Hypertension

Overview

Hypertension is defined as blood pressure >140-90mmHg on 3 separate readings. The majority of patients with hypertension are asymptomatic so regular screening (q3y) is important. Hypertension has many causes and many complications. Most cases are idiopathic. Lifestyle modification is the best initial treatment of choice. Do not jump straight to medical treatment in otherwise healthy patients. Anytime a patient is diagnosed with hypertension, they should get a comprehensive workup for other associated comorbidities.

Hypertension is the greatest risk factor for premature death and coronary artery disease. It causes 50% of vascular deaths (8 million per year). It is the #1 cause of Stroke, Coronary Artery Disease, Peripheral Artery Disease, and End-Stage Renal Disease. The etiology of hypertension is unknown in 95% of cases.

White coat hypertension: elevated clinical pressure, but normal Ambulatory Blood Pressure Monitoring (<135/85 on average per day)

Masked hypertension: normal clinical pressure, but elevated Ambulatory Blood Pressure Measurement (>135/85 on average per day)

• Causes of hypertension
  • Essential (Primary, Idiopathic) Hypertension (95%)
    • Genetics
    • Environmental influence
  • Secondary Hypertension
    • Cardiovascular
      • Coarctation of the aorta
      • Polyarteritis nodosa
      • High Intravascular volume
      • High CO
      • Rigidity of the aorta
    • Endocrine
      • Adrenocortical hyperfunction: Cushing syndrome, Hyperaldosteronism
      • Pheochromocytoma
      • Exogenous hormones: Glucocorticoids, estrogen
      • Pregnancy-induced: Preeclampsia, eclampsia
      • Monoamine oxidase inhibitors
      • Tyramine-containing foods (eg. Chocolate, cheese)
      • Hypercalcemia
      • Acromegaly
    • Renal
      • Acute glomerulonephritis
      • Chronic renal disease
      • Polycystic Kidney disease
      • Renal artery stenosis (Renovascular HTN)
      • Renin producing tumors
      • Obstructive uropathy
      • Renal vasculitis
      • Reninomas
    • Neurogenic
      • Acute stress (Surgery)
      • Psychogenic
      • High intracranial pressure
      • Sleep apnea
    • Physiological
      • Increase in growth hormone
      • Hypothyroidism (Retained fluids, Myxedema)
      • Hyperthyroidism
      • Pregnancy
• Pathogenesis of essential hypertension
  • Genetic factors
    • Aldosterone synthetase (11-B-hydroxylase, 17-a-hydroxylase): Leads to increased secretion of aldosterone, causing salt and water retention, and plasma and volume expansion
    • Angiotensin I and II receptor gene: Increased response of the ATI and ATII receptors causes vasoconstriction and an increase in TPR
    • ENaC mutations (Liddle syndrome): Mutations affect the beta and gamma subunit of ENaC causing increased sodium resorption and plasma volume expansion, also known as salt-sensitive hypertension
  • Environmental factors → Increased TPR, Intravascular volume, and Cardiac output
    • Stress: Stress causes increased Epinephrine and Norepinephrine → Epinephrine stimulates the RAAS and increases Cardiac output → Norepinephrine stimulates vasoconstriction and increases Total peripheral resistance
    • Increase in vasoconstrictors
      • Renin (RAAS): Renin → Angiotensinogen → AT I → AT II → Aldosterone
      • Catecholamines: Increases Cardiac Output and Total Peripheral Resistance
      • Endothelins: Vasoconstriction and increased Total peripheral resistance
    • Sodium retention: RAAS, Liddle syndrome, Gitleman syndrome
• Evidence that Na+ plays a role in the pathogenesis of Hypertension
  • Reduced Na+ results in Reduced BP
  • Na+ loosing diuretics cause a reduction in BP
  • Increased intake of Na+ results in Increased BP
  • There is increased Na+ in the intravascular space in Hypertension
  • Genetically predisposed animals given Na+ load develop Hypertension
• Pathophysiological changes associated with hypertension
  • Hyaline arteriolosclerosis: Seen in benign essential hypertension, old age, and diabetics. Collagen is laid down in the tunic media narrowing the lumen and decreasing compliance. Narrowing is worse at branch points.
  • Hyperplastic arteriosclerosis: seen in malignant hypertension, concentric laminated thickening of the arteriole walls, onion skin appearance, and luminal narrowing
  • Necrotizing arteritis: characterized by focal fibrinoid necrosis in hypertrophic vessels
• Complications of Hypertension
  • Hypertensive Heart Disease → Congestive Heart Failure or Arrhythmias
  • Cerebrovascular accident
  • Retinopathy
  • Nephropathy
  • Placental changes → Intrauterine Fetal Death, Intrauterine Fetal Growth Restriction

Establishing the Diagnosis of Essential Hypertension

A patient must have 3 abnormal readings AND no symptoms of the underlying cause to diagnose essential hypertension (and start pharmacotherapy). Most diagnoses of hypertension are made when the patient comes in for routine labs, diabetes checks, etc. If the patient comes with neurological or cardiac symptoms consider a hypertensive emergency.

Essential hypertension is 20 times more common than secondary hypertension.

Blood Pressure Cutoffs

Blood Pressure Cutoff	Population
BP > 130/90 (x3)	Cutoff for patients with Diabetes mellitus, renal disease, congestive heart failure, myocardial infarction, stroke, and peripheral artery disease
BP > 140/90 (x3)	Cutoff in otherwise healthy patients
BP > 160/110 (x3)	Cutoff for severe essential hypertension

• Investigations after establishing the diagnosis of hypertension
  • Urinalysis: screen for albuminuria and glucosuria (for hypertensive nephropathy)
  • U/E/C: Check K+, BUN, and Creatinine (for hypertensive nephropathy)
  • Random Blood Sugar: check hyperglycemia, the patient may have developed diabetes
  • Electrocardiography or Echocardiography: to check for structural abnormalities seen in hypertensive heart disease (Left Ventricular Hypertrophy)
  • Lipid Profile: check LDL (Hyperlipidemia + Hypertension multiplies risk for complications)
  • Investigations to exclude secondary causes
    • U/E/C: hypokalemia in Conn’s
    • Ca2+: hypercalcemia in hyperparathyroidism
    • Renal ultrasound: for renal artery stenosis
    • 24 urine meta-adrenaline: for phaechromocytoma
    • Urinary free cortisol: for cushing’s
    • Renin:aldosterone: for conn’s
    • Magnetic Resonance Aorta: for coarctation

Treating Essential Hypertension

Diuretics have the greatest reduction of mortality in essential hypertension 😃

JNC Classification of Hypertension

Start with Normal. add 20 to systolic and 10 to diastolic to reach the minimum BP required for the next stage. If it is an “or” statement – if either systolic or diastolic is in a stage call it the highest qualified stage

	Systolic (mmHg)	Diastolic (mmHg)	Treatment
Normal	< 120	and < 80	Lifestyle and diet
Prehypertension	120 – 139	or 80 – 80	Lifestyle and diet
Stage 1 hypertension	140 – 159	or 90 – 99	Monotherapy (Thiazide > **ACEi /ARB > CCB)
Stage 2 hypertension	> 160	or > 100	Comorbid specific combination therapy (Thiazide + CCB or ACEi or Beta-blocker)
Urgency	>180	or >110	PO antihypertensive (Nifedipine)
Emergency	Alarm symptoms		IV antihypertensive (Frusemide)

Treatment goal

Population	Target Blood Pressure
Hypertension	< 140/90 mmHg
Hypertension + Diabetes	<130/80 mmHg
Age > 80	150/90 mmHg

• Initial treatment for non-comorbid patients
  • Lifestyle modification (diet, exercise)
  • Thiazide diuretic (Hydrochlorothiazide)
  • Monitor for 3 to 6 months
• Treatment for severe essential hypertension (>160/110 x 3)
  • Thiazide diuretic (Hydrochlorothiazide) +
  • ACEi (lisinopril, captopril) or ****ARB **(**Losartan, Valsartan)

Individualized treatment

Patient Group	Medications
Pregnant	Diuretics are contraindicated. Use Methyldopa, Labetaolol, or CCBs
Diabetes	ACEi, ARB (goal <140/90)
African descent or ≥ 55 yo	CCB or Thiazide as first-choice (JNC-8 scrapped the recommendation for ARBs as first-line)
Congestive Heart Failure	BB + ACEi + ISDN + Hydralazine, Spironolactone
LDL > 100	Add a statin (Artovastatin)
Coronary Artery Disease	BB, ACEi/ARB, ISMN, CCB
Cerebrovascular accident	ACEi
CKD	ACEi (Thiazides do not work after Cr > 1.5 mg/dL
BPH	Alpha blocker
Depression and Asthma	Avoid BB
Hyperthyroidism	BB first
Osteoporosis	Thiazide

Hypertensive emergency (Symptomatic Essential Hypertension)

Defined as hypertension with organ-specific symptoms (usually >180/120, but not necessarily). Patients will present with hypertension (x1) with neurological, cardiac, or renal symptoms. May not necessarily have a history of essential hypertension. If a patient comes in with symptoms and diastolic BP >120 start treatment while doing the presentation and investigations. The goal of treatment is to keep diastolic BP at 100-130 mmHg, decrease MAP by 25% within 2-6 hours of admission, and to achieve normal MAP by 24 hours. A rapid decrease in BP should be avoided since it can cause stroke.

Malignant hypertension: an archaic term used to refer to hypertensive emergency accompanied by fundoscopic changes (raised ICP). Requires a CT scan

System	Manifestation
Neurological	Headache, Seizures, Encephalopathy (confusion, psychosis), Blurry vision, Papilloedema (may indicate intracranial bleeding)
Cardiac	Chest pain, Breathlessness, Palpitations
Renal	Hematuria

• Treatment of Hypertensive emergency ***Follow hospital guidelines. Don’t lower more than 25% in the first couple of hours
  • Admit
  • Establish IV lines
  • Crash box ready (can go into V-Fib)
  • Set up Cardiac monitor
  • Approach A
    • IV Furosemide 40mg + Hydralazine 10mg q15min until desired BP or until 50mg has been administered
    • Repeat total dose IM or IV after 6 hours or IV Sodium nitroprusside 0.25-10 ug/kg/min
  • Approach B
    • PO Nifedipine 20mg repeated after 1 hour
  • Switch to multiple oral therapy following BP control
    • Hydrochlorothiazide + Atenolol + Hydralazine or Nifedipine or Methyldopa or Captopril

Secondary Hypertension

Basically Hypertension with a cause. More frequent in very young (<30 years old, do not usually have hypertension) and very old (>65 years old, would have been diagnosed years before). Essential hypertension is still more prevalent in these age groups. Secondary hypertension is refractory to traditional treatment (HCTZ, ACEi/ ARB, etc.).

• Causes of Secondary Hypertension (7 Cs)
  • PheoChromocytoma
  • Cushing’s
  • Conn’s
  • Closing of the renal artery (renal artery stenosis)
  • Contraceptives (OCPs)
  • Congenital adrenal hyperplasia
  • Coarctation of the aorta
• Pathogenesis of hypertension due to renal artery stenosis
  • Narrowing leads to reduced renal blood flow → Increased renin secretion from Juxtaglomerular apparatus → Renin converts angiotensinogen to angiotensin I in the lung→ Angiotensin I is converted to angiotensin II by ACE → Angiotensin II leads to an increase in the production of aldosterone from the adrenals
    • → Aldosterone causes sodium and water retention. This raises cardiac output
    • → Aldosterone is also a potent vasoconstrictor. It raises total peripheral resistance.

Secondary cause	Symptoms	Diagnosis	Treatment
Pheochromocytoma	Pallor, Palpitations, Pain, Perspiration, Pressure	Urine vanillyl mandelic acid (VMA), Catecholamines, MNs; CT to localize the tumor	Start IV alpha-blocker THEN beta-blocker; Surgical resection of the tumor
Cushing’s disease	Weight gain, edema, hirsutism, buffalo hump, striae, weakness	U/E/C: Hypernatremia, Hypokalemia; 24-hr urine cortisol, Dexamethasone suppression test	Surgical resection of the tumor
Conn’s disease	Weakness, edema/weight gain	U/E/C: hypernatremia, hypokalemia; plasma aldosterone	Surgical resection of the tumor
Renal artery stenosis	Resistant hypertension, flank/renal bruit	Ultrasound; Renal arteriogram	Percutaneous transluminal angioplasty
Contraceptives	History of contraceptive use	Clinical diagnosis	Discontinue contraceptives; Intrauterine contraceptives or FP
Congenital adrenal hyperplasia	Hirsutism, masculinization	17-OH progesterone levels	Fludrocortisone
Coarctation of the aorta	Uneven pulses, Pediatric hypertension, Systolic murmur, Neonatal symptoms	Chest X-ray	Surgical repair

Hypertensive Heart Disease

Hypertensive heart disease is concentric hypertrophy of the left ventricle and ischemia as a result of hypertension, in the absence of any other conditions that may lead to left ventricular hypertrophy e.g. Aortic stenosis and cardiomyopathy. Its diagnosis is based on a History of previous hypertension.

• Pathogenesis of hypertensive heart disease
  • Increased Total Peripheral Resistance → Concentric Myocyte Hypertrophy in response to increased workload → Impaired diastolic filling since hypertrophic myocardium has lower compliance →Increased distance for oxygen and nutrient diffusion from adjacent capillaries due to individual myocyte hypertrophy
  • Associated atherosclerosis accompanies hypertension and contributes to ischemia contributes to ischemia
• Morphology of hypertensive heart disease
  • Gross morphology
    • Left concentric left ventricular hypertrophy: 20mm (normal 15 mm)
    • Cardiomegaly (Bull Heart): Weight > 500g ,
    • Increased Left-ventricular hypertrophy: diameter measured at the foot of the papillary muscle
    • Dilated ventricle: present in long standing systemic hypertension
    • Narrow lumen
  • Histology
    • Increased transverse diameter of myocardiocytes
    • Irregular myocardiocytes
    • Irregular nuclear enlargement
    • Boxing (Box-car nuclei) – gap between nucleus and myocardium
    • Fibrosis – due to ischemic changes, endocardial and myocardial (can lead to arrhythmia, asystole, and Ventricular tachyarrhythmia)
• Complications of hypertensive heart disease
  • Congestive Heart Failure (due loss of myocytes and decompensation)
  • Pulmonary edema (due to LHF)
  • Arrhythmias (A-fib is the most common. Can cause mural thrombi and thromboembolism)
  • Cerebrovascular accident as a result of A-fib

Hypertensive Retinopathy

• Pathogenesis of hypertensive retinopathy
  • Malignant hypertension → hyperplastic arteriosclerosis → acute vasospasm and narrowing of retinal vessels

Grades of hypertensive retinopathy

Grade	Feature
I	Silver or copper wiring (tortuous arteries with thick shiny walls)
II	AV nicking (narrowing where arteries cross veins)
III	Flame hemorrhage and cotton-wool spots
IV	Papilloedema

Hypertensive Nephropathy

• Pathogenesis of hypertensive nephropathy
  • Longstanding hypertension → hyaline arteriosclerosis → narrowing of renal blood vessels → reduced renal blood flow → glomerular and tubular ischemia → tubular atrophy and fibrosis of the glomeruli and interstitium → renal failure
  • Reduced renal blood flow triggers RAAS leading to a vicious cycle
• Morphology of hypertensive nephropathy
  • Gross morphology
    • Flea-bitten kidney (due to hemorrhages)
    • Large kidney during acute phases
    • Shrunken kidney in chronic renal disease with uniformly granular surface and capsular adhesion
  • Microscopy
    • Fibrinoid necrosis
    • Periglomerular fibrosis
    • Inflammatory cell infiltrate (necrotising arteritis)
    • Hyperplastic arteriolitis (Onion skin)
    • Necrotising glomerulonephritis – thrombosed capillaries, inflammatory cell infiltrate, infarcts
  • Morphology of arteriolar nephroscelrosis
    • Ischemic collapse of capillary loops due to hypo-perfusion
    • Thickening of bowman’s capsule
    • Arteriolar hyalinosis
    • Myointimal thickening due to proliferation of cells and collagen deposition resulting in luminal narrowing
  • APOL-1 associated glomerulosclerosis
    • Solidified glomerular tufts often with disappearing glomeruli
    • Vascular lesions and thyroidization type tubular atrophy