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Background: The choroid plexus (CP) is involved in neurodegenerative diseases. However, the association of CP with cardiovascular risk factors and cerebral small vessel disease in older adults remains unclear., Methods and Results: This population-based study included 1263 participants (60 years and older) from the MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China) substudy (2018-2020), of which 111 individuals completed diffusion tensor imaging examination. CP volume was automatically segmented. White matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds, and lacunes were assessed following the Standards for Reporting Vascular Changes on Neuroimaging 1. Peak width of skeletonized mean diffusivity and free water were derived from diffusion tensor imaging images. We used linear regression models to evaluate the association between CP volume and cardiovascular risk factors, WMH volumes, and diffusion tensor imaging metrics, and logistic regression models to examine the association between CP volume and EPVS, cerebral microbleeds, and lacunes. The CP volume increased with age ( P <0.001). Men (β coefficient=0.47 [95% CI, 0.29-0.64]) and participants with diabetes (β coefficient=0.16 [95% CI, 0.01-0.31]) had larger CP volumes than women and individuals without diabetes, respectively ( P <0.05). Greater CP volume was significantly associated with larger total and periventricular WMH volumes and moderate to severe EPVS in basal ganglia ( P <0.05) but not with deep WMHs, EPVS in centrum semiovale, lacunes, or cerebral microbleeds. In the diffusion tensor imaging subsample, enlarged CP was significantly associated with higher peak width of skeletonized mean diffusivity and free water of periventricular and deep white matter ( P <0.05)., Conclusions: An enlarged CP is associated with larger global and periventricular WMH volume and higher likelihoods of EPVS in basal ganglia and impaired white matter integrity, suggesting that an enlarged CP may represent a precursor of cerebral small vessel disease.

Importance: Cardiovascular-kidney-metabolic (CKM) syndrome-a novel, multistage, multisystem disorder as defined by the American Heart Association-is highly prevalent in the US. However, the prevalence of CKM stages by social determinants of health (SDOH) remains unclear., Objective: To investigate whether the prevalence of CKM stages varies by SDOH in US adults., Design, Setting, and Participants: This cross-sectional study used data from the National Health and Nutrition Examination Survey (1999-2018) and included a nationally representative sample of adults aged 30 to 79 years through complex, multistage probability sampling. Data were analyzed from April 1 to June 15, 2024., Exposures: The exposures included 5 CKM stages (ie, stages 0-4) reflecting progressive pathophysiology, with advanced (stages 3 or 4) and nonadvanced (stages 0, 1, or 2) disease. CKM stages were defined based on risk factors for metabolic syndrome, cardiovascular disease, and chronic kidney disease., Main Outcome and Measures: The main outcome was the age-standardized prevalence of CKM stages and advanced CKM stages across SDOH, including education, marital status, family income, food security, health insurance, employment, home ownership, and health care access., Results: Among 29 722 participants (weighted mean [SE] age, 50.8 [0.1] years; weighted 50.7% male), the age-standardized prevalence of CKM stages 0 to 4 was 13.6% (95% CI, 13.0%-14.3%), 29.9% (95% CI, 29.1%-30.7%), 43.7% (95% CI, 42.9%-44.5%), 4.7% (95% CI, 4.4%-5.0%), and 8.1% (95% CI, 7.6%-8.5%), respectively. Significant differences were observed in the prevalence of CKM stages across all unfavorable SDOH of interest compared with their favorable counterparts, with unemployment (18.8% [95% CI, 17.7%-20.1%] vs 11.4% [95% CI, 11.0%-11.9%]), low family income (16.1% [95% CI, 15.4%-16.8%] vs 10.1% [95% CI, 9.5%-10.7%]), and food insecurity (18.3% [95% CI, 17.1%-19.6%] vs 11.7% [95% CI, 11.2%-12.2%]) associated with an increased likelihood of advanced CKM stages. Participants with 2 or more unfavorable SDOH were more likely to have advanced CKM stages (age-standardized prevalence, 15.8% [95% CI, 15.2%-16.5%] vs 10.5% [95% CI, 9.9%-11.1%] with <2 unfavorable SDOH). Living in a rented home (15.9% [95% CI, 14.7%-17.0%] vs 9.3% [95% CI, 8.7%-9.9%] owning the home) or not living with a partner (13.2% [95% CI, 12.3%-14.3%] vs 9.2% [95% CI, 8.5%-9.8%] living with a partner) increased the likelihood of advanced CKM stages in female but not male participants., Conclusions and Relevance: In this cross-sectional study, disparities in the prevalence of CKM stages by SDOH, particularly family income, food security, and employment, with notable sex differences, were observed in US adults. These findings highlight the need to address inequities in CKM syndrome through targeted interventions.

Importance: The association between smoking cessation and cardiovascular disease (CVD) risk in relation to cumulative smoking exposure remains poorly understood., Objective: To evaluate the associations among smoking cessation, lifetime smoking burden, and CVD risk according to the number of years elapsed after smoking cessation., Design, Setting, and Participants: This retrospective cohort study of the Korean National Health Insurance Service database investigated smoking duration and intensity between January 2006 and December 2008. Participants were categorized by self-reported smoking habits as current, ex-, or never-smokers. Smoking records were updated every 2 years until December 2019, with participants whose smoking status changed or whose smoking status was unclear excluded. Data analysis was performed between June and December 2022., Exposures: Time-updated self-reported smoking status, years since quitting, and cumulative smoking amount (pack-years [PY])., Main Outcomes and Measures: The primary outcome was incidence and hazard ratio of CVD (composite of cardiovascular death, myocardial infarction, stroke, and heart failure)., Results: Overall, 5 391 231 participants (39.9% male; mean [SD] age, 45.8 [14.7] years; 853 756 [15.8%] current smokers, 104 604 [1.9%] ex-smokers, and 4 432 871 [82.2%] never smokers) were followed up for a mean (SD) of 4.2 (4.4) years. The median (IQR) baseline cumulative smoking amounts were 14.0 (7.5-20.0) PY in current smokers and 10.5 (5.3-20.0) PY in ex-smokers. The median (IQR) duration of smoking cessation was 4 (2-8) years for ex-smokers. Regardless of continued smoking, a dose-dependent association was evident between smoking and incident CVD. Compared with current smokers, ex-smokers with a lifetime smoking burden of less than 8 PY (light ex-smokers) experienced a significant reduction in CVD risk within 10 years of cessation, with a CVD risk similar to that of never-smokers. Conversely, ex-smokers with at least 8 PY (heavy ex-smokers) exhibited a slower decline in CVD risk than light ex-smokers, requiring more than 25 years for the residual CVD risk to disappear., Conclusions and Relevance: In this cohort study, smoking and CVD risk exhibited a dose-dependent association, with light ex-smokers having a CVD risk similar to that of never-smokers relatively soon after smoking cessation. For heavy ex-smokers, greater than 25 years might be required for the residual CVD risk to align with that of never-smokers.

Cardiovascular disease is a leading cause of death worldwide. There is limited evidence that exposure to current-use pesticides may contribute to cardiovascular disease risk. We examined the association between residential proximity to the application of agricultural pesticides and cardiovascular risk factors among 484 adult women in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a cohort based in an agricultural region of California. Outcome assessment was completed between 2010 and 2013. Using participant residential addresses and California's Pesticide Use Reporting database, we estimated agricultural pesticide use within 1 km of residences during the 2-year period preceding outcome assessment. We used Bayesian hierarchical modeling to evaluate associations between exposure to 14 agricultural pesticides and continuous measures of waist circumference, body mass index, and blood pressure. Each 10-fold increase in paraquat application around homes was associated with increased diastolic blood pressure (β = 2.60 mm Hg; 95% credible interval [CrI], 0.27-4.89) and each 10-fold increase in glyphosate application was associated with increased pulse pressure (β = 2.26 mm Hg; 95% CrI, 0.09-4.41). No meaningful associations were observed for the other pesticides examined. Our results suggest that paraquat and glyphosate pesticides may affect cardiovascular disease development in women with chronic environmental exposure. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk., Objective: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke., Methods: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was assessed at baseline (2000-2002) using a validated 120-item food frequency questionnaire. Two different aspects of protein diversity were assessed including count (number of protein food consumed at least once/week) and dissimilarity (diversity of the attributes of the protein sources consumed). Relationships with incident CVD outcomes through 2019 were assessed using Cox proportional hazards models adjusting for sociodemographic, lifestyle, and comorbidity factors., Results: During 83,430 person-years, 1045 CVD cases were identified, including 668 CHD and 332 stroke cases. In multivariable models, we found no significant associations between protein intake, overall and by food source, with incident CVD, CHD, or stroke. Protein count, but not protein dissimilarity, was weakly associated with CVD risk. We found no significant associations between diversity of consumption of animal or plant food source and CVD outcomes., Conclusions: Our findings suggest protein consumption may not significantly impact CVD risk in middle-aged adults.

Background: There has been a concerning rise in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) following noncardiac surgeries (NCS), significantly impacting surgical outcomes and patient prognosis. Glucose metabolism abnormalities induced by stress response under acute medical conditions may be a risk factor for postoperative MACCE. This study aims to explore the association between stress hyperglycemia ratio (SHR) and postoperative MACCE in patients undergoing general anesthesia for NCS., Methods: There were 12,899 patients in this perioperative cohort study. The primary outcome was MACCE within 30 days postoperatively, defined as angina, acute myocardial infarction, cardiac arrest, arrhythmia, heart failure, stroke, or in-hospital all-cause mortality. Kaplan-Meier curves visualized the cumulative incidence of MACCE. Cox proportional hazard models were utilized to assess the association between the risk of MACCE and different SHR groups. Restricted cubic spline analyses were conducted to explore potential nonlinear relationships. Additionally, exploratory subgroup analyses and sensitivity analyses were performed., Results: A total of 592 (4.59%) participants experienced MACCE within 30 days after surgery, and 1,045 (8.10%) within 90 days. After adjusting for confounding factors, compared to the SHR T2 group, the risk of MACCE within 30 days after surgery increased by 1.34 times (95% CI 1.08-1.66) in the T3 group and by 1.35 times (95% CI 1.08-1.68) in the T1 group respectively. In the non-diabetes group, the risk of MACCE within 30 days after surgery increased by 1.60 times (95% CI 1.21-2.12) in the T3 group and by 1.61 times (95% CI 1.21-2.14) in the T1 group respectively, while no statistically significant increase in risk was observed in the diabetes group. Similar results were observed within 90 days after surgery in the non-diabetes group. Additionally, a statistically significant U-shaped nonlinear relationship was observed in the non-diabetes group (30 days: P for nonlinear = 0.010; 90 days: P for nonlinear = 0.008)., Conclusion: In this large perioperative cohort study, we observed that both higher and lower SHR were associated with an increased risk of MACCE within 30 and 90 days after NCS, especially in patients without diabetes. These findings suggest that SHR potentially plays a key role in stratifying cardiovascular and cerebrovascular risk after NCS., (© 2024. The Author(s).)

Background: Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations., Methods: VITamin D and OmegA-3 TriaL (NCT01169259) was a randomized clinical trial testing vitamin D and n-3 FA for the prevention of CVD and cancer over a median of 5.3 years. Incident cases of T2D and CVD (including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) were matched 1:1 on age, sex, and fasting status to controls. Conditional logistic regressions adjusted for demographic, clinical, and adiposity-related factors were used to assess the adjusted odds ratio (aOR) per-standard deviation (SD) and 95%CI of baseline insulin, C-peptide, HbA1c, and IRS (Insulin×0.0295 + C-peptide×0.00372) with risk of T2D, CVD, and coronary heart disease (CHD)., Results: We identified 218 T2D case-control pairs and 715 CVD case-control pairs including 423 with incident CHD. Each of the four biomarkers at baseline was separately associated with incident T2D, aOR (95%CI) per SD increment: insulin 1.46 (1.03, 2.06), C-peptide 2.04 (1.35, 3.09), IRS 1.72 (1.28, 2.31) and HbA1c 7.00 (3.76, 13.02), though only HbA1c remained statistically significant with mutual adjustments. For cardiovascular diseases, we only observed significant associations of HbA1c with CVD (1.19 [1.02, 1.39]), and IRS with CHD (1.25 [1.04, 1.50]), which persisted after mutual adjustment. Randomization to vitamin D and/or n-3 FA did not modify the association of these biomarkers with the endpoints., Conclusions: Each of insulin, C-peptide, IRS, and HbA1c were associated with incident T2D with the strongest association noted for HbA1c. While HbA1c was significantly associated with CVD risk, a novel IRS appears to be associated with CHD risk. Neither vitamin D nor n-3 FA modified the associations between these biomarkers and cardiometabolic outcomes., (© 2024. The Author(s).)

Objectives: The aim of this study was to conduct a comparative analysis of the proportion of cardiovascular adverse events (AEs) associated with the utilization of memantine and cholinesterase inhibitors and to highlight the potential impact of sex differences in these AEs., Methods: Cardiac and vascular disorders AEs with antidementia medications were obtained from the FDA Adverse Event Reporting System database. The reporting odds ratio and its corresponding 95% confidence intervals were calculated. The chi-squared test was used to evaluate differences in categorical variables, and a two-way ANOVA followed by a Bonferroni post-test was used to compare the AEs reported for antidementia medications., Results: Memantine was associated with 544 selected cardiac and vascular disorder AEs. A signal for bradycardia, myocardial infarction, atrial fibrillation and cardiac arrest has been observed in patients receiving choline esterase inhibitors compared to those receiving memantine. On the other hand, cardiac failure and deep vein thrombosis AEs were found to be more common in patients receiving memantine. The majority of reported cardiac and vascular AEs were reported more frequently in female patients. More cases of cardiac failure, cardiac arrest, and deep vein thrombosis were reported in females than males taking memantine, but bradycardia was more common in males than females., Conclusion: Healthcare professionals should be aware of the potential for cardiovascular AEs during treatment with antidementia medications and the possibility of sex differences in this regard. Memantine differs from cholinesterase inhibitors in terms of cardiovascular AEs, and there may be sex-related differences in the proportion of these AEs., (© 2024 John Wiley & Sons Ltd.)

Background: Previously, most researchers explored the association between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). This study investigates the distinct influence of COVID-19 vaccination status on patients with both conditions., Objective: We investigate the relationship between COPD and CVD in a cohort of 838 individuals who presented with both conditions. Our aim is to understand how these conditions interact and how COVID-19 vaccination status affects patient outcomes., Methods: A retrospective analysis was conducted on 838 patients with COPD and CVD treated at DHQ Hospital in Muzaffargarh, Punjab, Pakistan, from November 2022 to April 2023. We employed multiple logistic regression and the Wilcoxon signed-rank test to assess the odds ratio and relative risk of COPD in patients with-CVD under various conditions. Additionally, we analyzed time-to-death and survival using Kaplan-Meier methods., Results: Findings reveal a 7.95 times higher risk of death in patients without COVID-19 vaccination compared with those who were vaccinated (95% CI, 6.12-10.33). Conversely, COVID-19-vaccinated patients exhibited a 0.221 times lower risk of recovery than their nonvaccinated counterparts (95% CI, 0.08-0.60). We also observed significant differences in time-to-death and recovery based on the presence of COPD and CVD, with vaccinated patients generally experiencing milder disease., Conclusion: Our study assessed the impact of COVID-19 vaccination status on patient outcomes in patients with overlapping COPD and CVD. Individuals diagnosed with COPD and CVD display significant differences in terms of their probability of survival, with those who have received vaccinations., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Aims: Elevated remnant cholesterol (= the cholesterol carried in triglyceride-rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol., Materials and Methods: We included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol. Elevated remnant cholesterol was defined as levels higher than those observed in individuals with non-high-density lipoprotein (non-HDL) cholesterol < 2.6 mmol/L (100 mg/dL), the European guideline goal. Results were replicated in the UK Biobank., Results: During 15 years of follow-up, 498 patients were diagnosed with ASCVD, 172 with peripheral artery disease, 185 with myocardial infarction and 195 with ischaemic stroke. In individuals with non-HDL cholesterol < 2.6 mmol/L (100 mg/dL) and in all individuals with diabetes, median remnant cholesterol levels were 0.5 mmol/L (20 mg/dL) and 0.8 mmol/L (31 mg/dL). The fraction of events attributable to elevated remnant cholesterol was 19% (95% confidence interval: 10%-28%) for ASCVD, 21% (5%-37%) for peripheral artery disease, 24% (10%-37%) for myocardial infarction and 17% (1%-31%) for ischaemic stroke; in the UK Biobank, corresponding values were 16% (9%-22%), 25% (12%-36%), 17% (8%-25%) and 7% (0%-19%), respectively., Conclusions: One in five ASCVD events in individuals with diabetes can be attributed to elevated remnant cholesterol. It remains to be determined in clinical trials if remnant cholesterol-lowering therapy may prevent ASCVD., (© 2024 John Wiley & Sons Ltd.)

Background/Objectives: Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the association (or "apparent effect") due to "regression dilution". Here, we evaluate how follow-up interval from baseline to "event" affects the relationship between baseline serum 25-hydroxyvitamin D [25(OH)D] concentration and the later incidence of stroke and major cardiovascular events (MACEs). Methods: Findings for the relative risk (RR) of stroke and MACEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke and nine studies for MACEs. Linear regression analyses were used to study data for follow-up periods of up to 10 years and for more than 10 years. Results: For stroke, the linear regression fit for 1-10 years is RR = 0.34 + (0.065 × follow-up [years]), r = 0.84, adjusted r 2 = 0.67, p < 0.001. No significant variations in association were found for studies with follow-up periods of 10-20 years. For MACEs, the linear fit for 1-8.1 years is RR = 0.61 + (0.055 × follow-up [years]), r = 0.81, adjusted r 2 = 0.59, p = 0.03. Discussion: The shorter the follow-up period, the greater the apparent effect of better vitamin D status in reducing risk of stroke and MACEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as great as the estimate based on average follow-up intervals for all studies. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MACEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MACEs, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D's role in reducing risk of stroke and MACEs could be considered causal on the basis of an evaluation of the evidence using Hill's criteria for causality in a biological system. Conclusions: Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MACEs prospectively and in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should, therefore, be recommended for everyone likely to be at risk for stroke or MACEs and indeed in the general population.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for cardiovascular disease. However, whether family members of individuals with MASLD also share an increased cardiovascular risk is unknown., Methods: We created a nationwide multigenerational cohort study identifying all family members of Swedish adults diagnosed with biopsy-proven MASLD (1969-2017) and of matched general population comparators (by age, sex, calendar year, and county of residence). We calculated incidence rates and used Cox models to calculate adjusted hazard ratios (aHRs) and 95% CIs for incident major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, hospitalization for heart failure, or cardiovascular death. Cox models were adjusted for education, country of birth, diabetes, hypertension, obesity, dyslipidemia, chronic kidney disease, chronic obstructive pulmonary disease, and the Charlson comorbidity index., Results: We identified 22 267 MASLD first-degree relatives (FDRs; parents, siblings, and offspring) and 5687 MASLD spouses, as well as 118 056 comparator FDRs and 29 389 comparator spouses without earlier cardiovascular disease. Overall, the mean age was 41.8 years (SD, 18.0), and 51.5% were females. Over a median of 24.6 years, the incidence rate for MACE was higher in MASLD FDRs than in comparator FDRs (65.0 versus 62.5/10 000 person-years; aHR, 1.06 [95% CI, 1.01-1.11]). MASLD FDRs had higher rates of acute myocardial infarction (23.0 versus 20.9/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18]) and cardiovascular death (aHR, 1.09 [95% CI, 1.01-1.18]). Across generations of FDRs, the risk of MACE was uniformly increased with no differences by relationship (ie, parents, siblings, and offspring; P interaction >0.05). MASLD spouses were also at an increased risk of MACE (117.6 versus 103.5/10 000 person-years; aHR, 1.09 [95% CI, 1.01-1.18])., Conclusions: First-degree relatives of individuals with biopsy-proven MASLD are at slightly higher risk of incident MACE, but absolute risks do not support early screening for cardiovascular disease. Shared lifestyle factors may be the main contributors, as spouses of MASLD patients also had higher risks of MACE., Competing Interests: F. Ebrahimi has served as an advisory board member for Boehringer Ingelheim. Dr Forss has served as a speaker for Janssen Corporation and Tillotts Pharma. Dr Ludvigsson has coordinated an unrelated study on behalf of the Swedish Inflammatory Bowel Disease Quality Register. That study received funding from Janssen Corporation. Dr Ludvigsson has also received financial support from MSD to develop a paper reviewing national health care registers in China. Ludvigsson has also a research collaboration on celiac disease with Takeda. Dr Hagström’s institutions have received research funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer. He has served as consultant or on advisory boards for Astra Zeneca, Bristol Myers-Squibb, Merck Sharp & Dohme, and Novo Nordisk, and has been part of hepatic events adjudication committees for Boehringer Ingelheim, KOWA, and GW Pharma. The other authors report no conflicts.

Air pollution, particularly fine particulate matter less than 2.5 μm in diameter (PM 2.5 ), contributes to respiratory and cardiovascular diseases and poses significant public health risks worldwide. This study evaluated the short-term effects of PM 2.5 on hospital admissions for cardiovascular and respiratory diseases, with additional analyses to identify vulnerable populations based on regional characteristics. The present study analyzed data from 249 Korean communities between 2006 and 2021. Data on daily hospital admissions for cardiovascular and respiratory diseases were obtained from the National Health Insurance Service. Data on PM 2.5 concentrations were sourced from air quality modeling. Additional data on regional characteristics, including the regional deprivation index, proportion of elderly residents, education levels, and greenness levels, were also collected. We used case time series analysis to assess the associations between PM 2.5 concentrations and hospital admissions for cardiovascular and respiratory diseases and explored effect modification by regional characteristics with stratified analyses. The mean numbers of daily cardiovascular admissions and respiratory admissions were 5.68 ± 5.46 and 6.46 ± 8.03, respectively. The mean PM 2.5 concentrations were 23.58 ± 13.66 μg/m 3 . A10 μg/m³ increment in daily PM 2.5 concentration was associated with increase of cardiovascular and respiratory hospitalization by 0.94% (95% CI: 0.84%, 1.04%) and 1.43% (95% CI: 1.34%, 1.52%), respectively. Regional characteristics analysis showed significant disparities, with higher risks for hospital admissions in areas with lower deprivation and low greenness. This study highlights the significant short-term health impacts of PM 2.5 on respiratory and cardiovascular hospital admissions in Korean communities. The findings underscore the critical role of regional and demographic factors in modulating these effects, identifying socio-economic areas, age structure of the population, lower education levels, and low greenness as key vulnerability factors., 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 Ltd. All rights reserved.)

Background and Purpose: The aim of the study was to provide valuable real-world long-term safety data of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in comparison of monotherapy with statins of moderate intensity., Materials and Methods: POSE study was an observational, comparative study conducted in three European countries. Patients treated or planned to be treated with pravastatin 40 mg/fenofibrate 160 mg or with a moderate-intensity statin in monotherapy were assessed over 3 years. The main safety endpoints included the incidence of renal or urinary disorder, musculoskeletal or connective tissue disorder, hepatobiliary disorder and cardiovascular events., Results: The study included 3075 patients treated for dyslipidaemia, with diabetes mellitus (47%), hypertension (56%) and/or established cardiovascular disease (61%). Over the 3 years of follow-up, the difference in incidence rate of safety events between the pravastatin 40 mg/fenofibrate 160 mg group and the statin group was not statistically significant (RR = 1.366 [95% CI = 0.967-1.929]). The most frequently occurring events were musculoskeletal and connective tissue disorders (AR = 0.030 in the pravastatin 40 mg/fenofibrate 160 mg group and 0.024 in the statin group), renal and urinary disorders (AR = 0.019 vs. 0.016, respectively) and aggravated diabetes mellitus (0.021 vs. 0.014). Most events occurred during the first year, then incidence decreased over the 3-year period. No statistically significant difference was observed between treatment groups regarding the cardiovascular events (RR = 1.209 [95% CI = 0.596-2.453]) and no new signal emerged from the long-term follow-up., Conclusions: This study demonstrates a reassuring long-term safety profile of the fixed pravastatin 40 mg/fenofibrate 160 mg combination in routine clinical practice, with low and similar incidence of events over the 3 years follow-up compared to a monotherapy with statins of moderate intensity., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization., Methods: Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest., Results: Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations., Conclusions: Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed., Competing Interests: Dr Khatana receives funding from the National Heart, Lung, and Blood Institute (K23HL153772 and R01HL171157) and the American Heart Association (20CDA35320251) and has received personal fees from AcademyHealth. Dr Damrauer receives research support from Novo Nordisk and RenalytixAI. Dr Nathan receives speaker fees and research funding from Abiomed, Inc, Biosense Webster, and Edwards Lifesciences. Dr Julien is an employee of Merck & Co. The other authors report no conflicts.

Objective: The objective of this study was to determine the unique clinical and cardiometabolic risk characteristics of weight-cyclers and identify differences between weight-cyclers and individuals with other weight-change trajectories., Methods: A deidentified database of 1,428,204 Vanderbilt University Medical Center patients from 1997 to 2020 was included based on having ≥5 years of recorded weights. Patients with a history of malignant neoplasm, bariatric surgery, implausible BMI (e.g., <15 or >80 kg/m 2 ), or missing documented height were excluded, yielding 83,261 participants categorized by weight trajectory, i.e., weight-stable, weight-gainer, weight-loser, or weight-cycler, based on criteria of ≥5% weight-change thresholds. Additionally, quartiles of average successive weight variability were evaluated to determine the effect of absolute differences among successive weight values., Results: Over half (55%) of participants were weight-cyclers, 23% were weight-gainers, 12% were weight-losers, and 10% were weight-stable over 5 years. Although baseline BMI did not differ among groups, weight-cyclers were more likely to have lower high-density lipoprotein cholesterol and higher blood glucose and triglyceride levels and to have been prescribed antihypertensive, dyslipidemia, and/or antidiabetic therapies. They were also younger and more likely to be smokers. Participants with the greatest weight variability (i.e., highest quartile of average successive weight variability) had higher cardiometabolic risk scores., Conclusions: Weight cycling was highly prevalent but yielded no meaningful overall change in body weight after 5 years. These findings support a paradigm shift in weight management in individuals with overweight/obesity toward reducing cardiometabolic risk with or without weight loss., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Objectives: To evaluate the association between toothbrushing behavior and cardiometabolic multimorbidity (CMM) among middle-aged and older adults., Methods: Data from the Beijing Health Service Survey were used to estimate the association between toothbrushing behavior and the risk of CMM using multilevel logistic models (N = 18,158)., Results: There were 554 patients with CMM, with a prevalence of 3.05%. We found a higher risk of CMM for those with toothbrushing once or less (OR = 2.16, 95%CI: 1.80, 2.59) compared with those brushed two or more times per day in the crude model. After adjusting for confounding factors, the association between the two remained significant (OR = 1.68, 95%CI: 1.39, 2.04). The effect size was higher in adults with a higher education level (OR = 2.32) compared to those with a lower education level (OR = 1.39, P forinteraction <0.01)., Conclusions: Poor toothbrushing practices were associated with CMM among middle-aged and older people. Longitudinal study can be considered to explore the causal association between the two and whether good toothbrushing habits can predict CMM and its progression., (© 2024. The Author(s).)

Objective: This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status., Method: We conducted a full-scale search from MEDLINE, EMBASE and the Cochrane Library database to identify eligible studies up to Jun 2024. All randomized controlled trials (RCTs) comparing cardio-renal outcomes and/or safety of SGLT2i in CKD patients with eGFR < 60 mL/min/1.73 m 2 were involved. The relative risk (RR) and 95% confidence interval (CI) for primary outcomes and adverse events were computed by random-effects mode. We used I 2 statistic to analyze heterogeneity. Publication bias was assessed by Egger's test., Results: Our study incorporated 17 RCTS, including 27,928 patients. In CKD patients with eGFR < 60 mL/min/1.73 m 2 , SGLT2i decreased risks of cardiovascular events (seven studies, 17,355 participants, RR 0.77, 95% CI 0.70-0.84), hospitalization for heart failure (HHF) (seven studies, 17,869 participants, RR 0.73, 95% CI 0.65-0.82), cardiovascular death (eight studies, 23,079 participants, RR 0.81, 95% CI 0.74 to 0.88) and renal composite outcomes (eight studies, 22,525 participants, RR 0.70, 95% CI 0.61-0.80) with lower risks of any serious adverse effects(fourteen studies, 19,654 participants, RR 0.91, 95% CI 0.87-0.95), hypoglycemia (nine studies, 16,412 participants, RR 0.91, 95% CI 0.84-0.98), hyperkalemia (four studies, 2693 participants, RR 0.68, 95% CI 0.51-0.93) and acute renal injury (five studies, 5424 participants, RR 0.79, 95% CI 0.65-0.95) compared to placebo. SGLT2i also slowed eGFR decline (total slopes: five studies, 10,370 participants, mean difference 1.17, 95%CI 0.86-1.49; chronic slopes: four studies, 8459 participants, mean difference 2.12, 95%CI 1.64-2.61). Further subgroup analyses revealed that SGLT2i decreased relative risks of cardiovascular outcomes(three studies, 1075 participants, RR 0.76, 95% CI 0.54-0.82), HHF(four studies, 1280 participants, RR 0.74, 95% CI 0.55-1.00) and renal composite outcomes (six studies,4375 participants, RR 0.78, 95% CI 0.68-0.88) with no increased adverse events in the CKD 4 patients., Conclusions: SGLT2i significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 60 mL/min/1.73 m2 and with eGFR < 30 mL/min/1.73 m2. Future large-scale RCTs are needed to confirm the robustness of these results., (© 2024. The Author(s).)

Obesity paradox refers to the clinical observation that when acute cardiovascular decompensation occurs, patients with obesity may have a survival benefit. This apparently runs counter to the epidemiology of obesity, which may increase the risk for non-communicable diseases (NCDs). The scientific community is split on obesity paradox, with some supporting it, while others call it BMI paradox. This review: (a) defines the obesity paradox, and its proposed role in overall mortality in NCDs; (b) delineates evidence for and against obesity paradox; (c) presents the importance of using different indices of body mass to assess the risk in NCDs; (d) examines the role of metabolically healthy obesity in obesity paradox, and emerging importance of cardio-respiratory fitness (CRF) as an independent predictor of CVD risk and all-cause mortality in patients with/without obesity. Evidence suggests that the development of obesity and insulin resistance are influenced by genetic (or ethnic) make up and dietary habits (culture) of the individuals. Hence, this review presents lean diabetes, which has higher total CVD and non-CVD mortality as compared to diabetics with obesity and the possibility of maternal factors programming cardiometabolic risk during fetal development, which may lead to a paradigm shift in our understanding of obesity., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Vitiligo is an autoimmune disease, characterized by specific destruction of melanocytes. While associations with numerous comorbid conditions, which potentially increase the risk of cardiovascular diseases have been described, data on the risk for cardiovascular disease is inconclusive. To address this relevant knowledge gap, this study aims to identify the risk of cardiovascular disease in vitiligo., Methods: The US Collaborative Network was accessed using the TriNetX platform, allowing retrospective data retrieval from electronic health records (EHRs) from 57 US based health care organizations (HCOs). Patients with vitiligo and controls were identified by their respective ICD10 codes. Risk of onset of several cardiovascular diseases was determined in patients within 15 years after diagnoses., Findings: A total of 94 diagnoses with a prevalence of ≥1% in both cohorts, which consisted of 96,581 individuals per group after propensity-score-matching, were identified. Of those, 54 displayed an increased risk in vitiligo. None of the cardiovascular diseases investigated were associated with a decreased risk in patients with vitiligo. Specifically, cerebral infarction occurred in 1.3% of patients with vitiligo, and 1.0% in controls. This difference translated into a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.11-1.32, p adj  < 0.001). Venous thromboembolism was recorded in 1.34% of cases and 1.02% of controls without vitiligo, resulting in an increased HR of 1.27 (95% CI 1.171-1.38, p adj  < 0.001). Further, major adverse cardiovascular events (MACE) as a composite endpoint was evaluated. The risk for MACE was increased following a vitiligo diagnosis (HR 1.28, 95% CI 1.22-1.35, p adj  < 0.001), which persisted in both sensitivity analyses., Interpretation: Patients with vitiligo display an increased risk of onset of cardiovascular diseases as compared to healthy individuals. Thus, vitiligo might require more precise monitoring and systemic treatment., Funding: This research was supported by the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein, by the Excellence Cluster Precision Medicine in Chronic Inflammation (DFG, EXC 2167), and by DFG Individual Grant LU 877/25-1., Competing Interests: Declaration of interests AO-S has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant from AbbVie, Allergan, Almirall, Janssen, Leo Pharma, Lilly, Medac, Novartis, Sandoz, Sanofi, Sunpharm. RJL has received honoraria for speaking or consulting or has obtained research grants from Monasterium Laboratories, Novartis, Lilly, Bayer, Dompe, Synthon, Argen-X, and Incyte during the last 3 years. GH is an employee of TriNetX. SS has received honoraria for speaking or consulting from AbbVie, Bristol-Myers Squibb, Janssen-Cilag, Pfizer and UCB. DT has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant from AbbVie, Amgen, Almirall, Bristol-Meiers-Squibb, Boehringer Ingelheim, Celltrion, Galderma, Leo Pharma, Lilly, New Bridge, Novartis, Janssen-Cilag, Pfizer, Regeneron, Sanofi, l, Sun Pharmaceuticals, and UCB and grants from AbbVie, Leo Pharma and Novartis. HZ has received support for attending meetings and/or travel from Pfizer, UCB Pharma, Almirall, Janssen, TriNetX. All other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease (CVD) remains a leading cause of mortality globally. Environmental pollutants, specifically volatile organic compounds (VOCs), have been identified as significant risk factors. This study aims to develop a machine learning (ML) model to predict CVD risk based on VOC exposure and demographic data using SHapley Additive exPlanations (SHAP) for interpretability., Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, comprising 5098 participants. VOC exposure was assessed through 15 urinary metabolite metrics. The dataset was split into a training set (70 %) and a test set (30 %). Six ML models were developed, including Random Forest (RF), Light Gradient Boosting Machine (LightGBM), Decision Tree (DT), Extreme Gradient Boosting (XGBoost), Multi-Layer Perceptron (MLP), and Support Vector Machines (SVM). Model performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUROC), accuracy, balanced accuracy, F1 score, J-index, kappa, Matthew's correlation coefficient (MCC), positive predictive value (PPV), negative predictive value (NPV), sensitivity (sens), specificity (spec) and SHAP was applied to interpret the best-performing model., Results: The RF model exhibited the highest predictive performance with an ROC of 0.8143. SHAP analysis identified age and ATCA as the most significant predictors, with ATCA showing a protective effect against CVD, particularly in older adults and those with hypertension. The study found a significant interaction between ATCA levels and age, indicating that the protective effect of ATCA is more pronounced in older individuals due to increased oxidative stress and inflammatory responses associated with aging. E-values analysis suggested robustness to unmeasured confounders., Conclusions: This study is the first to utilize VOC exposure data to construct an ML model for predicting CVD risk. The findings highlight the potential of combining environmental exposure data with demographic information to enhance CVD risk prediction, supporting the development of personalized prevention and intervention strategies., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of death among communicable and noncommunicable diseases, and its prevalence is going to rise even more by 2030. The discovery of different "functional" foods containing a plethora of bioactive compounds is considered an ally in the effort to reduce the global CVD burden in the context of primary prevention. It has been about 3 decades since the observation that red wine consumption in French population could lead to lower coronary heart disease risk despite the high dietary consumption of saturated fats, known as the "French paradox." Since then, numerous epidemiological studies, mainly observational, have emerged in order to investigate this association with great enthusiasm. However, due to the nature of these studies, the scientific community has raised concerns about the methodological approach of the studies and thus the generalization of their results. Therefore, the current review aims to summarize some of the major methodological issues deriving from observational studies on the association between red wine consumption and cardiovascular health and to highlight the importance of higher quality study design in the general effort of drawing safer conclusions on this topic.

We conducted a scoping review of peer-reviewed literature published between January 1, 1990 and October 31, 2021, to identify socioeconomic determinants that contribute to higher burden and adverse outcomes in diseases for which self-care is an important modality of treatment and prevention. We identified these diseases using over-the-counter medicines sales data sourced from IQVIA. We searched Ovid Medline, PubMed, and EMBASE databases for articles published in English using inclusion/exclusion criteria. We analyzed articles covering 42 diseases that qualified as cardiovascular disorders (219 studies including ischemic heart disease, myocardial infarction, stroke, and related risk factors such as hypertension, dyslipidemia and atrial fibrillation), nutritional disorders (66 studies including malnutrition which encompasses undernutrition and micronutrient deficiencies, and anemia), digestive disorders (40 studies including gastroesophageal reflux disorder, inflammatory bowel disease, and dyspepsia), allergy disorders (40 studies including asthma and allergic rhinitis), pain disorders (14 studies including lower back pain, knee pain, generalized musculoskeletal pain and headaches), dermatological disorders (23 studies including atopic dermatitis [eczema], occupational dermatosis, and facial dermatitis), respiratory disorders (11 studies including chronic cough, pneumonia, chronic bronchitis, wheezing, and influenza), and gynecological disorders (29 studies including bacterial vaginosis and trichomoniasis vaginosis). We found that lifestyle factors were the commonly reported risk factors, and residential segregation, education, and income were the commonly reported socioeconomic determinants. A closer analysis of income within each disorder revealed that it is more often associated with health conditions that are self-limiting. Although we did not find any discernible relationship between the commonly reported socioeconomic factors and the prevalence of self-medication for the health conditions considered, income plays an important role in the burden and outcomes of conditions that require more self-care compared to those that require less self-care.

Phthalates are endocrine disruptors of increasing concern for human health; however, previous studies have only assessed the association between internal exposure and human health. We aimed to assess the non-carcinogenic and carcinogenic risks of non-dietary exposure to phthalates in indoor environments among primary school children and their correlations with health indicators. A study involving 54 children was conducted in Jinan, Shandong Province, China. Questionnaires and health examinations were conducted, dust in hard-to-clean corners of students' classrooms and homes was collected, and airborne phthalates in the middle of classrooms and family living rooms were sampled. The gas-phase phthalate concentrations, individual exposure, and non-carcinogenic and carcinogenic risks were calculated. Associations were estimated using linear mixed models. The findings revealed that phthalates posed a non-carcinogenic risk to 7.4 % of the children and a moderate carcinogenic risk to 27.8 % of the children, with higher non-carcinogenic and carcinogenic risks to girls than to boys. Five phthalates were negatively correlated with body mass index, dimethyl phthalate and diethyl phthalate (DEP) were significantly correlated with waist circumference, and di-iso-butyl phthalate (DiBP) was negatively correlated with hip circumference. DiBP, di-n-butyl phthalate, and DEP, were significantly correlated with cardiovascular disease, DEP and di (2-n-butoxyethyl) phthalate were correlated with decreased lung function, and di-n-octyl phthalate influenced airway inflammation. The findings indicated that phthalate exposure may negatively impact children's health, thereby warranting further comprehensive research on the health effects of these chemicals., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: People with multiple sclerosis (PwMS) have an increased cardiovascular and cerebrovascular disease burden, but this could be mitigated by vascular risk factor management., Objectives: We compared the trajectories of vascular risk factors, vascular comorbidities and clinical management in PwMS against the general population post-MS diagnosis while controlling for frailty., Methods: Retrospective longitudinal analysis using English data from the Clinical Practice Research Datalink between 1987 and 2018 comprising PwMS matched with up to six controls without MS by age, sex and general practice., Results: We compared 12,251 PwMS with 72,572 matched controls; 3.8% of PwMS had mild-moderate frailty, 1.2% more than matched controls. Compared to controls, PwMS had an elevated incidence of Type 2 diabetes (HR 1.18, 95% CI (1.04, 1.34)), and starting antihypertensive medications (HR 1.40, 95% CI (1.33, 1.47)). Among those with hypertension at baseline, blood pressure trajectories did not differ between PwMS and controls. PwMS had increased rates of meeting targets for hypertension management (HR 1.25, 95% CI (1.12, 1.41))., Conclusion: The observation that PwMS with hypertension are more likely to meet treatment targets than matched controls is encouraging, but the elevated rates of vascular comorbidities suggest that tighter vascular management may be needed in this population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: In the last 3 years, R.P. has received support from the UK MS Society and has taken part in advisory boards/consultancy for MSD and Sanofi. In the last 3 years, J.C. has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society, and the Rosetrees Trust. He is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS society. A local principal investigator for commercial trials funded by Ionis, Novartis and Roche, and has taken part in advisory boards/consultancy for Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis and Roche. R.A.M. receives research funding from the Canadian Institutes of Health Research (CIHR), Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Research Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defence, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada.

Aims: To assess the individual and joint effects of diabetes and depression on all-cause mortality and cardiovascular disease (CVD) in the middle-aged and elderly Chinese populations., Methods: 9105 individuals without CVD from the China Health and Retirement Longitudinal Study (CHARLS) were included and followed up for 9 years. Participants were divided into four comparative groups: diabetes alone, depression alone, both conditions, and neither condition. Multivariate binary logistic regression models were performed to compare the risks of all-cause mortality and CVD among the four groups., Results: When compared to those without diabetes and depression, the multivariate adjusted odds ratios (aORs) for CVD in individuals who had diabetes only, depression only, and both diabetes and depression were 1.245 (95 % CI 1.023 to 1.515), 1.318 (95 % CI 1.171 to 1.485) and 1.722 (95 % CI 1.361 to 2.178), respectively. The aORs for all-cause mortality were 1.366 (95 % CI 1.035-1.804) for diabetes alone, 1.082 (95 % CI 0.916-1.279) for depression alone, and 1.590 (95 % CI 1.152-2.195) for both conditions when compared with those with neither condition., Conclusions: Individuals with both diabetes and depression had greater risk of CVD and all-cause mortality when compared to those with diabetes or depression alone, or those without either condition., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To explore the separate and joint association of estimated glucose disposal rate (eGDR) and high-sensitivity C-reactive protein (hsCRP) with cardiometabolic multimorbidity (CMM)., Methods: A total of 6900 participants aged 45 years or older with available data on eGDR and hsCRP and without cardiometabolic diseases at baseline from the China Health and Retirement Longitudinal Study were included. CMM was defined as the coexistence of two or more cardiometabolic diseases, including heart diseases, stroke, and diabetes., Results: During a median follow-up of 9.0 years, 464 (6.7 %) participants developed CMM. Low eGDR and high hsCRP separately and jointly increased the risk of CMM. The adjusted hazard ratio (HR) was 1.67 (95 % confidence interval [CI] 1.33-2.09) for low eGDR versus high eGDR, 1.43 (95 % CI 1.12-1.82) for high hsCRP versus low hsCRP) and 2.40 (95 % CI 1.77-3.27) for low eGDR plus high hsCRP versus high eGDR plus low hsCRP. The C-statistic, discriminatory power and risk reclassification significantly improved with the addition of combined eGDR and hsCRP for CMM (P < 0.001)., Conclusions: Low eGDR and high hsCRP were individually and jointly associated with increased risk of incident CMM. The findings highlighted the importance of joint evaluation of eGDR and hsCRP for primary prevention of CMM., 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.)

Introduction: Individuals with type 2 diabetes and increased albuminuria, a well-established marker of microvascular complications, are at a higher risk for cardiovascular disease (CVD) and premature mortality. Therefore, a better understanding of the underlying pathophysiology is needed to improve risk stratification and tailor prevention and intervention., Methods: We conducted a cross-sectional study including 463 individuals with type 2 diabetes, various degrees of albuminuria and without CVD. We analysed the association between albuminuria and markers of endothelial function (thrombomodulin and syndecan-1), thrombin generation (thrombin-antithrombin complex, prothrombin fragment 1 + 2), fibrinogen, platelet function (activation using soluble plasma selectin and aggregation using Multiplate® Analyzer) using regression models., Results: In the study cohort 33 % were women, the mean ± SD age was 65 ± 9 years, and median [IQR] diabetes duration was 15 [9-20] years. In total, 344 (74 %) individuals had normal albuminuria, 87 (19 %) moderately- and 32 (7 %) severely increased albuminuria levels. Higher markers of endothelial function and fibrinogen were independently associated with higher albuminuria levels (p < 0.01). No association between albuminuria and markers of thrombin generation and platelet was demonstrated., Conclusion: We demonstrated an independent association between albuminuria and markers of endothelial function and fibrinogen in individuals with type 2 diabetes and no history of CVD., Competing Interests: Declaration of competing interest LFFD, CGP, VRC, OBP, MFM, TWH and AMH report no conflicts of interest. NT is a full-time employee of Novo Nordisk Inc. PR has received grants for research to Steno Diabetes Center Copenhagen from Astra Zeneca, Bayer and Novo Nordisk, and has received honoraria to Steno Diabetes Center Copenhagen from Abbott, AstraZeneca, Bayer, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Sanofi and Gilead., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Sexual orientation can be measured across identity, attraction, and behavior. Sexual minorities are at increased risk of cardiovascular disease (CVD) and diabetes; however, it is not known whether cardiometabolic disease risk varies across these dimensions., Methods: We analyzed cross-sectional data from 36,309 adults who participated in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III; 2012-2013). Participants were categorized as heterosexual (reference), lesbian/gay, or bisexual across identity, attraction, and behavior using structured clinical interview data. Prevalent CVD (myocardial infarction, stroke, angina, or arteriosclerosis) and diabetes were assessed by self-report., Results: Demographics (age, sex, race/ethnicity, education, and income) adjusted logistic regression models revealed bisexual behavior (i.e., people reporting sexual activity with both man- and woman-identifying individuals), but not lesbian/gay behavior (i.e., people reporting sexual activity exclusively with same-sex individuals), was associated with an increased odds of prevalent CVD (OR = 1.44, 95% CI = 1.08-1.91, p = .013) and prevalent diabetes (OR = 1.39, 95% CI = 1.09-1.77, p = .007). Contrastingly, sexual minority identity (i.e., self-concept) and attraction (i.e., one's sexual/romantic feelings) were not associated with prevalent CVD or diabetes., Conclusions: Our results in a nationally representative sample indicate that the sexual orientation dimension of behavior is linked with prevalent CVD and diabetes. This finding suggests that assessing multiple sexual orientation dimensions may aid in identifying sexual minority subgroups in greatest need of cardiometabolic disease prevention efforts. Although mechanisms such as stigma and minority stress have been proposed, future studies are required to elucidate mechanisms underlying the bisexual behavior-cardiometabolic disease relationship., (Copyright © 2024 by the American Psychosomatic Society.)

Background and Objectives: Childhood risk factors are associated with cardiovascular events in adulthood. We compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a model that additionally included lipids to predict cardiovascular events in adulthood., Methods: The study comprised 11 550 participants from 7 longitudinal cohort studies in the United States, Australia, and Finland with risk factor measurements in adolescence and followed into adulthood. The adolescent risk factors were defined by using clinical standards including overweight or obesity, elevated blood pressure, smoking, and borderline high or high levels of total cholesterol and triglycerides. The main outcomes were medically adjudicated fatal or nonfatal cardiovascular disease events occurring after age 25., Results: Of 11 550 participants (55.1% female, mean age 50.0 ± 7.7 years), 513 (4.4%) had confirmed cardiovascular events. In a multivariable model (hazard ratio [95% confidence interval]), elevated blood pressure (1.25 [1.03-1.52]), overweight (1.76 [1.42-2.18]), obesity (2.19 [1.62-2.98]), smoking (1.63 [1.37-1.95]), and high total cholesterol (1.79 [1.39-2.31]) were predictors of cardiovascular events (P < .05). The addition of lipids (total cholesterol and triglycerides) into the nonlaboratory model (age, sex, blood pressure, BMI, and smoking) did not improve discrimination in predicting cardiovascular events (C-statistics for the lipid model 0.75 [SD 0.07] and nonlaboratory model 0.75 [0.07], P = .82)., Conclusions: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted adult cardiovascular events. The addition of lipid measurements to nonlaboratory risk factors did not improve the prediction of cardiovascular events., (Copyright © 2024 by the American Academy of Pediatrics.)

Cardiovascular risk factors (high blood pressure, smoking, overweight, type 2 diabetes, dyslipidemia, physical inactivity) substantially rise with increasing age, particularly after middle age, whereby women are affected to a much greater extent. In the population of Saxony-Anhalt the prevalence of cardiovascular risk factors is clearly increased and the population structure in Saxony-Anhalt is particularly characterized by a high average age as well as high morbidity and mortality rates due to cardiovascular diseases. Saxony-Anhalt therefore provides a model character for the demographic development in Europe. This review article discusses strategies for the implementation of target group-specific cardiovascular preventive strategies in the Federal State of Saxony-Anhalt with special consideration of age and sex. When preventive medicine facilities are established and innovative treatment possibilities for patients with cardiovascular risks are created, prevention should also become available in rural areas., (© 2024. The Author(s).)

Stent(s) insertion is a common form of surgery for patients with cardiovascular diseases, and is associated with a high rate of hospital readmission. This study aims to investigate the acute association between PM 2.5 exposure and hospital readmission for patients with cardiovascular disease and a history of stent(s) insertion. The records of hospital admission were collected from the Beijing Municipal Commission of Health and Family Planning Information Center between 1st January 2013 and 31st December 2017. Subsequent hospital readmission records for patients with a history of stent(s) insertion or without any surgery were extracted. The conditional logistic regression model was applied to investigate the association between PM 2.5 concentration and cardiovascular disease readmission in patients who had undergone stent(s) insertion or without any surgery. A total of 81,468 patients who had a history of stent(s) insertion were included in this study. Of these, 17,224 patients (21.1 % of the total number of patients) were readmitted 27,749 times due to cardiovascular disease. The median daily PM 2.5 concentration was 62.8 μg/m 3 with an interquartile range (IQR) of 71.5 μg/m 3 . The excess risk (ER) associated 10 μg/m 3 increase in PM 2.5 concentration for readmission due to cardiovascular disease was 0.48 % (95 % CI: 0.09 %, 0.87 %) in patients with a history of stent(s) insertion. Patients who had stent(s) insertion at the vessel bifurcation site showed the highest risk of readmission for cardiovascular disease when exposed to PM 2.5 ; the ER was 4.12 % (95 % CI: 1.60 %, 6.70 %). PM 2.5 was significantly associated with angina pectoris and readmission for chronic ischemic heart disease in patients with a history of stent(s) insertion. PM 2.5 had a significant association with cardiovascular readmission among patients with a history of insertion of stent(s). Patients who had vessel bifurcation treated showed the highest risk of readmission., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) led to new guidelines for statin use among people with HIV (PWH) with low to moderate risk for atherosclerotic cardiovascular disease (ASCVD). Little is known about the natural history of diabetes mellitus (DM) or mechanisms contributing to statin effects on DM among this population., Objective: To determine the contribution of known DM risk factors to excess risk for DM with pitavastatin in REPRIEVE., Design: Phase 3, primary ASCVD prevention trial over a median of 5.6 years of follow-up. (ClinicalTrials.gov: NCT02344290)., Setting: Global, multicenter trial., Participants: 7731 PWH aged 40 to 75 years with low to moderate ASCVD risk (by the pooled cohort equations from the American College of Cardiology and American Heart Association) without DM at study entry., Intervention: Random 1:1 assignment to pitavastatin, 4 mg daily, or placebo., Measurements: New-onset DM was determined at each visit by clinical diagnosis requiring initiation of medication treatment for DM. The incidence of new-onset DM was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. Treatment effects of pitavastatin on progression to new DM in key subgroups were determined., Results: Participants with at least 3 DM risk factors (vs. no risk factors) had increased risk for DM in each treatment group (incidence rate, 3.24 per 100 person-years [PY] vs. 0.34 per 100 PY [pitavastatin] and 2.66 per 100 PY vs. 0.27 per 100 PY [placebo]). The incidence of DM was highest in South Asia. In adjusted analyses, high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset DM (all P  < 0.005)., Limitation: Pitavastatin was the only statin assessed; DM was assessed clinically., Conclusion: Metabolic risk factors, including prediabetes and obesity, contributed to new-onset DM in statin- and placebo-treated participants. A clinically significant effect of pitavastatin on DM was seen primarily among those with multiple risk factors for DM at entry. Strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against DM among PWH., Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Although observational studies have linked primary aldosteronism (PA) with cardiovascular diseases (CVDs), the causality remains uncertain. In this study, we aimed to investigate whether PA is causally associated with CVD risk and cardiac magnetic resonance (CMR) parameters using the Mendelian randomization (MR) method. Independent and genome-wide significant single nucleotide polymorphisms for PA were extracted from genome-wide association study (GWAS) summary statistics. Genetic associations with the CVDs and CMR parameters were obtained from recent large-scale GWASs or genetic consortia. Inverse-variance weighted (IVW) method was utilized for the preliminary estimates, and multiple sensitivity analyses (including weighted median, Cochran's Q test, MR-Egger, MR-PRESSO, and leave-one-out analysis) were conducted to verify the robustness of the results. The MR analyses using the IVW method showed that genetically predicated PA was significantly associated with atrial fibrillation (OR = 1.046, 95% CI: 1.029-1.062, padj < 0.001), myocardial infarction (OR = 1.029, 95% CI: 1.005-1.053, padj = 0.027), heart failure (OR = 1.023, 95% CI: 1.004-1.042, padj = 0.027), any stroke (OR = 1.062, 95% CI: 1.031-1.095, padj < 0.001), any ischemic stroke (OR = 1.058, 95% CI: 1.022-1.095, padj = 0.004), and small vessel stroke (OR = 1.116, 95% CI: 1.041-1.196, padj = 0.004). Notably, PA also had a causal effect on adverse cardiac remodeling, including larger ventricular and atrial volumes, higher ventricular stroke volume, and reduced left atrial emptying fraction. Our findings support a causal role of PA in higher cardiovascular disease risk and adverse cardiac remodeling. Given the diagnostic delay and disease burden in PA, more attention should be paid to the screening and treatment of PA to reduce the incidence of cardiovascular outcomes., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Recurrent event data, which represent the occurrence of repeated incidences, are common in observational studies. Furthermore, collecting possible spatial correlations in health and environmental data is likely to provide more information for risk prediction. This article proposes a comprehensive proportional intensity model considering spatial random effects for recurrent event data using a Bayesian approach. The spatial information for areal data (where the spatial location is known up to a geographic unit such as a county) and georeferenced data (where the location is exactly observed) is examined. A traditional constant baseline intensity function, as well as a flexible piecewise constant baseline intensity function, are both under consideration. To estimate the parameters, a Markov chain Monte Carlo method with the Metropolis-Hastings algorithm and the adaptive Metropolis algorithm are applied. To assess the performance of model fitting, the deviance information criterion and log pseudo marginal likelihood are proposed. Overall, simulation studies demonstrate that the proposed model is significantly better than models that do not consider spatial effects if spatial correlations exist. Finally, our approach is implemented using a dataset related to the recurrence of cardiovascular diseases, which incorporates spatial information., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Youths with type 1 diabetes (T1D) exhibits higher levels of pulse wave velocity (PWV) compared to healthy controls. Higher PWV in T1D subjects is associated with increased hazard of progression in albuminuria, decline in eGFR, cardiovascular (CV) events and mortality. In the recently published work by Georeli et al., increased PWV was associated with poor glycemic control as expressed by time-in-range (TIR) < 50 % in T1D children, adolescents and young adults. This finding is of great interest, since it is well known that glycemic control, as measured by TIR, is an important contributor of CV risk. The duration of TIR < 50 % is not reported by the authors, but is of importance, knowing that CGM provide data for the last 3-6 months, depending on the CGM model. In conclusion, PWV looks promising for risk stratification in T1D, but its exact role in T1D still remains to be fully explored., Competing Interests: Declaration of competing interest None related to this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: This review highlights recent research in the field of celiac disease., Recent Findings: Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition., Summary: Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Proton pump inhibitors (PPIs) rank among the most frequently prescribed medications to treat acid-related diseases. Mounting concerns surround the potential for serious adverse events, including cardiovascular events, associated with their prolonged use/misuse., Areas Covered: This comprehensive review explores cardiovascular adverse events linked to PPI use among high-risk cardiovascular patients. A structured search was conducted on PubMed., Expert Opinion: Many patients with cardiovascular disease who require antiplatelet treatment will require long-term PPI treatment. Interpreting the published data is not straightforward. First, because there is no plausible mechanistic explanation for PPIs to induce cardiovascular events apart from the potential interaction with the metabolism of thienopyridines. Although several observational studies have shown an increased cardiovascular risk and mortality in patients taking long-term PPIs, most available clinical trials and meta-analyses of available studies do not. However, the absence of firm evidence of this link does not necessarily imply that this association does not exist, and other hypothesis must be explored. Anemia is a common event in patients who take antiplatelet therapy and PPIs, and it is a factor associated with cardiovascular events and death. Anemia in these patients is often attributed to erosive lesions of the small intestine, where PPI may play a key role by modifying the microbiota.

Aims: To investigate the impact of diagnosis age of type 2 diabetes mellitus (T2DM) on subsequent adverse outcomes within the Chinese population., Methods: 549,959 eligible T2DM patients were included from Ningbo and Jinhua city in Zhejiang province, China. Standardized ratio was used to evaluate the risks of coronary heart disease (CHD), stroke, cancer and all-cause death in different T2DM diagnosis age groups., Results: For all adverse outcomes, higher excess risks were observed in the youngest age group (30-39) than in the oldest age group (≥80) with T2DM. The standardized incidence ratios (SIR) were 5.93 (95% CI: 3.46, 10.14) for CHD, 5.45 (95% CI: 3.72, 7.99) for stroke and 1.85 (95% CI: 1.38, 2.49) for cancer in the youngest age group, and were 1.32 (95% CI: 1.08, 1.60) for CHD, 1.25 (95% CI: 1.08, 1.44) for stroke, and 0.78 (95% CI: 0.56, 1.09) for cancer, respectively, in the oldest age group. The standardized mortality ratios (SMR) for all-cause death were 3.15 (1.69, 5.84) vs. 1.12 (0.88, 1.43). These excess risks decreased with increasing diagnosis age (all P value < 0.001). Consistent results were observed when individuals were stratified by sex or further excluded with the time from T2DM diagnosis to endpoints less than 1 or 2 years., Conclusions: Th earlier the diagnosis of T2DM, the higher the risk for subsequent adverse outcomes. It is imperative to enhance the management and monitoring of early-onset patients during follow-up., 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 B.V. All rights reserved.)

Purpose: Gestational diabetes mellitus (GDM) could increase the risks of type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, evidence on its association with cardiometabolic multimorbidity (CMM) was limited. This study aimed to evaluate the association between GDM and the prevalence, incidence, patterns, and progression of CMM; and the role of body mass index (BMI) in such association., Methods: This study included 203,372 women who have given birth in UK Biobank. The diagnoses of GDM and cardiometabolic diseases (including stroke, coronary heart disease [CHD], and T2DM) were reported by participants or obtained through linkage to inpatient hospital data until 31st December 2020. BMI was assessed at the baseline assessment. CMM was defined as having two or more of included cardiometabolic diseases. Logistic regression models and Cox proportional hazard models were used to assess the association between GDM and CMM, and the modifications on both additive and multiplicative scales were assessed to evaluate the effect of BMI on such association., Results: A total of 1217 women had a history of GDM, 2351 participants had CMM at the end of follow-up and 1601 was newly diagnosed during follow-up. GDM was associated with higher prevalence (odds ratio [OR]=4.64, 95 % confidence interval [95 % CI]=3.54-6.08) and incidence (hazard ratio [HR]=3.62, 95 % CI=2.62-5.00) of CMM. In particular, GDM was associated with higher odds of T2DM, coexisting T2DM and vascular disease, and T2DM followed by vascular disease. Formal testing for effect modification suggested multiplicative modification by BMI for the association between GDM and incident CMM., Conclusions: GDM was associated with CMM in women's late life, with multiplicative modification effects of BMI. Our results suggest that maternal and lifestyle interventions (e.g., weight management) are warranted for the primary and secondary prevention of CMM, particularly in women with a history of GDM., 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: Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up., Methods: We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively)., Results: Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke ( P trend <0.011) and CVD ( P trend <0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group., Conclusions: The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD., Competing Interests: Dr Bhatt discloses the following relationships: advisory board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures, Hims, SFJ, and Youngene; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [Portopulmonary Hypertension Treatment With Macitentan: A Randomized Clinical Trial], funded by St. Jude Medical, now Abbott), Boston Scientific (chair: the PEITHO trial [Pulmonary Embolism Thrombolysis]), Cleveland Clinic, Contego Medical (chair: PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF [Safety and Efficacy of the Alleviant System for No-Implant Interatrial Shunt Creation in Patients With Chronic Heart Failure], funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT trial [Myocardial Ischemia and Transfusion]); honoraria: American College of Cardiology (senior associate editor: Clinical Trials and News, ACC.org; chair: ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; the RE-DUAL PCI [Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting] Clinical Trial Steering Committee funded by Boehringer Ingelheim; AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome] Executive Committee funded by CSL Behring), Belvoir Publications (editor-in-chief: Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease], funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief: Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair: interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (Continuing Medical Education [CME] steering committees), MJH Life Sciences, Oakstone CME (course director: Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] Operations Committee, Publications Committee, Steering Committee, and USA national coleader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital that assigned to Lexicon; neither he nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor: Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo. Dr Steg discloses the following relationships: employment: Assistance Publique-Hôpitaux de Paris and Université Paris-Cité; research grants: Bayer; consulting: Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, Pfizer, PhaseBio, Novartis, NovoNordisk, Regeneron, Sanofi, and Servier; and patent issued as coinventor of use of alirocumab to reduce cardiovascular risk (patent assigned to Sanofi). The other authors report no conflicts.

Aim: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis., Methods: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes., Results: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05)., Conclusion: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Orthostatic hypotension is associated with cardiovascular disease. It remains unclear if low standing blood pressure or high seated blood pressure is responsible for this association. We compared associations of orthostatic hypotension and hypertension with high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide., Methods: We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You, a randomized controlled trial funded by the National Institute on Aging, between July 2015 and May 2019. Participants were community-dwelling adults, 70 years or older. Blood tests for high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide were drawn at visits concurrent with blood pressure measurements. Secondary analysis occurred in 2023. We determined associations between blood pressure phenotypes and cardiac biomarkers., Results: Of 674 participants (mean age 76.5 ± 5.4 years, 43% female, 17.2% Black race), 29.1% had prior cardiovascular disease. Participants with seated hypertension had 10.1% greater high-sensitivity cardiac troponin I (95% confidence interval = 3.8-16.9) and 11.0% greater N-terminal pro-B-type natriuretic peptide (4.0-18.6) than those without seated hypertension. Participants with standing hypertension had 8.6% (2.7-14.9) greater high-sensitivity cardiac troponin I and 11.8% greater N-terminal pro-B-type natriuretic peptide (5.1-18.9) than those without standing hypertension. Hypotensive phenotypes were not associated with either biomarker., Conclusions: Both seated and standing hypertension were associated with greater high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide, but hypotensive phenotypes were not. Hypoperfusion may not be the principal mechanism behind subclinical cardiac injury among older adults with orthostatic hypotension., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. 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.)

Background: Findings of available randomized controlled trials (RCTs) on the effects of chia are inconsistent. Although previous meta-analyses summarized available findings in this regard, some limitations may distort their findings. Moreover, none of these meta-analyses examined the dose-response association of chia on cardiometabolic risk factors (CMRFs). Therefore, the present study aimed to evaluate the effect of chia consumption on CMRFs., Methods: Relevant RCTs were included by searching the ISI Web of Science, PubMed, and Scopus databases up to June 2, 2023. Mean differences (MD) and 95 % confidence intervals (CI) were pooled using random-effects model., Results: Ten publications were included in this systematic review and the meta-analysis. The results showed a significant reduction in systolic blood pressure (SBP) (MD = -7.87 mmHg; 95 % CI: - 12.92 to - 2.82; I 2 = 71.3 %, P heterogeneity = 0.004), diastolic blood pressure (MD = -6.33 mmHg; 95 %CI: - 7.33 to - 5.34, I 2 = 0 %, P heterogeneity = 0.42) and high-density lipoprotein cholesterol (HDL-c) (MD = -4.09 mg/dl; 95 %CI: - 6.76 to - 1.43, I 2 = 12.4 %, P heterogeneity = 0.33). However, the effects of chia on the other risk factors were not significant. Based on the dose-response analysis, a 10-g/d increase in chia consumption significantly reduced SBP (MD = -2.20 mmHg; 95 %CI: - 3.75 to - 0.66, I 2 = 78.9 %, P heterogeneity < 0.001) and HDL-c (MD = -1.10 mg/dl; 95 %CI: - 1.72 to - 0.49, I 2 = 0 %, P heterogeneity = 0.52)., Conclusion: Chia consumption might have a beneficial effect on lowering blood pressure. Chia consumption can also lead to a slight reduction in HDL-c levels. As the quality of the included studies was mostly low, the findings should be interpreted with caution. Well-designed trials with larger sample sizes and longer duration of follow-up are needed to provide additional insight into the dose-dependent effects of chia consumption., Competing Interests: Declaration of Competing Interest There was no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Risk estimation is an integral part of cardiovascular care. Local recalibration of guideline-recommended models could address the limitations of existing tools., Objective: To provide a machine learning (ML) approach to augment the performance of the American Heart Association's Predicting Risk of Cardiovascular Disease Events (AHA-PREVENT) equations when applied to a local population while preserving clinical interpretability., Design, Setting, and Participants: This cohort study used a New England-based electronic health record cohort of patients without prior atherosclerotic cardiovascular disease (ASCVD) who had the data necessary to calculate the AHA-PREVENT 10-year risk of developing ASCVD in the event period (2007-2016). Patients with prior ASCVD events, death prior to 2007, or age 79 years or older in 2007 were subsequently excluded. The final study population of 95 326 patients was split into 3 nonoverlapping subsets for training, testing, and validation. The AHA-PREVENT model was adapted to this local population using the open-source ML model (MLM) Extreme Gradient Boosting model (XGBoost) with minimal predictor variables, including age, sex, and AHA-PREVENT. The MLM was monotonically constrained to preserve known associations between risk factors and ASCVD risk. Along with sex, race and ethnicity data from the electronic health record were collected to validate the performance of ASCVD risk prediction in subgroups. Data were analyzed from August 2021 to February 2024., Main Outcomes and Measures: Consistent with the AHA-PREVENT model, ASCVD events were defined as the first occurrence of either nonfatal myocardial infarction, coronary artery disease, ischemic stroke, or cardiovascular death. Cardiovascular death was coded via government registries. Discrimination, calibration, and risk reclassification were assessed using the Harrell C index, a modified Hosmer-Lemeshow goodness-of-fit test and calibration curves, and reclassification tables, respectively., Results: In the test set of 38 137 patients (mean [SD] age, 64.8 [6.9] years, 22 708 [59.5]% women and 15 429 [40.5%] men; 935 [2.5%] Asian, 2153 [5.6%] Black, 1414 [3.7%] Hispanic, 31 400 [82.3%] White, and 2235 [5.9%] other, including American Indian, multiple races, unspecified, and unrecorded, consolidated owing to small numbers), MLM-PREVENT had improved calibration (modified Hosmer-Lemeshow P > .05) compared to the AHA-PREVENT model across risk categories in the overall cohort (χ23 = 2.2; P = .53 vs χ23 > 16.3; P < .001) and sex subgroups (men: χ23 = 2.1; P = .55 vs χ23 > 16.3; P < .001; women: χ23 = 6.5; P = .09 vs. χ23 > 16.3; P < .001), while also surpassing a traditional recalibration approach. MLM-PREVENT maintained or improved AHA-PREVENT's calibration in Asian, Black, and White individuals. Both MLM-PREVENT and AHA-PREVENT performed equally well in discriminating risk (approximate ΔC index, ±0.01). Using a clinically significant 7.5% risk threshold, MLM-PREVENT reclassified a total of 11.5% of patients. We visualize the recalibration through MLM-PREVENT ASCVD risk charts that highlight preserved risk associations of the original AHA-PREVENT model., Conclusions and Relevance: The interpretable ML approach presented in this article enhanced the accuracy of the AHA-PREVENT model when applied to a local population while still preserving the risk associations found by the original model. This method has the potential to recalibrate other established risk tools and is implementable in electronic health record systems for improved cardiovascular risk assessment.

Importance: The epidemiological link between immune-mediated diseases (IMIDs) and cardiovascular disease has often been attributed to systemic inflammation. However, the direction of causality and the biological mechanisms linking cardiovascular disease with IMIDs are incompletely understood. Given the robust epidemiological association and the growing body of supportive mechanistic evidence, psoriasis is an exemplary IMID model for exploring this relationship., Objective: To assess the bidirectional relationships between genetic predictors of psoriasis and the 2 major forms of cardiovascular disease, coronary artery disease (CAD) and stroke, and to evaluate the association between genetic predictors of cardiovascular disease with 9 other IMIDs., Design, Setting, and Participants: This was a genetic association study using mendelian randomization (MR), a powerful genetic tool to help distinguish causation from associations observed in epidemiological studies, to provide supportive evidence for causality between traits. The study conducted 2-sample MR analyses using summary-level data from large-scale genome-wide association meta-analysis studies (GWAS) for each trait. The analysis focused on individuals of European descent from GWAS meta-analyses, involving CAD, stroke, psoriasis, and 9 other IMIDs. Data were analyzed from January 2023 to May 2024., Exposures: Genetic predictors of CAD, stroke, psoriasis, and 9 other IMIDs., Main Outcomes and Measures: The primary outcomes were the associations of genetic predictors of CAD and stroke with the risk of psoriasis and 9 other IMIDs, determined using inverse-variance weighted (IVW) MR estimates., Results: This study included 181 249 cases and 1 165 690 controls with CAD, 110 182 cases and 1 503 898 controls with stroke, 36 466 cases and 458 078 controls with psoriasis, for a total of approximately 3 400 000 individuals, and 9 other IMIDs. In contrast to previous assumptions, genetic predictors of psoriasis were found to have no association with CAD or stroke. In the reverse direction, genetic predictors of both CAD (MR estimate IVW odds ratio [OR], 1.07; 95% CI, 1.04-1.10; P = .003) and stroke (IVW OR, 1.22; 95% CI, 1.05-1.41; P = .01) were found to have risk-increasing associations with psoriasis. Adjusting for stroke rendered the associations of genetically predicted CAD with psoriasis risk nonsignificant (and vice versa), suggesting that a shared effect underlying genetic risk for CAD and stroke associates with increased psoriasis risk. No risk-increasing associations were observed for genetic predictors of cardiovascular disease with other common IMIDs, including rheumatoid arthritis and inflammatory bowel disease., Conclusions and Relevance: Findings of this mendelian randomization study indicate that genetic predictors of cardiovascular disease were associated with increased psoriasis risk with no reciprocal effect or association with other IMIDs. Elucidating mechanisms underpinning this association could lead to novel therapeutic approaches in both diseases.

Background: Population-based studies of ideal cardiovascular health (CVH) and gestational diabetes mellitus (GDM) are scarce., Methods: We conducted a cross-sectional analysis of 2007-2018 National Health Examination and Nutrition Survey women aged ≥ 20 years, who had data on Life's Simple 7 (LS7) metrics and self-reported GDM history. Each LS7 metric was assigned a score of 0 (non-ideal) and 1(ideal) and summed to obtain total ideal CVH scores (0-7). We used logistic regression models to assess associations between LS7 ideal CVH scores (0-7) and GDM history, accounting for socio-demographic factors., Results: Among 9199 women (mean age: 46 years, 8 % with a GDM history), there was a progressive decrease in the odds of past GDM history across increasing ideal CVH scores. Compared to females with 0-1 ideal CVH scores, females with ideal CVH scores of 3, 4 and 5-7 had an associated 39 % lower [odds ratio: 0.61 (95 % CI: 0.41-0.90)], 50 % lower [0.50 (0.33-0.76)] and 66 % lower [0.34 (0.20-0.56)] odds of past GDM history, respectively. There were notable racial/ethnic and citizenship/nativity differences in these associations., Conclusions: Women with higher ideal CVH scores had lower odds of GDM history. Our findings underscore the importance of optimizing cardiometabolic health among women with GDM history., 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: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

Objectives: Little is known about the relationship between learning difficulties (LD) in adolescence and physical health in adulthood. This study investigates the gender-specific pathways through which LD is longitudinally associated with cardiometabolic risk in adulthood., Study Design: We used data from the National Longitudinal Study of Adolescent to Adult Health (N = 11,342). To assess cardiometabolic risk, 11 biomarkers related to cardiovascular functioning, glucose metabolism, lipid metabolism, and inflammation were utilized., Methods: We first estimated the association between LD in adolescence and cardiometabolic risk in adulthood. Then, we examined whether this association is mediated by educational attainment and body mass index (BMI). Finally, we employed a moderated mediation model to determine whether gender moderates these mediation patterns., Results: LD in adolescence was positively associated with cardiometabolic risk in adulthood (b = 0.165, p < 0.001). LD also predicted lower educational attainment (b = -0.724, p < 0.001) and higher BMI (b = 0.589, p < 0.05). Educational attainment and BMI explained 18 and 25 percent of the positive association between LD and cardiometabolic risk, respectively. A moderated mediation model revealed that indirect effects of LD on cardiometabolic risk via educational attainment and BMI were more pronounced among women than men., Conclusion: LD in adolescence is a significant predictor of cardiometabolic risk in adulthood. Interventions focusing on the academic and health behaviors of girls with LD may be effective in improving their adult physical health., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)