Systolic Hypertension

Etiology

Most patients with hypertension have primary hypertension, which is also known as essential hypertension. Rarely, isolated systolic hypertension is attributed to other causes of secondary hypertension such as hypothyroidism/hyperthyroidism, chronic kidney disease, peripheral vascular disease, diabetes mellitus, aortic insufficiency, arteriovenous fistula, anemia, Paget disease, and atherosclerotic renal artery stenosis.[3]

Epidemiology

Isolated systolic hypertension is common in the elderly population. Based on data from the National Health and Nutrition Examination Survey 1999-2010, approximately 30% of persons aged 60 years and older have untreated isolated systolic hypertension, as compared with 6% in adults aged 40 to 50 years and 1.8% in young adults aged 18 to 39 years.[3][4][5] As per the Framingham Heart Study, a person aged 65 years with normal blood pressure has a 90% lifetime risk of developing hypertension. Among the elderly group, women and non-Hispanic Blacks have a higher prevalence of hypertensive disorders.

Pathophysiology

Isolated systolic hypertension, in most cases, develops as a result of the reduced elasticity of the arterial system. This is commonly seen among the older adult population as there is an increased deposition of calcium and collagen to the arterial wall.[6] Hence, this may result in reduced compliance of the arterial vessels, decreased lumen-to-wall ratio, and increased thickening and fibrotic remodeling of the vascular intima and media. As a result, these stiffened conduit arteries lead to an increase in pulse pressure and pulse wave velocity, causing an elevation in SBP and a further decline in DBP. Similarly, chronic diseases such as the above causes of secondary hypertension may contribute to the same pathological process by accelerating the deposition of calcium and collagen to the arterial system and the fibrotic remodeling of the vascular walls.[6][7]

History and Physical

Isolated systolic hypertension, like any other hypertensive disorder, often results in end-organ damage when untreated. Hence, early diagnosis, addressing modifiable risk factors, and initiating appropriate treatment are prudent to decrease morbidity and mortality. The important aspects of the history of the hypertensive patient include the following:

• Intake of precipitating agents such as nonsteroidal anti-inflammatory drugs, steroids, sympathomimetics, cocaine, steroids, estrogen
• Risk factors such as smoking, diabetes, dyslipidemia, obesity, sedentary lifestyle, unhealthy diet
• Diet, including high salt, processed food, high fat, and alcohol intake
• Family history of hypertension, renal disease, diabetes, or cardiovascular disease
• Symptoms of secondary causes such as spells of tremor, sweating or tachycardia, muscle weakness, thinning of the skin, depression, hematuria, loud snoring, and daytime somnolence
• Symptoms of end-organ damage such as headaches, loss of visual acuity, dyspnea, chest pain, and claudication [2][8]

Physical Examination

Accurate blood pressure measurement

• Reassess normal blood pressure yearly.
• Take blood pressure after the patient rests for five minutes.
• The patient should sit in a chair with both feet flat on the ground and the back straight.
• The patient's arm should be placed on a flat surface at the level of the chest or heart.
• Choosing the right cuff size is important.
• SBP is the first Korotkoff sound.
• DBP is the fifth Korotkoff sound.
• Obtain an average of 2 to 3 blood pressure measurements on two or three separate occasions to confirm a hypertension diagnosis.

General appearance

• Body mass index calculation
• Signs of Cushing syndrome such as buffalo hump, moon face, thinning of the skin, and red or purple striae
• Restlessness
• Sweating
• Flushing
• Neurofibromatosis

Neck

• Thyroid enlargement
• Carotid bruits

Fundoscopy

• Papilledema
• Cotton wool spots
• Arteriolar narrowing
• Arteriovenous nicking
• Hemorrhage

Heart

• Gallop rhythm, S4
• Heave
• Jugular venous distension

Lungs

• Rales
• Rhonchi

Abdomen

• Enlarged kidneys
• Aorta or renal bruits

Neurologic

• Visual changes
• Confusion
• focal weakness

Extremities

• Peripheral pulses
• Pedal edema
• Cold peripheral limbs

Evaluation

Further Evaluation

When systolic hypertension is suspected based on reliable measurements, perform a further evaluation to determine the following: 

• The presence or absence of cardiovascular risk factors
• The extent of the end-organ damage
• Identifiable causes of hypertension
• Concomitant clinical conditions affecting prognosis and treatment [2][8]

Routine Laboratory and Clinical Investigation

These tests should be performed to evaluate cardiovascular risk and concomitant diseases.

• 12-lead electrocardiographic (left ventricular hypertrophy features, atrial dilation, and arrhythmias)
• Lipid panels (calculate 10-year atherosclerotic cardiovascular disease risk)
• Serum creatinine (with an estimation of glomerular filtration rate)
• Serum electrolytes (sodium and potassium)
• Thyroid-stimulating hormone
• Urine analysis (proteinuria)
• Urine microalbuminuria

Additional Tests

Perform the following tests based on the relevant history, physical examination, and routine laboratory findings.

• Hemoglobin A1c
• Serum uric acid
• Ankle-brachial index
• Renal ultrasound and renal Doppler ultrasonography
• Quantitative proteinuria (urine protein to creatinine ratio, 24-hour urine protein)
• Echocardiogram (patient with heart failure)
• Specific tests to search for secondary causes of hypertension (plasma-free metanephrines, 24-hour urinary cortisol, aldosterone-renin ratio)

Treatment / Management

New classifications of blood pressure according to the 2017 American College of Cardiology/American Heart Association guidelines:[2](A1)

Normal Blood Pressure

• SBP less than 120 mm Hg and DBP less than 80 mm Hg
• Promote lifestyle modification

Elevated Blood Pressure

• SBP 120 to 129 mm Hg and DBP less than 80 mm Hg
• Initiate nonpharmacologic therapy and reassess in 3 to 6 months

Hypertension Stage 1

• SBP 130 to 139 mm Hg or DBP 80 to 89 mm Hg
• Patients without ASCVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk less than 10%: Initiate nonpharmacologic therapy for all patients and reassess in 3 to 6 months
• Patient with ASCVD or 10-year ASCVD risk equal to or greater than 10%: initiate nonpharmacologic therapy and single oral antihypertensive agent and reassess patient in 1 month

Hypertension Stage 2

• SBP more than 139 mm Hg or DBP less than 89 mm Hg
• Initiate nonpharmacologic therapy and single oral antihypertensive agent and reassess patient in 1 month

*If the blood pressure goal is not met, assess and optimize adherence to therapy or consider intensification of therapy.

*If the blood pressure goal is met, reassess in 3 to 6 months.

Several clinical trials such as hypertension in the very elderly (HYVET) and systolic hypertension in the elderly program (SHEP) have shown that active treatment of isolated systolic hypertension in older adults resulted in significant reductions in the all-cause mortality (13%), cardiovascular mortality (18%), and stroke (30%) and coronary (23%) events as compared with placebo.

Treatment of hypertension can be divided into nonpharmacologic and pharmacologic therapy.[2][8](A1)

Nonpharmacologic Therapy

• Recommended for all patients, regardless of the reading of the blood pressure.
• Restrict dietary salt (aim for 1.5 g or less per day). Randomized controlled trials have shown that moderate sodium reduction can result in an average blood pressure reduction of 4.8/2.5 mmHg).
• Weight loss (every 1 pound or 0.45 kg of weight loss will result in a reduction of 1 mmHg blood pressure).
• Start dietary approaches to stop hypertension (DASH) diet (rich in fruits, vegetables, whole grains, fish, and low-fat dairy products). A clinical trial has shown that the DASH diet helps to reduce blood pressure by an average of 6/4 mm Hg.
• Increase physical activity. Aerobic and resistance training can reduce blood pressure by an average of 4/3 to 6/3 mm Hg, irrespective of body weight.
• Limit alcohol intake to no more than one alcoholic drink per day for women and two for men.
• Take a potassium supplement (unless contraindicated in chronic kidney disease patients).
• Quit smoking.
• Use stress management.

Pharmacologic Therapy

• In general, start off with a single-agent oral antihypertensive drug therapy, especially in the elderly because of the risk of orthostatic hypotension.
• An exception to the above is when the initial SBP is above 160 or blood pressure is 20/10 mm Hg above the goal of blood pressure, which often needs the initiation of two oral antihypertensive agents.
• The four major classes of oral antihypertensive agents include thiazide-like diuretics (chlorthalidone and indapamide), dihydropyridine calcium channel blockers (CCBs: amlodipine, nifedipine, nitrendipine), angiotensin-converting enzyme inhibitors (ACEi: lisinopril, ramipril), and angiotensin receptor blockers (ARBs: losartan, valsartan).
• Randomized controlled trials have shown that thiazide-like diuretics and CCBs are the preferred first-line agents in reducing the risk of stroke and other morbidities in patients with isolated systolic hypertension.
• The dose of the single oral antihypertensive agent should be titrated to the maximum before initiating a second oral antihypertensive agent.
• In patients who require two oral antihypertensive agents, a combination of thiazide-like diuretic and CCB is the preferred strategy.
• ACEi or ARB is often used in patients with compelling indications such as heart failure reduced ejection, post-myocardial infarction, diabetes, or chronic kidney disease.
• A combination of either ACEi or ARB with CCB or a thiazide-like diuretic can be considered.
• It is important to note that ACEi should never be used concomitantly with ARB under any circumstances.
• Patients with secondary causes of hypertension should have their respective diseases addressed concurrently.
• Studies have shown that the use of beta-blockers in the management of hypertension is inferior compared with ARB, ACEi, or CCB for cardiovascular and stroke risk reduction.

Blood Pressure Goals

• SHEP and HYVET trials have shown significant benefits of antihypertensive treatment in patients with the goal of SBP less than 150 mm Hg.[9]
• The valsartan in elderly isolated systolic hypertension (VALISH) trial showed no significant difference in the primary outcome of sudden death, fatal or nonfatal myocardial infarction and stroke, heart failure death, or other cardiovascular death among patients with strict (less than 140 mm Hg) and moderate (140 to 150 mm Hg) SBP control.[10]
• However, the VALISH trial was underpowered due to the low number of events.
• Hence, the optimal SBP in patients with hypertensive disorders remained a controversial topic.
• The most recent systolic blood pressure intervention trial (SPRINT) has shown that an intensive SBP target of less than 120 mm Hg improved cardiovascular outcomes and overall survival compared to the standard SBP target of 135 to 139 mm Hg.[11]
• However, aggressive SBP lowering may be harmful in the elderly and incite more adverse effects such as hypotension, end-organ hypoperfusion (causing acute kidney injury, and intracranial hypoperfusion which may link to cognitive decline), and polypharmacy.
• It is suggested that a goal blood pressure of less than 130/80 mmHg is appropriate as long as the patient tolerates it.
• Otherwise, less than 140/90 mmHg is considered reasonable in patients who are in the elderly population and patients with labile blood pressure or polypharmacy.
• Management strategies should always be patient-centered, with the aim of optimizing blood pressure control and avoiding polypharmacy, especially in the elderly.
(A1)

J-curve Phenomenon

• Various studies have shown a J-curve association between blood pressure and with risk of myocardial infarction and death.
• Patients with isolated systolic hypertension who receive antihypertensive treatment may precipitously drop their DBP as well.
• As myocardial perfusion occurs mainly during diastole, an excessive drop in DBP may increase the risk of cardiovascular disease and death.[12][13]

Differential Diagnosis

It is important to identify white coat hypertension and masked hypertension correctly as over- or under-treatment of hypertension can have significant morbidity and mortality.

Whitecoat Hypertension

• Consistently elevated office blood pressure but normal out-of-office blood pressure

Masked Hypertension

• Consistently elevated out-of-office blood pressure but normal office blood pressure

Pseudo-hypertension

• Result of calcified blood vessels that cause incompressible peripheral arteries
• The blood pressure cuff is unable to measure the intraluminal blood pressure accurately
• This causes a false elevation of blood pressure reading
• The use of standing blood pressure measurement can help to differentiate pseudo-hypertension from true hypertension
• Patients with poorly controlled blood pressure should be evaluated for pseudo-hypertension before being labeled as resistant hypertension [14]

Prognosis

Mild to moderate hypertension may be associated with a risk of atherosclerotic disease if left untreated in 30% of people and organ damage in 50% of people within 8 to 10 years after onset. Patients with resistant hypertension also have a higher risk for poor outcomes, especially for those with certain comorbidities (eg, chronic kidney disease and ischemic heart disease). Patients with resistant hypertension who have lower blood pressure appear to have a reduced risk for some cardiovascular events (eg, incident stroke, coronary heart disease, or heart failure).

Complications

Uncontrolled high systolic blood pressure can lead to the following complications:

• Stroke
• Myocardial infarction
• Heart failure
• Peripheral vascular disease
• Aneurysm
• Chronic kidney disease
• Retinopathy
• Erectile dysfunction