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Feline Hypertension_ Risks_ Diagnosis and Management - Proceedings

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Feline Hypertension_ Risks_ Diagnosis and Management - Proceedings Powered By Docstoc
					           Proceedings of the
World Small Animal Veterinary Association
        Sydney, Australia – 2007



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    Australian Small Animal     Australian Small Animal   Australian Small Animal
    Veterinary Association      Veterinary Association    Veterinary Association
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               FELINE HYPERTENSION: RISKS, DIAGNOSIS AND MANAGEMENT
                                     Clarke E. Atkins, DVM
                       Diplomate, ACVIM (Internal Medicine & Cardiology)
                 Department of Clinical Sciences, College of Veterinary Medicine
                           North Carolina State University, Raleigh NC

           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

           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% (Fig 1), 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 (Fig 1). 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
                         3                                          4
           hypertensive. with a range of 4 studies from 19-65%.

           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 The role of the Sympathetic
           Nervous System (SNS) in hypertension is illustrated in the figure below
           (Target Organ Damage: Cardiac Damage).




                          Proceedings of the WSAVA Congress, Sydney, Australia 2007
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           Diagnosis of Systemic Hypertension

             Table - Adapated from ACVIM Hypertension Consensus STatement Draft
                                            2004
                   Device                       Manufacturer                 Device Type
              Cardell Model 9401,2,3           Sharn Veterinary Inc.          Oscillometry
                                                     (800) 325-3671
                                             http://www.sharnvet.com


               Dinamap Model 8300                No longer available          Oscillometry
             Jorgensen Model J5373                   Jorgensen Labs             Doppler
                                                                           ultrasonography
                                                     (800) 525-5614
                                               http://www.jorvet.com


                    Memoprint,                       S & B medVET             Oscillometry
                  Memodiagnostic             http://www.submedvet.de


                Parks Model 811-B            Parks Medical Electronics          Doppler
                                                                           ultrasonography
                                                     (800) 547-6427
                                              http://www.parksmed.co
                                                         m


                      Vet-Dop                  Vmed Technology Inc              Doppler
                                                 (800)926-9622             ultrasonography
                                             http://www.vmedtech.com


              VetSpecs Model BP2,3               VetSpecs Medical              Pressure
                                                     Systems               plethysmography
                                                     (800) 599-2566
                                             http://www.vetspecs.com




                            Guidelines of ACVIM Panel on Hypertension*



                          Proceedings of the WSAVA Congress, Sydney, Australia 2007
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                   Status                                    SBP (mmHg)               DBP
                   (mmHg)          Rx/Monitor

                 Normal                               <140       and       <90            None
                 Pre-hypertensive                    140-159     or       90-99           None;
           Q3-6 mos
                 Stage 1 hypertension**              160-169     or       100-109
           ACE-I; Q1-3 mos
                 Stage 2 hypertension***              >180         or      >110
           ACE-I + Amlod; var.

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

           Diagnostic Methodology.

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




                          Proceedings of the WSAVA Congress, Sydney, Australia 2007
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           Arterial blood pressure (mmHg) values obtained from normal cats.
            (Adapted from ACVIM Consensus Statement Guidelines Draft 2004)
                   Method                  # Cats       SBP        MBP                DBP
                   Intra-arterial (Direct)
                                              6       125 ± 11      105 ± 10      89 ± 9
                   Brown et al, 1997

                   Belew et al, 1999            6     126 ± 9       106 ± 10      91 ± 11

                  Oscillometry

                   Bodey et al, 1998            104   139 ± 27      99 ± 27       77 ± 25

                   Mishina et al, 1998          60    115 ± 10      96 ± 12       74 ± 11

                   Doppler Method

                   Klevans et al, 1979          4     139 ± 8

                   Kobayashi et al, 1990        33    118 ± 11

                   Sparkes et al, 1999          50    162 ± 19




                          Proceedings of the WSAVA Congress, Sydney, Australia 2007
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           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 function11,12, and for proven
           effects in lowering blood pressure13,14; spironolactone for its aldosterone-
           antagonistic effects15; and furosemide (possibly with nitroglycerin) for use in
           heart failure accompanying hypertension (See Table).

           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 (See Fig), 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




                          Proceedings of the WSAVA Congress, Sydney, Australia 2007
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           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.


           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 (DilacorR 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). 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 (DilacorR at 30 mg PO bid) for amlodipine to better



                          Proceedings of the WSAVA Congress, Sydney, Australia 2007
Published in IVIS with the permission of the WSAVA                               Close window to return to IVIS



           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


                             Cardiovascular Formulary for the Hypertensive Cat
                   Drug       Trade Name* Formulation( Dosage               Use
                                             s)**
           Amlodipine         Norvasc        1.25 mg        .625 PO qd-bid Antihypertensive
                                             tablets
           Diltiazem          Cardizem       30 mg tablets 7.5 mg PO tid    Lusitrope,
                                                                            Vasodilator,
                                                                            Negative
                                                                            chronotrope
           Diltiazem - LA
                              Dilacor XR         180, 240 mg       30 mg PO bid        same
                                                 caps.
                              Cardizem CD        180, 240 mg       45 mg PO qd         same
                                                 caps.
           Enalapril          Enacard            1, 2.5, & 5 mg    .5 mg/kg PO qd ACE-I (CHF,
                              (Vasotec)          tablets                             Hypertension)
           Benazepril         Lotensin           5 & 10 mg         .25-.5 mg/kg      same
                              (Foretkor)         tablets           PO qd-bid
           Atenolol           Tenormin           25 mg tablets     6.25-12.5 mg      Negative
                                                                   PO qd             chronotrope,
                                                                                     Antiarrhythmic,
                                                                                     Lusitrope,
                                                                                     Antihypertensive
           Nitroglycerin      Nitrol, Nitro-     2% ointment       1/8–¼ inch        Venodilator (CHF)
                              Bid                                  topically tid for
                                                                   24 hours
           LMW Heparin        Fragmin            2500 U/.2 ml      100 U/kg SQ       Anticoagulant
                                                                   qd
           Aspirin                               81 mg             40-80 mg q72h Anticoagulant




                           Proceedings of the WSAVA Congress, Sydney, Australia 2007

				
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