scholarly journals The ceramide- and phosphatidylcholine- based Coronary Event Risk Test2 (CERT2) and cardiovascular mortality in men and women with type 2 diabetes

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Leiherer ◽  
A Muendlein ◽  
C H Saely ◽  
B Larcher ◽  
A Mader ◽  
...  

Abstract   The recently introduced Coronary Event Risk Test version 2 (CERT2) is a validated cardiovascular risk predictor score that uses circulating ceramide and phosphatidylcholine concentrations. The purpose of this study was to investigate the power of CERT2 to predict cardiovascular mortality in 280 male and 121 female patients with type 2 diabetes (T2DM). Prospectively, we recorded 55 cardiovascular deaths in men and 19 in women during a mean follow-up time of 7.6±3.6 and 8.1±3.4 years respectively. Overall, cardiovascular survival decreased with increasing CERT2 risk categories (figure 1). In Cox regression models, CERT2 significantly predicted the incidence of cardiovascular mortality in male patients with T2DM (unadj. HR 1.82 [1.39–2.37] per standard deviation; p<0.001), the unadj. HR in women was 1.36 [0.83–2.22]; p=0.228). After adjustment for age, BMI, current smoking, LDL cholesterol, HDL cholesterol, hypertension, and statin use the HR in men was 1.73 [1.31–2.29]; p<0.001) and 1.40 [083–2.36]; p=0.210 in women. Interaction terms CERT2 x gender were non-significant both in univariate analysis (p=0.354) and after multivariate adjustment (p=0.359). We conclude that sex does not significantly impact the association of CERT2 with cardiovascular mortality in patients with T2DM. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Leiherer ◽  
A Muendlein ◽  
C H Saely ◽  
R Laaksonen ◽  
M Laaperi ◽  
...  

Abstract Background The recently introduced Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. Purpose The purpose of this study was to investigate the power of CERT to predict cardiovascular mortality in patients with established cardiovascular disease (CVD) including patients with type 2 diabetes (T2DM). Methods We investigated a total of 1087 patients with established CVD, including 360 patients with T2DM. At baseline, the prevalence of T2DM increased through CERT categories (29.1, 31.1, 37.4, and 53.4%, respectively, ptrend<0.001). Prospectively, cardiovascular deaths were recorded during a mean follow-up time of 8.1±3.2 years. Results A total of 130 cardiovascular deaths occurred. Overall, cardiovascular mortality increased with increasing CERT categories (figure) and was higher in T2DM patients than in those who did not have diabetes (17.7 vs. 9.4%; p<0.001). In Cox regression models, CERT categories predicted cardiovascular mortality in patients with T2DM (unadjusted HR 1.60 [1.28–2.01]; p<0.001; HR adjusted for age, gender, BMI, smoking, LDL cholesterol, HDL cholesterol, hypertension, and statin use 1.65 [1.27–2.15]; p<0.001) and in those without diabetes (unadjusted HR 1.43 [1.10–1.85]; p=0.008 and adjusted HR 1.41 [1.07–1.85]; p=0.015). Cardiovascular survival of CVD patients Conclusion We conclude that CERT predicts cardiovascular mortality in CVD patients with T2DM as well as in those without diabetes.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 363-P
Author(s):  
ANDREAS LEIHERER ◽  
AXEL MUENDLEIN ◽  
CHRISTOPH H. SAELY ◽  
BARBARA LARCHER ◽  
ARTHUR MADER ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Leiherer ◽  
A Muendlein ◽  
C.H Saely ◽  
R Laaksonen ◽  
M Laaperi ◽  
...  

Abstract   The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. The purpose of this study was to investigate the power of CERT and CERT-2 to predict cardiovascular mortality in patients with cardiovascular disease (CVD). We investigated a cohort of 999 patients with established CVD. Overall, comparing survival curves (figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63 [2.09–6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02 [2.47–14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00 [1.44–6.23] using CERT and 7.06 [1.64–30.50] using CERT-2; the corresponding HRs among non-diabetic subjects were 2.99 [1.20–7.46] and 3.43 [1.03–11.43], respectively. We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D. Performance is even higher with CERT-2. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
A. Giandalia ◽  
A. Alibrandi ◽  
L. Giorgianni ◽  
F. Lo Piano ◽  
F. Consolo ◽  
...  

Abstract Background Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk. Aims To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women. Methods Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women. Results Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis. Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986–1.344 95% CI), together with age, tHcy, LDL-C and hypertension. Conclusions Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2522
Author(s):  
Chung ◽  
Kim ◽  
Kwock

This study aimed to examine the association between the incidence of type 2 diabetes and various risk factors including dietary patterns based on the rigorous proportional hazards assumption tests. Data for 3335 female subjects aged 40–69 years from the Korea Genome and Epidemiology Study were used. The assumption of proportional hazards was tested using the scaled Schoenfeld test. The stratified Cox regression was used to adjust the nonproportionality of diabetic risk factors, and the regression was adjusted for potential confounding variables, such as age, marital status, physical activity, drinking, smoking, BMI, etc. Metabolic syndrome and meat and fish pattern variables were positively associated with diabetes. However, dietary patterns and metabolic syndrome variables violated the proportional hazards assumption; therefore, the stratified Cox regression with the interaction terms was applied to adjust the nonproportionality and to allow the possible different parameters over each stratum. The highest quartile of meat and fish pattern was associated with diabetes only in subjects aged over 60 years. Moreover, subjects who were obese and had metabolic syndrome had higher risk in bread and snacks (HR: 1.85; 95% CI: 1.00–3.40) and meat and fish pattern (HR: 1.82; 95% CI: 1.01–3.26), respectively. In conclusion, a quantitative proportional hazards assumption test should always be conducted before the use of Cox regression because nonproportionality of risk factors could induce limited effect on diabetes incidence.


2020 ◽  
Vol 15 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Kathryn C.B. Tan ◽  
Ching-Lung Cheung ◽  
Alan C.H. Lee ◽  
Joanne K.Y. Lam ◽  
Ying Wong ◽  
...  

Background and objectivesProtein carbamylation is a consequence of uremia and carbamylated lipoproteins contribute to atherogenesis in CKD. Proteins can also be carbamylated by a urea-independent mechanism, and whether carbamylated lipoproteins contribute to the progression of CKD has not been investigated.Design, setting, participants, & measurementsA case-control study was performed to determine whether there were changes in plasma levels of carbamylated lipoproteins in individuals with type 2 diabetes with eGFR >60 ml/min per 1.73 m2 compared with a group of age- and sex-matched healthy controls. A cohort of 1320 patients with type 2 diabetes with baseline eGFR ≥30 ml/min per 1.73 m2 was longitudinally followed up to evaluate the association between carbamylated lipoproteins and progression of CKD. The primary kidney outcome was defined as doubling of serum creatinine and/or initiation of KRT during follow-up. Plasma carbamylated LDLs and HDLs was measured by ELISA.ResultsIn individuals with diabetes with eGFR >60 ml/min per 1.73 m2, both plasma carbamylated LDL and HDL levels were higher compared with healthy controls (P<0.001). After a mean follow-up of 9 years of the diabetic cohort, individuals in the top quartile of carbamylated LDL (hazard ratio, 2.21; 95% confidence interval, 1.42 to 3.46; P<0.001) and carbamylated HDL (hazard ratio, 4.53; 95% confidence interval, 2.87 to 7.13; P<0.001) had higher risk of deterioration of kidney function compared with those in the lowest quartile. On multivariable Cox regression analysis, plasma carbamylated LDL was no longer associated with kidney outcome after adjusting for baseline eGFR and potential confounding factors. However, the association between plasma carbamylated HDL and kidney outcome remained significant and was independent of HDL cholesterol.ConclusionsPlasma carbamylated HDL but not carbamylated LDL was independently associated with progression of CKD in patients with type 2 diabetes.


2021 ◽  
Author(s):  
Jiandong Zhou ◽  
Guoming Zhang ◽  
Carlin Chang ◽  
Oscar Hou In Chou ◽  
Sharen Lee ◽  
...  

Abstract Background To compare the rates of incident atrial fibrillation (AF), stroke, cardiovascular mortality, and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus. Methods This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1 st , 2000 and December 31 st , 2019. The primary outcome was new-onset AF or stroke. Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, Charlson comorbidity index, past comorbidities, and medication use. Cox regression was used to identify significant risk factors. Competing risk analysis was conducted using cause-specific and subdistribution hazard models. Sensitivity analysis using propensity score stratification, high dimensional propensity score and inverse probability of treatment weighting were conducted. Results A total of 36228 sulphonylurea users and 72456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% confidence interval [CI]: 2.75-2.77; P<0.0001), stroke (HR: 3.23, 95% CI: 3.01-3.45; P<0.0001), cardiovascular mortality (HR: 3.60, 95% CI: 2.62-4.81; P<0.0001), and all-cause mortality (HR: 4.35, 95% CI: 3.16-4.75; P<0.0001) compared to metformin users. Similarly significant results were observed using cause-specific and subdistribution hazard models. Sensitvity analysis using other propensity score techniques also yielded higher risks in sulphonylurea users. Conclusions Sulphonylurea use was associated with higher risks of incident AF, stroke, cardiovascular mortality and all-cause mortality compared to metformin.


2021 ◽  
Author(s):  
Annalisa GIANDALIA ◽  
Angela Alibrandi ◽  
Letterio Giorgianni ◽  
Federico Lo Piano ◽  
Francesca Consolo ◽  
...  

Abstract Background: Obesity- associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk.Aims: To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women.Methods: Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women.Results: Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P=0.013); conversely hsCRP were ~2X higher in T2DM women than in controls (P=0.0132) without any difference according to CHD history.At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independent predictors of resistin levels at stepwise regression analysis.Resistin levels were independent predictors of CHD, increasing the risk by 1.15 times (0.986-1.344 95% CI), together with age, tHcy, LDL-C and hypertension. Conclusions: Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.


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