Resistant hypertension: Why won’t my BP go down?

Clinical pearls for frontline PCPs

The patient is a 48-year-old man who presents to establish care with your practice. He has no specific symptoms to address. He recently moved to the area.

The patient’s medications consist of tizanidine and ibuprofen for back pain and tightness and venlafaxine for depression. His BP is 165 mm Hg/110 mm Hg, his heart rate is 80 and his BMI is 34 kg/m².

Philip A. Bain

The physical exam was unremarkable, and the fundoscopic exam was normal except for a few dot hemorrhages in both fundi. Mild bilateral peripheral edema was noted.

The patient does not use tobacco and drinks four to six beers per day. He takes a multivitamin and St. John’s wort (Hypericum perforatum) to help with depression.

You ask him whether he has been told that his BP has been elevated. He said that he has been told that it has been high at a few doctor appointments in the past 5 years. When asked about what he knows about high BP, he said “that it can kill you.”

The basic metabolic panel, including calcium, thyroid-stimulating hormone and complete blood count, was normal. Plasma renin activity and aldosterone were also normal. He denied headaches, heart racing or sweating. He does not snore loudly and does not note excessive daytime fatigue. His wife has never witnessed any apneic spells.

You explain to him what hypertension (HTN) is and why we check BP and treat it if needed. You give him a general handout on HTN and ask him to purchase a home BP monitor and to bring it in for validation. You start him on lisinopril 20 mg and hydrochlorothiazide 25 mg half-tab daily and have him seen in the nurse-run HTN clinic. You agree on a BP goal of less than 130 mm Hg/80 mm Hg. He was advised that the upper safe limit for alcohol consumption was two drinks per day or less.

The patient is seen in the HTN clinic and demonstrated proper use of the recently purchased upper arm Omron home BP cuff. He is using the appropriately sized cuff for his body habitus. He has stopped using salt at the table and no longer adds salt when cooking. Follow-up BP was 155 mm Hg/105 mm Hg. He was asked to increase his BP medication to one full tab daily.

He returns for follow-up to the HTN clinic. BP was now 150 mm Hg/100 mm Hg. When asked if he has noted any adverse effects with the medication, he said no. He was able to accurately describe how and when he takes his medication.

When asked if he has been taking his venlafaxine and tizanidine every day, he said yes.

Per HTN clinic protocol, amlodipine 5 mg daily was added.

He makes a follow-up, 3-month appointment with you. BP was 145 mm Hg/100 mm Hg. He answers open-ended questions about his medications, and he appears to be taking his BP medications regularly. He was asked to stop his tizanidine as this can cause elevated BP.

The patient continues to follow up with the HTN clinic. The HTN nurse has worked with the patient on increasing his exercise, reducing his alcohol consumption and weight loss. He has been able to lose 4 lbs since he was initially seen. Home BP readings on a validated cuff averaged 140 mm Hg/90 mm Hg. He had low-dose spironolactone added to his regimen.

At his 6-month visit, the patient’s home BP readings were reviewed. The average BP on a validated cuff was 130 mm Hg/80 mm Hg. He is tolerating his medications well and has lost another 2 lbs. With the help of the HTN clinic nurse, he is now exercising 3 to 4 days per week, walking 1 to 2 miles each time.

Lessons learned:

1. Resistant HTN is defined as BP that remains above the goal despite concurrent use of three BP-lowering medications from three different classes (all at maximally recommended doses or maximally tolerated doses) or controlled BP that requires four or more antihypertensive agents.
2. Only about 3% of patients with resistant HTN cannot get their BP controlled. These patients should be referred to an HTN specialist.
3. Pseudoresistant HTN is common and has many causes. See the Cleveland Clinic Journal of Medicine article referenced below.
4. It is important that patients understand what high BP is, why we treat it, how they can measure it at home and what non-drug approaches can help lower BP. You need buy-in from the patient.
5. It is very helpful to use a nurse-driven HTN clinic. They can provide education, monitor adherence, follow up frequently with the patient and make changes per protocol.
6. Most patients with high BP will need two to four medications to reach their BP target. Double and triple medication combinations are now available to improve compliance and reduce “pill burden.” ACD + S (Angiotensin-converting enzyme [ACE] inhibitor/Angiotensin receptor blocker [ARB] plus Calcium channel blocker plus Diuretic plus Spironolactone) should control the vast majority of patients with resistant HTN.
7. Refer to the acronym RECAP ABCDES to consider secondary causes of HTN. Untreated sleep apnea is an often-overlooked cause of difficult-to-control HTN.
8. Review the patient’s medications, alcohol and tobacco use, and supplement use because many of these can cause increased BP.
9. If BP is significantly elevated at the initial visit, consider combination ACE inhibitor/thiazide such as lisinopril 20 mg and hydrochlorothiazide 25 mg half-tab daily. It is easier psychologically to increase to a full tablet if needed vs. adding another pill.
10. Try to sort out if the HTN is renin-angiotensin system-based (volume sensitivity/excess plasma volume) or sympathetically mediated. The former can be treated with ACE inhibitor/ARB, thiazides, calcium channel blockers, beta blockers, alpha blockers and direct vasodilators. The latter can be treated with anxiolytic agents like selective serotonin reuptake inhibitors, beta blockers or clonidine (patch can help with compliance).
11. Remember to monitor for nonadherence. Ask open-ended nonaccusatory questions, like “Tell me how you take your BP medications,” or “Have you noticed any side effects with your BP medications?” Testing for HTN medications in the urine can confirm adherence.
12. Have the patient purchase an upper arm home BP machine from a reputable firm like Omron. Have the patient bring it in for validation.

References:

• Best home blood pressure monitors of 2023. https://www.consumerreports.org/health/blood-pressure-monitors/best-home-blood-pressure-monitors-of-the-year-a2729131535/. Accessed Aug. 25, 2023.
• Hypertensive retinopathy. https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/hypertensive-retinopathy. Accessed Aug. 25, 2023.
• The DASH diet and the Mediterranean diet. https://dashdiet.org/. Accessed Aug. 25, 2023.
• The Curbsiders Podcast: #390 resistant hypertension. https://thecurbsiders.com/curbsiders-podcast/390-resistant-hypertension. Published April 17, 2023. Accessed Aug. 25, 2023.
• Treatment of resistant hypertension. https://www.uptodate.com/contents/treatment-of-resistant-hypertension. Accessed Aug. 25, 2023.
• Whelton PK, et al. Hypertension. 2017;doi:10.1161/HYP.0000000000000065.
• Yahr J, et al. Cleve Clin J Med. 2023;doi:10.3949/ccjm.90a.22046.