Long-term Steroid Therapy Impacts Cardiac Fat Deposition
In total 122 patients were included in the final analysis: n = 61 patients received long-term steroid therapy due to underlying rheumatic disorder, n = 61 patients served as an age, gender and BMI-matched steroid-naïve control group. At inclusion, patients were 54 ± 16 years of age, predominantly female (71 %), with a mean BMI of 27 ± 6 kg/m . Median disease duration was 4.7 [0.8–8.2] years. Functional CMR parameters did not differ significantly between both groups. However, patients on steroid therapy showed larger epicardial 5.7 [3.5–9.1] cm, as well as pericardial 13.0 [6.1–26.8] cm fat areas compared to paired matched controls (4.2 [1.3–5.8] cm/6.4 [1.6–15.4] cm, p < 0.001, p < 0.01, respectively). Additional clinical characteristics can be viewed in Table 1.
In the steroid group, duration of steroid therapy was 30 [8–93] months with a median daily prednisone dose at inclusion of 10 mg. Of note, the prevalence of metabolic syndrome did not differ significantly between the steroid group and controls; two out of 61 patients in the steroid group fulfilled criteria of metabolic syndrome, no patient in the control group, p = 0.5.
The majority of steroid-treated patients presented with ANCA positive vasculitis (34 %), followed by patients with collagenosis (33 %), and patients with rheumatoid arthritis (16 %).
Clinical data of the steroid population divided in low-dose and high-dose steroid groups are displayed in Table 2. Twenty-five (out of 61) patients were in the low-dose steroid group, 36 (out of 61) patients were in the high-dose steroid group. BMI was higher in the high-dose steroid (28 ± 6 kg/m) compared to the low-dose steroid group (25 ± 5 kg/m, p < 0.05). Functional CMR parameters were similar between both groups. More patients in the high-dose steroid group (n = 7) had prevalent CAD than in the low-dose steroid group (n = 2; p = 0.29). Traditional cardiovascular risk factors did not differ significantly between both groups. Metabolic syndrome was present in two patients of the high-dose steroid group, no patient in the low-dose steroid group fulfilled criteria of metabolic syndrome, p = 0.51.
Focusing on patients with high-dose steroid therapy (>7.5 mg prednisone equivalent daily during the past 6 months) revealed, that those patients had significantly more epicardial fat compared to matched steroid-naïve controls: 7.2 [4.2–11.1] cm vs. 4.4 [1.0–6.0] cm, p < 0.001. Furthermore, patients on high-dose steroid therapy also had significantly more epicardial fat compared to patients on low-dose steroid therapy (<7.5 mg prednisone equivalent daily during the past 6 months): 7.2 [4.3–11] cm vs. 4.7 [2.1–7.5] cm, p < 0.01, see Fig. 2.
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Figure 2.
Values of epicardial and pericardial fat deposition in steroid-treated patients and matched steroid-naïve controls. a The high-dose steroid group (>7.5 mg prednisone equivalent daily) showed significant higher amounts of epicardial fat than the low-dose steroid group (<7.5 mg prednisone equivalent daily) and the age, sex and BMI matched steroid-naïve controls. In addition, the amount of epicardial fat was not significant different between low-dose steroid patients and the control group. b Likewise, these results could be confirmed for pericardial fat
Among patients on high-dose steroid therapy, CMR revealed significantly more pericardial fat compared to steroid-naïve controls: 18.6 [8.9–38.2] cm vs. 10.7 [4.7–26.8] cm, p < 0.05. Additionally, patients on high-dose steroid therapy had significantly more pericardial fat compared to patients on low-dose steroid therapy: 18.6 [8.9–38.2] cm vs. 8.3 [2.3–18.7] cm, p < 0.001.
No significant differences in epicardial and pericardial fat deposition could be detected between patients on low-dose steroid therapy and paired matched controls, see also Fig. 2.
Intra-observer reproducibility was high with an ICC of 0.97 for epicardial fat and 0.98 for pericardial fat assessment, respectively. Inter-observer reproducibility showed an ICC of 0.95 for epicardial and 0.96 for pericardial fat, respectively.
We found a correlation between epicardial and pericardial fat and the BMI of patients in the steroid group, see Fig. 3. This holds also true for epicardial fat and BMI in the high-dose steroid group (p < 0.001), as well as for pericardial fat in the low-dose steroid group, p < 0.05. Furthermore, statistical analysis revealed a trend for pericardial fat in the high-dose steroid group to be related to BMI (p = 0.06), and also for epicardial fat in the low-dose steroid group (p = 0.1). No correlation of epicardial or pericardial fat deposition with BMI could be detected in the control group, see Fig. 3.
(Enlarge Image)
Figure 3.
Correlation of multiple parameters in steroid-treated patients and matched steroid-naïve controls. a, b Epicardial and pericardial fat with BMI in patients with steroid therapy. c, d Epicardial and pericardial fat in age, sex and BMI matched steroid-naïve controls. e, f Epicardial and pericardial fat with BMI in the low-dose steroid group (<7.5 mg prednisone equivalent daily). g, h Epicardial and pericardial fat with BMI in the high-dose steroid group (>7.5 mg prednisone equivalent daily)
Dividing patients on steroids and matched controls in an obese (BMI > 25 kg/m) and a non-obese group (BMI < 25 kg/m) revealed, that steroid patients with a BMI > 25 kg/m showed significantly more epicardial fat than steroid patients with a BMI < 25 kg/m (p < 0.0001). Similar results could be found for pericardial fat in the steroid-treated group (p = 0.001), see Fig. 4. However, no statistical significant difference in cardiac fat distribution between obese and non-obese control patients could be reported. Typical CMR results are displayed in Fig. 5.
(Enlarge Image)
Figure 4.
Comparison of epicardial and pericardial fat deposition in steroid-treated patients vs. controls with BMI >25 and BMI <25. a Amounts of epicardial fat in steroid-treated patients with BMI >25 (obese) and <25 (non-obese) compared to steroid-naïve controls. b Amounts of pericardial fat in steroid-treated patients with BMI >25 and <25 compared to steroid-naïve controls
(Enlarge Image)
Figure 5.
Patient examples of 4-chamber oriented end-diastolic images for determination of epicardial and pericardial fat. a, b 55-year old male with high-dose steroid treated rheumatoid arthritis for more than 8 years. Patients BMI was 27.8 kg/m, beside arterial hypertension he suffered from diabetes. CMR 4-chamber view revealed extensive epicardial fat deposition (shown in red) and pericardial fat deposition (shown in blue). c, d Age, sex and BMI matched steroid-naïve control to the high-dose steroid-treated patient in panels A/B with less amounts of epicardial and pericardial fat. e, f 49-year old steroid-naïve female (control group) with moderate epi- and pericardial fat deposition despite a high elevated BMI of 41.2 kg/m (obese class III). g, h 69-year old steroid-naïve female (control group) with a BMI of 26.8 kg/m. Despite only moderate elevated BMI and no history of steroid intake, this patient showed considerable amounts of epi- and pericardial fat, underlining the lack of association between BMI and amounts of epi- and pericardial fat in the steroid-naïve control group
Results
Patient Population
In total 122 patients were included in the final analysis: n = 61 patients received long-term steroid therapy due to underlying rheumatic disorder, n = 61 patients served as an age, gender and BMI-matched steroid-naïve control group. At inclusion, patients were 54 ± 16 years of age, predominantly female (71 %), with a mean BMI of 27 ± 6 kg/m . Median disease duration was 4.7 [0.8–8.2] years. Functional CMR parameters did not differ significantly between both groups. However, patients on steroid therapy showed larger epicardial 5.7 [3.5–9.1] cm, as well as pericardial 13.0 [6.1–26.8] cm fat areas compared to paired matched controls (4.2 [1.3–5.8] cm/6.4 [1.6–15.4] cm, p < 0.001, p < 0.01, respectively). Additional clinical characteristics can be viewed in Table 1.
In the steroid group, duration of steroid therapy was 30 [8–93] months with a median daily prednisone dose at inclusion of 10 mg. Of note, the prevalence of metabolic syndrome did not differ significantly between the steroid group and controls; two out of 61 patients in the steroid group fulfilled criteria of metabolic syndrome, no patient in the control group, p = 0.5.
The majority of steroid-treated patients presented with ANCA positive vasculitis (34 %), followed by patients with collagenosis (33 %), and patients with rheumatoid arthritis (16 %).
Low-dose Steroid Group vs. High-dose Steroid Group
Clinical data of the steroid population divided in low-dose and high-dose steroid groups are displayed in Table 2. Twenty-five (out of 61) patients were in the low-dose steroid group, 36 (out of 61) patients were in the high-dose steroid group. BMI was higher in the high-dose steroid (28 ± 6 kg/m) compared to the low-dose steroid group (25 ± 5 kg/m, p < 0.05). Functional CMR parameters were similar between both groups. More patients in the high-dose steroid group (n = 7) had prevalent CAD than in the low-dose steroid group (n = 2; p = 0.29). Traditional cardiovascular risk factors did not differ significantly between both groups. Metabolic syndrome was present in two patients of the high-dose steroid group, no patient in the low-dose steroid group fulfilled criteria of metabolic syndrome, p = 0.51.
Epicardial and Pericardial Fat
Focusing on patients with high-dose steroid therapy (>7.5 mg prednisone equivalent daily during the past 6 months) revealed, that those patients had significantly more epicardial fat compared to matched steroid-naïve controls: 7.2 [4.2–11.1] cm vs. 4.4 [1.0–6.0] cm, p < 0.001. Furthermore, patients on high-dose steroid therapy also had significantly more epicardial fat compared to patients on low-dose steroid therapy (<7.5 mg prednisone equivalent daily during the past 6 months): 7.2 [4.3–11] cm vs. 4.7 [2.1–7.5] cm, p < 0.01, see Fig. 2.
(Enlarge Image)
Figure 2.
Values of epicardial and pericardial fat deposition in steroid-treated patients and matched steroid-naïve controls. a The high-dose steroid group (>7.5 mg prednisone equivalent daily) showed significant higher amounts of epicardial fat than the low-dose steroid group (<7.5 mg prednisone equivalent daily) and the age, sex and BMI matched steroid-naïve controls. In addition, the amount of epicardial fat was not significant different between low-dose steroid patients and the control group. b Likewise, these results could be confirmed for pericardial fat
Among patients on high-dose steroid therapy, CMR revealed significantly more pericardial fat compared to steroid-naïve controls: 18.6 [8.9–38.2] cm vs. 10.7 [4.7–26.8] cm, p < 0.05. Additionally, patients on high-dose steroid therapy had significantly more pericardial fat compared to patients on low-dose steroid therapy: 18.6 [8.9–38.2] cm vs. 8.3 [2.3–18.7] cm, p < 0.001.
No significant differences in epicardial and pericardial fat deposition could be detected between patients on low-dose steroid therapy and paired matched controls, see also Fig. 2.
Intra-observer reproducibility was high with an ICC of 0.97 for epicardial fat and 0.98 for pericardial fat assessment, respectively. Inter-observer reproducibility showed an ICC of 0.95 for epicardial and 0.96 for pericardial fat, respectively.
Cardiac Fat and BMI
We found a correlation between epicardial and pericardial fat and the BMI of patients in the steroid group, see Fig. 3. This holds also true for epicardial fat and BMI in the high-dose steroid group (p < 0.001), as well as for pericardial fat in the low-dose steroid group, p < 0.05. Furthermore, statistical analysis revealed a trend for pericardial fat in the high-dose steroid group to be related to BMI (p = 0.06), and also for epicardial fat in the low-dose steroid group (p = 0.1). No correlation of epicardial or pericardial fat deposition with BMI could be detected in the control group, see Fig. 3.
(Enlarge Image)
Figure 3.
Correlation of multiple parameters in steroid-treated patients and matched steroid-naïve controls. a, b Epicardial and pericardial fat with BMI in patients with steroid therapy. c, d Epicardial and pericardial fat in age, sex and BMI matched steroid-naïve controls. e, f Epicardial and pericardial fat with BMI in the low-dose steroid group (<7.5 mg prednisone equivalent daily). g, h Epicardial and pericardial fat with BMI in the high-dose steroid group (>7.5 mg prednisone equivalent daily)
Dividing patients on steroids and matched controls in an obese (BMI > 25 kg/m) and a non-obese group (BMI < 25 kg/m) revealed, that steroid patients with a BMI > 25 kg/m showed significantly more epicardial fat than steroid patients with a BMI < 25 kg/m (p < 0.0001). Similar results could be found for pericardial fat in the steroid-treated group (p = 0.001), see Fig. 4. However, no statistical significant difference in cardiac fat distribution between obese and non-obese control patients could be reported. Typical CMR results are displayed in Fig. 5.
(Enlarge Image)
Figure 4.
Comparison of epicardial and pericardial fat deposition in steroid-treated patients vs. controls with BMI >25 and BMI <25. a Amounts of epicardial fat in steroid-treated patients with BMI >25 (obese) and <25 (non-obese) compared to steroid-naïve controls. b Amounts of pericardial fat in steroid-treated patients with BMI >25 and <25 compared to steroid-naïve controls
(Enlarge Image)
Figure 5.
Patient examples of 4-chamber oriented end-diastolic images for determination of epicardial and pericardial fat. a, b 55-year old male with high-dose steroid treated rheumatoid arthritis for more than 8 years. Patients BMI was 27.8 kg/m, beside arterial hypertension he suffered from diabetes. CMR 4-chamber view revealed extensive epicardial fat deposition (shown in red) and pericardial fat deposition (shown in blue). c, d Age, sex and BMI matched steroid-naïve control to the high-dose steroid-treated patient in panels A/B with less amounts of epicardial and pericardial fat. e, f 49-year old steroid-naïve female (control group) with moderate epi- and pericardial fat deposition despite a high elevated BMI of 41.2 kg/m (obese class III). g, h 69-year old steroid-naïve female (control group) with a BMI of 26.8 kg/m. Despite only moderate elevated BMI and no history of steroid intake, this patient showed considerable amounts of epi- and pericardial fat, underlining the lack of association between BMI and amounts of epi- and pericardial fat in the steroid-naïve control group
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