scholarly journals Coronary perivascular inflammation in type 2 diabetes mellitus patients: the missing piece in the puzzle of their increased cardiovascular risk?

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Cecere ◽  
S De Kreutzenberg ◽  
R Motta ◽  
F Benvenuti ◽  
S Iliceto ◽  
...  

Abstract Background Coronary atherosclerosis is a frequent complication of type 2 diabetes mellitus (DM2). Considering the contiguity with the vascular wall, perivascular adipose tissue (PVAT) could play a crucial role in the pathogenic microenvironment of atherosclerosis. The PVAT attenuation index (p-FAI) is a non-invasive marker that reveals the change in peri-coronary adipose tissue (PCAT). High values of p-FAI are associated with increased cardiovascular mortality and poor prognosis. Emerging as an indication, contributor to, and therapeutic target for atherosclerosis, PCAT warrants further investigation in DM2. Purpose We aimed to characterize the association of PCAT by p-FAI and DM2, and to compare coronary inflammation in DM2 versus non DM2 patients with coronary artery disease (CAD), and versus healthy controls. Methods 15 consecutive DM2 patients (9 male, age 63±10 years) without symptoms/signs of cardiovascular disease were included in the study and compared to 8 non DM2 patients with CAD and 13 healthy volunteers without cardiovascular diseases, matched for age and sex. All patients and controls underwent coronary computed tomography angiography (CCTA) for the evaluation of coronary arteries and p-FAI. All scans were performed using a 320-slice multidetector computed tomography (Toshiba Aquilion) and a prospective ECG-triggered sequential acquisition. p-FAI analysis was performed using a dedicated workstation (Aquarius iNtuition Edition version 4.4.13. P3; TeraRecon Inc., Foster City, CA, USA). The proximal 40-mm segment of the right coronary artery (RCA) was identified and the inner and the outer wall were automatically traced, excluding the 10 mm from the ostium. The adipose tissue localized within a radial distance from the outer wall equal to a medium diameter of the RCA was evaluated. Voxel histograms of CT attenuation were traced and included between −190 to −30 HU within the PCAT volume. p-FAI was calculated as the median CT attenuation value of PCAT of the proximal 40-mm segment of the RCA (Figure 1). Results CAD was present in 10 DM2 patients (5 males, aged 63.1±10.5 years); in 5 DM2 patients (4 males, aged 63±11 years) epicardial coronary arteries were normal. p-FAI was higher in DM2 patients than in healthy controls (p=0.004). The presence of CAD did not impact on p-FAI in DM2 patients, presenting a comparable value (p=0.37). p-FAI was higher in DM2 patients with CAD than in non DM2 patients with CAD (p=0.04). Moreover, p-FAI was higher in DM2 patients without CAD than in non DM2 patients with CAD (p=0.002, Figure 2). Finally, p-FAI was not different in non DM2 patients with CAD compared to healthy controls (p=0.65), suggesting the limited role of CAD in the progression of peri-coronary inflammation when compared to DM2. Conclusions Coronary inflammation evaluated by p-FAI measurement was higher in DM2 patients, also without CAD. Therefore, our results suggest that DM2 is a determinant of coronary inflammation stronger than CAD. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

2019 ◽  
Vol 16 (4) ◽  
pp. 360-368
Author(s):  
Hani Zaidi ◽  
Rune Byrkjeland ◽  
Ida U Njerve ◽  
Sissel Åkra ◽  
Svein Solheim ◽  
...  

Background: Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes – insulin resistance) and body mass index at baseline were further assessed. Methods: 137 patients (aged 41–81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months. Results: No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes – insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed. Conclusion: No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Hani Zaidi ◽  
Rune Byrkjeland ◽  
Ida U. Njerve ◽  
Sissel Åkra ◽  
Svein Solheim ◽  
...  

Abstract Background Investigate effects of long-term exercise on the remodeling markers MMP-9, TIMP-1, EMMPRIN and Galectin-3 in combined type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) patients. Any associations between these biomarkers and glucometabolic variables were further assessed at baseline. Methods 137 patients (age 41–81 years, 17.2% females) were included and randomized to a 12-months exercise program or to a control group. Fasting blood samples and subcutaneous adipose tissue (AT) samples were taken at inclusion and after 12-months. The intervention was a combination of aerobic and strength training for a minimum of 150 min per week. Circulating protein levels were measured by ELISA methods and RNA was extracted from AT and circulating leukocytes. Expression levels were relatively quantified by PCR. Results After 12 months of intervention, both AT-expression and circulating levels of EMMPRIN were increased in the exercise group (p < 0.05, both) with significant difference in change between the two groups (p < 0.05 both). No significant effect was observed on MMP-9, TIMP-1 and Galectin-3. Levels of TIMP-1 (AT-expression and circulating) were significantly correlated to insulin, and HOMA2- after Bonferroni correction (p = 0.001, by 48 performed correlations). Conclusion The increase in levels of EMMPRIN after long-term exercise training, might indicate some degree of AT remodeling in these patients after 12-months of exercise, whether beneficial or not. The remodeling markers were to some extent associated with glucometabolic variables in our population with the combined disease. Trial registration clinicaltrials.gov, NCT01232608. Registered 2 November 2010


2021 ◽  
Vol 17 ◽  
Author(s):  
Dipayan Roy ◽  
Purvi Purohit ◽  
Anupama Modi ◽  
Manoj Khokhar ◽  
Ravindra Kumar Gayaprasad Shukla ◽  
...  

Background: Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India, and poses significant morbidity, mortality, and socioeconomic burden. Introduction: Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations. Methodology: We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were done. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as housekeeping gene. The data were analyzed on R programming platform using RStudio. Results: Serum GDF15 was significantly higher (p<0.001) in T2DM subjects (median 1445.47 pg/mL) compared to prediabetes (627.85 pg/mL) and healthy controls (609.01 pg/mL). Using the ΔΔCt method, the VAT GDF15 expression was 1.54 fold and 1.57 fold upregulated in T2DM (n=17) compared to control subjects (n=29), and obese (n=12) compared to non-obese (n=34)subjects, respectively. The optimal cut-off point following the Youden’s index method was found to be 868.09 pg/mL. ROC curve analysis revealed that serum GDF15 had a sensitivity, specificity, and area under the curve (AUC) of 90.41%, 79.52%, and 0.892 respectively. GDF15 levels were significantly associated with age, BMI, HbA1c, fasting blood sugar, and insulin resistance indices. Conclusion: Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.


2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Jiang ◽  
Yuan Li ◽  
Ke Shi ◽  
Jin Wang ◽  
Wen-Lei Qian ◽  
...  

Abstract Background The effect of comorbid hypertension and type 2 diabetes mellitus (T2DM) on coronary artery plaques examined by coronary computed tomography angiography (CCTA) is not fully understood. We aimed to comprehensively assess whether comorbid hypertension and T2DM influence coronary artery plaques using CCTA. Materials and methods A total of 1100 T2DM patients, namely, 277 normotensive [T2DM(HTN−)] and 823 hypertensive [T2DM(HTN +)] individuals, and 1048 normotensive patients without T2DM (control group) who had coronary plaques detected on CCTA were retrospectively enrolled. Plaque type, coronary stenosis, diseased vessels, the segment involvement score (SIS) and the segment stenosis score (SSS) based on CCTA data were evaluated and compared among the groups. Results Compared with patients in the control group, the patients in the T2DM(HTN−) and T2DM(HTN +) groups had more partially calcified plaques, noncalcified plaques, segments with obstructive stenosis, and diseased vessels, and a higher SIS and SSS (all P values < 0.001). Compared with the control group, T2DM(HTN +) patients had increased odds of having any calcified and any noncalcified plaque [odds ratio (OR) = 1.669 and 1.278, respectively; both P values < 0.001]; both the T2DM(HTN-) and T2DM(HTN +) groups had increased odds of having any partially calcified plaque (OR = 1.514 and 2.323; P = 0.005 and P < 0.001, respectively), obstructive coronary artery disease (CAD) (OR = 1.629 and 1.992; P = 0.001 and P < 0.001, respectively), multivessel disease (OR = 1.892 and 3.372; both P-values < 0.001), an SIS > 3 (OR = 2.233 and 3.769; both P values < 0.001) and an SSS > 5 (OR = 2.057 and 3.580; both P values < 0.001). Compared to T2DM(HTN−) patients, T2DM(HTN +) patients had an increased risk of any partially calcified plaque (OR = 1.561; P = 0.005), multivessel disease (OR = 1.867; P < 0.001), an SIS > 3 (OR = 1.647; P = 0.001) and an SSS > 5 (OR = 1.625; P = 0.001). Conclusion T2DM is related to the presence of partially calcified plaques, obstructive CAD, and more extensive coronary artery plaques. Comorbid hypertension and diabetes further increase the risk of partially calcified plaques, and more extensive coronary artery plaques.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Jiang ◽  
Tong Pang ◽  
Rui Shi ◽  
Wen-lei Qian ◽  
Wei-feng Yan ◽  
...  

BackgroundThe effect of smoking on coronary artery plaques examined by coronary computed tomography angiography (CCTA) in type 2 diabetes mellitus (DM) patients is not fully understood. This study explored the effect of smoking on coronary artery plaques by comparing the characteristics of plaques between diabetes patients with and without a smoking history and among those with different smoking durations.Materials and MethodsIn total, 1058 DM patients found to have coronary plaques on CCTA were categorized into the smoker (n=448) and nonsmoker groups (n=610). Smokers were stratified by smoking duration [≤20 years (n=115), 20~40 years (n=233) and &gt;40 years (n=100)]. The plaque types, luminal stenosis [obstructive (&lt;50%) or nonobstructive (≥50%) stenosis], segment involvement score (SIS), and segment stenosis score (SSS) of the CCTA data were compared among groups.ResultsCompared to nonsmokers, smokers demonstrated increased odds ratios (ORs) of any noncalcified plaques (OR=1.423; P=0.014), obstructive plaques (OR=1.884; P&lt;0.001), multivessel disease (OR=1.491; P=0.020), SIS≥4 (OR=1.662; P&lt;0.001), and SSS≥7 (OR=1.562; P=0.001). Compared to diabetes patients with a smoking duration ≤20 years, those with a smoking duration of 20~40 years and &gt;40 years had higher OR of any mixed plaques (OR=2.623 and 3.052, respectively; Ps&lt;0.001), obstructive plaques (OR=2.004 and 2.098; P=0.003 and 0.008, respectively), multivessel disease (OR=3.171 and 3.784; P&lt;0.001 and P=0.001, respectively), and SSS≥7 (OR=1.605 and 1.950; P=0.044 and 0.020, respectively). Diabetes with a smoking duration &gt;40 years had a higher OR of SIS≥4 (OR=1.916, P=0.034).ConclusionSmoking is independently associated with the presence of noncalcified, obstructive, and more extensive coronary artery plaques in diabetes patients, and a longer smoking duration is significantly associated with a higher risk of mixed, obstructive, and more extensive plaques.


2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Rhanderson Cardoso ◽  
Ramzi Dudum ◽  
Richard A. Ferraro ◽  
Marcio Bittencourt ◽  
Ron Blankstein ◽  
...  

The incidence and prevalence of type 2 diabetes mellitus are increasing in the United States and worldwide. The individual-level risk of atherosclerotic cardiovascular disease events in primary prevention populations with type 2 diabetes mellitus is highly heterogeneous. Accurate risk stratification in this group is paramount to optimize the use of preventive therapies. Herein, we review the use of the coronary artery calcium score as a decision aid in individuals with type 2 diabetes mellitus without clinical atherosclerotic cardiovascular disease to guide the use of preventive pharmacotherapies, such as aspirin, lipid-lowering mediations, and cardiometabolic agents. The magnitude of expected risk reduction for each of these therapies must be weighed against its cost and potential adverse events. Coronary artery calcium has the potential to improve risk stratification in select individuals beyond clinical and laboratory risk factors, thus providing a more granular assessment of the expected net benefit with each therapy. In patients with diabetes mellitus and stable chest pain, coronary computed tomography angiography increases the sensitivity for coronary artery disease diagnoses compared with functional studies because of the detection of nonobstructive atherosclerosis. Most importantly, this anatomic approach may improve cardiovascular outcomes by increasing the use of evidence-based preventive therapies informed by plaque burden. We therefore provide an updated discussion of the pivotal role of coronary computed tomography angiography in the workup of stable chest pain in patients with diabetes mellitus in the context of recent landmark trials, such as PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), SCOT-HEART trial (Scottish Computed Tomography of the Heart), and ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches). Finally, we also outline the current role of coronary computed tomography angiography in acute chest pain presentations.


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