Approach to young hypertensive patients

brief introduction to approach to young hyperte

1. Approach to young hypertensive patients Moderator Speaker Prof. G. Subramanian Dr. Chandan Kumar MD,DM,FIAE,FISC,FCSI,FMMC

2. Introduction Persistent elevation of office blood pressure >140/90 mmHg based on the evidence from RCTs that in patients with these BP values treatment-induced BP reductions are beneficial European Heart Journal (2013) 34, 2165

3. Hypertensive urgency : B lood pressure ≥180 /120 mm Hg in the absence of progressive target organ dysfunction Hypertensive emergency : persistent ≥180/120 mmHg associated with impending or progressive organ dysfunction, such as major neurological changes, hypertensive encephalopathy , stroke, acute LVF, acute pulmonary edema , aortic dissection, renal failure, or e clampsia Malignant hypertension: is a syndrome a/w an abrupt increase of BP with ischemic organ dysfunction (retina, kidney, heart or brain ) in a patient with underlying hypertension or related to the sudden onset of hypertension in a previously normotensive individual Accelerated hypertension: recent significant increase of baseline BP a/w target organ damage (vascular damage) seen as presence of retinal flame shaped hemorrhage or exudate without papilledema National Heart Foundation Hypertension Guideline – 2016  

4. Risk factors for hypertension in young Yan LL, Liu K, Matthews KA, et al. Psychosocial factors and risk of hypertension. The Coronary Artery Risk Development in Young Adults (CARDIA) study. JAMA 2003;290 (16):2138–2148 . Manolio TA, Burke GL , Savage PJ, et al. Exercise blood pressure response and 5-year risk of elevated blood pressure in a cohort of young adults: the CARDIA Study . Am J Hypertens . 1994;7:234–241. 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 1 In one study, 20-35 year age group, having exaggerated response to exercise towards SBP & DBP 2

5. 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 1 Among adolescents and young adults (18 – 39 years old) the incidence is >10% 2 Worryingly, there has been a startling increase, with the prevalence approximately doubling in this age group within a decade 3 Epidemiology: ( 18-39 year age group) Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update. A report from the American Heart Association. Circulation. 2014;129 : e28 –e292 . Shisana O, Labadarios D, Rehle T, et al. South African National Health and Nutrition Examination Survey (SANHANES-1): 2014. Cape Town: HSRC Press, 2014 . Bradshaw D, Steyn K, Levitt N, Nojilana B. Non-communicable Diseases: A Race Against Time. Cape Town : Medical Research Council South Africa, 2011 .

6. 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., “ H ypertensive 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.)

7. Primary hypertension Primary hypertension (also called essential hypertension) has no specific cause,genetic and environmental factors play an important role 1 More than 90% (85-95%) of young people with hypertension have primary hypertension 2,3 It is often associated with a family history of hypertension and frequently accompanied by obesity or the metabolic syndrome Novel mechanisms implicated in the pathogenesis include: Low birth weight ( Barker -Brenner hypothesis ) Weber M, Schiffrin E, White W, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. A Statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens 2014;32(1):3-15. Assadi F. The growing epidemic of hypertension among children and adolescents: A challenging road ahead . Pediatr Cardiol 2012;33(7):1013-1020. [http:// dx.doi.org /10.1007/s00246-012-0333-5 ] Flynn JT. Hypertension in children. In: Kaplan N, ed. Kaplan’s Clinical Hypertension. 9th ed. Philadelphia : Lippincott Williams and Wilkins, 2006 .

8. 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 1 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 ) 1 Secondary hypertension is curable with appropriate treatment Assadi F. The growing epidemic of hypertension among children and adolescents: A challenging road ahead . Pediatr Cardiol 2012;33(7):1013-1020. [http:// dx.doi.org /10.1007/s00246-012-0333-5]

9. General Approach to the Patient Proper history including patient ’s diet, habits & family history P hysical examination Investigation : O riented 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 . Management S Afr Med J 2016;106(1):36-38. DOI:10.7196/SAMJ.2016.v106i1.10329

10. I nitial evaluation for hypertension accomplishes following goals : Accurate measurement of blood pressure/confirmation Assessment of the patient’s overall cardiovascular risk Detection of target organ disease Detection of secondary forms of hypertension Evaluation of the p atient :

11. Retinal photographs showing the stages of hypertension retinopathy. A, Mild diffuse arteriolar narrowing. B, Arterial-venous nicking. C, Hemorrhages and exudates. D, Papilledema. (From Grosso A, Veglio F, Porta M, et al: Hypertensive retinopathy revisited: some answers, more questions. Br J Ophthalmol 89:1646, 2005.)

12. Technique for Office Blood Pressure Measurement The patient should be resting comfortably for 5 minutes in the seated position with back support with no talking and patients’s legs should not be crossed Choose a cuff of bladder size matched to the size of the arm with bladder width ≈40 % & length 80–100 % of arm circumference Place the lower edge of cuff 3 cm above elbow crease and bladder centered over brachial artery Increase the pressure rapidly 30 mmHg above the level of extinguished radial pulse Cuff deflation rate must be of 2 mmHg per beat for accurate systolic & diastolic estimation European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents 2016 Accurate measurement of blood pressure

13. White coat hypertension: W hich encompasses subjects with office systolic/diastolic blood pressure readings of ≥140/90 mm Hg and a 24-hour blood pressure <130/80 mm  Hg White-coat hypertension occurs in 15 % - 30 % of subjects with an elevated office blood pressure O’Brien E,  Parati  G,  Stergiou  G, et al; on behalf of the European Society of Hypertension Working Group on Blood Pressure Monitoring. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens . 2013; 31 :1731– 1767

14. When to suspect white coat hypertension If office blood pressure is ≥140/90 mm Hg on ≥3 separate office visits If ≥ 2 blood pressure readings taken outside the office are <140/90 mm  Hg If no evidence of hypertensive target organ damage Staessen  JA,  Asmar  R,  DeBuyzere  M, Imai Y,  Parati  G, Shimada K,  Stergiou  G,  Redón   J,Verdecchia  P; Participants of the 2001 Consensus Conference on Ambulatory Blood Pressure Monitoring. Task Force II: blood pressure measurement and cardiovascular outcome. Blood Press Monit . 2001; 6 :355– 370

15. Masked hypertension: If office blood pressure lesser than out -of- office blood pressure This may be due to sympathetic over-activity in daily life caused by job or stress , tobacco abuse, or other adrenergic stimulation It may affect >10 % of patients and clearly increases cardiovascular risk, despite normal office blood pressure readings Courtesy Dr. R.G. Victor, Cedars-Sinai Medical Center, Los Angeles.

16. It involves measuring blood pressure (BP) at regular intervals (usually every 20–30 min.) over a 24 hour period while patients undergo normal daily activities, including sleep The portable monitor is worn on a belt connected to a standard cuff on the upper arm and uses an oscillometric technique to detect systolic, diastolic and mean BP with heart rate Australian Family Physician Vol. 40, No. 11 ,November 2011 877-880 Ambulatory blood pressure monitoring (ABPM):

17. Indications of ABPM : Suspected white-coat hypertension (including in pregnancy) Suspected masked hypertension Suspected nocturnal hypertension or no night time reduction/dipping in BP Hypertension despite appropriate treatment Suspected episodic hypertension Australian Family Physician Vol. 40, No. 11, november 2011 877- 880

18. ABPM can also be used in : Titrating antihypertensive therapy Borderline hypertension Hypertension detected early in pregnancy Syncope or other symptoms suggesting orthostatic hypotension, that may not be demonstrated in the clinic Australian Family Physician Vol. 40, No. 11, N ovember 2011 877- 880

19. Canadian Journal of Cardiology  2015 31, 549-568DOI: (10.1016/j.cjca.2015.02.016)

20. Cardiovascular risk increases dramatically with hypertensive target organ damage and with additional cardiovascular risk factors Assessment of the overall cardiovascular risk Mancia G, De Backer G, Dominiczak A, et al: 2007 guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 28:1462, 2007 . Lowering SBP by 10–12 mmHg and DBP by 5–6 mmHg decease in relative risk by 35 –40% for stroke and 12–16% for CHD within 5 years

21. Detection of target organ disease Heart: This is because of structural and functional adaptations may result into LVH, CHF, coronary artery disease Early detection and aggressive control of HTN may reverse LVH and reduces CVD risk CHF may be due to Systolic as well as diastolic dysfunction(≈33%) or both Diastolic dysfunction may be assessed by:- Electrocardiography Echocardiography Angiography

22. ECG changes in hypertension: Features of chronic hypertension:- Sign of LVH due to systolic overload Left axis deviation Earliest features of left ventricular overload:- T-wave in lead V 1 taller than T-wave in V 6 U-wave become inverted in left oriented leads Frontal plane of QRS-T angle begins to increase and exceeds 45° Evidence of left atrial abnormality Increase in VAT in left oriented leads

23. Brain: Stroke: Hypertension accounts for 50% of strokes* In hypertensive persons , 80 - 85% of strokes are ischemic (thrombotic or embolic) and 15 - 20 % are hemorrhagic(ICH,SAH) Hypertensive encephalopathy: Occurs due to failure of cerebral blood flow autoregulation i.e., malignant hypertension resulting into vasodilation & hyper-perfusion May present as Severe headache, Nausea/Vomiting, focal neurological signs, altered mental status. May progress into coma, seizure and death

24. Kidney: Renal risk occurs more in black than white Renal compromise is more related to raised systolic blood pressure Raised systolic pressure Hypertension related vascular i njury on p reglomerular arterioles Direct damage to glomerular capillaries d ue to hyperperfusion Ischemic changes in g lomeruli & post-glomerular structure Glomerular injury Autoregulation failure & GFR Glomerulosclerosis Tubular ischemia & atrophy

25. Malignant hypertension may cause:- F ibrinoid necrosis of afferent arteriole Focal necrosis of glomerular tuft, if involve glomerulus Micro( Urinary albumin/ creatinine r atio 30-300 mg/g) & macroalbuminuria (>300 mg/g) are early markers of renal injury Gross pathologic change of small , scarred kidneys (Hypertensive nephrosclerosis )

26. Perpheral vessels: Atherosclerotic changes occurs in vessels due to long standing hypertension Risk is overwhelming if there is:- Aortic dissection (distal > proximal) Abdominal aortic aneurysm Peripheral arterial disease Ankle brachial index i.e., ratio of SBP of ankle to brachial, is useful approach to asymptomatic patient or with intermittent claudication ABI <0.9 diagnostic to PAD & a/w >50% stenosis to at least one major limb vessels

27. 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

28. Causes of secondary Hypertension Renal/ Renovascular : Renal parenchymal disease Renal artery stenosis Fibromuscular dysplasia V ascular : Coarctaction of aorta E ndocrinological : Thyroid associated Cortisole excess associated M ineralocorticoid excess associated C atecholamine associated Drugs Obstructive Sleep Apnea Syndrome Lifestyle – Diet / Nutrition

29. Omura M, Saito J, Yamaguchi K, Kakuta Y, Nishikawa T. Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens Res . 2004;27(3):193-202 . Haas DC, Foster GL, Nieto FJ, et al. Age-dependent associations between sleep-disordered breathing and hypertension: importance of discriminating between systolic/diastolic hypertension and isolated systolic hypertension in the Sleep Heart Health Study. Circulation . 2005;111(5):614-621.

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

31. 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 Approach to renal/ renovascular hypertension

32. Physical Examination Findings: Abdominal bruits Other bruits Advanced fundal changes 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 Approach to renal/ renovascular hypertension

33. S pecial 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 Approach to renal/ renovascular hypertension

34. Renal CT angiogram with 3D reconstruction Severe prox. atherosclerotic stenosis of the Rt. renal artery and mild stenosis of the left renal artery C lassic “ string-of-beads” lesion of fibromuscular dysplasia

35. Fibromuscular Dysplasia, before and after PTRA

36. 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

37. Screening for hyperaldosteronism : Serum K + and HCO 3 - & serum Na + and Mg 2+ Plasma aldosteron /plasma renin activity Oral salt loading suppression test Adrenal vein sampling 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)

38. Cortisole excess hypertension Clinical feature: S uspected 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

39. Deoxycorticosteron excess hypertension If hypertension with pseudohermaphroditism / virilisation / musculinization Screening for hyperaldosteronism : Serum K + and HCO 3 - & serum Na + Plasma aldosteron /plasma renin activity

40. C atecholamine 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 : H istamine , Nicotine , Caffeine , ß-blockers , TCA,MAO inhibitors Manipulation of tumors: abdominal palpation, urination

41. 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) I 131 Metaiodobenzylguanidine (MIBG) scintigraphy

42. 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

43. 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

44. Hormone related hypertension H alf 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.)

45. Treatment of hypertension in young 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 E xercise programme or joining an organised sports programme Alcohol use needs to be moderated and tobacco product use discontinued Falkner B, Daniels S. Summary of the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Hypertension 2004;44(4):387-388.

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

47. Take home message: First to identify the actual hypertensive patients Take proper history f or symptoms, life style, habits and family history & other risk factor Complete physical examination from head to toe and order to run basic lab tests E xtensive 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 * S Afr Med J 2016;106(1):36-38. DOI:10.7196/SAMJ.2016.v106i1.10329

48. Thank you