Secondary Hypertension

Hypertension in the presence of underlying cause is referred to as secondary hypertension. Hypertension in itself is defined as systolic blood pressure reading of more than 140 on multiple occasions and diastolic reading of more than 90 on multiple occasions. 

Less than 5% of patients have secondary hypertension. It can be caused by a number of diseases of blood vessels, heart, kidney, endocrine system, etc.

Symptoms of secondary hypertension depends on its cause.

The presentation depends on the individual cause. For example:

• renovascular disease gives an abdominal bruit,
• Cushing’s disease gives weight gain, moon like facies, striae and ecchymosis,
• pheochromcytoma gives episodic hypertension associated with headache, palpitations and sweating,
• primary aldosteronism (Conns syndrome) gives muscle weakness and polyuria/polydypsia from hypokalemia, etc..

Secondary hypertension can be caused by a number of diseases.

Renal causes (2.5-6%) of hypertension include the renal parenchymal diseases and renal vascular diseases, as follows:

• Polycystic kidney disease
• Chronic kidney disease
• Urinary tract obstruction
• Renin-producing tumor
• Liddle syndrome
• Renovascular hypertension (RVHT) causes 0.2-4% of cases. 

Vascular causes include the following:

• Coarctation of aorta
• Vasculitis
• Collagen vascular disease
• Endocrine causes account for 1-2% and include exogenous or endogenous hormonal imbalances. 

Exogenous causes include administration of steroids. The most common form of secondary hypertension is a renal cause (although the true prevalence of hyperaldosteronism is not clear).

• Another common cause is endocrine: oral contraceptive use. Activation of the renin-angiotensin-aldosterone system (RAAS) is the likely mechanism, because hepatic synthesis of angiotensinogen is induced by the estrogen component of oral contraceptives. 

Approximately 5% of women taking oral contraceptives may develop hypertension, which abates within 6 months after discontinuation. The risk factors for oral contraceptive–associated hypertension include mild renal disease, familial history of essential hypertension, age older than 35 years, and obesity. It would be better to group oral contraceptives and steroids with drug-induced hypertension (see Table 1, below).

• Exogenous administration of the other steroids used for therapeutic purposes also increases blood pressure (BP), especially in susceptible individuals, mainly by volume expansion. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) may also have adverse effects on BP. NSAIDs block both cyclooxygenase-1 (COX-1) and COX-2 enzymes. The inhibition of COX-2 can inhibit its natriuretic effect, which, in turn, increases sodium retention. 

NSAIDs also inhibit the vasodilating effects of prostaglandins and the production of vasoconstricting factors—namely, endothelin-1. These effects can contribute to the induction of hypertension in a normotensive or controlled hypertensive patient.

Endogenous hormonal causes include the following:

• Primary hyperaldosteronism
• Cushing syndrome
• Pheochromocytoma
• Congenital adrenal hyperplasia

Neurogenic causes include the following:

• Brain tumor
• Bulbar poliomyelitis
• Intracranial hypertension

Drugs and toxins that cause hypertension include the following:

• Alcohol
• Cocaine
• Cyclosporine, tacrolimus
• NSAIDs
• Erythropoietin
• Adrenergic medications
• Decongestants containing ephedrine
• Herbal remedies containing licorice (including licorice root) or ephedrine (and ephedra)
• Nicotine

Other causes include the following:

• Hyperthyroidism and hypothyroidism
• Hypercalcemia
• Hyperparathyroidism
• Acromegaly
• Obstructive sleep apnea
• Pregnancy-induced hypertension
• Multiple studies have shown OSA to be an independent risk factor for the development of essential hypertension, even after adjusting for age, gender, and degree of obesity.
• Approximately half of individuals with hypertension have OSA, and approximately half with OSA have hypertension. 
• Numerous studies have shown that treatment of OSA by continuous positive airway pressure (CPAP) or position therapy lowers the awake and 24-hour blood pressure levels. Unfortunately, most cases of OSA go undiagnosed.

There are several parts to making an accurate diagnosis of Secondary Hypertension. 

A: ACCURACY, APNEA, And ALDOSTERONISM

Accuracy

The first, most practical step in evaluating an elevated blood pressure reading is to investigate its accuracy. A blood pressure cuff that is too small, tight-fitting sleeves that are not removed, or a brachial artery that is noncompressible because of calcification (sometimes seen in the elderly) can cause falsely elevated readings. 

White-coat hypertension (blood pressure that is elevated in the physician's office but normal at other times) accounts for about 20 percent of patients with elevated readings. JNC-VI recommends confirming high blood pressure readings outside of the office setting.

Apnea

Obstructive sleep apnea (OSA), a repetitive mechanical obstruction of the upper airway during sleep, is an independent risk factor for hypertension. At least one half of patients with OSA have hypertension. Treatment of OSA with surgery or nasal continuous positive air way pressure reduces hypertension in these patients. 

Aldosteronism

Primary hyperaldosteronism is defined as overproduction of aldosterone independent of its usual regulator, the renin-angiotensin system. The resulting retention of excess salt and water suppresses renin levels.

Increased urinary excretion of potassium signals hyperal-dosteronism, which should be suspected in all hypertensive patients with unprovoked (i.e., not diuretic-induced) hypokalemia. The next diagnostic test should be demonstration of an elevated ratio of plasma aldosterone levels to plasma renin activity.

B: BRUITS, BAD KIDNEYS (RENAL PARENCHYMAL DISEASE)

Bruits

Renovascular hypertension is defined as hypertension resulting from compromised arterial supply to the kidneys. About 65 percent of renovascular disease is secondary to atherosclerosis in the renal arteries, usually seen after age 50 in patients at risk for arterial compromise (e.g., smokers, patients with diabetes, and patients with known atherosclerotic disease). The remainder of patients will demonstrate fibromuscular dysplasia (FMD) and will tend to be younger (25 to 50 years of age) at the time of diagnosis.

Abdominal bruits heard in both systole and diastole is more suggestive of renovascular hypertension than systolic bruits alone. 

Magnetic resonance angiography (MRA) is a more sensitive noninvasive imaging modality for detection of renal artery stenosis. MRA best delineates the proximal renal vasculature and is therefore useful as an initial diagnostic tool for patients suspected of having atherosclerotic renal artery stenosis. Patients suspected of having FMD, which tends to involve the distal renal artery, should undergo conventional angiography or computed tomographic angiography.

Another initial diagnostic test is the captopril-augmented radio isotopic reno-gram.But the disadvantage of this test is that this test is not as useful if stenosis is present bilaterally.

Duplex ultrasound scanning is another diagnostic option, but it can be limited by its dependence on operator skill and experience. Renal arteriography remains the gold standard for defining the vessel anatomy.

Bad Kidneys

Diagnosis is based on loss of renal cortical function (demonstrated by elevated serum creatinine levels and decreased creatinine clearance), although it may be impossible to tell if the renal dysfunction is primary or secondary to the hypertension.

C: CATECHOLAMINES, COARCTATION, CUSHING'S SYNDROME

• Factors which suggest co-arctation of aorta include decreased lower-extremity (femoral) pulses with upper-extremity hypertension, dyspnea on exertion, and chest radiographic findings of notched ribs (from dilated collateral vessels) and dilation of the aorta above and below the constriction (the 3 sign).
• Cushing's Syndrome
• Diagnosis of Cushing’s syndrome is made via dexamethasone-suppression test.

D: DRUGS, DIET

Drugs

Many prescription and nonprescription drugs can cause or exacerbate hypertension. The best way to come to come to a conclusion involves proper history taking about use of drugs and associated problems.

Diet

The dietary impact on blood pressure can be concluded by proper history taking about salt intake and amount other minerals that have a direct impact on blood pressure.

E: ERYTHROPOIETIN, ENDOCRINE DISORDERS

Erythropoietin

Order for serum erythropoietin levels in patients suspected to have elevated blood pressure due to erythropoietin based disorders.

Endocrine Disorders

Hypothyroidism can cause a more prominent rise in diastolic blood pressure than in systolic blood pressure. Conversely, hyperthyroidism causes a greater increase in systolic blood pressure. A thyroid-stimulating hormone level is the best diagnostic screening test for thyroid disorders.

Hyperparathyroidism (primary or secondary to chronic renal insufficiency) is a potentially reversible cause of hypertension. 

Pregnancy-induced hypertension has an incompletely understood neurohumoral mechanism (possibly initiated by inadequate establishment of blood supply to the developing placenta) and occasionally can develop in the immediate postpartum period.

Pheochromocytoma is another endocrine cause of hypertension. The classic symptoms include headache, diaphoresis, palpitations, and paroxysmal hypertension. The usual screening test has been urinary measurement of catecholamine metabolites (vanillylmandelic acid, metanephrines, normetanephrines).

Acromegaly (elevated growth hormone) is a rare endocrine cause of hypertension. The diagnosis is on the basis of elevated IGF-1 levels.

According to JNC8 recommendations, treatment for Secondary Hypertension is as follows:

• In patients aged 60 years or older, initiate therapy in those with systolic BP levels at 150 mm Hg or greater or whose diastolic BP levels are 90 mm Hg or greater; treat to below those thresholds
• In patients younger than 60 years as well as those older than 18 years with either chronic kidney disease (CKD) or diabetes, the BP treatment initiation and goals should be 140/90 mm Hg
• In nonblack hypertensive patients, begin treatment with either a thiazide-type diuretic, CCB, ACE inhibitor, or ARB
• In hypertensive black patients, initiate therapy with a thiazide-type diuretic or CCB
• Regardless of race or diabetes status, in patients 18 years or older with CKD, initial or add-on therapy should consist of an ACE inhibitor or ARB
• Do not use an ACE inhibitor in conjunction with an ARB in the same patient
• If a patient's goal BP is not achieved within 1 month of treatment, increase the dose of the initial agent or add an agent from another of the recommended drug classes; if 2-drug therapy is unsuccessful for reaching the target BP, add a third agent from the recommended drug classes
• In patients whose goal BP cannot be reached with 3 agents from the recommended drug classes, use agents from other drug classes and/or refer the patients to a hypertension specialist.
• A joint AHA/ACC/CDC algorithm in the report includes the following recommendations:
• BP: Recommended goal of 139/89 mm Hg or less
• Stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg): Can be treated with lifestyle modifications and, if needed, a thiazide diuretic
• Stage 2 hypertension (systolic BP >160 mm Hg or diastolic BP >100 mm Hg): Can be treated with a combination of a thiazide diuretic and an ACE inhibitor, an angiotensin receptor blocker, or a calcium channel blocker
• Patients who fail to achieve BP goals: Medication doses can be increased and/or a drug from a different class can be added to treatment

             JNC-7 makes the following recommendations:

• The goals of antihypertensive therapy is the reduction of cardiovascular and renal morbidity and mortality, with the focus on controlling the systolic BP, as most patients will achieve diastolic BP control when the systolic BP is achieved
• Prehypertension (systolic 120-139 mm Hg, diastolic 80-89 mm Hg) requires health-promoting lifestyle modifications to prevent the progressive rise in BP and cardiovascular disease
• In uncomplicated hypertension, a thiazide diuretic, either alone or combined with drugs from other classes, should be used for the pharmacologic treatment of most cases
• In specific high-risk conditions, there are compelling indications for the use of other antihypertensive drug classes (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], beta blockers, calcium channel blockers)
• Two or more antihypertensive medications will be required to achieve goal BP (< 140/90 mm Hg or < 130/80 mm Hg) for patients with diabetes and chronic kidney disease
• For patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using 2 agents, one of which usually will be a thiazide diuretic, should be considered
• Regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan.

Five key strategies to prevent secondary hypertension are:

• Avoid processed and junk food because they are rich in Trans fatty acids which are not good for health. Ideally, DASH diet is the best diet recommended to lower B.P.
• Schedule your eating pattern in such a way so as to promote efficient energy use. That means eating specific calories during specific window of the day and avoiding other calories at other times of the day.
• Making whole, ideally organic food focus of your diet.
• Swapping carbs for healthy fats.
• Exercise regularly.
• Low salt diet.

Lifestyle modifications are necessary in order to cope with secondary hypertension.

Healthy eating, active living, and achieving a healthy weight have a major impact on prevention and management of hypertension.

More specifically, the risk factors of overweight, physical inactivity, and high sodium intake appear to be major independent contributors to hypertension. Indeed, clustering these risk factors into low-risk or high-risk groupings allows us to identify individuals at high or low risk of developing hypertension.

• The Canadian Hypertension Education Program (CHEP) recommends that “Hypertensive patients and normotensive individuals at increased risk of developing hypertension consume a diet that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources and that is reduced in saturated fat and cholesterol.”
• The DASH (Dietary Approaches to Stop Hypertension) diet which was developed specifically to address hypertension and traditionally referenced as the recommended dietary guideline along with other DASH-like diets. 

The DASH diet is known to result in substantial reductions in blood pressure, even when sodium intake is not reduced.

Best practices and patient resources 

Supporting patients who are making lifestyle changes aimed at preventing or managing hypertension calls for a comprehensive, structured, multidisciplinary, and sustained approach.

Clinicians can support self-management and help patients access ap¬propriate, culturally sensitive, clear, and affordable resources and supports in the community. 

Healthy eating, sodium reduction, physical activity, healthy weight, moderate alcohol consumption, and stress management are the best recommendations that a health care physician can give to his patient.