ISFM Consensus Guidelines on the Diagnosis and Management of Hypertension in Cats

Abstract

Practical relevance:

Feline hypertension is a common disease in older cats that is frequently diagnosed in association with other diseases such as chronic kidney disease and hyperthyroidism (so-called secondary hypertension), although some cases of apparent primary hypertension are also reported. The clinical consequences of hypertension can be severe, related to ‘target organ damage’ (eye, heart and vasculature, brain and kidneys), and early diagnosis followed by appropriate therapeutic management should help reduce the morbidity associated with this condition.

Clinical challenges:

Despite being a common disease, routine blood pressure (BP) monitoring is generally performed infrequently, probably leading to underdiagnosis of feline hypertension in clinical practice. There is a need to: (i) ensure BP is measured as accurately as possible with a reproducible technique; (ii) identify and monitor patients at risk of developing hypertension; (iii) establish appropriate criteria for therapeutic intervention; and (iv) establish appropriate therapeutic targets. Based on current data, amlodipine besylate is the treatment of choice to manage feline hypertension and is effective in the majority of cats, but the dose needed to successfully manage hypertension varies between individuals. Some cats require long-term adjuvant therapy and, occasionally, additional therapy is necessary for emergency management of hypertensive crises.

Evidence base:

These Guidelines from the International Society of Feline Medicine (ISFM) are based on a comprehensive review of the currently available literature, and are aimed at providing practical recommendations to address the challenges of feline hypertension for veterinarians. There are many areas where more data is required which, in the future, will serve to confirm or modify some of the recommendations in these Guidelines.

Introduction

Systemic arterial hypertension (referred to simply as hypertension in these Guidelines) is a well recognised condition in cats, but probably remains significantly underdiagnosed. The clinical consequences of hypertension can be severe, due to target organ damage (TOD) affecting the eyes, heart, brain and kidneys, ¹ and some damage may be irreversible. Unless marked TOD is detected, the presence of hypertension is unlikely to be immediately apparent. Therefore, more widespread routine monitoring of feline blood pressure (BP) would likely enable an earlier diagnosis of hypertension and facilitate the prompt provision of effective therapy to prevent TOD and hopefully reduce the morbidity associated with hypertension.

Indirect measurement of BP in cats can be readily performed, although care is needed with both the choice and use of the equipment to ensure meaningful and accurate results are obtained. Systolic blood pressure (SBP) has been shown to increase with age in cats, ² as does the risk of hypertension. ³ The majority of cats diagnosed with hypertension have other systemic disease(s) which may cause or contribute to the hypertension,^3,4 although in up to 20% of cases no underlying cause is found.^5–7 Cats with an underlying disease are often referred to as having ‘secondary hypertension’, although the relationship between the hypertension and the underlying disease may not always be understood. When secondary hypertension is found, there is a need to manage both the hypertension and the underlying disease concurrently.

These Guidelines have been created to offer practitioners up-to-date information on the causes, clinical signs, diagnosis and management of feline hypertension, as well as practical advice on measurement of BP and interpretation of results. Where clinical studies and scientific data are not available, the Guidelines represent consensus opinion of the Panel.

Regulation of blood pressure

Blood pressure (BP) is the product of cardiac output (CO), which in turn is the product of heart rate and stroke volume (HR x SV), and systemic vascular resistance (SVR). Thus: BP = HR x SV x SVR.

In health, despite potential changes to blood volume, CO and SVR, complex neural and hormonal homeostatic mechanisms involving the brain, heart, vasculature and kidneys combine with local tissue factors to maintain BP within a relatively narrow range (Figure 1).

Figure 1.

Overview of some of the important mechanisms involved in the regulation of blood pressure. RAAS = renin–angiotensin–aldosterone system

The predominant factor controlling SVR is arteriolar size, which is affected by many systemically circulating, local tissue and endothelial-derived factors (Figure 1). ⁶ Blood volume is regulated by the kidneys, mainly through pressure natriuresis and the renin-angiotensin-aldosterone system (RAAS). Pressure natriuresis couples water and sodium excretion in response to changes in blood volume and CO (through alterations in renal perfusion), while the RAAS directly affects SVR via the potent vasoconstrictor angiotensin II, and affects blood volume through renal reabsorption of sodium and water via aldosterone.

Some organs, including the kidney, have the capacity to regulate their own BP (‘autoregulation’) to some extent. As a result, renal blood flow and glomerular filtration rate are maintained over a range of SBP (~80–160 mmHg). Outside of these limits, and also when significant kidney disease is present, direct transfer of elevated pressures to the glomerular capillaries results in glomerular hypertension and the potential for glomerulosclerosis.

Classification of feline hypertension

Hypertension is classified as: ¹

• Idiopathic (or primary) where there is no apparent underlying disease; or

• Secondary (thought to be due to underlying diseases or the use of therapeutic agents).

‘White coat hypertension’ is the increase in BP that occurs as a consequence of excitement- or anxiety-related sympathetic activation. This is important in veterinary medicine as the neurohormonal changes associated with the stress and/or excitement surrounding a veterinary visit can create a temporary physiological increase in BP.^16,17

Idiopathic hypertension

It is reported that 13-20% of hypertensive cats have idiopathic hypertension.^5–7 Further work is required to determine the degree to which non-azotaemic chronic kidney disease (CKD) might be a factor in some of these patients, and whether there are environmental factors or genetic predispositions, as have been identified in humans with ‘essential hypertension’. ¹⁸

Secondary hypertension

Secondary hypertension may be seen with many diseases including CKD, hyperthy-roidism, primary hyperaldosteronism (PHA), hyperadrenocorticism (HAC) and phaeo-chromocytoma. Secondary hypertension is the most common form of hypertension seen in cats.

Chronic kidney disease

CKD is the most common condition associated with feline hypertension. Azotaemia has been found in up to 74% of hypertensive cats, and conversely between 19% and 65% of cats with CKD have been found to be hyper-tensive.^19–22 However, the prevalence and severity of hypertension does not appear to be related to the severity of the CKD.^2,19,23

In humans, factors such as sodium and water retention, activation of the RAAS and the sympathetic nervous system, structural changes to arterioles, endothelial dysfunction, oxidative stress and genetics all play a role in the pathogenesis of CKD-associated hypertension. ⁸

Less is known about the pathogenesis of hypertension in feline CKD, but the limited change in renin, aldosterone or BP in response to the use of angiotensin-converting enzyme (ACE) inhibitors,^24,25 suggests systemic RAAS activation is unlikely to be the major factor involved. Elevated aldosterone independent of RAAS activation is recognised in some hypertensive humans, and may also play a role in cats with hypertension.^13,26 Some mechanisms worthy of investigation in cats with CKD-associated hypertension include local (tissue-specific) RAAS activation (independent of systemic RAAS), and impaired sodium handling by the tubules or collecting ducts,^18,27–29 although there is limited evidence to suggest salt-sensitive hypertension exists in cats.^30–32 The profound response of cats with CKD-associated hypertension to amlodipine ⁵ suggests that increased vascular tone may be particularly important, although this has not been specifically investigated.

Hyperthyroidism

Hypertension has been documented in 10–23% of cats with hyperthyroidism at the time of diagnosis,^21,33–35 although some of these cats may also have had CKD. Additionally, nearly 25% of hyperthyroid cats normotensive at the time of diagnosis may develop hypertension after successful control of their hyperthyroidism.^34–36

The pathophysiology of hyperthyroid-associated hypertension remains poorly understood. Studies in other species suggest that hyperthyroidism may increase cardiac sensitivity to circulating catecholamines, and thyroid hormones may also have direct effects on cardiac myocytes. ³⁷ Hyperthyroidism may also decrease SVR (through direct and indirect effects on blood vessels), with subsequent stimulation of the RAAS. ³⁸ However, in studies of hyperthyroid cats, there is no evidence that RAAS activation causes hypertension, although RAAS dysfunction may be present in some cats that develop hypertension after treatment for their hyperthyroidism. ³⁶

Primary hyperaldosteronism

PHA is an excess of aldosterone independent of its regulator, angiotensin II. Hypertension is reported in around 40–60% of cats with PHA.^39,40 It could initially be the consequence of sodium retention and volume expansion leading to increased CO, but sustained hypertension should result in pressure natri-uresis, returning plasma volume to normal. This, together with the fact that not all cats with PHA develop hypertension, suggests that other mechanisms are involved; ⁴¹ potentially these include effects on blood vessels, vascular tone, vascular remodelling and responses to sympathetic stimulation.^42–44

Other diseases

Diabetes mellitus (DM) is a well recognised risk factor for hypertension in humans, but there is little current evidence to show the same is true in cats, although further work is needed. Severe hypertension in cats with DM appears uncommon,^7,45 and the prevalence of hypertension in cats with DM is typically low, but often confounded by the presence of concomitant conditions such as CKD.^7,46 However, BP in cats with DM has been found to be higher than in healthy, age-matched controls, ⁴⁷ and hypertensive ocular disease has occasionally been reported in diabetic cats with no other underlying cause identified, ⁷ suggesting a link could exist.

Phaeochromocytomas are rare tumours in cats^48–52 associated with excessive circulating catecholamines, and can result in sustained or paroxysmal bouts of hypertension. There is also a report of severe hypertension in a cat associated with HAC, ⁵³ although the prevalence of hypertension in cats with this disease is unknown.

Consequences and clinical signs of hypertension

Hypertension is most likely to cause disease in tissues with a rich arteriolar supply^1,54 and in the cardiovascular system as a result of increased SVR.^1,54 The eyes, brain, kidneys and myocardium are thus particularly vulnerable to hypertensive injury (TOD).^1,20,54 Clinical manifestations of TOD can be striking and may be the reason for presentation to the vet-erinarian.^7,20,55 However, TOD is not always present and in some cats clinical signs of their underlying disease may predominate^5,19,56 or there may be no overt clinical signs.

Target organ damage: eyes

Hypertensive ocular changes have been reported in approximately 50% of hypertensive cats,^6,21,22,57 and studies suggest that retinal changes can develop at an SBP of approximately 160 mmHg and above.^58,59 However, the high prevalence of reported ocular lesions may reflect the relatively late diagnosis of hypertension in many studies.

The retina and choroid have separate blood supplies and both can suffer hypertensive damage, ⁶⁰ with an array of fundic lesions visible on ophthalmoscopy:^7,61

• Hypertensive retinopathy can manifest as haemorrhages of varying size and number^21,55 (Figure 2).

• Hypertensive choroidopathy can cause changes in the appearance of the retinal vessels. ⁷ Retinal oedema and breakdown of the blood-ocular barrier in the retinal pigment epithelium can create the impression that the vessels, particularly the arterioles, are narrowed ⁶¹ (Figure 3).

• Hypertensive choroidopathy can also cause retinal detachment, which can appear bullous, flat, or may involve the whole retina ⁶¹ (Figure 4), with the overlying retinal arterioles often appearing more tortuous than normal. ⁶¹ Photoreceptors often sustain irreversible damage from retinal detachment. ⁶²

• Hypertensive optic neuropathy is diagnosed rarely in cats, possibly because the nerve head appears recessed, making pathology more difficult to appreciate. ⁶¹

Figure 2.

SBP 182 mmHg. Left eye. Dorsal to the optic nerve head is substantial fresh vitreal haemorrhage. There are also some areas of retinal thinning and laterally there is retinal degeneration

Figure 3.

SBP 172 mmHg. Left eye. Note the generalised tapetal retinal oedema and retinal vessel attenuation. Throughout the tapetal fundus there are areas of hyperreflectivity due to retinal thinning and hyporeflectivity because of localised retinal oedema

Figure 4.

SBP 170 mmHg. Left eye. There is a large bullous retinal detachment, with several smaller foci of detachment lateral to this. Throughout the fundus are multifocal areas of pigmentary disturbance

Other ocular signs associated with hypertension include hyphaema and vitreal haemorrhage (Figure 5), ⁷ and hyphaema can in turn lead to secondary glaucoma. ⁵⁵

Figure 5.

SBP 195 mmHg. The right eye of this cat has vitreal haemorrhages present; the fundus was not visible

Many cats with severe hypertensive ocular damage present with blindness and bilateral mydriasis resulting from complete retinal detachments and / or intraocular haemorrhage; the changes are often irreversible.^7,20,21 Lesions that are not associated with an impaired menace response or pupillary light deficits (Figure 6) are much more amenable to anti-hypertensive treatment, ⁷ highlighting the importance of early diagnosis and management. Detection of early hypertensive ocular lesions requires an ocular examination to be performed on all cats at risk of developing lesions.

Figure 6.

SBP 167 mmHg. Left eye. Note the large bullous retinal lesion associated with a blood vessel; smaller bullous lesions are also present. This eye had an intact menace response and pupillary light reflex, and was completely visual

Target organ damage: brain

Hypertensive encephalopathy occurs when BP is high enough and sustained long enough to overcome the autoregulatory ability of the cerebral vasculature. ⁶³ Cerebral oedema and arteriosclerosis have been described in cats with hypertensive encephalopathy.^64,65 Studies have reported neurological signs in 15-46% of hypertensive cats,^{7,20,57,66,67} including disorientation, seizures, ataxia, depression and vestibular signs. Confirmation that clinical signs are due to hypertension is rarely achieved without advanced imaging, but a presumptive diagnosis can be made if signs improve following normalisation of BP. ⁶⁵ Anecdotally, owners often report improvement in some behavioural signs (eg, depression, lethargy) after antihypertensive therapy.

Target organ damage: heart and vasculature

The elevated SVR associated with hypertension can increase left ventricular wall stress and result in concentric left ventricular hypertrophy (LVH). This may commonly produce auscultatory abnormalities such as gallop sounds, and perhaps less commonly murmurs and arrhythmias, in hypertensive cats.^7,20,57 Echocardiography frequently reveals LVH,^57,68 although the degree of hypertrophy does not correlate with the magnitude of hypertension. ⁶⁹ Occasionally severe complications such as heart failure^7,20 or aortic dissection^70,71 have been reported in affected cats.

Target organ damage: kidneys

A controlled study of over 200 cats demonstrated increased glomerulosclerosis and arteriosclerosis in cats with higher BP, ⁷² supporting the concept of kidney TOD in feline hypertension. However, such lesions are not solely caused by hypertension; and, as many cats with hypertension have concomitant CKD, the importance of hypertension in causing nephrosclerosis and in causing or contributing to the progression of CKD remains uncertain. ⁷³

There is an association between SBP and the magnitude of proteinuria in cats with CKD, ⁷⁴ and treatment with amlodipine reduces the proteinuria. ⁶ This may be important, as pro-teinuria has been linked to reduced survival in cats with either CKD^74,75 or hypertension, ⁶ although managing hypertension has not yet been demonstrated to provide a survival benefit. In contrast, hypertension is recognised as both an important causal factor in human CKD, and a factor contributing to disease progression in human and canine CKD.^8,76

Patient groups benefiting from blood pressure measurement

Hypertension is much more common in older cats (>10 years old), with current studies suggesting a median age at diagnosis of 13–15 years,^6,7,57 although it has been reported in cats as young as 5–7 years.^{7,12,20,22,53,59,65} As early diagnosis (and management) of hypertension is considered valuable to help prevent TOD, this data helps to provide a rationale for which cats should undergo routine BP assessment (Table 1).

Table 1.

Recommendations for monitoring of SBP

Category	Frequency of SBP monitoring
Healthy adult cats (3–6 years of age)	Consider every 12 months*
Healthy senior cats (7–10 years of age)	At least every 12 months
Healthy geriatric cats (⩾11 years of age)	At least every 6–12 months
Cats with recognised risk factors including: • Underlying diseases: CKD, hyperthyroidism (including treated cats), PHA, HAC, phaeochromocytoma, etc • Drug therapy (eg, erythropoietin)77,78 • Evidence of TOD	Measure immediately and reassess at least every 3–6 months

^*The main purpose of monitoring in this age group is to obtain baseline measurements for the individual cat. As few cats in this age category have hypertension, great care is needed in the interpretation of elevated BP measurements, especially in the absence of TOD or a clear underlying disease SBP = systolic blood pressure; CKD = chronic kidney disease; PHA = primary hyperaldosteronism; HAC = hyperadrenocorticism; TOD = target organ damage

Additionally, as secondary hypertension is common in cats, individuals with recognised risk factors such as CKD, hyperthyroidism or PHA should undergo more frequent BP measurement. Further, the presence of any unexplained disease compatible with hypertensive TOD (eyes, brain, kidneys and heart) warrants careful BP assessment.

Recommended equipment and procedures for measuring blood pressure

Direct assessment of BP (via arterial cannulation) accurately measures SBP, dias-tolic blood pressure (DBP) and mean arterial pressure (MAP). Radiotelemetric implants allow direct BP measurements to be monitored over time in conscious animals, without direct intervention. However, this technique is not practical for clinical use in client-owned cats.^54,79

Equipment for routine clinical use

In clinical settings and with conscious cats, BP is usually measured using indirect techniques such as Doppler sphygmomanometry (Figure 7a) or oscillometry. The Doppler technique has been extensively used in feline medicine, with investigators demonstrating good correlation and accuracy compared with direct BP assessment. ⁸⁰ It has been shown that traditional oscillometry is less accurate than Doppler in conscious cats, often underestimating BP at higher values, and there are many cats for which it is difficult or impossible to achieve BP measurements with this equipment.^80–85

Figure 7.

Examples of (a) Doppler sphygmomanometry and (b) high-definition oscillometry (HDO) equipment

Recently, high-definition oscillometry (HDO) equipment (Figure 7b) has been developed to overcome the problems of traditional oscillom-etry. Although there are fewer reports of its use in cats, it has been compared with direct BP assessment in conscious cats over a range of different BPs and has shown to provide accurate results. ⁸⁶ It also appears that there are fewer cats for which it is difficult to obtain a reading compared with traditional oscillometry.^86,87

It should be noted that neither the Doppler nor HDO technique has been fully validated according to the ACVIM 2007 criteria.^1,88 Although HDO equipment will generate figures for SBP, DBP and MAP, it has been shown that in conscious cats it is only the SBP value that has acceptable accuracy. ⁸⁶ Further, although DBP can be measured with Doppler equipment, this measurement also lacks acceptable accuracy and repeatability.^80,89 However, systolic hypertension is generally thought to be the most clinically important form of hypertension; although isolated diastolic hypertension may occur in cats, ¹ the limitations of current measurement methodologies make this challenging to diagnose and any clinical significance uncertain.

As in other species, BP in cats is labile and varies considerably within and between individuals, depending in part on their level of arousal, activity or stress.^16,79,90 Clinical assessment of SBP is also affected by many external variables including the operator, conditions, environment, equipment, position of the cat, size of the cuff, and site of measurement.^{16,17,80,81,87,89,91–94}

Defining normal blood pressure

Some studies have evaluated direct SBP, DBP and MAP in healthy cats using radiotelemetry (Table 2), the results of which were not dissimilar to those of other mammalian species, including humans.^16,79,90,95 These studies also highlight the lability of feline BP in individual cats, with one demonstrating up to 80 mmHg change in SBP in response to a simulated clinic visit, ¹⁶ showing the potential magnitude of ‘white coat hypertension’ in healthy cats.

Table 2.

Direct blood pressure measurements (mmHg) in studies of healthy conscious cats

Study (number of cats)	SBP mean ± SD	MAP mean ± SD	DBP mean ± SD
Brown et al (n = 6) 95	125 ± 11	105 ± 10	89 ± 9
Belew et al (n = 6) 16	126 ± 9	106 ± 10	91 ± 11
Slingerland et al (n = 21) 79	132 ± 9	115 ± 8	96 ± 8
Mishina et al (n = 16) 90	117 ± 12	94 ± 11	78 ± 10

SBP = systolic blood pressure; MAP = mean arterial pressure; DBP = diastolic blood pressure

Figure 8.

Positioning of the cuff for blood pressure measurement. Forelimb (a) and tail (b) for Doppler measurement; tail (c) for measurement by high-definition oscillometry

Figure 9.

HDO traces recorded on a computer. (a) Good trace, providing a reliable reading. (b) Poor trace showing interference (as a result of patient movement)

Figure 10.

Example of a blood pressure assessment form. This document is available to download from jfms.com as a supplementary material file

Establishing reference intervals for estimated SBP in healthy cats using Doppler or oscil-lometric equipment is fundamental to the clinical diagnosis of hypertension, and also for determining therapeutic targets in affected cats. Results of studies in healthy cats are shown in Table 3, but it should be noted that there is a wide discrepancy between different studies; this reflects, at least in part, the different populations examined, and differences in types of equipment and the way equipment was used. Thus, having a standardised technique is of paramount importance.

Table 3.

Indirect SBP (mmHg) measurements in studies of healthy conscious cats

Equipment used (number of cats)	SBP (mean ± SD)
Traditional oscillometry *
Bodey and Sansom (n = 104) 56	139 (± 27)
Mishina et al (n = 60) 94	115 (± 10)
Curtet et al (n = 72) 92	123
Morar et al (n = 54) 97	124
Haberman et al (n = 13) 80	133 (± 28)
Doppler sphygmomanometry
Kobayashi et al (n = 33) 19	118 (± 11)
Sparkes et al (n = 50) 17	162 (± 19)
Lin et al (n = 53) 98	134 (± 16)
Bijsmans et al (n = 124) 2	131
Conti et al (n = 30) 91	135 (± 21)
Haberman et al (n = 13) 80	146 (± 50)

^*Note that traditional oscillometry is not suitable for assessing clinical hypertension as it tends to underestimate BP at higher values, and produces less reliable readings – see text

BP = blood pressure; SBP = systolic blood pressure

Unlike in humans, to date in feline medicine no gender effects on BP have been identi-fied;^56,94 in addition, there are no documented breed effects on feline BP.^56,94 Similar to humans, however, a recent large longitudinal study of cats established a small but significant increase in BP as cats age, ² equating to ~1-2 mmHg per annum for cats >9 years old. Humans with a higher baseline BP may be at increased risk of future development of hypertension (termed pre-hypertension),^99–101 and there is evidence that the same may be true of cats. ²

The majority of cats reported in the literature to have TOD associated with hypertension have had indirect SBP measurements in excess of 160 mmHg,^{5,7,14,20,22,53,55–57,59,64,65,71,102} although there are occasional exceptions to this. ⁵⁸ The International Renal Interest Society (IRIS) has proposed four categories of BP in cats – based on potential risk of TOD – to help with the diagnosis of hypertension (Table 4). ¹⁰³ However, along with the lability of BP already noted, it is likely the TOD in hypertension will not only be related to the severity of the hypertension, but also to the duration and relative change in BP that occurs, thus strict categorisation is problematic.

Table 4.

International Renal Interest Society staging for SBP ¹⁰³

SBP (mmHg)	Category	Risk of TOD
<150	Normotensive	Minimal
150–159	Borderline hypertensive	Low
160–179	Hypertensive	Moderate
⩾180	Severely hypertensive	High

SBP = systolic blood pressure; TOD = target organ damage

Routine treatment of hypertension

Whenever hypertension is diagnosed, it is important to search for, and treat, underlying diseases as most cases of feline hypertension are secondary. Treatment of underlying diseases is outside the scope of these Guidelines, but does not obviate the need for appropriate antihypertensive therapy.

The goal of therapy for hypertension is to decrease the risk of TOD, and help maintain or improve the health of the cat. This is generally achieved with an initial target SBP of <160 mmHg. ¹ Given that the IRIS group ¹⁰³ suggests the risk of TOD is minimal if SBP is <150 mmHg, and that some cats with TOD have pressures below 160 mmHg, a target of <150 mmHg may be an appropriate long-term goal.

Amlodipine besylate

Based on current data,^{5,6,9,11,12,14,66} the dihydro-pyridine calcium channel blocker amlodipine besylate is the drug of choice for the management of hypertension in cats, and there is now a product licensed for feline use in some countries.

Amlodipine is a potent peripheral arterial dilator that acts directly on vascular smooth muscle, causing a reduction in SVR and BP with minimal cardiac effects. ¹⁵ The reduction in SBP following treatment of hypertensive cats is generally around 30–70 mmHg,^{5,6,11,12,14,66} with 60–100% of cats responding to amlodipine as a monotherapy, albeit with dose adjustment being needed in some.^5,6,9,12,14 Amlodipine has also been shown to reduce the magnitude of proteinuria in hypertensive cats with CKD.^6,74 Adverse events associated with amlodipine therapy appear to be uncommon.^12,15 Although hypotension is a rare complication,^5,15 monitoring of SBP is always recommended. ¹⁵

Figure 11.

(a) 18-year-old, female, domestic shorthair cat with an SBP of 180 mmHg. Left eye. There is a large bullous retinal detachment medial to the optic nerve head. Also focal areas of retinal oedema lateral to the optic nerve head, with an area centrally that has coalesced to form a region of serous retinal detachment. (b) Same eye, 10 weeks after commencing amlodipine besylate treatment (current dose 1.25 mg q24h). The bullous lesion has resolved and the area of serous retinal detachment appears now as a hyporeflective, thickened area of the retina

Other treatments

ACE inhibitors,^{24,25,106–108} angiotensin receptor blockers (ARBs) ¹⁰⁷ and beta-blockers ⁴ have all been used to treat feline hypertension. They appear to have poorer efficacy in reducing SBP than amlodipine (typically only achieving a reduction in SBP of 10–20 mmHg),^{24,25,106–109} and fewer cats respond adequately to their use as monotherapy. These drugs are, therefore, best considered as second (or occasionally third) agents to add in to therapy if treatment with amlodipine is not sufficent to control the SBP (Table 5), ¹¹⁰ or if their use is indicated by any concurrent or underlying disease.

Table 5.

Drugs used for management of feline hypertension

Drug	Suggested dose	Comments
Amlodipine	0.625–1.25 mg/cat (0.125–0.25 mg/kg) q24h PO	Calcium channel blocker and drug of first choice. Dose may be doubled if response is inadequate up to a maximum of 2.5 mg/cat (0.5 mg/kg) q24h1,12
Benazepril	0.5–1.0 mg/kg q24h PO	ACE inhibitor24,25,108,110
Enalapril	0.5 mg/kg q12–24h PO	ACE inhibitor24,25
Ramipril	0.125–0.25 mg/kg q24h PO	ACE inhibitor 106
Telmisartan	1 mg/kg q24h PO (experimentally, a dose of 3 mg/kg produced a greater effect on blood pressure) 107	ARB, licensed at 1 mg/kg q24h in some regions for management of CKD-associated proteinuria. Not assessed clinically for managing feline hypertension, but one study showed greater response than benazepril to angiotensin I-induced pressor response when given at 1-3 mg/kg 107
Atenolol	1–2 mg/kg q12h PO	3-blocker 109

PO = orally; ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker

The choice of adjunctive therapy to help manage hypertension may in part be dictated by any concurrent or underlying disease. For example, ACE inhibitors or ARBs may be indicated in CKD patients to help manage proteinuria; atenolol may be indicated in some hyperthyroid cats to manage tachycardia; prazosin (an alpha-adrenergic blocker) may be indicated in phaeo-chromocytoma; and spironolactone in hyper-aldosteronism. These drugs are usually combined with amlodipine and titrated to effect.

Table 6.

Parenteral drugs for emergency management of hypertension

Drug	Suggested dose	Comments
Hydralazine	0.2–0.5 mg/cat SC; repeat after 15 mins if necessary	Direct arterial vasodilator. Add a 3-blocker if reflex tachycardia occurs1,102,112
Acepromazine	50–100 ng/cat IV or SC	Phenothiazine and a-blocker, non-specific vasodilator102,117
Nitroprusside	1 ng/kg/min CRI; titrate up to 3 ng/kg/min if needed	Nitric oxide donor, non-specific vasodilator 112
Labetolol	0.25 mg/kg IV over 2 mins, repeat up to a total of 3.75 mg/kg, then 25 mg/kg/min as CRI	α- and β-blocker 1
Esmolol	50–100 ng/kg/min CRI	β-blocker1,112

SC = subcutaneously; IV = intravenously; CRI = constant rate infusion

Emergency treatment of hypertension

Hypertension is generally a chronic condition, although some cats may present with an acute onset of severe clinical signs associated with TOD (usually ocular, neurological or cardiovascular). Acute elevations of BP may also be seen in some diseases such as acute kidney injury. Although hypertensive emergencies are not as clearly established as in humans, ¹¹¹ the severity of TOD may prompt more aggressive antihypertensive therapy,^1,112 despite a lack of definitive evidence that this approach is any more beneficial, and a potentially greater risk of adverse events. ¹¹³

Emergency treatment is aimed at halting ongoing TOD and preventing further damage. In human medicine, the initial goal of emergency therapy is to smoothly reduce SBP by up to 25% in the first 1–2 h, and then towards a level of 160 mmHg within a total of 6 h. ⁹⁹ Uncontrolled, abrupt reduction in SBP or development of hypotension can precipitate myocardial, cerebral or renal ischaemia and should be avoided.^114,115

Cats requiring emergency therapy should be hospitalised to allow close monitoring of BP and treatment adjustments. Where feasible, direct arterial pressure monitoring is preferred, to provide the most accurate measurement of BP. Generally, anti-hypertensive agents (especially parenteral agents) should be titrated upward to effect.^116,117 Amlodipine monotherapy may still be effective in emergency situations and should be used whenever oral administration is possible, safe and likely to be adequate. Detailed pharmacokinetic data for amlodipine use in cats are lacking. In humans, peak serum concentrations occur after 6–8 h. ¹¹⁸ Data provided for licensing in cats suggest peak serum concentrations are reached at 3–6 h in this species, with a half-life of 53 h. ¹¹⁹ Amlodipine has also been reported to have a BP lowering effect within 4 h and to last up to 30 h in clinical cases. ¹⁰ Parenteral treatments may need to be considered if the oral route cannot be used, if the response to oral therapy is inadequate, or if an underlying disease dictates their use.