High Risk Of Cardiovascular Events Research Articles

Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46-A birth cohort study.

The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, long-term population-based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM. A prospective population-based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Study participants were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment. At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT-detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high-density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001). Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.

Obicetrapib on top of maximally tolerated lipid‐modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a) and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure.

Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all-cause death using adjusted time-to-event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person-years (95% CI, 231-233), with a higher rate in women than in men (248 per thousand person-years [95% CI, 247-250] versus 219 per thousand person-years [95% CI, 217-220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13-1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15-1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28-1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99-1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88-0.90]) and a lower risk of all-cause death than men (HR, 0.96 [95% CI, 0.95-0.97]). Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality.

Abstract PO4-13-07: Association of clonal hematopoiesis (CH) with clinical outcomes among survivors of breast cancer (BC)

Abstract Background: Clonal hematopoiesis (CH) refers to the identification of clonal expansion of hematopoietic cells due to somatic mutations in leukemia-associated genes without evidence of hematologic anomalies. CH, particularly with variant allele frequency (VAF) ≥ 10%, has been associated with adverse outcomes, including reduced survival in advanced malignancies and higher risk of cardiovascular events. The aim of this study was to evaluate the biological and prognostic relevance of CH in survivors of breast cancer (BC). Methods: CANTO (NCT01993498) is a prospective, multicenter cohort enrolling patients diagnosed with stage I-III BC. CANTO collects clinical, tumor and treatment-related characteristics at diagnosis (dx). Follow-up visits are scheduled at 1, 2, 4 and 6 years after dx and data on disease status, type of recurrence, and survival status are collected. We assessed CH among pts ≥ 40 years, without previous solid or hematological cancer, with blood samples available at dx and year 4 or experiencing death or disease recurrence before year 4. CH was determined using Next-Generation Sequencing with unique molecular identifiers (HaloPlexHS, Agilent Technologies) for 17 genes (including DNMT3A, TET2, ASXL1, PPM1D, ATM, JAK2 and TP53) on blood samples obtained at dx. Outcomes of interest included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS) defined according to STEEP criteria. Kaplan-Meier estimator, log-rank test and multivariate Cox models assessed prognostic role of CH. Results: In the cohort with available CH data (N=1219) mean age (SD) was 57.5 (10.1) years, 62% of pts were postmenopausal, 40.9% were current or former smokers, 46.2% had stage I BC, 77.7% had HR+/HER2- BC, 53.5% received chemotherapy and 80.8% hormonal therapy. CH was detected with a VAF ≥ 1% in 306 pts (25.1%) including 207 pts (67.6%) with DNMT3A mutation, ≥ 2% in 186 (15.3%) and ≥ 10% in 45 (3.7%) pts. Pts with CH ≥ 10% were more frequently older (65.3 vs 57.2 years, p&amp;lt; .0001) and with a previous history of cardiovascular disease (53.3% vs 37.3%, p&amp;lt; 0.02). At a median (IQR) follow-up of 7.0 (6.2-7.8) years 246 iDFS, 161 DDFS and 118 OS events were observed. Only 8 cases of new hematological malignancies were observed. Pts harboring CH with a VAF ≥ 10% had worse OS (log-rank p=0.04) and CH with a VAF ≥ 10% was associated with higher risk of death (HR= 2.4, 95%CI 1.04-5.6); presence of CH with lower VAF was not associated with worse OS. Table displays complete results for all tested associations. Conclusions: CH at dx was identified in 25% of pts with stage I-III BC aged ≥ 40 years in the CANTO cohort, including 4% with a VAF ≥ 10%. In a large, prospective cohort of survivors of BC, we confirmed known associations of CH with older age and cardiovascular history. We observed few secondary hematological malignancies. CH with a VAF ≥ 10% was significantly associated with higher risk of death while adjusting for other relevant prognostic factors. Furthermore, a trend towards higher risk of DDFS events was observed among pts harboring CH with a VAF ≥ 10%. Table. Citation Format: Davide Soldato, Antonin Della Noce, Antonio Di Meglio, Christophe Marzac, Barbara Pistilli, Anne-Laure Martin, Sibille Everhard, Marie Breckler, Sandrine Boyault, Marina Rousseau, Olivier Trédan, Charles Coutant, Paul Cottu, Olivier Rigal, Christelle Levy, Christelle Jouannaud, Baptiste Sauterey, Nathalie Droin, Bastien Job, Aurélie Bertaut, Fabrice André, Ines Vaz Luis, Jean-Baptiste Micol. Association of clonal hematopoiesis (CH) with clinical outcomes among survivors of breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-07.

Abstract 3110: Association Of Non-O Blood Group With Cardiovascular Outcomes Among Covid-19 Patients

Introduction: Patients with COVID-19 are at an increased risk of cardiovascular complications. Studies indicating an association between ABO blood groups and risk of cardiovascular outcomes were limited by small sample size or use of administrative claims data with uncertain validity. Aim: To study the association of non-O blood group and cardiovascular outcomes among patients with COVID-19 in a large cohort with adjudicated cardiovascular events. Methods: We examined patients from the CORONA-VTE Network registry with confirmed COVID-19 and ABO blood group data. The main outcome was major cardiovascular events including venous or arterial thrombosis, heart failure, myocarditis, new atrial fibrillation/flutter, and cardiovascular death. Outcomes were assessed at 90-day follow-up and adjudicated by independent physicians. Adjusted analyses were conducted accounting for age, sex, cancer, history of cardiovascular disease, history of hemodialysis, history of prior venous thromboembolism, and clustering of patients within sites. Results: Among 3,224 patients of whom 1,658 were inpatients (mean age: 66 ± 17.8) and 1,566 were outpatients (mean age: 52 ± 17.8), 767 (23.8%) inpatients and 728 (22.6%) outpatients had blood group O. Among inpatients, 90-day cumulative incidence of cardiovascular events was 16.9% (95% CI: 14.1-19.5%) for blood group O and 20.8% (95% CI: 18.1- 23.4%) for non-O blood group. Compared with patients with blood group O, those with non-O blood group had a higher risk of cardiovascular events in unadjusted (HR: 1.28, 95% CI: 1.02-1.60%, p=0.03), and adjusted analyses (HR: 1.26, 95% CI: 1.02-1.57%, p=0.04). In outpatients, 90-day event rates were 2.9% (95% CI: 1.7- 4.1%) for blood group O and 4.2% (95% CI: 2.8- 5.6%) for non-O blood group. The risk of cardiovascular events in outpatients with non-O blood group did not reach statistical significance, in unadjusted (HR: 1.46, 95% CI: 0.9-2.5, p=0.172) or adjusted analyses (HR: 1.36, 95% CI: 0.9-2.1, p=0.162). Conclusion: Inpatients with COVID-19 with non-O blood group have a higher risk of cardiovascular events in unadjusted and adjusted analyses. Future studies should explore if patients with non-O blood group may benefit from preventive strategies to mitigate this risk.

ASSOCIATION OF HYSTERECTOMY WITH HYPERTENSION INCIDENCE IN KOREAN WOMEN: A NATIONWIDE COHORT STUDY

Objective: Although several observational studies have reported a higher risk of cardiovascular events in women who underwent hysterectomy, the underlying mechanism is unclear, and limited data exist regarding the effect of hysterectomy on the incidence of hypertension. We sought to evaluate the association between hysterectomy and the development of hypertension in Korean women aged 40–59 years. Design and method: In this Korean nationwide cohort study, 803,255 women aged 40-59 years were selected for analysis from January 1, 2002, to December 31, 2011. In total, 13,650 pairs were included in the hysterectomy and non-hysterectomy groups after 1:1 propensity score matching for age at 5-year intervals, year of inclusion, socioeconomic status, body mass index, residential region, Charlson comorbidity index, menarcheal age, menopause, diabetes, dyslipidemia, physical activity, smoking history, alcohol consumption, menopausal hormone therapy before inclusion, adnexal surgery history, uterine leiomyoma, and endometriosis. The primary outcome was the development of hypertension during follow-up. The participants were followed-up until December 31, 2020. Data analysis was performed from July 16, 2022 to January 07, 2023. Results: During median follow-up periods (10.6 years [IQR 9.2-12.6]; 10.9 years [IQR 9.2-12.7]), the incidence of hypertension was 22/1,000 person-years and 20/1,000 person-years for the hysterectomy and non-hysterectomy groups, respectively. The hysterectomy group had a significantly higher rate of development of hypertension than that of the non-hysterectomy group (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.05-1.17). The risk was prominent in women whose hemoglobin level increased by &gt;2g/dL post-hysterectomy. In women who had an adnexa-sparing hysterectomy, the incidence of hypertension was higher (HR, 1.15; 95% CI 1.08-1.23, P &lt;0.001) than that in the non-hysterectomy group. Conclusions: In this nationwide cohort study of Korean women revealed that hysterectomy was independently associated with an increased risk of hypertension among women aged 40 to 59. In particular, this risk elevation was prominent when the hemoglobin level increased by &gt;2g/dL after hysterectomy, suggesting that hemorheologic changes following hysterectomy may have an impact on the occurrence of hypertension.

RENAL DENERVATION RESULTS IN SUBSTANTIAL NOCTURNAL BP REDUCTION IN PATIENTS WITH A REVERSED DIPPING PATTERN

Objective: We characterized patients with reverse blood pressure (BP) dipping pattern and uncontrolled hypertension (HTN) at baseline referred for radiofrequency renal denervation (RF RDN), and their subsequent BP changes. Design and method: Patients with HTN were enrolled into the Global SYMPLICITY Registry (GSR) DEFINE and underwent RF RDN. Patients were grouped into different BP dipping patterns defined by night/daytime BP ratio: dippers (ratio 0.9 or below), non-dippers (ratio 0.9 to 1.0 or below), reverse dippers (ratio &gt;1.0). Baseline characteristics and BP changes through 3yrs were compared between groups based on dipper patterns. Statistical significance was defined as p&lt;0.05. Results: As of March 2023, 3331 patients with uncontrolled BP were enrolled, 2276 of whom had 24-h BP measures and could be categorized by dipping patterns. Majority of the patients were non-dippers (44.3%), followed by dippers (34.6%) and reverse dippers (21.1%). Reverse dippers (n=480) were the oldest (62±12yrs; p=0.0024), more likely to have cardiac disease (54.2%; p&lt;0.0001), diabetes (48.1%; p&lt;0.0001) and renal disease (38.9%; p&lt;0.0001). Reverse dippers had the highest baseline 24-h ambulatory systolic BP (SBP) (156±19mmHg; p&lt;0.0001) and nighttime SBP (163±21; p&lt;0.0001). In contrast, they had the lowest daytime SBP (153±19mmHg; p&lt;0.0001) and heart rate (66±11bpm; p&lt;0.0001). Reverse dippers were prescribed the most antihypertensive drugs (5.2±1.7; p=0.0058). 3yrs after RF RDN, significant overall 24-h ambulatory SBP reduction from baseline was observed within all dipping patterns, and the largest reduction was observed within reverse dippers (-11.8±25.1mmHg; Figure), particularly in the nighttime (-21.1±23.8mmHg). Conclusions: Reverse dippers with uncontrolled HTN referred for RDN were prescribed more antihypertensive drugs and had more comorbidities compared to patients with other dipping patterns. After RF RDN, significant SBP changes from baseline were observed irrespective of dipping status. The largest BP reduction was observed in nighttime BP in patients with reverse dipping pattern. RF RDN may offer an effective adjunctive therapy to drugs to lower nighttime BP patients with a reverse dipping pattern, who have the highest risk of cardiovascular events.

ARTERIAL HYPERTENSION AND DYSLIPIDEMIA: ROLE OF LIPOPROTEIN(A)

Objective: Dyslipidemia is a common risk factor in patients with arterial hypertension (AH). Besides LDL cholesterol, also increased levels of Lipoprotein(a) (LpA) are associated with higher risk of cardiovascular events. Despite this, there are no established ways to treat LpA, because traditional hypolipidemic drugs have none or only modest effect on LpA levels; however, several promising drugs are in testing. Contrary to the current guidelines, due to absence of effective therapy, LpA levels aren’t routinely evaluated at clinical practice. Aim of our study was to measure LpA in outpatients with AH to see how many of them would be eligible for future treatment. Design and method: We included 55 outpatients who were examined at our department between October and December of 2023. Standard laboratory tests including LpA, basic history, anthropometric and clinical evaluation were carried out. LpA was measured using Randox kit and reported in mg/dl. LpA levels were expressed as median and interquartile range (IQR). Patients with normal LpA levels were defined as &lt; 30 mg/dl and patients with elevated levels were defined as &gt; 50 mg/dl. Results: We examined 55 patients with AH (29 men, 26 women) aged 71,36±10,19 years. Median level of Lp(a) was 18 mg/dl [IQR 8-46]. Normal LpA levels were in 65,5% patients and elevated LpA levels in 23,6% patients. There were no significant differences of LpA between genders, nor we found any significant correlation between LpA and total, LDL and HDL cholesterol, glycemia, creatinine, ALT, TSH, BMI or NTproBNP. However, there was a significant correlation between LpA and triacylglycerols (r = 0,307; p=0,024). We did not find higher levels of LpA in patients with previous myocardial infarction, stroke, or peripheral artery disease. Conclusions: In our study we found 23,6% patients with AH had LpA &gt; 50 mg/dl. Some of these patients might be eligible for targeted LpA treatment in future.

Abstract 1003: Blood Pressure Metrics In Predicting Successful Thoracic Endovascular Aortic Repair

Blood pressure (BP) is a well-known risk factor for propagation of type B aortic dissections; however, there is limited data on its impact following surgical repair. While metrics such as BP variability have been associated with higher risk of cardiovascular events, such metrics has not been explored post TEVAR where management has largely focused on reducing systolic BP. By pairing unique BP metrics with preoperative aortic geometry, which has been shown to predict post-TEVAR outcomes, we can better understand what BP metrics are most useful. BP data collected in the first 24 hours after TEVAR for a cohort of 31 patients was used to calculate 24 unique BP metrics, including measures of centrality, variability, and stationarity. Preoperative CTA imaging data were used to create surface models for each aorta, which were then used to define aortic geometry as a unique point in the validated shape-size feature space. Logistic regression models with the BP and aortic geometry metrics were created to predict successful TEVAR outcomes using standard feature selection procedures and were validated using cross-validation (CV). Training and cross-validation accuracy were then compared between the models to determine the most generalizable model. A simple model using only preoperative aortic geometry in the two-dimensional shape-size feature space yielded a training accuracy of 77.4% and CV accuracy of 74.8%. An overfit model with all 24 BP metrics calculated from all available BP data (18.1 ± 6.0 BPs, range 5 - 29) had a 100% training accuracy but CV accuracy of 77.6%. Using the coefficients from this overfit model, we selected the most important features to train the next model. This resulted in a model using aortic geometry in addition to two systolic BP stationarity metrics and diastolic BP standard deviation. This model yielded a 96.8% training accuracy and 93.8% CV accuracy. Adding BP metrics creates a novel multi-dimensional aortic geometric-physiologic feature space and improves our ability to predict post-TEVAR outcomes. The BP variables that best contributed to this model were all measures of variability and stationarity, indicating that trends in BP must be evaluated to better identify patients at risk of poor outcomes.

Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

CELIAC DISEASE AND CARDIOVASCULAR DISEASES

Background: Celiac disease, an immune-mediated enteropathy that occurs in susceptible individuals after gluten ingestion, has clinical manifestations that go beyond the classical malabsorption syndrome and can affect other systems. Objective: To review the current literature for cardiovascular changes described in patients with celiac disease. Method: We conducted a search in the PubMed database and selected articles based on their relevance to the objective. Results: Celiac patients have a 1.2 times higher risk of cardiovascular events compared to non-celiac patients. The most common cardiovascular manifestations include atherosclerosis, cardiac arrhythmias (especially atrial fibrillation), myocarditis, coronary artery disease, dilated cardiomyopathy, impaired aortic function, and cerebrovascular diseases. There are several possible explanations for this relationship, including: prothrombotic changes, accelerated atherosclerosis compared to patients without celiac disease, associated comorbidities, such as antiphospholipid syndrome and Type 1 Diabetes mellitus, subclinical chronic inflammation and genetic factors. Celiac disease patients have a 38% higher risk of developing atrial fibrillation and a 19% higher risk of coronary artery disease. Furthermore, celiac patients have a 22% higher risk of coronary artery disease-related death, regardless of small intestine histopathology. Patients with celiac disease also show an increased prevalence of dilated cardiomyopathy (5.7%) and a 73% higher risk of developing dilated cardiomyopathy, particularly within the first year of celiac disease diagnosis. Conclusion: Celiac disease may be associated with cardiovascular changes, especially in newly diagnosed patients who have not adhered to a gluten-free diet. Therefore, cardiovascular assessment should be considered as part of the initial assessment and follow-up of individuals with celiac disease.

Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study.

Severe functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, particularly heart failure (HF) and mortality. MicroRNAs (miRNAs) have been recently identified as novel biomarkers in different cardiovascular conditions, but no studies have focused on FTR. We sought to (1) to identify and validate circulating miRNAs as regulators of FTR and (2) to test association of miRNA with heart failure and mortality in FTR. Consecutive patients with isolated severe FTR (n=100) evaluated in the outpatient Heart Valve Clinic and age- and gender-matched subjects with no TR (controls, n=50) were prospectively recruited. The experimental design included (1) a screening phase to identify candidate miRNA differentially expressed in FTR (n=8) compared with controls (n=8) through miRNA array profiling of 192 miRNAs using quantitative reverse transcription PCR arrays [qRT-PCR]) and (2) a validation phase in which candidate miRNAs identified in the initial screening were selected for further validation by qRT-PCR in a prospectively recruited cohort of FTR (n=92) and controls (n=42). Bioinformatics analysis was used to predict their potential target genes and functional pathways elicited. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Initial screening identified 16 differentially expressed miRNAs in FTR compared with controls, subsequently confirmed in the validation phase (n=16 were excluded due to significant haemolysis). miR-186-5p, miR-30e-5p, and miR-152-3p identified FTR with high predictive value [AUC of 0.93 (0.88-0.97), 0.83 (0.75-0.91) and 0.84 (0.76-0.92), respectively]. During a median follow-up of 20.4months (IQR 8-35months), 32% of FTR patients reached the combined endpoint. Patients with low relative expression of miR-15a-5p, miR-92a-3p, miR101-3p, and miR-363-3p, miR-324-3p, and miR-22-3p showed significantly higher rates of events (log-rank test for all P<0.01). Both miR-15a-5p [hazard ratio: 0.21 (0.06-0.649, P=0.007) and miR-92a-3p (0.27 (0.09-0.76), P=0.01] were associated with outcomes after adjusting for age, gender, and New York Heart Association functional class. Circulating miRNAs are novel diagnostic and prognostic biomarkers in severe FTR. The quantification of miR-186-5p, miR-30e-5p, and miR-152-3p held strong diagnostic value, and the quantification of miR-15a-5p and miR-92a-3p are independently associated with outcomes. The recognition of specific miRNAs offers a novel perspective for TR evaluation.

Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease

Abstract Background COVID-19 is associated with cardiovascular outcomes in the general population, but it is unknown whether people with chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related factors may modify this risk in these people. Methods Primary and secondary care data from the National Health Service England were used to define a population of adults in England with COVID-19 (index date) between 1 January 2020 and 30 November 2021. Adjusted Cox proportional hazard regression was used to quantify the association between CRD, asthma-related factors, chronic obstructive pulmonary disease (COPD)-related factors, and risk of cardiovascular events. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes. Results Of 3 670 455 people, those with CRD had a higher risk of cardiovascular events [adjusted hazard ratio (HRadj), 1.08; 95% confidence interval (CI) 1.06–1.11], heart failure (HRadj, 1.17; 95% CI, 1.12–1.22), angina (HRadj, 1.13; 95% CI, 1.06–1.20) and pulmonary emboli (HRadj, 1.24; 95% CI, 1.15–1.33) compared with people without CRD. In people with asthma or COPD, baseline exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj, 1.36; 95% CI, 1.27–1.00 and HRadj, 1.35; 95% CI, 1.24–1.46, respectively). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. Conclusions Higher risk of cardiovascular events post-COVID-19 might be explained by the underlying severity of the CRD, and COVID-19 vaccines were beneficial to both people with and those without CRD with regards to cardiovascualr events.

Risk factors and outcomes in patients who switched from peritoneal dialysis to physician-oriented or patient-oriented kidney replacement therapy

Background We aimed to compare the cardiovascular events and mortality in patients who underwent either physician-oriented or patient-oriented kidney replacement therapy (KRT) conversion due to discontinuation of peritoneal dialysis (PD). Methods Patients with end-stage kidney disease who were receiving PD and required a switch to an alternative KRT were included. They were divided into physician-oriented group or patient-oriented group based on the decision-making process. Logistic regression analysis was used to explore the influencing factors related to KRT conversion in PD patients. The association of physician-oriented or patient-oriented KRT conversion with outcomes after the conversion was assessed by using Cox proportional hazards models. Results A total of 257 PD patients were included in the study. The median age at catheterization was 35 years. 69.6% of the participants were male. The median duration of PD was 20 months. 162 participants had patient-oriented KRT conversion, while 95 had physician-oriented KRT conversion. Younger patients, those with higher education levels, higher income, and no diabetes were more likely to have patient-oriented KRT conversion. Over a median follow-up of 39 months, 40 patients experienced cardiovascular events and 16 patients died. Physician-oriented KRT conversion increased nearly 3.8-fold and 4.0-fold risk of cardiovascular events and death, respectively. After adjusting for confounders, physician-oriented KRT conversion remained about a 3-fold risk of cardiovascular events. Conclusion Compared to patient-oriented KRT conversion, PD patients who underwent physician-oriented conversion had higher risks of cardiovascular events and all-cause mortality. Factors included age at catheterization, education level, annual household income, and history of diabetes mellitus.

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence have prompted the development and implementation of novel drugs in clinical practice with the aim of treating the 'specific cause' of kidney disease (including chronic kidney disease, glomerular disease, and genetic kidney disorders) and the main immunological complications following kidney transplantation. Herein, we provide an overview of the principal emerging drug classes with proved efficacy in the context of the aforementioned clinical conditions. This can represent a simplified guide for clinical nephrologists to remind them of the vast and heterogeneous armamentarium of drugs that should be used in the present and the future to improve the management of patients suffering from kidney disease.

Effect of Gamification, Financial Incentives, or Both to Increase Physical Activity Among Patients at High Risk of Cardiovascular Events: The BE ACTIVE Randomized Controlled Trial.

Physical activity is associated with a lower risk of major adverse cardiovascular events, but few individuals achieve guideline-recommended levels of physical activity. Strategies informed by behavioral economics increase physical activity, but their longer-term effectiveness is uncertain. We sought to determine the effect of behaviorally designed gamification, loss-framed financial incentives, or their combination on physical activity compared with attention control over 12-month intervention and 6-month postintervention follow-up periods. Between May 2019 and January 2024, participants with clinical atherosclerotic cardiovascular disease or a 10-year risk of myocardial infarction, stroke, or cardiovascular death of ≥7.5% by the Pooled Cohort equation were enrolled in a pragmatic randomized clinical trial. Participants received a wearable device to track daily steps, established a baseline, selected a step goal increase, and were randomly assigned to control (n=151), behaviorally designed gamification (n=304), loss-framed financial incentives (n=302), or gamification+financial incentives (n=305). The primary outcome of the trial was the change in mean daily steps from baseline through the 12-month intervention period. A total of 1062 patients (mean±SD age, 67±8; 61% female; 31% non-White) were enrolled. Compared with control subjects, participants had significantly greater increases in mean daily steps from baseline during the 12-month intervention in the gamification arm (adjusted difference, 538.0 [95% CI, 186.2-889.9]; P=0.0027), financial incentives arm (adjusted difference, 491.8 [95% CI, 139.6-844.1]; P=0.0062), and gamification+financial incentives arm (adjusted difference, 868.0 [95% CI, 516.3-1219.7]; P<0.0001). During the 6-month follow-up, physical activity remained significantly greater in the gamification+financial incentives arm than in the control arm (adjusted difference, 576.2 [95% CI, 198.5-954]; P=0.0028), but it was not significantly greater in the gamification (adjusted difference, 459.8 [95% CI, 82.0-837.6]; P=0.0171) or financial incentives (adjusted difference, 327.9 [95% CI, -50.2 to 706]; P=0.09) arms after adjustment for multiple comparisons. Behaviorally designed gamification, loss-framed financial incentives, and the combination of both increased physical activity compared with control over a 12-month intervention period, with the largest effect in gamification+financial incentives. These interventions could be a useful component of strategies to reduce cardiovascular risk in high-risk patients. URL: https://clinicaltrials.gov; Unique Identifier: NCT03911141.

Uncovering atherosclerotic cardiovascular disease by PET imaging.

Assessing atherosclerosis severity is essential for precise patient stratification. Specifically, there is a need to identify patients with residual inflammation because these patients remain at high risk of cardiovascular events despite optimal management of cardiovascular risk factors. Molecular imaging techniques, such as PET, can have an essential role in this context. PET imaging can indicate tissue-based disease status, detect early molecular changes and provide whole-body information. Advances in molecular biology and bioinformatics continue to help to decipher the complex pathogenesis of atherosclerosis and inform the development of imaging tracers. Concomitant advances in tracer synthesis methods and PET imaging technology provide future possibilities for atherosclerosis imaging. In this Review, we summarize the latest developments in PET imaging techniques and technologies for assessment of atherosclerotic cardiovascular disease and discuss the relationship between imaging readouts and transcriptomics-based plaque phenotyping.

Syphilis and cardiovascular risk: a Taiwanese registry.

Studies on the impact of syphilis on the cardiovascular system in large populations are limited. This study investigated the effects of syphilis on cardiovascular outcomes. Medical records from 2010 to 2015 were retrieved from the Taiwan National Health Insurance Research Database, linked to the Notifiable Infectious Diseases database from the Taiwan Centers for Disease Control. Patients with syphilis were identified, excluding those with missing information, under 20 years of age, or with a history of human immunodeficiency virus infection, acute myocardial infarction, heart failure, aortic regurgitation, replacement of the aortic valve, aneurysm and/or dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, and venous thromboembolism. Primary outcomes included new-onset acute myocardial infarction, heart failure, aortic regurgitation, aneurysm and dissection of the aorta, atrial fibrillation, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, cardiovascular death, and all-cause mortality. A total of 28 796 patients with syphilis were identified from 2010 to 2015. After exclusions and frequency matching, 20 601 syphilis patients and 20 601 non-syphilis patients were analysed. The relative rate (RR) was utilized in the analysis, as the competing risk of death was not considered. Compared with patients without syphilis, patients with syphilis had increased risks of acute myocardial infarction (RR 38%, 95% confidence interval [CI] 1.19-1.60, P < .001), heart failure (RR 88%, 95% CI 1.64-2.14, P < .001), aortic regurgitation (RR 81%, 95% CI 1.18-2.75, P = .006), atrial fibrillation (RR 45%, 95% CI 1.20-1.76, P < .001), ischaemic stroke (RR 68%, 95% CI 1.52-1.87, P < .001), haemorrhagic stroke (RR 114%, 95% CI 1.74-2.64, P < .001), venous thromboembolism (RR 67%, 95% CI 1.23-2.26, P = .001), cardiovascular death (RR 155%, 95% CI 2.11-3.08, P < .001), and all-cause death (RR 196%, 95% CI 2.74-3.19, P < .001) but not for aneurysm and dissection of the aorta. This study demonstrates that patients with syphilis have a higher risk of cardiovascular events and all-cause mortality compared with those without syphilis.

Role of Small Dense Low-density Lipoprotein Cholesterol in Cardiovascular Events in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Receiving Statin Treatment.

There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

Natriuretic Peptides and Prognosis in Patients With Type 2 Diabetes Mellitus and High Risk for Cardiovascular Events

BackgroundThe prognosis of individuals with and without an established heart failure (HF) diagnosis and similarly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels is not well-known. Methods and ResultsCANVAS (Canagliflozin Cardiovascular Assessment Study) trial participants were stratified according to baseline NT-proBNP quartiles and history of HF at baseline. Adjusted event rates per 1000 patient-years of follow-up for hospitalizations for HF, cardiovascular mortality, and kidney events were assessed, and hazard ratios (HR) were calculated using Cox proportional hazard models. Of the 3507 participants with available NT-proBNP concentrations, 471 (13.4%) had history of HF. The incidence rate per 1000 patient-years for hospitalizations for HF increased across the NT-proBNP quartiles in patients with (0, 2.8, 13.4, and 40.1; P < .001) and without (1.8, 3.1, 6.0, and 19.1; P < .001) HF, with a significantly higher risk in patients with HF compared with those without (with HF, quartile 3 HR 9.28 [interquartile range (IQR) 1.15–75.05]; P = .04; without HF, quartile 4 HR 4.86 [95% CI, 2.08–11.35]; P < .001). A similar higher risk for kidney events was seen in HF patients (with HF, quartile 4 HR 6.94 [95% CI, 2.66–18.08]; P = .001; without HF, quartile 4 HR 4.85 [95% CI, 3.02–7.80]; P = .001). Similar trends were seen for cardiovascular mortality. ConclusionsAmong patients with type 2 diabetes and cardiovascular risk, an elevated NT-proBNP level was associated with worse HF and kidney outcomes in general, regardless of history of HF; however, the presence of a clinical diagnosis of HF at baseline was associated with an incrementally higher risk, particularly in higher NT-proBNP quartiles.