Hypertension Flashcards
Hypertension classification (ACVIM 2020)
Hypertension is classified by risk of TOD:
Normotensive (minimal TOD risk) SBP <140 mm Hg
Prehypertensive (low TOD risk) SBP 140-159 mm Hg
Hypertensive (moderate TOD risk) SBP 160-179 mm Hg
Severely hypertensive (high TOD risk)SBP ≥ 180 mm Hg
Approach to hypertension - when to investigate and how, when to treat
Assess BP if: evidence of TOD, presence of conditions known to cause SHT
(screening in young healthy animals not recommended by consensus due to unknown prevalence in healthy population, though in older dogs/cats it may be considered)
pre-hypertensive - increase monitoring of BP every 3-6 months
BP>160 with no TOD repeat measurement a few times ver 8 weeks. If persistently elevated investigate for underlying disease and commence antihypertensives
BP>180 reassess twice over 14 days. if persistent then look for underlying cause and treat
evidence of TOD - look for underlying cause and commence treatment
Presence of TOD justifies commencement of anti-hypertensive medications, but in most cases results should be confirmed by repeat measurement
Drugs associated with hypertension
glucocorticoids; mineralocorticoids, EPO; phenylpropanolamine; phenylephrine; ephedrine; pseudoephedrine; toceranib; high dose NaCl;
Toxins: cocaine; methamphetamine; 5-hydroxytryptophan
ACVIM recommended investigations for hypertension
CBC, Biochemistry,
Urinalysis, UPCR, SDMA,
TT4, cortisol levels (ACTH/LDDST), serum/urine aldosterone levels, adrenal/renal ultrasound
Ophthalmic exam
Neurological exam - MRI if deficits
Auscultation and thoracic rads/echo/ecg if audible abnormalities
Goal of antihypertensive Tx in ACVIM 2020
maximally decrease the risk of TOD (SBP < 140 mm Hg) and that antihypertensive treatment should be adjusted on re-evaluation if SBP is ≥ 160 mm Hg, with a minimal goal of treatment being to achieve a decrease in SBP to ≤ 160 mm Hg
Blood pressure <120 mm Hg, combined with clinical findings of weakness, syncope, or tachycardia, indicates systemic hypotension and treatment should be adjusted accordingly
Recommended first line treatment in dogs with SHTT
Address underlying cause
RAAS inhibitors and calcium channel blockers (CCB) are the most widely recommended antihyper-tensive agents for use in dogs
(unless phaemochromocytoma or aldosterone producing adrenal tumour)
RAAS inhibitors are often chosen as first-line antihypertensive agents in dogs
- In dogs with concurrent CKD, a clinically relevant decrease in proteinuria (UPCR decreased by ≥50%, preferably to <0.5) is a secondary goal of antihypertensive treatment
- coadministration of a RAAS inhibitor and a CCB is recommended in severely hypertensive patients (BP >200mmHg)
- Use of CCB as monotherapy in dogs should be avoided because CCB preferentially dilate the renal afferent arteriole potentially exposing the glomerulus to damaging increases in glomerular capillary hydrostatic pressure
Diuretics in patients with clinically apparent volume overload
ACVIM recommended SHT treatment in cats
- Ca channel blockers (amlodipine) are first choice because of established efficacy in cats with CKD or idiopathic hypertension. Research evaluating plasma amlodipine concentration indicates that the need for dose escalation to adequately control BP appears to relate to severity of the hypertension rather than to body weight or amlodipine pharmacokinetics. Patients with severe hypertension may benefit from commencing treatment at the higher dosage
→ Despite dramatic antihypertensive efficacy, longitudinal control of SBP with amlodipine besylate has not been shown to increase survival time in hypertensive cats. Use may activate intrarenal RAAS
Telmisartan - proven efficacy in hypertensive and proteinuric cats, not proven if ocular/CNS TOD or if SBP >200mmHg
Studies on the use of telmisartan in the management of hypertension have revealed a mean decrease of approximately 20–25 mmHg in the SBP of treated cats
higher starting dosage of 2 mg/kg Po q24h recommended for systemic hypertension in cats compared with the licensed dosage of 1 mg/kg Po q24h for an antiproteinuric effect
ACEi - not recommended as first line as only cause small decrease in SBP which is usually not sufficient in cats. Can bemused as second line where amlodipine not enough. Rare reports of uraemic crisis in cats prescribed ACEi - may be due to efferent glomerular dilation causing reduced GFR
Spironolactone - indicated if primary hyperaldosteronism (based on renin:aldosterone ratio) prior to adrenalectomy or combined with amlodipine if needed (monitor K+
Mechanisms that kidney senses alterations in BP - outcomes of perceived changes
Renal afferent arteriolar stretch receptors, which detect renal perfusion pressure,
Macula densa at the start of the distal convoluted tubule, which detects the rate of chloride ion delivery in tubular fluid.
Perceived decrease in SBP will be accompanied by a decrease in renal sodium excretion –> increased ECV
Increased SBP –> pressure natriuresis
Cause, outcome and reason for RAAS activation in CKD
reduced renal blood flow perceived (due to diuresis from renal dysfunction through renal afferent stretch receptors or reduced Cl delivery to macula densa)
-> renin release -> AngI -> AngII -> vascular remodelling, aldosterone release, NA retention
Increased RAAS activation is an expected physiological compensatory response to progressive loss of nephrons during CKd, as angiotensin ii works to increase single nephron glomerular filtration rate (GFR) via preferential constriction of the efferent arteriole
Increased sympathetic activity driven by dysfunctional renal afferent nerve activity is also thought to contribute to development of hypertension in CKd
Endothelial dysfunction from chronic AngII -> impaired ability of the endothelial layer of blood vessels to release vasodilator substances
Challenge with diagnosis of idiopathic hypertension
Because subclinical kidney disease is present frequently in people and animals with hyper-tension, a valid diagnosis of primary or essential hypertension can be difficult to establish.
Furthermore, the presence of chronically increased BP suggests that one or more of the neurohumoral and renal systems responsible for regulating BP is abnormal.
Increased BP may also induce polyuria through pressure diuresis - so a low USG does not indicate CKD. However, a high USG suggests CKD is unlikely.
Evidence for use of telmisartan in feline SHT
Jfms 2019 - Telmisartan in healthy cats compared to placebo. SBP values were significantly lower in cats treated with TEL at all tested dosages by the second week of treatment
JVIM 2019 - prospective trial of telmisartan in SHT 252 cats vs placebo (excluded severely affected cats)
52% of telmisartan‐treated cats had SABP <150 mmHg at Day 28
Mean SABP reduction by telmisartan in severe (≥180 mmHg) and moderate HT (160‐179 mmHg) was comparable and persistent over time
excluded from this study were cats with SBP >200 mm Hg, cats with evidence of ocular or central nervous system (CNS) TOD and those already being treated with vasoactive agents. Efficacy of telmisartan in severely hypertensive cats and in those with overt ocular and CNS hypertensive TOD has not been demonstrated
JVIM 2019 - prospective, randomized, double‐blind, placebo‐controlled, parallel group, efficacy phase and a 154‐day extended‐use telmisartan phase
By day 14 SBP decrease was significantly larger in telmisartan‐treated compared to placebo and persisted over 6 month trial
JVIM 2021 In comparison to group ACEi alone, combination treatment of an ACEi with TEL significantly reduced systolic blood pressure by 13 mm Hg
Amlodipine and an ACEi or amlodipine and an ARB is reportedly well tolerated, studies exploring any additional survival benefit of add-on antiproteinuric agents in hypertensive cats that remain protei- nuric after BP control with amlodipine besylate are lacking
ACVIM definition, targets and recommended Tx for hypertensive emergency
marked increases in BP are accompanied by signs of ongoing acute TOD (usually ocular or neurological)
The therapeutic target in patients with acute hypertensive emergencies is an incremental decrease in SBP rather than acute normalization of BP. In cases of chronic hypertension, autoregulatory vascular beds in the brain and kidneys may have adapted to higher perfusion pressure, and acute marked BP reduction may result in hypoperfusion.
SBP should be decreased by approximately 10% over the first hour and another approximately 15% over the next few hours, followed by gradual return to normal BP.
optimal acute management of hypertensive emergencies requires parenteral treatment that can be titrated to effect, with rapid onset and conclusion of action
Fenoldopam - dopamine R agonist, causes renal arterial vasodilation, natriuresis, and increased GFR in normal dogs
Hydralazine
Supported by recent JFMS article on the presentation and outcome in cats with hypertensive encephalopathy
