular hypertension

20. TA: Indian studies  TA In one study from Chandigarh by Sharma et al Takayasu’s arteritis was found as the leading cause of hypertension in hospitalised patients Involvement: 50% cases bilateral and in 28% unilateral  Indicating that this condition must be kept in mind as one of the important causes, especially in northern India, whenever one is considering RVH Angiology 1985; 36: 370-8

21. TA: Indian studies (Contd)  Study at PGI Chandigarh 205 patients with hypertension were shown to have a renovascular aetiology over 16 years. Of these,  125 (61 %) Takayasu's arteritis,  58 (28.3 %) fibromuscular dysplasia,  16 (7.8 %) atherosclerosis,  five (2.4 %) polyarteritis nodosa and  one (0.5 %) renal artery aneurysm Q J Med. 1992;85:833-43.

22. TA: Indian studies (Contd)  Study at PGI Chandigarh (Contd)  Among patients with TA, males were affected as commonly as females  The mean age of these patients at the time of detection was 26.8 +/- 8.6 years (range 5-52 years) Type I arteritis in nine (7.2 %), Type II in 40 (32 %) and Type III in 76 (60.8 %) patients  The abdominal aorta was involved in 117 (93.3 %) patients TA was associated with ulcerative colitis in two patients and with renal amyloidosis and focal segmental glomerulosclerosis with a nephrotic syndrome in one patient each Q J Med. 1992;85:833-43.

23. TA: Indian studies (Contd)  Seth GS Medical College & KEM Hospital, Parel, Mumbai Medical records of 54 patients with RVH showed Aortoarteritis 44 (81.5%), Atherosclerotic disease 7 (31.5%) and Fibromuscular dysplasia 3 (5.6%) as etiologies of RVH 32nd Annual Conference of Indian Society of Nephrology September, 2001

24. TA (Contd)  TA is a chronic vasculitis involving mainly the aorta and its branches, as well as the pulmonary and coronary arteries  Classical definition of TA is that of Chronic, progressive, inflammatory, occlusive disease of the aorta and its branches Eur J Vasc Endovasc Surg 2007;33, 578-82

25. TA: Aetiology  Remains enigmatic  Various mechanisms such as post- infective, autoimmune, ethnic susceptibility and a genetic predisposition have been postulated  Autoimmunity appears to be the most plausible mechanism Eur J Vasc Endovasc Surg 2007;33, 578-82

26. TA: Diagnostic criteria  Following table mentions Sensitivity and specificity for the various diagnostic criteria Eur J Vasc Endovasc Surg 2007;33, 578-82

27. TA: Diagnostic criteria Eur J Vasc Endovasc Surg 2007;33, 578-82 Modified diagnosis criteria for TA: Sharma et al

28. TA: Diagnostic criteria (Contd) Eur J Vasc Endovasc Surg 2007;33, 578-82 Modified diagnosis criteria for TA: Sharma et al (Contd)

29. TA: Diagnostic criteria (Contd) Eur J Vasc Endovasc Surg 2007;33, 578-82  Type I is limited to the aortic arch and its branches  Type II affects the descending thoracic and abdominal aorta  Type III is extensive form involving the arch and the thoracic and abdominal aorta  Type IV is designated to those cases with pulmonary involvement in addition to the features of type I, II, or III

30. TA: Clinical features  TA classically progresses through 3 stages: An early systemic illness usually associated with constitutional symptoms and fever A vascular inflammatory phase The inflammation settles down or burns out Eur J Vasc Endovasc Surg 2007;33, 578-82

31. TA: Clinical features (Contd) Eur J Vasc Endovasc Surg 2007;33, 578-82

32. Fibromuscular dysplasia (FMD)  10% of cases of RVH are due to FMD Mainly in younger women Bilateral renal artery involvement with extension into the distal portion of the artery and its branches is common US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

33. FMD (Contd)  Vascular disorder of unknown etiology that has a predilection for the renal arteries, causing narrowing that leads to decreased renal perfusion  In young adults, particularly women, FMD is one of the most common causes of secondary hypertension  Patients with renal artery stenosis may have an audible high-pitched holosystolic renal artery bruit Am Fam Physician 2010 Dec 15;82(12):1471-8.

34. FMD (Contd)  Compared with patients without such a finding, those in whom a renal artery bruit is detected have a relative risk of approximately 5.0 for renal artery stenosis; these patients should all have further testing Am Fam Physician 2010 Dec 15;82(12):1471-8.

35. FMD (Contd)  Although angiography is the diagnostic standard for detecting renal artery stenosis, it is invasive and should not be used as an initial diagnostic test  MRI with gadolinium contrast media and computed tomography (CT) angiography are equally accurate in visualizing stenosis Am Fam Physician 2010 Dec 15;82(12):1471-8.

36.  CT angiogram obtained in a 45 y.o. woman presenting with new onset RVH  Aneurysmal dilation and vascular occlusion beyond a fibromuscular lesion is present in the right kidney associated with loss of perfusion to the entire upper pole of the kidney FMD (Contd)

37. Fibromuscular Dysplasia, before and after PTRA Safian & Textor. NEJM 344:6;

38. FMD (Contd)  MRI Does not use radiation and can determine the physiologic degree of stenosis Can also be used for patients with poor renal function, particularly when used without gadolinium, although with a slight decrease in sensitivity and specificity  If MRI and CT angiography are contraindicated, renal Doppler can be used;  Doppler Provides useful information regarding blood flow, but Its accuracy is affected by body habitus and operator skill Am Fam Physician 2010 Dec 15;82(12):1471-8.

39. FMD (Contd)  Captopril-augmented renography has Poor sensitivity and specificity, which translate into likelihood ratios close to 1.0, No longer considered a good first-line test Am Fam Physician 2010 Dec 15;82(12):1471-8.

40. Thyroid dysfunction  Thyroid hormone affects cardiac output and systemic vascular resistance, which in turn affect BP Hypothyroidism can cause an elevation in diastolic BP, whereas Hyperthyroidism can cause an isolated elevation of systolic BP, leading to a widened pulse pressure Am Fam Physician 2010 Dec 15;82(12):1471-8.

41. Thyroid dysfunction Contd)  Although hypothyroidism is one of the more common secondary causes of hypertension in young adults, There is actually an increased incidence of hypothyroidism with age, peaking in a patient’s 60s  In contrast, hyperthyroidism is significantly associated with elevated BP in 20- to 50-year-olds Am Fam Physician 2010 Dec 15;82(12):1471-8.

42. Thyroid dysfunction (Contd)  Because thyroid dysfunction occurs across multiple age groups, testing for it should be considered if there are any suggestive symptoms  Thyroid-stimulating hormone is a sensitive marker used for initial diagnosis of either condition Am Fam Physician 2010 Dec 15;82(12):1471-8.

43. Accuracy of Diagnostic Tests for Causes of Secondary Hypertension Am Fam Physician 2010 Dec 15;82(12):1471-8.

44. Algorithmic approach to the initial evaluation of patients with suspected secondary hypertension CT = computed tomography; MRI = magnetic resonance imaging; TSH = thyroid-stimulating hormone Am Fam Physician 2010 Dec 15;82(12):1471-8.

45. Conclusions  Prevalence and etiology of hypertension varies with age  Young/early onset hypertension should be approached with evaluation of Symptoms  (e.g., flushing and sweating s/o pheochromocytoma), Examination findings  (e.g., a renal bruit s/o renal artery stenosis), or Laboratory abnormalities  (e.g., hypokalemia s/o aldosteronism) s/o- suggestive of

46. Conclusions (Contd)  In young adults, particularly women, renal artery stenosis caused by fibromuscular dysplasia is one of the most common secondary etiologies FMD can be detected by abdominal magnetic resonance imaging or computed tomography  Takayasu’s arteritis is common cause for hypertension in young adults in Asian countries must keep in mind

47. Any questions?