Hypertension
Synonyms and keywords: Blood pressure; hypertension; high blood pressure; systolic blood pressure; essential hypertension

# Overview
Hypertension is a major risk factor for cardiovascular disease and a major public health problem. The prevalence of hypertension increased among the united states due to changing The previous cut-off 140/90 mmHg (the previous 2003 threshold from the Joint National Committee (JNC) 7 guideline 3) to a lower threshold of greater than or equal to 130/80 mmHg. Hypertension is a leading cause of mortality worldwide. More than half of hypertensive patients are not aware of the disorder and some diagnosed patients do not take the medication. The new guideline recommends considering the average of reading BP 2 visits office. Home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM) are better than clinic or home blood pressure readings to determine masked hypertension or white coat hypertension out of the office.

# Historical Perspective
- Hypertension was first discovered by Scipione Riva-Rocci, an Italian physician, in 1896 following the invention of the cuff-based mercury sphygmomanometer and measurement of the peak systolic blood pressure by noting the cuff pressure  at which the radial pulse was no longer palpable.
- In 1905, the sound after cuff deflation of sphygmomanometer was first identified by Russian physician Nikolai.
- Between 1910 and 1914, essential hypertension and malignant hypertension  were described.

# Classification
Hypertension classified based on presence of underlying disorders into two groups:
- Chronic hypertension, also called primary hypertension or essential hypertension, (90-95%)
- Gradually rising in blood pressure
- History of environmental exposure (weight gain, high-sodium diet, decreased physical activity, job change leading increased travel, excessive consumption of alcohol
- Family history of hypertension
- Secondary hypertension, (5%), due to underlying disorder
- BP lability, suddenly rising BP with pallor and dizziness (pheochromocytoma)
- Snoring, hypersomnolence (obstructive sleep apnea)
- Prostatism (chronic kidney disease due to post-renal urinary tract obstruction)
- Muscle cramps, weakness (hypokalemia from primary aldosteronism or secondary aldosteronism due to renovascular disease)
- Weight loss, palpitations, heat intolerance (hyperthyroidism)
- Edema, fatigue, frequent urination (kidney disease or kidney failure)
- History of coarctation repair (residual hypertension associated with coarctation)
- Central obesity, facial rounding, easy bruisability (Cushing syndrome)
- Medication or substance use (alcohol, NSAIDS, cocaine, amphetamines)
- Absence of family history of hypertension
- Resistant hypertension is defined as a higher level of BP above the goal in spite of concurrent use of three antihypertensive drugs including a long-acting calcium channel blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and a diuretic and requires  medications.
- Refractory hypertension is explained as failing to control hypertension with at least five classes of antihypertensive drugs including long-acting thiazide-type diuretic, such as chlorthalidone, and a mineralocorticoid receptor antagonist, such as spironolactone.

# Comparison between two guidelines of hypertension

# 2017/ACC/AHA Guideline of hypertension
- Hypertension can be classified based on the guideline into 2 stages:

# Pathophysiology
- The pathogenesis of hypertension is characterized by a malfunction in the renin-angiotensin-aldosterone system (RAAS), natriuretic peptides ,endothelium, sympathetic nervous system (SNS),immune system.
- Allelic variants of several genes have been associated with the development of primary hypertension.
- Endothelial dysfunction and increased TGF-B  was shown in salt sensitivity patients lead to increased systolic blood pressure 10 mmHg following ingestion of 5 gr salt.

# Causes
Common causes of hypertension include:
- Genetic susceptibility
- Hypertension is a Polygenic disorder
- Findings of 25 rare mutations,120 single-nucleotide polymorphisms in hypertensive patients
- Monogenic forms of hypertension in conditions such as: Glucocorticoid-remediable aldosteronism, Liddle syndrome, Gordons syndrome
- Association between high blood pressure and older age with increased defects in the gene
Environmental exposure
- Overweight, obesity
- Direct relationship between body mass index and BP
- Strong relationship between waist-to hip ratio, distribution of central fat and BP
- Relation between obesity at a young age with further hypertension
- Sodium intake
- Association between sodium intake and BP in migrants
- Triat of salt sensitivity in blacks, older adults, patients with higher level of BP, CKD, DM, metabolic syndrome
- Potassium
- Inverse relation with BP
- Inverse relation with stroke
- Higher level of potassium may reduce the effect of sodium on BP
- Physical fitness
- Inverse relation between physical fitness and physical activity with BP
- Modest exercise activity reduces the risk of BP
- Alcohol

# Differentiating hypertension from other Diseases
- Differential diagnosis of hypertension includes:

# Epidemiology and Demographics
- The prevalence of hypertension is approximately 45,600 per 100,000 individuals worldwide.
- Between the years 2000-2002, the incidence of hypertension was estimated to be 5680 for whites, 8490 for African-Americans, 6570 for Hispanics, and 5220 for Chinese cases per 100,000 individuals in United States.

## Age
- Hypertension is more commonly observed among elderly patients

## Gender
- Males are more commonly affected with hypertension than females.

## Race
- Hypertension usually affects individuals of the black race, Asians and Hispanic Americans.

# Risk Factors
- Common risk factors in the development of hypertension are:
- Diabetes mellitus
- Family history of hypertension
- Dyslipidemia
- Increased age
- Obesity
- Low socioeconomic state
- Physical inactivity/low fitness
- Male sex
- Unhealthy diet
- Obstructive sleep apnea
- Psychological stress
- Common risk factors associated with resistant hypertension include:
- Older age
- Obesity
- CKD
- Black race
- DM

# Natural History, Complications and Prognosis
- The patients with primary hypertension usually remain asymptomatic. 
- The clinical features of secondary hypertension dependent on the characteristics of an underlying disorder.
- If hypertension left untreated, 33% of patients with hypertension may progress to developheart attack and stroke.
- Common complications of resistant hypertension include MI, stroke, ESRD, and death that are 2-7 times higher compared with patients without resistant hypertension.
- Prognosis is generally poor without treatment, and the 10 year mortality rate of patients with hypertension is approximately 11%.

# Diagnosis

## Diagnostic Criteria
- The diagnosis of hypertension is made when at least three of the following diagnostic criteria are met:
- Accurate measurement of BP
- Assessment of cardiovascular risk
- Assessment about secondary hypertension
Abbreviations:
SBP: Systolic blood pressure;
DBP: Diastolic blood pressure;
BP: Blood pressure
Abbreviations:
ABPM: Ambulatory blood pressure monitoring;
HBPM: Home blood pressure monitoring;
BP: Blood pressure
Abbreviations:
ABPM: Ambulatory blood pressure monitoring;
HBPM: Home blood pressure monitoring;
BP: Blood pressure
Abbreviations:
ABPM: Ambulatory blood pressure monitoring;
HBPM: Home blood pressure monitoring;
BP: Blood pressure

## History and Symptoms
- Primary hypertensive patients are usually asymptomatic.
- Symptoms related to underlying causes of secondary hypertension may include the following:
- Palpitation
- Headache
- Sweeting
- Abdominal pain
- Urinary symptoms
- Muscle cramps
- Abdominal mass
- Skin lesions
- Edema

## Physical Examination
- Patients with primary hypertension usually are asymptomatic.
- In secondary hypertension physical examination may be remarkable for :
- Arterial bruit
- Irregular pulses, Tachycardia, Absent femoral pulses
- Fine tremor
- Acute abdominal pain, abdominal mass
- Skin stigmata, Violaceous striae
- Hirsutism
- Warm skin, moist skin, Skin pallor
- Central obesity
- Moon face
- Dorsal and supraclavicular fat pads
- Loss of normal nocturnal blood pressure fall
- Orthostatic hypotension
- Periorbital puffiness,Coarse skin, Cold skin, Slow movement,Goiter
- continuous murmur over back or chest
- Abdominal bruit

## Laboratory Findings
- Basic laboratory test should be taken in patients with the diagnosis of hypertension include:
- Fasting blood sugar
- Complete blood count
- Lipid profile
- Serum creatinine with eGFR
- Serum sodium, potassium, calcium
- Thyroid-stimulating hormone
- Urinalysis
- Optional laboratory test in hypertensive patients include:
- Uric acid
- Urinary albumin to creatinine ratio

## Electrocardiogram
- An ECG may be helpful in the diagnosis of left ventricular hypertrophy associated hypertension. Findings on an ECG suggestive of left ventricular hypertrophy include
- Cornell criteria: R wave in aVL + S wave in V3> 28 millimeters in males or greater than 20 mm in females
- Modified Cornell Criteria: R wave in aVL> 12 mm
- Sokolow-Lyon Criteria: S wave in V1 + R wave in V5 or V6> 35mm
- Romhilt-Estes: If the score equals 4, LVH is present with 30% to 54% sensitivity. If the score is greater than 5, LVH is present with 83% to 97% specificity.
- The amplitude of the largest R or S in limb leads  20 mm = 3 points
- The amplitude of S in V1 or V2  30 mm = 3 points
- The amplitude of R in V5 or V6  30 mm = 3 points
- ST and T wave changes opposite QRS without digoxin = 3 points
- ST and T wave changes opposite QRS with digoxin = 1 point
- Left Atrial Enlargement = 3 points
- Left Axis Deviation = 2 points
- QRS duration  90 ms = 1 point
- Intrinsicoid deflection in V5 or V6 > 50 ms = 1 point

## Chest X-ray
- Finding on a chest x-ray associated target organ damage in hypertension include widening aortic knob.
- Ascending aorta dilation and increased cardiothoracic ratio may be associated with hypertension.

## Echocardiography or Ultrasound
Echocardiography may be helpful in the diagnosis of complications of hypertension, which include left ventricular hypertrophy (LVH), left ventricular (LV) diastolic dysfunction and left atrial dilation.

## CT scan
- CT scan may be helpful in the diagnosis of underlying causes of secondary hypertension such as hyperaldosteronism, pheochromocytoma, hyperparathyroidism, aortic coarctation.
- CT scan may also show the complication of hypertension including:
- Cardiovascular system: aortic aneurysm, acute aortic syndrome
- Central nervous system: stroke, subarachnoid hemorrhage, posterior reversible encephalopathy syndrome

## MRI
- Cardiac MRI is a reliable tool in the diagnosis of hypertensive heart disease by evaluation of left ventricular hypertrophy, left ventricular mass, biventricular function, valvular disease, inflammation and stress myocardial perfusion-fibrosis.

## Other Imaging Findings
- There are no other imaging findings associated with hypertension.

## Other Diagnostic Studies
- There are no other diagnostic studies associated with hypertension.

# Treatment

## Medical Therapy
- The mainstay of treatment for hypertension is: Initiation of treatment with one or more of three classes of first-line  BP lowering agents:
- Calcium channel blocker (CCB)
- Renin-angiotensin-convertng enzyme inhibitors (ACEI or ARB)
- Thiazide-like diuretic
- Betablocker is first line therapy in the presence of angina and heart failure.
- Second-line lowering BP agents are used in resistant hypertension or specific conditions.
- The mainstay of therapy for resistant hypertension is:
- Improving medications adherence
- Diagnosis and treatment of the causes of secondary hypertension
- Adding spironolactone or hydralazine or minoxidil to first line therapy (CCBs, inhibitors of RAS, chlorthalidone.

## Surgery
- Surgical procedure may be performed for patients with secondary hypertension such as coarctation of aorta, primary aldosteronism.

## Prevention
- Effective measures for the primary prevention of hypertension include: 
- Weight loss: Reduction 1 mmHg in blood pressure for every one kilogram weight reduction
- Healthy diet: A diet rich in fruits, vegetables, whole grains, low-fat dairy products, reduced content of saturated and total fat
- Reduced intake of dietary sodium: Less than 1000-15000 mg/day
- Enhanced intake of dietarypotassium:35005000 mg/d by intaking rich diet with potassium
- Physical activity: Aerobic ( 90150 min/week), dynamic resistance (90150 min/week), Isometric resistance (4  2 min handgrip, 1 min rest between exercises, 3 sessions per week)
- Reduced alcohol intake: Men 2 drinks daily, Women 1 drink daily
- Once diagnosed and treated, patients with hypertension are followed-up every month for evaluation of medication adherence and response to treatment.