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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

Sometimes when I’m desperately trying to fall asleep I instead think of all the things that might kill me. Alligators, drunk drivers, hurricanes, and running out of cookies usually top the list. Do you know what doesn’t top the list? High blood pressure. It really should though. High blood pressure is a leading preventable cause of premature death, affecting well over a billion people worldwide and causing upwards of 9 million deaths a year. Maybe the alligators can chew on those facts for a while. So what is high blood pressure, why is it such a big deal, why do we get it, and what can we do?

High blood pressure is exactly what it sounds like; when the blood in your arteries is being forced through more strongly than normal. The medical name for high blood pressure is hypertension. Hyper– means over or above, and -tension, in this case, indicates the stress of your arteries. Hypertension is excessive stress on your arteries.  Blood pressure can be split into two numbers, systolic and diastolic. These refer to the action of the heart, where systolic is the contracted, pumping blood pressure, and diastolic is the relaxed blood pressure. When you get your blood pressure checked, these are reported as two numbers “over” each other. A reading of 140/90 mmHg or higher is high blood pressure, but there is an increased risk of complications with blood pressure above 120/80 mmHg.

High blood pressure is particularly dangerous. It is easy to see why: the bloodstream is how we deliver oxygen to the cells, and it touches every cell in the entire body. Two of the biggest dangers with elevated blood pressure are ischemic heart disease and stroke, conditions where the blood supply doesn’t reach the heart or brain. High blood pressure can also cause brain bleeds, chronic kidney damage, and other types of heart damage. All of these organs are vital to our survival, so a condition that potentially damages all of them is life-threatening. 

What are the causes of high blood pressure? High blood pressure is calculated the same as in any pipe at its most basic level. The amount of blood coming out of the heart is counteracted by the resistance from the arteries. More output or more resistance makes blood pressure rise. High blood pressure on its own isn’t bad, it’s adaptive for critical situations. When we see a lion and it charges us, we become stressed and initiate the sympathetic nervous system, also known as fight, flight, and freeze. Part of this system’s job is to constrict blood vessels and raise the heart rate to deliver large amounts of oxygen to cells. We see damage when we have high blood pressure for long amounts of time. Some body systems that cause prolonged elevations in blood pressure are:

• Kidneys regulate the volume of blood in veins, using urine to get rid of extra fluid
• Blood vessels can constrict and dilate to regulate resistance. They can also stiffen, lose muscle, and become inflamed or damaged
• The brain activates the kidneys and blood vessels. Constant stress or disorders can keep them active for too long and keep blood pressure high
• Inflammation is caused by inflammatory cells and hormones, including angiotensin, which can accumulate (sometimes due to salt) in blood vessels and the kidney
• Several other systems and mechanisms are at play, including genetics, the microbiome, and reactive oxidative stress

These are the major players in primary or essential hypertension. Secondary hypertension is caused by another identifiable disease, like kidney disease.

So what can we do? Some outcomes depend on things we can’t easily change, like access to quality healthcare and blood pressure medication. Many lifestyle options can be changed to improve our blood pressure:

• Relax! Lowering stress has many positive effects, including lowering blood pressure as well as the feelings of not being stressed (being not stressed is recommended).
• Alcohol has mixed results. Consuming a small amount corresponds to lower blood pressure, but there isn’t great evidence of it causing lower blood pressure. Avoid excessive drinking.
• Physical activity can have big effects. Even a daily light walk can reduce hypertension.
• Obesity has a direct, linear relationship with blood pressure. For each kilogram (~2.2 pounds) you lose, blood pressure decreases by around 1 mmHg.
• Diet can be hard to change, but can also affect blood pressure.
  • Avoid: red and processed meats, sweetened foods, saturated and trans fats
  • Consider eating: fruits and veggies, nuts and seeds, lean dairy, vegetarian and mediterranean diets
• Sodium (salt) intake matters:  salt directly affects how much fluid is in the bloodstream. The average person consumes almost 4000 mg of sodium per day, the recommended amount is under 2300 mg. Though lowering sodium decreases blood pressure, studies are mixed with regard to heart disease outcomes
• Potassium acts in direct opposition to sodium. Increasing the amount of potassium can lower blood pressure – don’t go too crazy, though! Extreme amounts can slow or stop the heart (stopping your heart is not recommended).

Even though we have good evidence for lifestyle changes lowering blood pressure, the biggest difference between countries in terms of controlling blood pressure is access to medicine. Blood pressure medicines have saved countless lives and helped stem the blood tide of hypertension. There are several types of blood pressure medicines on the market. Diuretics get rid of sodium and water in the blood. Angiotensin-converting-enzyme (ACE) inhibitors and Angiotensin-receptor blockers (ARB) help ease inflammation, relax the blood vessels, and keep them from constricting. Calcium channel blockers reduce heart rate. These all have side effects, but the biggest challenge with them is that they are daily oral medications, which can be forgotten, missed, or hard to adhere to. Longer-term solutions are in clinical trials and may be available to you if you qualify. So don’t sleep on your high blood pressure. Check with your local ENCORE Research office to see what studies are enrolling. See ya’ later, alligators!

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

Listen to the article here:

Sources:

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://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.121.318082 

Lifton, R. P., Gharavi, A. G., & Geller, D. S. (2001). Molecular mechanisms of human hypertension. Cell, 104(4), 545-556. https://doi.org/10.1016/S0092-8674(01)00241-0

Mills, K. T., Stefanescu, A., & He, J. (2020). The global epidemiology of hypertension. Nature Reviews Nephrology, 16(4), 223-237. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998524/

Listen to the article here:

Hypertension is one of the most prevalent conditions on the planet. Scientists estimate that it affects 30-45% of adults, somewhere over a billion people! Hypertension is the chronic elevation of blood pressure. The CDC defines it as above 130 mmHg systolic or above 80 mmHg diastolic. For short periods of time, elevated blood pressure can be useful – for exercise, say. People can have high blood pressure for years without symptoms. For long periods of time, however, hypertension is deadly serious. Unfortunately, living with high blood pressure can lead to a host of problems. Hypertension can lead to heart attack and stroke, and damage to the heart, brain, kidneys, and even eyes!       

Everyone is at risk of high blood pressure. In America, men have a higher likelihood of hypertension. There are also differences in ethnicity and race, non-Hispanic Black or African American adults are at the highest risk. Unfortunately, even the lowest risk categories still have around a 40% prevalence of high blood pressure. Clearly this is a large issue in America and around the world.           

The big culprit behind hypertension is the Renin–angiotensin–aldosterone system (RAAS). RAAS is a critical system for maintaining blood pressure. It regulates two primary factors: the amount of blood and how constricted blood vessels are. It does this through the kidney, liver, and adrenal gland (just above the kidneys). In response to body signals, the kidneys release an enzyme to the liver. In response, the liver produces the hormone angiotensin I. Another enzyme, angiotensin-converting enzyme (ACE) converts this to angiotensin II, which goes to work.  

Angiotensin II has wide-ranging effects to increase sodium and water retention. It also causes blood vessels to constrict. Angiotensin II is very short-lived, only lasting 1-2 minutes. One of its many effects is to get the adrenal gland to produce aldosterone. Aldosterone has similar effects as angiotensin II, but instead of a few minutes, it takes hours or days to take effect. The end result is that two major hormones – one fast-acting and one slow-acting – cause high blood pressure.          

There are many medications available to fight hypertension. Most of these, such as diuretics or beta-blockers, have wide-ranging side effects. This is because they are system-wide, indiscriminate actors on the body. Beta-blockers, for instance, slow the heart. This is helpful in lowering blood pressure but obviously leads to other effects on the body. RAAS-acting specific medications may be more helpful in combating hypertension with minimal side effects. ACE inhibitors, for instance, stop the fast-acting angiotensin II from having its effect on the body. This targeted approach to hypertension can lead to fewer side effects in some patients. Unfortunately, by acting on only the fast-acting portion of RAAS, they must be taken daily. Even worse, a few missed doses can have longer-term effects on blood pressure. Luckily, researchers are investigating other targeted methods of reducing the effect of RAAS, and blood pressure! Keep an eye out for a clinical research study to help investigate this exciting part of the fight against hypertension.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience

Sources

Fountain, J. H., & Lappin, S. L. (2017). Physiology, renin angiotensin system.

National Center for Chronic Disease Prevention and Health Promotion, Division for Heart Disease and Stroke Prevention. (September 27, 2027). Facts about hypertension. U.S. Department of Health and Human Services. https://www.cdc.gov/bloodpressure/facts.htm