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Abstract: A "restrictive" red blood cell transfusion threshold, a hemoglobin concentration <7 to 8 g/dL, has long been recommended for most hospitalized patients including anemic patients with stable cardiovascular disease (CVD). Although no threshold recommendation is given for acute coronary syndromes (ACSs), recent evidence suggests that "liberal" rather than "restrictive" transfusion strategies are associated with significantly improved safety for hospitalized patients with stable CVD and/or ACS. This finding suggests that previously available data were misinterpreted. Conclusions drawn from earlier transfusion trigger trials have been confounded by unintentional trial design and analysis flaws that have contributed to erroneous recommendations regarding the safety of a restrictive threshold. Subsequently, these conclusions have been incorporated into widely accepted guidelines and clinical practice. Management with a restrictive vs liberal transfusion strategy (<10 g/dL) increases the risk of new-onset ACS in patients with CVD by ∼2%. We estimate that since 2019, using hospital databases and a recent meta-analysis, this practice may have resulted in ∼700 excess ACS events per year in orthopedic surgical patients. Given these findings, transfusion practices in other clinical conditions, particularly those derived from similar transfusion trigger trials, should be questioned. Restrictive and liberal transfusion policies merit a general reconsideration. Rather than a single numerical transfusion trigger, transfusion therapy should be personalized. Consideration of an individual patient's age, clinical status, and comorbidities is integral to transfusing. To avoid making similar errors, future trials of transfusion therapy should determine common practices before study inception and incorporate them as a usual-care "control" comparator arm into the trial design. Such studies should more reliably improve current transfusion practice.

Background: During the COVID-19 pandemic sex-related differences concerning the spectrum of cardiovascular complications have been observed in the acute infection, and during recovery. This study aims to emphasize sex-related disparities regarding left ventricular systolic function (LVSF), right ventricular function (RVF), diastolic dysfunction (DD), and pericardial pathologies during the post-COVID-19 syndrome., Methods: 274 patients with post-acute COVID-19 syndrome, 127 men and 147 women, aged under 55, were evaluated within 90 days after the acute illness and followed at 3 and 6 months., Results: Based on detailed transthoracic echocardiography (TTE), we identified significantly more frequently (p˂0.001) altered LVSF in men, while in women impaired RVF, and DD were significantly more common (p˂0.001). Pericardial impairment did not seem to be influenced by gender. The TTE parameters characterizing these patterns were correlated with the severity of the initial infection and the time elapsed since and alleviated in time. The multivariate regression analysis confirmed these sex-related associations and their impact on patients' functional status., Conclusions: Male patients had a higher tendency to develop altered LVSF, while female subjects had more frequently impaired RVF and DD. These abnormalities alleviated in time and exerted a significant influence on patients' functional status., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with OSA are at increased risk of postoperative cardiorespiratory complications and death. Attempts to stratify this risk have been inadequate, and predictors from large, well-characterized cohort studies are needed., Research Question: What is the relationship between OSA severity, defined by various polysomnography-derived metrics, and risk of postoperative cardiorespiratory complications or death, and which metrics best identify such risk?, Study Design and Methods: In this cohort study, 6,770 consecutive patients who underwent diagnostic polysomnography for possible OSA and a procedure involving general anesthesia within a period of 2 years before and at least 5 years after polysomnography. Participants were identified by linking polysomnography and health databases. Relationships between OSA severity measures and the composite primary outcome of cardiorespiratory complications or death within 30 days of hospital discharge were investigated using univariable and multivariable analyses., Results: The primary outcome was observed in 5.3% (n = 361) of the cohort. Although univariable analysis showed strong dose-response relationships between this outcome and multiple OSA severity measures, multivariable analysis showed its independent predictors were: age older than 65 years (OR, 2.67 [95% CI, 2.03-3.52]; P < .0001), age 55.1 to 65 years (OR, 1.47 [95% CI, 1.09-1.98]; P = .0111), time between polysomnography and procedure of ≥ 5 years (OR, 1.32 [95% CI, 1.02-1.70]; P = .0331), BMI of ≥ 35 kg/m 2 (OR, 1.43 [95% CI, 1.13-1.82]; P = .0032), presence of known cardiorespiratory risk factor (OR, 1.63 [95% CI, 1.29-2.06]; P < .0001), > 4.7% of sleep time at an oxygen saturation measured by pulse oximetry of < 90% (T90; OR, 1.91 [95% CI, 1.51-2.42]; P < .0001), and cardiothoracic procedures (OR, 7.95 [95% CI, 5.71-11.08]; P < .0001). For noncardiothoracic procedures, age, BMI, presence of known cardiorespiratory risk factor, and percentage of sleep time at an oxygen saturation of < 90% remained the significant predictors, and a risk score based on their ORs was predictive of outcome (area under receiver operating characteristic curve, 0.7 [95% CI, 0.64-0.75])., Interpretation: These findings provide a basis for better identifying high-risk patients with OSA and determining appropriate postoperative care., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: D. R. H. received a grant from Philips Healthcare to support the study. None declared (M. A., R. P., G. C., S. K., N. M., B. S.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

OSA is diagnosed and managed by a metric called the apnea-hypopnea index (AHI). The AHI quantifies the number of respiratory events (apnea or hypopnea), disregarding important information on the characteristics and physiologic consequences of respiratory events, including degrees of ventilatory deficit and associated hypoxemia, cardiac autonomic response, and cortical activity. The oversimplification of the disorder by the AHI is considered one of the reasons for divergent findings on the associations of OSA and cardiovascular disease (CVD) in observational and randomized controlled trial studies. Prospective observational cohort studies have demonstrated strong associations of OSA with several cardiovascular diseases, and randomized controlled trials of CPAP intervention have not been able to detect a benefit of CPAP to reduce the risk of CVD. Over the last several years, novel methodologies have been proposed to better quantify the magnitude of OSA-related breathing disturbance and its physiologic consequences. As a result, stronger associations with cardiovascular and neurocognitive outcomes have been observed. In this review, we focus on the methods that capture polysomnographic heterogeneity of OSA., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. A. reports grant support from Somnifix and serves as a consultant for Somnifix, Respicardia, Eli Lilly, Inspire, Cerebra, and Apnimed. Apnimed is developing pharmacological treatments for Obstructive Sleep Apnea. A. A.’s interests were reviewed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their institutional policies. A. W. works as a consultant for Apnimed, Nox, Inspire, and Somnifix International LLC. He has received grants from Sanofi and Somnifix. He also has a financial interest in Apnimed Corp., a company developing pharmacologic therapies for sleep apnea. A. W.’s interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. None declared (G. L., Y. K.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Thyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality., Objective: The purpose of this study was to investigate the potential causal relationships of thyroid-stimulating hormone (TSH), free thyroxine, hypothyroidism, and hyperthyroidism with cardiovascular outcomes, including atrial fibrillation (AF), coronary artery disease, myocardial infarction, heart failure, and ischemic stroke, as well as their effect on cardiac structure and function assessed by cardiac magnetic resonance imaging., Methods: A comprehensive 2-sample Mendelian randomization analysis was performed using summary data from large-scale meta-analyses of European ancestry individuals., Results: Genetically determined lower TSH levels (odds ratio 0.928; 95% confidence interval 0.884-0.974; P = .003) and genetic risk of hyperthyroidism (odds ratio 1.049; 95% confidence interval 1.016-1.083; P = .003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable Mendelian randomization revealed height as a key mediator between TSH/hyperthyroidism and AF. These findings were further corroborated in the independent FinnGen cohort. However, no clear evidence was found for relationships between thyroid function and other cardiovascular outcomes and cardiac structure and function., Conclusion: Our study shows that reduced TSH levels and hyperthyroidism heighten AF risk, with height serving as an important mediator in these associations. The primary focus of thyroid management in cardiovascular health should be on preventing and treating arrhythmias, particularly AF. Our research highlights the importance of routine screening and timely treatment of thyroid dysfunction to optimize the prevention and management of arrhythmias., Competing Interests: Disclosures The authors declare that the study was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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.)

Objectives: Evidence suggests that some COVID-19 survivors experience a wide range of post-COVID-19 sequelae; however, the majority of studies were conducted before the emergence of the milder Omicron variant. We examined the post-acute risk of new-incident cardiovascular complications after SARS-CoV-2 infection in a multi-ethnic Asian population, during Omicron predominance., Methods: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals with confirmed SARS-CoV-2 infection during Omicron BA.1/2 transmission and a contemporaneous test-negative group. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular complications using doubly robust competing-risks survival analysis. Risks were reported using two measures: hazard ratio and excess burden., Results: We included 375 903 test-positive, infected individuals (mean age 48 years) and 619 379 test-negative controls (mean age 47 years). The majority (97.5%, 366 593/375 903) of infected individuals had mild infection not requiring hospitalization. There was no overall increased risk of new-incident cardiovascular complications, (adjusted hazards ratio, aHR = 1.01 [0.97-1.07]) amongst COVID-19 survivors when compared against test-negatives. A modestly increased risk and excess burden of dysrhythmias amongst COVID-19 survivors (aHR = 1.09 [1.01-1.19]) was observed. Risk and burdens of new-incident cardiovascular complications predominantly accrued in hospitalized (aHR = 2.81 [2.26-3.50]) and severe COVID-19 cases (aHR = 5.52 [3.76-8.10])., Discussion: No significantly increased overall risk of any cardiovascular complication was observed in the 300 days following COVID-19 infection during the Omicron-dominant period when compared against test-negatives, with the exception of a small increased occurrence of dysrhythmias., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. 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.)

In the general population, decreases in glomerular filtration rate (GFR) are associated with subsequent development of chronic kidney disease (CKD), cardiovascular disease (CVD), and death. It is unknown if low estimated GFR (eGFR) before or early after kidney donation was also associated with these risks. One thousand six hundred ninety-nine living donors who had both predonation and early (4-10 weeks) postdonation eGFR were included. We studied the relationships between eGFR, age at donation, and the time to sustained eGFR<45 (CKD stage 3b) and <30 mL/min/1.73m 2 (CKD stage 4), hypertension, diabetes mellitus (DM), CVD, and death. Median follow-up was 12 (interquartile range, 6-21) years. Twenty-year event rates were 5.8% eGFR<45 mL/min/1.73m 2 ; 1.2% eGFR<30 mL/min/1.73m 2 ; 29.0% hypertension; 7.8% DM; 8.0% CVD; and 5.2% death. The median time to eGFR<45 mL/min/1.73m 2 (N = 79) was 17 years, and eGFR<30 mL/min/1.73m 2 (N = 22) was 25 years. Both low predonation and early postdonation eGFR were associated with eGFR<45 mL/min/1.73m 2 (P < .0001) and eGFR<30 mL/min/1.73m 2 (P < .006); however, the primary driver of risk for all ages was low postdonation (rather than predonation) eGFR. Predonation and postdonation eGFR were not associated with hypertension, DM, CVD, or death. Low predonation and early postdonation eGFR are risk factors for developing eGFR<45 mL/min/1.73m 2 (CKD stage 3b) and <30 mL/min/1.73m 2 (CKD stage 4), but not CVD, hypertension, DM, or death., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Medicare/Medicaid insurance receive metabolic and bariatric surgery (MBS) at lower rates than privately insured (PI) patients. Although studies on some surgical procedures report that Medicare/Medicaid insurance confers increased postoperative complication rates and a longer length of stay, less is known about these outcomes after MBS. Among often-feared postoperative complications are major adverse cardiovascular and cerebrovascular events (MACEs). Although these events are rare after MBS, they have a significant impact on morbidity and mortality., Objectives: This study aimed to examine the effect of insurance payor status on MACEs after MBS., Setting: The Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS)., Methods: HCUP-NIS was queried for cases including sleeve gastrectomy or Roux-en-Y gastric bypass between 2012 and 2019. Bivariate associations between patient-level factors and MACEs were assessed via Rao-Scott χ 2 tests. Adjusted and unadjusted risks of insurance payor status for MACEs were evaluated using logistic regression., Results: Incidence of MACEs was higher in both Medicare (.75% versus .11%; P < .001) and Medicaid (.15% versus .11%; P < .001) groups than in the PI group. After adjustment for high-risk demographics, high-risk co-morbidities, socioeconomic variables, and hospital factors, insurance status of Medicare (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.23, 2.07; P = .0026) or Medicaid (OR: 1.55, 95% CI: 1.12, 2.16; P = .0026) remained an independent risk factor for MACEs., Conclusions: Our findings underscore the significance of Medicaid/Medicare payor status as an independent predictor of postoperative MACEs in MBS. The results of this study can have a significant impact on deepening our understanding of socioeconomic and health system-related issues that can be targeted to improve outcomes in both MBS and other surgical specialties., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest There is no conflict of interest.

Background: To test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event., Methods: In this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event., Results: We observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0440)., Conclusions: Dietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: An updated understanding of global prevalence of primary aldosteronism (PA) is essential for the development of primary prevention and management strategies for PA. We aimed to provide update global and regional prevalence of PA and to evaluate cardiovascular risk of PA compared to essential hypertension (EH)., Methods: We systematically searched PubMed, Web of Science, and Embase for studies on the prevalence of PA or cardiovascular risk of PA published up to July 31, 2022 for this meta-analysis. Global prevalence of PA was calculated using random-effects inverse-variance models and cardiovascular risk of PA was estimated using random-effects models., Results: We identified 39 articles for meta-analysis of PA prevalence, and 13 articles were included in the meta-analysis of cardiovascular risk. Global prevalence of PA was 9.4% (95% CI: 8.3-10.5), with a higher prevalence in males than in females. Prevalence of PA was higher in the South-East Asia than in other regions, and higher in lower middle-income countries than in other economic levels, with greater country-specific differences. Compared with EH, PA had an increased risk of coronary artery disease (OR=1.88, 95% CI: 1.41-2.50), stroke (OR=2.50, 95% CI: 2.08-3.02), heart failure (OR=2.06, 95% CI: 1.33-3.19), and atrial fibrillation (OR=3.17, 95% CI: 2.09-4.80)., Conclusion: The management of the increasing number of patients with PA and its associated burden of cardiovascular disease is likely to place increasing pressure on health systems. Early detection of PA is essential to reduce the associated burden, especially in areas where the assessment of PA has not received sufficient attention., 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 Inc. All rights reserved.)

Background: Some patients with diabetes are unaware that they are prescribed medications for diabetes. The purpose of this study is to determine, using a Japanese nationwide epidemiologic database, the association between unawareness of being prescribed medication for diabetes and the risk of developing cardiovascular disease (CVD) in patients with diabetes., Methods: This observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 94,048 patients with diabetes treated with medications. The primary endpoint was a composite endpoint including myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF)., Results: We identified 7561 composite CVD endpoints during a mean follow-up of 1199 ± 902 days. Overall, 7779 (8.3 %) patients were unaware of being prescribed medications for diabetes. Those who did not know they were prescribed drugs were younger and had better glycemic control, but these individuals were at higher risk of developing combined CVD [hazard ratio (HR) 1.13, 95 % confidence interval (95 % CI) 1.04-1.22]. HRs of unawareness of being prescribed medications for diabetes were 1.33 (95 % CI 1.06-1.68) for MI, 1.13 (95 % CI 0.97-1.31) for stroke, 1.10 (95 % CI 1.00-1.21) for HF, and 1.19 (95 % CI 0.97-1.47) for AF, respectively., Conclusions: In patients with diabetes taking medications for diabetes, even if they are young and have good glycemic control, unawareness of being prescribed medications for diabetes was associated with a greater risk of developing CVD. It is important that they receive adequate education from their healthcare providers to accurately identify their treatment status., Competing Interests: Declaration of competing interest Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan Co., Ltd., Boston Scientific Japan Co., Ltd., Biotronik Japan, Simplex Quantum Co., Ltd., and Fukuda Denshi, Central Tokyo Co., Ltd., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: Low-carbohydrate-diets (LCDs) are gaining popularity in individuals with type 1 diabetes (T1D). However, the impact of such diets on glycemia and cardiovascular risk factors is debated. This study aims to evaluate associations between low-carbohydrate intakes using LCD score with glycemia and cardiovascular risk factors (lipid profile) in adults with T1D or LADA in Québec, Canada., Methods and Results: This is a cross-sectional study using data collected in the BETTER registry (02/2019 and 04/2021) including self-reported 24-h dietary recalls to calculate LCD scores, waist circumference, level-2 and level-3 hypoglycemic episodes and measured biochemical data (HbA1c, LDL-cholesterol and non-HDL-cholesterol). Participants were divided into quartiles (Q) based on LCD scores. Two hundred eighty-five adults (aged 48.2 ± 15.0 years; T1D duration 25.9 ± 16.2 years) were included. Categorical variables underwent Chi-squared/Fisher's Exact tests, while continuous variables underwent ANOVA tests. Mean carbohydrate intake ranged from 31.2 ± 6.9% (Q1) to 56.5 ± 6.8% (Q4) of total daily energy. Compared to Q4, more people in Q1 reported HbA1c ≤ 7% [≤53.0 mmol/mol] (Q1: 53.4% vs. Q4: 29.4%; P = 0.011). The same results were found in the models adjusted for age, sex and T1D duration. A greater proportion of participants in Q1 never experienced level-3 hypoglycemia compared to Q3 (Q1: 60.0% vs. Q3: 31.0%; P = 0.004). There were no differences across quartiles for frequency of level-2 hypoglycemia events and lipid profile (LDL-cholesterol and non-HDL-cholesterol)., Conclusions: Low-carbohydrate intakes are associated with higher probabilities of reaching HbA1c target and of never having experienced level-3 hypoglycemia. No associations with level-2 hypoglycemia frequency, nor cardiovascular risk factors were observed., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well established in patients with advanced chronic kidney disease (CKD). We conducted a systematic review and meta-analysis to identify potential risks and benefits from RAAS blockade in patients with CKD stage 4-5., Methods: A Medline search from inception to November 2022 was conducted to identify randomised controlled trials (RCTs) in patients with CKD stage 4-5 (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m 2 ) comparing RAAS blockade vs placebo or alternative antihypertensive therapy. Different intervention strategies were assessed (RAAS use vs nonuse, initiation vs placebo/alternative therapy, or discontinuation vs continuation). The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were all-cause mortality and major adverse cardiovascular events (MACE). The risk ratio (RR) was estimated with the use of a random-effects model., Results: Nine RCTs (1150 patients) were included. RAAS blockade was associated with a significant reduction in progression to ESKD: RR 0.84 (95% confidence interval [CI] 0.74-0.96; P = 0.01). There was no benefit from RAAS blockade on all-cause mortality or MACE: RR 1.02 (95% CI 0.63-1.65; P = 0.93) and RR 0.87 (95% CI 0.49-1.57; P = 0.65), respectively., Conclusions: RAAS blockade may be considered in selected patients with CKD stage 4-5 to delay progression to ESKD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, the mean survival rate of children after a cancer diagnosis has significantly improved. At the same time, a growing interest in short and long-term cardiovascular (CV) complications of cancer therapy, as well as long-term CV risk in childhood cancer survivors (CCS) developed, along with proposals of protocols for the diagnosis, management, and prevention of cancer therapy-related CV toxicity (CTR-CVT) in this population. Many clinical and individual risk factors for CTR-CVT have been identified, and a non-negligible prevalence of traditional CV risk factors has been described in this population, potentially associated with a further worsening in both CTR-CVT and long-term CV risk. Physical exercise (PE) represents a promising, free-of-cost and free-of-complications, helpful therapy for primary and secondary prevention of CTR-CVT in CCS. The present narrative review aims to summarize the most critical evidence available about CTR-CVT in CCS, focusing on the role of PE in this clinical scenario., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cardiovascular diseases (CVD) is the major cause of mortality globally, with increasing evidence suggesting a link between periodontitis, and CVD. This study aims to explore the association between periodontitis and CVD, and the impact of periodontal therapy on cardiovascular health., Methods: This review synthesized findings from preclinical and clinical studies, without publication year restrictions, examining periodontitis and CVD through various lenses. Scientific databases were inspected with keywords related to periodontitis and CVD., Results: The review identifies a substantial association between periodontitis and an increased risk of several CVD, supported by both epidemiological and interventional studies. Results suggest the complexity of the relationship, influenced by factors like the severity of periodontitis and the presence of other systemic conditions. Clinical data indicates that periodontal therapy, particularly non-surgical periodontal therapy, may reduce systemic inflammatory markers and thus may play a role in the primary and secondary prevention of CVD events, highlighting the potential of periodontal therapy to not only maintain oral health but also to modulate cardiovascular risk factors., Conclusions: Current evidence supports a significant association between periodontitis and increased cardiovascular risk, promoting integrated healthcare approaches that consider oral health as a key-component of cardiovascular care and wellbeing., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Nutrition can play a key role in cardiovascular disease risk reduction, and its risk factors modification. This paper aims to present, compare, and summarize the main dietary concepts for preventing the main cardiovascular disease risk factors - obesity, hypertension, and dyslipidemia. The dietary models and macronutrient intakes were compared between main cardiovascular risk factors prevention recommendations. Dietary recommendations related to selected cardiovascular risk factors share the points, that can be suggested as crucial for overall cardiovascular risk factors reduction. Recommendations suggest limiting saturated fatty acids intake to <10% of total caloric intake in obesity, and <7 % in hypercholesterolemia, along with an increased intake of mono- and polyunsaturated fatty acids. In addition, daily dietary fiber intake should reach a level of 25-40 g. The vegetables and fruits should be consumed at a daily minimum level of 200g (or 4-5 portions) each. Salt intake should not exceed 5g/day. Alcohol should be generally avoided, and moderate intake levels (sex-specific) should not be exceeded. It is also worth noting, that proteins are essential for tissue formation and regeneration. Carbohydrates are the main source of energy, but it is necessary to choose products with a low glycemic index. Dietary antioxidants help combat free radicals and prevent cell damage., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: . The long-term impact of gestational complications on cardiovascular outcomes in women remains a subject of debate., Aim: To assess the 5-year risk of cardiovascular events and all-cause mortality in women with gestational diabetes and hypertension., Methods: Retrospective study utilising an health research network(TriNetX). The primary outcome was the composite risk of a cardiovascular event within 5 years with secondary outcomes being its components (all-cause death, acute heart failure, myocardial infarction, ischaemic stroke). Women were categorised into 8 different groups based on the ICD-codes for pregnancy related complications recorded 9 months before the delivery:1) gestational diabetes,2) gestational hypertension,3) gestational diabetes with gestational hypertension,4) gestational diabetes with gestational hypertension without pre-eclampsia or eclampsia,5) gestational diabetes with pre-eclampsia or eclampsia,6) gestational hypertension without pre-eclampsia or eclampsia,7) pre-eclampsia or eclampsia,and 8) no gestational complications. Cox-regression analyses were used to produce hazard ratios (HRs) and 95 % confidence intervals (CI) before and after propensity score matching (PSM)., Results: We identified, 24,402 women with gestational diabetes and gestational hypertension and 920,478 without gestational complications. After PSM, compared to women without pregnancy complications, women with gestational diabetes and gestational hypertension had a higher 5-year risk of composite outcome(HR 2.25,95 %CI 2.02-2.51), all-cause death(HR 1.64,95 %CI 1.31-2.06), acute heart failure(HR 2.06,95 %CI 1.69-2.52), myocardial infarction(HR 2.46,95 %CI 1.93-3.14), and ischemic stroke(HR 2.37,95 %CI 2.06-2.74). Women who experienced pre-eclampsia or eclampsia showed the highest risk of primary and secondary outcomes., Conclusions: Gestational complications are associated with worse long-term cardiovascular outcomes. There is a clear call to action required to improve the longitudinal management of gestational complications to improve women's long-term health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GYHL is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. GYHL is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 899871. AM is funded by a National Institute for Health Research Advanced Fellowship. CLM is funded by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (17/0005712), the European Foundation for the Study of Diabetes - Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974) and the NIHR Biomedical Research Centre in Leicester, UK. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. All other authors report no disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is common in patients with prostate cancer and is an important cause of death. Cardiovascular risk factors are frequent in this population and are often not addressed to thresholds recommended by cardiovascular practice guidelines. Androgen deprivation therapy (ADT) reduces muscle strength and increases adiposity, thereby increasing the risk of diabetes and hypertension, although its relationship with adverse cardiovascular events requires confirmation. Androgen receptor signaling inhibitors and CYP17A1 inhibitors may confer incremental risks of hypertension and cardiovascular events to ADT. Lower cardiovascular risk with gonadotropin-releasing hormone antagonists as compared with agonists requires prespecified randomized clinical trial confirmation., Competing Interests: Disclosure D.P. Leong reports consultancy fees or advisory boards from Abbvie, Ipsen, Janssen, Jazz Pharmaceuticals, Myovant, Novartis, Sanofi, Antev, Bayer, Boston Scientific; speaker fees from Ferring, Pfizer, AstraZeneca; and research grants from Tolmar and Novartis. J.H. Pinthus reports consultancy fees or advisory boards from Ferring, Myovant and Antev; speaker fees from Ferring and research grants from Ferring. F. Cirne has no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations., Objective: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers., Methods: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates., Results: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs., Conclusion: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population., 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. Published by Elsevier B.V.)

There is strong evidence that PAPP-A, a local regulator of insulin-like growth factor signaling through proteolytic cleavage of inhibitory binding proteins, is involved in multiple physiological processes associated with cardiovascular disease. This review will describe the various roles of PAPP-A with a focus on atherosclerosis, neointimal hyperplasia, and acute coronary syndrome in animal models and in humans., Competing Interests: Declaration of competing interest The author declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Studies have found that a high Life's Essential 8 (LE8) score is associated with a reduced risk of cardiovascular disease(CVD) in cancer populations and young adults. However, the association between LE8 and the risk of CVD in hyperuricemia (HUA) is not fully understood., Methods: The main analysis included 6814 HUA participants. In a secondary analysis, 5,418 participants were selected from the main analysis to model the trajectory of uric acid (UA) levels from 2006 to 2010. Cox regression model was used to investigate the relationship between LE8 total score and cardiovascular disease risk in different populations., Results: Follow-up of 15.79 years in the main analysis, 986 CVD events occurred. With tertile 1 as the control group, the HR and 95 % CI of CVD in tertile 2 and tertile 3 were 0.75(0.65,0.87) and 0.56(0.47,0.66). In the secondary analysis, the HR and 95 %CI of individuals with low and medium levels of UA reduced CVD were 0.49(0.26,0.89) and 0.56(0.41,0.76), respectively, but this association was not found in individuals with sustained high UA levels. The risk of CVD was different between the sexes. There are differences in cardiovascular disease risk among different age groups., Conclusions: The risk of CVD in HUA population decreased with the increase of LE8 score, especially in young and middle-aged people and women. However, it is important to note that LE8 may not reduce the risk of CVD in individuals with sustained high UA levels., 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. Published by Elsevier Inc.)

Mindfulness training has gained increasing attention as a potential intervention to improve cardiovascular health, particularly in populations with chronic conditions, such as type 2 diabetes. Given the heightened cardiovascular risk associated with type 2 diabetes, identifying effective non-pharmacological strategies to mitigate these risks is crucial. This critical review assessed the current evidence on the impact of mindfulness training on cardiovascular health in individuals with type 2 diabetes. A comprehensive literature search was conducted using the PubMed database, and studies were selected based on stringent inclusion and exclusion criteria. The search strategy was meticulously designed to filter out high-quality articles and ensure that only the most relevant and rigorous studies were included in the analysis. The findings from this review suggest that while mindfulness training has the potential to improve cardiovascular health in individuals with type 2 diabetes, evidence remains mixed. Some studies have reported significant improvements in cardiovascular markers, such as blood pressure and inflammation, while others have shown limited or no effects. This variability highlights the need for further research to better understand the mechanisms underlying these outcomes and identify the most effective mindfulness interventions for this population. In conclusion, mindfulness training appears to be a promising approach for enhancing cardiovascular health in Type 2 diabetes patients, yet the current evidence is inconclusive. Future research should focus on standardizing mindfulness interventions, conducting larger clinical trials, and exploring the long-term benefits of these interventions on cardiovascular outcomes in high-risk populations., Competing Interests: Declaration of competing interest The authors declare that they have no other conflicts of interest related to the research, writing, or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's Disease (AD) neuropathology start decades before clinical manifestations, but whether risk factors are associated with early cognitive and brain changes in midlife remains poorly understood. We examined whether AD risk factors were associated with cognition and functional connectivity (FC) between the Locus Coeruleus (LC) and hippocampus - two key brain structures in AD neuropathology - cross-sectionally and longitudinally in cognitively healthy midlife individuals. Neuropsychological assessments and functional Magnetic Resonance Imaging were obtained at baseline (N=210), and two-years follow-up (N=188). Associations of cognition and FC with apolipoprotein ε4 (APOE ε4) genotype, family history of dementia, and the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score were investigated. Cross-sectionally, higher CAIDE scores were associated with worse cognition. Menopausal status interacted with the CAIDE risk on cognition. Furthermore, the CAIDE score significantly moderated the relationship between cognition and LC-Hippocampus FC. Longitudinally, the LC-Hippocampus FC decreased significantly over 2 years. These results suggest that cardiovascular risk of dementia is associated with brain-behaviour changes in cognitively healthy, middle-aged individuals., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD., 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 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objectives: Air pollution and traffic noise are detrimental to cardiovascular health. However, the effects of different sources of these exposures on cardiovascular biomarkers remain unclear. We explored the associations of long-term exposure to source-specific air pollution (vehicular exhausts and residential woodsmoke) at low concentrations and road-traffic noise with systemic inflammation and cardiovascular disease biomarkers., Material and Methods: Modeled outdoor exposure to fine particulate matter (aerodynamic diameter ≤2.5 μm; PM 2.5 ) from vehicular exhausts and residential woodsmoke, nitrogen dioxide (NO 2 ) from road traffic, and road-traffic noise were linked to the home addresses of the participants (Finnish residents aged 25-74) in the FINRISK study 1997-2012. The participants were located in the cities of Helsinki, Vantaa, and the region of Turku, Finland. The outcomes were high-sensitivity C-reactive protein (CRP), a biomarker for systemic inflammation, and cardiovascular disease biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I. We performed cross-sectional analyses with linear and additive models and adjusted for potential confounders., Results: We found no association between PM 2.5 from vehicular exhausts (% CRP difference for 1 μg/m 3 increase in PM 2.5 : -0.9, 95% confidence interval, CI: -7.2, 5.8), or from residential woodsmoke (% difference: -8.1, 95% CI: -21.7, 7.9) and CRP (N = 4147). Road-traffic noise >70 dB tended to be positively associated with CRP (% CRP difference versus noise reference category of ≤45 dB: 18.3, 95% CI: -0.5, 40.6), but the association lacked significance and robustness (N = 7142). Otherwise, we found no association between road-traffic noise and CRP, nor between NO 2 from road traffic and NT-proBNP (N = 1907) or troponin I (N = 1951)., Conclusion: Long-term exposures to source-specific, fairly low-level air pollution from vehicular exhausts and residential woodsmoke, or road-traffic noise were not associated with systemic inflammation and cardiovascular disease biomarkers in this urban area., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tanja Zeller has patent #397 WO2022043229A1 licensed to a computing device to estimate the probability of myocardial infarction. Tanja Zeller is shareholder of the ART.EMIS GmbH Hamburg. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between stage 1 hypertension and the risk of cardiovascular disease (CVD) has not been established in older adults. Furthermore, little is known about whether lowering blood pressure (BP) is beneficial in older adults with stage 1 hypertension., Methods: This cohort study analyzed nationwide data collected from the Japanese DeSC database, including 476,654 individuals aged ≥60 years. Individuals were categorized into four groups according to the 2017 ACC/AHA BP guidelines: normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension. The primary outcome was a composite CVD event, including myocardial infarction, angina pectoris, stroke, and heart failure., Results: During a mean follow-up of 3.1 years, 53,946 composite CVD events were recorded. Hazard ratios of stage 1 hypertension for composite CVD events, myocardial infarction, angina pectoris, stroke, and heart failure were 1.10 (95 % CI, 1.07-1.13), 1.16 (95 % CI, 1.03-1.31), 1.06 (95 % CI, 1.01-1.10), 1.13 (95 % CI, 1.08-1.18), and 1.13 (95 % CI, 1.09-1.16), respectively. Individuals with a ≥5 mmHg decrease in systolic BP over one year had a lower risk of stroke among individuals with stage 1 hypertension. The positive association between stage 1 hypertension and composite CVD events was attenuated in individuals aged ≥75 years., Conclusions: Stage 1 hypertension is associated with a higher risk of developing CVD events among older adults. The 2017 ACC/AHA BP guidelines could be applied to older populations; however, the applicability of these guidelines to older adults aged ≥75 years requires further investigations., Competing Interests: Declaration of competing interest Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan Co., LTD, Abbott Medical Japan Co., LTD, Boston Scientific Japan Co., LTD, and Fukuda Denshi, Central Tokyo Co., Ltd. Speaker fees from AstraZeneca, Ono Pharmaceutical, Nippon Boehringer Ingelheim; Scholarship donation from Idorsia, Sanofi, Toa Eiyo; Affiliation with endowed chairs from Idorsia Pharmaceuticals Japan, Novo Nordisk Pharma, Toa Eyo Co, Takara Bio Inc., Nippon Boehringer Ingelheim Co., BioStream, Inc. (Issei Komuro). Other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background & Aims: The mechanisms underlying the association of steatotic liver disease with cardiovascular and cancer outcomes are poorly understood. We aimed to use MRI-derived measures of liver fat and genetics to investigate causal mechanisms that link higher liver fat to various health outcomes., Methods: We conducted a genome-wide association study on 37,358 UK Biobank participants to identify genetic variants associated with liver fat measured from MRI scans. We used a Mendelian randomisation approach to investigate the causal effect of liver fat on health outcomes independent of BMI, alcohol consumption and lipids using data from published genome-wide association studies and FinnGen., Results: We identified 13 genetic variants associated with liver fat that had differing effects on the risks of health outcomes. Genetic variants associated with impaired hepatic triglyceride export showed liver fat-increasing alleles to be correlated with a reduced risk of coronary artery disease and myocardial infarction but an elevated risk of type 2 diabetes, while variants associated with enhanced de novo lipogenesis showed liver fat-increasing alleles to be linked to a higher risk of myocardial infarction and coronary artery disease. Genetically higher liver fat content increased the risk of non-alcohol-related cirrhosis, hepatocellular carcinoma, and intrahepatic bile duct and gallbladder cancers, exhibiting a dose-dependent relationship, irrespective of the mechanism., Conclusion: This study provides fresh insight into the heterogeneous effect of liver fat on health outcomes. It challenges the notion that liver fat per se is an independent risk factor for cardiovascular disease, underscoring the dependency of this association on the specific mechanisms that drive fat accumulation in the liver. However, excess liver fat, regardless of the underlying mechanism, appears to be causally linked to cirrhosis and cancers in a dose-dependent manner., Impact and Implication: This research advances our understanding of the heterogeneity in mechanisms influencing liver fat accumulation, providing new insights into how liver fat accumulation may impact various health outcomes. The findings challenge the notion that liver fat is an independent risk factor for cardiovascular disease and highlight the mechanistic effect of some genetic variants on fat accumulation and the development of cardiovascular diseases. This study is of particular importance for healthcare professionals including physicians and researchers, as well as patients, as it allows for more targeted and personalised treatment by understanding the relationship between liver fat and various health outcomes. The findings emphasise the need for a personalised management approach and a reshaping of risk assessment criteria. It also provides room for prioritising a clinical intervention aimed at reducing liver fat content (likely via intentional weight loss) that could help protect against liver-related fibrosis and cancer., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Celiac disease (CD) is an immune-mediated disease with patients being prone to a proinflammatory state. With recent studies showing an association between adverse cardiovascular events in patients with CD, we aim to further elucidate this relationship. Furthermore, when risk-stratifying patients with cardiovascular disease (CVD), chronic inflammatory conditions such as CD are not included in these calculations. We conducted a retrospective analysis using the National Inpatient Sample database from 2016 to 2019 to investigate the relationship between CD and adverse cardiovascular events. Our secondary endpoints include examining patient demographics, underlying comorbidities, in-hospital mortality, and cost of hospitalization. In addition, we performed a subgroup analysis in the CD cohort to assess if concomitant iron deficiency anemia increased CVD. Our study aims to examine the association between atherosclerosis and inflammation and aims to be a stepping stone for future long-term randomized controlled trials for the incorporation into atherosclerotic CVD risk score stratification., Competing Interests: Declaration of competing interest All of the authors declare that there is no conflict of interest regarding the publication of this article, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) remains a significant global health challenge despite advancements in prevention and treatment. Elevated Lipoprotein(a) [Lp(a)] levels have emerged as a crucial risk factor for CVD and aortic stenosis, affecting approximately 20 of the global population. Research over the last decade has established Lp(a) as an independent genetic contributor to CVD and aortic stenosis, beginning with Kare Berg's discovery in 1963. This has led to extensive exploration of its molecular structure and pathogenic roles. Despite the unknown physiological function of Lp(a), studies have shed light on its metabolism, genetics, and involvement in atherosclerosis, inflammation, and thrombosis. Epidemiological evidence highlights the link between high Lp(a) levels and increased cardiovascular morbidity and mortality. Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients., 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 Inc. All rights reserved.)

UVR is a skin carcinogen, yet no studies link sun exposure to increased all-cause mortality. Epidemiological studies from the United Kingdom and Sweden link sun exposure with reduced all-cause, cardiovascular, and cancer mortality. Vitamin D synthesis is dependent on UVB exposure. Individuals with higher serum levels of vitamin D are healthier in many ways, yet multiple trials of oral vitamin D supplementation show little benefit. Growing evidence shows that sunlight has health benefits through vitamin D-independent pathways, such as photomobilization of nitric oxide from cutaneous stores with reduction in cardiovascular morbidity. Sunlight has important systemic health benefit as well as risks., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Bedrest as an experimental paradigm or as an in-patient stay for medical reasons has negative consequences for cardiovascular health. The effects of severe inactivity parallel many of the changes experienced with natural aging but over a much shorter duration. Cardiac function is reduced, arteries stiffen, neural reflex responses are impaired, and metabolic and oxidative stress responses impose burden on the heart and vascular systems. The effect of these changes is revealed in studies of integrative function. Aerobic fitness progressively deteriorates with bedrest and tolerance of upright posture is rapidly impaired. In this review we consider the similarities of aging and bedrest-induced cardiovascular deconditioning. We concur with many recent clinical recommendations that early and regular mobility with upright posture will reduce likelihood of hospital-associated disability related to bedrest., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The study aimed to investigate the association of second and fourth-digit (2D:4D) ratios with metabolic syndrome (MS) and cardiovascular disease risk (CVR)., Method: This case-control study was conducted between February and March 2024 with 200 participants (100 patients +100 controls). Biochemical parameters (glucose, total cholesterol, HDL, LDL, triglycerides, haemogram, HbA1C) were recorded. All participants were evaluated in terms of MS diagnostic criteria. CVR was calculated with the ESC CVD Risk Calculator. Second-digit and fourth-digit measurements were performed and the 2D:4D ratio of both hands and the difference between 2D:4D of both hands (Dr-l) were obtained. The relationship between 2D:4D and MS, CVR, and gender was evaluated. p < .05 was considered statistically significant., Results: Forty-one percent of the study participants were male. The right-hand 2D:4D (R2D:4D) ratio was 1.009 ± 0.04 and the left-hand 2D:4D (L2D:4D) ratio was 0.991 ± 0.04 (p < .001). R2D:4D ratio was 1.010 ± 0.04 in women and 0.985 ± 0.03 in men (p = .019). R2D:4D (p < .001), Dr-l (p = .001), and CVR (p < .001) were significantly higher in men with MS (+) compared to MS (-)., Conclusion: In our study, the R2D:4D ratio was found to be associated with MS and CVR in men. Low intrauterine androgen exposure may affect the development of MS, but this effect is more prominent in males., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Post-traumatic stress disorder (PTSD) is increasingly recognized for its effects beyond mental health, with emerging evidence suggesting a significant association with cardiovascular diseases (CVD). This systematic review and meta-analysis aimed to synthesize available evidence on the association between PTSD and various cardiovascular outcomes., Methods: We conducted a comprehensive literature search in databases until March 15, 2024. Studies were included if they were observational in design and assessed the association between PTSD and cardiovascular outcomes. Data were extracted on study characteristics, participant demographics, PTSD assessment, cardiovascular outcomes, and effect estimates. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. All statistical analyses were conducted using R software version 4.3., Results: Twenty studies met the inclusion criteria, encompassing a total of over 335,000 participants. The pooled analyses demonstrated a statistically significant increased risk of any CVD (HR = 1.417, 95 % CI: 1.313-1.522), MI (HR = 1.415, 95 % CI: 1.331-1.500), and stroke (HR = 2.074, 95 % CI: 1.165-2.982) associated with PTSD. Substantial heterogeneity was observed across the studies for stroke and MACE, and evidence of publication bias was noted., Conclusion: This meta-analysis confirms a significant association between PTSD and an increased risk of several cardiovascular outcomes, indicating the importance of integrating cardiovascular risk management with psychiatric care for PTSD patients to mitigate the heightened risk of CVDs. Future research should focus on exploring the underlying mechanisms and potential interventions to manage both PTSD and its associated cardiovascular risks effectively., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Air pollution, a pervasive environmental threat that spans urban and rural landscapes alike, poses significant risks to human health, exacerbating respiratory conditions, triggering cardiovascular problems, and contributing to a myriad of other health complications across diverse populations worldwide. This article delves into the multifarious impacts of air pollution, utilizing cutting-edge research methodologies and big data analytics to offer a comprehensive overview. It highlights the emergence of new pollutants, their sources, and characteristics, thereby broadening our understanding of contemporary air quality challenges. The detrimental health effects of air pollution are examined thoroughly, emphasizing both short-term and long-term impacts. Particularly vulnerable populations are identified, underscoring the need for targeted health risk assessments and interventions. The article presents an in-depth analysis of the global disease burden attributable to air pollution, offering a comparative perspective that illuminates the varying impacts across different regions. Furthermore, it addresses the economic ramifications of air pollution, quantifying health and economic losses, and discusses the implications for public policy and health care systems. Innovative air pollution intervention measures are explored, including case studies demonstrating their effectiveness. The paper also brings to light recent discoveries and insights in the field, setting the stage for future research directions. It calls for international cooperation in tackling air pollution and underscores the crucial role of public awareness and education in mitigating its impacts. This comprehensive exploration serves not only as a scientific discourse but also as a clarion call for action against the invisible but insidious threat of air pollution, making it a vital read for researchers, policymakers, and the general public., Competing Interests: Declaration of Competing Interest We, the authors of this review, hereby declare that there are no financial or non-financial conflicts of interest related to the content of this manuscript. Our work has been conducted and presented with full academic integrity, free from any undisclosed influences or conflicts that could affect the objectivity or credibility of our research and findings., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune and multisystemic rheumatic disease. Patients with SLE have decreased functional and aerobic capacity, as well as increased prevalence of Cardiovascular Diseases (CVD), which are the primary causes of morbimortality in this condition. Dietary intake and physical activity are well-known modifiable cardiovascular risk factors. The aim of this study is to describe food consumption, sedentary behavior, physical activity level, and functional and aerobic capacity in a sample of SLE patients with high cardiovascular risk. This was a cross-sectional study in which patients were assessed for (i) Demographic, anthropometric, and disease-related parameters; (ii) Food consumption; (iii) Physical activity level and sedentary behavior; (iv) Functional and aerobic capacity. Patients averaged 41.7 ± 9 years, and most were classified as overweight/obese (87%). Average macronutrient intake was within recommendations; however, fiber (16 ± 9g) and calcium (391 ± 217 mg) intakes were below, and sodium intake (2.9 ± 1.3 mg) was above recommendations. Besides, food consumption assessed by the Nova system showed a predominance of unprocessed foods (43.8 ± 14.0%TEI), although ultraprocessed food intake (20.0 ± 13.9%TEI) was slightly higher than that seen in the Brazilian population. Patients also exhibited high sedentary behavior (8.2 ± 2.2h) and only eighteen participants reached the minimum recommended amount of moderate-to-vigorous physical activity. Overall, patients had a low functional and aerobic capacity compared to the general population. Data from this study may help design dedicated clinical trials aiming to investigate the effects of lifestyle intervention to mitigate CVD in SLE., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Background: The AUB-HAS2 Cardiovascular Risk Index is a newly derived tool for preoperative cardiovascular evaluation. It is based on six data elements: history of heart disease, symptoms of angina or dyspnea, age ≥ 75 years, hemoglobin < 12 g/dl, vascular surgery, and emergency surgery. This study compares the performance of this new index among emergency and elective surgeries., Methods and Results: The study population consisted of 1,167,414 non-cardiac surgeries registered in the American College of Surgeons National Surgical Quality Improvement Program database (153,715 were emergency and 1,013,699 were elective). Each patient was given an AUB-HAS2 score of 0, 1, 2, 3, or >3 depending on the number of data elements s/he has. The outcome measure (death, myocardial infarction, or stroke at 30 days after surgery) was higher in emergency than elective surgeries (7.0 % vs 1.4 %, p < 0.0001). The AUB-HAS2 index was able to stratify risk in both types of surgeries with a gradual increase in risk as the score increased (p < 0.0001). The discriminatory power of the AUB-HAS2 index, measured by the area under the receiver operator characteristic curves, was good and similar in the two types of surgeries (0.804 for emergency vs 0.791 for elective surgeries)., Conclusion: The AUB-HAS2 index is a versatile tool that can effectively and equally stratify risk in both emergency and elective surgeries with a good discriminatory power., Competing Interests: Declaration of competing interest None of the authors has any disclosures to declare, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Plant-based meat alternatives (PBMAs) are highly processed food products that typically replace meat in the diet. In Canada, the growing demand for PBMAs coincides with public health recommendations to reduce ultra-processed food consumption, which prompts the need to investigate the long-term health implications of PBMAs. This review assesses the available literature on PBMAs and cardiovascular disease (CVD), including an evaluation of their nutritional profile and impact on CVD risk factors. Overall, the nutritional profiles of PBMAs vary considerably but generally align with recommendations for improving cardiovascular health; compared with meat, PBMAs are usually lower in saturated fat and higher in polyunsaturated fat and dietary fibre. Some dietary trials that have replaced meat with PBMAs have reported improvements in CVD risk factors, including total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B-100, and body weight. No currently available evidence suggests that the concerning aspects of PMBAs (eg, food processing and high sodium content) negate the potential cardiovascular benefits. We conclude that replacing meat with PBMAs may be cardioprotective; however, long-term randomised controlled trials and prospective cohort studies that evaluate CVD events (eg, myocardial infarction, stroke) are essential to draw more definitive conclusions., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Metabolic-dysfunction-associated Steatotic liver disease (MASLD) is a high-risk condition for both liver fibrosis and cardiovascular disease (CVD). Therefore, therapeutic strategies to prevent both liver fibrosis and atherosclerotic CVD are required for the treatment of MASLD. Metabolic dysfunction-associated steatohepatitis (MASH) is the more severe form of MASLD, is defined histologically by the presence of lobular inflammation and hepatocyte ballooning and is associated with a greater risk of fibrosis progression. While CVD is the leading cause of mortality in patients with MASLD, those with more severe liver fibrosis are at increased risk of liver-related mortality, with the risk increasing exponentially with fibrosis stage. MASH has been found in 63% of patients with MASLD undergoing liver biopsy in an Asian multi-center cohort. Multiple complex pathways are involved in the association between MASLD and CVD. The visceral accumulation of fat around the liver and other organs, including the pericardium, leads to the release of fat-derived metabolites with the activation of several inflammatory pathways Cardiac rhythm abnormalities are prevalent in MASLD, such as prolongation of the QT interval, ventricular arrhythmias, and atrial fibrillation. Therapeutic interventions that improve cardiometabolic risk factors may be beneficial for an improvement in MASLD. The effects of such therapeutic interventions on lipid, lipoprotein and apoprotein accumulation in the liver and on hepatic steatosis and fibrosis still remain unelucidated. Which lipid factor is crucial for developing MASLD also remains largely unknown., 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. Published by Elsevier Inc.)

Impaired lipid metabolism is a pivotal driver of cardiovascular disease (CVD). In this regard, the accumulation of ceramides within the circulation as well as in metabolically active tissues and atherosclerotic plaques is a direct consequence of derailed lipid metabolism. Ceramides may be at the nexus between impaired lipid metabolism and CVD. Indeed, although on one hand ceramides have been implicated in the pathogenesis of CVD, on the other specific ceramide subspecies have also been proposed as predictors of major adverse cardiovascular events. This review will provide an updated overview of the role of ceramides in the pathogenesis of CVD, as well as their pathogenetic mechanisms of action. Furthermore, the manuscript will cover the importance of ceramides as biomarkers to predict cardiovascular events and the role of diet, both in terms of nutrients and dietary patterns, in modulating ceramide metabolism and homeostasis., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The independent effect of waist-to-height ratio (WHtR) and body fat percentage (BF%) on ischemic cardiovascular disease (CVD) remains uncertain., Objectives: This study aimed to investigate the independent associations of WHtR and BF% with ischemic CVD., Methods: This prospective cohort study used data from the UK Biobank. BF% was calculated as fat mass divided by body weight, measured by bioimpedance. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for overall and sex-specific associations of BF% and WHtR with risks of ischemic CVD and its main subtypes [myocardial infarction (MI) and ischemic stroke (IS)], adjusted for a range of potential confounders, including mutual adjustment for BF% and WHtR., Results: In total, 468,333 participants without existing CVD were included in the analysis. During 12 y of follow-up, 20,151 ischemic CVD events, 13,604 MIs, and 6681 ISs were recorded. WHtR was linearly associated with ischemic CVD, MI, and IS, with an HR per 5% increase of 1.23 (95% CI: 1.20, 1.25), 1.24 (95% CI: 1.21, 1.27), and 1.22 (95% CI: 1.18, 1.26), respectively, independent of BF%. A stronger association between WHtR and MI was seen in females than in males. The association of BF% with these outcomes was substantially attenuated in both sexes after adjustment for WHtR. For example, in females, the HR (highest compared with lowest fifth) was reduced from 1.94 (95% CI: 1.76, 2.15) to 1.04 (95% CI: 0.90, 1.01) for ischemic CVD, from 2.04 (95% CI: 1.79, 2.32) to 0.97 (95% CI: 0.81, 1.16) for MI, and from 1.81 (95% CI: 1.54, 2.13) to 1.07 (95% CI: 0.85, 1.33) for IS., Conclusions: WHtR, when used as a proxy measure for central obesity, is linearly associated with ischemic CVD in both sexes, which is independent of BF%. In contrast, the relationship of BF% with these health outcomes is predominantly driven by its correlation with WHtR., Competing Interests: Conflict of interest MW does consultancy for Amgen and Freeline outside the submitted work; no support from any organization for the submitted work; no other relationships or activities that could appear to have influenced the submitted work. All other authors report no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)