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What do Star Wars, Nazi-occupied France, and surge protectors have in common? We root for the resistance to win! But what if the resistance is evil and bad? Meet resistant hypertension. This little devil is a special, particularly damning form of hypertension that resists medications. Not just one or two medications, either! Resistant hypertension avoids at least three separate medications of three separate types (called classes)! 

Resistant hypertension is when blood pressure remains over 140/90 mmHg while seated, even when the patient is taking the maximum tolerated dose of three or more different classes of hypertension medications. It can damage the heart, eyes, and kidneys and lead to heart attack, stroke, end-stage renal disease, and death. It can be caused by a narrowing of the veins, but the prevalence isn’t narrow at all. It affects 6-9 million Americans, with the highest incidence in Black males. A few conditions are associated with resistant hypertension, including diabetes, obesity, and chronic kidney disease.

To understand how this disease works, we must first understand how blood pressure works. Blood pressure is controlled by three main components: heart rate, volume pumped, and blood vessel size. This may seem like a simple system, but each of these three components are affected by a myriad of body systems. Think of it like trying to maintain peace in the middle east. It might seem like you could balance the needs of religion, economics, tradition, and foreign influence, but it turns out: no. Other big actors in the blood pressure realm include the brain and kidneys. The brain directs other organs how to act and the kidneys regulate the fluid in the bloodstream (which we call blood). On top of these big organs, blood pressure is affected by interconnected systems, genes, inflammation, salt, even the bacteria in our gut! One of the biggest systems involved with blood pressure is the Renin-Angiotensin-Aldosterone System, or RAAS (or RAS). This system involves the kidneys and uses hormones to regulate blood pressure. It relies on a few key hormones and enzymes, and is also affected by other systems like the natriuretic peptide system and the brain.

In hypertension, one or more of these systems no longer functions properly. We have four major classes of medication to help get the body back on track. Long-acting calcium channel blockers (CCB) reduce the amount that the heart and arteries can contract, relaxing the system. Angiotensin is a hormone that causes blood vessels to narrow. Angiotensin-converting enzyme inhibitors (ACEI) block angiotensin from being made and angiotensin receptor blockers (ARB) block it from acting on blood vessels. Finally, diuretic medications remove water and salt from the blood, lowering the volume of fluid that the heart pumps. Each of these medications targets the body in slightly different ways. Different medications work better for some people, and side effects may present differently. A good doctor will look for a blood pressure medication (or two (or three (or more))) that brings blood pressure to healthy levels without too many side effects.

When we do not achieve healthy blood pressure levels even at the maximum tolerated dose of three or more medications we have resistant hypertension. Patients with resistant hypertension are at a higher risk of major cardiac events because they can’t get blood pressure under control with available medications. Prolonged high blood pressure leads to damage throughout the cardiovascular system.

So what can be done? The best first step is to lower modifiable risks. This is actually a good first step for literally anything that is dangerous. Weight loss is a good opening move if you are obese. Lowering alcohol and salt intake may help. Talking to a doctor about any medications or conditions that may be raising blood pressure is important. Finally, clinical trials may be underway to look for specialty medications that target those with resistant hypertension. Hopefully we can find a way to crush resistance without succumbing to the dark side of the force (or becoming nazis).

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

References:

Harrison, D. G., Coffman, T. M., & Wilcox, C. S. (2021). Pathophysiology of hypertension: the mosaic theory and beyond. Circulation research, 128(7), 847-863. https://doi.org/10.1161/CIRCRESAHA.121.318082 

Myat, A., Redwood, S. R., Qureshi, A. C., Spertus, J. A., & Williams, B. (2012). Resistant hypertension. Bmj, 345. https://doi.org/10.1136/bmj.e7473

Sarafidis, P. A., Georgianos, P., & Bakris, G. L. (2013). Resistant hypertension—its identification and epidemiology. Nature Reviews Nephrology, 9(1), 51-58. https://www.nature.com/articles/nrneph.2012.260