Abstract
Hypertension is the single greatest contributor to human disease and mortality affecting over 75 million people in the United States alone. Hypertension is defined according to the American College of Cardiology as systolic blood pressure (SBP) greater than 120 mm Hg and diastolic blood pressure (DBP) above 80 mm Hg measured on two separate occasions. While there are multiple medication classes available for blood pressure control, fewer than 50% of hypertensive patients maintain appropriate control. In fact, 0.5% of patients are refractory to medical treatment which is defined as uncontrolled blood pressure despite treatment with five classes of antihypertensive agents. With new guidelines to define hypertension that will increase the incidence of hypertension world-wide, the prevalence of refractory hypertension is expected to increase. Thus, investigation into alternative methods of blood pressure control will be crucial to reduce comorbidities such as higher risk of myocardial infarction, cardiovascular accident, aneurysm formation, heart failure, coronary artery disease, end stage renal disease, arrhythmia, left ventricular hypertrophy, intracerebral hemorrhage, hypertensive enchaphelopathy, hypertensive retinopathy, glomerulosclerosis, limb loss due to arterial occlusion, and sudden death. Recently, studies demonstrated efficacious treatment of neurological diseases with deep brain stimulation (DBS) for Tourette’s, depression, intermittent explosive disorder, epilepsy, chronic pain, and headache as these diseases have defined neurophysiology with anatomical targets. Currently, clinical applications of DBS is limited to neurological conditions as such conditions have well-defined neurophysiology and anatomy. However, rapidly expanding knowledge about neuroanatomical controls of systemic conditions such as hypertension are expanding the possibilities for DBS neuromodulation. Within the central autonomic network (CAN), multiple regions play a role in homeostasis and blood pressure control that could be DBS targets. While the best defined autonomic target is the ventrolateral periaqueductal gray matter, other targets including the subcallosal neocortex, subthalamic nucleus (STN), posterior hypothalamus, rostrocaudal cingulate gyrus, orbitofrontal gyrus, and insular cortex are being further characterized as potential targets. This review aims to summarize the current knowledge regarding neurologic contribution to the pathophysiology of hypertension, delineate the complex interactions between neuroanatomic structures involved in blood pressure homeostasis, and then discuss the potential for using DBS as a treatment for refractory hypertension.
Highlights
Hypertension affects 32.6% of the US adult population and is one of the greatest risk factors for cardiovascular disease (Elijovich et al, 2016)
The 2017 guidelines by the American College of Cardiology define hypertension as systolic blood pressure (SBP) above 120 mm Hg and diastolic blood pressure (DBP) above 80 mm Hg measured on two occasions, with stage 1 hypertension defined as SBP of 130–139 mm Hg or DBP of 80–89 mm Hg, and stage 2 hypertension as SBP greater than 140 mm Hg and DBP greater than 90 mm Hg (Whelton et al, 2017)
Refractory hypertension is defined as uncontrolled blood pressure in patients taking more than five classes of antihypertensive agents including a mineralocorticoid receptor (MR) antagonist as well as a thiazide-like diuretic that has a long duration of action (Dudenbostel et al, 2015, 2017)
Summary
Hypertension affects 32.6% of the US adult population and is one of the greatest risk factors for cardiovascular disease (Elijovich et al, 2016). Refractory hypertension is defined as uncontrolled blood pressure in patients taking more than five classes of antihypertensive agents including a mineralocorticoid receptor (MR) antagonist as well as a thiazide-like diuretic that has a long duration of action (Dudenbostel et al, 2015, 2017). Resistant hypertension is distinct from refractory hypertension and is defined as an elevated blood pressure despite using three or more medications (as opposed to five) (Armario et al, 2017), including a diuretic (Dudenbostel et al, 2017). Other potential mechanisms include an informational lesion, neurochemical effects such as increased extracellular adenosine or dopamine, disruption of pathological oscillations (especially beta at 12–30 Hz in Parkinson’s disease), desynchronization, or shifting of resonant frequency, alterations in synaptic plasticity by long-term potentiation or other mechanisms, large-scale network reorganization, or neuroprotection/neurogenesis. Mechanisms are likely to be different for different effects based on the timing of therapeutic benefit after application of stimulation: tremor responds in seconds, rigidity in minutes, axial Parkinson’s symptoms in hours, and dystonia after several months
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