Chapter 153 Vascular Diseases
Diseases of blood vessels are quite common in small animal patients. Hypertension represents a fundamental disorder of the vascular system with wide-ranging impact. The vascular endothelium or vessel wall can become a target tissue for a multisystemic disease. Vascular obstruction or disease also impairs organ function by limiting tissue perfusion or obstructing venous return.
SYSTEMIC HYPERTENSION
Overview of Blood Pressure
Blood pressure can be normal, low, or high. The precise limits of normal arterial blood pressure (ABP) in dogs and cats is still a subject of investigation and some debate. Low blood pressure or hypotension is discussed elsewhere, in the Chapters on Shock (Chapter 156) and Heart Failure (Chapter 147). Systemic arterial hypertension is an increase in systolic or diastolic ABP and is considered in this chapter.
Systolic Blood Pressure
• Peak ABP depends on the prior diastolic pressure, the ventricular stroke volume, and the compliance of the arterial system (especially the aorta). Systolic pressure is most often used for the diagnosis of systemic hypertension because systolic blood pressure is easier to measure accurately than diastolic pressure, and because the majority of hypertensive dogs and cats have systolic or combined systolic/diastolic hypertension.
• The upper limit of normal for ABP depends on the species, the method of measurement, and the conditions of examination.
• In dogs, pressures >160 mm Hg (by the Doppler-flow method) are suspicious for hypertension. Values persistently greater than 180 mm Hg are diagnostic of hypertension, provided the dog is quiet, does not have tachycardia, and is not struggling.
• In cats, pressures >150 mm Hg are suspicious for hypertension, and values persistently greater than 160 mm Hg are considered diagnostic for hypertension (although some authors propose 170 mm Hg as the cutoff). Although “white-coat hypertension” related to the stress of examination has been reported in cats more frequently than dogs, both cats and dogs may have stress- or excitement-related elevations of blood pressure.
Diastolic Blood Pressure
• Vasodilation associated with systemic diseases (anemia, hyperthyroidism) or arterial vasodilator therapy often lowers diastolic pressure. Conversely, spontaneous or drug-induced vasoconstriction increases diastolic (as well as systolic) ABP.
• Diastolic pressure is detected with variable accuracy by oscillometric recording devices, but is more difficult to estimate with the Doppler flow method.
Mean Blood Pressure
• The mean arterial pressure is the geometric mean pressure during the cardiac cycle and is closer to the diastolic than the systolic reading.
Arterial Pulse Pressure
• The pulse pressure, or difference between systolic and diastolic ABP, is the basis for the palpable pulse identified during physical examination. The systolic and diastolic pressures are closely related in most circumstances so that each will increase or decrease proportionately. However, as indicated above, there are differences in the determinants of each pressure and situations are encountered where maximal and minimal pressures diverge.
• Aortic input impedance affects systolic ABP. For example, a potential reason for isolated systolic hypertension in older cats is the increase in aortic stiffness associated with idiopathic aortic dilation.
• Stroke volume has a marked effect on systolic ABP. Stroke volume is increased in cases of increased left ventricular filling (Frank-Starling effect) and increased sympathetic activity. Simply increasing stroke volume usually increases both systolic and diastolic pressures. But there are situations in which stroke volume increases but diastolic pressure decreases. This is especially likely in the setting of peripheral vasodilation, abnormal run-off of aortic blood flow, or when the heart rate is especially slow. Examples include:
Etiology
• Hyperadrenocorticism—both Cushing’s disease in dogs (with glucocorticoid excess) and Conn’s disease in cats (associated with mineralocorticoid excess and hypokalemia) can lead to hypertension.
• Drugs—particularly the alpha-adrenergic agonists (such as phenylpropanolamine) that lead to vasoconstriction.
Clinical Signs
Brain Abnormalities
• Cerebral or brainstem injury can result from hypertension owing to brain edema or hemorrhagic stroke. Clinical signs include signs of intracranial abnormalities, including abnormal mentation, neurologic deficits, head tilt, seizures, and coma. Presumably, as with human patients with hypertension, dogs and cats also develop “headaches” and this may account for some of the inactivity observed in affected small animals.
Ocular Abnormalities
• Ocular abnormalities include retinal edema, hemorrhage, and detachments. These lesions can progress to blindness. Sudden blindness also may develop due to intraocular hemorrhage and hyphema. Recognition requires careful ophthalmic examination. Acute lesions are often superimposed on chronic retinal changes.
Cardiac Abnormalities
• The heart generates the pressure in hypertension and may also be injured by work and the high pressures distributed across the coronary vascular system.
• A systolic cardiac murmur of uncertain cause or an atrial (S4) gallop sound may indicate hypertensive heart disease. A systolic heart murmur may represent mitral regurgitation, flow into a dilated aorta, or dynamic ventricular outflow tract obstruction related to the hypertrophic disease.
• Concentric left ventricular hypertrophy and resultant cardiomegaly are the markers for chronic hypertension and can be identified by an echocardiogram (most sensitive), electrocardiogram (increased voltages or left-axis deviation), or thoracic radiograph (least sensitive).
• While congestive heart failure (CHF) stemming from hypertensive heart disease is relatively uncommon in dogs and cats, distinguishing left ventricular hypertrophy due to systemic hypertension from primary hypertrophic cardiomyopathy or hyperthyroid heart disease in cats can be a challenge. In dogs with chronic mitral valve disease, systemic hypertension increases the load on the left ventricle and increases the regurgitant volume. Persistent hypertension may prevent effective drug control of CHF in these dogs.
Kidney Abnormalities
• The kidneys are both a source and target of hypertension. Abnormal renal contour or size, proteinuria, and mild-to-moderate azotemia often are found in hypertensive animals. Hypertension injures glomerular vessels and damages renal tissues. In some cases it may be difficult to discern if hypertension is the cause or the consequence of renal disease and hypertension secondary to chronic renal disease promotes further glomerular damage.
Diagnosis
• When evaluating the hypertensive patient, search for an underlying cause, as treatment may reduce the need for antihypertensive drugs.
• Consider the history, and determine if any medications that might increase ABP have been prescribed (such as thyroid hormone; alpha-adrenergic agonists; antihistamine combinations with vasoconstricting properties).
• At a minimum, perform routine diagnostic studies that include a full serum biochemical profile; complete urinalysis; serum thyroxin; and either abdominal radiographs or optimally an abdominal ultrasound examination with particular attention to the kidneys and adrenal glands.
• Diagnosis of hypertension requires measurement of ABP using either an arterial puncture attached to a pressure transducer or an indirect determination that uses a reliable technology and consistent technique.
• Both oscillometric methods and Doppler flow methods have been used successfully for measuring ABP in dogs. Systolic ABP is slightly underestimated by the oscillometric technique.
• Systolic pressures can be readily determined in cats using Doppler flow meter and occlusion cuff on a fore or hind limb. Oscillometric measurements can be obtained from cats using an appropriately-sized cuff at the tailhead in the sternal animal. Oscillometric measurements using a tail cuff may underestimate Doppler-obtained blood pressure.
• Care must be taken to consider normal variation in excited animals. Slight differences (5-10 mm Hg) between front and back limbs are normal in many animals, and the cuff size (diameter) is critical to prevent overestimation (too small a cuff) or underestimation (too wide a cuff).
Since the development of systemic hypertension is usually an indication for life-long therapy, the diagnosis should be as certain as possible. One or two high pressure readings in the setting of overt target-organ injury are sufficiently conclusive. However, in otherwise healthy animals, repeated measures—preferably over a number of days—should be obtained before establishing a diagnosis.
Technique for Measuring Blood Pressure
• Practice on numerous animals of different sizes. Practice improves skill and confidence. Train others to measure ABP and compare results. When using Doppler methods, learn to evenly decrease the pressure in the cuff and manometer.
• Measure ABP in calm animals that are comfortably restrained—in many clinical situations, it is advantageous to let the pet rest in its caretaker’s arms or lap for the measurements. Avoid measuring ABP in sedated animals.
• Have a supply of different-sized pediatric cuffs (e.g., #1–#6 pediatric cuffs) available. Place nonelastic, self-adhesive tape (such as Vetwrap) around the cuff to prevent slippage.
• Measure the limb and use an appropriate sized cuff. The cuff must compress the limb evenly and occlude the artery with the approximate pressure recorded by the manometer. Use the smallest cuff appropriate for the limb size. Cuff diameter should be 40% of the limb circumference in dogs and between 30% and 40% of the limb circumference in cats. There is often a 10- to 20-mm Hg difference between next sized cuffs; wider variations suggest a technical error in recording or a cuff problem.
• Place the cuff around the distal radius (antebrachium), metatarsus or tailhead, around a relatively cylindrical portion of the appendage. Secure the cuff with wrap and attach it to the manometer. The inflatable bladder of the cuff should be positioned directly over the underlying artery.
• Place the patient in either lateral or sternal recumbency on a padded table, in a quiet room, with calm people. Gently restrain the patient, and give the pet time to acclimatize to the environment.
• Measure heart rate (HR). If it is high (e.g., >160 in a dog; >240 in a cat), try to help the animal relax before proceeding.
• Consider the site of measurement relative to heart level. The cuff should be at the level of the heart during measurement. ABP should not be measured in a standing animal unless a tail cuff is used.
• Inflate the cuff one or two times, slowly and gently, and allow the animal to experience what will happen during measurement. Then record the pressure.
• With a Doppler method, place the crystal palmar (or plantar) and just distal to the large carpal (metatarsal) pad. Use subtle medial-lateral; anterior-posterior movements to detect the arterial signal. In cats and small dogs, or in patients with low blood pressure, use a light touch and copious ultrasound gel (not rectal jelly) to obtain an optimal acoustic signal. Clipping the hair can be helpful. Once a reading is obtained, repeat the measurement two more times noting the values and the concurrent HR.
• For Doppler flow systems, consider using earphones attached to the available output plug to reduce the loud, popping on/off sound of crystal movement, a noise that may startle the patient. At a minimum, do not place the audio speaker near the patient’s head.
• If using an automated oscillometric device, attach the cuff at the tail base, the antebrachium, or the metatarsus. Place the two cuff lines on either side of the artery (which is generally ventral and slightly medial). Measure HR with a stethoscope. It should correspond almost exactly with the automated monitor. If it does not, do not accept the displayed values.
• If the ABP value is “low” (systolic pressure < 90 mm Hg) try the next smaller cuff. If it is still low, go to the hind limb to verify the value. If the animal is not symptomatic, interpret the clinical situation and determine the most likely cause (for example, volume depletion, sedatives, or cardiovascular drugs).
• If the ABP is high (systolic pressures of >180 mm Hg in dogs; >160 mm Hg in cats), try the next sized larger cuff, as this will more easily compress the artery. If ABP is still high (or <20 mm Hg lower than the last measurement), the initial measurement is probably accurate, but verify it by placing the cuff at an alternative site (e.g., from forelimb to metatarsus or tail).
• Labile hypertension may indicate a “white-coat” effect from examination stress or, in some patients, a true labile situation (as with pheochromocytoma in dogs).
• With either measurement method, obtain 3 to 5 measurements with approximately 30 seconds between measurements. Discard any obviously spurious readings and use the average of the repeated measurements to obtain a representative reading for that session.
• Interpret the findings of elevated ABP in conjunction with other clinical findings. In animals with ocular, renal, CNS, or cardiac disease, an elevated ABP measurement is more likely to represent a true finding of hypertension. If other clinical findings are negative, measure the pressure at another time or day.
Treatment: General Measures
• Treat the underlying problem (e.g., hyperthyroidism or hyperadrenocorticism) whenever possible; however, remember that in some cases there may be more than one reason for hypertension and that correction of one problem will not insure a normotensive state. For example, many older cats have preexisting renal disease as one risk factor and later develop hyperthyroidism, which can compound the hypertension.
• If pressure is very high (>200 mm Hg) or if target organ injury is evident (especially if there is ocular or cerebral disease), treat the hypertension before addressing the underlying disorder.
• Modest dietary sodium restriction is reasonable in treating hypertension, however, there is little evidence that severe sodium restriction will benefit most dogs and cats with hypertension. Attempting to control significant hypertension by diet alone is ill-advised, and diet should be viewed as simply an adjunct to antihypertensive drug therapy.
• Drug therapy is generally required to treat hypertension. ABP can be lowered pharmacologically by reducing cardiac output or reducing systemic vascular resistance by dilating systemic arterioles.
• Therapy of systemic hypertension usually involves a stepwise approach, starting with a moderate dosage of one drug, increasing the dose to the desired effect as needed, or adding other drugs if required.
• There are also some particular situations wherein a specific regimen of drugs is more desirable, for example, in glomerular disease or in hypertension associated with pheochromocytoma.
Drug Therapy for Systemic Hypertension
Calcium Channel Blockers
• Most clinicians initiate treatment of systemic hypertension in cats with the calcium-channel antagonist/vasodilator amlodipine besylate (Norvasc). Dihydropyridines such as amlodipine and felodipine are more vascular selective than other calcium channel blockers such as diltiazem. Although diltiazem may slow heart rate, it is not recommended as a primary therapy for systemic hypertension.
• Amlodipine is an effective and well-tolerated therapy for hypertension in cats, based on a number of small, but convincing, clinical studies. Clinical experience indicates amlodipine at higher doses is effective for blood pressure control in dogs.
• The starting dose in cats is 1/4 of a 2.5-mg tablet PO once daily. In some cases, higher doses, up to 1.25 mg PO q12h, may be needed.
• In hypertensive dogs, amlodipine is dosed initially at 0.1 to 0.2 mg/kg PO q12h. Response is variable in dogs, though it tends to be very good at higher dosage ranges of 0.2 to 0.5 mg/kg PO q12h.
• Amlodipine has a relatively slow onset in dogs, and a prolonged duration of action. Unless urgent control of ABP is needed, increase the dose gradually, over several weeks to target ABP levels (usually <140 mm Hg).
• Amlodipine monotherapy works better than an angiotensin-converting enzyme inhibitor (ACEI), beta-blocker, or diuretic in cats, and is the drug of choice for hypertension that is severe (>200 mm Hg systolic ABP) or associated with overt target organ injury (retinal or CNS signs).
• Comparison to ACEI: amlodipine is more effective than benazepril in lowering ABP, but is not considered directly renoprotective (aside from reducing ABP) in patients with significant proteinuria.
• The combination of amlodipine with benazepril or enalapril is reasonable in cats or in dogs with documented renal disease with proteinuria. Optimal ABP control may be facilitated by the amlodipine besylate, whereas benazepril may reduce proteinuria and delay progression of renal disease, especially in cats.
• Amlodipine is relatively expensive, compared to generic or veterinary enalapril or benazepril, and this may be an important issue in large dogs wherein combined therapy may allow for dose reduction of amlodipine.
• One approach to combination therapy is administration of amlodipine once daily in the morning and the ACEI once daily after noon. If higher doses of both drugs are needed, they can be administered together, twice daily. In addition, there is a combination capsule of 10 mg amlodipine/2.5 mg benazepril (Lotrel) that may be useful in some larger patients or might be compounded for individual use.
Angiotensin-Converting Enzyme Inhibitors
• Hypertension in dogs or cats can be treated with an ACEI, typically benazepril (human Lotensin in the United States; veterinary Fortecor in many other countries) or enalapril (veterinary Enacard).
• An ACEI is particularly reasonable therapy in dogs and cats with mild hypertension and concurrent glomerular disease (see Chapter 77).
Diuretics
• In comparison to human patients, diuretic therapy of hypertension of dogs and cats is inferior and rarely undertaken.
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