Occurrence Of Cardiovascular Disease Research Articles

The interaction between polyphenol intake and genes (MC4R, Cav-1, and Cry1) related to body homeostasis and cardiometabolic risk factors in overweight and obese women: a cross-sectional study.

Cardiovascular disease (CVD), which is an important global health challenge, is expanding. One of the main factors in the occurrence of CVD is a high genetic risk. The interaction between genetic risk in CVD and nutrition is debatable. Polyphenols are one of the important dietary components that may have a protective role in people who have a high genetic risk score (GRS) for cardiometabolic risk factors. This study, conducted in overweight and obese women, examines the interaction between polyphenol intake and specific genes (MC4r, Cav-1, and Cry1) related to maintaining body balance and their interaction with cardiometabolic risk factors. This cross-sectional study included 391 women who were overweight or obese, aged 18 to 48 years, with a body mass index (BMI) between 25 and 40 kg/m2. Body composition was measured using the InBody 770 scanner. Total dietary polyphenol intake (TDPI) was assessed with a validated 147-item food frequency questionnaire (FFQ), and polyphenol intakes were determined using the Phenol-Explorer database. Serum samples underwent biochemical tests. The Genetic Risk Score (GRS) was calculated based on the risk alleles of three genes: MC4r, Cav-1, and Cry1. The mean ± standard deviation (SD) age and BMI of women were 36.67 (9.1) years and 30.98 (3.9) kg/m2, respectively. The high GRS and high TDPI group had a significant negative interaction with fasting blood glucose (FBS) (p = 0.01). Individuals who had a high GRS and a high phenolic acid intake were found to have a significant negative interaction with Triglyceride (p = 0.04). Similarly, individuals with high GRS and a high intake of flavonoids had a significant negative interaction with TG (p < 0.01) and a significant positive interaction with High-density lipoprotein (HDL) (p = 0.01) in the adjusted model. According to our findings, those with a high GRS may have a protective effect on cardiometabolic risk factors by consuming high amounts of polyphenols. Further studies will be necessary in the future to validate this association.

Legumain in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, having become a global public health problem, so the pathophysiological mechanisms and therapeutic strategies of CVDs need further study. Legumain is a powerful enzyme that is widely distributed in mammals and plays an important role in a variety of biological processes. Recent research suggests that legumain is associated with the occurrence and progression of CVDs. In this review, we provide a comprehensive overview of legumain in the pathogenesis of CVDs. The role of legumain in CVDs, such as carotid atherosclerosis, pulmonary hypertension, coronary artery disease, peripheral arterial disease, aortic aneurysms and dissection, is discussed. The potential applications of legumain as a biomarker of these diseases are also explored. By understanding the role of legumain in the pathogenesis of CVDs, we aim to support new therapeutic strategies to prevent or treat these diseases.

Unveiling the Potential of Migrasomes: A Machine-Learning-Driven Signature for Diagnosing Acute Myocardial Infarction.

Recent studies have demonstrated that the migrasome, a newly functional extracellular vesicle, is potentially significant in the occurrence, progression, and diagnosis of cardiovascular diseases. Nonetheless, its diagnostic significance and biological mechanism in acute myocardial infarction (AMI) have yet to be fully explored. To remedy this gap, we employed an integrative machine learning (ML) framework composed of 113 ML combinations within five independent AMI cohorts to establish a predictive migrasome-related signature (MS). To further elucidate the biological mechanism underlying MS, we implemented single-cell RNA sequencing (scRNA-seq) of cardiac Cd45+ cells from AMI-induced mice. Ultimately, we conducted mendelian randomization (MR) and molecular docking to unveil the therapeutic effectiveness of MS. MS demonstrated robust predictive performance and superior generalization, driven by the optimal combination of Stepglm and Lasso, on the expression of nine migrasome genes (BMP1, ITGB1, NDST1, TSPAN1, TSPAN18, TSPAN2, TSPAN4, TSPAN7, TSPAN9, and WNT8A). Notably, ITGB1 was found to be predominantly expressed in cardiac macrophages in AMI-induced mice, mechanically regulating macrophage transformation between anti-inflammatory and pro-inflammatory. Furthermore, we showed a positive causality between genetic predisposition towards ITGB1 expression and AMI risk, positioning it as a causative gene. Finally, we showed that ginsenoside Rh1, which interacts closely with ITGB1, could represent a novel therapeutic approach for repressing ITGB1. Our MS has implications in forecasting and curving AMI to inform future diagnostic and therapeutic strategies for AMI.

Evaluating the effect of green tea intake on cardiovascular diseases: A Mendelian randomization study in European and East Asian populations.

Previous research shows that more than 70% of cardiovascular diseases (CVDs) are attributed to modifiable risk factors. Here, we investigated relationship between consumption of green tea in European and East Asian populations and risk of CVDs using Mendelian randomization (MR). Instrumental variables for green tea intake were obtained from genome-wide association studies (GWASs) of 64,949 Europeans and 152,653 East Asians. GWASs for CVDs were derived from UK BioBank and BioBank Japan projects. The main method selected for MR analysis was either the inverse variance weighted (IVW) or Wald ratio, depending on the quantity of single nucleotide polymorphisms. Furthermore, we performed sensitivity analyses to confirm the reliability of the findings. Based on the results of IVW, there is no causal relationship between consumption of green tea and risk of 4 CVDs among Europeans (atrial fibrillation: OR = 1.000, 95% CI: 0.995-1.005, P = .910; heart failure: OR = 1.003, 95% CI: 0.994-1.012, P = .542; ischemic stroke: OR = 1.002, 95% CI: 0.993-1.011, P = .690; coronary artery disease: OR = 1.001, 95% CI: 0.996-1.007, P = .677). Sensitivity analyses and supplementary MR analyses also verify the robustness of the findings. Likewise, there was no correlation between the consumption of green tea and the occurrence of CVDs in East Asians. The consumption of green tea is not associated with a reduced risk of CVDs in populations from Europe and East Asia. This means that those who are trying to reduce their risk of CVDs by drinking more green tea may not benefit from doing so.

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.

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.

Estimated effects of reductions in processed meat consumption and unprocessed red meat consumption on occurrences of type 2 diabetes, cardiovascular disease, colorectal cancer, and mortality in the USA: a microsimulation study

High consumption of processed meat and unprocessed red meat is associated with increased risk of multiple chronic diseases, although there is substantial uncertainty regarding the relationship for unprocessed red meat. We developed a microsimulation model to estimate how reductions in processed meat and unprocessed red meat consumption could affect rates of type 2 diabetes, cardiovascular disease, colorectal cancer, and mortality in the US adult population. We used data from two versions of the US National Health and Nutrition Examination Survey, one conducted during 2015-16 and one conducted during 2017-18, to create a simulated US population. The starting cohort was restricted to respondents aged 18 years or older who were not pregnant and had 2 days of dietary-recall data. First, we used previously developed risk models to estimate the baseline disease risk of an individual. For type 2 diabetes we used a logistic-regression model and for cardiovascular disease and colorectal cancer we used Cox proportional-hazard models. We then multiplied baseline risk by relative risk associated with individual processed meat and unprocessed red meat consumption. Prevented occurrences of type 2 diabetes, cardiovascular disease, colorectal cancer, and mortality were computed by taking the difference between the incidence in the baseline and intervention scenarios. All stages were repeated for ten iterations to correspond to a 10-year time span. Scenarios were reductions of 5%, 10%, 30%, 50%, 75%, and 100% in grams consumed of processed meat, unprocessed red meat, or both. Each scenario was repeated 50 times for uncertainty analysis. The total number of individual respondents included in the simulated population was 8665, representing 242 021 876 US adults. 4493 (51·9%) of 8665 individuals were female and 4172 (48·1%) were male; mean age was 49·54 years (SD 18·38). At baseline, weighted mean daily consumption of processed meat was 29·1 g, with a 30% reduction being 8·7 g per day, and of unprocessed red meat was 46·7 g, with a 30% reduction being 14·0 g per day. We estimated that a 30% reduction in processed meat intake alone could lead to 352 900 (95% uncertainty interval 345 500-359 900) fewer occurrences of type 2 diabetes, 92 500 (85 600-99 900) fewer occurrences of cardiovascular disease, 53 300 (51 400-55 000) fewer occurrences of colorectal cancer, and 16 700 (15 300-17 700) fewer all-cause deaths during the 10-year period. A 30% reduction in unprocessed red meat intake alone could lead to 732 600 (725 700-740 400) fewer occurrences of type 2 diabetes, 291 500 (283 900-298 800) fewer occurrences of cardiovascular disease, 32 200 (31 500-32 700) fewer occurrences of colorectal cancer, and 46 100 (45 300-47 200) fewer all-cause deaths during the 10-year period. A 30% reduction in both processed meat and unprocessed red meat intake could lead to 1 073 400 (1 060 100-1 084 700) fewer occurrences of type 2 diabetes, 382 400 (372 100-391 000) fewer occurrences of cardiovascular disease, 84 400 (82 100-86 200) fewer occurrences of colorectal cancer, and 62 200 (60 600-64 400) fewer all-cause deaths during the 10-year period. Reductions in processed meat consumption could reduce the burden of some chronic diseases in the USA. However, more research is needed to increase certainty in the estimated effects of reducing unprocessed red meat consumption. The Wellcome Trust.

Thermal Influence on the Heart: The Impact of Hot Weather on Cardiovascular Conditions.

Dear Editor, We are cognisant of the fact that cardiovascular diseases (CVDs) have a considerable impact on public healthcare systems. Cardiovascular disorders rank as the primary global reason of fatality, claiming an estimated 17.9 million lives in 2019, which equates to 32% of all global fatalities. The majority of these deaths, around 85 percent, result from heart attacks and strokes. Low- and middle-income countries tolerate the brunt of heart-related fatalities, accounting for over three quarters of all deaths attributed to these conditions. Additionally, out of the 17 million premature deaths caused by noncommunicable diseases in 2019, CVDs were responsible for 38 percent.1 The prevailing cardiovascular risk factors encompass increasing age, hypertension (commonly referred to as a double-edged sword), diabetes mellitus, tobacco use, obesity, dyslipidaemia, and stress.1,2 A sedentary lifestyle together with poor eating habits have also led to an increased rate of CVS-related illnesses.1 Often overlooked as a risk factor, experiencing high temperatures significantly adds to the increased occurrence of cardiovascular diseases. Multiple studies support the connection between extreme temperatures and heightened cardiovascular risks.2-5 Being exposed to higher temperatures can lead to intravascular volume depletion, haemoconcentration, a hypercoagulable state, electrolyte imbalance, and raised sympathetic activity, placing substantial stress on the heart, especially in individuals with pre-existing cardiovascular disease.3 To investigate cardiovascular mortality associations with extremes of temperatures, Barrak Alahmad et al. assembled daily counts of specific cardiovascular causes of death from 567 cities across 5 continents in overlapping periods ranging from 1979 to 2019, and the city-specific daily ambient temperatures were noted. The findings indicated that higher temperature extremes (99th percentile for heat and 1st percentile for cold) were linked to an increased probability of mortality from various cardiovascular conditions, including ischaemic heart disease, stroke, and heart failure.4 In a case-crossover study conducted using the England and Wales MINAP database, involving 24,861 participants (hospital admissions for myocardial infarction) during the warmest months (June to August) from 2003 to 2009, it was found that each 1-degree Celsius increase in temperature beyond the established threshold of 20 °C temporarily increased the risk of heart attack by 1.9 percent.5 The cardiovascular-related illness and fatalities are quite prevalent in Pakistan. Pakistan due to her geographical location, usually encounters summer temperatures ranging from 45 to 55 degrees Celsius across most areas of the country. ---Continue

Socioeconomic status and risk of cardiovascular diseases in patients with retinal vein occlusion: A Danish nationwide cohort study

PurposeThis study examines the association between socioeconomic status and the occurrence of both cardiovascular diseases and mortality following retinal vein occlusion (RVO), a condition known to elevate the risk of cardiovascular health issues. Despite recognition of the impact socioeconomic factors might have on a patient's course through the healthcare system, its association with cardiovascular outcomes post-RVO has not previously been thoroughly explored. DesignNationwide cohort study. MethodsWe included all subjects with RVO from the Danish nationwide registries diagnosed between 2000 and 2018. Information was combined using a personal identification number each Danish resident is given at birth or upon immigration. We categorized participants by their socioeconomic levels to evaluate the five-year incidence rate of cardiovascular conditions and overall mortality. The analysis was further refined by sex and age groups to elucidate any differential impacts. Furthermore, the cumulative incidence was estimated using the Aalen-Johansen estimator and the differences between the socioeconomic groups were quantified using a cox proportional hazard model. Key quantitative results were summarized, including hazard rate ratios (HR), confidence intervals (CI), and p-values ResultsThe cohort was comprised of 14,041 individuals with RVO. Our analysis revealed a relationship between educational attainment and cardiovascular health outcomes. Lower education levels were consistently linked with heightened risks of mortality, diabetes, ischemic heart disease, myocardial infarction, and peripheral artery disease following RVO. Individuals with a middle educational level also exhibited a higher prevalence of peripheral artery disease when compared to those with the highest education levels. In terms of income, the lowest earners faced increased risks across several categories, including mortality, diabetes, heart failure, ischemic heart disease, myocardial infarction, and peripheral artery disease, when compared to the highest-income earners. The middle-income group also showed elevated risks for mortality, heart failure, and peripheral artery disease. Being unmarried was additionally associated with higher risks of mortality and heart failure compared to being married. ConclusionSocioeconomic status was significantly associated with clinically relevant differences in post-RVO risk of cardiovascular diseases and death. Our data suggests that socioeconomic factors should be considered in the attempt to reduce the risk of cardiovascular disease and death in patients with RVO.

Long-term blood pressure variability and risk of cardiovascular diseases in populations with different blood pressure status: an ambispective cohort study.

We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension). In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs. Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable. Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV.

Interpretation of the 2024 American Diabetes Association guidelines for the comprehensive management of non-alcoholic fatty liver disease combined with diabetes mellitus

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study

BackgroundTo evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings.MethodsWe built a cohort of people with a first DFD episode during 2010–2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events.ResultsOverall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7–22.6, HR: 15.1, 95% CI: 13.8–16.5, respectively) was found.ConclusionsAlthough DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.Graphical

Physiopathological mechanisms of orthostatic arterial hypertension

The definition, prognostic role and clinical importance of orthostatic arterial hypertension (OHTA) have long remained unclear, in the context in which this pathology is little studied. Recent data have reported evidence that OHT correlates with masked arterial hypertension and target organ damage resulting from elevated blood pressure, the occurrence of various cardiovascular diseases, as well as an increased risk of mortality. Most of the evidence comes from studies in which OHT was defined using, as a benchmark, the increase in systolic blood pressure, while the clinical relevance of the increase in diastolic blood pressure values, currently, still remains unclear. The most recent consensus regarding the term orthostatic hypertension is provided by the Japanese Society of Hypertension, which defines it as an increase in systolic BP of ≥20 mmHg, associated with a systolic blood pressure value of at least 140 mmHg, when passing from the clinoin orthostatism. The pathophysiological mechanisms underlying this phenotype of hypertension are still controversial, varying with age. In young people, excessive activity of the neurohumoral system seems to be the determining cause, while with age, vascular stiffness plays a significant role in the occurrence of orthostatic arterial hypertension. Analyzing the latest data from the specialized literature, we observe that pathologies such as diabetes, activity disorders of the baroreflex system, essential arterial hypertension, can also induce the appearance of OHT. People with a tendency to increase blood pressure values, need to be subjects to periodic measurements of blood pressure values, including clino and otostatism.

Cross-species signaling pathways analysis inspire animal model selections for drug screening and target prediction in vascular aging diseases.

Age is a significant contributing factor to the occurrence and progression of cardiovascular disease (CVD). Pharmacological treatment can effectively alleviate CVD symptoms caused by aging. However, 90% of the drugs have failed in clinics because of the loss of drug effects or the occurrence of the side effects. One of the reasons is the disparity between animal models used and the actual physiological levels in humans. Therefore, we integrated multiple datasets from single-cell and bulk-seq RNA-sequencing data in rats, monkeys, and humans to identify genes and pathways with consistent/differential expression patterns across these three species. An approach called "Cross-species signaling pathway analysis" was developed to select suitable animal models for drug screening. The effectiveness of this method was validated through the analysis of the pharmacological predictions of four known anti-vascular aging drugs used in animal/clinical experiments. The effectiveness of drugs was consistently observed between the models and clinics when they targeted pathways with the same trend in our analysis. However, drugs might have exhibited adverse effects if they targeted pathways with opposite trends between the models and the clinics. Additionally, through our approach, we discovered four targets for anti-vascular aging drugs, which were consistent with their pharmaceutical effects in literatures, showing the value of this approach. In the end, software was established to facilitate the use of "Cross-species signaling pathway analysis." In sum, our study suggests utilizing bioinformatics analysis based on disease characteristics can help in choosing more appropriate animal models.

심장주위지방과 심장혈관 석회화의 평가 및 관리

Although epicardial adipose tissue and coronary artery calcification are not traditional metabolic risk factors, recent research results have reported that they are also related to decreased cardiac function, occurrence of cardiovascular diseases, and increased metabolic risks. In the case of epicardial adipose tissue, there is morphological and functional similarity to abdominal visceral fat, and an increase in epicardial fat is associated with an increase of risk of heart disease. In addition, coronary artery calcification is also caused by an imbalance in the normal calcification process and causes atherosclerosis and coronary artery stenosis. Epicardial fat and coronary artery calcification require periodic evaluation in people at risk through coronary artery computed tomography and traditional management methods such as smoking cessation, exercise, weight loss, and use of statins, as well as vitamin D and vitamin K to prevent calcification, are used to reduce risk. It may be an additional consideration for those who have the risks.

#1258 Moderate-severe intrarenal arteriosclerosis and circulating GDF-15 levels may influence the cardiac-renal prognosis of IgAN patients

Abstract Background and Aims The cardiovascular risk among patients with IgA nephropathy (IgAN) is gradually garnering increased attention. The KDIGO guidelines explicitly emphasize the importance of evaluating cardiovascular risk in the management of IgAN patients and implementing appropriate interventions when necessary. The aim of this study was to investigate the risk factors affecting cardiac-renal prognosis in patients with IgAN. Method This is a retrospective study. A total of 353 IgAN patients with regular follow-up for at least 1 year at Beijing Anzhen Hospital were recruited. Patients were divided into group A (n = 85, yes) and group B (n = 268, no) according to the occurrence of cardio-renal composite endpoint events. Clinical and pathological characteristics of the two groups were compared and analyzed. The risk factors affecting the cardiac and renal prognosis in IgAN patients were analyzed by univariate and multivariate Cox models. In addition, serum GDF-15 of IgAN patients were detected. Results Approximately 14.7% (52/353) of IgAN patients presented with cardiovascular diseases at the time of renal biopsy. 55.8% (197/353) patients presented with hypertension. Prognostic analysis showed that hypertension (HR, 1.810; 95% confidence interval, 1.073 to 3.053; P = 0.026), 24-hour urinary protein (24 hUTP) (HR, 1.081; 95% confidence interval, 1.006 to 1.162; P = 0.033), eGFR (HR, 0.980; 95% confidence interval, 0.973 to 0.987; P&amp;lt;0.001), the presence of endocapillary proliferation (E1) (HR, 1.697; 95% confidence interval, 1.079 to 2.669; P = 0.022), tubular atrophy/interstitial fibrosis (T2) (HR, 3.757; 95% confidence interval, 1.959 to 7.203; P &amp;lt; 0.001), and moderate-severe intrarenal arteriosclerosis (HR, 3.320; 95% confidence interval, 1.289 to 8.548; P = 0.013) are independent risk factors affecting the cardiac-renal prognosis of IgAN. In IgAN patients with moderate-severe intrarenal arteriosclerosis, 24-hour urinary protein (24 hUTP) (HR, 1.131; 95% confidence interval, 1.014 to 1.261; P = 0.028), eGFR (HR, 0.982; 95% confidence interval, 0.971 to 0.993; P = 0.001) and E1 (HR, 2.583; 95% confidence interval, 1.379 to 4.841; P = 0.003) are independent risk factors affecting the cardiac-renal prognosis of IgAN patients. The serum GDF-15 level is positively correlated with 24 hUTP (r = 0.405, P &amp;lt; 0.001) and negatively correlated with eGFR (r = −0.606, P &amp;lt; 0.001). Compared with those with benign cardio-renal composite outcome, the serum level of GDF-15 in IgAN with poor cardio-renal composite outcome were significantly higher (1591.69 (1001.65, 2546.36) pg/ml vs 775.85 (546.82, 1310.29) pg/ml, P &amp;lt; 0.001). Conclusion The occurrence of cardiovascular diseases in patients with IgAN is frequently observed. In addition to the conventional risk factors associated with IgAN, including hypertension, initial proteinuria, eGFR, E1 and T2 lesion, moderate-severe intrarenal arteriosclerosis also contributes to the cardiac-renal prognosis of individuals with IgAN. In IgAN patients with moderate-severe intrarenal arteriosclerosis, Oxford-E lesion is an independent risk factor affecting the cardiac-renal prognosis of IgAN patients. This study suggested that the impairment of endothelial cells could potentially serve as a link between heart and kidney disease. The circulating levels of GDF-15 might contribute to the cardiac-renal prognosis of IgAN.

#2201 Assessment of long-term cardiovascular comorbidities in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract Background and Aims ANCA associated vasculitis (AAV) is closely correlated to elevated cardiovascular disease (CVD) rates, positioning it a one of the leading causes of death among these patients. The impact of AAV on the risk of CVD has not been described in large prospective cohorts with a long-term follow up. The aim of our study was to evaluate the occurrence of cardiovascular events, encompassing major adverse cardiovascular events (MACE), to delineate associated risk factors, and to draw comparisons with other cohorts of patients diagnosed with CKD. Method We included 848 patients with a diagnosis of AAV who participated in 7 EUVAS RCTs (NORAM, CYCAZAREM, CYCLOPS, MEPEX, IMPROVE, RITUXVAS, and MYCYC), recruited from 74 centers in 17 European countries. The three-point MACE outcome was defined as acute myocardial infarction (AMI), stroke, or death from cardiovascular event. We used multivariate logistic regression analysis to assess the risk factors of MACE. Patients from our cohort were compared to the patients from the Chronic Renal Insufficiency Cohort (CRIC), which is a multicenter, prospective observational cohort study of participants with CKD. Results During the median follow up of 8 years (range 0-24.5, IQR: 2.9-13.6), 100 (11.8%) patients developed diabetes, 98 (13.4%) coronary heart disease (CHD), 90 (12.1%) hypertension, 70 (9.6%) deep vein thrombosis (DVT), 43 patients (5.9%) had a stroke and 28 (3.8%) an AMI. The number of MACE during FU was 144 (17%). MACE was more frequent among patients older than 65 years (n = 62 (43.1%); p-value: 0.013). CVD was the primary cause of death in 43 patients (14%). During the first 5 years after randomization, there was a significant increase in the number of cardiovascular events compared to the period 6 years- end of follow up (CHD: n = 55 vs n = 23, p ≤ 0.001; DVT: n = 55 vs n = 29; p &amp;lt; 0.001; stroke: n = 35 vs n = 24, p-value &amp;lt; 0.001). The prognostic factors for MACE in our cohort were hemodialysis dependency during RCT, age, male sex, previous history of CHD and stroke, and occurrence of diabetes during follow up. Within the subset of patients who underwent kidney biopsy, those in the crescentic class (n = 16) followed by the mixed class (n = 15) exhibited a significant higher incidence of MACE (p = 0.02). When compared to the cohort of patients with CKD from the CRIC study, the risk for CHD was higher (13.4% (95% CI: 11.16-16.11) vs 5.4% (95% CI 4.5-6.5); respectively; RR: 2.49 (95% CI 1.91-3.24); p-value&amp;lt;0.01). Additionally, there was a higher risk for stroke (5.6% (95% CI 4.2-7.4) vs 2.8% (95% CI 2.2- 3.7); RR 1.97 (95% CI: 1.33- 2.91) p-value: 0.0006). Conclusion Patients with AAV had an increased risk of stroke and CHD compared to patients with CKD from other etiologies. During the first years after diagnosis, there is an increased risk for CVD occurrence. The prognostic factors for MACE in our cohort were hemodialysis dependency, age, male sex, previous story of CHD and stroke, and diabetes during follow up. Patients with AAV should be considered at high cardiovascular risk; therefore, the therapeutic approach should include the management of traditional cardiovascular risk factors and lifestyle modification. Efforts should be made to meet strict therapeutic targets and to implement early CVD detection programs.

Defective natriuresis contributes to hyperkalemia in db/db mice during potassium supplementation.

Potassium supplementation reduces blood pressure and the occurrence of cardiovascular diseases, with K + -induced natriuresis playing a potential key role in this process. However, whether these beneficial effects occur in diabetes remains unknown. In this study, we examined the impact of high-K + intake on renal Na + /K + transport by determining the expression of major apical Na + transporters, diuretics responses (as a proxy for specific Na + transporter function), urinary Na + /K + excretion, and plasma Na + /K + concentrations in db/db mice, a model of type 2 diabetes mellitus. Although db/m mice exhibited increased fractional excretion of sodium (FE Na ) and fractional excretion of potassium (FE K ) under high-K + intake, these responses were largely blunted in db/db mice, suggesting impaired K + -induced natriuresis and kaliuresis in diabetes. Consequently, high-K + intake increased plasma K + levels in db/db mice, which could be attributed to the abnormal activity of sodium-hydrogen exchanger 3 (NHE3), sodium-chloride cotransporter (NCC), and epithelial Na + channel (ENaC), as high-K + intake could not effectively decrease NHE3 and NCC and increase ENaC expression and activity in the diabetic group. Inhibition of NCC by hydrochlorothiazide could correct the hyperkalemia in db/db mice fed a high-K + diet, indicating a key role for NCC in K + -loaded diabetic mice. Treatment with metformin enhanced urinary Na + /K + excretion and normalized plasma K + levels in db/db mice with a high-K + diet, at least partially, by suppressing NCC activity. Collectively, the impaired K + -induced natriuresis in diabetic mice under high-K + intake may be primarily attributed to impaired NCC-mediated renal K + excretion, despite the role of NHE3.

The Role of Leukemia Inhibitory Factor in Cardiovascular Disease: Signaling in Inflammation, Coagulation, and Angiogenesis

Background: Cardiovascular disease (CVD) is one of the principal causes of mortality in the world. Various factors have been identified in the pathogenesis of CVD. Leukemia inhibitory factor (LIF) as a secretory cytokine is one of these factors. The LIF receptor is located on endothelial cells and plays a role in the expression of specific genes in these cells. Endothelial cells are the innermost cells of blood vessels, and defects in these cells cause endothelial dysfunction and eventually CVD. Methods: The present study is based on PubMed database information (1982–2022) using the following words: “cardiovascular disease,” “endothelial cells,” “leukemia inhibitory factor,” and “angiogenesis.” Results: LIF can cause arteriosclerotic plaques by activating inflammatory mechanisms in monocytes through the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. LIF can also induce vascular endothelial growth factor expression by activating signaling pathways, eventually leading to angiogenesis. Additionally, it can activate the coagulation cascade by factor VII production promotion within endothelial cells. Conclusion Understanding the interplay between LIF and the inflammation pathways, coagulation, and angiogenesis as key factors in CVD occurrence raises the possibility of targeting this factor as a potential strategy to mitigate CVD risk.

The association between triglyceride-glucose index and related parameters and risk of cardiovascular disease in American adults under different glucose metabolic states

BackgroundCardiovascular disease (CVD) encompasses an array of cardiac and vascular disorders, posing a significant threat to global health. It remains unclear whether there exists an association between triglyceride-glucose index (TyG) and its derived indices and the incidence of cardiovascular disease, and in particular, the strength of the association in populations with different glucose metabolisms is not known.MethodsData extracted from the National Health and Nutrition Examination Survey (NHANES) covering the period from 1999 to 2020, involving a cohort of 14,545 participants, were leveraged for the analysis. Statistical assessments were executed utilizing R software, employing multivariable logistic regression models to scrutinize the correlation between TyG and its associated parameters with the incidence of cardiovascular disease across diverse glucose metabolism categories. Interaction analyses and restricted cubic splines were applied to evaluate potential heterogeneity in associations and investigate the link between TyG and its derivatives with the occurrence of cardiovascular disease. Furthermore, receiver operating characteristic curves were constructed to evaluate the extent of variability in the predictive performance of TyG and its derived parameters for cardiovascular disease across distinct glucose metabolic statuses.ResultsThis study found that TyG and its related parameters were differentially associated with the occurrence of cardiovascular disease in different glucose metabolic states. Curvilinear correlations were found between TyG in the IFG population and TyG-WC, TyG-BMI, and TyG-WHtR in the impaired glucose tolerance (IGT) population with the occurrence of cardiovascular disease. In addition, the introduction of TyG and its derived parameters into the classical Framingham cardiovascular risk model improved the predictive performance in different glucose metabolism populations. Among them, the introduction of TyG-WHtR in the normal glucose tolerance (NGT), impaired fasting glucose (IFG), IFG & IGT and diabetes groups and TyG in the IGT group maximized the predictive power.ConclusionsThe findings provide new insights into the relationship between the TyG index and its derived parameters in different glucose metabolic states and the risk of cardiovascular disease, offering important reference value for future clinical practice and research. The study highlights the potential for improved risk stratification and prevention strategies based on TyG and its derived parameters.