Impact of long-term steroid therapy on epicardial and pericardial fat deposition: a cardiac MRI study

Cardiovascular Diabetology

Simon Greulich³  Heiko Mahrholdt³  M. Dominik Alscher⁴  Udo Sechtem³  Niko Braun⁴  Maik Backes¹  Stefan Birkmeier³  Joerg Henes²  Joerg Latus⁴  Daniel Kitterer⁴ 

[1] Department of Radiology, Robert-Bosch-Medical Center, Auerbachstrasse 110, Stuttgart, 70376, Germany;Division of Rheumatology, Department of Internal Medicine II, Universitätsklinik Tübingen, Tübingen, Germany;Department of Cardiology, Robert-Bosch-Medical Center, Auerbachstrasse 110, Stuttgart, 70376, Germany;Division of Nephrology, Department of Internal Medicine, Robert-Bosch-Medical Center, Auerbachstrasse 110, Stuttgart, 70376, Germany

关键词: Rheumatic disorder;    Steroid therapy;    Pericardial fat;    Epicardial fat;    Cardiac MRI;   

Others  :  1228715
DOI  :  10.1186/s12933-015-0289-x

 received in 2015-08-14, accepted in 2015-09-11,  发布年份 2015

【 摘 要 】

Background

Increased cardiac fat has been identified as a risk factor for coronary artery disease. Metabolic syndrome is associated with increased cardiac fat deposition. Steroids are known to imitate some effects of metabolic syndrome and are frequently used in patients with rheumatic disorders. Primary aim was to evaluate the impact of long-term steroid use on cardiac fat deposition in patients with rheumatic disorders. In addition, we sought to investigate if this effect might be dose-dependent.

Methods

Patients were enrolled as follows: (1) rheumatic disorder; and (2) long-term steroid therapy, and (3) underwent cardiovascular magnetic resonance (CMR) imaging. Patients were stratified in a high-dose (>7.5 mg prednisone equivalent/day for at least 6 months) and a low-dose steroid group (<7.5 mg prednisone equivalent/day) and compared to steroid-naïve controls without rheumatic disorders.

Results

122 patients were included (n = 61 steroid patients, n = 61 controls). N = 36 were classified as high-dose, n = 25 as low-dose steroid group. Steroid patients showed larger epicardial 5.7 [3.5–9.1] cm ²and pericardial 13.0 [6.1–26.8] cm ²areas of fat than controls 4.2 [1.3–5.8] cm ² /6.4 [1.6–15.4] cm ² , p < 0.001, p < 0.01, respectively. High-dose steroid patients had more epi- and pericardial fat both than controls: 7.2 [4.2–11.1] cm ²vs. 4.4 [1.0-6.0] cm ² , p < 0.001; 18.6 [8.9–38.2] cm ²vs. 10.7 [4.7–26.8] cm ² , p < 0.05, and patients in the low-dose steroid group (p < 0.01, p < 0.001, respectively).

Conclusion

The present data suggest increased cardiac fat deposition in steroid-treated patients with rheumatic disorders. Furthermore, this accumulation of cardiac fat seems to be dose-dependent, pointing towards a cumulative effect of steroids.

【 授权许可】

   
2015 Kitterer et al.

【 图 表 】

Fig.1.

Fig.2.

Fig.3.

Fig.4.

Fig.5.

【 参考文献 】

• [1]Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G et al.. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010; 121(7):948-954.
• [2]Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C et al.. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34(38):2949-3003.
• [3]Nyman K, Graner M, Pentikainen MO, Lundbom J, Hakkarainen A, Siren R et al.. Cardiac steatosis and left ventricular function in men with metabolic syndrome. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson. 2013; 15:103.
• [4]Ding J, Hsu FC, Harris TB, Liu Y, Kritchevsky SB, Szklo M et al.. The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2009; 90(3):499-504.
• [5]Tamarappoo B, Dey D, Shmilovich H, Nakazato R, Gransar H, Cheng VY et al.. Increased pericardial fat volume measured from noncontrast CT predicts myocardial ischemia by SPECT. JACC Cardiovasc Imaging. 2010; 3(11):1104-1112.
• [6]Aslanabadi N, Salehi R, Javadrashid A, Tarzamni M, Khodadad B, Enamzadeh E et al.. Epicardial and pericardial fat volume correlate with the severity of coronary artery stenosis. J Cardiovasc Thorac Res. 2014; 6(4):235-239.
• [7]Cheng VY, Dey D, Tamarappoo B, Nakazato R, Gransar H, Miranda-Peats R et al.. Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. JACC Cardiovasc Imaging. 2010; 3(4):352-360.
• [8]Mahabadi AA, Berg MH, Lehmann N, Kalsch H, Bauer M, Kara K et al.. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol. 2013; 61(13):1388-1395.
• [9]Mason JC, Libby P. Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premature cardiovascular events in rheumatologic conditions. Eur Heart J. 2015; 36(8):482-9c.
• [10]Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E. Standardized cardiovascular magnetic resonance (CMR) protocols 2013 update. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson. 2013; 15:91.
• [11]Mahrholdt H, Goedecke C, Wagner A, Meinhardt G, Athanasiadis A, Vogelsberg H et al.. Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation. 2004; 109(10):1250-1258.
• [12]Graner M, Siren R, Nyman K, Lundbom J, Hakkarainen A, Pentikainen MO et al.. Cardiac steatosis associates with visceral obesity in nondiabetic obese men. J Clin Endocrinol Metab. 2013; 98(3):1189-1197.
• [13]Huscher D, Thiele K, Gromnica-Ihle E, Hein G, Demary W, Dreher R et al.. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009; 68(7):1119-1124.
• [14]Furst DE, Saag KG. Determinants of glucocorticoid dosing. Up to date 2015. 2013. http://www.uptodate.com/contents/determinants-of-glucocorticoiddosing?source=search_result&search=glucocorticoid&selectedTitle=4~150. Accessed 15 Sept 2015.
• [15]Kim SH, Chung JH, Kwon BJ, Song SW, Choi WS. The associations of epicardial adipose tissue with coronary artery disease and coronary atherosclerosis. Int Heart J. 2014; 55(3):197-203.
• [16]Chen O, Sharma A, Ahmad I, Bourji N, Nestoiter K, Hua P et al.. Correlation between pericardial, mediastinal, and intrathoracic fat volumes with the presence and severity of coronary artery disease, metabolic syndrome, and cardiac risk factors. Eur Heart J Cardiovasc Imaging. 2015; 16(1):37-46.
• [17]Alberti KG, Zimmet P, Shaw J. Metabolic syndrome–a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med J Br Diabet Assoc. 2006; 23(5):469-480.
• [18]Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V et al.. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006; 55(3):420-426.
• [19]Gulliford MC, Charlton J, Latinovic R. Risk of diabetes associated with prescribed glucocorticoids in a large population. Diabetes Care. 2006; 29(12):2728-2729.
• [20]Gurwitz JH, Bohn RL, Glynn RJ, Monane M, Mogun H, Avorn J. Glucocorticoids and the risk for initiation of hypoglycemic therapy. Arch Intern Med. 1994; 154(1):97-101.
• [21]Saruta T, Suzuki H, Handa M, Igarashi Y, Kondo K, Senba S. Multiple factors contribute to the pathogenesis of hypertension in Cushing’s syndrome. J Clin Endocrinol Metab. 1986; 62(2):275-279.
• [22]Whitworth JA. Studies on the mechanisms of glucocorticoid hypertension in humans. Blood Press. 1994; 3(1–2):24-32.
• [23]Mancini T, Kola B, Mantero F, Boscaro M, Arnaldi G. High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin Endocrinol. 2004; 61(6):768-777.
• [24]Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med. 2004; 141(10):764-770.
• [25]Gorter PM, van Lindert AS, de Vos AM, Meijs MF, van der Graaf Y, Doevendans PA et al.. Quantification of epicardial and peri-coronary fat using cardiac computed tomography; reproducibility and relation with obesity and metabolic syndrome in patients suspected of coronary artery disease. Atherosclerosis. 2008; 197(2):896-903.
• [26]Macfarlane DP, Raubenheimer PJ, Preston T, Gray CD, Bastin ME, Marshall I et al.. Effects of acute glucocorticoid blockade on metabolic dysfunction in patients with Type 2 diabetes with and without fatty liver. Am J Physiol Gastrointest Liver Physiol. 2014; 307(7):G760-G768.
• [27]Ichikawa R, Daimon M, Miyazaki T, Kawata T, Miyazaki S, Maruyama M et al.. Influencing factors on cardiac structure and function beyond glycemic control in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2013; 12:38. BioMed Central Full Text
• [28]Yuen KC, Roberts CT, Frystyk J, Rooney WD, Pollaro JR, Klopfenstein BJ et al.. Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency. J Clin Endocrinol Metab. 2014; 99(10):E1862-E1869.
• [29]Geer EB, Shen W, Gallagher D, Punyanitya M, Looker HC, Post KD et al.. MRI assessment of lean and adipose tissue distribution in female patients with Cushing’s disease. Clin Endocrinol. 2010; 73(4):469-475.
• [30]Rockall AG, Sohaib SA, Evans D, Kaltsas G, Isidori AM, Monson JP et al.. Computed tomography assessment of fat distribution in male and female patients with Cushing’s syndrome. Eur J Endocrinol/Eur Fed Endocr Soc. 2003; 149(6):561-567.
• [31]Wajchenberg BL, Bosco A, Marone MM, Levin S, Rocha M, Lerario AC et al.. Estimation of body fat and lean tissue distribution by dual energy X-ray absorptiometry and abdominal body fat evaluation by computed tomography in Cushing’s disease. J Clin Endocrinol Metab. 1995; 80(9):2791-2794.
• [32]Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983; 67(5):968-977.
• [33]Dusserre E, Moulin P, Vidal H. Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochim Biophys Acta. 2000; 1500(1):88-96.
• [34]Katagiri H, Yamada T, Oka Y. Adiposity and cardiovascular disorders: disturbance of the regulatory system consisting of humoral and neuronal signals. Circ Res. 2007; 101(1):27-39.
• [35]Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H et al.. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003; 108(20):2460-2466.
• [36]Taguchi R, Takasu J, Itani Y, Yamamoto R, Yokoyama K, Watanabe S et al.. Pericardial fat accumulation in men as a risk factor for coronary artery disease. Atherosclerosis. 2001; 157(1):203-209.
• [37]Picard FA, Gueret P, Laissy JP, Champagne S, Leclercq F, Carrie D et al.. Epicardial adipose tissue thickness correlates with the presence and severity of angiographic coronary artery disease in stable patients with chest pain. PLoS One. 2014; 9(10):e110005.
• [38]Hoes JN, Jacobs JW, Boers M, Boumpas D, Buttgereit F, Caeyers N et al.. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2007; 66(12):1560-1567.
• [39]Oyama N, Goto D, Ito YM, Ishimori N, Mimura R, Furumoto T et al.. Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume? Jpn J Radiol. 2011; 29(2):104-109.