The letter omega (Ω) is the last letter in the Greek alphabet. As such, omega is often used to denote the last, or the ultimate end, of a list. Therefore, it is a fitting topic for December, the final month of the year. In addition, omega symbolizes the ohm, the unit of electrical resistance. The ohm is named after the German scientist George Ohm who described the mathematical formula of electrical resistance. There is a further connection between electrical resistance and resistant hypertension, since external energy can potentially be used to bring down the blood pressure. What is resistant hypertension and how is it treated? Can new treatments be the omega of high blood pressure?
Elevated blood pressure (hypertension) is the leading risk factor for cardiovascular disease, stroke and death. It affects about 1.4 billion people worldwide. In the US, approximately 10 to 30% of patients with high blood pressure have treatment resistant hypertension (10-12 million people). Resistant hypertension is defined as blood pressure above goal despite taking the maximally tolerated doses of three different classes of blood pressure medications. In the past, the goal was a blood pressure under 140/90, but a new definition now moves the goal to under 130/80. The three medications should include a diuretic (a “water pill”), an ACE or ARB (for example, lisinopril, ramipril, losartan or olmesartan) and a calcium channel blocker (usually amlodipine). A structured approach to resistant hypertension has been developed by the American Heart Association. The first step is to make sure the blood pressure is truly high (not white coat hypertension; high blood pressure in office, but normal at home). The next step is to ensure the patient is taking his or her medications (and correctly). After that, lifestyle modifications may be necessary if the patient is not following a low sodium diet, not exercising, or drinking excess alcohol. In addition, many medications can raise blood pressure. These should be eliminated or reduced. Medications that can raise blood pressure include non-steroidal anti-inflammatory agents (such as ibuprofen or naproxen), over the counter cold medications, oral contraceptives, corticosteroids (for example prednisone), some cancer chemotherapy agents and many supplements (ephedra, ginseng, saw palmetto). Lastly in the lifestyle category is obstructive sleep apnea. Obstructive sleep apnea occurs when the upper airway collapses, air movement into the lungs ceases causing the oxygen level in the body to fall. This prompts the person to wake up and take deep breaths. These periods of low oxygen disrupt the sleep cycle and prevent the person from getting enough time in the deep sleep, restorative stages of sleep. Because the body does not get enough rest, the person feels “revved up” all the time. Over time, this causes hypertension. Treating sleep apnea can reduce blood pressure.
The next step in managing resistant hypertension is to evaluate for secondary causes of high blood pressure. A variety of disease processes can raise blood pressure (including kidney, adrenal, and aortic diseases). Identifying such a process and treating it will bring down the blood pressure. One such entity is renal artery stenosis (a severe blockage in the artery supplying blood to a kidney). The most common cause of renal artery stenosis is atherosclerosis of the kidney artery (the same process that causes blockage in a heart artery). It is characterized by a sudden increase in blood pressure, low potassium levels in the blood and an extra “whooshing” sound (bruit) heard over the abdomen. The diagnosis is made by ultrasound, CT scan or angiogram of the blood flow to the kidneys. In the appropriate patient, opening up the blockage, placing a stent and restoring blood flow to the kidney can reduce blood pressure.
If the blood pressure is still elevated after all of these evaluations, the next step is to add further medications. The next medication that is recommended is spironolactone, which blocks the synthesis of aldosterone, a hormone that promotes salt retention and increases blood pressure. Spironolactone has been used for many, many years and is quite effective at lowering blood pressure. However it does have side effects including raising the potassium level in the blood (a potentially dangerous situation). If the potassium goes above a certain level, the medication has to be discontinued.
Even though resistant hypertension affects millions of people, no new blood pressure lowering agent has been approved since 2007. A couple of new strategies for lowering blood pressure are on the horizon and look promising. The data for a new medication, baxdrostat, was just published this past month. Baxdrostat lowers aldosterone levels by a different mechanism from spironolactone. In the trial just reported, baxdrostat lowered blood pressure in resistant hypertensive patients 11 mmHg more than placebo, a statistically significant amount. There was no significant increase in potassium.
Are there any other therapies besides medication to treat resistant hypertension? A new procedure called renal denervation has been extensively studied recently. Renal relates to the kidneys and denervation means to deaden the signal the nerves give off. One of the ways in which blood pressure is controlled is via the nerves to the kidney arteries. The nerves send a signal to the kidneys, prompting the kidney to start retaining more salt (sodium) and increase blood pressure. In addition the nerves from the kidneys send signals back to the brain. This causes the brain to send signals to the arteries throughout the body, making them contract and stiffen, also raising blood pressure. These are normal mechanisms the body uses to regulate blood pressure, but in some people the nerves are overactive resulting in continuously high blood pressure and resistant hypertension. Renal denervation is a procedure where a catheter is placed in the kidney arteries. The nerves are then deadened using radiofrequency or ultrasound. Many trials have been conducted comparing renal denervation with a sham procedure (the catheter is placed but no energy is given). In patients with resistant hypertension, renal denervation lowered blood pressure by 7 to 11 mmHg. These reductions were sustained at 6 months and 3 years. In addition, renal denervation increased the time in therapeutic range (< 140 in office blood pressure, < 130 in home readings) as well as decreased major cardiac events. One of the advantages to renal denervation is that it is always “on”; the blood pressure effect is there, night or day and is not dependent on whether medication is taken or whether medication has worn off during the course of the day. Taking multiple medications every day, often with several doses spaced across the day, 365 days of the year is a difficult task. If approved, renal denervation may be a reasonable option for people with resistant hypertension.
