Disease Events Research Articles

Low chronotropic response in post-myocardial infarction exercise test predicts worse prognosis in patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background Chronotropic incompetence is common in post-myocardial infarction (MI) patients and is associated with reduced exercise capacity. However, its prognostic significance and a determination of threshold values for prognosis remain unclear. Methods & Results We assessed 96 post-MI patients 4 weeks after their initial event with left ventricular ejection fraction (LVEF) ≥ 40%. All patients underwent combined stress echocardiography and cardiopulmonary exercise tests. The chronotropic response was measured as a percent of the maximal predicted heart rate at peak exercise (%MPHR). Exclusion criteria included patients with exercise limitations for pulmonary or peripheral reasons and those who declined to complete the study. Follow-up was conducted in 86 patients. The primary outcome measured was a composite of all-cause mortality or hospitalization for ischemic heart disease events (acute MI, unstable angina, or revascularization procedures) or heart failure exacerbation. The median follow-up duration was 4.0 (IQR 2, 5.6) years. The median patient age was 60 (IQR 53, 65) years, 64% of patients were males, and 84% were on beta-blockers. Median LVEF was 57 (IQR 51, 62)%, and median peak VO2 was 19 (IQR 15, 22) mL/kg/min. There were 15 composite end-point events, including 3 deaths, during the follow-up period. The %MPHR threshold of 67% had the best predictive value with an area under the curve (AUC) of 77% for predicting the primary outcome (PPV 31%, NPV 97%, sensitivity 93%, specificity 55%). A significant difference (p = 0.0022) in the occurrence of the composite end-point was noted between patients with a %MPHR below versus above this threshold (Figure. Kaplan-Meier curves for survival free of primary outcome). In the multivariate Cox regression analysis adjusting for demographic, clinical variables, and beta-blocker doses, only chronotropic response and current smoking correlated with the primary end-point (Table. The Cox proportional hazards regression model for prediction of the primary outcome). Conclusions A low chronotropic response to exercise is a negative prognostic marker in post-myocardial infarction patients with either preserved or mildly reduced left ventricular ejection fraction.Figure.Table.

ASCVD risk scores versus a novel cancer-specific Machine Learning-based calculator among patients with breast, colorectal, lung or prostate cancer

Abstract Background Patients with cancer have up to a 3-fold higher risk for cardiovascular disease (CVD) than the general population. Consequently, traditional risk scores developed to predict CVD in the general population (i.e., Pooled Cohort Equations (PCE), Predicting Risk of cardiovascular disease EVENTs [PREVENT]) may provide less accurate risk prediction for this population. Purpose Compare cancer-specific Machine Learning (ML)-based score to PCE and PREVENT to predict 10-year CVD risk in patients with breast cancer (BC), colorectal cancer (CRC), lung cancer (LC), or prostate cancer (PC). Methods Patients aged ≥18 years, diagnosed with BC, CRC, LC, or PC between 2005-2012 at a large hybrid academic-community practice in Northeast Ohio, United States, were included. An ML Extreme Gradient Boosting (XGBoost) algorithm, adapted for survival modeling, was developed using a training subset of the cohort (55% train + 20% test) and ranked 40 to 50 covariates (including social determinants of health, cancer treatment) for predicting 10-year CVD risk for each cancer type using SHAP (SHapley Additive exPlanations) values. The top 10 ML predictors were utilized to create a predictive equation using logistic regression models. This equation was then tested in the cohort validation subset (25%) and subsequently compared to the PCE and PREVENT (both simple and enhanced versions) using the area under the curve (AUC) of the time-dependent receiver operating characteristic curve. The CVD events were identified using ICD codes corresponding to Acute Coronary Syndrome, Ischemic Stroke, and Heart Failure. CVD risk was assessed through Kaplan-Meier. Results We included 10,240 patients (Table 1). The actual 10-year CVD events were: BC 21% (95% CI 19-23), CRC 10% (95% CI 8-12), LC 27% (95% CI 24-30), and PC 20% (95% CI 17-23). The ACC/AHA PCE predicted mean 10-year CVD risks of 16% (95% CI 15-18) for BC, 19% (95% CI 17-21) for CRC, 28% (95% CI 25-32) for LC, and 19% (95% CI 19-20) for PC, with corresponding AUCs of 0.75, 0.65, 0.76, and 0.61, respectively. The PREVENT simple version predicted mean 10-year CVD risks of 13% (95% CI 13-14) for BC, 13% (95% CI 12-13) for CRC, 15% (95% CI 14-15) for LC, and 16% (95% CI 12-19) for PC, with AUCs of 0.55, 0.55, 0.55, and 0.53, respectively. The PREVENT enhanced equation predicted mean 10-year CVD risks of 17% (95% CI 17-18) for BC, 15% (95% CI 14-15) for CRC, 15% (95% CI 15-16) for LC, and 17% (95% 16-19) for PC, with AUCs of 0.75, 0.62, 0.79, and 0.63, respectively. The predictive equation derived from the top 10 ML predictors (Table 2) achieved AUCs of 0.84 for BC, 0.76 for CRC, 0.83 for LC, and 0.71 for PC. Conclusion(s) Conventional CVD equations inadequately assess the risk in patients with BC, CRC, LC, or PC, often resulting in underestimation or overestimation. Cancer-specific ML-derived equations show good performance and emphasize the importance of integrating cancer-related covariates for precise prediction.Table 1Table 2

The effectiveness and barrier of reverse cascade screening for paediatric familial hypercholesterolaemia

Abstract Background Familial Hypercholesterolaemia (FH) is an autosomal dominant genetic disorder that is prevalent in one out of every 300 individuals in the general population. Recognized as an actionable condition, early diagnosis of FH in children is crucial to prevent the onset of atherosclerosis, and equally important is the identification of parents before the development of coronary artery disease events. Therefore, the significance of universal FH screening during childhood combined with reverse cascade screening has been increasingly acknowledged. To achieve these objectives, in our region, universal lipid screening is conducted in elementary schools for children aged 9 or 10 years, annually screening approximately 8,000 individuals, with those identified being referred through a three-step process to four major healthcare facilities within the prefecture. However, the effectiveness of reverse-cascade screening remains unclear. Purpose Our study aimed to assess the effectiveness of and identify barriers to implementing reverse cascade screening in conjunction with universal lipid screening. Methods We conducted a single-center, retrospective observational study from January 2018 to July 2023 and evaluated the utility of reverse cascade screening for children genetically diagnosed with FH following universal screening. This study analysed prevalent barriers and identified families with suspected FH through reverse cascade screening, counting those with Potential FH among second-degree relatives. Beyond successful identification, we categorized the frequently encountered barriers into five distinct categories: bereavement, prior cardiovascular events, dyslipidaemia with unspecified LDL-C levels, incomplete family history information, and inadequate disease awareness of FH. Reverse FH diagnosis adhered to current guidelines. Results and Discussion Of 151 paediatric patients referred to our facility, 67 were genotypically confirmed to have FH. Excluding 8 cases of divorce and 4 cases of tracking challenges, 55 patients were finally analysed. 62 patients were diagnosed with reverse FH, and appropriate treatment was initiated. Notably, 158 cases of Potential FH were identified. (25 first-degree and 133 second-degree relatives). While a higher number of reverse FH diagnoses were observed in first-degree relatives (55 cases), the diagnostic yield was lower among second-degree relatives (seven cases). Common barriers for second-degree relatives included dyslipidaemia with unspecified LDL-C levels (42 cases) and incomplete family history information (66 cases). Conclusion Integrating universal screening with reverse cascade screening facilitates the identification of new FH cases. A comprehensive strategy for diagnosing reverse FH is paramount, raising disease awareness, genetic testing, the development of a family-based care plan, and enhancing access to information and communication technologies.

Cost-Effectiveness of Artificial Intelligence-Enabled Electrocardiograms for Early Detection of Low Ejection Fraction: A Secondary Analysis of the Electrocardiogram Artificial Intelligence-Guided Screening for Low Ejection Fraction Trial

ObjectiveTo investigate the cost-effectiveness of using artificial intelligence (AI) to screen for low ejection fraction (EF) in routine clinical practice using a pragmatic randomized controlled trial (RCT). Patients and MethodsIn a post hoc analysis of the electrocardiogram (ECG) AI-guided screening for low ejection fraction trial, we developed a decision analytic model for patients aged 18 years and older without previously diagnosed heart failure and underwent a clinically indicated ECG between August 5, 2019, and March 31, 2020. In the previously published RCT, the intervention arm underwent an AI-guided targeted screening program for low EF with a workflow embedded into routine clinical practice—AI was applied to the ECG to identify patients at high-risk and recommended clinicians to order an ECG and the control arm received usual care without the screening program. We used results from the RCT for rates of low EF diagnosis and a lifetime Markov model to project the long-term outcomes. Quality-adjusted life years (QALYs), costs of intervention and treatment, disease event costs, incremental cost-effectiveness ratio (ICER), and cost for the number needed to screen. Multiple scenario and sensitivity analyses were performed. ResultsCompared with usual care, AI-integrated ECG was cost effective, with an incremental cost-effectiveness ratio of $27,858/QALY. The program remained cost effective even with a change in patient age and follow-up time duration, although the specific ICER values varied for these parameters. The program was more cost effective in outpatient settings (ICER $1651/QALY) than in inpatient or emergency room settings. ConclusionImplementing AI-guided targeted screening for low EF in routine clinical practice was cost effective.

An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification.

The triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (eLDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker. Using least-square regression analysis, the following eLDL-TG equation was developed: . LDL-TG was measured by the β-quantification (BQ) reference method (N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and eLDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (N = 14,632). eLDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that eLDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high eLDL-TG had a similar risk as the high LDL-C/high eLDL-TG group. Furthermore, these same two groups with the highest eLDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower eLDL-TG groups. Using eLDL-TG > 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29-1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using eLDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules. Like LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, eLDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.

2024 Latin American Society of Hypertension guidelines on the management of arterial hypertension and related comorbidities in Latin America.

Hypertension is responsible for more than two million deaths due to cardiovascular disease annually in Latin America (LATAM), of which one million occurs before 70 years of age. Hypertension is the main risk factor for cardiovascular morbidity and mortality, affecting between 20 and 40% of LATAM adults. Since the publication of the 2017 LASH hypertension guidelines, reports from different LATAM countries have confirmed the burden of hypertension on cardiovascular disease events and mortality in the region. Many studies in the region have reported and emphasized the dramatically insufficient blood pressure control. The extremely low rates of awareness, treatment, and control of hypertension, particularly in patients with metabolic disorders, is a recognized severe problem in LATAM. Earlier implementation of antihypertensive interventions and management of all cardiovascular risk factors is the recognized best strategy to improve the natural history of cardiovascular disease in LATAM. The 2024 LASH guidelines have been developed by a large group of experts from internal medicine, cardiology, nephrology, endocrinology, general medicine, geriatrics, pharmacology, and epidemiology of different countries of LATAM and Europe. A careful search for novel studies on hypertension and related diseases in LATAM, together with the new evidence that emerged since the 2017 LASH guidelines, support all statements and recommendations. This update aims to provide clear, concise, accessible, and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated cardiovascular risk factors in the region.

Beyond the plaque: immunological implications of risk factors in atherosclerosis

The formation of atherosclerotic plaque results from the complex interaction between modifiable and non-modifiable risk factors, through immune mechanisms that orchestrate both inflammatory and anti-inflammatory processes. Atherosclerosis often culminates in ischemic heart disease or cerebrovascular events, which are the leading causes of mortality worldwide. Currently, primary prevention focuses on controlling modifiable risk factors. Therefore, understanding the molecular mechanisms underlying the damage induced by these risk factors is essential to develop more effective treatments. This article provides a detailed review of the immunological processes underlying the initiation and progression of atheroma plaque, exploring their relationship with traditional risk factor such as smoking, diabetes mellitus, dyslipidemia, and hypertension, as well as a new potential risk factor: microbiota dysbiosis. Furthermore, the attributable risk of each factor is independently assessed, and the effectiveness of risk factor control measures is demonstrated as the best strategy to date for the regression of atherosclerosis and the prevention of its complications.

Lower Perceived Social Support Associated With Greater Hopelessness in Patients After an Acute Ischemic Heart Disease Event.

Hopelessness is present in up 52% of patients with ischemic heart disease (IHD) and is associated with increased morbidity and mortality. Lower perceived social support (PSS) has been associated with greater hopelessness in a pilot study of patients with IHD reporting moderate-severe hopelessness but has not been examined in a larger sample reporting none-severe levels of hopelessness and while controlling for covariates. The aim of this study was to determine the relationship between PSS and hopelessness in patients with IHD. Using a cross-sectional design, 178 participants were enrolled while hospitalized for an IHD event at 1 large hospital in the United States. Data collection occurred 2 weeks after hospital discharge using the State-Trait Hopelessness Scale, ENRICHD Social Support Inventory, Patient Health Questionnaire-9, a demographic form, and a medical record abstraction form. Linear models were used to assess the association between variables in unadjusted models and models adjusted for demographic and medical history. Most participants were male (67%), married (67%), and non-Hispanic White (92%) and underwent coronary artery bypass surgery (61%). There was a moderate inverse correlation between PSS and state (r = -0.31, P < .001) and trait (r = -0.28, P < .001) hopelessness in unadjusted models. The relationships remained significant in adjusted models and did not differ by sex, type of IHD event, or marital status. Lower PSS was associated with greater hopelessness in patients with IHD. Assessing PSS and hopelessness during hospitalization for an IHD event may enable clinicians to provide targeted interventions to reduce risk of hopelessness and improve secondary prevention in patients with IHD.

A community-centric model for conference co-creation: the world conference on CDG for patients, families and professionals

BackgroundPatient and public co-creation and involvement in health initiatives have been witnessing great expansion in recent years. From healthcare to research settings, collaborative approaches are becoming increasingly prevalent and diverse, especially in the field of rare diseases which faces complex challenges. Conference development and implementation, however, have been primarily guided by passive, information-sharing models. There is a need for conferences to evolve towards more inclusive, interactive, collaborative, and problem-solving platforms. Here, we aimed to report on a pioneer model, emphasizing a community partnership approach to conference co-creation that takes the World Conference on Congenital Glycosylation Disorders (CDG) as an exemplary case.MethodsTo answer the need to overcome the lack of access to high-quality information which limits CDG diagnosis, research and treatment options, the World CDG Organization has been refining a community-centric model for conference co-creation. Focusing on the 5th edition of the conference, data on stakeholders’ preferences was collected using an online survey and a poll to define the conference agenda, guide its development and select optimal dates for an all-stakeholder inclusive, relevant and participatory event.ResultsWe describe the complexities of the community-centric conference co-creation model, detailing its refined methodology and the outcomes achieved. The model is grounded on a participative approach to promote people-centered research and care for CDG patients. The involvement of the public in the conference co-creation and in participatory methods allowed the generation of knowledge on community needs and preferences.ConclusionThis paper describes a reliable, highly adaptable conference co-creation model that fosters community-building, disseminates understandable information, and serves as a borderless platform to incentivize multiple stakeholder collaborations towards CDG research and drug development. We argue this is a reproducible model that can be endorsed and more widely adopted by other disease communities and events.

Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patients.

Diabetes mellitus is characterized by insulin resistance (IR) and dysfunctional insulin secretion from pancreatic β-cells. However, little research has been conducted on the relationship between IR and β-cell function in relation to diabetic complications among Korean diabetic patients. This study aimed to examine the differential associations between IR and β-cell function and various diabetic complications among Korean diabetic patients. The analysis employed a common data model (CDM). IR and β-cell function were quantified using the homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. Hazard ratios for diabetic nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) events were calculated. The study cohort consisted of 2,034 diabetic patients aged over 20 years who visited EUMC between January 2001 and December 2019. Among diabetic patients in the highest quartile of HOMA-IR, the adjusted hazard ratio for total CVD events was 1.76 (95% confidence interval [CI], 1.20-2.57) compared with those in the lowest quartile of HOMA-IR (P = 0.004). In contrast, diabetic patients in the lowest quartile of HOMA-β exhibited an adjusted hazard ratio of 3.91 (95% CI, 1.80-8.49) for diabetic retinopathy compared to those in the highest quartile of HOMA-β (P = 0.001). Insulin resistance and β-cell function exhibited different associations with diabetic complications among Korean diabetic patients. Specifically, lower β-cell function was associated with an increased risk of diabetic retinopathy, whereas higher IR was associated with an increased risk of CVD events. Individuals with pronounced IR should prioritize CVD prevention measures, and those with significant β-cell dysfunction may benefit from early, intensive surveillance for diabetic retinopathy.

Pulse Pressure and Cardiovascular and Kidney Outcomes by Age in the Chronic Renal Insufficiency Cohort (CRIC).

Wide pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to kidney failure. PP naturally widens with age, but it is unclear whether the risks associated with greater PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with (i) atherosclerotic cardiovascular disease (ASCVD) events or death and (ii) a 50% reduction in estimated glomerular filtration rate or kidney failure in the chronic renal insufficiency cohort (CRIC). We evaluated the association of time-updated PP with these outcomes, accounting for time-updated confounders using inverse probability weighting. Among 5,621 participants with CKD, every 10-mmHg greater PP was associated with a 6% higher risk of an ASCVD event or death (hazard ratio [HR] = 1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite kidney outcome (HR = 1.17, 95% CI 1.16, 1.18). Greater PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years), but a higher risk of the composite kidney outcome in the oldest age tertile (71-79 years). While wide PP in participants that experienced the primary outcomes was predominantly driven by elevated SBP, PP remained significantly associated with the composite kidney outcome across all ages and with ASCVD events or death in the first age tertile when SBP was added to the Cox regression model. Our findings suggest that the mechanism by which PP is associated with adverse outcomes may differ by age.

Approaches to the Diagnosis and Management of Paediatric Ovarian Tumours and Oncological Outcomes in a Single-centre Study. Evidence in Support Of IPSO Reccomendations

BackgroundApproaches to paediatric ovarian tumours vary. Cross-sectional imaging is reliable but not always performed. Laparoscopic tumourectomy, although popular, is not recommended by International Paediatric Surgical Oncology Society (IPSO); tumour spillage remains the main concern. We aimed to investigate the reliability of preoperative evaluation and identify perioperative factors associated with adverse outcomes. MethodsSingle-centre retrospective study (2015–2022) of clinical presentation, preoperative investigation, operative approaches and oncological outcomes in all females <18 years treated for ovarian tumours. Logistic regression was used to identify predictors of malignancy and of second disease events. Data are presented as median (IQR) or rates. ResultsSixty girls aged 12.5 (10–15) years with follow-up of 51 (30.5–76.3) months were included. Incidence of malignant and low malignant potential tumours was 19/60 (32%). Tumour size and consistency proved predictive of malignancy. Clinical assessement, tumour markers and cross-sectional imaging combined showed 75% sensitivity, 100% specificity and 7% misclassified malignancy rate. Second disease events (11/60, 18%) were associated with misclassified malignancy (2/11 vs. 1/49, p = 0.04) and positive margins (4/11 vs. 5/49, p = 0.02). Ovarian-sparing surgery did not influence second events (5/11 vs. 28/49, p = 0.48). There was no significant association between second events and laparoscopic tumourectomy (3/11 vs. 20/49, p = 0.40); spillage rate was however more frequent with laparoscopy (5/11 vs. 2/32, p = 0.008). ConclusionMisclassified malignancy, noted in 7% of patients undergoing optimal work-up, adversely impacted outcomes, highlighting the importance of oncological principles in both oophorectomy and ovarian-sparing surgery. Malignancy incidence and misclassification can be underestimated when tumours with malignant behaviour potential, such as immature teratomas and borderline tumours, are grouped as benign. There was no direct association between operative approaches and second events. Laparoscopy, however, failed to maintain oncological principles more frequently than open surgery and hence risks upstaging of paediatric ovarian pathology. Level of evidenceIII.

Risk of Inflammatory Central Nervous System Diseases After Tumor Necrosis Factor–Inhibitor Treatment for Autoimmune Diseases

Tumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents. To evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors. Separate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024. Observational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group. Study eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis. The primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors. Eighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I2, 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I2, 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I2, 0%). Compared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.

Synergies between diabetes and hyperhomocysteinaemia: New insights to predict and prevent adverse cardiovascular effects.

To explore the association of hyperhomocysteinaemia (HHcy) and diabetes synergies with cardiovascular events in the adult population of northern China. Data were collected from the Asymptomatic Polyvascular Abnomalities Community study for 2010 to 2019. Serum homocysteine (Hcy) levels were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their Hcy levels and diabetes status: non-diabetes/non-HHcy, non-diabetes/HHcy, diabetes/non-HHcy and diabetes/HHcy. The composite endpoint consisted of the occurrence of first-ever stroke, myocardial infraction (MI) or all-cause mortality. Cox regression analyses were performed to evaluate the associations of diabetes and HHcy with cardiovascular disease (CVD) events. In total, 5278 participants were eligible (average age 55.1 years, 60% male). Over a follow-up of 9.1 years, 618 events were identified, 202 stroke, 52 MI and 406 all-cause deaths. Compared with the non-diabetes/non-HHcy group, hazard ratios with 95% confidence intervals in the diabetes/HHcy group for stroke, MI, major adverse cardiovascular event (MACE), all-cause death and composite endpoint were 1.85 (1.12-3.04), 1.33 (0.42-4.23), 1.78 (1.13-2.80), 2.24 (1.56-3.23) and 1.97 (1.47-2.65), respectively. Significant interactions between HHcy and diabetes status were found for stroke, MI and MACE (P for interaction = .002, .027 and .044, respectively). In addition, the association of diabetes/HHcy with stroke was modified by age (< 60 and ≥ 60 years; P for interaction = .016). The findings highlight the synergistic impact of diabetes and HHcy on CVD. Joint assessments of diabetes and Hcy levels should be emphasized for risk stratification and primary prevention of CVD.

Coronary heart disease evaluation using PCAT radiomics model based on coronary CT angiography and pericoronary adipose tissue.

To explore the clinical application value of radiomics model based on pericoronary adipose tissue (PCAT) in predicting coronary heart disease. A retrospective analysis was performed for inpatients who had undergone coronary computed tomography angiography from January to December 2023, and 164 cases of coronary artery lesions were screened as the lesion group and 190 cases of normal coronary artery samples were selected as the control group. The clinical data and imaging data of all patients were collected, the radiomics features were extracted by relevant software, and the "region of interest" of pericoronary fat was delineated, and the selection operator and multivariate logistic regression were used to screen the radiomic features of pericoronary fat. A coronary heart disease evaluation model was constructed by the best radiomics features. Area under the curve values of the PCAT radiomics scoring model for predicting the receiver operating characteristic curve of coronary heart disease were 0.863 and 0.851 in training and test sets, respectively. After calibration curve analysis, PCAT radiomics scoring model has a high consistency between the predictive evaluation results and the actual results of coronary heart disease events. In addition, in the training set, the PCAT radiomics scoring model has a net benefit on all threshold probabilities. In the test set, the model has a negative net return with only a small number of threshold probabilities. After combining the clinical characteristics model, the evaluation accuracy of the model for coronary heart disease can reach 0.896. PCAT radiomics model based on coronary computed tomography angiography can effectively predict and evaluate coronary heart disease, which is of great value for the clinical diagnosis of coronary artery disease.

Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis.

Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition. A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition defined as any of the following: BP-specific International Classification of Diseases, Tenth Revision, diagnosis; problem list entry; specialty referral; diagnostic testing; repeat visit; or antihypertensives. Dichotomized as underpre versus at or over 13 years of age, analyses utilized interrupted time series and multivariable-adjusted logistic regression. From preintervention (children, n=105 674; adolescents, n=54 365) to postintervention (children, n=87 917; adolescents, n=56 470), the proportion measured with high BP declined in children and adolescents (30% versus 14% and 30% versus 15%, respectively, each P<0.001). Post-intervention, high BP provider recognition was 58% higher in children (4.6%-7.3%) and 43% higher in adolescents (7.9% versus 11.3%; P<0.001 for both). The improvement was not different in disadvantaged race, ethnicity, or zip codes. A comprehensive BP initiative was associated with more appropriate high BP measurement and recognition including in disadvantaged populations. Future work may address the low overall and nonsustained recognition and consideration of electronic decision support for pediatric BP management and mitigating disparities.

Unlocking the power of tobacco taxation to mitigate the social costs of smoking in Mexico: a microsimulation model.

Despite being the most cost-effective tobacco control policy, tobacco taxation is the least implemented component of the World Health Organization MPOWER package to reduce smoking worldwide. In Mexico, both smoking prevalence and taxation have remained stable for more than a decade. This study aims to provide evidence about the potential effects of taxation to reduce the burden of tobacco-related diseases and the main attributable social costs in Mexico, including informal (unpaid) care costs, which are frequently ignored. We employ a first-order Monte Carlo microsimulation model that follows hypothetical population cohorts considering the risks of an adverse health event and death. First, we estimate tobacco-attributable morbidity and mortality, direct medical costs and indirect costs, such as labour productivity losses and informal care costs. Then, we assess the potential effects of a 50% cigarette price increase through taxation and two alternative scenarios of 25% and 75%. The inputs come from several sources, including national surveys and vital statistics. Each year, 63 000 premature deaths and 427 000 disease events are attributable to tobacco in Mexico, while social costs amount to MX$194.6 billion (US$8.5)-MX$116.2 (US$5.1) direct medical costs and MX$78.5 (US$3.4) indirect costs-representing 0.8% of gross domestic product. Current tobacco tax revenue barely covers 23.3% of these costs. Increasing cigarette prices through taxation by 50% could reduce premature deaths by 49 000 over the next decade, while direct and indirect costs averted would amount to MX$87.9 billion (US$3.8) and MX$67.6 billion (US$2.9), respectively. The benefits would far outweigh any potential loss even in a pessimistic scenario of increased illicit trade. Tobacco use imposes high social costs on the Mexican population, but tobacco taxation is a win-win policy for both gaining population health and reducing tobacco societal costs.

The relationship between serum HDL-cholesterol, cardiovascular disease and mortality in community-based people with type 2 diabetes: the Fremantle Diabetes Study phase 2

BackgroundOlder general population-based studies found an inverse association between serum HDL-cholesterol and both cardiovascular disease (CVD) events and mortality, but more recent data have suggested a U-shaped relationship. Whether this applies to type 2 diabetes is uncertain. The aim of this study was to assess the prognostic significance of serum HDL-cholesterol concentrations in representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2).MethodsWe followed 1,479 FDS2 participants with confirmed type 2 diabetes (713 females, mean age 65.6 years; 763 males, mean age 65.9 years) from entry (2008–2011) to death/end-2021. Major adverse cardiovascular events (non-fatal myocardial infarction (MI), non-fatal stroke, cardiovascular death; 3-point MACE), and all-cause mortality were ascertained from prospectively collected data and validated administrative databases. Independent associates of 3-point MACE by sex, excluding participants with prior MI/stroke, were assessed using Cox and competing risk models with sex-specific quintiles of HDL-cholesterol added to the most parsimonious models. Predictors of all-cause mortality were identified using Cox proportional hazards modelling.ResultsIn females, with baseline serum HDL-cholesterol quintile 2 (1.04–1.22 mmol/L) as reference, both quintiles 1 (< 1.04 mmol/L) and 5 (> 1.59 mmol/L) were significant independent predictors of 3-point MACE (P < 0.027) and all-cause death (P < 0.019) after adjustment for a full range of demographic, clinical and laboratory variables. In males, serum HDL-cholesterol quintile did not add to the most parsimonious model for 3-point MACE, but quintile 1 (< 0.90 mmol/L) was a significant predictor of death (P = 0.026 versus quintile 4 (1.15–1.31 mmol/L) as reference) after adjustment. Competing risk analyses for 3-point MACE showed similar results to the Cox models for both sexes.ConclusionThere was a significant U-shaped relationship between serum HDL-cholesterol and both 3-point MACE and all-cause death in females with type 2 diabetes after adjustment for confounders. There was no such relationship for 3-point MACE in males but a low HDL-cholesterol was associated with all-cause mortality. These data have sex-specific implications for assessment of serum lipid profiles in the clinical management of type 2 diabetes.

Predictors in Youth of Adult Cardiovascular Events.

Childhood risk factors are associated with cardiovascular events in adulthood. We compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a model that additionally included lipids to predict cardiovascular events in adulthood. The study comprised 11 550 participants from 7 longitudinal cohort studies in the United States, Australia, and Finland with risk factor measurements in adolescence and followed into adulthood. The adolescent risk factors were defined by using clinical standards including overweight or obesity, elevated blood pressure, smoking, and borderline high or high levels of total cholesterol and triglycerides. The main outcomes were medically adjudicated fatal or nonfatal cardiovascular disease events occurring after age 25. Of 11 550 participants (55.1% female, mean age 50.0 ± 7.7 years), 513 (4.4%) had confirmed cardiovascular events. In a multivariable model (hazard ratio [95% confidence interval]), elevated blood pressure (1.25 [1.03-1.52]), overweight (1.76 [1.42-2.18]), obesity (2.19 [1.62-2.98]), smoking (1.63 [1.37-1.95]), and high total cholesterol (1.79 [1.39-2.31]) were predictors of cardiovascular events (P < .05). The addition of lipids (total cholesterol and triglycerides) into the nonlaboratory model (age, sex, blood pressure, BMI, and smoking) did not improve discrimination in predicting cardiovascular events (C-statistics for the lipid model 0.75 [SD 0.07] and nonlaboratory model 0.75 [0.07], P = .82). Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted adult cardiovascular events. The addition of lipid measurements to nonlaboratory risk factors did not improve the prediction of cardiovascular events.

Device-measured stationary behaviour and cardiovascular and orthostatic circulatory disease incidence.

Previous studies have indicated that standing may be beneficially associated with surrogate metabolic markers, whereas more time spent sitting has an adverse association. Studies assessing the dose-response associations of standing, sitting and composite stationary behaviour time with cardiovascular disease (CVD) and orthostatic circulatory disease are scarce and show an unclear picture. To examine associations of daily sitting, standing and stationary time with CVD and orthostatic circulatory disease incidence. We used accelerometer data from 83 013 adults (mean age ± standard deviation = 61.3 ± 7.8; female = 55.6%) from the UK Biobank to assess daily time spent sitting and standing. Major CVD was defined as coronary heart disease, heart failure and stroke. Orthostatic circulatory disease was defined as orthostatic hypotension, varicose vein, chronic venous insufficiency and venous ulcers. To estimate the dose-response hazard ratios (HR) we used Cox proportional hazards regression models and restricted cubic splines. The Fine-Gray subdistribution method was used to account for competing risks. During 6.9 (±0.9) years of follow-up, 6829 CVD and 2042 orthostatic circulatory disease events occurred. When stationary time exceeded 12 h/day, orthostatic circulatory disease risk was higher by an average HR (95% confidence interval) of 0.22 (0.16, 0.29) per hour. Every additional hour above 10 h/day of sitting was associated with a 0.26 (0.18, 0.36) higher risk. Standing more than 2 h/day was associated with an 0.11 (0.05, 0.18) higher risk for every additional 30 min/day. For major CVD, when stationary time exceeded 12 h/day, risk was higher by an average of 0.13 (0.10, 0.16) per hour. Sitting time was associated with a 0.15 (0.11, 0.19) higher risk per extra hour. Time spent standing was not associated with major CVD risk. Time spent standing was not associated with CVD risk but was associated with higher orthostatic circulatory disease risk. Time spent sitting above 10 h/day was associated with both higher orthostatic circulatory disease and major CVD risk. The deleterious associations of overall stationary time were primarily driven by sitting. Collectively, our findings indicate increasing standing time as a prescription may not lower major CVD risk and may lead to higher orthostatic circulatory disease risk.