Hypertension by Harrison Mbohe

MBChB student JKUAT

1. Hypertension (htn) Harrison Mbohe , MBChB level 4 JKUAT

2. Definition of terms Hypertension – Chronic elevation in BP (systolic ≥140 mmHg and/or diastolic ≥90 mmHg) in subjects aged 18 years and above. The above applies to individuals on antihypertensive medications even if current blood pressure is <140/90mmHg. Hypertensive urgency – Severe elevations in BP (systolic >180 mmHg or diastolic >120 mmHg) without progressive end – organ damage. Hypertensive emergency – Severe elevations in BP (systolic >180mmHg or diastolic >120mmHg) associated with progressive end – organ damage. Malignant hypertension – Abrupt elevations in BP in pts with chronic hypertension or sudden onset of severe hypertension, with DBP often >130mmHg.

3. Definition of terms Resistant hypertension – BP of >140/90 mmHg despite Rx with three antihypertensive agents of different classes (one of which should be a diuretic) in adequate doses and after exclusion of false hypertension. White coat/ isolated office hypertension – persistently elevated BP in the clinic while BP is normal outside the clinic . Masked/ isolated ambulatory Hypertension – normal BP in the office and abnormally elevated out of the clinic setting.

4. GRADING OF HTN

5. epidemiology Estimated global prevalence – 31% of adults in 2010 ; 28.5% in HIC and 31.5 in LMIC. Contributes to >7.1 million deaths annually. Increased prevalence (may be as high as 50%) in patients > 65yrs. In Africa , prevalence is about 25% - 35% in patients of 25 – 65 yrs. In Kenya , according to STEP survey 2015; 24 % either had HTN or were on treatment for HTN. > 56 % of Kenyans have never been screened for HTN. Only 15 % of those with HTN are aware of their status, only 8% are on treatment and only 4.6% of those on treatment are well controlled.

6. classification Hypertension is broadly classified into 2 groups : Primary or Essential hypertension Unknown etiology . Tends to be familial. Consequence of an interaction between environmental and genetic risk factors . Constitutes about 80-95 % of cases in adults. Secondary hypertension Constitutes 5 – 20% of the cases in adults Stems from specific etiology causing BP elevation which can be identified and possibly treated.

7. Risk factors for primary htn Age > 45yrs (60 years in women) Race (more in blacks) Familial history Overweight/central obesity Sedentary lifestyle Tobacco use High dietary sodium Low dietary potassium Low vitamin D Stress Chronic/heavy alcohol use

8. CAUSES OF SECONDARY HTN Chronic parenchymal kidney disease e.g. diabetic nephropathy Renovascular disease e.g. renal artery stenosis Catecholamine secreting tumors e.g. pheochromocytoma and neuroblastoma Hyperaldosteronism Cushing’s syndrome Thyroid disorders (hyper and hypothyroidism) Congenital heart disease - Coarctation of the aorta Drugs (anabolic steroids; estrogen ; NSAIDS; sympathomimetic drugs ; psychoactive/recreational drugs: amphetamines, cocaine ) Obstructive sleep apnea Pregnancy – induced.

9. Pathogenesis of essential htn Multifactorial and highly complex. Important factors implicated include: Genetics - specific angiotensinogen polymorphisms and angiotensin II receptor variants have been linked to HTN. Activation of neurohormonal systems such as the sympathetic nervous system and RAAS. Environmental factors - stress, obesity, smoking, physical inactivity, and high levels of salt consumption modify the impact of genetic determinants. The interplay of the factors above lead to altered renal sodium handling and increased vascular resistance which ultimately contribute to essential hypertension.

10. Clinical symptoms Most pts are asymptomatic . A “ hypertensive headache ” generally occurs only in patients with severe hypertension – characteristically occurs in the morning and localized to the occipital region. Other nonspecific symptoms include Dizziness Palpitations Easy fatigability Impotence (in men) Presence of symptoms mostly indicative of hypertensive cardiovascular disease or to manifestations of secondary hypertension .

11. Complications (hmod) SYSTEM COMPLICATIONS CVS LVH: most common overall complication AMI: most common cause of death associated with hypertension Atherosclerosis; Aortic aneurysms and dissections CNS Intracerebral hematoma: rupture of Charcot-Bouchard aneurysms Berry aneurysm: rupture produces a subarachnoid hemorrhage. Lacunar infarcts: small infarcts due to hyaline arteriolosclerosis. Cerebral edema associated with malignant HTN CVA Renal Benign nephrosclerosis: kidney disease of hypertension; due to hyaline arteriolosclerosis; causes atrophy of the tubules and sclerosis of the glomeruli; progresses to renal failure Hyperplastic arteriolosclerosis of renal vessels Eyes Hypertensive retinopathy

12. Approach to the patient: history Presence, character and duration of symptoms Time of first diagnosis of HTN, records of any previous screening and hospitalizations. Current and past BP values. Current and past anti-HTN medications and any other medications – responses and side effects. Familial history of HTN and other cardiovascular disease. Lifestyle evaluation – exercise, body weight changes, diet history, smoking (pack years), alcohol consumption, recreational drug use, sleep history, impact of treatment on sexual function. History of any comorbidities such as DM.

13. Approach to the patient: history Evidence of secondary hypertension: history of renal disease; change in appearance; muscle weakness; spells of sweating, palpitations, tremor; erratic sleep, snoring, daytime somnolence; symptoms of hypo- or hyperthyroidism; use of agents that may increase blood pressure Evidence of target organ damage: history of TIA, stroke, transient blindness ; angina, myocardial infarction, congestive heart failure; sexual function

14. Approach to the patient: physical examination Body habitus, including weight and height. Waist circumference - diagnose metabolic syndrome and T2DM risk Measurement of the pulse rate and BP. Neck palpation to check for thyroid enlargement and assessment of signs of hypo- and hyperthyroidism. Auscultation for bruits over the carotid and femoral arteries, and palpation of femoral and pedal pulses – if absent indicative of PAD. Examination of the heart may reveal - Loud second heart sound; S4 gallop; Left ventricular hypertrophy - enlarged , sustained, and laterally displaced apical impulse . An abdominal bruit, that lateralizes and extends throughout systole into diastole - renovascular hypertension.

15. Approach to the patient: physical examination Fundoscopy is also an essential part of the examination and blood vessel anomalies are graded according to the Keith–Wagener classification : Grade 1 – tortuosity of the retinal arteries with increased reflectiveness (silver wiring). Grade 2 – grade 1 + the appearance of arteriovenous nipping produced when thickened retinal arteries pass over the retinal veins. Grade 3 – grade 2 + flame-shaped haemorrhages and soft ‘ cotton wool’ exudates actually due to small infarcts . Grade 4 – grade 3 + papilledema Kidneys of patients with polycystic kidney disease may be palpable in the abdomen. The physical examination also should include evaluation for signs of CHF and a neurologic examination which may reveal signs of previous stroke.

16. arteriovenous (AV) nicking in this patient’s left retina.

17. F lame-shaped hemorrhages (white solid arrows) and a cotton-wool spot (white interrupted arrow) in a patient with hypertension.

18. Approach to the patient: laboratory evaluation

19. Further lab workups Thyroid disease - TFTs. Renal artery stenosis - MRA, captopril radionuclide scan, renal duplex U/S, renal arteriography. Cushing’s syndrome - dexamethasone suppression test, urinary cortisol. Pheochromocytoma - 24-h urine collection for catecholamines, metanephrines and vanillylmandelic acid and/or measurement of plasma metanephrine. Primary hyperaldosteronism - depressed plasma renin activity and hypersecretion of aldosterone, both of which fail to change with volume expansion.

20. Diagnosis: office bp measurement

21. Diagnosis cont’d ABPM Patient wears a portable BP measuring device, usually on the non-dominant arm, for a 24–25 hr period. Gives info on BP during daily activities and at night during sleep. Better predictor of cardiovascular events such as MI and CVA better then office BP. HBPM Self-measurement of BP at home . Precautions are as outlined above. Recording will be as advised by health practitioner.

22. Diagnostic cut offs for office and out of office BP measurements

23. treatment Aims of the treatment Adequate control of blood pressure Control of other risk factors with the overall aim of reducing morbidity and mortality from the complications . Treatment involves Lifestyle interventions Pharmacological therapy

24. Lifestyle interventions Abstinence or moderate alcohol consumption. Avoidance of all forms of tobacco Daily adequate physical exercise : at least 40 min of moderate-vigorous dynamic aerobic exercise (walking, jogging, cycling or swimming ) on 3-4 days per week DASH : consumption of vegetables and fresh fruits, low-fat dairy products, dietary and soluble fiber, whole grains and protein from plant sources , reduced in saturated fat and cholesterol. Avoid added salt and high salt food ( no more than 2,400 mg/day). Weight reduction : for overweight and obese hypertensive patients ( to attain BMI <25 kg/m 2 ).

25. Pharmacological therapy Indicated in elevated SBP and/or DBP measurements confirmed on at least 3 separate occasions over 2-month period cardiovascular risk level of the patient . There are six major classes of antihypertensive agents: RAAS Inhibitors – Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs); β -blockers (BBs); Calcium Channel Blockers (CCBs); Thiazide or thiazide-like diuretics; Aldosterone antagonists/mineralocorticoid receptor antagonists . Others (sympatholytics, adrenergic blockers, centrally acting alpha2- antagonists and direct arterial vasodilators.

26. CLASS/EXAMPLES MOA INDICATIONS C’INDICATIONS SIDE EFFECTS RAAS Inhibitors ACEIs (enalapril, captopril, lisinopril) Block the conversion of angiotensin I to angiotensin II; Block the degradation of bradykinin CHF, LVF , post-MI or established CAD Diabetic nephropathy Secondary stroke prevention Pregnancy Renovascular Disease Hx of angioedema w/ previous ACEI Hypersensitivity Persistent dry cough Voice changes Chest pain Tachycardia GI disturbances Hyperkalemia ARBs (losartan, candesartan, valsartan) Selectively block the AT 1 receptors for angiotensin II. HTN Pregnancy Hypersensitivity to the drug Hypotension URTI Headache Dizziness Hyperkalemia Beta blockers (atenolol, carvedilol, propranolol) Antagonize effects of sympathetic nerve stimulation or circulating catecholamines HTN, CHF, Angina, Arrhythmias. Hx of asthma, sick sinus syndrome, cardiogenic shock, pheochromocytoma, metabolic acidosis, hypoglycemia Bradycardia Bronchospasm Hypotension Heart failure GI disturbance

27. CLASS/EXAMPLES MOA INDICATIONS C’INDICATIONS SIDE EFFECTS CCBs (amlodipine, nifedipine, felodipine, verapamil, diltiazem) Reduce vascular resistance through L-channel blockade, which reduces intracellular calcium and blunts vasoconstriction. Angina pectoris, Mild-moderate HTN Pregnancy Hypersensitivity to the drug Porphyria Cardiogenic shock GI disturbances Flushing Dizziness Lethargy Fatigue Aggravation of angina Thiazide diuretics (Chlorthalidone, HCTZ)/ thiazide like diuretics (indapamide) inhibit the Na + /Cl − pump in the distal convoluted tubule and hence increase sodium excretion. They decrease vascular resistance HTN, symptomatic edema. Hypersensitivity to the drug Hepatic encephalopathy Hypokalemia Severe renal failure Hypokalemia Hyperuricemia Hyperglycemia Hypercalcemia Reversible impotence Aldosterone antagonists (spironolactone, eple renone ) Non-selective aldosterone antagonist low-renin essential hypertension, resistant hypertension, and primary aldosteronism; CHF Hypersensitivity to the drug Hyperkalemia Dizziness Diarrhea Hyperkalemia Fatigue Impotence

28. CLASS/EXAMPLES MOA INDICATIONS C’INDICATIONS SIDE EFFECTS Centrally acting agents (clonidine, reserpine, methyl dopa) Decrease peripheral resistance by inhibiting sympathetic outflow. Patients with autonomic neuropathy who have wide variations in blood pressure due to baroreceptor denervation. Pregnancy Hypersensitivity to the drug Somnolence, dry mouth, and rebound hypertension on withdrawal Direct arterial vasodilators (hydralazine, minoxodil) Decrease peripheral resistance and concomitantly activate mechanisms that defend arterial pressure Essential HTN, CHF, Severe aortic insufficiency after valve replacement Severe tachycardia Cor pulmonale Dissecting aortic aneurysm Idiopathic SLE Headache Anorexia Fluid retention Postural hypotension Nasal congestion

29. DOSAGES

30. JNC-8 TREATMENT STRATEGY

31. references Dan L. Longo, Dennis L. Kasper, J. Larry Jameson, Anthony S. Fauci, Stephen L. Hauser, Joseph Loscalzo. 2012. Harrison’s Principles of Internal Medicine . New York City : McGraw Hill, 2012. Division of Non-communicable Diseases – Ministry of Health. 2018. KENYA NATIONAL GUIDELINES FOR CARDIOVASCULAR DISEASE MANAGEMENT . Nairobi, 2018. Goljan, Edward F. 2019. RAPID REVIEW PATHOLOGY . Philadelphia, PA : Elsevier Inc., 2019. Vinay Kumar, Abul K. Abbas, Jon C. Aster. 2013. Robbins Basic Pathology. Philadelphia, PA : Elseviers Inc., 2013 . James PA, Ortiz E, et al. 2014 evidence-based guideline for the management of high blood pressure in adults : (JNC8). JAMA. 2014 Feb 5; 311(5):507-20

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