P4992The ceramide-based Coronary Event Risk Test (CERT) predicts cardiovascular mortality in cardiovascular disease patients with type 2 diabetes mellitus as well as in those without diabetes

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.

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

European Heart Journal ◽

10.1093/eurheartj/ehab724.2483 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A Leiherer ◽

A Muendlein ◽

C H Saely ◽

B Larcher ◽

A Mader ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Univariate Analysis ◽

Hdl Cholesterol ◽

Coronary Event ◽

Interaction Terms ◽

Event Risk ◽

Risk Predictor

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

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416-P: The Ceramide-Based Coronary Event Risk Test (CERT) Predicts Cardiovascular Mortality in Cardiovascular Disease Patients with Type 2 Diabetes Mellitus as Well as in Those without Diabetes

Diabetes ◽

10.2337/db19-416-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 416-P

Author(s):

ANDREAS LEIHERER ◽

AXEL MUENDLEIN ◽

CHRISTOPH H. SAELY ◽

REJO LAAKSONEN ◽

MITJA LAAPERI ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 2 Diabetes Mellitus ◽

Cardiovascular Mortality ◽

Coronary Event ◽

Event Risk

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The ceramide-based coronary event risk test (CERT) predicts cardiovascular mortality in cardiovascular disease patients with type 2 diabetes as well as in those without diabetes

Atherosclerosis ◽

10.1016/j.atherosclerosis.2020.10.232 ◽

2020 ◽

Vol 315 ◽

pp. e74-e75

Author(s):

A. Leiherer ◽

A. Muendlein ◽

C.H. Saely ◽

R. Laaksonen ◽

M. Laaperi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cardiovascular Mortality ◽

Coronary Event ◽

Event Risk

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Comparison of two recent ceramide-based coronary risk prediction scores: CERT and CERT-2

European Heart Journal ◽

10.1093/ehjci/ehaa946.2922 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Leiherer ◽

A Muendlein ◽

C.H Saely ◽

R Laaksonen ◽

M Laaperi ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Coronary Event ◽

Cardiovascular Death ◽

Survival Models ◽

Risk Category ◽

Net Reclassification Improvement ◽

Event Risk ◽

Risk Predictor ◽

Risk Categories

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

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Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study

Cardiovascular Diabetology ◽

10.1186/s12933-019-0953-7 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 7

Author(s):

You-Bin Lee ◽

Kyungdo Han ◽

Bongsung Kim ◽

Seung-Eun Lee ◽

Ji Eun Jun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Cox Regression ◽

Early Mortality ◽

Hazard Ratios ◽

Epidemiological Characteristics

Abstract Background Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes. Methods We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline. Results During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death]. Conclusions In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.

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363-P: The Ceramide- and Phosphatidylcholine-Based Coronary Event Risk Test 2 (CERT2) and Cardiovascular Mortality in Men and Women with Type 2 Diabetes

Diabetes ◽

10.2337/db21-363-p ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 363-P

Author(s):

ANDREAS LEIHERER ◽

AXEL MUENDLEIN ◽

CHRISTOPH H. SAELY ◽

BARBARA LARCHER ◽

ARTHUR MADER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Mortality ◽

Coronary Event ◽

Men And Women ◽

Event Risk

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Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study

10.2337/figshare.14173313 ◽

2021 ◽

Author(s):

Maoxiang Zhao ◽

Lulu Song ◽

Lan Sun ◽

Miao Wang ◽

Chi Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cox Regression ◽

Age Groups ◽

Onset Age ◽

Onset Type ◽

Diabetes Onset ◽

All Cause Mortality

Objective We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in Chinese population. Research design and methods This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan study. All participants were followed biennially until December 31, 2017. A total of 11,384 participants were diagnosed as type 2 diabetes during follow-up. For each case, one control was randomly selected matched for age (±1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% confidence intervals (CIs) of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus controls across age groups. Results During a median follow-up of 5.57 years, 1794 incident events (907 CVD events, of which were 725 strokes, and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age < 45 years had the highest risks of CVD and all-cause mortality relative to the matched controls, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. Conclusions The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age groups, and the associations were more evident in younger-onset type 2 diabetes.

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Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.11710919 ◽

2020 ◽

Vol 15 (3) ◽

pp. 359-366 ◽

Cited By ~ 1

Author(s):

Kathryn C.B. Tan ◽

Ching-Lung Cheung ◽

Alan C.H. Lee ◽

Joanne K.Y. Lam ◽

Ying Wong ◽

...

Keyword(s):

Type 2 Diabetes ◽

Confidence Interval ◽

Cox Regression ◽

Hdl Cholesterol ◽

Hazard Ratio ◽

Healthy Controls ◽

Cox Regression Analysis ◽

Control Study

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.

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Plasma fibrin clot properties and cardiovascular mortality in patients with type 2 diabetes: a long‐term follow‐up study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01230-9 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Agata Hanna Bryk ◽

Małgorzata Konieczyńska ◽

Maciej Polak ◽

Dariusz Plicner ◽

Maciej Bochenek ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cardiovascular Mortality ◽

Multivariable Analysis ◽

Fibrin Clot ◽

Rate Of Increase ◽

Fibrinolytic Proteins

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM. Methods We studied 133 T2DM patients aged 43–83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-Dmax) and rate of increase in D-dimer concentration (D-Drate) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded. Results Cardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-Dmax (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99–14.79), or decreased D-Drate (< 0.07 mg/l/min, HR 2.97, 95% CI 1.07–8.23), or increased peak thrombin (> 283.5 nM, HR 5.65, 95% CI 2.07–15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02–18.96; HR 8.98, 95% CI 2.99–26.96; and HR 5.35, 95% CI 1.62–17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-Dmax > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l. Conclusions This study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.

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