Hypertension is the most important cardiovascular disease of the aged cat and the most important vascular disease in cats. Hence, its recognition and appropriate treatment is emerging as a critical component of small animal geriatric medicine. There are a host of target organs of hypertension. Our experience has shown that hypertensive cats have associated disease, in order of prevalence, of the eye, kidney, heart, and central nervous system.¹

Etiology of Hypertension

Hypertension in animals has largely been thought to be secondary to other disease (e.g., renal disease and endocrinopathies), as opposed to idiopathic (primary, essential), as is the case in most human hypertensives. This has recently been called into question. A report of 69 hypertensive cats, seen at North Carolina State University (NCSU) for ocular disease, revealed that at least 17%, and possibly as many as 50%, of cats had no identifiable cause for their systemic hypertension (primary or essential hypertension).¹ Elliott and associates showed that approximately 20% of hypertensive cats, diagnosed in "primary-care" practice, were idiopathic².

Described and potential etiologies of secondary hypertension include chronic and acute renal disease, hyperthyroidism, hypothyroidism, hyperadrenocorticism, hyperaldosteronism, pheochromocytoma, diabetes mellitus, and obesity. Clearly chronic renal disease has the greatest association with hypertension and may often be causal. A recent report suggested approximately 29% of elderly cats with chronic renal disease were hypertensive³ with a range of 4 studies from 19-65%.⁴

Pathogenesis

The pathogenesis of hypertension is complex, not well understood, and beyond the scope of this work. However, several studies have indicated that the renin-angiotensin-aldosterone system (RAAS) is probably abnormally activated in many or, perhaps, most cats with systemic hypertension, particularly with concurrent renal disease, and certainly after therapy with such drugs as loop diuretics and vasodilators.^5,6

Target Organ Damage

Autoregulation. Many tissues, including the eye, brain and kidney are able to protect the microcirculation from pressure fluctuation by "autoregulation". One can see that in the normal individual, the glomerular pressure is maintained constant between 60 and 160 mmHg. However, in hypertension, this protective measure is lost and elevated systemic pressures are translated directly to the capillary bed in a nearly linear relationship (dashed line) producing barotraumas.

Ocular Damage. The eye is the organ at greatest risk, not because of the frequency that it is affected but because of its vulnerability to the insult. The eye, when exposed to hypertension, loses its ability to autoregulate the pressures "seen" by the optic structures. Hypertension thereby disrupts "blood-ocular barriers" and produces "protective" vasoconstriction, then secondary vascular hypertrophy/hyperplasia and vascular dysfunction with leakage of blood components into ocular tissues & fluids. Clinical findings include arteriolar tortuosity, retinal edema, hemorrhage, detachment; and hyphema.

Blindness, often results and is usually, but not inevitably, permanent. Early detection is imperative, arguing strongly for yearly ophthalmic examination in aged cats.

Renal Damage. Failure of renal autoregulation results in high intraglomerular capillary pressure and ongoing renal destruction. This may occur with acute or chronic renal disease and, adding to the confusion in understanding the pathogenesis of hypertensive renal disease, renal disease begets hypertension and hypertension begets renal disease. Furthermore, activation of the RAAS contributes to renal damage and ACE-Inhibitors have been shown to spare renal disease by reducing intraglomerular pressures, inhibiting mesangial cell growth and fibrosis, and possibly by reducing proteinuria. The vessels themselves are damaged and contribute to the pathogenesis (see vascular damage, below).

The kidney, like the eye is an important target organ for hypertension. As renal disease and failure is a major problem in the aging cat population, correction of hypertension is one way which the duration and quality of life can be improved. Yearly or more frequent fundic examination, urinalysis, microalbuminuria-screening, and measurement of serum urea and creatinine, coupled with measurement of systemic blood pressure is essential in this population.

CNS Damage. With hypertension, the CNS also loses its ability to autoregulate similar. Cerebral blood flow is normally kept constant at systemic pressures of 60-150 mmHg. Higher pressures, however, are transmitted to the vasculature resulting in their damage, leakiness, and cerebral edema, possibly with brainstem herniation. Hypertension-induced over-perfusion also contributes to the edema. Vascular barotrauma may induce ischemia and brainstem hemorrhage. Signs include cranial nerve signs, seizures, somnolence and behavioral abnormalities.

Vascular Damage. Hypertension produces endothelial dysfunction with impaired vasodilation, begetting hypertension. Over time arteriosclerosis and myointimal hyperplasia result. These changes in anatomy and function alter the vessels' ability to protect other target organs through autoregulation. Schiffrin has shown that control of blood pressure alone does not reverse these changes, but blunting of the RAAS normalizes both vascular function and anatomy.

Cardiac Damage. Hypertension and the vascular change attendant to it produce increased cardiac afterload. This is compounded by SNS activation, which explains the well-recognized "white-coat effect". Cardiac hypertrophy and fibrosis is produced by the combination of hypertension (increased afterload) and RAAS activation.

Hypertension and cardiac damage are complicated by the SNS.

A study of 99 hypertensive cats revealed that the vast majority had suffered cardiac changes. Auscultatory abnormalities (murmur and/or gallops) were identified in 73%. Cardiomegaly was recognized in 52%, while 68% had electrocardiographic evidence of hypertensive heart disease. Echocardiography revealed left ventricular hypertrophy in 76%. Interestingly, only 3% of these cats developed heart failure.

Diagnosis of Systemic Hypertension

Table 1. Adapted from ACVIM Hypertension Consensus Statement Draft 2004

Table 2: Guidelines of ACVIM Panel on Hypertension*

*ACVIM Consensus Panel on Hypertension
**Kidneys at risk
***All target organs at risk
**** Treatment, monitoring interval

Diagnostic Methodology. Table 1 above lists 6 currently available blood pressure monitors. They use one of 3 different methods, as can be seen in column 3. We currently use the Doppler method, which has the distinct disadvantage of not providing diastolic or mean blood pressures in most instances. We use the tail as our first appendage for blood pressure measurement, followed by the palmar surface of the front leg and finally dorsal surface of the rear leg.

Cuff width is important and should approximate 30-40% of the circumference of the appendage used. Too small a cuff tends to overestimate and too large to underestimate true systemic blood pressure. The cuff position should approximate the level of the heart.

Current recommendations are that blood pressure be measured in a quiet area prior to examining the patient, typically in the presence of the owner and after a 5-10 minute period of acclimation. The ACVIM Panel on Hypertension suggests discarding the first measurement, then obtaining a minimum of 3, preferably 5-7, consecutive measurements with less than 20% variability in systolic blood pressure. The conditions (including animal's disposition), cuff size, site and all measurements should be recorded in the medical record. Many clinicians require that hypertension be documented on more than one occasion before accepting the diagnosis.

Below (table 3) are published values for feline systemic blood pressures (systolic = SBP, mean = MBP, diastolic = DBP) obtained by various means.

Table 3. Arterial blood pressure (mmHg) values obtained from normal cats.

(Adapted from ACVIM Consensus Statement Guidelines Draft 2004)

Therapy

Therapies for feline hypertension have varied and have not often been systematically evaluated. Therapies that have been employed and reported upon include diuretics (furosemide and spironolactone), angiotensin-converting enzyme inhibitors (ACE-I; captopril, enalapril, lisinopril, and benazepril), beta-blockers (propranolol and atenolol), and calcium channel blockers (diltiazem and amlodipine). Littman, retrospectively evaluated 24 cats with chronic renal failure (CRF), found that the most effective antihypertensive therapy was the combination of a beta-blocker and an ACE-I and that there was a poor response to furosemide.⁷ Jensen prospectively studied 12 similarly affected cats and found that the response to an ACE-I or beta-blocker alone was poor.⁸ Another retrospective study of 12 hypertensive cats with CRF and unresponsive to other therapy, showed amlodipine to lower blood pressure by >20% in 11.⁹ Snyder demonstrated blood pressure control in a randomized, blinded, placebo-controlled study of amlodipine in hypertensive cats, as well.¹⁰ Finally, the NCSU study retrospectively found amlodipine to lower blood pressure >20% in 30 of 32 hypertensive cats with 28 of 32 becoming normotensive.¹ Diltiazem and beta-blockers alone or with ACE-I also lowered blood pressure in the majority of cats so treated. The literature and clinical experience would, nevertheless, lead one to appropriately conclude that amlodipine is the single best agent for the management of feline systemic hypertension. This said, beta-blockers have a specific role in slowing heart rate and blocking the cardiovascular effects of T₃ in hyperthyroidism; ACE-I in combating drug-induced or spontaneous activation of the RAAS, for preserving renal function^11,12, and for proven effects in lowering blood pressure^13,14; spironolactone for its aldosterone-antagonistic effects¹⁵; and furosemide (possibly with nitroglycerin) for use in heart failure accompanying hypertension (See Table 4).

Other therapeutic considerations include: whether there is activation of the RAAS (initially or iatrogenically), the role of the sympathetic nervous system, renal function and the effects of hypertension on renal function, salt intake, presence of heart failure (uncommon), and the presence of reversible causes of hypertension (e.g., hyperthyroidism, diabetes mellitus, adrenal tumors). Additionally, I try to limit the number of pills to 1 (or 2) daily to reduce strain on the human-animal bond.

In deciding on a therapeutic approach, the author divides cats as follows: reversible cause--yes or no; with or without presumed RAAS activation (renal failure, heart failure, or treatment with vasodilators or loop diuretics); and by presence or absence of tachycardia (>200 bpm). The only common treatable cause of feline hypertension is hyperthyroidism, which is treated with methimazole, surgery, or ¹³¹I. In these cats, because of the effects of T₃ on beta receptors, I employ a beta-blocker, such as atenolol (6.25-12.5 mg PO daily), to reverse the cardiovascular effects of hyperthyroidism prior to or until more definitive therapy is efficacious. If unsuccessful, I add enalapril at 0.5 mg/kg/day PO. In all cases, I employ a moderately salt-restricted diet (one designed for kidney patients) to lessen total body sodium without worsening renal function or severely activating the RAAS.

In the euthyroid, non-tachycardic cat with hypertension, the somewhat complex algorithm described below can be avoided by merely administering amlodipine and enalapril each day. I advise 1 tablet in the AM and 1 in the PM, if the owners' schedule allows. If blood pressure control is not successful, see the material below.

Goals in Managing Systemic Hypertension

 Reduce blood pressure

 Correct causal conditions

 Blunt Renin-Angiotensin-Aldosterone

 Avoid stress, blunt SNS

 Spare target organs in other ways

 Minimize sodium intake

 Control heart rate

 Weight loss, if obese

 Avoid hypotension (rare)

Algorithmic Approach to Hypertension (see Fig below)

RAAS not activated. If the RAAS is not thought to be activated (this may be an erroneous assumption) and tachycardia is not problematic, the approach is as follows: amlodipine (0.625 mg to 1.25 mg PO daily, or even higher if unresponsive) plus a moderately salt-restricted diet and enalapril. The ACE-I is used to counteract activation of the RAAS, produced by amlodipine.⁶ If unsuccessful, I first double the dosage of amlodipine, then sequentially add atenolol and finally diuretics (furosemide at 6.25-12.5 mg daily or spironolactone at 1-2 mg/kg daily PO), if needed. It should be pointed out that, in cats unresponsive to amlodipine plus a second drug, owner compliance should be evaluated.

If tachycardia is present (without RAAS activation), I begin with moderate salt restriction and atenolol. With atenolol monotherapy, even though heart rate typically falls, blood pressure control is often inadequate. In that circumstance, I, sequentially add amlodipine plus enalapril, then, if needed, double the amlodipine dosage, and finally add a diuretic. On the other hand, if heart rate control is not initially successful, the atenolol dose is first increased. If this does not bring the exam room heart rate to <160 or the at home heart rate to <140, I would substitute diltiazem (Dilacor® at 30 mg PO bid) for amlodipine to better control heart rate and then follow the same sequence.

RAAS abnormally activated. When conditions (heart failure, renal failure, or drug therapy) indicate the RAAS is inappropriately activated, I begin therapy with amlodipine, a moderately salt-restricted diet and enalapril (See Fig above). If a normotensive state does not result, I add, sequentially, atenolol and finally diuretics (furosemide or spironolactone).

Alternatively, if tachycardia is a concern, moderate salt restriction, atenolol, and enalapril would be used initially. If unsuccessful control of hypertension results, amlodipine would be added, and followed sequentially, as needed, by a doubling of the amlodipine dosage, and finally diuretic therapy if needed. If after initial therapy, heart rate control is inadequate, the atenolol dose is first increased. If this does not adequately control heart rate, I would substitute long-acting diltiazem (Dilacor® at 30 mg PO bid) for amlodipine to better control heart rate and then follow the step-wise sequence mentioned above for blood pressure control, if needed.

Heart failure secondary to hypertension is rare and will not be discussed except to say that diuretics will likely be necessary in such patients to control signs and that enalapril is indicated. Lastly, if renal failure or significant renal disease is present, the etiology should be sought (at least by urinalysis and culture) in the hopes of finding a reversible cause. Otherwise, treatment of renal disease is standard and beyond the scope of this manuscript. It is wise to consider the routes of excretion of the drugs being used in deciding dosage and dosing interval in the face of renal insufficiency. Lastly, hypotension may infrequently occur as a result of over-exuberant anti-hypertensive therapy. This should be avoided as it may further compromise renal function.

The prognosis, overall, for hypertension is guarded but not grave. Vision lost rarely returns but survival averages have ranged from 18-21 months from the date of diagnosis.^1,3

Table 4. Cardiovascular Formulary for the Hypertensive Cat

References

1.  Maggio F, DeFrancesco TC, Atkins CE, et al. Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998). J Am Vet Med Assoc 2000;217:695-702.

2.  Elliott J, Fletcher M, Syme H. Idiopathic feline hypertension: Epidemiological study. J Vet Intern Med 2003;17:254.

3.  Elliott J, Rawlings PJ, Markwell PJ, et al. Incidence of hypertension in cats with naturally-occuring chronic renal failure. J Vet Intern Med 1999;13:251.

4.  Brown SA, Atkins CE, Bagley R, et al. ACVIM Consensus Statement: Guidelines for the identification, evaluation and management of systemic hypertension in dogs and cats. J Vet Intern Med 2004;in preparation.

5.  Haggstrom J, Hansson K, Karlberg BE, et al. Effects of long-term treatment with enalapril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation. Am J Vet Res 1996;57:1645-52.

6.  Atkins CE, Rausch WR, Gardner SY, et al. The Effect of Amlodipine and the Combination of Amlodipine and Enalapril on the Renin-Angiotensin-Aldosterone System in the Dog. J Vet Intern Med Submitted.

7.  Littman MP. Spontaneous systemic hypertension in 24 cats. J Vet Intern Med 1994;8:79-86.

8.  Jensen J, Henik RA, Brownfield M, et al. Plasma renin activity and angiotensin I and aldosterone concentrations in cats with hypertension associated with chronic renal disease. Am J Vet Res 1997;58:535-40.

9.  Henik RA, Snyder PS, Volk LM. Treatment of systemic hypertension in cats with amlodipine besylate. J Am Anim Hosp Assoc 1997;33:226-34.

10. Snyder PS. Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension. J Vet Intern Med 1998;12:157-62.

11. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 1996;334:939-45.

12. Brown SA BC, Jacobs G, et al. Hemodynamic effects of angiotensin converting enzyme inhibition (benazepril) in cats with chronic renal insufficiency (abst). J Vet Intern Med 1999;13:250.

13. Miller RH LL, Smeak DD, et al. Effect of enalapril on blood pressure, renal function, and the renin-angiotensin-aldosterone system in cats with autosomal dominant polycystic kidney disease. J Vet Intern Med 1999;60:1516-1525.

14. Grauer GF, Greco DS, Getzy DM, et al. Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis. J Vet Intern Med 2000;14:526-33.

15. Brilla CG ML, Weber KT. Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 1993;71:12A-16A.