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Cardiovascular diseases (CVD), primarily ischemic heart disease and stroke, remain leading global health burdens. Environmental risk factors have a major role in the development of CVD, particularly exposure to heavy metals. The Triglyceride Glucose Index (TyG), a measure of insulin resistance and CVD risk, is the primary focus of this study, which summarizes the most recent findings on the effects of lead (Pb), arsenic (As), and cadmium (Cd) on CVD risk. A higher risk of CVD is correlated with an elevated TyG index, which has been linked to insulin resistance. Exposure to Cd is associated with disturbance of lipid metabolism and oxidative stress, which increases the risk of CVD and TyG. Exposure reduces insulin secretion and signaling, which raises the TyG index and causes dyslipidemia. Pb exposure increases the risk of CVD and TyG index via causing oxidative stress and pancreatic β-cell destruction. These results highlight the need of reducing heavy metal exposure by lifestyle and environmental modifications in order to lower the risk of CVD. To comprehend the mechanisms and create practical management plans for health hazards associated with heavy metals, more study is required., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Insulin resistance (IR) is a major risk factor for cardiovascular disease. Recently, a novel index (triglyceride-glucose index-TyG) has been proposed as a surrogate marker of IR and a better expression of IR than the Homeostatic Model Assessment of IR (HOMA-IR) index. Few and heterogeneous data are so far available on the relationship between vascular damage and this novel index. Therefore, we aimed to estimate the predictive role of TyG, in comparison with the HOMA-IR, on the development of arterial stiffening (AS), defined as a pulse pressure>60 mmHg, in an 8-year follow-up observation of a sample of non-diabetic adult men (the Olivetti Heart Study)., Methods and Results: The analysis included 527 non-diabetic men, with normal arterial elasticity at baseline and not on antihypertensive or hypolipidemic treatment. TyG was significantly greater in those who developed AS than those who did not (p = 0.006). On the contrary, the HOMA-IR index was not different between the two groups (p = 0.24). Similar trends were shown by logistic regression analysis adjusting for main confounders. After the stratification by the optimal cut-off point, values of TyG >4.70 were significantly associated with the development of AS, also after adjustment for main confounders. On the contrary, the HOMA-IR index >1.90 was not associated with the risk of AS development in multivariate models., Conclusion: The results of this study indicate a predictive role of TyG on AS, independently of the main potential confounders. Moreover, the predictive power of TyG seems to be greater than that of the HOMA-IR index., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients to be included in the study. No animal studies were carried out by the authors for this article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable., Objectives: To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients., Methods: In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed., Results: Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped C-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a C-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death., Conclusion: Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this first-of-its-kind risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities., Competing Interests: Declaration of competing interests S.K. has received funding from the Jubiläumsstiftung SwissLife, the Lindenhof Foundation, the Novartis Foundation for Medical-Biological Research, the Swiss Heart Foundation, the Swiss Society of Cardiology, and the Theodor-Ida-Herzog-Egli Foundation, and materials and equipment from Roche Diagnostics. He has received travel support from the European Atherosclerosis Society, the European Society of Cardiology, the European Society of Clinical Investigation, Sphingotec GmbH, the 4TEEN4 Pharmaceuticals GmbH, and the PAM Theragnostics GmbH. L.L. is a co-inventor on the international patent WO/2020/226993 filed in April 2020. The patent relates to the use of antibodies that specifically bind IL-1α to reduce various sequelae of ischemia–reperfusion injury to the central nervous system. He further reports speaker fees from Daiichi Sankyo outside the submitted work. Moreover, he is counselor of the European Society for Clinical Investigation and has received fundings from the Novartis Foundation for Medical-Biological Research, the Swiss Heart Foundation, and the Italian Ministry of Health. T.M.S. declares funding from the Lindenhof Foundation. F.A.W. is supported by a grant of the Lindenhof Foundation (through S.K., T.F.L, and T.M.S.) and the Foundation for Cardiovascular Research—Zurich Heart House. He has received funding from the Fonds zur Förderung des akademischen Nachwuchses of the University of Zurich, the European Society of Cardiology, 4TEEN4 Pharmaceuticals GmbH, PAM Theragnostics GmbH, and Sphingotec GmbH outside the submitted work. Outside this work, I.P. reports honoraria for lectures from Bayer, BMS/Pfizer, and Sanofi and participation in advisory boards from Bayer and BMS/Pfizer. Outside this work, T.F.L. declares research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, and Vifor and honoraria from Amgen, Dacadoo, Daiichi Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Philips, and Pfizer. He holds leadership positions at the European Society of Cardiology, Swiss Heart Foundation, and the Foundation for Cardiovascular Research—Zurich Heart House. C.A. reports honoraria for lectures from Bayer, Daiichi Sankyo, BMS/Pfizer, and Sanofi and participation in advisory boards from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and BMS/Pfizer. F.Moik reports honoraria for lectures from BMS and MSD and participation in advisory boards from BMS. All other authors have no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women., Methods and Results: We included 15,575 postmenopausal women aged 35-75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59-4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16-1.72) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48-2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories., Conclusion: In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Artificial intelligence has increasingly become an integral part of our daily activities. ChatGPT, a natural language processing technology developed by OpenAI, is widely used in various industries, including healthcare. The application of ChatGPT in healthcare is still evolving, with studies exploring its potential in clinical decision-making, patient education, workflow optimization, and scientific literature. ChatGPT could be exploited in the medical field to improve patient education and information, thus increasing compliance. ChatGPT could facilitate information exchange on major cardiovascular diseases, provide clinical decision support, and improve patient communication and education. It could assist the clinician in differential diagnosis, suggest appropriate imaging modalities, and optimize treatment plans based on evidence-based guidelines. However, it is unclear whether it will be possible to use ChatGPT for the management of patients who require rapid decisions. Indeed, many drawbacks are associated with the daily use of these technologies in the medical field, such as insufficient expertise in specialized fields and a lack of comprehension of the context in which it works. The pros and cons of its use have been explored in this review, which was not written with the help of ChatGPT., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Objective: Type 1 diabetes mellitus (DM1) and obesity represent two chronic pediatric diseases characterized by increased risk for renal impairment and cardiovascular disease. The potential usefulness of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9), two novel biomarkers, for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity, was investigated in this cross-sectional study., Patients and Methods: Serum samples were obtained from children and adolescents aged 12.7 ± 3.8 years old with DM1 (n = 38) or obesity (n = 34) and normal renal function, as well as from healthy controls (n = 24). NGAL and MMP-9 concentrations were measured using commercially available sandwich ELISA kits (NGAL: DY1757-05, MMP-9: DMP900; R&D systems, Minneapolis, MN, USA)., Results: NGAL serum values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with DM1 with diabetes duration, and in the total population with body mass index (BMI) z-score. Also, serum MMP-9 levels were significantly increased in patients with DM1 and in patients with obesity compared to controls., Conclusions: Circulating NGAL and MMP-9 levels may prove useful as surrogate biomarkers to creatinine, glomerular filtration rate (GFR), and albumin excretion rate for early detection of kidney injury and cardiovascular complications in children and adolescents with DM1 or obesity.

Endothelial dysfunction and microvascular remodeling underly the development and progression of a host of cardiovascular disease (CVD). However, current methods to assess coronary epicardial microvascular function are invasive, time-intensive, and costly. Optical coherence tomography angiography (OCTA) is an established technology within ophthalmology that provides a quick, noninvasive assessment of vascular structures within the retina. As a growing body of evidence reveals strong associations between the retinal changes on OCTA and the development and progression of CVD, OCTA may indeed be a surrogate test for end-organ dysfunction. OCTA has potential to enhance diagnostic performance, refine cardiovascular risk assessment, strengthen prognostication, and ultimately, improve patient care. We explore the current literature on OCTA in cardiovascular diseases to summarize the clinical utility of retinal OCTA imaging and discuss next-generation cardiovascular applications., Competing Interests: Declaration of competing interest Dr. Srivastava received contracted research funding to institution from Regeneron, Eyevensys, Eyepoint, Gilead, and consulting fees from Adverum, Novartis, Zeiss, Bausch and Lomb. Dr. Sharma received contracted research funding to institution from Gilead, Abbvie, Genentech/Roche, Santen, IONIS, and received consulting fees from Alimera, Abbvie, Apellis, Clearside, Eyepoint, Iveric Bio, Genentech/Roche, Bausch and Lomb, Regenxbio, Regeneron, Ripple. Dr. Tang received consulting fees from Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, WhiteSwell, Boston Scientific, CardiaTec Biosciences, Intellia Therapeutics, Bristol Myers Squibb, Alleviant Medical, Alexion Pharmaceuticals, Salubris Biotherapeutics, BioCardia Inc., and received honoraria from Springer, Belvoir Media Group, and American Board of Internal Medicine. All other authors have no relationships to disclosure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: The relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and mortality in individuals with diabetes remains uncertain. This study aimed to explore the relationship between serum UHR and all-cause and cardiovascular disease (CVD) mortality in adults with diabetes., Methods and Results: A total of 5,665 patients with diabetes were enrolled from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Mortality data were determined through the National Death Index (NDI) until December 31, 2019. The multivariate hazard ratio (HR) and 95% confidence interval (CI) were examined by Cox proportional risk modeling and threshold effects analysis. Stratified analyses were conducted to identify the populations with high-risk mortality. Among the participants with diabetes, 1,088 all-cause mortality, containing 310 CVD mortality occurred. Following adjustment for multivariate, higher UHR was significantly and nonlinearly associated with increased all-cause mortality (HR 1.02, 95% CI 1.02-1.02) and CVD mortality (HR 1.03, 95% CI 1.03-1.03). Furthermore, a U-shaped relationship between UHR and all-cause and CVD mortality, with a plateau at 12.57% for all-cause mortality and 9.86% for CVD mortality. Below the inflection points, a higher UHR was associated with a 4% reduced risk for all-cause mortality. Conversely, exceeding the inflection points, a 4% higher risk for all-cause and a 3% higher risk for CVD mortality associated with elevated UHR., Conclusions: Nonlinearity of UHR with all-cause and CVD mortality was observed in adults with diabetes in the United States, with thresholds identified at 12.57% for all-cause and 9.86% for CVD mortality respectively., Competing Interests: Declaration of competing interest All authors have no conflicts of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Chronic kidney disease (CKD) is a major healthcare challenge, affecting >800 million people worldwide. Implications for population health result from the strong associations of CKD with increased rates of cardiovascular disease, heart failure, progressive CKD leading to kidney failure, acute kidney injury (AKI), and mortality. In addition to a single disease perspective, CKD commonly coexists alongside other long-term conditions, in particular type 2 diabetes and cardiovascular disease. CKD is therefore an important component of multimorbidity that influences individual management and impacts prognosis. CKD is defined by abnormalities of kidney structure or function of any cause with implications for health that are present for longer than 3 months. The diagnosis is usually made on the basis of an abnormal glomerular filtration rate (GFR < 60 mL/min/1.73 m 2 ) and/or the presence of proteinuria (urine albumin to creatinine ratio > 30 mg/g or >3 mg/mmol). GFR is usually estimated from serum creatinine concentration using a variety of validated equations. However, serum creatinine is closely related to muscle mass and may therefore not be an accurate marker of GFR in people with high or low muscle mass (sarcopaenia). Cystatin C is an alternative endogenous marker of GFR that is increasingly being used but also has limitations. An estimate of GFR based on both creatinine and cystatin C is the most accurate. Diagnosis should be followed by classification and risk stratification to guide the development of a risk-based, personalized care plan. Improved detection and widespread implementation of optimal CKD management has the potential to bring major benefits to population health., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Sedentary behavior, such as excessive sitting, increases risk of cardiovascular disease and premature mortality in the general population, but this has not been assessed in type 1 diabetes. Occupational sitting is increasingly ubiquitous and often constitutes the largest portion of daily sitting time. Our aim was to identify clinical factors associated with excessive occupational sitting in type 1 diabetes and, in a prospective setting, to explore its association with cardiovascular events and all-cause mortality, independent of leisure-time physical activity., Methods: An observational follow-up study of 1,704 individuals (mean age 38.9 ± 10.1 years) from the Finnish Diabetic Nephropathy Study. Excessive occupational sitting, defined as ≥ 6 h of daily workplace sitting, was assessed using a validated self-report questionnaire. Data on cardiovascular events and mortality were retrieved from national registries. Multivariable logistic regression identified independently associated factors, while Kaplan-Meier curves and Cox proportional hazard models were used for prospective analyses., Results: Factors independently and positively associated with excessive occupational sitting included a high occupational category [OR 6.53, 95% CI (4.09‒10.40)] and older age [1.02 (1.00‒1.03)], whereas negatively associated factors included current smoking [0.68 (0.50‒0.92)], moderate albuminuria [0.55 (0.38‒0.80)], and high leisure-time physical activity [0.52 (0.36‒0.74)]. During a median follow-up of 12.5 (6.5-16.4) years, 163 individuals (9.6%) suffered cardiovascular events, and during a median follow-up of 13.7 (9.4-16.6) years, 108 (6.3%) deaths occurred. Excessive occupational sitting increased cardiovascular event risk (hazard ratio [HR] 1.55 [95% CI 1.10‒2.18]) after adjustment for confounders and other covariates. Furthermore, in a stratified multivariable analysis among current smokers, excessive occupational sitting increased the risk of all-cause mortality (2.06 [1.02‒4.20])., Conclusions: Excessive occupational sitting is associated with a higher risk of cardiovascular events and all-cause mortality in individuals with type 1 diabetes. This association persists regardless of leisure-time physical activity, after adjusting for independently associated variables identified in our cross-sectional analyses. These findings underscore the need to update physical activity guidelines to better address sedentary behavior and improve outcomes for individuals with type 1 diabetes. Targeting occupational sitting should be considered a key focus for interventions aimed at reducing overall sedentary time., (© 2024. The Author(s).)

Background: Dementia is a major public health burden, particularly among the older persons with significant implications for individuals, caregivers, and society. Identifying mild cognitive impairment early can facilitate timely intervention and care.This cross-sectional study aims to investigate the association between Framingham risk score (FRS), a widely used tool for cardiovascular disease (CVD) risk prediction, and cognitive impairment among older persons with chronic illness in Malaysia., Methods: A total of 289 participants aged 60 years and above with chronic illness were recruited from Klinik Primer Hospital Tuanku Chanselor Muhriz via simple random sampling via computer generator. The Montreal Cognitive Assessment Bahasa Malaysia version (MoCA-BM) was used to assess cognitive function and the FRS was calculated on the basis of CVD risk factors., Results: The prevalence of cognitive impairment among the participants was found to be 19.7%. Multiple Logistic Regression revealed that age (AOR 1.101, 95% CI = 1.041,1.163, p < 0.001), systolic blood pressure (AOR 1.048, 95%CI = 1.024, 1.072, p < 0.001) diabetes (AOR 2.655, 95% CI = 1.194, 5.906, p = 0.017) increased the odds of having cognitive impairment among older persons with chronic illness whereas secondary education ( AOR 0.087, 95% CI = 0.008, 0.963, p = 0.047) and higher education ( AOR 0.037, 95% CI = 0.002, 0.833, p = 0.038) reduced the likelihood of having cognitive impairment. Individuals with higher FRS were more likely to have cognitive impairment (AOR 1.099, 95% CI = 1.049, 1.172, p < 0.001). The optimal cutoff point for the FRS to determine cognitive impairment is 30 for males with a sensitivity and specificity of 84.4% and 51.2% while the optimal cut off point for females is 18.5 with a sensitivity and specificity of 76% and 63.1% respectively., Conclusions: These findings suggest that the FRS which was originally designed for CVD risk assessment may also serve as a valuable predictive tool for cognitive impairment among older persons with chronic illness. Integrating FRS into routine primary care assessments could enhance the early identification of individuals at risk and enable appropriate cognitive screenings and interventions. Further research such as a longitudinal cohort study in a larger and more diverse population is warranted to validate the association of CVD risks with the development of dementia., (© 2024. The Author(s).)

Background: Cardiovascular diseases are characterized by chronic inflammation, leading to increased inflammatory markers that can cause cell damage and death. Phase angle has emerged as a marker of cellular health. It is considered a prognostic factor in various acute and chronic conditions. However, few studies have examined its association with cardiovascular disease risk measures. This study aims to investigate the relationship between phase angle, the general Framingham risk score, and the HEARTS cardiovascular risk score., Methods: This cross-sectional study included a convenience sample of adult patients of 2 primary health care services. Phase angle was measured using multifrequency bioimpedance analysis at 50 kHz. The risk of cardiovascular events was calculated using the Framingham and HEARTS risk scores. Statistical analysis included generalized linear regression models, unadjusted and adjusted according to sex and age, to determine the association between scores, risk factors, and phase angle., Results: The study included 164 individuals with a mean age 52.2 (SD 17.9). According to the HEARTS score, low-risk patients had higher phase angle values than those with high or very high risk [ß = -0.57 (95% CI -0.95; -0.19), P = 0.003]. Framingham scores showed a trend toward significance for higher mean phase angle values in low-risk than high-risk patients [ß = -0.43 (95% CI -0.88 to 0.02), P = 0.06]., Conclusion: Phase angle values were lower in high and very high-risk patients than in low-risk patients, which shows that phase angle is a promising risk predictor for patients with cardiovascular diseases., (© 2024. The Author(s).)

Cardiovascular disease (CVD) is the leading cause of mortality, disability, and healthcare costs, with a significant impact on the elderly and contributing to premature deaths across various age groups, including those below age 70. Despite decades of transformative discoveries and clinical efforts, the challenges of diagnosis, prevention, and treatment of CVD persist on a massive scale. This study aimed to unravel potential CVD-associated biomarkers and establish a machine learning model for the risk assessment of CVD. Untargeted metabolic assay with ultra-high performance liquid chromatography-tandem mass spectrometry and routine clinical biochemistry test were undertaken on the fasting venous blood specimens from 57 subjects. Four relevant clinical traits and 164 CVD-associated metabolites were identified, especially those related to glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. The machine learning model achieved from an integrated biomarker panel of palmitic amide, oleic acid, 138-pos (the 138th detected metabolomic feature in positive ion mode), phosphatidylcholine, linoleic acid, age, direct bilirubin, and inorganic phosphate, was able to improve the accuracy of CVD risk assessment up to a high satisfactory value of 0.91. The findings indicate that disorders in the metabolic processes of biological membranes and energy are significantly associated with increased risk of vascular damage in CVD patients. With machine learning methods, the pivotal metabolites and clinical biomarkers offer a promising potential for the efficient risk assessment and diagnosis of CVD., (© 2024. The Author(s).)

Despite significant progress in cardiovascular pharmacotherapy and interventional strategies, cardiovascular disease (CVD), in particular ischaemic heart disease, remains the leading cause of morbidity and mortality among women in the UK and worldwide. Women are underdiagnosed, undertreated and under-represented in clinical trials directed at management strategies for CVD, making their results less applicable to this subset. Women have additional sex-specific risk factors that put them at higher risk of future cardiovascular events. Psychosocial risk factors, socioeconomic deprivation and environmental factors have an augmented impact on women's cardiovascular health, highlighting the need for a holistic approach to care that considers risk factors specifically related to female biology alongside the traditional risk factors. Importantly, in the UK, even in the context of a National Health Service, there exist significant regional variations in age-standardised mortality rates among patients with CVD. Given most CVDs are preventable, concerted efforts are necessary to address the unmet needs and ensure parity of care for women with CVD. The present consensus document, put together by the British Cardiovascular Society (BCS)'s affiliated societies, specifically portrays the current status on the sex-related differences in the diagnosis and treatment of each of the major CVD areas and proposes strategies to overcome the barriers in accessing diagnoses and treatments among women. This document aims at raising awareness of the scale of the current problem and hopes to stimulate a multifaceted approach to address sex disparities and enable future comprehensive sex- and gender-based research through collaboration across different affiliated societies within the BCS., Competing Interests: Competing interests: VK is an associate editor for Heart BMJ and is NIHR National Cardiovascular Research Lead, Research Delivery Network., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The neutrophil-to-lymphocyte ratio (NLR) has emerged as a novel inflammatory marker related to disease prognosis, this study aimed to evaluate the association between NLR and mortality in metabolic syndrome (MetS) patients., Methods: This study used data from 13,156 participants with MetS, derived from the National Health and Nutrition Examination Survey from 1999 to 2020. The NLR was calculated, and its associations with cardiovascular disease (CVD) mortality and all-cause mortality were assessed by multivariate Cox regression, restricted cubic spline and Kaplan-Meier curves. The study performed subgroup analyses to validate the robustness of the findings in different populations. The predictive ability of NLR was evaluated using time-dependent receiver operating characteristic curve. The indirect impact of eGFR was explored by mediation analysis., Results: As NLR values increased, there was an obvious rise in the risk of mortality in MetS. The fully adjusted continuous model revealed a 16.0%, 14.4% elevated risk of CVD mortality (HR = 1.160; 95% CI: 1. 090-1.234, p < 0.0001) and all-cause mortality (HR = 1.144; 95% CI: 1. 086-1.206, p < 0.0001), respectively, with each one-unit increment in NLR. Comparing the highest to the lowest quartile of NLR, the top quartile exhibited a significantly increased risk of CVD mortality (HR = 2. 447; 95% CI: 1. 561-3. 836, p < 0.0001), and all-cause mortality (HR = 1. 53; 95% CI: 1. 188-1. 972, p = 0.001) among individuals with MetS. Subgroup analyses substantiated the stability of these associations in most populations. The curve under area for the 3, 5, and 10 years were 0.650, 0.716, and 0.645 for CVD mortality, and 0.746, 0.688, and 0.635 for all-cause mortality. Significantly, the eGFR acted as an intermediary in the relationship of NLR with CVD mortality and all-cause mortality, accounting for 9.85% and 9.86% of the effect, respectively., Conclusion: The NLR served as a significant indicator for assessing the risk of mortality in the MetS population. Consequently, we recommended the regular assessment of NLR in MetS populations as a potentially advantageous method for evaluating their risk of mortality., (© 2024. The Author(s).)

Background: Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). There is a paucity of data on the pattern of first manifestation of CVD and the outcome among patients with T2DM in Cameroon., Objectives: We aimed to examine the pattern of the first manifestation of CVD and the outcome among patients with T2DM., Methods: Between January 2017 and December 2023, files of patients with T2DM hospitalized for the first observed CVD were reviewed. We identified cases of three incident overt clinically manifest CVD complications (acute myocardial infarction [AMI], stroke, and heart failure) in hospitalized T2DM patients. Patients with a previous history of CVD were excluded., Results: Out of the 1091 patients hospitalized with T2DM, we identified 261(23.9%) patients with clinically overt CVD, of whom 129 (49.4%) were females. The mean age was 63.9 ± 12.1 years and ranged from 15 to 91 years. Women were significantly older compared to men (65.4 ± 11.4 years vs. 62.5 ± 12.6 years; p = 0.042). Hypertension was reported in 201 (77%; 95% CI: 71.4-82) patients. Any form of chronic kidney disease was seen in 15 (5.8%; 95% CI: 3.3-9.3) patients. HIV infection was seen in 5 (1.9%; 95% CI: 0.6-4.4) patients. Stroke was the most common incident clinically overt CVD in 144 (55.2%; 95% CI: 48.9-61.3) patients, followed by heart failure in 105 (40.2%; 95% CI: 34.2-46.5) patients, and Acute MI in 12 (4.6%; 95% CI: 2.4-7.9) patients. The mean length of hospital stay was 9.7 ± 6.6 days. Patients with stroke had a significantly longer hospital stay > 7 days (63% vs. 48.7%, p = 0.021). The in-hospital case fatality was seen in 35 (13.4%; 95% CI: 9.5-18.2) patients., Conclusion: Nearly 1 out of 4 hospitalized patients with T2DM was hospitalized for a first CVD. Stroke and heart failure are the most common initial manifestations of CVD. More than three-quarters of the patients had concomitant hypertension and the in-hospital case fatality was high., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Background: In this study, we aimed to investigate whether there is a relationship between aortic arch calcification (AAC) and hidradenitis suppurativa (HS) in HS patients without cardiovascular disease., Methods: In this study, patients over 18 years of age who applied to the dermatology outpatient clinic between January 2023 and February 2024 were followed up with the diagnosis of HS without cardiovascular disease, and a healthy control group matched in terms of age and gender were included retrospectively., Results: In total, 130 patients with HS without cardiovascular disease and 130 control patients were included in the study. AAC was significantly higher in the HS group compared to the control group (p = 0.028). In the multivariate analysis, we found that age and HS were independent predictors of AAC (OR: 1.048 (1.009-1.089); p = 0.015, OR: 3.158 (1.181-8.445); p = 0.022, respectively). When we divided the groups as having AAC (grade 1-3) and not having AAC (grade 0), the rate of HS disease was significantly higher in the group with AAC compared to the group without AAC (75.0% vs. 47.5% p = 0.010)., Conclusions: AAC is observed more frequently in patients with HS without cardiovascular disease than in healthy individuals. Moreover, HS can be considered as an independent predictor of AAC. AAC may contribute to developing treatment strategies in HS patients without cardiovascular disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Impedance cardiography (ICG) is essential in evaluating cardiac function in patients with cardiovascular diseases. Aiming at the problem that the measurement of ICG signal is easily disturbed by motion artifacts, this paper introduces a de-noising method based on two-step spectral ensemble empirical mode decomposition (EEMD) and canonical correlation analysis (CCA). Firstly, the first spectral EEMD-CCA was performed between ICG and motion signals, and electrocardiogram (ECG) and motion signals, respectively. The component with the strongest correlation coefficient was set to zero to suppress the main motion artifacts. Secondly, the obtained ECG and ICG signals were subjected to a second spectral EEMD-CCA for further denoising. Lastly, the ICG signal is reconstructed using these share components. The experiment was tested on 30 subjects, and the results showed that the quality of the ICG signal is greatly improved after using the proposed denoising method, which could support the subsequent diagnosis and analysis of cardiovascular diseases.

Background: A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes., Methods: The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006-2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%)., Results: With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min - 1 ·1.73 m - 2 . The median difference was 4.10 ml·min - 1 ·1.73 m - 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations., Conclusion: Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min - 1 ·1.73 m - 2 , but virtually no impact on mortality prediction., Trial Registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008., (© 2024. The Author(s).)

Background: The Steno Type 1 Risk Engine (ST1RE) was developed to aid clinical decisions in primary prevention for individuals with type 1 diabetes (T1D), as existing cardiovascular (CV) risk models for the general population and type 2 diabetes tend to underestimate CV risk in T1D. However, the applicability of ST1RE in different populations remains uncertain, as prediction models developed for one population may not accurately estimate risk in another. This study aimed to evaluate the performance of the ST1RE in predicting CV events among ethnically mixed T1D individuals and its association with the progression of microangiopathy complications., Methods: A retrospective survey of 435 adults with T1D who were free of CV events at baseline was assessed by ST1RE and chronic diabetes complications at 5 and 10 years of follow-up. The estimated CV risk rates were compared with the observed rates at 5 and 10 years using statistical analyses, including Receiver Operating Characteristic (ROC) curve analysis, Hosmer-Lemeshow test, Kaplan-Meier curves analysis and Cox-regression models., Results: Among 435 patients (aged 25 years; interquartile range [IQR]: 21-32) with a median T1D duration of 13 years (IQR: 9-18), only 5% were categorized into the high ST1RE group. Within a median follow-up of 9.2 years (IQR 6.0-10.7), 5.5% of patients experienced a CV event (1.6%, 14.9%, and 50% from the low, moderate, and high-risk groups, respectively). The hazard ratios (HRs) for CV events were greater in the high-risk group (HR 52.02; 95% CI 18.60-145.51, p < 0.001) and in the moderate-risk group (HR 8.66; 95% CI 2.90-25.80, p < 0.001) compared to the low-risk group. The ST1RE estimated CV events were similar to the observed at 5 years (3.4% vs. 3.5%; χ 2  = 10.12, p = 0.899) and 10 years (6.8% vs. 9.9%; χ 2  = 14.80, p = 0.676) of follow-up. The progression of microangiopathies was greater in the high vs. low for retinopathy (p = 0.008), diabetic kidney disease (p < 0.001), peripheral neuropathy (p = 0.021), and autonomic neuropathy (p = 0.008)., Conclusions: ST1RE performed well in predicting CV events at 5 and 10 years of follow-up. Moreover, higher ST1RE scores were associated with the progression of microangiopathy complications in this genetically heterogeneous T1D population., (© 2024. The Author(s).)

Background: The need for classification systems for cardiovascular disease (CVD) that is population-specific is important towards understanding the clinical disease and diagnostics associated with the disease. This paper presents the form and validation results of this classification system., Method: The survey data used was captured from 778 participants, 526 persons with no prior CVD, and 252 who reported prior CVD. Binomial logistic regression and Discriminant analysis were utilised to develop classification models. This classification system provided a general measure of severity of disease by utilising scores estimated from two algorithms developed from 13 routine physiologic measurements, along with demographic information of age and ethnicity, inter alia , and previous health status., Results: For each model, specific score ranges were identified, which gave the best classification for those with a prior CVD incident (higher scores) and for others labelled as non-CVD (lower scores). The two classification models (Logistic Regression Model and Discriminant Analysis Model) developed had high area under the receiver-operating characteristic (AUROC) values (98% & 99%) and sensitivity (86 and 90%), which improved discrimination between Non-CVD and CVD participants and, more importantly, correctly classified a greater proportion of CVD participants. New to this type of research was the estimation and detailed evaluation of a range of scores, labelled non-differentiating, which fell in the middle of the spectrum and which contained the higher-end scores for the non-CVD individuals and the lower-end scores for CVD patients, all of whom were incorrectly classified, based on their prior history., Conclusion: The classification system of scores is able to differentiate the CVD status of individuals, with good predictability, and could assist physicians with recommending different treatment plans. The two models in this classification system each individually outperformed the three established models in terms of the strength of their correct classifications of individuals with or without prior reported CVD incidents. More importantly, they have smaller non-differentiating ranges than the three known models and, in that range, the two new models have lower CVD/non-CVD ratios suggesting they are more likely to misclassify non-CVD individuals compared to CVD patients, which is a more benign misclassification. Further, when used in combination, the two models increased the sensitivity, in classifying individuals of different ethnicities, beyond that of either one used independently or of any of the three standard European/North American models. These efforts will be instrumental in advancing personalised CVD management strategies and improving health outcomes across diverse populations., Competing Interests: Valerie A. Stoute owns V.A.S Consulting., (©2024 Hosein et al.)

Background: Patients with low-to-normal body mass index (BMI; < 25.0 kg/m 2 ) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials., Methods: This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0-22.4, 22.5-24.9, 25.0-29.9, 30.0-34.9, and 35.0 ≤ kg/m 2 ). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category., Results: Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m 2 , 1.9% [n = 5,350]; 20.0-22.4 kg/m 2 , 8.5% [n = 23,818]; and 22.5-24.9 kg/m 2 , 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m 2 , HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0-22.4 kg/m 2 , HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5-24.9 kg/m 2 , HR [95%CI] = 0.92 [0.84 to 1.01])., Conclusions: The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors., (© 2024. The Author(s).)

Incorporating biomarkers into cardiovascular studies, including nursing research, is a common approach when identifying underlying mechanisms and providing targets for intervention. However, effective utilization of biomarker data demands careful consideration. In the analysis, interpretation, and reporting phase, there are many facets to consider, including non-normality of the data, normalization procedures, and potential confounding influences of other clinical data. Furthermore, as many studies focus on patient-reported outcomes (PROs), it is important that the analysis and interpretation of biomarkers in relation to PROs is rigorous and reproducible. In this article, Part 2 of 2, we provide an overview of considerations for the analysis, interpretation, and reporting phases of biomarker studies. We also provide an example of these steps., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clinical medicine requires the integration of various forms of patient data including demographics, symptom characteristics, electrocardiogram findings, laboratory values, biomarker levels, and imaging studies. Decision-making on the optimal management should be based on a high probability that the envisaged treatment is appropriate, provides benefit, and bears no or little potential harm. To that end, personalized risk-benefit considerations should guide the management of individual patients to achieve optimal results. These basic clinical tasks have become more and more challenging with the massively growing data now available; artificial intelligence and machine learning (AI/ML) can provide assistance for clinicians by obtaining and comprehensively preparing the history of patients, analysing face and voice and other clinical features, by integrating laboratory results, biomarkers, and imaging. Furthermore, AI/ML can provide a comprehensive risk assessment as a basis of optimal acute and chronic care. The clinical usefulness of AI/ML algorithms should be carefully assessed, validated with confirmation datasets before clinical use, and repeatedly re-evaluated as patient phenotypes change. This review provides an overview of the current data revolution that has changed and will continue to change the face of clinical medicine radically, if properly used, to the benefit of physicians and patients alike., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The use of statins for the primary prevention of cardiovascular diseases (CVD) is associated with various beneficial outcomes, alongside certain undesirable effects. This study aims to determine optimal risk thresholds above which statin therapy yields a net benefit, considering both the positive effects and potential adverse effects, as well as their probabilities and patient preferences., Methods: Quantitative benefit-harm balance modeling was applied to the Iranian general population aged 40 to 75 years with no history of CVD. The analysis utilized data from prior studies, including statin effect estimates for different outcomes from a meta-analysis, patient preferences obtained from an Iranian survey, and baseline incidence rates of adverse outcomes sourced from the Global Burden of Disease study for Iran. Outcomes were defined as angina, myocardial infarction, fatal coronary heart disease, fatal or non-fatal stroke, and heart failure. Benefit-harm balance indices were calculated for various combinations of age, sex, and 10-year CVD risk., Results: Statin therapy was found to be advantageous at a lower 10-year CVD risk threshold in men (18-23%) compared to women (24-28%). Furthermore, individuals aged 40-45 years exhibited a lower risk threshold (18% in men, 24% in women) than those aged 70-75 years (23% in men, 28% in women)., Conclusion: The desirable 10-year risk thresholds for statin prescription in the primary prevention of CVD vary by age and gender, ranging from 18 to 28%, encompassing a spectrum of outcomes from angina to CVD mortality. These results suggest hard-CVD risk thresholds of 7.5% to 10% for both sexes., (© 2024. The Author(s).)

Cardiovascular diseases (CVDs) present a significant global public health threat, contributing to a substantial number of cases involving morbidity and mortality. Therefore, the early and accurate detection of CVDs plays an indispensable role in enhancing patient outcomes. Decades of extensive research on electrocardiography at high frequencies have yielded a wealth of knowledge regarding alterations in the QRS complex during myocardial ischemia, as well as the methodologies to assess and quantify these changes. In recent years, the analysis of high-frequency QRS (HF-QRS) components has emerged as a promising non-invasive approach for diagnosing various cardiovascular conditions. Alterations in HF-QRS amplitude and morphology have demonstrated remarkable sensitivity as diagnostic indicators for myocardial ischemia, often surpassing measures of ST-T segment changes. This comprehensive review aims to provide an intricate overview of the current advancements, challenges, and prospects associated with HF-QRS analysis in the field of CVDs., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine.)

Background: Beyond the acute phase, a considerable proportion of patients recovering from the coronavirus disease 2019 (COVID-19) experience long-term sequelae that profoundly impact their quality of life, particularly their physical fitness. This study aims to assess the effect of home-based breathing and chest mobility exercise on the cardiorespiratory functional capacity of long COVID with cardiovascular comorbidity., Methods: In this randomized, controlled, single-blind clinical trial, 46 long COVID with cardiovascular comorbidities were randomly assigned to either intervention or control group. The intervention group (n = 23) received additional home-based breathing and chest mobility exercise 3x/week for 12 weeks supervised by attending physicians, whereas the control group only received a home-based cardiac rehabilitation program. Baseline and post-intervention assessments consisted of laboratory (D-Dimer and CRP levels) and functional capacity, assessed through 6-minute walking test (6-MWT), exercise stress test's metabolic equivalents (METS), and predicted peak oxygen consumption (VO 2 peak ), peak expiratory flow rate (PEFR), peak cough flow (PCF), chest expansion, and EuroQoL's quality of life. Intention to treat analysis was performed., Results: At the 12th week, intervention subjects had significantly greater functional capacity with higher mean PEFR (p = .031) and PCF (p = .016). Similarly, 6-MWT was higher in the group receiving home-based breathing and chest mobility training (p = .032). The bottom part of the chest circumference was statistically different between the two groups (p = .01). METS and predicted VO2 peak were also higher in the intervention group. However, laboratory parameters and quality of life did not differ markedly (p > .05)., Conclusions: Home-based respiratory and chest mobility exercise could be an adjunct to cardiac rehabilitation in long COVID with cardiovascular comorbidities for improving cardiorespiratory functional capacity., Trial Registration: The study protocol was registered at http://ClinicalTrial.gov.id NCT05077943 (14/10/2021)., (© 2024. The Author(s).)

Cardiovascular diseases (CVDs) are among the primary causes of mortality globally, highlighting the critical need for early detection to mitigate their impact. Phonocardiograms (PCGs), which record heart sounds, are essential for the non-invasive assessment of cardiac function, enabling the early identification of abnormalities such as murmurs. Particularly in underprivileged regions with high birth rates, the absence of early diagnosis poses a significant public health challenge. In pediatric populations, the analysis of PCG signals is invaluable for detecting abnormal sound waves indicative of congenital and acquired heart diseases, such as septal defects and defective cardiac valves. In the PhysioNet 2022 challenge, the murmur score is a weighted accuracy metric that reflects detection accuracy based on clinical significance. In our research, we proposed a mean teacher method tailored for murmur detection, making full use of the Phyionet2022 and Phyionet2016 PCG datasets, achieving the SOTA (State of Art) performance with a murmur score of 0.82 and an AUC score of 0.90, providing an accessible and high accuracy non-invasive early stage CVD assessment tool, especially for low and middle-income countries (LMICs).

Competing Interests: Conflict of interest: none declared

Background: Older 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)., Methods: We 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., Results: In 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., Conclusion: There 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., (© 2024. The Author(s).)

Clinical features of hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility syndrome (HMS) have classically focused on dysfunctions related to the musculoskeletal system. A growing body of literature suggests substantial multisystemic involvement, although this has not been recapitulated in a pediatric/young adult population. Leveraging a large United States healthcare claim database illuminates multisystem disorders among patients diagnosed with hEDS and HMS in the age range of 10 to 24. This was a retrospective review of patient records within the de-identified healthcare claims database, PearlDiver. Patients with a diagnosis of hEDS or HMS, and those without these diagnoses who were seen for their annual physical examination, between the ages of 10 and 24, were queried for the presence of additional medical conditions. Descriptive statistics were used to define the frequency of multisystem diagnoses. Nineteen thousand seven hundred ninety hEDS patients, 17,509 HMS patients, and 4,959,713 patients from the general population were analyzed. Within 2 years following hEDS or HMS diagnosis, digestive disorders were the most prevalent diagnosis, followed by cardiovascular conditions. Digestive disorders occurred in 54.6% of patients with hEDS and 41.6% of patients with HMS, compared to 28.5% of the general population. Cardiovascular disorders occurred in 43.6% of patients with hEDS and 21.8% of patients with HMS compared to 10.3% of the general population. Anxiety, respiratory disorders, and developmental disorders occurred in approximately 25% of the hEDS group and 20% of the HMS group, compared to ~15% of the general population, all statistically significantly higher in the hEDS and HMS groups. This study highlights multisystem diagnoses within the pediatric hEDS/HMS populations. hEDS patients had higher rates of multisystem diagnoses compared to HMS patients. These results suggest a high multisystem disease burden for young hEDS/HMS patients. Future research is needed to understand the timing and presentation of clinical symptoms for this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cardiovascular disease remains the leading cause of death worldwide, with mortality rates increasing annually. This underscores the urgent need for accurate diagnostic and monitoring tools. Electrochemical detection has emerged as a promising method for swiftly and precisely measuring specific biomarkers in bodily fluids. This approach is not only cost-effective and efficient compared to traditional clinical methods, but it can also be tailored to detect individual biomarkers, which makes it particularly well-suited for point-of-care (POC) applications. The ability to conduct testing at the point of care is crucial for timely interventions and personalized disease management, empowering healthcare providers to tailor treatment plans based on real-time biomarker data. Thanks to recent advancements in nanomaterials, we've seen significant progress in electrochemical detection, leading to the development of specialized rapid immunoassay systems. These systems utilize specific antibodies to target molecules, expanding the range of detectable biomarkers. This innovation has the potential to revolutionize the diagnosis and treatment of cardiovascular diseases by enhancing detection sensitivity and specificity. Ultimately, these advancements aim to improve patient outcomes by enabling earlier diagnosis, more precise monitoring, and personalized therapeutic interventions, which will contribute to more effective management of cardiovascular health globally.

Competing Interests: Conflict of interest: Dr Bueno receives research funding from the European Union (EU4H-2022-JA-03), Instituto de Salud Carlos III, Spain (FORTALECE program, PI21/01572), Sociedad Española de Cardiología, AstraZeneca, Boehringer Ingelheim, Janssen, and Novartis; and has received in the past consulting/speaking fees from Astra-Zeneca, Novartis, Novo Nordisk and Organon.

Competing Interests: Conflict of interest: None declared.

Aims: Identifying patients with established cardiovascular disease (CVD) who are at high risk of type 2 diabetes (T2D) may allow for early interventions, reducing the development of T2D and associated morbidity. The aim of this study was to develop and externally validate the CVD2DM model to estimate the 10-year and lifetime risks of T2D in patients with established CVD., Methods and Results: Sex-specific, competing risk-adjusted Cox proportional hazard models were derived in 19 281 participants with established CVD and without diabetes at baseline from the UK Biobank. The core model's pre-specified predictors were age, current smoking, family history of diabetes mellitus, body mass index, systolic blood pressure, fasting plasma glucose, and HDL cholesterol. The extended model also included HbA1c. The model was externally validated in 3481 patients from the UCC-SMART study. During a median follow-up of 12.2 years (interquartile interval 11.3-13.1), 1628 participants with established CVD were diagnosed with T2D in the UK Biobank. External validation c-statistics were 0.79 [95% confidence interval (CI) 0.76-0.82] for the core model and 0.81 (95% CI 0.78-0.84) for the extended model. Calibration plots showed agreement between predicted and observed 10-year risk of T2D., Conclusion: The 10-year and lifetime risks of T2D can be estimated with the CVD2DM model in patients with established CVD, using readily available clinical predictors. The model would benefit from further validation across diverse ethnic groups to enhance its applicability. Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle., Competing Interests: Conflict of interest: M.W. has received consultancy fees from Amgen and Freeline. The other authors have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: It is well-known that serum uric acid (SUA) can increase the risk of hypertension, diabetes, obesity and dyslipidemia. However, its independent association with the risk of cardiovascular diseases (CVD) is controversial particularly in different populations. Hence, this study was aimed to assess an independent association of SUA with CVD risk in a Punjabi Pakistani cohort., Methods: This is a retrospective observational study in which 502 human subjects having CVD, hypertension and/or diabetes were grouped based on SUA levels as normouricemia (n = 266) and hyperuricemia (n = 236). Role of SUA was assessed in increasing the risk of CVD independent of other key confounding factors (i.e. age, gender, dyslipidemia, hypertension, diabetes, dietary and life-style habits). All clinical and biochemical data were analyzed in SPSS (ver. 20)., Results: Subjects aged 55 ± 13 years were of both genders (males: 52%). SUA levels were significantly different among clinical subtypes of CVD [i.e. acute coronary syndrome (ACS), myocardial infarction (MI) and heart failure (HF)]. Spearman correlation showed a significantly positive association between CVD and SUA (rho = 0.149, p < 0.001). Multivariate logistic regression of SUA quartiles showed that hyperuricemia is associated with CVD [3 rd quartile: OR: 1.78 (CI: 1.28-2.48), p = 0.001 and 4 th quartile: OR: 2.37 (CI: 1.72-3.27), p < 0.001]. Moreover, this association remained significant even after adjusting for confounding factors., Conclusion: This study showed that SUA is positively associated with CVD, thus it can act as an independent risk factor for CVD., (© 2024. The Author(s).)

Background: Stress is today a common feature of patients seeking medical care and a growing public health issue in society. A method has been developed to measure biological chronic stress by Hair Cortisol Concentrations (HCC). This biomarker, for chronic stress, captures information about cumulative cortisol levels over the course of several months. Long-term stress might be one of the factors contributing to the onset of cardiovascular conditions and also affecting different risk factors. The aim of this study was to analyse the association between Hair Cortisol Concentrations and previous cardiovascular diseases and cardiovascular risk factors., Methods: The method of measuring chronic stress by Hair Cortisol Concentration was applied in a large Swedish national observational cross-sectional study. A population-based random sample of N = 4,821 Swedish middle-aged men and women was analysed for hair cortisol levels in relation to diagnosed previous cardiovascular diseases and biologically measured cardiovascular risk factors., Results: Long-term stress, measured by hair cortisol, was significantly associated with the classical cardiovascular risk factors hypertension and high cholesterol, but not smoking. Those with elevated HCC levels also had a significantly increased pre-history of myocardial infarction, type 2 diabetes, atrial fibrillation and by-pass surgery, but not regarding stroke, angina pectoris or sleep apnoea. Higher HCC was significantly associated (p < 0.001) with Body mass index and waist circumference, but only for females. HCC was also associated with the risk markers leukocytes, and high-sensitivity CRP, indicating a possible linkage between HCC and inflammation and hypothetically also the bodily immune defense. No association was found between perceived stress and HCC., Conclusions: An overall conclusion of our results is that health care should put more emphasis on patients reporting that they have been exposed to long term stress. Altogether, these analyses of Hair cortisol levels in a large middle-aged population show that chronically elevated cortisol levels represent a relevant and significant factor associated with cardiovascular diseases and classical cardiovascular risk factors., (© 2024. The Author(s).)

Aims: Examine whether the low-density lipoprotein cholesterol (LDL -C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease., Methods and Results: We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the region directly measure LDL -C whereas four laboratories calculate LDL -C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL -C determined during 2018-2019. There were 202 807 people who had LDL -C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL -C measurement. The median reported LDL -C was 3.40 mmol/L [interquartile range (IQR) 2.90-4.00] for those with a direct measurement vs. 3.00 mmol/L (IQR 2.40-3.50) for those with calculated LDL -C. For those with direct measurement, re-calculated LDL -C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL -C measurement. Among those with directly measured LDL -C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL -C. Direct LDL -C measurement led to higher odds of having a statin initiated compared with calculated LDL -C (adjusted odds ratio 1.23, 95% CI 1.17-1.30); for those with triglycerides >1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30-1.52)., Conclusion: Differences in the reporting of LDL -C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: A number of health issues, including high serum uric acid (SUA) and cardiovascular disease (CVD), have been linked to obesity based on observational evidence, though it's currently unclear how these issues are causally related. In order to determine whether obesity mediates this association, we set out to investigate the causal relationship between SUA, obesity, and CVD., Methods and Results: From publicly available genome-wide association studies, we acquired instrumental variables that had a strong correlation to SUA and body mass index (BMI). We employed multiple two-step Mendelian randomization (MR) analyses, using genetic and clinical data from various publicly available biological databases. The mediating role of BMI was examined through mediation analysis. SUA was genetically correlated with BMI [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. There was a positive causal effect of SUA on AF [OR = 0.892, 95% CI: 0.804-0.990, P = 0.032], CAD [OR = 0.942, 95% CI: 0.890-0.997, P = 0.037], and EHT [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. Among them, BMI mediated the effects of SUA on AF (42.2%; 95% CI, 35.3%-51.9%), CAD (76.3%; 95% CI, 63.4%-92.0%), and EHT (10.0%; 95% CI, 0%-20.0%)., Conclusion: Our research revealed a causal relationship between high SUA exposure and an increased risk of obesity. Additionally, a high SUA level was linked to an increased risk of various CVDs. Given that individuals with high SUA are more likely to be susceptible to AF, CAD, and EHT, attention must be given to their weight status., Competing Interests: Declaration of competing interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Considering the previous research that suggested that screen time (ST), sleep duration, physical activity (PA), obesity and cardiometabolic risk factors are related, it is essential to identify how these variables are associated over time, to provide knowledge for the development of intervention strategies to promote health in pediatric populations. Also, there is a lack of studies examining these associations longitudinally. The aims of the present study were: (1) to investigate the longitudinal relationships between ST, sleep duration, leisure PA, body mass index (BMI), and cardiometabolic risk score (cMetS) in children and adolescents; and (2) to verify scores and prevalence of cMetS risk zones at baseline and follow-up., Methods: This observational longitudinal study included 331 children and adolescents (aged six to 17 years; girls = 57.7%) from schools in a southern city in Brazil. ST, sleep duration, and leisure PA were evaluated by a self-reported questionnaire. BMI was evaluated using the BMI z-scores (Z&#95;BMI). The cMetS was determined by summing sex- and age-specific z-scores of total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, glucose, and systolic blood pressure and dividing it by four. A two-wave cross-lagged model was implemented., Results: ST, sleep duration, and leisure PA were not associated with cMetS after 2-years. However, it was observed that higher ST at baseline was associated with shorter sleep duration at follow-up (B=-0.074; 95%IC=-0.130; -0.012), while higher Z&#95;BMI from baseline associated with higher cMetS of follow-up (B = 0.154; 95%CI = 0.083;0.226). The reciprocal model of relationships indicated that the variance of ST, sleep time, leisure PA, Z&#95;BMI, and cMetS explained approximately 9%, 14%, 10%, 67% and 22%, respectively, of the model. Individual change scores and prevalence indicated that cMetS had individual changes from 2014 to 2016., Conclusion: Sleep duration, ST and leisure PA were not associated with cMetS after 2 years. ST showed an inverse association with sleep duration, and Z&#95;BMI was positively associated with cMetS after a 2-year follow-up. Finally, the prevalence of no clustering of risk factors increased after two years. These findings suggest the need to promote healthy lifestyle habits from childhood and considering individual factors that can influence cardiometabolic health in children and adolescents., (© 2024. The Author(s).)

Background: An updated definition was developed to better evaluate cardiovascular health (CVH). We aimed to investigate whether optimal or improvement of six CVH metrics defined by new Life's Essential 8 (LE8) may counteract the risk of subclinical atherosclerosis among patients with hyperglycemia., Methods: We conducted a prospective analysis of 5225 participants without prior cardiovascular diseases, of whom 4768 had complete data on CVH change. Subjects with CVH scores of 0-49, 50-79, and 80-100 points were categorized as having low, moderate, or high CVH, respectively. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity, pulse pressure and albuminuria, both separately and in combination., Results: Of the 5225 participants, 1937 (37.1%) had normal glucose regulation, while 3288 (62.9%) had hyperglycemia. The multivariable-adjusted odds ratio (OR) for composite subclinical atherosclerosis was 2.34 (95% confidence interval [CI], 1.88-2.91), 1.43 (95% CI, 1.21-1.70), and 0.74 (95% CI, 0.46-1.18), for participants with hyperglycemia who had low, moderate, or high overall CVH scores, respectively, compared with participants with normal glucose regulation. In addition, compared with those with stable CVH and normal glucose regulation, participants who exhibited greater improvements in overall CVH from 2010 to 2014 had a reduced risk of composite subclinical atherosclerosis with an OR of 0.72 (95% CI, 0.53-0.98) for those with normal glucose regulation, and 1.13 (95% CI, 0.87-1.48) for those with hyperglycemia., Conclusions: The novel defined CVH using six metrics was inversely associated with subsequent risk of subclinical atherosclerosis. Both the status of CVH and its changes modified the relationship between hyperglycemia and subclinical atherosclerosis., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Patients with systemic lupus erythematosus (SLE) experience greater cardiovascular morbidity and mortality compared to the general population. It is known that endothelial dysfunction, an early indicator of atherosclerosis development, can arise even without the presence of conventional cardiovascular risk factors. In fact, the risk factors contributing to cardiovascular disease can be classified into traditional risk factors and those uniquely associated with SLE such as disease activity, autoantibodies, etc.Furthermore, the pathogenesis of cardiovascular disease in SLE is linked to the activation of both the innate and adaptive immune systems. Given these findings, it is essential for clinicians to acknowledge the heightened CVD risk in SLE patients, perform comprehensive screenings for cardiovascular risk factors, and implement aggressive treatment strategies for those who exhibit signs of clinical CVD. The aim of this review is to summarize the findings on cardiovascular disease in SLE and to examine potential screening and therapeutic strategies for clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP)., Methods and Results: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (β = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (β = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH levels were associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014)., Conclusion: In a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors., Competing Interests: Conflicts of interest The authors declare they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Cardiovascular diseases (CVD) is a major threat to public health, while cardiorespiratory fitness (CRF) is a key predictor of chronic disease. Given this, the purpose of this study was to investigate the relationship between estimated CRF (eCRF) and CVD in middle-aged and elderly Chinese people., Methods and Results: The China Health and Retirement Longitudinal Study (CHARLS) with 4761 individuals were included in analysis. Participants were divided into three groups according to eCRF quantile in sex subgroups. Cox proportional hazards regression models were used to explore the correlation of eCRF with CVD (stroke or cardiac events). In total, 4761 participants were included in this cohort study (2500 [52.51%] women). During a 7-year follow-up from 2011 to 2018, 796 CVDs (268 Strokes and 588 cardiac events) were recorded. In multivariable-adjusted analyses, for per 1 SD increase of eCRF, the age-adjusted risk of CVD was reduced by about 18% (HR = 0.82; 95% CI, 0.72-0.93) in men, and was reduced by about 29% (HR = 0.71; 95% CI, 0.62-0.81) in women. Similar associations were also found between eCRF and stroke and cardiac events. Both subgroup and interaction analyses showed that the interaction of age had a statistically significant effect on CVD risk., Conclusion: ECRF was inversely associated with CVD risk (stroke or cardiac events) in both men and women. Remarkable sex and age differences exist in the effectiveness of increasing eCRF to reduce the risk of CVD. As a potential, efficient and cost-effective risk prediction tool, eCRF deserves further attention and wide application., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Blood tests are vital to prevention, diagnosis, and management of chronic diseases. Despite this, it can be challenging to construct a comprehensive view of the clinical importance of blood testing because relevant literature is typically fragmented across different disease areas and patient populations. This lack of collated evidence can also make it difficult for primary care providers to adhere to best practices for blood testing across different diseases and guidelines. Thus, this review article synthesizes the recommendations for, and importance of, blood testing across several common chronic conditions encountered in primary care and internal medicine, including cardiovascular diseases, diabetes mellitus, chronic kidney disease, vitamin D deficiency, iron deficiency, and rheumatoid arthritis. Future research is needed to continue improving chronic disease management through clearer dissemination and awareness of clinical guidelines among providers, and better access to blood testing for patients (e.g., via pre-visit laboratory testing)., Competing Interests: Conflicts of Interest Imelda Cabalar received consulting fees from Becton, Dickinson and Company, was on the Advisory Board for Gilead Sciences in January 2020, and served as a Consultant for Cardinal Health in March 2020. Thu Le received consulting fees from Becton, Dickinson and Company and served on the Advisory Board for Mineralys in September 2023. Abigail Silber and Matthew O'Hara are employed by Trinity Life Sciences and received consulting fees from Becton, Dickinson and Company. Bilal Abdallah and Monisha Parikh are employed by Becton, Dickinson and Company. Robert Busch received consulting fees from Becton, Dickinson and Company, is on the Speaker Bureau for Novo Nordisk, Eli Lilly, Amgen, and AstraZeneca, provides research support for Novo Nordisk, Eli Lilly, and Corcept Pharmaceuticals, and is on the Advisory Board for Novo Nordisk., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Dr Rodriguez is supported by grants from the National Institutes of Health (1R01 HL158156, 75N92019D00011, 1U01HL146204-01, 5R01HL144707) and the American Heart Association (U54HL120163), has received research support from and advisory board fees from Amgen, and honoraria from the AHA and Merck. Dr Lloyd-Jones has no relationship with industry. He has served as an unpaid fiduciary officer of the AHA and is a volunteer member of the national board of directors for AHA. Drs Carnethon and Arnett have no disclosures.

Background: Home blood pressure (BP) is more closely associated with cardiovascular event risk than office BP, but cardiovascular risk prediction based on home BP variability is lacking. This study developed a simple cardiovascular event prediction score, including home BP variability data, from the J-HOP study (Japan Morning Surge-Home Blood Pressure)., Methods: The J-HOP study extended follow-up from December 2017 to May 2018 generated the study data set (4231 patients). Cardiovascular events included fatal/nonfatal stroke (n=94), coronary heart disease (n=124), heart failure (n=42), and aortic dissection (n=8). Cox proportional hazards models were used to predict overall cardiovascular risk. Potential covariates included age, sex, body mass index, smoking, history of diabetes, statin use, history of cardiovascular disease, total cholesterol:high-density lipoprotein cholesterol ratio, office systolic BP (SBP), mean of morning-evening average (MEave), home SBP, and average real variability of MEave home SBP. A risk score and models were constructed, and model performance was assessed., Results: Model performance was best when average real variability of MEave SBP was included (C statistic, 0.760). The risk score assigns points for age (5-year bands), sex, cardiovascular disease history, high-density lipoprotein cholesterol, mean MEave home SBP, and average real variability of MEave home SBP. Estimated 10-year cardiovascular risk ranged from ≤0.6% (score ≤0) to >32% (score ≥26). Calibration 2 statistics values for the model (2.66) and risk score (5.29) indicated excellent goodness of fit., Conclusions: This simple cardiovascular disease prediction algorithm, including day-by-day home BP variability, could be used as part of a home BP-centered approach to hypertension management in clinical practice., Competing Interests: K. Kario has received research funding from Omron Healthcare Co, Fukuda Denshi and A&D Co. The other authors report no conflicts.