SECONDARY CAUSES OF HYPERTENSION Flashcards
Indications for Evaluation of Secondary HTN
Drug-resistant HTN
Indications for Evaluation of Secondary HTN
Refractory HTN:
Failure to achieve goal blood pressure (i.e., <140/90 mm Hg), despite being treated by a HTN specialist over at least three visits over a 6-month period or longer
Refractory HTN patients tend to have higher heart rate (81 vs. 70) compared to those who are controlled, despite being on more β-blocker use. Sympathetic dysregulation is thought to play a role.
Specific Causes of Secondary HTN
Top three causes: renal parenchymal disease, aldosteronism, renal artery disease.
Specific Causes of Secondary HTN
Obesity
Proposed contributing factors: hyperleptinemia, hyperinsulinemia, endothelial dysfunction, sympathetic nervous system (SNS) activation, kidney injury, fructose ingestion, hyperaldosteronism driven by circulating oxidized fatty acids (linoleic acid) or uric acid, concurrent obstructive sleep apnea (OSA)
Specific Causes of Secondary HTN
Obesity
Fructose gets phosphorylated rapidly intracellularly leading to → local adenosine triphosphate depletion and uric acid generation → uric acid–induced endothelial dysfunction, SNS activation.
Specific Causes of Secondary HTN
Obesity
OSA:
OSA occurs in 30% of patients with HTN and up to 70% to 90% of patients with drug resistant HTN.
The association between OSA and HTN is dependent on OSA severity and presence of obesity. Association is not significant in individuals with BMI < 25 kg/m2 (National health and Evaluation Survey).
Specific Causes of Secondary HTN
Obesity
OSA:
Signs and symptoms to consider OSA in hypertensive patients: snoring, gasping/choking, daytime somnolence particularly with associated functional impairment (e.g., “sleeping on the job”).
Specific Causes of Secondary HTN
Obesity
OSA:
Physical risks: older men (>50 years old), “crowded” oropharynx, large neck circumference (>50 cm or >20 inches)
Specific Causes of Secondary HTN
Obesity
OSA:
Treatment with continuous positive airway pressure (CPAP) ventilation:
Improves BP control with use >4 hours in young patients (2 to 5 mm Hg reduction)
Recommended for symptomatic patients
Specific Causes of Secondary HTN
Obesity
OSA:
β-blockers are most effective antihypertensive agent in OSA due to sympathetic overactivity.
Specific Causes of Secondary HTN
Obesity
OSA:
Renal denervation improves office BP (average reduction of 34/13 mm Hg), but no significant effect on ambulatory BP (average reduction of 8 mm Hg) in small case series involving 10 patients.
Bariatric surgery versus lifestyle modifications/medical therapy
greater weight loss, greater BP reduction, lower antihypertensive drug requirement with bariatric surgery compared with lifestyle modifications/medical therapy alone, even in patients without morbid obesity
Neurogenic HTN
Cerebral blood flow = cerebral perfusion pressure/cerebrovascular resistance, where
Cerebral perfusion pressure = MAP − ICP and should be >60 mm Hg.
Neurogenic HTN
HTN after stroke:
Contributing factors: cushing reflex, catecholamine and cortisol release, lesion involving brain stem or hypothalamus, nonspecific response, acute stress.
Neurogenic HTN
HTN after stroke:
BP management per American Heart/American Stroke Associations:
For stroke patients receiving thrombolytic therapy:
Before thrombolytics: lower BP if SBP > 185 mm Hg or DBP > 110 mm Hg.
After thrombolytics: lower BP if SBP > 180 mm Hg or DBP > 105 mm Hg.
Neurogenic HTN
HTN after stroke:
Nonthrombolytic therapy stroke patients:
Antihypertensive medications should be withheld unless SBP > 220 mm Hg or DBP > 120 mm Hg.
When indicated, lowering BP by ~15% is reasonable.
Neurogenic HTN
HTN after stroke:
For acute cerebral hemorrhage:
If SBP > 200 mm Hg or MAP > 150 mm Hg, consider aggressive BP reduction (goal MAP 130 mm Hg if increased ICP, otherwise MAP 110 mm Hg).
If SBP > 180 mm Hg or MAP > 130 mm Hg plus evidence of or suspicion for elevated ICP, consider monitoring of ICP and reducing BP to keep cerebral perfusion pressure > 60 mm Hg.
If SBP > 180 mm Hg or MAP > 130 mm Hg and no evidence of or suspicion of elevated ICP, consider modest reduction of BP (e.g., MAP of 110 mm Hg or target BP of 160/90 mm Hg).
Most common agents used: IV labetalol and nicardipine
Antihypertensive agent selection in acute cerebrovascular hypertension
LABETALOL
Effect on Cerebral Blood Flow: Neutral
Effect on Intracranial Pressure: Neutral
Comments: Do not affect Cerebral Autoregulation
Antihypertensive agent selection in acute cerebrovascular hypertension
ESMOLOL
Effect on Cerebral Blood Flow: Neutral
Effect on Intracranial Pressure: Neutral
Comments: Concensus guidelines suggest IV Labetalol and Nicardipine as first line agents in acute hypertensive phase of stroke. This one is Contraindicated if bradycardic. May be used in the setting of cerebral ischemia or increased ICP.
Antihypertensive agent selection in acute cerebrovascular hypertension
NICARDIPINE
Effect on Cerebral Blood Flow: Neutral
Effect on Intracranial Pressure: May Increase
Comments: Long duration of action. Variabe effect on Cerebral Autoregulation. May be used in patients with acute ICH and SAH. Nimodipine is routinely used in patients with SAH, has been shown to improve outcome, presumably from a neuroprotective effect. Nifedipine is not recommended due to potential for hypotension.
Antihypertensive agent selection in acute cerebrovascular hypertension
HYDRALAZINE
Effect on Cerebral Blood Flow: May cause both Cerebral and arterial venodilation.
Effect on Intracranial Pressure: May increase ICP. May be used in patients with small to moderate-sized ICH or SAH if no ICP.
Comments: May be used when Beta-Blockers are contraindicated (e.g., bradycardia)
Antihypertensive agent selection in acute cerebrovascular hypertension
SODIUM NITROPRUSSIDE
Effect on Cerebral Blood Flow: May cause both Cerebral and arterial venodilation.
Effect on Intracranial Pressure: May increase ICP. May be used in patients with small to moderate-sized ICH or SAH if no ICP.
Comments: There is a concern for cyanide toxicity, reduced platelet aggregation. Cerebral steal possible in pts with cerebral ischemia
Antihypertensive agent selection in acute cerebrovascular hypertension
NITROGLYCERIN
Effect on Cerebral Blood Flow: May cause both Cerebral and arterial venodilation.
Effect on Intracranial Pressure: May increase ICP. May be used in patients with small to moderate-sized ICH or SAH if no ICP.
Comments: There is a concern for cyanide toxicity, reduced platelet aggregation. Cerebral steal possible in pts with cerebral ischemia
Antihypertensive agent selection in acute cerebrovascular hypertension
ENALAPRILAT
Effect on Cerebral Blood Flow: Neutral
Effect on Intracranial Pressure: —
Comments: Long duration of action.
Neurogenic HTN
HTN after carotid endarterectomy and endovascular procedures (e.g., angioplasty, stenting
Contributing factors: carotid baroreceptor impairment after surgical manipulation, elevated catecholamine levels, activation of trigeminovascular axon reflex
Neurogenic HTN
HTN after carotid endarterectomy and endovascular procedures (e.g., angioplasty, stenting
Carotid hyperperfusion syndrome following carotid endarterectomy:
Occurs during first week after surgery
Cerebral hyperperfusion is defined as having a postoperative increase in cerebral flow of >100% compared with preoperative flow on the ipsilateral side.
Ipsilateral symptoms: pulsatile headaches, seizures, intracranial hemorrhage, cerebral edema
Contralateral symptoms: neurological deficits
Neurogenic HTN
HTN after carotid endarterectomy and endovascular procedures (e.g., angioplasty, stenting
Management:
Continuous intra- and postoperative BP monitoring
Strict BP control with SBP < 120 mm Hg
Preferred agents: intravenous labetalol or clonidine
AVOID: vasodilators such as nitroglycerin, sodium nitroprusside
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Defined as SBP > 20% from baseline with associated change in heart rate (brady- to tachycardia), and at least one of the following: headache, facial flushing, blurry vision, stuffy nose, sweating, piloerection. Flush sweaty skin above lesion levels is due to brain stem parasympathetic activation.
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Occurs in up to 70% of patients with spinal injury affecting the sixth thoracic spinal nerve or higher level
Occurs in up to 90% of pregnant women during labor and delivery. Use of epidural or spinal anesthesia may reduce risk.
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Pathophysiology:
Immediately following spinal injury: loss of supraspinal sympathetic control leading to initial period of muscle flaccidity and “spinal shock,” clinically evident as bradycardia and hypotension
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Pathophysiology:
Weeks to months following injury: extrajunctional sprouting of α-receptors, denervation hypersensitivity, impaired presynaptic uptake of norepinephrine, and derangement of spinal glutamatergic neurons
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Pathophysiology:
Noxious stimuli below neurologic level of the lesion triggers a spinal reflex arc that results in increased sympathetic tone and HTN.
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Pathophysiology:
Common noxious stimuli are from urinary overdistention and fecal impaction. Others: sympathomimetic medications and sildenafil citrate used for sperm retrieval
Neurogenic HTN
HTN after spinal cord injury affecting the sixth or above the sixth thoracic spinal nerve (autonomic dysreflexia):
Management:
Preventive measures: good bowel, bladder, and skin care
Treatment:
Position patient upright to precipitate orthostatic BP.
Remove noxious stimuli (e.g., tight clothing, devices, fecal disimpaction, bladder catheterization as applicable).
Medications: select fast-acting, short-lived agents for persistent SBP elevation > 150 mm Hg. Consider other noxious stimuli, hospitalization if no resolution.
Parenchymal kidney disease
is the most common cause of secondary HTN
Simple renal cysts and HTN
Association thought to be due to cyst compression on adjacent renal parenchyma resulting in focal ischemia and activation of the renin–angiotensin–aldosterone system.
Simple renal cysts and HTN
Association with HTN is strengthened with increased number of cysts (≥2) and increased cystic size > 1.4 to 2.0 cm.
Simple renal cysts and HTN
Management:
Cyst decompression anecdotal reports of reducing BP.
Use of RAAS blockers may be beneficial.
Proteinuria and HTN
Proteinuria with loss of plasminogen in urine, leads to the formation of plasmin by tubular urokinase-like plasminogen activator. Plasmin directly stimulates the distal tubular sodium epithelial channel ENaC and sodium reabsorption (thus HTN) via the proteolytic cleavage of ENaC extracellular α- and γ-subunits.
Proteinuria and HTN
Potential role of amiloride or triamterene as preferred agent in the management of edema and salt sensitivity in patients with proteinuria and HTN.
Renovascular HTN
Clinical manifestations:
Clinical manifestations:
Activation of renin–angiotensin–aldosterone system: seen in early phase in bilateral renal artery stenosis, but sustained in unilateral disease
Paroxysmal symptoms due to SNS activation
Loss of nocturnal BP dipping
Renovascular HTN
Clinical manifestations:
Accelerated end-organ damage: left ventricular hypertrophy, microvascular disease, renal fibrosis
Abdominal systolic–diastolic bruits, sensitivity 39% to 63%, specificity 90% to 99%
Slow progression of renovascular HTN is thought to be associated with an adaptive response to tissue hypoxia thereby minimizing structural damage.
Renovascular HTN
Diagnostic studies:
Contrast angiography: gold standard: provides both structural and functional information; Risks: procedure-related vascular injury, contrast-induced AKI (CI-AKI).
Spiral computed tomographic angiography: good images of vessels; Risks: CI-AKI
Renovascular HTN
Magnetic resonance angiography with gadolinium: good structural and functional images of vessels; Risks: nephrogenic systemic fibrosis if gadolinium is used in patients with eGFR < 30 mL/min/1.73 m2; Other disadvantages: high interobserver variability; limited sensitivity for mid and distal vascular lesions associated with FMD. A lternative MRI contrast in patients with eGFR < 30 mL/min/1.73 m2: Feraheme
Renovascular HTN
Captopril renography (renal nuclear scan): provides information on renal blood flow (uptake/appearance of isotope [MAG3] phase) and filtration (excretory phase), hence information on size and excretory capacity of kidney. Delayed excretory phase following captopril administration suggests significant role of AII in maintaining GFR. Advantage: high negative predictive value, that is negative test essentially rules out clinically significant renal artery stenosis.
Renovascular HTN
Renal arterial Doppler (ultrasonography): most effective for detection of lesions in proximal main renal artery (thus likely not great study for fibromuscular dysplasia [FMD] where lesions are typically more distal). Advantages: inexpensive, readily available; Disadvantages: no functional information.
Renovascular HTN
Renal vein renin measurements: used to predict BP response to renal revascularization: a ratio > 1.5 (stenotic kidney):1.0 (nonstenotic kidney), predicts good BP response in > 90% of patients. However, nonlateralization may also have good response in ~50%.
Renovascular HTN
HTN occurs in the presence of a critical stenosis (e.g., >70% to 80%); Stenotic lesions < 60 % typically do not lead to clinically significant reduction in renal arterial flow to induce systemic activation of vasopressors to cause HTN.
Renovascular HTN
Unilateral stenosis
Unilateral stenosis (one-clip, two-kidney HTN model): one stenosed (experimental clipping of one renal artery) + one normal kidney
Renovascular HTN
Unilateral stenosis
Stenosed “clipped” kidney has reduced renal perfusion pressure → stimulation of neuronal NO synthase and cyclooxygenase 2 in macula densa → release of renin from juxtaglomerular apparatus → activation of RAAS, (i.e., increased angiotensin II (AII) and aldosterone) → systemic BP increases to restore renal perfusion pressure, increased sodium retention.
Renovascular HTN
Unilateral stenosis
Normal contralateral kidney undergoes pressure natriuresis to restore sodium and volume balance, thus counteracts the stenosed kidney’s attempt to improve its own perfusion → continued RAAS activation by stenosed kidney → angiotensin II-dependent HTN; aldosterone-induced renal K+ and H+ secretion in the contralateral kidney, hence hypokalemia and metabolic alkalosis.