Many patients are asking if they have a higher cardiovascular risk as a result of Cushing’s. This article will focus on this question in a group of patients in long-term remission of Cushing’s syndrome.

Cardiovascular risk in active Cushing’s Syndrome

 Cardiovascular disease, for example, myocardial infarction or cerebral infarction, is the main cause of death during active Cushing’s. Furthermore, many scientific studies in the past have shown that blood vessels are being damaged due to Cushing’s and that patients have more atherosclerosis. It has been suggested that this is caused by the increase in abdominal fat, diabetes, increased blood pressure and increased lipid levels that are caused by Cushing’s.

Cardiovascular risk after successful treatment

Previous research has suggested a significant decrease in cardiovascular risk and mortality after successful surgery for Cushing’s. Until recently, it was unknown whether cardiovascular health fully restored to normal in the long term after cure of Cushing’s. Full recovery is not self-evident, as the increase in abdominal fat persists even after long-term remission of Cushing’s, as was discussed in the Winter, 2015 newsletter by my colleague Dr. Margreet Wagenmakers.

Does cardiovascular health fully restore after Cushing’s?

To answer this question we investigated all adult patients who were treated in the Radboud University Medical Center Nijmegen and the Leiden University Medical Center in the Netherlands who had been successfully treated for Cushing’s and were cured for more than 4 years. The medical records of all patients were reviewed to evaluate the type of Cushing’s, the type of treatment received, the duration of cure, and presence of hormonal deficiencies and comorbidities such as high blood pressure, diabetes and increased lipid levels. In total we investigated 63 patients. For each patient, a healthy control subject was recruited of similar gender, age and body mass index (BMI).

In 58 of these patients we assessed a number of blood values that are markers for vascular health, especially the health of the inside lining of the blood vessels, called the “endothelium”. These markers; plasminogen activator inhibitor-1 (PAI-1), intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and soluble E-selectin, are only used for scientific research. They are not available for regular endocrinologists and general practitioners. Furthermore, we performed a number of ultrasound measurements of arteries in the neck which provide information about vascular health and the amount of atherosclerosis in the body.

In a smaller group of 14 patients we performed direct measurements of the health of the “endothelium” by means of ultrasound measurements on the blood vessels in the arms and by means of direct stimulation of the endothelium with chemical substances that were infused in the arm. Again these measurements are not routinely used in clinical practice and are purely used for scientific research purposes.

Altogether, these measurements provide a complete overview of the health of the large- (macro-) and small blood vessels (microvascular health). We compared the findings in our patients to the findings in the matched group of healthy control subjects.

Vascular health of patients in remission of Cushing’s is not different from that seen in healthy people!

The main finding of our study was that vascular health of patients in remission of Cushing’s is not any different from the healthy control subjects in our study. This finding suggests that cardiovascular health fully restores after Cushing’s. Some previous studies found in the literature have claimed the opposite. They did not find any improvement of vascular health after cure of Cushing’s. However these studies included patients who were only cured for a short period of time compared to the 4 plus years in our study. Other studies that also claimed a persistence of decreased vascular health included patients that had significantly more uncontrolled co-morbidities such as high blood pressure, increased lipid levels and diabetes. The patients in our study were very well treated for these comorbidities with medication.

The mean age of the patients in our study was approximately 50 years, so this study is not able to fully exclude increased vascular risk later in life.

What should I ask my doctor when I am concerned about my vascular health?

The results of our study emphasize that your doctor should be especially worried about treating your comorbidities adequately. You should ask your doctor to keep your blood pressure, blood sugars and blood lipids within the normal range. When these parameters are kept within the normal range it is likely that your vascular health and cardiovascular risk fully restores to that of healthy people and remains normal even later in life. Furthermore, our study showed that patients who were smoking were at increased risk of poor vascular health. When you have Cushing’s it is wise to stop smoking (which also applies to healthy people!). Because our study included BMI matched controls, we did not study the impact of weight on cardiovascular health. However, it has been well reported in the medical literature that weight does impact cardiovascular health.

Conclusion

In conclusion, the vascular health of patients in long-term remission of Cushing’s seems to be comparable with that of healthy gender-, age-, and BMI-matched people, provided the patients have no, or adequately controlled, comorbidities. Therefore, the effects of the previous Cushing’s per se on the vasculature may be reversible. This accentuates the need for stringent individualized treatment of comorbidities in these patients.

Full text article: Vascular Health in Patients in Remission of Cushing’s Syndrome is Comparable with that in BMI-Matched Controls. J Clin Endocrinol Metab. 2016 Nov;101(11):4142-4150. Epub 2016 Aug 23.

By Dr. Sean Roerink, Spring, 2017

Editor’s Note: Dr. Sean Roerink is a resident in Internal Medicine at the Rijnstate hospital Arnhem, The Netherlands. Under the supervision of Prof. Ad Hermus, Prof. Jan Smit and Dr. Netea Maier at the Radboud University Medical Center Nijmegen, the Netherlands, he is completing his PhD on the long-term effects of endocrinological tumours. In the future Dr. Roerink hopes be a practicing clinical endocrinologist and to continue research in the long-term effects of endocrinological diseases.