ESSENTIAL HYPERTENSION

SECONDARY HYPERTENSION

 

Definition

Hypertensive is defined as an abnormal elevation in diastolic pressure and/or systolic pressure. In past years, the diastolic value was emphasized in assessing hypertension.  However, elevations in systolic pressure (“systolic hypertension”) are also associated with increased incidence of coronary and cerebrovascular disease (e.g., stroke). Therefore, we now recognize that both systolic and diastolic pressure values are important to note.

Hypertension is staged according to the latest U.S. national guidelines (JNC 7 Report).

African-Americans are more likely to develop hypertension and to develop it at a younger age. Genetic research suggests that African-Americans seem to be more sensitive to salt. In people who have a gene that makes them salt-sensitive, just a half-teaspoon of salt can raise blood pressure by 5 mm Hg. Diet and excessive weight can play a role, as well.

 

Two Classes of Hypertension

In 90-95% of patients presenting with hypertension, the cause is unknown.  This condition is called primary (or essential) hypertension.  Hypertension that results secondarily from renal disease, endocrine disorders, or other identifiable causes is called secondary hypertension.

 

Hypertension and Sodium

Sodium, a major component of salt, can raise blood pressure by causing the body to retain fluid, which leads to a greater burden on the heart. The American Heart Association recommends eating less than 1,500 milligrams of sodium per day. Processed foods contribute up to 75% of our sodium intake. Canned soups and lunch meats are prime suspects.

Hypertension and Stress

Stress can make the blood pressure spike, but there’s no evidence that it causes high blood pressure as an ongoing condition. However, stress may affect risk factors for heart disease, so it may have an indirect connection to hypertension. Stress may lead to other unhealthy habits, such as a poor diet, alcohol use, or smoking, which can contribute to high blood pressure and heart disease.

Hypertension and Weight

Being overweight places a strain on the heart and increases a risk of high blood pressure. That is why diets to lower blood pressure are often also designed to control calories. They typically call for cutting fatty foods and added sugars, while increasing fruits, vegetables, lean protein, and fiber. Even losing 10 pounds can make a difference.

Hypertension and Alcohol

Guidelines from the American Heart Association state for limitation  the amount to no more than two drinks a day for men, or one a day for women. They define a drink as one 12-ounce beer, four ounces of wine, 1.5 ounces of 80-proof spirits, or one ounce of 100-proof spirits.

Hypertension and Caffeine

It might have a temporary effect, but studies haven’t shown any link between caffeine and the development of hypertension. According to the American Heart Association is safely to drink one or two cups a day.

 Hypertension and Pregnancy

Gestational hypertension is a kind of high blood pressure that occurs in the second half of pregnancy. Without treatment, it may lead to a serious condition called preeclampsia that endangers both the mother and baby. The condition can limit blood and oxygen flow to the baby and can affect the mother’s kidneys and brain. After the baby is born, the mother’s blood pressure usually returns to its normal level.

Hypertension and Medicine

Cold and flu medicines that contain decongestants are one of several classes of medicine that can cause your blood pressure to rise. Others include NSAID pain relievers, steroids, diet pills, birth control pills, and some antidepressants.

‘White Coat’ Hypertension

The initial visit to the physician’s office is often the cause of an artificially high blood pressure that may disappear with repeated testing after rest and with follow-up visits and blood pressure checks. One out of four people that are thought to have mild hypertension actually may have normal blood pressure when they are outside the physician’s office. An increase in blood pressure noted only in the doctor’s office is called ‘white coat hypertension.’ A diagnosis of white coat hypertension might imply that it is not a clinically important or dangerous finding.

Etiology

·                     Kidney disease

1.     Diabetes complications (diabetic nephropathy).

2.     Polycystic kidney disease. In this inherited condition, cysts in the kidneys prevent the kidneys from working normally, and can raise blood pressure.

3.     Glomerular disease.

4.     Renovascular hypertension. This is a type of secondary hypertension caused by stenosis of one or both arteries leading to the kidneys. Renovascular hypertension can cause severe hypertension and irreversible kidney damage. It’s often caused by the same type of fatty plaques that can damage also coronary arteries (atherosclerosis) or a condition in which the muscle and fibrous tissues of the renal artery wall thicken and harden into rings (fibromuscular dysplasia).

·                     Endocrinological disorders

1.     Cushing’s syndrome. In this condition, corticosteroid medications, a pituitary tumor or other factors cause overproduction of adrenal glands hormones. This raises blood pressure.

2.     Aldosteronism. A tumor in the adrenal gland cause releasing an excessive amount of the hormone aldosterone, which raises blood pressure.

3.     Pheochromocytoma. This rare tumor, usually found in an adrenal gland, increases production of the hormones adrenaline and noradrenaline, which can lead to long-term high blood pressure or short-term spikes in blood pressure.

4.     Thyroid problems (hypothyroidism or hyperthyroidism)

5.     Hyperparathyroidism. The glands secrete too much parathyroid hormone, the amount of calcium in the blood rises — which triggers a rise in blood pressure.

·                     Coarctation of the aorta. This congenital disorder, in turn, raises blood pressure — particularly in the arms.

·                     Sleep apnea.

·                     Obesity. In overweight (obese) patients the amount of blood circulating through the body increases. This puts added pressure on the artery walls, increasing the blood pressure. In addition, excess weight often is associated with an increase in heart rate and a reduction in the capacity of the blood vessels to transport blood. All of these factors can increase blood pressure.

·                     Pregnancy. Pregnancy can make existing high blood pressure worse, or may cause high blood pressure to develop (pregnancy-induced hypertension or preeclampsia).

Medications and supplements. Drug-induced hypertension is among the most common causes of secondary hypertension and is frequently encountered in everyday clinical practice. The administration of offending drugs can result in excessive blood pressure elevation in some individuals, while most individuals will experience little or no increases of blood pressure. This variability represents a rule without exception. Therefore, it would be very important to identify predictors of blood pressure elevation, in order to individualize drug treatment.

Various prescription medications — from pain relievers to antidepressants can cause or aggravate high blood pressure in some people. Birth control pills, decongestants and certain herbal supplements may have the same effect.

NSAIDs-Induced Hypertension.

The most common cause of drug-induced hypertension is the use of  NSAIDs. Osteoarthritis and hypertension often coexist, since both conditions are age related. It has been reported that approximately 50% of patients with osteoarthritis suffer from hypertension. NSAIDs affect blood pressure levels via different mechanisms: activation of the renin-angiotensin-aldosterone system, sodium and water retention, induction of vasoconstriction through endothelin-1 and arachidonic acid metabolites, and mainly inhibition of renal vasodilatory prostaglandins (E2 and I2)

Oral Contraceptives. Women using oral contraceptives had an 80% higher risk of developing hypertension compared to women that were not using such drugs.

Anti-VEGF Agents. Another class of agents that emerged as inducers of hypertension are the antineoplastic drugs

that target the VEGF pathway.

 

Renal artery stenosis (renovascular disease)

 

Renal artery disease can cause of narrowing of the vessel lumen. The reduced lumen diameter decreases the pressure at the afferent arteriole in the kidney and reduces renal perfusion. This stimulates renin release by the kidney, which increases circulating angiotensin II (AII) and aldosterone. These hormones increase blood volume by enhancing renal reabsorption of sodium and water. Increased AII also causes systemic vasoconstriction and enhances sympathetic activity.  Chronic elevation of AII promotes cardiac and vascular hypertrophy. The net effect of these renal mechanisms is an increase in blood volume that augments cardiac output by the Frank-Starling mechanism. Therefore, hypertension caused by renal artery stenosis results from both an increase in systemic vascular resistance and an increase in cardiac output.

 

Chronic renal disease

·                     Any number of pathologic processes (e.g., diabetic nephropathy, glomerulonephritis) can damage nephrons in the kidney. When this occurs, the kidney cannot excrete normal amounts of sodium which leads to sodium and water retention, increased blood volume, and increased cardiac output by the Frank-Starling mechanism. Renal disease may also result in increased release of renin leading to a renin-dependent form of hypertension. The elevation in arterial pressure secondary to renal disease can be viewed as an attempt by the kidney to increase renal perfusion and restore glomerular filtration. 

 

 

Primary hyperaldosteronism

Increased secretion of aldosterone generally results from adrenal adenoma or adrenal hyperplasia.  Increased circulating aldosterone causes renal retention of sodium and water (see figure), so blood volume and arterial pressure increase.  Plasma renin levels are generally decreased as the body attempts to suppress the renin-angiotensin system; there is also hypokalemia associated with the high levels of aldosterone.

 

Diagnosing Secondary Hypertension

Secondary hypertension is elevated blood pressure that results from an underlying, identifiable, often correctable cause. Only about 5 to 10 percent of hypertension cases are thought to result from secondary causes. The ABCDE mnemonic can be used to help determine a secondary cause of hypertension:

·        Accuracy of diagnosis, obstructive sleep Apnea, Aldosteronism

·         presence of renal artery Bruits (suggesting renal artery stenosis), renal parenchymal disease (Bad kidneys)

·        excess Catecholamines, Coarctation of the aorta, Cushing’s syndrome,

·        Drugs, Diet,

·        excess Erythropoietin, and Endocrine disorders.

An algorithm showing the general strategy to help screen for factors involved in secondary hypertension is presented. Routine urinalysis, complete blood cell count, blood chemistry profile (potassium, sodium, creati-nine, fasting glucose, fasting lipid levels), and a 12-lead electrocardiogram are recommended for all patients with hypertension.

Patients with hypertension have some underlying mechanism that elevates their blood pressure. Conceptually, it is useful to think of patients with hypertension as having either essential hypertension (systemic hypertension of unknown cause) or secondary hypertension (hypertension that results from an underlying, identifiable, often correctable cause).¹

Although only about 5 to 10 percent of hypertension cases are thought to result from secondary causes, hypertension is so common that secondary hypertension probably will be encountered frequently by the primary care practitioner.^2–4

The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI)⁵ defines four goals for the evaluation of the patient with elevated blood pressure: detection and confirmation of hypertension; detection of target organ disease (e.g., renal damage, congestive heart failure); identification of other risk factors for cardiovascular disorders (e.g., diabetes mellitus, hyperlipidemia); and detection of secondary causes of hypertension. Physicians can use the mnemonic ABCDE to help determine secondary causes in the patient with elevated blood pressure (Table 1).

TABLE 1
Findings That Suggest Secondary Hypertension

Findings	Disorder suspected	Further diagnostic studies
Snoring, daytime somnolence, obesity	Obstructive sleep apnea	Sleep study
Hypernatremia, hypokalemia	Aldosteronism	Ratio of plasma aldosterone to plasma renin activity, CT scan of adrenal glands
Renal insufficiency, atherosclerotic cardiovascular disease, edema, elevated blood urea nitrogen and creatinine levels, proteinuria	Renal parenchymal disease	Creatinine clearance, renal ultrasonography
Systolic/diastolic abdominal bruit	Renovascular disease	Magnetic resonance angiography, captopril (Capoten)-augmented radioisotopic renography, renal arteriography
Use of sympathomimetics, perioperative setting, acute stress, tachycardia	Excess catecholamines	Confirm patient is normotensive in absence of high catecholamines.
Decreased or delayed femoral pulses, abnormal chest radiograph	Coarctation of aorta	Doppler or CT imaging of aorta
Weight gain, fatigue, weakness, hirsutism, amenorrhea, moon facies, dorsal hump, purple striae, truncal obesity, hypokalemia	Cushing’s syndrome	Dexamethasone-suppression test
Use of drug in	Drug side effect	Trial off drug, if possible
High salt intake, excessive alcohol intake, obesity	Diet side effects	Trial of dietary modification
Erythropoietin use in renal disease, polycythemia in COPD	Erythropoietin side effect	Trial off drug, if possible
Paroxysmal hypertension, headaches, diaphoresis, palpitations, tachycardia	Pheochromocytoma	Urinary catecholamine metabolites (vanillylmandelic acid, metanephrines, normetanephrines)
		Plasma free metanephrines
Fatigue, weight loss, hair loss, diastolic hypertension, muscle weakness	Hypothyroidism	TSH levels
Heat intolerance, weight loss, palpitations, systolic hypertension, exophthalmos tremor, tachycardia	Hyperthyroidism	TSH levels
Kidney stones, osteoporosis, depression, lethargy, muscle weakness	Hyperparathyroidism	Serum calcium, parathyroid hormone levels
Headaches, fatigue, visual problems, enlargement of hands, feet, tongue	Acromegaly	Growth hormone level

CT = computed tomography; COPD = chronic obstructive pulmonary disease; TSH = thyroid-stimulating hormone.

Traditionally, the principal target organ for aldosterone was said to be the kidney; MR are found in high concentration in the renal distal nephron as well as other epithelial sites, such as the colon and ducts of sweat and salivary glands (10). However, MR have also been identified  ionepithelial sites, such as heart, brain, vascular smooth muscle, liver, and peripheral blood leukocytes

 

 

 

TABLE 3
Risk Factors for Secondary Hypertension

Poor response to therapy (resistant hypertension)

Worsening of control in previously stable hypertensive patient

Stage 3 hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg)

Onset of hypertension in persons younger than age 20 or older than age 50

Significant hypertensive target organ damage

Lack of family history of hypertension

Findings on history, physical examination, or laboratory testing that suggest a secondary cause (Table 1)

Information from references 5,32, and 33.

Evaluation for Secondary Causes of Hypertension

FIGURE 1.General strategy for diagnosing a secondary cause of hypertension.

 

TABLE 4
Routine Screening Laboratory Tests for Hypertension

Urinalysis

Complete blood count

Blood chemistries (potassium, sodium, creatinine, fasting glucose)

Fasting lipid profile (LDL, HDL, triglycerides, total cholesterol)

12-lead electrocardiogram

LDL = low-density lipoprotein; HDL = high-density lipoprotein.

Information from Joint National Committee. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413–46.

 

 

Hypertensive emergencies

By definition, a hypertensive emergency involves an elevated BP (usually 180 mmHg systolic) in association with signs and/or symptoms of target organ damage. The resultant vascular compromise of the affected organ may include hypertensive encephalopathy, acute heart failure with pulmonary edema (flash pulmonary edema), dissecting aortic aneurysm, acute renal failure, and unstable angina. Management requires acute hospitalization for administration of parenteral antihypertensives, with continuous BP monitoring to lower BP rapidly yet not initially to a normal level. Normalization of BP immediately can lead to coronary and cerebral hypoperfusion syndromes. Therefore, BP should be lowered no more than 25% in the first 2 hours, with gradual lowering over the first

6 hours to a target of less than 160/100 mmHg. In comparison with emergencies, hypertensive urgencies are situations requiring BP lowering within 24 hours in order to avoid target organ damage. Again, gradual lowering of

BP is indicated, and can be obtained by administering oral agents in the setting of close follow-up.

 

Complications:

·                     Neurologic – Hypertensive encephalopathy, cerebral vascular accident/cerebral infarction. subarachnoid hemorrhage, intracranial hemorrhage

·                     Cardiovascular – Myocardial ischemia/infarction, acute left ventricular dysfunction, acute pulmonary edema, aortic dissection

·                     Other – Acute renal failure/insufficiency, retinopathy, eclampsia, microangiopathic hemolytic anemia

Age-associated trends in clinical hypertension

1.                 Sodium sensitivity increases with age, as does the hypotensive response to diuretics 2.                 Isolated systolic hypertension becomes more frequent than systolic–diastolic hypertension 3.                 Arterial stiffness increases 4.                 There is a greater incidence of endothelial dysfunction 5.                 The frequency of ‘white coat effect’ increases   Prognosis Most individuals diagnosed with hypertension will have increasing BP as they age. Untreated hypertension is notorious for increasing the risk of mortality and is often described as a silent killer. Mild-to-moderate hypertension, if left untreated, is associated with a risk of atherosclerotic disease in 30% of people and organ damage in 50% of people after only 8-10 years of onset. Death from both ischemic heart disease and stroke increase progressively as BP increases. For every 20 mm Hg systolic or 10 mm Hg diastolic increase in BP above 115/75 mm Hg, the mortality rate for both ischemic heart disease and stroke doubles. The morbidity and mortality of hypertensive emergencies depend on the extent of end-organ dysfunction on presentation and the degree to which BP is controlled subsequently. With BP control and medication compliance, the 10-year survival rate of patients with hypertensive crises approaches 70%. In the Framingham Heart Study, the age-adjusted risk of congestive heart failure was 2.3 times higher in men and 3 times higher in women when highest blood pressure was compared to the lowest.  The relative risk for stroke ranged from 3.6-19.2. The population-attributable risk percentage for coronary artery disease varied from 2.3-25.6%, whereas the population-attributable risk for stroke ranged from 6.8-40%. The Framingham Heart Study found a 72% increase in the risk of all-cause death and a 57% increase in the risk of any cardiovascular event in patients with hypertension who were also diagnosed with diabetes mellitus. Nephrosclerosis is one of the possible complications of long-standing hypertension. The risk of hypertension-induced end-stage renal disease is higher in black patients, even when blood pressure is under good control. Furthermore, patients with diabetic nephropathy who are hypertensive are also at high risk for developing end-stage renal disease. Comparative data from NHANES I and III showed a decrease in mortality over time among hypertensive adults, but the mortality gap between hypertensive and normotensive adults remains high.