Cardiovascular manifestations of mast cell disease: Part 3 of 5

Recurrent or perpetual elevation in blood pressure has been observed in multiple studies and may affect up to 31% of patients with mast cell activation disease (systemic mastocytosis, mast cell activation syndrome/disorder, monoclonal mast cell activation syndrome). Despite this high prevalence, many providers continue to believe that this symptom cannot be inherently from mast cell activation.

A number of mast cell mediators are vasoconstrictors, narrowing the blood vessels and elevating blood pressure. Histamine can both increase and lower blood pressure depending on which receptor it acts upon (H1: hypotension; H2: hypertension).

Several mediators participate in the angiotensin-renin pathway. Angiotensin II, the level of which is largely determined by mast cell mediators like renin, strongly elevates blood pressure. Chymase, involved in the angiotensin-renin pathway, can also either increase or lower blood pressure depending on concentration relative to other mediators present. Carboxypeptidase A can also affect angiotensin II level as well. Renin regulates the level of a molecule that becomes angiotensin II and can increase blood pressure this way.

Phospholipases, which help produce the molecule needed to make prostaglandins, leukotrienes and thromboxanes can contribute to either high or low blood pressure depending upon which molecule is made. Prostaglandin D2 (PGD2) is a vasodilator, lowering blood pressure; but its metabolite, 9a,11b-PGF2, increases blood pressure. (Author’s note: I personally believe this to be the reason for the rapid blood pressure fluctuations in mast cell patients, but do not have evidence to directly support this.) Thromboxane A2, a molecule related to prostaglandins and leukotrienes, increases blood pressure, as do leukotrienes.

Management of high blood pressure is complicated in mast cell patients by the interaction of common antihypertensives with mast cell activation. Beta blockers are contraindicated in mast cell patients because they interfere with epinephrine, both naturally produced and medicinally.  Use of beta blockers is a risk factor for fatal anaphylaxis.  Any patient on beta blockers that carries an epipen should also carry a glucagon pen, which can be administered prior to the epipen to increase efficacy.

ACE inhibitors interfere with angiotensin converting enzyme, which increases blood pressure through the angiotensin II pathway.  ACE inhibitors affect bradykinin levels, a mast cell mediator that is also mast cell activating.  For this reason, ACE inhibitors can increase mast cell reactivity and symptoms like angioedema.

Author’s note:  I extended this series to four posts to discuss heart failure in mast cell patients.  Following this series, I will be posting a series dedicated exclusively to Kounis Syndrome, including diagnosis and treatment.  Sit tight!

References:

Kolck UW, et al. Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research 2016; x:1-10.

Gonzalez-de-Olano D, et al. Mast cell-related disorders presenting with Kounis Syndrome. International Journal of Cardiology 2012: 161(1): 56-58.

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013; 138: 53-65.

 

3 Responses

  1. Colleen Pisaneschi April 28, 2016 / 10:16 am

    Thanks so much for this series! I’ve just been diagnosed with POTS and MCAD.
    Last year an SIADH diagnosis had led to restricted liquids (1200 cc x day) so in hot weather I was carted off by ambulance for intense chest pain. I’d been passing out several times daily, sometimes still do.
    Increased liquids (difficult to keep sodium levels within the norm) have helped, but the propranolol beta blocker made my legs and feet swell to over twice normal size, even with compression clothing.
    I’ll take this info to my cardiologist and see what we can put together. Hoping to stay off the beta blockers for good!
    Thanks again for all you do,
    CP

  2. Lisa VanWinkle April 28, 2016 / 11:39 am

    I am on benicar and being investigated for mcas. I know Benicar is an angiotension II receptor blocker, but do not know if this would interfer with mast cells like the ACE inhibitors. I was tried before this on beta blockers and ACE inhibitors (was on 3 meds at one time withe one being HCT that made my electrolytes nuts), both not helping blood pressure and causing side effects like itching, dizziness, and and occasional passing out spell which I now think was blood pressure dropping from a reaction from the medicine. The Benicar works most of the time when I get the 150/100 (sometimes the bottom is 110) blood pressure, but sometimes it takes two pills and other times my blood pressure is 130/75 and I have to watch if I take a pill then it will bottom out. Is there any medicine that is shown to act better than others to help the blood pressure spikes?

    • Lisa Klimas April 29, 2016 / 11:21 am

      ARBs do not interact with the biology of mast cell disease like beta blockers or ACE inhibitors. Calcium channel blockers like verapamil are pretty well tolerated by mast cell patients. Benzodiazepines are actually sometimes used to lower blood pressure and some mast cell patients use them for this. They have the benefit of acting pretty quickly. Benzos also seen to “quiet” mast cells, for lack of better word. We don’t know why, but binding to the benzo receptors on mast cells seems to decrease reactivity. So that could be a good option too.

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