Cardiovascular health and mortality in Cushing’s disease

Coulden, Amy; Hamblin, Ross; Wass, John; Karavitaki, Niki

doi:10.1007/s11102-022-01258-4

Cited by 22 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The use of novel diagnostic modalities demonstrated that excessive fat accumulation in young and middle-aged patients with CD, already at the early stages of the disease, is associated with some hemodynamic changes in the cardiovascular system, which—at that stage—may still be undetectable in routine assessments. These findings support the need for the early detection of subclinical heart dysfunction in patients with CD to enable early treatment and help prevent cardiovascular complications [ 1 , 34 , 35 , 36 ].…”

Section: Discussionsupporting

confidence: 70%

Obesity-Related Hemodynamic Alterations in Patients with Cushing’s Disease

Jurek,

Krzesiński,

Uziębło-Życzkowska

et al. 2024

JCM

View full text Add to dashboard Cite

Background: Cushing’s disease (CD) is associated with a specific form of metabolic syndrome that includes visceral obesity, which may affect cardiovascular hemodynamics by stimulating hypercortisolism-related metabolic activity. The purpose of this study was to evaluate the relationship between obesity and the hemodynamic profile of patients with CD. Methods: This prospective clinical study involved a hemodynamic status assessment of 54 patients newly diagnosed with CD with no significant comorbidities (mean age of 41 years). The assessments included impedance cardiography (ICG) to assess such parameters as stroke index (SI), cardiac index (CI), velocity index (VI), acceleration index (ACI), Heather index (HI), systemic vascular resistance index (SVRI), and total arterial compliance index (TACI) as well as applanation tonometry to assess such parameters as central pulse pressure (CPP) and augmentation index (AI). These assessments were complemented by echocardiography to assess cardiac structure and function. Results: Compared with CD patients without obesity, individuals with CD and obesity (defined as a body mass index ≥ 30 kg/m2) exhibited significantly lower values of ICG parameters characterizing the pumping function of the heart (VI: 37.0 ± 9.5 vs. 47.2 ± 14.3 × 1*1000−1*s−1, p = 0.006; ACI: 58.7 ± 23.5 vs. 76.0 ± 23.5 × 1/100/s2, p = 0.005; HI: 11.1 ± 3.5 vs. 14.6 ± 5.5 × Ohm/s2, p = 0.01), whereas echocardiography in obese patients showed larger heart chamber sizes and a higher left ventricular mass index. No significant intergroup differences in blood pressure, heart rate, LVEF, GLS, TACI, CPP, or AI were noted. Conclusions: Hemodynamic changes associated with obesity already occur at an early stage of CD and manifest via significantly lower values of the ICG parameters illustrating the heart’s function as a pump, despite the normal function of the left ventricle in echocardiography.

show abstract

Section: Discussionsupporting

confidence: 70%

Obesity-Related Hemodynamic Alterations in Patients with Cushing’s Disease

Jurek,

Krzesiński,

Uziębło-Życzkowska

et al. 2024

JCM

View full text Add to dashboard Cite

show abstract

“…A major challenge in patients with CS is the management of blood pressure [5, 53]. More so it was intriguing that we saw strong effects on endothelia cells and smooth muscle cell abundance, as well as important genes for the vascular system like Vegfa (VEGFA) and VWF (VWF).…”

Section: Discussionmentioning

confidence: 99%

A unique gene expression signature in visceral adipose tissue identifies a high blood pressure group in patients with Cushing’s syndrome

Stifel

Vogel

Caratti

et al. 2023

Preprint

View full text Add to dashboard Cite

Cushing’s syndrome (CS) is a rare disease caused by excess cortisol levels with high cardiovascular morbidity and mortality. Hypertension is a frequent feature of Cushing’s syndrome, promoting hypercortisolism-associated cardiovascular events. Adipose tissue is a highly plastic tissue with most of the major cell types strongly affected in their function by the excess cortisol exposure. We hypothesized that the molecular and cellular changes of visceral adipose tissue (VAT) in response to cortisol excess can impact on systemic blood pressure levels in patients with CS. We, therefore, investigated gene expression signatures in VAT from patients with CS collected during curative adrenal surgery identifying significant alterations. During active CS we observed a strong downregulation of gene programs associated with immunity and inflammation in the VAT. In addition, we observed an clustering of the patients based on VAT gene expression profiles into two groups (CSLowand CSHigh) according to blood pressure levels. The two clusters showed significant differences in gene expression pattens of the renin-angiotensin-aldosterone-system (RAAS). Renin (REN) was the strongest regulated gene compared to control patients and its expression correlated with increased blood pressure observed in our patients while systemic renin plasma levels were suppressed indicative of an abnormal blood pressure and volume status in response to VAT RAAS activation. Here we show for the first time a relevant contribution of the local RAAS system on systemic blood pressure levels in patients with CS. Patients from the CSHighgroup had still a significant increased blood pressure levels 6 months into remission, highlighting the importance of local tissue effects on long-term systemic effects observed in CS.

show abstract

“…A major challenge in patients with CS is the management of blood pressure. 12 , 62 More so it was intriguing that we saw strong effects on endothelia cells and smooth muscle cell abundance, as well as on important genes for the vascular system like VEGFA and VWF . It has already been shown that cortisol excess can lead to an increase of thickness in arteries and, therefore, modulate systemic blood pressure and persistent modulation of the vascular system, even after achieving remission of endogenous cortisol excess.…”

Section: Discussionmentioning

confidence: 99%

Unique Gene Expression Signature in Periadrenal Adipose Tissue Identifies a High Blood Pressure Group in Patients With Cushing Syndrome

Stifel,

Vogel,

Caratti

et al. 2023

Hypertension

View full text Add to dashboard Cite

Background: Cushing syndrome (CS) is a rare disease caused by excess cortisol levels with high cardiovascular morbidity and mortality. Hypertension in CS promotes hypercortisolism-associated cardiovascular events. Adipose tissue is a highly plastic tissue with most cell types strongly affected by the excess cortisol exposure. We hypothesized that the molecular and cellular changes of periadrenal adipose tissue in response to cortisol excess impact systemic blood pressure levels in patients with CS. Methods: We investigated gene expression signatures in periadrenal adipose tissue from patients with adrenal CS collected during adrenal surgery. Results: During active CS we observed a downregulation of gene programs associated with inflammation in periadrenal adipose tissue. In addition, we observed a clustering of the patients based on tissue gene expression profiles into 2 groups according to blood pressure levels (CS low blood pressure and CS high blood pressure). The 2 clusters showed significant differences in gene expression pattens of the renin-angiotensin-aldosterone-system. Renin was the strongest regulated gene compared with control patients and its expression correlated with increased blood pressure observed in our patients with CS. In the CS high blood pressure group, systemic renin plasma levels were suppressed indicative of an abnormal blood pressure associated with periadrenal adipose tissue renin-angiotensin-aldosterone-system activation. Conclusions: Here, we show for the first time a relevant association of the local renin-angiotensin-aldosterone-system and systemic blood pressure levels in patients with CS. Patients from the CS high blood pressure group still had increased blood pressure levels after 6 months in remission, highlighting the importance of local tissue effects on long-term systemic effects observed in CS.

show abstract

Cardiovascular health and mortality in Cushing’s disease

Cited by 22 publications

References 17 publications

Obesity-Related Hemodynamic Alterations in Patients with Cushing’s Disease

Obesity-Related Hemodynamic Alterations in Patients with Cushing’s Disease

A unique gene expression signature in visceral adipose tissue identifies a high blood pressure group in patients with Cushing’s syndrome

Unique Gene Expression Signature in Periadrenal Adipose Tissue Identifies a High Blood Pressure Group in Patients With Cushing Syndrome

Contact Info

Product

Resources

About