Risk Of Cardiovascular Disease In Type Research Articles

Association of serum gamma-glutamyl transferase levels with cardiovascular disease risk in type 2 diabetes patients: a prospective cohort study

To investigate the associations of serum gamma-glutamyl transferase (GGT) levels with the risk of cardiovascular disease (CVD) and its subtypes in patients with type 2 diabetes mellitus (T2DM) in Jiangsu Province. Methods: The participants were enrolled in the Comprehensive Research project regarding 'Prevention and Control of Diabetes' in Jiangsu Province. The baseline survey was conducted from 2013 to 2014, and follow-up until December 31, 2021. After excluding the participants who self-reported with chronic liver disease/stroke/coronary heart disease at baseline survey and those with incomplete information on GGT, a total of 16 147 T2DM patients were included in the final analysis. Cox proportional hazard regression models were used to calculate the hazard ratio (HR) and their 95%CI of GGT for CVD, myocardial infarction, and stroke. Restricted cubic spline models were applied to analyze the dose-response relationship between GGT and the risk of CVD and its subtypes. Results: During the median follow-up time of 8.02 years, 2 860 CVD cases were registered, including 196 cases of myocardial infarction and 2 730 cases of stroke. Multivariate Cox proportional risk regression model indicated that compared to the lowest serum GGT level group, the highest GGT level group had a 24% increased risk of CVD (HR=1.24, 95%CI: 1.09-1.41) and a 23% increased risk of stroke (HR=1.23, 95%CI: 1.08-1.40). The restricted cubic spline model showed a nonlinear dose-response relationship between GGT and the risk of CVD, myocardial infarction, and stroke in T2DM patients. Conclusions: High levels of GGT may be associated with an increased risk of cardiovascular disease in T2DM patients, which needs further exploration and validation in future clinical practice.

Evaluating cardiovascular disease risk in type 2 diabetes mellitus patients in a tertiary care hospital in Hyderabad, Sindh, Pakistan

Type 2 Diabetes Mellitus (DM) is the most common type of diabetes. The main adverse effect of diabetes type 2 involves a higher risk of cardiovascular disease. Diabetes patients with this type are more likely to suffer cardiovascular problems. Consequently, this study investigated demographics, CVR factors, age, gender, physical activity, BMI, hemodynamics, HbA1c stage, and lipid profile of 120 patients with type 2 diabetes in Hyderabad, Sindh, Pakistan. The current study covered 120 patients with type 2 diabetes, out of which 40 were male (33.3%) and 80 were female (66.6%), aged 50 to 70. Out of these 120 patients, 17 (14.1%) had coronary artery disease, 15 (12.5) had atherosclerosis, and 8% (6.6) experienced a stroke, according to the findings. Approximately 37.5% of patients had overweight obesity, 54% had poor diabetes control, and 10% had reasonable control based on their HbA1c readings. Furthermore, 55% were hypertensive, and around 12.5% had both macro and microvascular problems. In general, around 33.3% of all Type 2 DM patients have cardiovascular diseases (CVD), indicating that patients with Type 2 DM have a greater risk of increasing CVD. As a result, proper strategies should be implemented to avoid catastrophic outcomes and disease development.

The link between serum neuregulin-1 and atherogenic index in type 2 diabetes mellitus.

Neuregulin-1(NRG-1) is a protein that belongs to the group of epidermal growth factors. It plays vital roles in anti-fibrotic effects on the myocardium. The current paper explores the role of NRG-1 in type 2 diabetes mellitus (T2DM) and its relation to atherogenic index as a factor for increasing cardiovascular disease(CVD) risk. In this study, 79 diabetes mellitus patients are independent insulin. These patients consisted of 53 females and 26 males their age were ranged 40-67 years. They were divided into two groups depending on the atherogenic index of plasma (AIP). Group I including48 diabetic patient with high risk of CVD and group II including 31 diabetic patients without risk CVD. Forty healthy individuals were included as control. When compared to the control group, the serum levels of NRG-1 were significantly lower (p = 0.01). Additionally, group I had a much lower NRG-1level than group II. The results of multiple stepwise regression showed that the only independent predictor for NRG-1 level prediction was AIP (β = - 0.600, P = 0.040). When comparing the diabetic patients with high risk factors for CVD to the healthy subject group, the AUC was outstanding (AUC = 0.889, P = 0.001) and had a high diagnosis. We proved low NRG-1 levels in diabetic patients and the association of highest NRG-1 amounts to a better AIP. Moreover, the measurement of NRG-1 levels could be beneficial as laboratory markers to monitor for increasing CVD risk in type 2 diabetes mellitus.

DNA methylation and 28-year cardiovascular disease risk in type 1 diabetes: the Epidemiology of Diabetes Complications (EDC) cohort study

BackgroundThe potential for DNA methylation (DNAm) as an early marker for cardiovascular disease (CVD) and how such an association might differ by glycemic exposure has not been examined in type 1 diabetes, a population at increased CVD risk. We thus performed a prospective epigenome-wide association study of blood leukocyte DNAm (EPIC array) and time to CVD incidence over 28 years in a childhood-onset (< 17 years) type 1 diabetes cohort, the Pittsburgh Epidemiology of Diabetes Complications (EDC) study (n = 368 with DNA and no CVD at baseline), both overall and separately by glycemic exposure, as measured by HbA1c at baseline (split at the median: < 8.9% and ≥ 8.9%). We also assessed whether DNAm-CVD associations were independent of established cardiometabolic risk factors, including body mass index, estimated glucose disposal rate, cholesterol, triglycerides, blood pressure, pulse rate, albumin excretion rate, and estimated glomerular filtration rate.ResultsCVD (first instance of CVD death, myocardial infarction, coronary revascularization, ischemic ECG, angina, or stroke) developed in 172 participants (46.7%) over 28 years. Overall, in Cox regression models for time to CVD, none of the 683,597 CpGs examined reached significance at a false discovery rate (FDR) ≤ 0.05. In participants with HbA1c < 8.9% (n = 180), again none reached FDR ≤ 0.05, but three were associated at the a priori nominal significance level FDR ≤ 0.10: cg07147033 in MIB2, cg12324048 (intergenic, chromosome 3), and cg15883830 (intergenic, chromosome 1). In participants with HbA1c ≥ 8.9% (n = 188), two CpGs in loci involved in calcium channel activity were significantly associated with CVD (FDR ≤ 0.05): cg21823999 in GPM6A and cg23621817 in CHRNA9; four additional CpGs were nominally associated (FDR ≤ 0.10). In participants with HbA1c ≥ 8.9%, DNAm-CVD associations were only modestly attenuated after cardiometabolic risk factor adjustment, while attenuation was greater in those with HbA1c < 8.9%. No pathways were enriched in those with HbA1c < 8.9%, while pathways for calcium channel activity and integral component of synaptic membrane were significantly enriched in those with HbA1c ≥ 8.9%.ConclusionsThese results provide novel evidence that DNAm at loci involved in calcium channel activity and development may contribute to long-term CVD risk beyond known risk factors in type 1 diabetes, particularly in individuals with greater glycemic exposure, warranting further study.

Clinical utility of a novel test for assessing cardiovascular disease risk in type 2 diabetes: a randomized controlled trial

BackgroundThe risk for and treatment of cardiovascular disease (CVD) in type 2 diabetes (T2DM) is often incorrect and delayed. We wished to determine if a novel test improved physicians’ ability to risk stratify, diagnose, and treat patients with T2DM.MethodsIn a 2-phase randomized controlled trial comparing the clinical workup, diagnosis, and management of online, simulated patients with T2DM in a nationwide sample of cardiologists and primary care physicians, participants were randomly assigned to control or one of two intervention groups. Intervention participants had access to standard of care diagnostic tools plus a novel diagnostic CVD risk stratification test.ResultsIn control, there was no change in CV risk stratification of simulated patients between baseline and round 2 (37.1 to 38.3%, p = 0.778). Pre-post analysis showed significant improvements in risk stratification in both Intervention 1 (38.7 to 65.3%) and Intervention 2 (41.9 to 65.8%) (p < 0.01) compared to controls. Both intervention groups significantly increased prescribing SGLT2 inhibitors/GLP1 receptor agonists versus control, + 18.9% for Intervention 1 (p = 0.020) and 1 + 9.4% for Intervention 2 (p = 0.014). Non-pharmacologic treatment improved significantly compared to control (+ 30.0% in Intervention 1 (p < 0.001) and + 22.8% in Intervention 2 (p = 0.001). Finally, monitoring HgbA1C, blood pressure, and follow-up visit frequency improved by + 20.3% (p = 0.004) in Intervention 1 and + 29.8% (p < 0.001) in Intervention 2 compared with control.ConclusionUse of the novel test significantly improved CV risk stratification among T2DM patients. Statistically significant increases treatments were demonstrated, specifically SGLT2 inhibitors and GLP1 receptor antagonists and recommendations of evidence-based non-pharmacologic treatments.Trial registration ClinicalTrials.gov, NCT05237271

Using Machine Learning to Predict Abnormal Carotid Intima-Media Thickness in Type 2 Diabetes.

Carotid intima-media thickness (c-IMT) is a reliable risk factor for cardiovascular disease risk in type 2 diabetes (T2D) patients. The present study aimed to compare the effectiveness of different machine learning methods and traditional multiple logistic regression in predicting c-IMT using baseline features and to establish the most significant risk factors in a T2D cohort. We followed up with 924 patients with T2D for four years, with 75% of the participants used for model development. Machine learning methods, including classification and regression tree, random forest, eXtreme gradient boosting, and Naïve Bayes classifier, were used to predict c-IMT. The results showed that all machine learning methods, except for classification and regression tree, were not inferior to multiple logistic regression in predicting c-IMT in terms of higher area under receiver operation curve. The most significant risk factors for c-IMT were age, sex, creatinine, body mass index, diastolic blood pressure, and duration of diabetes, sequentially. Conclusively, machine learning methods could improve the prediction of c-IMT in T2D patients compared to conventional logistic regression models. This could have crucial implications for the early identification and management of cardiovascular disease in T2D patients.

NT-proBNP point-of-care measurement as a screening tool for heart failure and CVD risk in type 2 diabetes with hypertension

AimsWe used N-terminal pro-B-type natriuretic peptide (NT-proBNP) point-of-care testing (POCT) for heart failure risk stratification of individuals with type 2 diabetes for >10 years and hypertension. MethodsOverall 259 participants aged 50 years or older with type 2 diabetes (duration of >10 years), hypertension, and no overt cardiovascular disease (CVD) were recruited at two study centers. Patients' data were acquired and NT-proBNP levels were measured using the CARDIAC proBNP+ test (Roche) and the cobas h232 instrument (Roche). Participants were clustered into two groups according to their NT-proBNP concentration value: with NT-proBNP <125 pg/ml and with NT-proBNP ≥125 pg/ml. ResultsMean age of the participants was 66.1 ± 9.2 years, 55.2 % were female, 60.6 % (n = 157) had a NT-proBNP <125 pg/ml and 39.4 % (n = 102 ≥ 125 pg/ml). Differences were observed among those with low and high NT-proBNP in mean age (63.4 ± 8.8 years vs. 70.1 ± 8.2 years, p < 0.001), diabetes duration (15.4 ± 5.9 years vs. 17.9 ± 7.3 years, p = 0.003), and estimated glomerular filtration rate (eGFR) (86 ± 16 ml/min/1.73 m2 vs. 76 ± 20 ml/min/1.73 m2, p < 0.001). ConclusionsNT-proBNP POCT is practical and can be pragmatically targeted for screening people with type 2 diabetes and hypertension for heart failure risk stratification in routine clinical practice.

Reconsidering the role of glycaemic control in cardiovascular disease risk in type 2 diabetes: A 21st century assessment.

It is well known that the multiple factors contributing to the pathogenesis of type 2 diabetes (T2D) confer an increased risk of developing cardiovascular disease (CVD). Although the relationship between hyperglycaemia and increased microvascular risk is well established, the relative contribution of hyperglycaemia to macrovascular events has been strongly debated, particularly owing to the failure of attempts to reduce CVD risk through normalizing glycaemia with traditional therapies in high-risk populations. The debate has been further fuelled by the relatively recent discovery of the cardioprotective properties of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Further, as guidelines now recommend individualizing glycaemic targets, highlighting the importance of achieving glycated haemoglobin (HbA1c) goals safely, the previously observed negative influences of intensive therapy on CVD risk might not present if trials were repeated using current-day treatments and individualized HbA1c goals. Emerging longitudinal data illuminate the overall effect of excess glucose, the impacts of magnitude and duration of hyperglycaemia on disease progression and risk of CVD complications, and the importance of glycaemic control at or early after diagnosis of T2D for prevention of complications. Herein, we review the role of glucose as a modifiable cardiovascular (CV) risk factor, the role of microvascular disease in predicting macrovascular risk, and the deleterious impact of therapeutic inertia on CVD risk. We reconcile new and old data to offer a current perspective, highlighting the importance of effective, early treatment in reducing latent CV risk, and the timely use of appropriate therapy individualized to each patient's needs.

Serum Orotidine: A Novel Biomarker of Increased CVD Risk in Type 2 Diabetes Discovered Through Metabolomics Studies.

To identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD. We conducted a global serum metabolomics analysis using the Metabolon platform in a discovery set from the Joslin Kidney Study having a nested case-control design comprising 409 individuals with T2D. Logistic regression was applied to evaluate the association between incident CVD events and each of the 671 metabolites detected by the Metabolon platform, before and after adjustment for renal function and other CVD risk factors. Significant metabolites were followed up with absolute quantification assays in a validation set from the Joslin Heart Study including 599 individuals with T2D with and without clinical evidence of significant coronary heart disease (CHD). In the discovery set, serum orotidine and 2-piperidinone were significantly associated with increased odds of incident CVD after adjustment for glomerular filtration rate (GFR) (odds ratio [OR] per SD increment 1.94 [95% CI 1.39-2.72], P = 0.0001, and 1.62 [1.26-2.08], P = 0.0001, respectively). Orotidine was also associated with increased odds of CHD in the validation set (OR 1.39 [1.11-1.75]), while 2-piperidinone did not replicate. Furthermore, orotidine, being inversely associated with GFR, mediated 60% of the effects of declining renal function on CVD risk. Addition of orotidine to established clinical predictors improved (P < 0.05) C statistics and discrimination indices for CVD risk (ΔAUC 0.053, rIDI 0.48, NRI 0.42) compared with the clinical predictors alone. Through a robust metabolomics approach, with independent validation, we have discovered serum orotidine as a novel biomarker of increased odds of CVD in T2D, independent of renal function. Additionally, orotidine may be a biological mediator of the increased CVD risk associated with poor kidney function and may help improve CVD risk prediction in T2D.

Cardiovascular risk associated with co-morbid insomnia and sleep apnoea (COMISA) in type 2 diabetics.

ObjectiveIn the general population, co-morbid insomnia and sleep apnoea (COMISA) is associated with higher risk of cardiovascular diseases (CVD). However, despite a high prevalence of COMISA in type 2 diabetics, no study has investigated its potential implication in the negative cardiovascular outcome of this particular subpopulation. The aim of this study was therefore to examine the risk of CVD associated with COMISA in type 2 diabetics.MethodsData from 471 type 2 diabetics recruited from the clinical database of the Erasme Hospital sleep laboratory were analysed. Only type 2 diabetics with SCORE index ≥5% were included in the group at high risk of CVD. Logistic regression analyses were conducted to examine the risk of CVD associated with COMISA in type 2 diabetics.ResultsA high risk of CVD was present in 32.9% of type 2 diabetics. After adjustment for the main confounding factors associated with cardiovascular risk, multivariate logistic regression analysis revealed that unlike obstructive sleep apnoea syndrome or insomnia alone, only COMISA was associated with higher risk of CVD in type 2 diabetics.DiscussionIn our study, we have demonstrated that unlike its components alone, only COMISA was associated with higher risk of CVD in type 2 diabetics, which highlights the importance of the central role played by the negative synergistic effect of COMISA on the cardiovascular outcome in this particular subpopulation. Thus, given these elements, more systematic research and adequate therapeutic management of COMISA seem to be necessary to allow better cardiovascular prevention in type 2 diabetics.

Profile of cardiovascular disease risk in type 2 diabetes mellitus patients receiving statin therapy: A cross-sectional study

BackgroundCardiovascular disease is still the number 1 cause of death globally. Meanwhile, type 2 diabetes mellitus (T2DM) is a risk factor for atherosclerosis vascular disease (ASCVD), so an assessment using Framingham Risk Score (FRS) is needed to predict the risk of ASCVD in the future. ObjectiveAnalyzing the risk factor of ASCVD using the Framingham Risk Score (FRS) in T2DM patients. MethodsThis study was conducted from July 2020 to July 2021, which the participants were measured for FRS including age, gender, current smoking, diabetes, blood pressure (systolic), high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), and ASCVD risk score. The analysis employed multiple linear tests and ANOVA tests with p < 0.05. ResultsSeveral ASCVD risk factors in T2DM patients were found, including gender (t = 6.015; p < 0.001), age (t = 6.901; p < 0.001), HDL level (t = 2.287; p = 0.024), CT level (t = 5.273; p < 0.001), blood pressure (t = 5.850; p < 0.001), and current smoking (t = 2.638; p = 0.009). The results of analysis between ASCVD risk factor and level of ASCVD risk obtained a significant association (F = 36,642; p < 0.001). ConclusionRisk factors of ASCVD in T2DM patients such as gender, age, HDL level, CT level, blood pressure, and current smoking.

Genetic risk score constructed from common genetic variants is associated with cardiovascular disease risk in type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (T2DM) experience a two-fold increased risk of cardiovascular diseases. Genome-wide association studies (GWAS) have identified T2DM susceptibility genetic variants. Interestingly, the genetic variants associated with cardiovascular disease risk in T2DM Han Chinese remain to be elucidated. The present study aimed to investigate the genetic variants associated with cardiovascular disease risk in T2DM. We performed bootstrapping, GWAS and an investigation of genetic variants associated with cardiovascular disease risk in a discovery T2DM cohort and in a replication cohort. The discovery cohort included 326 cardiovascular disease patients and 1209 noncardiovascular disease patients. The replication cohort included 68 cardiovascular disease patients and 317 noncardiovascular disease patients. The main outcome measures were genetic variants for genetic risk score (GRS) in cardiovascular disease risk in T2DM. In total, 35 genetic variants were associated with cardiovascular disease risk. A GRS was generated by combining risk alleles from these variants weighted by their estimated effect sizes (log odds ratio [OR]). T2DM patients with weighted GRS ≥ 12.63 had an approximately 15-fold increase in cardiovascular disease risk (odds ratio = 15.67, 95% confidence interval [CI] = 10.33-24.00) compared to patients with weighted GRS < 10.39. With the addition of weighted GRS, receiver-operating characteristic curves showed that area under the curve with conventional risk factors was improved from 0.719 (95% CI = 0.689-0.750) to 0.888 (95% CI = 0.866-0.910). These 35 genetic variants are associated with cardiovascular disease risk in T2DM, alone and cumulatively. T2DM patients with higher levels of weighted genetic risk score have higher cardiovascular disease risks.

Quantitative measure of asymptomatic cardiovascular disease risk in Type 2 diabetes: Evidence from Indian outpatient setting

BackgroundThe cardiovascular (CV) risk of patients with Type 2 diabetes (T2D) of Indo-Asian descent has never been objectively assessed, although it is documented that they have a higher prevalence of CV disease (CVD). AimsTo identify groups of Indian patients with asymptomatic T2D who are at high risk of CVD as per the QRISK calculator. MethodAfter an adequate power calculation, a nation-wide study of patients with asymptomatic T2D was conducted. The QRISK3 scores of these patients were used to derive a 10-year risk of CV events. High CVD risk was defined as ≥20% risk of CV event in 10 years. ResultsFor a total of 1538 patients across 154 outpatient departments, the QRISK3 scores were collated. Median 10-year CVD risk was 22.2%. Mean 10-year CVD risk was 28.4% (standard deviation 22.1%), representing a 5.7-fold increase vs. controls (i.e., matched healthy adults). Absolute CVD risk increased linearly with age. Over 50% of T2D males aged above 45 years had a high (>20%) CVD risk. Women aged more than 55 years had a high risk of CVD. More than 50% of patients with a T2D duration of more than 5 years had a high risk of CVD as per the QRISK3 calculator.

P2483Differential effects of novel antidiabetics on arterial stiffness in patients with type 2 diabetes mellitus

Abstract Background Arterial stiffness flags increased cardiovascular disease risk in type 2 diabetes mellitus (T2DM) patients. There is limited data on how novel anti-diabetic agents affect arterial stiffness. Purpose To investigate the effects of novel anti-diabetic agents on arterial stiffness in T2DM patients. Patients and methods We enrolled 64 consecutive patients under stable antidiabetic therapy who did not achieve therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; dipeptidyl peptidase-4 inhibitor (DPP4i, n=14), glucagon like peptide-1 receptor agonist (GLP1RA, n=21), sodium/glucose cotransporter-2 inhibitor (SGLT2i, n=21) or long-acting insulin (n=8). Glycosylated hemoglobin (HbA1c) as well as carotid-femoral pulse wave velocity (PWV) and augmentation index (Alx) were measured (as indices of arterial stiffness) were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups in traditional risk factors, or baseline HbA1c, PWV and Alx levels (p=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up (for DPP4i: 7.4±0.2% vs 6.7±0.2%, for GLP1RA: 8.3±0.2% vs 6.9±0.1%, for SGLT2i: 7.5±0.1% vs 6.7±0.1% and for insulin 9.8±0.5% vs 7.7±0.4%, p&lt;0.001 for all). PWV decreased from 10.0±0.84 to 9.1±0.43 m/sec (p=0.092) in the DPP4i group, from 11.7±0.72 to 10.2±0.74 m/sec (p&lt;0.001) in the GLP1RA group, from 1.3±0.54 to 9.6±0.59 m/sec (p=0.001) in the SGLT2i group and from 11.6±1.04 to 11.1±1.02 m/sec (p=0.219) in the insulin group. Alx was also decreased from 34.2±1.89 to 31.5±2.17% (p=0.023) in the DPP4i group, from 29.1±1.52 to 25.6±2.09% (p&lt;0.001) in the GLP1RA group, from 29.9±1.44 to 24.2±1.48% (p&lt;0.001) in SGLT2i group, and from 28.2±2.33 to 26.2±1.64% (p=0.153) in insulin group. Conclusions These preliminary data provide evidence that treatment intensification -particularly with GLP1RA, and SGLT2i- benefits vascular properties, a finding which could partly explain the positive findings of recent randomized clinical trails in this field. Acknowledgement/Funding None

Immune Complexes and the Risk of CVD in Type 1 Diabetes.

We investigated whether the composition of modified forms of LDL in circulating immune complexes (LDL-ICs) was associated with cardiovascular disease (CVD) outcomes, including any CVD, major adverse cardiac and cerebrovascular events (MACCE), myocardial infarction (MI), and coronary artery disease, in type 1 diabetes (T1D). Our results demonstrate that the baseline levels of oxidized LDL (oxLDL), MDA-modified LDL (MDA-LDL), and advanced glycosylation-modified LDL (AGE-LDL) in circulating ICs were associated with the four CVD outcomes in unadjusted models, and adjustment by age and mean HbA1c only resulted in minimal reduction of these associations. After adjustments were made for other cardiovascular risk factors, particularly LDL cholesterol, oxLDL-IC and MDA-LDL-IC remained independently associated with the risk of CVD, and oxLDL-IC was independently associated with the risk of MACCE and MI. In the majority of cases, the baseline levels of modified LDL-IC (measured many years before the occurrence of any CVD event) were associated with the risk of CVD over a 25-year period even after adjustment for other risk factors (including LDL cholesterol). Therefore, modified LDL biomarkers may help identify patients with T1D at high risk for MACCE and CVD events very early in the evolution of the disease, before other signals of disease are apparent.

439-P: Assessing the Relationship between Asthma and Cardiovascular Disease Risk in Type 2 Diabetes Using Revised Risk Estimates

Purpose: Type 2 diabetes (T2D) and asthma are independent risk factors for cardiovascular disease (CVD), but CVD risk is reduced in individuals with T2D + Asthma compared to those with T2D alone when using the 2013 ACC/AHA CVD Risk Score. Because these guidelines may overestimate CVD risk by up to 20%, revised risk equations have recently been proposed. We hypothesize that using these revised risk score equations will not alter the relationship between asthma, T2D, and CVD Risk Score. Methods: Data were extracted from Electronic Health Record using ICD-9/10 codes. Patients with both T2D and Asthma (n=603) were identified and compared to a group of matched patients with T2D Alone (n=603). Estimates of the 10-year risk of a major CVD event were derived using generalized linear models. Results: As shown in the Table, 10 year CVD risk was significantly increased in the T2D Alone group compared to the T2D + Asthma group using both the 2013 ACC/AHA CVD Risk Score estimates and the revised 2018 CVD Risk Score estimates. CVD risk is approximately 2% higher in both groups using the newer estimates. Conclusions: In this matched, case controlled retrospective study, Asthma conferred a protective effect against CVD risk over the next 10 years for patients with co-morbid T2D. This result was initially demonstrated with the 2013 ACC/AHA Risk Score estimates and confirmed with the 2018 revised Risk Score estimates. Disclosure M.R. Burge: None. K.L. Aldrete: None. M. Ehrhart: None. C. Murray-Krezan: None. Funding National Institutes of Health

Novel concept of non-HDL cholesterol - A predictor of cardiovascular disease risk in type II diabetes mellitus patients

Novel concept of non-HDL cholesterol - A predictor of cardiovascular disease risk in type II diabetes mellitus patients

Oxidative Stress and Cardiovascular Risk in Type 1 Diabetes Mellitus: Insights From the DCCT/EDIC Study

BackgroundHyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus.Methods and ResultsA random subcohort of 349 participants was selected from the DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT, and 1 to 2 years post‐DCCT (EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F2α. Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F2α, an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P<0.003; −5.3% risk for 10% higher 2,3 dinor‐8 iso prostaglandin F2α, P=0.0092). In contrast, the oxidative markers myeloperoxidase and F2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments.ConclusionsHeightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00360815 and NCT00360893.

Bone markers and cardiovascular risk in type 2 diabetes patients

BackgroundVascular calcifications are associated with a three- to fourfold increased risk of cardiovascular disease (CVD) and are highly prevalent in type 2 diabetes patients. Emerging evidence indicates that vascular calcification is a process of active bone formation regulated by stimulators and inhibitors of calcification. Therefore, this study aimed to evaluate whether six bone markers are associated with CVD risk in patients with type 2 diabetes.MethodsWe used data of a case-cohort study, nested in the EPIC-NL cohort, comprising 134 CVD cases and a random subcohort of 218 participants, all with type 2 diabetes at baseline. Six bone markers (osteocalcin, osteopontin, osteonectin, osteoprotegerin, alkaline phosphatase and sclerostin) were measured in baseline plasma samples with multiplex assays and information on CVD events was obtained. The association of bone makers with CVD risk was evaluated using Cox proportional hazard analyses.ResultsHigher concentrations of plasma osteopontin were associated (ptrend < 0.01) with an increased CVD risk with a hazard ratio of 2.00 (95%-CI 1.20–3.35) for the highest versus the lowest quartile in a multivariable adjusted model. The other bone markers were not associated with CVD risk.ConclusionsHigher osteopontin concentrations were associated with an increased CVD risk in type 2 diabetes patients. No consistent associations were found for the other five bone markers and risk of CVD in type 2 diabetes patients.

A randomized intervention study to evaluate the effect of calcitriol therapy on the renin-angiotensin system in diabetes.

Background:Prior studies suggest that vitamin D therapy may decrease cardiovascular disease risk in type 2 diabetes (T2DM) by lowering renin-angiotensin system (RAS) activity. However, randomized human intervention studies to evaluate the effect of vitamin D receptor (VDR) agonists on RAS activity are lacking.Objective:The objective of this article is to investigate the effect of direct VDR activation with calcitriol on circulating RAS activity and vascular hemodynamics in T2DM.Methods:A randomized, double-blinded, and placebo-controlled study wherein 18 participants with well-controlled T2DM without chronic kidney disease (CKD) were administered calcitriol or placebo for three weeks was conducted. Outcome measures included plasma renin activity (PRA), serum and urinary aldosterone, mean arterial pressure (MAP) before and after an infusion of angiotensin II, and renal plasma flow (RPF) via para-aminohippurate clearance.Results:Despite an increase in 1,25(OH)2D with calcitriol administration (45.4 to 61.8 pg/ml, p = 0.03) and no change with placebo, there were no significant differences in PRA, serum or urinary aldosterone, baseline and angiotensin II-stimulated MAP, or basal and angiotensin II-stimulated RPF between interventions.Conclusion:In this randomized and placebo-controlled study in participants with T2DM without CKD, calcitriol therapy to raise 1,25(OH)2D levels, when compared with placebo, did not significantly change circulating RAS activity or vascular hemodynamics.