Cardiovascular Disease Group Research Articles

Serum Tenascin-C and Alarin Levels Are Associated with Cardiovascular Diseases in Type 2 Diabetes Mellitus.

Background Tenascin-C (TNC), an extracellular matrix glycoprotein, is elevated in inflammatory and cardiovascular pathologies, whereas alarin, a novel orexigenic peptide, participates in insulin resistance and glycometabolism. The roles of these molecules in individuals with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), clinical conditions associating with metabolic disorders, and chronic inflammation, remain controversial. Our study aimed at determining the potential role of TNC and alarin in CVD adult patients with T2DM. Methods This was a cross-sectional study. Basic and clinical information for 250 patients with T2DM were analyzed. Based on their cardiovascular disease status, participants were assigned into the CVD and non-CVD groups. Serum TNC and alarin levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results Serum TNC and alarin concentrations in the CVD group were significantly higher than those of the non-CVD group. Moreover, serum TNC levels were positively correlated with age, waist circumference, and waist-hip ratio; however, they were negatively correlated with TC, LDL-C, and eGFR levels. Alarin levels were positively correlated with BMI, waist circumference, and hip circumference. In logistic regression models, TNC and alarin were also established to be independent determinants for CVD in T2DM patients and their increases were associated with CVD severity. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) values for TNC and alarin were 0.68 and 0.67, respectively. TNC and alarin were good predictors of CVD occurrence. When the cutoff value for TNC was 134.05 pg/mL, its sensitivity was 69.47% while its specificity was 61.29%. When the cutoff value for alarin was 142.69 pg/mL, sensitivity and specificity were 38.95% and 90.97%, respectively. Conclusion Elevated TNC and alarin levels are independently associated with the occurrence and severity of CVD in T2DM individuals. Therefore, these two biomarkers are potential diagnostic and prognostic indicators for CVD in diabetics.

The Economic Impact of Optimizing a COVID-19 Management Protocol in Pre-Existing Cardiovascular Disease Patients

This study answers the question of whether the health care costs of managing COVID-19 in preexisting cardiovascular diseases (CVD) patients increased or decreased as a consequence of evidence-based efforts to optimize the initial COVID-19 management protocol in a CVD group of patients. A retrospective cohort study was conducted in preexisting CVD patients with COVID-19 in Hamad Medical Corporation, Qatar. From the health care perspective, only direct medical costs were considered, adjusted to their 2021 values. The impact of revising the protocol was a reduction in the overall costs in non-critically ill patients from QAR15,447 (USD 4243) to QAR4337 (USD 1191) per patient, with an economic benefit of QAR11,110 (USD 3051). In the critically ill patients, however, the cost increased from QAR202,094 (USD 55,505) to QAR292,856 (USD 80,433) per patient, with added cost of QAR90,762 (USD 24,928). Overall, regardless of critical care status, the optimization of the initial COVID-19 protocols in patients with preexisting CVD did not reduce overall health care costs, but increased it by QAR80,529 (USD 22,117) per patient.

Lipidomic risk scores are independent of polygenic risk scores and can predict incidence of diabetes and cardiovascular disease in a large population cohort.

Type 2 diabetes (T2D) and cardiovascular disease (CVD) represent significant disease burdens for most societies and susceptibility to these diseases is strongly influenced by diet and lifestyle. Physiological changes associated with T2D or CVD, such has high blood pressure and cholesterol and glucose levels in the blood, are often apparent prior to disease incidence. Here we integrated genetics, lipidomics, and standard clinical diagnostics to assess future T2D and CVD risk for 4,067 participants from a large prospective population-based cohort, the Malmö Diet and Cancer-Cardiovascular Cohort. By training Ridge regression-based machine learning models on the measurements obtained at baseline when the individuals were healthy, we computed several risk scores for T2D and CVD incidence during up to 23 years of follow-up. We used these scores to stratify the participants into risk groups and found that a lipidomics risk score based on the quantification of 184 plasma lipid concentrations resulted in a 168% and 84% increase of the incidence rate in the highest risk group and a 77% and 53% decrease of the incidence rate in lowest risk group for T2D and CVD, respectively, compared to the average case rates of 13.8% and 22.0%. Notably, lipidomic risk correlated only marginally with polygenic risk, indicating that the lipidome and genetic variants may constitute largely independent risk factors for T2D and CVD. Risk stratification was further improved by adding standard clinical variables to the model, resulting in a case rate of 51.0% and 53.3% in the highest risk group for T2D and CVD, respectively. The participants in the highest risk group showed significantly altered lipidome compositions affecting 167 and 157 lipid species for T2D and CVD, respectively. Our results demonstrated that a subset of individuals at high risk for developing T2D or CVD can be identified years before disease incidence. The lipidomic risk, which is derived from only one single mass spectrometric measurement that is cheap and fast, is informative and could extend traditional risk assessment based on clinical assays.

Impact of Physical Activity on All-Cause Mortality According to Specific Cardiovascular Disease.

BackgroundPatients with cardiovascular disease (CVD) tend to have higher mortality rates and reduced physical activity (PA). We aimed to evaluate the effect of PA on mortality in older adults with specific CVD.MethodsWe enrolled 68,223 participants (n = 23,871 with CVD, n = 44,352 without CVD) aged ≥65 years with available physical activity data between 2005 and 2012 from the Korean National Health Insurance Service of Korea-Senior database. CVD was defined as a history of ischemic stroke, transient ischemic attack, heart failure, myocardial infarction, and peripheral artery disease.ResultsPatients with CVD were older than those without CVD. Compared with the sedentary group, the physically active groups with and without CVD had a lower incidence and risk of all-cause death during a median follow up period of 42 (interquartile range 30–51) months. A 500 metabolic equivalent task-min/week increase in PA resulted in an 11% and 16% reduction in the risk of mortality in the non-CVD and CVD groups, respectively. With regard to specific CVDs, the risk of mortality progressively reduced with increasing PA in patients with heart failure or myocardial infarction. However, the reduction reached a plateau in patients with stroke or peripheral artery disease, but was significantly greater in patients with stroke (20% vs. without stoke, 11%, Pint = 0.006) or heart failure (13% vs. without heart failure, 11%; Pint = 0.045)ConclusionsPA was associated with a reduced risk of all-cause mortality in older adults with and without CVD. The benefits of PA in patients with CVD, especially patients with stroke or heart failure, were greater than those without.

Racial Differences in Nontraditional Risk Factors Associated with Cardiovascular Conditions in Pregnancy Among U.S. Women Veterans.

Background: Pregnancy-related cardiovascular (CV) conditions are important predictors of future cardiovascular disease (CVD). Nontraditional factors, such as depression and chronic stress, have been associated with CVD, but their role in pregnancy-related CVD conditions (pCVD) remains unknown. To determine the association between nontraditional factors and CV conditions in pregnancy, and to explore if this risk varies by race. Methods: Using data from a prospective study of pregnant women within the veterans affairs health system (COMFORT study), we described the prevalence of nontraditional factors (e.g., depression, post-traumatic stress disorder [PTSD], chronic stress) and used logistic regression to determine the association between nontraditional factors and pregnancy-related CV conditions (pre-eclampsia/eclampsia, gestational hypertension, gestation diabetes, or preterm delivery). Analyses were then stratified by race. Results: Among 706 enrollees, 26% had pregnancy-related CV conditions. These women had significantly higher rates of depression (62% vs. 45%, p < 0.01), anxiety (50% vs. 37%, p = 0.01), PTSD (44% vs. 29%, p < 0.01), and high stress levels before pregnancy (22% vs. 16%, p = 0.05) compared with women with normal pregnancies. Overall, these factors were not associated with increased adjusted odds of pCVD. Overall, Black women had disproportionately higher rates of prepregnancy hypertension compared with White women (22% vs. 6%, p < 0.01). Conclusions: Women Veterans with pCVD are a high-risk group for future CVD, with disproportionately high rates of depression, anxiety, PTSD, and chronic stress. Racial disparities exist in pregnancy-related CV risk factors, which may further compound existing racial disparities in CVD among women Veterans.

The Linkage Between Bone Densitometry and Cardiovascular Disease.

Dual-energy X-ray absorptiometry (DXA) has been traditionally used to assess body composition covering bone, fat and muscle content. Cardiovascular disease (CVD) has deleterious effects on bone health and fat composition. Therefore, early detection of bone health, fat and muscle composition would help to anticipate a proper diagnosis and treatment plan for CVD patients. In this study, we leveraged machine learning (ML)-based models to predict CVD using DXA, demonstrating that it can be considered an innovative approach for early detection of CVD. We leveraged state-of-the-art ML models to classify the CVD group from non-CVD group. The proposed logistic regression-based model achieved nearly 80% accuracy. Overall, the bone mineral density, fat content, muscle mass and bone surface area measurements were elevated in the CVD group compared to non-CVD group. Ablation study revealed a more successful discriminatory power of fat content and bone mineral density than muscle mass and bone areas. To the best of our knowledge, this work is the first ML model to reveal the association between DXA measurements and CVD in the Qatari population. We believe this study will open new avenues of introducing DXA in creating the diagnosis and treatment plan of cardiovascular diseases.

Association between peri-implantitis and cardiovascular diseases: A case-control study.

This study assesses the association between peri-implantitis and cardiovascular diseases (CVD). One hundred and twenty-eight patients with dental implants were recruited to evaluate the prevalence of peri-implantitis in patients with or without CVD (CVD group, n=82, control group, n=46, respectively). Diagnosis of peri-implantitis followed the 2017 World Workshop guidelines and the severity was defined as mild, moderate, and severe form when the radiographic bone loss (RBL) was<2, 2 to 4, and>4mm. Multivariable logistic regression was performed to test the association between two diseases. A trend of higher prevalence of peri-implantitis defined by detectable RBL beyond the physiologic bone remodeling was found in the CVD group (64.6%) when compared with the controls (56.5%). A significant higher prevalence (48.8%) of moderate to severe peri-implantitis was identified in CVD compared with controls(30.4%) with a significant crude association between moderate to severe peri-implantitis and CVD (odds ratio=2.18, 95% CI, 1.02 to 4.67; P=0.04). The CVD group had a trend of higher prevalence of deep pockets (≥7mm) and higher numbers of sites with bleeding on probing (>66%) when compared with controls (P> 0.05). However, after controlling for multiple confounders including age, hypertension, smoking, family history of heart attack, and periodontitis, the significant association was not found. CVD group had significantly higher prevalence of moderate to severe peri-implantitis (RBL ≥2mm). The association between the two diseases did not exist after controlling multiple confounders for CVD. Future studies with a larger sample size controlling for the patient- and implant-related confounders are needed to better understand the link between peri-implantitis and CVD.

Annual Increase of Acute Inpatients with Both Cancer and Cardiovascular Diseases in Japan 2011-2015: Analysis From National Database of Health Insurance Claims and Specific Health Checkups of Japan.

Patients with cancer were able to live longer due to improvements in cancer treatment. Additionally, cardiovascular disease (CVD) is the second leading cause of mortality in cancer survivors. However, epidemiological data on onco-CVD have not been sufficiently provided. We aimed to investigate the clinical characteristics of cancer in CVD patients using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). The NDB sampling dataset used in this study was randomly sampled 10% from the whole Diagnosis Procedure Combination (DPC) records from every January, April, July, and October from 2011 to 2015. The significance of the increase trend in the percentage of records in each disease group to the total number of all DPC records from 2011 to 2015 was checked with Chi-square test with a Bonferroni correction. The percentage of records in cancer with the CVD group to the total number of all DPC records significantly increased over time, and their average age also increased since 2011. Their proportion over 75 years was approximately 56 % in 2015. There was no difference in the cancer sites. However, the prevalence of heart failure dramatically elevated. We were able to assess the increase in cancer among CVD patients using DPC inpatient records obtained from the NDB. Both cardiologists and oncologists should be more aware of this phenomenon.

Investigation on the Prediction of Cardiovascular Events Based on Multi-Scale Time Irreversibility Analysis

Investigation of the risk factors associated with cardiovascular disease (CVD) plays an important part in the prevention and treatment of CVD. This study investigated whether alteration in the multi-scale time irreversibility of sleeping heart rate variability (HRV) was a risk factor for cardiovascular events. The D-value, based on analysis of multi-scale increments in HRV series, was used as the measurement of time irreversibility. Eighty-four subjects from an open-access database (i.e., the Sleep Heart Health Study) were included in this study. None of them had any CVD history at baseline; 42 subjects had cardiovascular events within 1 year after baseline polysomnography and were classed as the CVD group, and the other 42 subjects in the non-CVD group were age matched with those in the CVD group and had no cardiovascular events during the 15-year follow-up period. We compared D-values of sleeping HRV between the CVD and non-CVD groups and found that the D-values of the CVD group were significantly lower than those of the non-CVD group on all 10 scales, even after adjusting for gender and body mass index. Moreover, we investigated the performance of a machine learning model to classify CVD and non-CVD subjects. The model, which was fed with a feature space based on the D-values on 10 scales and trained by a random forest algorithm, achieved an accuracy of 80.8% and a positive prediction rate of 86.7%. These results suggest that the decreased time irreversibility of sleeping HRV is an independent predictor of cardiovascular events that could be used to assist the intelligent prediction of cardiovascular events.

Abstract 9094: Intensive Lifestyle Medicine for Primary &amp; Secondary Prevention for Cardiovascular Risk Reduction in Patients With Diabetes

Introduction: Cardiovascular disease (CVD) carries significant morbidity and mortality, especially for patients with diabetes. Intensive Cardiac rehabilitation (ICR) has proven benefits for patients with CVD through a high fiber low fat diet, peer support, exercise and stress reduction; which may help in diabetes management. However, outcomes of ICR in patients with diabetes with and without CVD are unknown. Hypothesis: ICR can improve outcomes in diabetic patients with or without CVD. Methods: We conducted a retrospective cohort study of 4793 diabetic patients who were offered ICR at 46 CR centers across USA from January 2016 to December 2020. Five ICR centers in Hawaii had patients enrolled with diabetes without any CVD as Hawaii is the only state in US which has approved ICR for diabetic patients without CVD for primary prevention. ICR sessions are 4-hours long, twice weekly for 9-weeks of lifestyle modification aiming at high fiber low fat diet, peer support, exercise and stress reduction. Diabetic patients were divided into two groups: CVD group (known CVD) - 3723 patients (78%) and Non-CVD group (without CVD) - 1070 patients (22%). Primary endpoints were change in HbA1C, LDL and BP. Secondary outcomes were change in BMI, triglycerides, cholesterol, HDL, dietary fat intake, dietary fiber intake, depression scores (CESD) and exercise minutes per week. We used t tests to compare variables pre and post ICR. Results: The mean age of patients was 66.5 ± 0.2 years, 43% were females and 44% were white. ICR completion rate &amp; number of ICR sessions was higher in Non-CVD group (Non-CVD: 60.11 ± 27.16 vs. CVD: 55.67 ± 33.15, p&lt;0.01). Primary (HBA1c, BP, LDL) and secondary outcomes improved in both groups Pre and Post ICR as shown in table. Conclusions: Significant improvement in diabetes &amp; ICR outcomes were achieved for both groups after completing ICR. Although long term outcomes are unknown, diabetic patients should continue to participate in ICR for further risk reduction.

Abstract 13655: DUSP-1 May Be a Key Regulator of NK Cell Function in Obesity Potentially Accelerating Cardiovascular Disease in African American Women

Background: Obesity disproportionately affects African American (AA) women and contributes to disparate cardiovascular disease (CVD) outcomes. Natural killer cells have been shown to be functionally impaired by obesity. However, underlying mechanisms regulating NK cell function in obesity are largely unknown. Therefore, we sought to elucidate potential signaling pathways involved in obesity-related NK cell function loss in AA women. Methods: All experiments were performed with freshly isolated naïve NK cells. NK cells were isolated from AA women (n=29; 15 BMI&lt;25, 14 BMI&gt;30). NK cell function was measured by flow cytometry by determining the ability of NK cells to degranulate towards K562 cells. NK cell gene expression profile was determined by RNA sequencing to identify important signaling pathways, which were verified using chemical pathway inhibitors. Publicly available datasets were analyzed to determine the importance of identified target genes. Results: NK cells isolated from AA women with obesity displayed diminished capacity to induce K562 cell death as determined by decreased degranulation (decreased surface CD107a expression and decreased intracellular IFNγ and TNFα expression). RNA sequencing analysis of NK cells isolated from lean vs AA women with obesity revealed 1645 significantly regulated genes with DUSP-1 being in the top 50 and displaying a 2.8-fold upregulation in AA women with obesity (p=0.0009). Furthermore, DUSP-1 gene expression was significantly correlated with BMI (R 2 =0.72, p=0.02). In vitro experiments revealed a DUSP-1 inhibitor to enhance NK cell function. Additionally, analysis of publicly available RNA sequencing dataset (GSE20129) in women revealed an increase of DUSP-1 mRNA expression in Black and Latinx women with CVD when compared to women without CVD group; this difference was not observed in White women. Conclusion: Our data demonstrate that NK cells are functionally impaired in NK cells isolated from AA women with obesity. We identified DUSP-1 as a crucial regulator of the observed NK cell dysfunction in obesity, which may be of particular importance in CVD development and progression in AA women, a population disproportionally affected by obesity and CVD.

Relationship Between Circulating Immune Complexes and Diabetes Mellitus in Cardiovascular Disease at Older Patients

BackgroundModifications in immunological function may play a role in both the pathogenesis of some types of diabetes as well as its associated complications. Oxidatively modified lipoproteins (LDL ox) and the composition of lipid fatty acids have the ability to induce an immune response that leads to the production of autoantibodies and therefore to the formation of immune complexes containing LDL in patients with type 2 diabetes, suggesting that it contributes to the development of cardiovascular disease (CVD). Objective: In the present study, we determinated oxidatively modified lipoproteins of the circulating immune complexes in two study groups of older patients (aged 71 ± 5 years): a group of patients with CVD (group I) and a group of patients with CVD and type 2 diabetes (group II). MethodsThe LDL content in circulating immune complexes was evaluated by measuring total cholesterol levels in polyethylene glycol (PEG 8000) precipitates (immune cholesterol). ResultsResults we obtained for the group II of patients, showed a significant increase for the cholesterol of circulating immune complexes, compared to the group I (20.06 ± 7.35 vs. 9.16 ± 5.81 µg cholesterol/ ml serum). Conclusion: Increased oxidative stress in diabetes may serve to reduce levels of endogenous antioxidants in LDL and thus contribute to an increased susceptibility to oxidation. Thus, circulating immune complexes containing modified LDL are highly proinflammatory contributing to the progression of CVD in type 2 diabetes, indicating that their quantification has a higher predictive value than the traditional risk markers that are currently used.

Association of ANGPTL3 polymorphisms with high-density lipoprotein cholesterol uptake capacity in patients with cardiovascular disease.

IntroductionPrevious studies have shown the importance of angiopoietin‐like 3 (ANGPTL3) as a modulator of lipid profiles. Cholesterol uptake capacity (CUC) is one means for assessing high‐density lipoprotein (HDL) functionality. This study for the first time has investigated the relationship between genetic ANGPTL3 polymorphism and CUC in patients with cardiovascular disease.MethodsFive hundred three subjects comprising 350 healthy subjects and 153 individuals who developed a cardiovascular disease (CVD) event during follow‐up were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. A modified CUC method was used to determine the CUC of serum samples. Applied amplification refractory mutation system PCR was performed for ANGPTL3 variants genotyping including: rs10789117, rs1748195, and rs11207997. Sanger sequencing was applied to confirm the genotypes.ResultsThe results showed that there was a significant relationship between the rs1748195 genotypes and HDL concentration in the CVD group (p = 0.02). Moreover, individuals with a GG genotype of the rs1748195 were associated with a lower risk of CVD (OR = 0.49, 95% CI = 0.24–0.98, p = 0.04) compared with CC genotype in the CUC ≤ 1.7 a.u subgroup. Moreover, the CT genotype of rs11207997 was associated with a lower risk of CVD (OR = 0.74, 95% CI = 0.41–1.3, p = 0.01) compared with CC genotype in CUC > 1.7 a.u subgroup.ConclusionThe results showed that the CT genotype of the rs11207997 variant was associated with a lower risk of incident CVD in patients with higher HDL functionality. As well, the rs1748195 gene variant may contribute to a reduced risk of CVD.

Anti-gout Medications and Risk of Cardiovascular Disease: A Nested Case-Control Study.

Introduction: Gout is the leading cause of inflammatory arthritis and is also correlated with multiple comorbidities, including cardiovascular disease (CVD), whose future risk can be lowered by urate-lowering therapy (ULT) in gout patients. It is, however, still not clear whether its effect is associated with the days of usage and the adherence rate of ULT.Methods: Data were collected from Taiwan's National Health Insurance Research Database. The study period was from 1999/1/1 to 2013/12/31. In addition, patients with newly diagnosed gout from 2000 to 2012 and usage of antigout preparations (allopurinol or benzbromarone) within half a year among age ≥20 years old were enrolled in the study. The outcome of interest is CVD. New diagnosis of CVD after half a year of diagnosis of gout was included in the CVD group. Moreover, conditional logistic regression was used to evaluate the odds ratio of CVD in relation to the days of usage and to the adherence rate of ULT after the adjustment for potentially confounding variables.Results: A total of 3,706 gout patients with and without CVD have been included in the final analysis after a 1:1 propensity score that matched for age, sex, comorbidities, aspirin, and statin. The days of usage of allopurinol was <180 days and benzbromarone, in its turn, presupposed a higher risk of CVD. The adherence rate of allopurinol and benzbromarone at ≥ 0.7 both have a lower CVD risk: allopurinol (adjusted OR: 0.66 95% CI: 0.46–0.96), benzbromarone (adjusted OR: 0.68 95% CI: 0.50–0.91). The subgroup analysis revealed an adherence rate of ≥0.7 of ULT with a lower CVD was only found to be present in males and at age <65. Furthermore, the correlations were more pronounced in the ischemic heart disease subgroup than in the cerebrovascular disease group.Conclusion: This study reveals that gout patients taking ULT (allopurinol and benzbromarone) with an adherence rate of ≥0.7 are at a lower risk of developing CVD, especially with a younger age (<65) and if they are male. On top of this, the benefit is more pronounced in ischemic heart disease. Despite further prospective trials needing to be warranted to confirm our findings, health care providers may, bearing these conclusions in mind, emphasize the importance of adherence to ULT in gout patients.

Insulin resistance and decreased spexin in Indian Patients with Type 2 Diabetes Mellitus.

Spexin is novel biomarker, which plays a potential role in glucose and lipid metabolisms. However, there was paucity of serum spexin levels in obesity and diabetes mellitus subjects. Hence the current study was aimed to find the relationship between the serum spexin levels in type 2 Diabetes mellitus (type 2 DM) with extrapolation of cardiovascular disease (CVD) risk. A cross-sectional study included 330 participants, subdivided as control (n=110), type 2 DM (n=110) and type 2 DM with CVD groups (n=110). HbA1c, insulin, lipid profile, spexin & leptin including blood pressure and body mass index were analyzed from all the participants. The serum spexin levels (ng/ml) were significantly decreased in type 2 DM (mean ± sd: 0.65 ± 0.03) and type 2 DM with CVD (0.48 ± 0.02) groups compared to the control (0.79 ± 0.03) group (p<0.001). The decreased spexin levels were observed in type 2 DM, and further more decreased in type 2 DM with CVD patients compared to controls indicating that spexin levels could be served as an early prediction of obesity-induced T2DM with CVD risk.

Subclinical Hypothyroidism as a Risk Factor for Cardiovascular Disease

Nowadays, more than 485 million people in the world suffer from cardiovascular diseases (CVD). According to large epidemiological studies, the group of CVD is the leading cause of death in the world. One of the neurohumoral mechanisms that appears to be a risk factor for CVD is thyroid dysfunction. In this regard, in recent years, more and more attention is paid to the study the influence of subclinical hypothyroidism on the occurrence and development of cardiovascular disorders. MeSH words: cardiovascular diseases, subclinical hypothyroidism

Prevalence trends of depression and anxiety symptoms in adults with cardiovascular diseases and diabetes 1995\u20132019: The HUNT studies, Norway

BackgroundSymptoms of depression and anxiety are common in adults with cardiovascular diseases (CVDs) and diabetes mellitus (DM). The literature on depression and anxiety in CVDs and DM populations is extensive; however, studies examining these relationships over time, directly compared to adults without these conditions, are still lacking. This study aimed to investigate trends in depression and anxiety symptom prevalence over more than 20 years in adults with CVDs and DM compared to the general population.MethodsWe used data from the population-based Trøndelag Health Study (HUNT), Norway, including adults (≥ 20 years) from three waves; the HUNT2 (1995–97; n = 65,228), HUNT3 (2006–08; n = 50,800) and HUNT4 (2017–19; n = 56,042). Depressive and anxiety symptom prevalence was measured independently by the Hospital Anxiety and Depressions scale (HADS) in sex-stratified samples. We analyzed associations of these common psychological symptoms with CVDs and DM over time using multi-level random-effects models, accounting for repeated measurements and individual variation.ResultsOverall, the CVDs groups reported higher levels of depression than those free of CVDs in all waves of the study. Further, depressive and anxiety symptom prevalence in adults with and without CVDs and DM declined from HUNT2 to HUNT4, whereas women reported more anxiety than men. Positive associations of depression and anxiety symptoms with CVDs and DM in HUNT2 declined over time. However, associations of CVDs with depression symptoms remained over time in men. Moreover, in women, DM was associated with increased depression symptom risk in HUNT2 and HUNT4.ConclusionsDepression and anxiety symptoms are frequent in adults with CVDs. Further, our time trend analysis indicates that anxiety and depression are differentially related to CVDs and DM and sex. This study highlights the importance of awareness and management of psychological symptoms in CVDs and DM populations.

MO453SERUM AND VASCULAR FIBROBLAST GROWTH FACTOR 23 (FGF23) ARE ASSOCIATED WITH VASCULAR CALCIFICATION

Abstract Background and Aims Mineral metabolism imbalances and inflammation are related to the development of vascular calcification (VC). Fibroblast growth factor-23 (FGF23) is the main regulator of phosphate homeostasis and various studies have shown the existence of an association between elevated levels of FGF23 and the appearance of cardiovascular disease (CVD). We conducted a case-control study to test the hypothesis that serum and vascular levels of FGF23 are associated with the presence of VC. In addition, we determined the influence of inflammation in these levels. Method One hundred and thirty-three patients diagnosed with clinical atherosclerotic disease undergoing elective vascular surgery, and 20 cadaveric organ donors with no medical history of CVD, were included in this study. Serum levels of intact FGF23 (iFGF23), together with tumor necrosis factor-alpha (TNFα), interleukin (IL)10, were determined by ELISA. Vascular fragments of aorta, carotid and femoral arteries were obtained for assaying the gene expression of FGF23, TNF, IL10 and RUNX2 by qPCR. Immunohistochemical procedures were employed to determine vascular protein levels of FGF23, TNFα and IL10. VC was diagnosed by imaging techniques and confirmed by histological procedures including von Kossa staining. Results Case group presented a higher prevalence of hypertension, hypercholesterolemia and reduced estimated glomerular filtration rate, with no differences regarding other parameters. Serum iFGF23 and TNFα/IL10 ratio were higher in the case group (P&amp;lt;0.01 and P&amp;lt;0.001, respectively). Vascular expression of FGF23 was detected in 58.6% of CVD patients vs 35% of donors, with mean expression levels significantly higher in the first group (P&amp;lt;0.01). Vascular expression of TNF/IL10 was also increased (P&amp;lt;0.001) in CVD patients. FGF23 immunoreactivity was detected in 84% of CVD patients and only in 35% of controls. Immunoreactivity for FGF23 and TNFα/IL10 ratio were significantly higher in CVD patients (P&amp;lt;0.001 and P&amp;lt;0.0001, respectively). Stratified analysis according to serum iFGF23 levels showed a higher prevalence of VC in the upper tertiles. Patients with VC presented increased levels of all the FGF23 variables including serum [1.5 (1.2-1.6) vs. 1.4 (0.9-1.5) pg/mL, P&amp;lt;0.01], vascular mRNA [26.1 (14.3-67.4) vs. 18.8 (8.8-312.9) log AU, P&amp;lt;0.01] and vascular immunoreactivity [4.6 (3.8-4.9) vs. 3.7 (3.1-4.1) log µm2, P&amp;lt;0.05]. Moreover, FGF23 immunoreactivity was detected in 92.3% of fragments with VC and only in 53.6% of those without VC. Serum TNFα/IL10 and RUNX2 mRNA levels were also higher in this group (P&amp;lt;0.01 for both). Correlation analysis showed associations of serum iFGF23 with serum TNFα (r=0.375, P&amp;lt;0.001), neutrophil/lymphocyte (r=0.142, P&amp;lt;0.05), vascular RUNX2 mRNA (r=0.55, P&amp;lt;0.05), and vascular FGF23 immunoreactivity (r=0.281, P&amp;lt;0.05) in the CVD group. Vascular FGF23 expression correlated with RUNX2 mRNA (r=0.315, P&amp;lt;0.05) and FGF23 immunoreactivity (r=0.254, P&amp;lt;0.05). Multiple regression analysis showed that iFGF23 levels were determined by UAE, HDL, FGe, calcium and TNFα levels (adjusted R2= 0.473, P&amp;lt;0.0001) and that vascular FGF23 mRNA expression was determined by TNFα, PCR, glucose and age (adjusted R2= 0.795, P&amp;lt;0.0001). Multivariate logistic regression, with VC as dependent variable, showed that both iFGF23 and vascular mRNA constitute independent risk factors for the existence of VC [OR (95% CI): 1.05 and 1.12, P&amp;lt;0.05 for both]. Conclusion Patients with atherosclerosis and VC present significantly higher serum concentrations of FGF23, as well as higher immunoreactivity and gene expression levels in the vascular wall compared to patients without VC. Moreover, both serum and vascular mRNA levels of FGF23 are associated with the inflammatory status. Whether the increase in systemic and vascular FGF23 can directly promote or favor the calcifying process in the vascular bed is currently an issue under discussion.

MO037EPIGENETIC REGULATION OF KLOTHO IN PERIPHERAL BLOOD CIRCULATING CELLS IS ASSOCIATED CELLS IS ASSOCIATED WITH SOLUBLE PROTEIN SERUM IN CARDIOVASCULAR DISEASE

Abstract Background and Aims The antiaging factor α-Klotho (KL) has been related to cardiovascular diseases (CVD), including coronary artery disease, heart failure and peripheral arterial disease. The soluble form of this protein (sKL), which is mainly produced by the kidneys, have demonstrated to display different protective effects on the cardiovascular system, e.g., prevention of vascular calcification, oxidative stress, or cardiac fibrosis. Likewise, different clinical studies have pointed out that CVD is a state of sKL deficiency, even when the renal function is still preserved. It has been demonstrated that peripheral blood circulating cells (PBCCs) also express KL, but little is known about its expression profile during CVD. The aim of this work is to determinate if the expression of KL gene and its promoter methylation in PBCCs are correlated with serum levels of the soluble protein, and if there exist any association with the underlying inflammatory process that occurs during CVD. Method Forty-four patients diagnosed with clinical atherosclerotic vascular disease (case group) and 15 subjects without CVD background (control group) were included in the study. Whole blood and serum samples were obtained from all participants. We performed gene expression analysis for KL expression in PBCCs by qPCR, as well as for DNMT1 and DNMT3A (members of the DNA-methyltransferases family), TNF, IL10 and NFKB1 (inflammatory parameters). We assessed the degree of methylation of the KL gene promoter in these cells by bisulfite sequencing. Furthermore, we determined circulating levels of sKL, TNFα and IL10 by ELISA immunoassay in serum samples of both groups. Results Results showed a lower expression of KL gene in PBCCs of patients with CVD compared to controls (45% reduction, P&amp;lt;0.001), which was accompanied by a higher degree of methylation of its promoter (36.7±6.3% vs. 15.9±4.8%, P&amp;lt;0.05). The case group also presented significantly higher levels of DNMT1 and DNMT3A transcripts in these cells (P&amp;lt;0.0001 for both), as well as higher values of proinflammatory parameters (gene expression of TNF and NFKB1, and TNF/IL10 ratio; P&amp;lt;0.001 for all of them). Serum levels of sKL were decreased in the CVD group compared to controls (a reduction of 57.5%, P&amp;lt;0.0001). KL expression in PBCCs correlated directly with systemic levels of sKL (r=0.20, P&amp;lt;0.05), but inversely with expression of DNMT1 (r=-0.33, P&amp;lt;0.01) and inflammatory parameters (r=-0.37, P&amp;lt;0.01 for NFKB1 expression; r=-0.38, P&amp;lt;0.01 for TNF/IL10 expression ratio; and r=-0.39, P&amp;lt;0.01 for serum TNFα/IL10 ratio). No significant associations were found between inflammatory markers and methylation degree of KL gene promoter. Conclusion These results indicate an association between epigenetic regulation of KL gene in PBCC and systemic levels of the soluble protein in CVD, which could be influenced by the proinflammatory state present in these disorders.

Machine Learning-Based Cardiovascular Disease Prediction Model: A Cohort Study on the Korean National Health Insurance Service Health Screening Database.

Background: This study proposes a cardiovascular diseases (CVD) prediction model using machine learning (ML) algorithms based on the National Health Insurance Service-Health Screening datasets. Methods: We extracted 4699 patients aged over 45 as the CVD group, diagnosed according to the international classification of diseases system (I20–I25). In addition, 4699 random subjects without CVD diagnosis were enrolled as a non-CVD group. Both groups were matched by age and gender. Various ML algorithms were applied to perform CVD prediction; then, the performances of all the prediction models were compared. Results: The extreme gradient boosting, gradient boosting, and random forest algorithms exhibited the best average prediction accuracy (area under receiver operating characteristic curve (AUROC): 0.812, 0.812, and 0.811, respectively) among all algorithms validated in this study. Based on AUROC, the ML algorithms improved the CVD prediction performance, compared to previously proposed prediction models. Preexisting CVD history was the most important factor contributing to the accuracy of the prediction model, followed by total cholesterol, low-density lipoprotein cholesterol, waist-height ratio, and body mass index. Conclusions: Our results indicate that the proposed health screening dataset-based CVD prediction model using ML algorithms is readily applicable, produces validated results and outperforms the previous CVD prediction models.