Development Of Cardiovascular Disease Research Articles

A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease.

Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption. Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease,ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.

Bridging the Gap: The Need to Implement Dietary Guidance to Address Cardiovascular Health.

Cardiovascular disease (CVD) is the leading cause of death in the U.S. and globally. Research demonstrates that diet is a leading contributor to the development of CVD, its prevention and management, and the overall promotion of cardiovascular health. This article describes the current state of the evidence, including research on the DASH and Mediterranean diets to promote cardiovascular health and prevent CVD. The article suggests approaches to implement evidence-based diets and federal dietary guidance to promote the adoption and integration of these interventions in both community and clinical settings. It highlights the current U.S. federal interest in "Food is Medicine" and its importance in addressing diet-related chronic diseases and promoting cardiovascular health.

Neuroimmune crosstalk : How mental stress fuels vascular inflammation.

Cardiovascular diseases are the leading cause of death worldwide. Pathophysiologically, metabolic and inflammatory processes contribute substantially to the development and progression of cardiovascular diseases. Over the past decade, the role of disease-propagating inflammatory processes has been strengthened and reframed, leading to trials testing anti-inflammatory drugs for the treatment of atherosclerosis and its complications. Despite these achievements, further research in both pre-clinical and clinical studies is warranted to explore new targets, to better identify responders, and to refine therapy strategies to combat inflammation in human disease. Environmental disturbances, so-called lifestyle-associated cardiovascular risk factors, greatly alter the immune system in general and leukocytes in particular, thus affecting the progression of atherosclerosis. Epidemiological studies have shown that exposure to mental stress can be closely linked to the occurrence of cardiovascular disease. Here, we describe how acute and chronic mental stress alter the immune system via neuroimmune interactions, thereby modifying vascular inflammation. In addition, we identify gaps that still need to be addressed in the future.

Endothelial Protection by Sodium-Glucose Cotransporter 2 Inhibitors: A Literature Review of In Vitro and In Vivo Studies.

Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on the endothelium. In this review, we summarize the current knowledge on the direct in vitro effects of SGLT2is on endothelial cells, as well as the systematic observations in preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and endothelial cell survival and proliferation. Both in vitro and in vivo studies suggest that SGLT2is share a class effect on attenuating reactive oxygen species (ROS) and on enhancing the NO bioavailability by increasing endothelial nitric oxide synthase activity and by reducing NO scavenging by ROS. Moreover, SGLT2is significantly suppress inflammation by preventing endothelial expression of adhesion receptors and pro-inflammatory chemokines in vivo, indicating another class effect for endothelial protection. However, in vitro studies have not consistently shown regulation of adhesion molecule expression by SGLT2is. While SGLT2is improve endothelial cell survival under cell death-inducing stimuli, their impact on angiogenesis remains uncertain. Further experimental studies are required to accurately determine the interplay among these mechanisms in various cardiovascular complications, including heart failure and acute myocardial infarction.

Association between augmented levels of the gut pro-hormone Proneurotensin and subclinical vascular damage

Elevated levels of the gut pro-hormone Proneurotensin (proNT) have been found to predict development of cardiovascular disease. However, it is still unknown whether higher proNT levels are associated with subclinical vascular damage. Herein, we investigated the relationship between higher proNT concentrations and augmented pulse pressure (PP) and carotid intima-media thickness (cIMT), indicators of increased arterial stiffness and subclinical atherosclerosis, respectively. Clinical characteristics, PP and cIMT were evaluated in 154 non-diabetic individuals stratified into tertiles according to fasting serum proNT concentrations. We found that, subjects with higher proNT levels exhibited a worse lipid profile and insulin sensitivity, increased C-reactive protein levels, along with higher values of PP and cIMT as compared to the lowest proNT tertile. Prevalence of elevated PP (≥ 60 mmHg) and subclinical carotid atherosclerosis (IMT > 0.9 mm) was increased in the highest tertile of proNT. In a logistic regression analysis adjusted for several confounders, subjects with higher proNT levels displayed a fivefold raised risk of having elevated PP values (OR 5.36; 95%CI 1.04–27.28; P = 0.05) and early carotid atherosclerosis (OR 4.81; 95%CI 1.39–16.57; P = 0.01) as compared to the lowest proNT tertile. In conclusion, higher circulating levels of proNT are a biomarker of subclinical vascular damage independent of other atherosclerotic risk factors.

Differing genetic variants associated with liver fat and their contrasting relationships with cardiovascular diseases and cancer

The underlying mechanisms for the link between steatotic liver disease and cardiovascular and cancer outcomes are poorly understood. We aimed to use MRI-derived measures of liver fat and genetics to investigate causal mechanisms that link higher liver fat to various health outcomes. We conducted a genome-wide association study on 37,358 UK Biobank participants to identify genetic variants associated with liver fat measured from MRI scans. We used Mendelian randomization approach to investigate the causal effect of liver fat on health outcomes independent of BMI, alcohol consumption and lipids using data from published GWAS and FinnGen. We identified 13 genetic variants associated with liver fat that showed differing risks to health outcomes. Genetic variants associated with impaired hepatic triglyceride export showed liver fat-increasing alleles to be correlated with a reduced risk of coronary artery disease and myocardial infarction but an elevated risk of type 2 diabetes; and variants associated with enhanced de novo lipogenesis showed liver fat-increasing alleles to be linked to a higher risk of myocardial infarction and coronary artery disease. Genetically higher liver fat content increased the risk of non-alcohol liver cirrhosis, hepatocellular and Intrahepatic bile ducts and gallbladder cancers, exhibiting a dose-dependent relationship, irrespective of the mechanism. This study provides fresh insight into the heterogeneous effect of liver fat on health outcomes. It challenges the notion that liver fat per se is an independent risk factor for cardiovascular disease, underscoring the dependency of this association on the specific mechanisms that drive fat accumulation in the liver. However, excess liver fat, regardless of how achieved, appears to be causally linked to liver cirrhosis and cancers in a dose dependent manner. This research advances our understanding of the heterogeneity in mechanisms influencing liver fat accumulation, providing new insights into how liver fat accumulation may impact various health outcomes. The findings challenge the notion that liver fat is an independent risk factor for cardiovascular disease and highlight the mechanistic effect of some genetic variants on fat accumulation and the development of cardiovascular diseases. This study is of particular importance for healthcare professionals including physicians and researchers as well as patients as it allows for more targeted and personalised treatment by understanding the relationship between liver fat and various health outcomes. The findings emphasise the need for a personalised management approach and a reshaping of risk assessment criteria. It also provides room for prioritising a clinical intervention aimed at reducing liver fat content (likely by intentional weight loss, however, achieved) that could help protect against liver related fibrosis and cancer.

Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

Determination of the derivatization reactivity between α/β-dicarbonyl compounds and standard citrullinated peptides based on matrix-assisted laser desorption ionization-time-of-flight mass spectrometry

Protein citrullination is an irreversible post-translational modification process regulated by peptidylarginine deiminases (PADs) in the presence of Ca2+. This process is closely related to the occurrence and development of autoimmune diseases, cancers, neurological disorders, cardiovascular and cerebrovascular diseases, and other major diseases. The analysis of protein citrullination by biomass spectrometry confronts great challenges owing to its low abundance, lack of affinity tags, small mass-to-charge ratio change, and susceptibility to isotopic and deamidation interferences. The methods commonly used to study the protein citrullination mainly involve the chemical derivatization of the urea group of the guanine side chain of the peptide to increase the mass-to-charge ratio difference of the citrullinated peptide. Affinity-enriched labels are then introduced to effectively improve the sensitivity and accuracy of protein citrullination by mass spectrometry. 2,3-Butanedione or phenylglyoxal compounds are often used as derivatization reagents to increase the mass-to-charge ratio difference of the citrullinated peptide, and the resulting derivatives have been observed to contain α-dicarbonyl structures. To date, however, no relevant studies on the reactivity of dicarbonyl compounds with citrullinated peptides have been reported. In this study, we determined whether six α-dicarbonyl and two β-dicarbonyl compounds undergo derivatization reactions with standard citrullinated peptides using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Among the α-dicarbonyl compounds, 2,3-butanedione and glyoxal reacted efficiently with several standard citrullinated peptides, but yielded a series of by-products. Phenylglyoxal, methylglyoxal, 1,2-cyclohexanedione, and 1,10-phenanthroline-5,6-dione also derivated efficiently with standard citrullinated peptides, generating a single derivative. Thus, a new derivatization method that could yield a single derivative was identified. Among the β-dicarbonyl compounds, 1,3-cyclohexanedione and 2,4-pentanedione successfully reacted with the standard citrullinated peptides, and generated a single derivative. However, their reaction efficiency was very low, indicating that the β-dicarbonyl compounds are unsuitable for the chemical derivatization of citrullinated peptides. The above results indicate that the α-dicarbonyl structure is necessary for realizing the efficient and specific chemical derivatization of citrullinated peptides. Moreover, the side chains of the α-dicarbonyl structure determine the structure of the derivatives, derivatization efficiency, and generation (or otherwise) of by-products. Therefore, the specific enrichment and precise identification of citrullinated peptides can be achieved by synthesizing α-dicarbonyl structured compounds containing affinity tags. The proposed method enables the identification of citrullinated proteins and their modified sites by MS, thereby providing a better understanding of the distribution of citrullinated proteins in different tissues. The findings will be beneficial for studies on the mechanism of action of citrullinated proteins in a variety of diseases.

Association of carotid atheroma plaque with IL-18 levels and with polymorphisms in the IL-18 receptor gene in a Mediterranean population

BackgroundAtherosclerosis is an inflammatory disease. Interleukin 18 (IL-18) is an inflammatory molecule that has been linked to the development of atherosclerosis and cardiovascular disease. ObjectiveTo evaluate the possible relationship between plasma levels of IL-18 and the presence of atherosclerosis evaluated at the carotid level, as well as to analyze the possible modulation by different polymorphisms in a Mediterranean population. Material and methods746 individuals from the metropolitan area of ​​Valencia were included, recruited over a period of 2 years. Hydrocarbon and lipid metabolism parameters were determined using standard methodology and IL-18 using ELISA. In addition, carotid ultrasound was performed and the genotype of 4 SNPs related to the IL-18 signaling pathway was analyzed. ResultsPatients with higher plasma levels of IL-18 had other associated cardiovascular risk factors. Elevated IL-18 levels were significantly associated with higher carotid IMT and the presence of atheromatous plaques. The genotype with the A allele of the SNP rs2287037 was associated with a higher prevalence of carotid atheromatous plaque. On the contrary, the genotype with the C allele of the SNP rs2293224 was associated with a lower prevalence of atheromatous plaque. ConclusionsHigh levels of IL-18 were significantly associated with a higher carotid IMT and the presence of atheromatous plaques, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the IL-18 receptor gene and the presence of atheroma plaque.

Evaluation and management of cardiovascular disease and metabolic syndrome in pediatric-adolescent patients with psoriasis

Psoriasis is strongly associated with cardiovascular disease (CVD) and metabolic syndrome, with pediatric and adolescent patients having an increased risk of each compared to the general population. This increased risk is based on shared underlying genetic and cytokine profiles, as well as similar environmental risks. Many screening guidelines do not address the development of CVD and metabolic syndrome in these predisposed patients, particularly in the adolescent population. These deficits are evidenced by the absence of validated 10-year CVD risk calculators for pediatric and adolescent patients with chronic inflammatory diseases, as well as insufficient screening guidelines for insulin resistance in patients with psoriasis. This manuscript aims to contribute literature regarding allopathic and lifestyle recommendations to the most recent 2017 consensus guideline for the pediatric/adolescent population with psoriasis. PubMed, COCHRANE Database of Systematic Reviews and Google Scholar were reviewed by a panel of clinicians with clinical and research expertise in psoriasis and pediatric subspecialties. The patient-centered Strength of Recommendation Taxonomy (SORT) method was utilized to grade the quality of the evidence available. Updates in management surrounding the role of lipoprotein(a) in lipid panels, recommendations for exercise and weight management to decrease insulin resistance, as well as guidance for heart rate and blood pressure management were discussed. Screening and managing pediatric and adolescent patients with psoriasis for the associated comorbidities of CVD and metabolic syndrome is imperative. Future high-quality studies are needed to strengthen the evidence provided throughout this review, which acts as a framework for clinical practice. Key words: Psoriasis, Comorbidity, Exercise, Treatment, Coronary heart disease

The Role of Long Non-Coding RNAs in the Pathogenesis of Essential Hypertension

Abstract: Hypertension, a condition characterized by elevated blood pressure, poses a significant medical risk, particularly in relation to the development of cardiovascular disease. The pathogenesis of hypertension can be influenced by a combination of genetic and environmental factors. Recent scientific studies have shed light on the involvement of long-non-coding RNAs (lncRNAs) in various diseases, including pulmonary arterial and essential hypertension. These lncRNAs have been found to play crucial roles at the transcriptional, post-transcriptional, and post-translational levels. By targeting endothelial cell proliferation, migration, apoptosis, and angiogenesis, lncRNAs can induce dysfunction in arterial endothelial cells, contributing to the progression of hypertension-related pathological events. Therefore, the abnormal expression of lncRNAs has emerged as a significant factor in the understanding of essential hypertension and its associated mechanisms. To further our understanding, we conducted a comprehensive review focusing on unraveling the functional roles of lncRNAs in essential hypertension.

Female Psammomys obesus Are Protected from Circadian Disruption-Induced Glucose Intolerance, Cardiac Fibrosis and Adipocyte Dysfunction.

Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian disruption causes glucose intolerance, cardiac fibrosis and adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur in female P. obesus is unknown. Male and female P. obesus were fed a high energy diet and exposed to a neutral (12 light:12 dark, control) or short (5 light:19 dark, circadian disruption) photoperiod for 20 weeks. Circadian disruption impaired glucose tolerance in males but not females. It also increased cardiac perivascular fibrosis and cardiac expression of inflammatory marker Ccl2 in males, with no effect in females. Females had reduced proapoptotic Bax mRNA and cardiac Myh7:Myh6 hypertrophy ratio. Cardiac protection in females occurred despite reductions in the clock gene Per2. Circadian disruption increased adipocyte hypertrophy in both males and females. This was concomitant with a reduction in adipocyte differentiation markers Pparg and Cebpa in males and females, respectively. Circadian disruption increased visceral adipose expression of inflammatory mediators Ccl2, Tgfb1 and Cd68 and reduced browning marker Ucp1 in males. However, these changes were not observed in females. Collectively, our study show that sex differentially influences the effects of circadian disruption on glucose tolerance, cardiac function and adipose tissue dysfunction.

Role of Physical Activity and Sedentary Behaviors on Vascular and Myocardial Structure and Function in Type 1 Diabetes

To estimate associations between physical activity and sedentary behaviors and early markers of cardiovascular diseases (CVD) in adolescents with and without type 1 diabetes. Cross-sectional data stem from CARDEA, a study investigating early CVD development in 100 adolescents with type 1 diabetes recruited at Sainte-Justine University Hospital Diabetes Clinic and 97 healthy adolescents without diabetes (14-18 years), in Montréal, Canada. Outcomes included arterial stiffness by pulse-wave velocity, endothelial function (VTI) by flow-mediated dilation test, and cardiac magnetic resonance imaging markers. Moderate-to-vigorous physical activity (MVPA) and sedentary time were estimated by accelerometry and leisure screen time by questionnaire. We estimated multivariable linear regression models stratified by group. In adolescents with type 1 diabetes, 10-minutes daily increase in MVPA was associated with 3.69 g/m (95% CI: -1.16; 8.54) higher left ventricular (LV) mass/height and 1-h increase in device-measured sedentary time with 0.68 mm (0.20; 1.16) higher wall thickness but only in those with glycated hemoglobin ≤7.5%. In healthy adolescents, a 10-minute increase in MVPA was associated with 1.32 g/m (-0.03; 2.66) higher LV mass/height. Every 1-hour increase in sedentary time was associated with -1.82 cm (-3.25; -0.39) lower VTI, -2.99 g/m (-5.03; -0.95) lower LV mass/height, and -0.47 mm (-0.82; -0.12) lower wall thickness. Being active and limiting sedentary time appears beneficial for cardiac structure and endothelial function in healthy adolescents; however adequate glycemic control combined with higher levels of MVPA may be required for adolescents with type 1 diabetes to overcome the impact of diabetes.

Life’s Essential 8 is inversely associated with high-sensitivity C-reactive protein

Life’s Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2–6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.

A case-control study investigating cardiovascular health in maintenance hemodialysis patients through oxidative stress biomarkers and carotid artery intima-media thickness

Introduction: Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Aim: This study aims to evaluate biomarkers of oxidative stress (OS) and carotid artery intima-media thickness as predictors of cardiovascular health among MHD patients. Materials and methods: We divided 135 participants in this prospective case-control study into three groups: group A included 45 healthy controls, group B included 45 ESRD patients receiving MHD for less than three years, and group C included 45 ESRD patients receiving MHD for more than three years. Participants aged 18–50 years, not taking antioxidant supplements, and willing to participate were included, excluding those with chronic illnesses, prior cardiac disease, or acute renal failure. Data collected included demographics, MHD duration, medical history, lipid profile, common carotid artery intima-media thickness (CCA-IMT), and some biochemical parameters such as oxidized LDL (Ox-LDL), malondialdehyde (MDA), and superoxide dismutase (SOD). Results: This study included 135 participants divided into three groups (A, B, and C) based on the MHD duration. Significant differences were observed in OS markers and lipid profiles across the groups (p<0.001). Group C exhibited the highest levels of Ox-LDL and MDA, indicating increased OS, and the lowest SOD levels compared to groups A and B. Positive correlations were found between Ox-LDL and LDL-cholesterol (LDL-C) levels, with the strongest correlation in group C (r=0.684, p<0.05). CCA-IMT progressively increased from group A to group C, with significant differences in right, left, and mean CCA-IMT (p<0.001). Multivariate analysis revealed a positive association between Ox-LDL levels and CCA-IMT (p<0.01). Conclusion: Increased OS, evident by elevated Ox-LDL and reduced antioxidant levels, is linked to unfavorable lipid profiles and carotid atherosclerosis progression in MHD patients. Prolonged MHD duration contributes to heightened OS and increased atherosclerosis development. Ox-LDL emerges as a predictor of CVD risk in this population.

Does the time spent in retirement improve health? An IV-Poisson assessment on the incidence of cardiovascular diseases

In recent decades, pension reforms have been implemented to address the financial sustainability of social security systems, resulting in an increase in the retirement age. This adjustment has led to ongoing debates about the relationship between retirement and health.This study investigates the impact of time spent in retirement on the risk of cardiovascular disease (CVD) in Italy. It uses a comprehensive dataset that includes socioeconomic, health, and behavioural risk factors, which is linked to administrative hospitalisation and mortality registers. To address the potential endogeneity of retirement, we employ an instrumental variables approach embedded in a Poisson rate model.The results show that, on average, years spent in retirement have a beneficial effect on the risk of CVD for both men and women. Each additional year spent in retirement reduces the incidence of such diseases by about 17% for men and 29% for women. Stratified analyses and robustness tests show that the benefits of retirement appear to be more robust and pronounced in men and in certain groups, particularly men in manual occupations or with poor ergonomic conditions at work.These results highlight that delaying access to retirement may lead to an increased burden of CVD in the older population. In addition, the protective effect of retirement on the development of CVD among workers with poorer ergonomic conditions underlines the different impact of increasing the retirement age on different categories of workers and the need for targeted and differentiated policies to avoid hitting the more vulnerable.

CVD Case Series: Screening and Risk Reduction

Undetected cardiovascular disease is one of the leading causes of complications during pregnancy in the United States. Maternal mortality reviews indicate that lack of suspicion and delays in diagnosis are the primary drivers of CVD-related mortality. Purpose of this study is to examine the effect of implementing the CVD (Cardiovascular Disease) Risk Assessment tool developed by the California Maternal Quality Care Collaborative (CMQCC) team in 2018. Eligibility of patients in the case series was determined through CVD risk screen score of 4 or higher using a standardized stool adopted from the CMQCC. The patient was scored at the point of hospital entry. Factors used in scoring included symptoms, vitals and risk factors. Patients who scored positive were sent for further work up. This included in-depth analysis of other significant clinical factors influencing patient presentation and subsequent management. The CV patient cases presented in this case series illustrate the benefits of early identification and implementation of standardized CVD risk assessment. There are significant benefits in early use of the CV screening tool contributing to mortality risk reduction including continued close antenatal surveillance, postpartum follow-up, and continued collaborative multidisciplinary care. Patients with risk factors underwent continued surveillance and received appropriate specialized follow-up that allowed for improved maternal outcomes. Proper implementation of CVD risk assessment tool for patients who are at-risk of development of CVD in pregnancy can effectively reduce adverse maternal outcomes related to cardiac disease.

Polymorphism in the matrix metallopeptidase genes is associated with coronary artery disease risk with concomitant metabolic syndrome

Background: Metabolic syndrome (MS) and its components are the reasons of the development and progression of cardiovascular diseases. Nowadays, the association between coronary artery disease and MS remains ambiguous. The central role of matrix metallopeptidases (MMP) in the metabolism of connective tissue proteins, cell matrix remodeling, tissue repair and other complex biochemical processes has been shown, which implies their involvement in the pathogenesis of cardiovascular diseases. The aim of the study: To study the associations of polymorphic variants in the MMP genes with the risk of stable coronary artery disease with concomitant metabolic syndrome. Materials and methods: 170 patients with stable coronary artery disease concomitant with a visceral type of obesity in combination with two or more pathological conditions (elevated serum blood glucose level, elevated serum blood cholesterol level, hypertension) were included in the case group. Conditionally healthy volunteers (n=182) were recruited in the control group. Genotyping of five polymorphic sites in the four genes MMP1 (rs514921), MMP3 (rs6796620 and rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) was performed by real-time PCR. The serum blood level of MMP was measured by ELISA. Gene-gene interactions were analyzed using MDR v.3.0.2 software. Results: The frequency of heterozygous C/T genotype in the MMP3 gene (rs626750) was higher in the control group (37.90%) compared to the case group (23.20%), which indicates its protective effect on the risk of coronary artery disease with concomitant metabolic syndrome (OR=0.47, 95%CI 0.29-0.75). 2.6-fold increased risk of coronary artery disease with concomitant metabolic syndrome was demonstrated for carriers of the A/G genotype in the TIMP2 gene (rs2277698) according to the codominant inheritance model. We found no associations of polymorphic variants in the MMP1 (rs514921), MMP3 (rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) genes with the serum blood level of MMP, as well as their inhibitors. Four-loci model of gene-gene interactions (MMP9 (rs17576) – MMP3 (rs626750) – MMP1 (rs514921) – TIMP2 (rs2277698)) characterized by high sensitivity, specificity and risk effect to the coronary artery disease with concomitant metabolic syndrome development was discovered. Conclusion: This study revealed the association of polymorphic variants in the MMP genes and their inhibitors with the risk of coronary artery disease with concomitant metabolic syndrome. In addition, a four-locus model of intergenic interactions with high sensitivity and specificity was obtained.

CVD Case Series: Screening and Risk Reduction

Undetected cardiovascular disease is one of the leading causes of complications during pregnancy in the United States. Maternal mortality reviews indicate that lack of suspicion and delays in diagnosis are the primary drivers of CVD-related mortality. Purpose of this study is to examine the effect of implementing the CVD (Cardiovascular Disease) Risk Assessment tool developed by the California Maternal Quality Care Collaborative (CMQCC) team in 2018. Eligibility of patients in the case series was determined through CVD risk screen score of 4 or higher using a standardized stool adopted from the CMQCC. The patient was scored at the point of hospital entry. Factors used in scoring included symptoms, vitals and risk factors. Patients who scored positive were sent for further work up. This included in-depth analysis of other significant clinical factors influencing patient presentation and subsequent management. The CV patient cases presented in this case series illustrate the benefits of early identification and implementation of standardized CVD risk assessment. There are significant benefits in early use of the CV screening tool contributing to mortality risk reduction including continued close antenatal surveillance, postpartum follow-up, and continued collaborative multidisciplinary care. Patients with risk factors underwent continued surveillance and received appropriate specialized follow-up that allowed for improved maternal outcomes. Proper implementation of CVD risk assessment tool for patients who are at-risk of development of CVD in pregnancy can effectively reduce adverse maternal outcomes related to cardiac disease.

Prediction model for cardiovascular disease in patients with diabetes using machine learning derived and validated in two independent Korean cohorts

This study aimed to develop and validate a machine learning (ML) model tailored to the Korean population with type 2 diabetes mellitus (T2DM) to provide a superior method for predicting the development of cardiovascular disease (CVD), a major chronic complication in these patients. We used data from two cohorts, namely the discovery (one hospital; n = 12,809) and validation (two hospitals; n = 2019) cohorts, recruited between 2008 and 2022. The outcome of interest was the presence or absence of CVD at 3 years. We selected various ML-based models with hyperparameter tuning in the discovery cohort and performed area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort. CVD was observed in 1238 (10.2%) patients in the discovery cohort. The random forest (RF) model exhibited the best overall performance among the models, with an AUROC of 0.830 (95% confidence interval [CI] 0.818–0.842) in the discovery dataset and 0.722 (95% CI 0.660–0.783) in the validation dataset. Creatinine and glycated hemoglobin levels were the most influential factors in the RF model. This study introduces a pioneering ML-based model for predicting CVD in Korean patients with T2DM, outperforming existing prediction tools and providing a groundbreaking approach for early personalized preventive medicine.