Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis

Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis: Analysis of Noninvasive Coronary Angiography Using Multidetector Computerized Tomography

Journal of Clinical Endocrinology and Metabolism, 05/21/2013  Clinical Article

  1. Nicola M. Neary*,
  2. O. Julian Booker*,
  3. Brent S. Abel,
  4. Jatin R. Matta,
  5. Nancy Muldoon,
  6. Ninet Sinaii,
  7. Roderic I. Pettigrew,
  8. Lynnette K. Nieman and
  9. Ahmed M. Gharib

Author Affiliations


  1. Program in Reproductive and Adult Endocrinology (N.M.N., L.K.N., B.S.A.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Laboratory of Cardiac Energetics (O.J.B.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; Integrative Cardiovascular Imaging Laboratory (J.R.M., R.I.P., A.M.G.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Critical Care Medicine (N.M.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; and Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
  1. Address all correspondence and requests for reprints to: Ahmed M. Gharib, MB, ChB, National Institutes of Health, Building 10, Room 3-5340, Mail Stop Code 1263, 10 Center Drive, Bethesda, MD 20892. E-mail: agharib@mail.nih.gov.
  1. * N.M.N. and O.J.B. contributed equally to this work.

Abstract

Background: Observational studies show that glucocorticoid therapy and the endogenous hypercortisolism of Cushing’s syndrome (CS) are associated with increased rates of cardiovascular morbidity and mortality. However, the causes of these findings remain largely unknown.

Objective: To determine whether CS patients have increased coronary atherosclerosis.

Design: A prospective case-control study was performed.

Setting: Subjects were evaulated in a clinical research center.

Subjects: Fifteen consecutive patients with ACTH-dependent CS, 14 due to an ectopic source and 1 due to pituitary Cushing’s disease were recruited. Eleven patients were studied when hypercortisolemic; 4 patients were eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen control subjects with at least one risk factor for cardiac disease were matched 1:1 for age, sex, and body mass index.

Primary outcome variables: Agatston score a measure of calcified plaque and non-calcified coronary plaque volume were quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional variables included fasting lipids, blood pressure, history of hypertension or diabetes, and 24-hour urine free cortisol excretion.

Results: CS patients had significantly greater noncalcified plaque volume and Agatston score (noncalcified plaque volume [mm3] median [interquartile ranges]: CS 49.5 [31.4, 102.5], controls 17.9 [2.6, 25.3], P < .001; Agatston score: CS 70.6 [0, 253.1], controls 0 [0, 7.6]; P < .05). CS patients had higher systolic and diastolic blood pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123, 136], P < .02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P < .05).

Conclusions: Increased coronary calcifications and noncalcified coronary plaque volumes are present in patients with active or previous hypercortisolism. Increased atherosclerosis may contribute to the increased rates of cardiovascular morbidity and mortality in patients with glucocorticoid excess.

  • Received October 29, 2012.
  • Accepted March 7, 2013.

From JCEM

Monday, 12 Weeks Post-Op

falling-behind

Looks like I’m falling w-a-y behind again.  That’s a pretty good thing since that means normal life is resuming.

When we started rehab, DH was the only student – now there are 5 and they seem to get along pretty well.  Slowly but surely, the challenges are getting greater.  Today (or soon) he will start using weights.

Today’s hav is 14 of 36, just over 1/3 of the way through.

He’s been driving pretty normally for a few weeks but still can’t walk the dog.  Maybe that will come after the weights get started.

We had our class with the dietician and there was only one other woman in the class so it was more of a private session.  At the end, 3 of the guys from Mended Hearts came in to see if we had questions.  One said that he liked having me in the meetings and talking about the role of the caregiver!  This is just not me, talking in any group!

Last week, we had out one-on-one with the dietician.  I’d pretty much already learned most of it from online and books but it was good to check.

This week, on Tuesday, we have a class on how the surgery is performed.  I’ve seen videos but it will be nice to see what they have to offer.  We can also observe a live surgery.  We’ll see!

Last week, on Tuesday, we had the privilege of attending a Congressional Caucus on Rare Diseases.  I took the opportunity (of course!) to say a few words about Cushing’s.  If you’re interested, my write-up is here:  Cushing’s on Capitol Hill.

I have an opportunity for a conference in San Francisco in June.  I happened to have airplane credits so I, without thinking, I got 2 tickets.  Hopefully, DH has the go-ahead to fly by then!

I’m amazed at how well things are going at the 3 month mark.  Hopefully, it’s smooth sailing from here on out!

Cushing’s syndrome increased risk for coronary arterial atherosclerosis

cushings-ladyNeary NM. Clin Endocrinol Metab. 2013;doi:10.1210/jc.2012-3754.

In a recent study supported by the NIH, researchers determined that patients with Cushing’s syndrome have a greater risk for developing coronary arterial atherosclerosis, increasing their rate of cardiovascular morbidity. These findings were published in the Journal of Clinical Endocrinology & Metabolism.

The researchers conducted a prospective case-control study of 15 consecutive patients with adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome who were matched with 15 controls (aged 32 to 66 years) with at least one risk factor for cardiac disease (ie, diabetes, hypertension, hyperlipidemia, family history of early-onset coronary artery disease and previous or current smoking).

Researchers used a multidetector CT (MDCT) coronary angiogram scan to measure calcified and noncalcified coronary plaque volume and Agatston scores. Additional variables included fasting lipids, BP, history of hypertension or diabetes and 24-hour urine free cortisol excretion.

According to data, patients with Cushing’s syndrome had significantly greater noncalcified plaque volume and Agatston scores compared with controls (noncalcified plaque volume median [interquartile ranges]: 49.5 vs. 17.9,P<.001; Agatston score: 70.6 vs. 0, P<.05).

Patients with Cushing’s syndrome also demonstrated higher systolic (143 mm Hg) and diastolic (86 mm Hg) BP compared with controls (systolic: 134 mm Hg, diastolic: 76 mm Hg).

The limitations of the study include the small cohort of patients and potential selection bias due to ectopic ACTH secretion. However, the researchers wrote that these findings demonstrate a significant difference between the two groups included in the study.

“Overall, the findings point to the possible causes of cardiovascular morbidity in patients treated with exogenous steroids and indicate the need for further studies of that population,” they wrote.

Disclosure: The researchers report no relevant financial disclosures.

~~~~~~~~~~~~~~

PERSPECTIVE

Alice C. Levine, MD Alice C. Levine

  • It has long been recognized that endogenous hypercortisolism (Cushing’s syndrome) and administration of supraphysiologic doses of glucocorticoids are associated with increased mortality, primarily due to cardiovascular disease. Excess glucocorticoids induce all of the features of the metabolic syndrome including obesity with central weight gain, hypertension, impaired glucose tolerance/diabetes mellitus and dyslipidemia, all of which increase cardiovascular risk. In this small but well-designed study, the authors attempt to determine whether excess glucocorticoids have a direct adverse effect on the coronary vasculature. Utilizing multidetector computerized tomographic (MDCT) coronary angiography, a validated noninvasive method of assessing calcified and noncalcified coronary plaques, they compared measurements of coronary plaques (Agatston score) in 15 patients with ACTH-dependent Cushing’s syndrome (CS) vs. 15 age-, sex- and body weight-matched controls with at least one risk factor for cardiac disease. They found significantly greater coronary calcifications and noncalcified coronary plaque volumes in patients with active or previous hypercortisolism.There are obvious limitations to the study; most notably the small sample size, the predominance of patients with CS due to ectopic ACTH (14/15) and significantly more hypertension in the CS vs. the control group. However, other than the HTN, the groups were well-matched and there was no statistical difference in the Framingham risk scores between groups. This is the first study to demonstrate direct effects of CS on coronary plaque burden.The findings, while unsurprising, underscore several important features of CS which endocrinologists need to consider. Firstly, as there were no statistical differences in plaque burden in patients with CS who were eucortisolemic (4/15) vs. those who were hypercortisolemic (11/15) at the time of study, the effects of CS on the coronary vasculature may persist even after biochemical cure. Many previous studies in larger cohorts have similarly demonstrated that the adverse effects of high glucocorticoids on cardiovascular, metabolic, psychiatric and neurocognitive function may be only partially reversible with disease remission. Secondly, even adjusting for all the confounding variables, hypercortisolism seems to be an independent risk factor for the development of coronary artery disease. The possible mechanisms underlying this observation are discussed and include increases in prothrombotic factors, circulating levels of vascular endothelial growth factor (VEGF) and angiogenesis. It is also plausible that cortisol increases atherosclerosis through the mineralocorticoid rather than the glucocorticoid receptor, suggesting the possibility of treating this particular deleterious effect of hypercortisolism with a mineralocorticoid-receptor blocker such as spironolactone.

    Within the CS group, no significant correlations were observed between the coronary plaque volumes and the duration of CS or urinary free cortisol (UFC) either at presentation or at the time of MDCT. Although this lack of correlation may also be attributable to the small sample size, it is well known that the onset of Cushing’s syndrome is often insidious and it is impossible to pinpoint the exact duration of the abnormality in most patients. This study’s finding of direct, adverse and possibly irreversible effects of hypercortisolism on the coronary vasculature should make endocrinologists even more vigilant in diagnosing and treating the disease as early as possible in its course.

    • Alice C. Levine, MD
    • Professor of medicine, division of endocrinology, diabetes and bone diseases
      Co-Director of The Adrenal Center
      Icahn School of Medicine
      Mount Sinai, New York, NY
  • Disclosures: Levine reports no relevant financial disclosures.

From Healio.com

I know that this is currently a “heart blog” but I’ve mentioned Cushing’s a few times, and Cushing’s is my life so I’m reblogging this older post…

Laika's MedLibLog

ResearchBlogging.orgApril 8th is Cushing’s Awareness Day. This day has been chosen as a day of awareness as it is the birthday of Dr. Harvey Cushing, a neurosurgeon, who discovered this illness.

Cushing’s disease is a rare hormone disease caused by prolonged exposure to high levels of the stress hormonecortisol in the blood, whereas Addison’s disease is caused by the opposite: the lack of cortisol. For more background information on both see this previous post. Ramona Bates MD, of Suture for a Living, has written an excellent review (in plain language) about Cushing’s Disease on occasion of Cushing Awareness Day at EmaxHealth.

From this you can learn that Cushing’s disease can be due to the patient taking cortisol-like glucocorticoids, such as prednisone for asthma (exogenous cause), but can also arise because people’s bodies make too much of cortisol itself.  This may be due to a…

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