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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. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion Asciminib, a novel allosteric BCR::ABL1 inhibitor, targets the ABL1 myristoyl pocket to potentially reduce toxicity and enhance efficacy. It is approved for Philadelphia chromosome‐positive chronic‐phase chronic myeloid leukemia (CML‐CP) in patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs) or those with the T315I mutation.This retrospective analysis evaluated patients with CML treated with asciminib under a managed‐access program across eight Israeli centers from July 2019 to August 2022. We assessed treatment responses, toxicities, event‐free survival (EFS), and overall survival (OS) using Kaplan–Meier methods.The study included 30 patients who had received a median of three prior TKIs, with 73% starting asciminib due to intolerance. After a median follow‐up of 7.1 months, 85% of those without prior complete cytogenetic response (CCyR) achieved CCyR, and 60% previously not in major molecular response (MMR) attained MMR. Resistance was rare (10%), with no cardiovascular events reported despite high baseline comorbidity (73%). Median EFS was 47 months; median OS was not reached.Asciminib demonstrates significant efficacy and tolerability in heavily pretreated patients with CML‐CP, with no new cardiovascular events observed. Further long‐term studies are necessary to explore its full cardiovascular impact. [ABSTRACT FROM AUTHOR]

The relationship between the differential protective effect of salt substitute between hypertensive and normotensive individuals and the use of cardiovascular medications remains unclear. This study involved 4211 individuals with a history of stroke or hypertension who participated in the Salt Substitute and Stroke Study (SSaSS) from 120 villages in Shanxi Province. The aim of this study was to investigate the differences in major adverse cardiovascular events and blood pressure changes between the salt substitute and the regular salt group in the subgroups of participants taking different antihypertensive medications. Mixed models were employed and adjusted for the cluster effect (village) and potential confounding variables. During the average follow‐up period of 4.66 years, a significantly protective effect of salt substitute on reducing the risk of cardiovascular events was observed in the participants who taking antihypertensive medications (rate ratio: 0.81, 95% CI: 0.68 to 0.95. p = 0.011), whereas no significant effect in participants not taking antihypertensive medications (rate ratio: 0.91, 95% CI: 0.62 to 1.32, p = 0.612). Significant effects to lower systolic blood pressure of the salt substitutes were observed in the participants who took different antihypertensive medications. This study emphasized that the use of salt substitutes might enhance the efficacy of anti‐hypertensive medications in lowering blood pressure and reducing the risk of adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality. Methods: Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality. Results: Over the 30‐year follow‐up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38–2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09–4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19–1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58–2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all‐cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group. Conclusion: IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required. [ABSTRACT FROM AUTHOR]

Central blood pressure confers cardiovascular risk prediction ability, but whether the association between central systolic blood pressure (cSBP) and cardiovascular endpoints is independent of peripheral systolic blood pressure (pSBP) remains controversial. This systematic review and meta‐analysis aim to investigate the associations between cSBP and cardiovascular endpoints in models including and excluding pSBP, respectively. Observational studies assessing the risk of composite cardiovascular endpoints with baseline cSBP were searched in PubMed, Embase, Scopus, Web of Science, and Cochrane Library to May 31, 2022. Risk of bias was assessed by the Newcastle‐Ottawa Quality Assessment Scale, and random‐effects models were used to pool estimates. Finally, 48 200 participants from 19 studies with a mean age of 59.0 ± 6.9 years were included. Per 10 mmHg increase of cSBP was associated with higher risk of composite cardiovascular outcomes (risk ratio [RR]: 1.14 [95%CI 1.08–1.19]) and cardiovascular death (RR: 1.18 [95%CI 1.08–1.30]), and the associations still existed after adjusting for pSBP (RR: 1.13 [95%CI 1.05–1.21] for composite cardiovascular endpoints; RR: 1.25 [95%CI 1.09–1.43] for cardiovascular death). In pSBP‐unadjusted studies, increased cSBP was also associated with higher risk of all‐cause mortality and stroke, but not in the pSBP‐adjusted studies. Both cSBP and pSBP were similarly significantly associated with composite cardiovascular endpoints in models containing them separately and simultaneously. cSBP was significantly associated with cardiovascular events, independently of pSBP. Central or peripheral SBP could supplement cardiovascular risk assessment besides each other. [ABSTRACT FROM AUTHOR]

Background: Osteoprotegerin (OPG) is a secretory glycoprotein known for its involvement in bone metabolism and immune regulation. Research has extended OPG's significance in cardiovascular diseases (CVDs). Elevated OPG levels have been associated with increased cardiovascular risks, prompting interest in its role as a potential biomarker. Main Body: This study summarizes several studies that investigated the relationship between OPG levels and the incidence of CVD. The studies indicate that higher plasma levels of OPG are associated with an increased incidence of all‐cause death, cardiovascular death, and heart failure, even after adjusting for clinical confounders. Moreover, the findings suggest that OPG has the potential to serve as a predictive biomarker for adverse cardiovascular events in the patient population studied. The findings suggest that OPG could aid in risk stratification, allowing clinicians to identify high‐risk patients who might benefit from intensified preventive measures or tailored therapeutic interventions. Therefore, early identification of individuals at risk for adverse cardiovascular events could lead to improved patient outcomes and reduced disease burden. Conclusions: OPG's role in bone health and immune regulation has expanded to potential use as a biomarker for adverse cardiovascular events in stable coronary artery disease (CAD) patients. Despite limitations, its association with cardiovascular risks highlights its importance in risk assessment and personalized interventions. [ABSTRACT FROM AUTHOR]

Aims: Growth differentiation factor‐15 (GDF15), a cytokine in the transforming growth factor family, is up‐regulated in stress and inflammatory conditions and is elevated in patients with heart failure (HF). However, the age‐specific attributes and prognostic significance of GDF15 across age remain unknown in chronic HF (CHF). Methods and results: Serum levels of GDF15 were examined in 942 hypertensive patients (median 68 years) with CHF from the SUPPORT trial across the four age groups [under 50 (n = 73), 51–59 (n = 158), 60–69 (n = 296), and 70–79 years (n = 415)] and in the continuous spectrum. Clinical correlates of GDF15 were explored using the classic stepwise and LASSO (least absolute shrinkage and selection operator) regression approaches. Interaction terms with age were tested in the LASSO regression approach. The associations with the composite outcome of HF hospitalization or all‐cause death were investigated across ages. Median GDF15 levels (pg/mL) increased along with aging, from 691 in under 50 years to 855 in 51–59 years, 1114 in 60–69 years, and 1516 in 70–79 years (trend P < 0.001). Age, sex, systolic blood pressure, history of diabetes, ischaemic heart disease, left ventricular (LV) end‐systolic dimension, LV ejection fraction, estimated glomerular filtration rate, haemoglobin, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), troponin, C‐reactive protein, and the use of angiotensin‐converting enzyme inhibitors, diuretics, and statins were mutually selected as clinical covariates of GDF15. The LASSO regression analysis identified significant interactions between age and the history of diabetes and NT‐proBNP, with particularly robust associations in patients aged between 60 and 70 years. During the mean follow‐up of 8.6 years, 474 composite endpoints of HF hospitalization or death occurred. GDF15 was associated with a higher risk of HF hospitalization or all‐cause death [adjusted hazard ratio 1.84 (95% confidence interval 1.45–2.33)], with a particularly heightened risk in patients aged around 70 years (Pinteraction = 0.0008). The model with GDF15 on top of other established risk factors yielded marginally higher C‐statistics compared with the model without GDF15 (0.803 and 0.796, P = 0.045). The additive value of GDF15 on top of other established risk factors appeared similar across ages. A universal cut‐off value of 1400 pg/mL performed well in discriminating between those with and without HF hospitalization or death. Conclusions: Some clinical correlates of GDF15 have an interaction with age. GDF15 is an important determinant of cardiovascular endpoints, particularly in patients aged around 70 years. The additive value of GDF15 appeared consistent across ages, suggesting the use of a universal cut‐off value. [ABSTRACT FROM AUTHOR]

Objective: We prospectively determined incident cardiovascular events and their association with risk factors in rural India. Methods: We followed up with 7935 adults from the Rishi Valley Prospective Cohort Study to identify incident cardiovascular events. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) with 95% confidence intervals (95% CI) for associations between potential risk factors and cardiovascular events. Population attributable fractions (PAFs) for risk factors were estimated using R ('averisk' package). Results: Of the 4809 participants without prior cardiovascular disease, 57.7% were women and baseline mean age was 45.3 years. At follow‐up (median of 4.9 years, 23,180 person‐years [PYs]), 202 participants developed cardiovascular events, equating to an incidence of 8.7 cardiovascular events/1000 PYs. Incidence was greater in those with hypertension (hazard ratio [HR] [95% CI] 1.73 [1.21–2.49], adjusted PAF 18%), diabetes (1.96 [1.15–3.36], 4%) or central obesity (1.77 [1.23, 2.54], 9%) which together accounted for 31% of the PAF. Non‐traditional risk factors such as night sleeping hours and number of children accounted for 16% of the PAF. Conclusions: Both traditional and non‐traditional cardiovascular risk factors are important contributors to incident cardiovascular events in rural India. Interventions targeted to these factors could assist in reducing the incidence of cardiovascular events. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the long‐term influence of a diet and/or exercise intervention on long‐term mortality and cardiovascular disease (CVD) events. Methods: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet‐only, exercise‐only and diet‐plus‐exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow‐up the participants for up to 24 years after the end of 6‐year intervention. In total, 540 participants completed the follow‐up, while 36 subjects lost in follow‐up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. Results: Compared with controls, the diet‐only intervention in people with IGT was significantly associated with a reduced risk of all‐cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61‐0.97)], CVD death [HR 0.67, 95% CI (0.46‐0.97)] and CVD events [HR 0.72, 95% CI (0.54‐0.96)]. The diet‐plus‐exercise intervention was significantly associated with a decreased risk of all‐cause death [HR 0.64, 95% CI (0.48‐0.84)], CVD death [HR 0.54, 95% CI (0.30‐0.97)] and CVD events [HR 0.68, 95% CI (0.52‐0.90)]. Unexpectedly, the exercise‐only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. Conclusions: A diet‐only intervention and a diet‐plus‐exercise intervention in people with IGT were significantly associated with a reduced risk of all‐cause death, CVD death and CVD events, while an exercise‐only intervention was not. It suggests that diet‐related interventions may have a potentially more reliable influence on long‐term vascular complications and mortality. [ABSTRACT FROM AUTHOR]

Aims: The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase‐4 inhibitors (DPP4i). Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. Results: After up to 5 years of follow‐up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24–0.82). SGLT2i was related to reduced risks of AF‐related hospitalisation (HR: 0.72, 95% CI: 0.56–0.93), stroke (HR: 0.75, 95% CI: 0.60–0.94), and all‐cause death (HR: 0.33, 95% CI: 0.24–0.44). The protective effects were consistent irrespective of the concurrent use of non‐vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF‐related hospitalisation, stroke, and all‐cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i. [ABSTRACT FROM AUTHOR]

Breakfast consumption is generally considered a health‐promoting habit for cardiometabolism, particularly with regard to chrononutrition. Glucose uptake is enhanced by proper insulin secretion triggered by the pancreatic clock, averting metabolic dysregulation related to insulin resistance. Breakfast skipping, in turn, is often considered a behaviour detrimental to health, in part due to putative inverse metabolic actions compared to breakfast consumption, such that breakfast skipping may promote circadian desynchrony. However, most ill health concerns about breakfast skipping are inferred from observational research, and recent well‐controlled randomized clinical trials have shown benefits of breakfast skipping for cardiovascular risk factors. Accordingly, this review describes the effects of breakfast consumption versus breakfast skipping on cardiovascular risk factors (blood pressure and glycaemic and lipid indices). In addition, the view of breakfast consumption as an opportunity for functional food ingestion is considered to provide further insights into decision‐making practice. Collectively, both breakfast consumption and breakfast skipping can be considered viable habits, but they depend on individual preferences, planning, and the specific foods being consumed or omitted. When consumed, breakfast should consist primarily of functional foods typical for this meal (e.g., eggs, dairy products, nuts, fruits, whole grains, coffee, tea, etc.). While breakfast consumption aligns with chrononutrition principles, breakfast skipping can contribute to a calorie deficit over time, which has the potential for widespread cardiometabolic benefits for patients with overweight/obesity. The concepts and practical considerations discussed in the present review may aid health care personnel in personalising breakfast consumption recommendations for diverse patient populations. [ABSTRACT FROM AUTHOR]

Background: Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear.SS Aims: To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. Methods: Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all‐cause mortality. Results: Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow‐up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74–0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69–0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64–0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta‐regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. Conclusions: The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF. [ABSTRACT FROM AUTHOR]

Background: Usual measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time. We aimed to demonstrate the effect of a novel time‐weighted BP on cardiovascular outcomes using a post hoc analysis of two published randomized trials. Hypothesis: Time‐weighted blood pressure is associated with cardiovascular risk among patients with or without diabetes. Methods: The limited‐access ACCORD and SPRINT data sets were used for the current study. Time‐weighted BP is obtained by dividing cumulative BP by the total follow‐up time. Time‐weighted BP burden above a threshold is also determined after deriving the time‐weighted BP by re‐zeroing the interpolated pressure values at two different hypertension thresholds (>140/90 and >130/80 mmHg). Results: Eighteen thousand five hundred forty‐one patients from the two clinical trials were enrolled in this study. A J‐curve relation was observed between time‐weighted BP and major cardiovascular events (MACE). The systolic blood pressure (SBP) burden independently predicted MACE across the two trials at different thresholds (ACCORD: SBP > 130 mmHg, HR = 1.05 [1.03−1.06]; SBP > 140 mmHg, HR = 1.06 [1.04−1.08]; SPRINT: SBP > 130 mmHg, HR = 1.04 [1.03−1.05]; SBP > 140 mmHg, HR = 1.05 [1.04−1.07]). Consistent results were found for diastolic blood pressure (DBP) burden (ACCORD: DBP > 80 mmHg, HR = 1.10 [1.06−1.15]; DBP > 90 mmHg, HR = 1.20 [1.11−1.30]. SPRINT: DBP > 80 mmHg, HR = 1.06 [1.02−1.09]; DBP > 90 mmHg, HR = 1.12 [1.06−1.18]). Significant associations were also observed for stroke, myocardial infarction, cardiovascular death, and all‐cause mortality. Conclusion: Both time‐weighted SBP and DBP independently influenced the risk of adverse cardiovascular events among patients with and without diabetes, regardless of the definition of hypertension (130/80 or <140/90 mmHg). Keypoints: A novel approach was introduced to assess the time‐weighted systolic blood pressure (SBP) and diastolic blood pressure (DBP) as predictors of major adverse cardiovascular events (MACE).Both time‐weighted SBP and DBP independently influenced the risk of MACE in patients with and without diabetes, regardless of how hypertension was defined (<130/80 or <140/90 mmHg).This study highlights the significance of consistently maintaining adequate control of both SBP and DBP throughout an individual's lifespan to prevent cardiovascular events. [ABSTRACT FROM AUTHOR]

Aims/Introduction: High glycated hemoglobin (HbA1c) variability has been reported to be linked with cardiovascular events in type 2 diabetes patients. Only a few studies have been carried out on Asian patients. This study aimed to investigate the association of prediabetes and type 2 diabetes in Asian patients by performing a post‐hoc analysis of a multicenter, prospective, observational study. Materials and methods: Data for prediabetes and type 2 diabetes patients were retrieved from a multicenter national registry entitled "CORE‐Thailand study." The primary outcome was 4P‐MACE (major adverse cardiovascular events, including non‐fatal myocardial infarction, heart failure hospitalization, non‐fatal stroke and all‐cause death). Patients were stratified according to quartiles of HbA1c standard deviation. The Cox proportional hazards regression model was used to estimate the association of HbA1c variability with incident cardiovascular disease. Results: A total of 3,811 patients with prediabetes and type 2 diabetes were included. The median follow‐up duration was 54 months. In the fully adjusted model, the highest quartile of HbA1c variability showed a statistically significant association with 4P‐MACE (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.77–4.35), fatal and non‐fatal myocardial infarction (HR 6.91, 95% CI 1.90–25.12), hospitalization for heart failure (HR 3.34, 95% CI 1.20–9.26) and all‐cause death (HR 3.10, 95% CI 1.72–5.57). All these outcomes were statistically significantly different among four quartiles of HbA1c (log‐rank P‐value <0.05). Fatal and non‐fatal stroke showed no statistically significant association with high HbA1c variability. Conclusion: High HbA1c variability in the highest quartile showed a statistically significant association with multiple adverse cardiovascular events in an Asian population. Minimizing HbA1c fluctuation during long‐term follow up should be another important objective for type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Background: Optimal systolic BP (SBP) control in nursing home residents is uncertain, largely because this population has been excluded from clinical trials. We examined the association of SBP levels with the risk of cardiovascular (CV) events and mortality in Veterans Affairs (VA) nursing home residents on different numbers of antihypertensive medications. Methods: Our study included 36,634 residents aged ≥65 years with a VA nursing home stay of ≥90 days from October 2006–June 2019. SBP was averaged over the first week after admission and divided into categories. Cause‐specific hazard ratios (HRs) of SBP categories with CV events (primary outcome) and all‐cause mortality (secondary outcome) were examined using Cox regression and multistate modeling stratified by the number of antihypertensive medications used at admission (0, 1 or 2, and ≥3 medications). Results: More than 76% of residents were on antihypertensive therapy and 20% received ≥3 medications. In residents on antihypertensive therapy, a low SBP < 110 mmHg (compared with SBP 130 ~ 149 mmHg) was associated with a greater CV risk (adjusted HR [95% confidence interval]: 1.47 [1.28–1.68] in 1 or 2 medications group, and 1.41 [1.19–1.67] in ≥3 medications group). In residents on no antihypertensives, both low SBP < 110 mmHg and high SBP ≥ 150 mmHg were associated with higher mortality; while in residents receiving any antihypertensives, a low SBP was associated with higher mortality and the highest point estimates were for SBP < 110 mmHg (1.36 [1.28–1.45] in 1 or 2 medications group, and 1.47 [1.31–1.64] in ≥3 medications group). Conclusions: The associations of SBP with CV and mortality risk varied by the intensity of antihypertensive treatment among VA nursing home residents. A low SBP among those receiving antihypertensives was associated with increased CV and mortality risk, and untreated high SBP was associated with higher mortality. More research is needed on the benefits and harms of SBP lowering in long‐term care populations. See related Editorial by Pajewski et al. in this issue. [ABSTRACT FROM AUTHOR]

Introduction: The clinical benefit of vitamin D receptor activators (VDRA) in patients with well‐controlled secondary hyperparathyroidism undergoing dialysis remains unclear. Methods: This post hoc analysis of the LANDMARK study investigates if VDRA use is associated with cardiovascular benefits. Data of 2135 patients undergoing hemodialysis who were at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity‐score matching. Results: The hazard ratio (HR) for VDRA use was 0.99 (95% confidence interval [CI]: 0.67–1.46; p = 0.945) for cardiovascular events and 0.89 (95% CI: 0.62–1.28; p = 0.541) for all‐cause mortality at baseline. Among patients who always used VDRA, the HR was 1.12 (95% CI: 0.67–1.89; p = 0.666) for cardiovascular events and 1.11 (95% CI: 0.67–1.85; p = 0.688) for all‐cause mortality compared to those who never used VDRA. Conclusion: The use of VDRA does not reduce the risks of cardiovascular events or all‐cause mortality in patients on dialysis with well‐controlled secondary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

The advantages and disadvantages of using corticosteroids in children undergoing cardiac surgery is still contentious. To examine how perioperative corticosteroids affect postoperative mortality and clinical outcomes in pediatric cardiac surgery with cardiopulmonary bypass (CPB). We used MEDLINE, EMBASE, and the Cochrane Database to conduct a comprehensive search up through January 2023. Children aged 0–18 undergoing cardiac surgery were included in the meta‐analysis of randomized controlled studies comparing perioperative corticosteroids with other therapeutic therapies, placebo, or no treatment. All‐cause hospital mortality was the primary endpoint of the study. Hospitalization duration was a secondary result. The Cochrane Risk of Bias Assessment Tool was used to evaluate the research quality. Ten trials and 7798 pediatric participants were included in our analysis. Children taking corticosteroids had no significant difference in all‐cause in‐hospital mortality using a random‐effect model with relative risk (RR) = 0.38, 95% confidence interval (CI) = 0.16–0.91, I2 = 79%, p =.03 for methylprednisolone and RR = 0.29, 95% CI = 0.09–0.97, I2 = 80%, p =.04. For the secondary outcome, there was a significant difference between the corticosteroid and placebo groups, with pooled standard mean difference (SMD) = −0.86, 95% CI = −1.57 to −0.15, I2 = 85%, p =.02 for methylprednisolone and SMD = −0.97, 95% CI −1.90 to −0.04, I2 = 83%, p =.04 for dexamethasone. Perioperative corticosteroids may not improve mortality, but they reduce hospital stay compared to placebo. Further evidence from randomized controlled studies with larger samples is required for approaching at a valid conclusion. Highlights: The role of perioperative corticosteroids in preventing all‐cause mortality events in pediatric cardiac surgery patients is still doubtful.This systematic review and meta‐analysis sought to determine the effect of corticosteroids on mortality during cardiopulmonary bypass (CPB)‐assisted pediatric heart surgery.The administration of perioperative corticosteroids may not significantly improve the clinical outcomes of all‐cause mortality and length of hospital stay in children undergoing heart surgery. [ABSTRACT FROM AUTHOR]

Aims: There is limited research using real‐world data to evaluate protective cardiovascular effects of glucagon‐like peptide‐1 (GLP‐1) agonists among adults with type 2 diabetes (T2D) early in treatment. Materials and Methods: We conducted a retrospective, active comparator cohort study using 2011–2015 administrative claims data to compare cardiovascular disease (CVD) event rates following initiation of exenatide extended‐release (E‐ER), exenatide immediate‐release (E‐IR) or liraglutide in T2D adults who previously received no other antidiabetic medication (ADM) except metformin. The primary outcome was time to first major adverse CVD event (ischaemic heart disease, stroke, congestive heart failure or peripheral arterial disease) after starting GLP‐1. Cox proportional hazards regression was used to model the association between index GLP‐1 and CVD events, adjusting for baseline patient, prescriber and plan characteristics. Primary analyses included all patients with ≥2 prescription fills for the index GLP‐1, regardless of subsequent refill adherence or initiation of other ADM after index date. Results: Compared with liraglutide, neither E‐ER nor E‐IR was associated with risk of composite major CVD events (hazard ratios [HRs] for E‐ER and E‐IR: 1.33 [95% C.I. 0.73–2.39] and 1.30 [0.81–2.09]). No associations were observed between event rates for individual CVD components. The HR for an ischaemic event with E‐IR relative to liraglutide was 1.85 (95% C.I. 0.97–3.53). Adjusting for time‐varying exposure to other ADM and CVD medications after index date produced similar results. Conclusions: Initiating either immediate or extended‐release exenatide rather than liraglutide was not associated with significant differences in CVD risk in this observational real‐world study. [ABSTRACT FROM AUTHOR]

Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in‐patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin‐converting‐enzyme‐inhibitor (ACE‐I) or an angiotensin‐receptor‐blocker (ARB) with a calcium‐channel‐blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE‐I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all‐cause death, cardiovascular (CV) hospitalization/death, CV death, non‐CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all‐cause death, all‐cause death/hospitalization, CV death, CV death/hospitalization and non‐CV death. Conclusions: Guidelines‐suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the effect of targeted therapies on cardiovascular risk in psoriasis (PsO) and psoriatic arthritis (PsA) via a meta‐analysis of randomized controlled trials (RCTs). Methods: Pubmed, Embase, Cochrane Library, and Scopus were searched for RCTs reporting targeted therapies in patients with PsO/PsA published until 28 October 2021. The primary and secondary outcomes included the relationship between targeted therapies and all cardiovascular events (CVEs), major adverse cardiovascular events (MACEs), myocardial infarction (MI), heart failure, and stroke in PsO/PsA. The outcome risk ratios (RRs) were calculated using the Mantel–Haenszel fixed‐effect method. Results: A total of 81 articles involving 88 RCTs were included. There was no statistically significant difference regarding the occurrence of all CVEs for all targeted therapies (RR = 1.03, 95% CI 0.74‐1.43, P =.85) compared to placebo in PsO/PsA. No statistically significant difference existed between drugs and placebo in patients with PsA on all CVEs (RR = 0.81, 95% CI 0.48‐1.36, P =.43). Surprisingly, the incidence of all CVEs was higher in the low dosage group compared to the high dosage group of all targeted therapies (RR = 1.97, 95% CI 1.19‐3.27, P =.008) and prominently anti‐interleukin‐17 agent (RR = 2.20, 95% CI 1.05‐4.58, P =.04). Conclusion: Current targeted therapies are not associated with the risk of CVEs. Based on the existing evidence, we reported here that a dosage reduction of targeted therapies was not recommended. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all‐comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non‐improved EF (niEF), respecively. Methods and results: This is a retrospective sub‐analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow‐up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow‐up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter‐defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow‐up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305–0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396–0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228–0.511). Compared with niEF, iEF was significantly and independently associated with lower all‐cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469–0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317–0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381–0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT‐proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup. Conclusions: Improvement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT‐proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the influence of febuxostat on adverse events and mortality in gout. Methods: We retrospectively enrolled patients with newly diagnosed gout and prescribed urate‐lowering therapy between 2006 and 2017 from the Taiwan National Health Insurance Database. These patients were divided into 2 groups: with and without comorbidities (n = 294 847 and 194 539). An interrupted time series analysis with adjustments for demographics, comorbidities, and comedication by propensity score‐based stabilized weights was used to compare the trend of adverse events and mortality before vs after febuxostat was introduced in 2012. Results: The proportion of febuxostat use gradually increased from 0% in 2012 to 30% in those with comorbidities and 10% in those without comorbidities in 2017. Allopurinol use decreased from 30% in 2012 to 10% in 2017. The slope of the 1‐year incidence rate of Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (per 10 000 patients) significantly reduced after 2012 in those with and without comorbidities (−0.375 per quarter, P =.015 and −.253 per quarter, P =.049). The slope of the 3‐year incidence rate of acute myocardial infarction (AMI) (per 1000 patients), percutaneous coronary intervention (PCI) (per 1000 patients), and all‐cause mortality (per 100 patients) significantly increased after 2012 in those with comorbidities (+0.207 per quarter, P =.013; +.389 per quarter, P =.002; +.103 per quarter, P =.001). Conclusions: Febuxostat may reduce SJS and TEN in all gout patients but increase AMI, PCI, and all‐cause mortality in gout patients with comorbidities. [ABSTRACT FROM AUTHOR]

Aim: To clarify the importance of HbA1c reduction and antidiabetic drug use in preventing major adverse cardiovascular events (MACE) for patients with type 2 diabetes (T2D). Materials and Methods: We conducted an updated systematic review of contemporary large randomized controlled trials assessing the relative efficacy and safety of antidiabetic drugs with less hypoglycaemia risk in adult T2D patients. Mixed‐effects meta‐regression was performed to examine the associations of HbA1c reduction with subsequent risk of macrovascular and microvascular events. We evaluated the potential mediating role of HbA1c reduction in the relationship between antidiabetic drugs and MACE. Results: Eighteen placebo‐controlled trials comprising 155 610 participants were included. The effects of treatment differed among antidiabetic drug classes for most adverse outcomes with high heterogeneity (I2: 63.7%‐95.8%). Mean HbA1c reduction was lowest with dipeptidyl peptidase‐4 inhibitors (0.30%), followed by sodium‐glucose co‐transporter‐2 inhibitors (0.46%), and was highest with glucagon‐like peptide‐1 receptor agonists (0.58%) and thiazolidinediones (0.60%). Lower relative risks of MACE were significantly associated with larger reductions in achieved HbA1c (β −0.3182; 95% CI: −0.5366 to −0.0998; P =.0043), even after adjusting for drug classes. When considering HbA1c lowering as a mediator to be controlled, beneficial effects owing to specific antidiabetic treatment for MACE were not observed (χ2 = 1.4494; P =.6940). The proportion mediated by HbA1c reduction was 50.0%‐63.5% for these antidiabetic agents. Conclusions: The main benefits of antidiabetic agents might result from the reduction in blood sugar levels and are generally independent of drugs used. Risk reduction in MACE was proportional to the magnitude of HbA1c decrease conferred by antidiabetic agents with less hypoglycaemic hazard. [ABSTRACT FROM AUTHOR]

Methods: Three hundred thirty‐nine patients (230 men, 109 women) treated with lipoprotein apheresis in Saxony, Germany, in 2018 are described in terms of age, lipid pattern, risk factors, cardiovascular events, medication, and number of new admissions since 2014, and the data are compared with figures from 2010 to 2013. Results: Patients were treated by 45.5 physicians in 16 lipoprotein apheresis centers. With about 10 patients per 100 000 inhabitants, the number of patients treated with lipoprotein apheresis in Saxony is twice as high as in Germany as a whole. The median treatment time was 3 years. Almost all patients had hypertension; type 2 diabetes mellitus was seen significantly more often in patients with low Lipoprotein(a). Cardiovascular events occurred in almost all patients before initiation of lipoprotein apheresis, under apheresis therapy the cardiovascular events rate was very low in this high‐risk group. For some cardiovascular regions even no events could be observed. Conclusions: The importance of lipoprotein apheresis in Saxony had been increasing from 2010 to 2018. [ABSTRACT FROM AUTHOR]

There is an increased risk of congestive heart failure (CHF) following anthracycline‐based chemotherapy in patients with Diffuse Large B‐cell lymphoma (DLBCL). Little is known about risk factors of CHF, other cardiovascular events (CVE), and CVE effect on outcomes. We conducted a retrospective review of 463 newly diagnosed DLBCL patients treated between 2002 and 2016 with anthracycline containing regimens. At a median follow up of 71.3 months, 10.4% patients developed new CHF, 4.97% had new atrial fibrillation and 3.2% had new coronary artery disease. Age over 65, advanced stage DLBCL and diabetes were associated with increased cumulative incidence of CVE. Patients with prior diabetes had decreased progression‐free survival and overall survival in comparison to non‐diabetics. Patients who had a CVE in the first year had significant worse OS then patients who did not have a CVE (Hazard Ratio 10.0, 95% CI, 7.24–13.88). A risk score incorporating age at DLBCL diagnosis, baseline lymphocyte count, disease stage and diabetes stratified into groups with low, intermediate and high risk for CVE, with 1‐year cumulative incidence of CVE of 5.3%, 7.9% and 13.4%. Diffuse large B‐cell lymphoma patients treated with anthracycline containing regimens have high incidence of CVE, which are not limited to CHF. Clinical variables at the time of diagnosis can identify the group of DLBCL patients at highest risk of CVE, for whom preventive interventions should be considered. [ABSTRACT FROM AUTHOR]

Aims: Recent studies suggested that both left ventricular ejection fraction (LVEF) lower than 60% or higher than 65% were associated with an increased mortality in the general population. Uncertainty remains regarding adverse outcomes across LVEF in coronary artery disease (CAD). The common understanding was that LVEF <40% was associated with an increased risk of mortality. But the threshold at LVEF of 40% was arbitrary because quite a lot of adverse outcomes existed in patients with ejection fraction >40%. We aimed to evaluate the relationship between LVEF and mortality or adverse events in CAD patients undergoing percutaneous coronary intervention (PCI). Methods and results: A total of 10 252 CAD patients undergoing PCI from an observational cohort were studied. All‐cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) were set as outcomes. Kaplan–Meier curves, adjusted Cox regression models, and restricted cubic spline analyses were used for evaluation. A total of 137 (1.3%) patients had all‐cause mortality, and 816 (8.0%) patients had MACCE during a median of 2.4 years of follow‐up. The median LVEF was 64%. All‐cause mortality and MACCE rates changed substantially across LVEF categories, and a linear inverse relationship of LVEF with all‐cause mortality and MACCE risk was observed. All‐cause mortality or MACCE risk increased significantly below an LVEF of 55 or 65%, respectively. Patients with LVEF <55% had a more than 3.5‐fold higher mortality than those with LVEF ≥55%. Patients with LVEF <65% had a more than 1.3‐fold higher MACCE than those with LVEF ≥65%. Below 55 or 65%, there was a rise in mortality or MACCE. A gradient–response relationship was observed, with an all‐cause mortality risk range between 8.6‐fold and 3.0‐fold increase from LVEF <40 to 50–54.9% and MACCE risk range between 2.4‐fold and 1.4‐fold from LVEF <40 to 60–64.9%. Conclusions: In CAD patients undergoing PCI, LVEF lower than 55% or LVEF lower than 65% was correlated with increased all‐cause mortality and MACCE respectively, whereas higher LVEF was not. [ABSTRACT FROM AUTHOR]

Background: This study examined the longitudinal associations of baseline psychosocial stress subgroups with cardiovascular disease (CVD) events and whether social support, neighborhood cohesion, and physical activity modified these associations in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods and Results: Data from 6,349 adults (aged: 62.2±10.2 years; 52.9% women) from the MESA study with no prior CVD in 2000-2002 were used in this analysis. Latent class analysis (LCA) was used to specify distinct psychosocial stress subgroups based on self-reported stressors stemming from respondents' neighborhood and social environment. Adjudicated CVD events (fatal and nonfatal events) were ascertained annually through the year 2019. Cox proportional hazards models were used to examine the associations between subgroup membership and CVD events. Five distinct psychosocial stress subgroups were identified via LCA and were labeled 'moderate neighborhood noise' (12.1%), 'excessive neighborhood noise' (6.4%), 'multiple high stressors' (6.3%), 'high discrimination' (21.4%), and 'optimal' (53.8%). By the year 2019, 1,121 participants had experienced a CVD event. Membership in the 'high discrimination' (HR: 1.29; 95%CI: 1.10, 1.51) subgroup was associated with higher risk of a CVD event when adjusted for sociodemographic characteristics and cardiovascular health metrics. Neither social support, neighborhood cohesion, nor physical activity modified this association ( p s>0.05)., Conclusions: Distinct subgroups of individuals with high self-reported psychological distress-particularly related to discrimination and chronic stress are associated with high incident cardiovascular events.

Background: Neighborhood-level income is inversely associated with cardiovascular events; however, it is uncertain whether this association varies with immigration status., Methods and Results: We conducted a population-based cohort study of 5.2 million (53% women, 19% immigrants) urban-dwelling people aged ≥40 years without a prior history of cardiovascular disease in Ontario, Canada. Neighborhood-level income was measured in quintiles from quintile 1 (lowest) to quintile 5 (highest), and immigrants were defined as those born outside of Canada who moved to Canada after 1985. We estimated the association between neighborhood-level income and the rate of incident cardiovascular events (hospitalization for stroke or myocardial infarction, or cardiovascular death) using multivariable cause-specific hazards models and added an interaction term to see if the association varies by immigration status. The absolute difference in the rate of cardiovascular events across income quintiles was less pronounced in immigrants than in long-term residents: age- and sex-adjusted rate per 1000 person-years in quintile 1 versus quintile 5: 5.69 versus 4.10 in immigrants and 8.37 versus 5.87 in long-term residents. In adjusted models, the interaction between immigration status and neighborhoodl evel was significant ( P <0.001). The hazard of cardiovascular events declined with increasing income among long-term residents (hazard ratio [HR] interaction <0.001). The hazard of cardiovascular events declined with increasing income among long-term residents (hazard ratio [HR] Q1vsQ5 , 1.46 to HR Q4vsQ5 , 1.10) and immigrants, albeit with a smaller gradient (HR Q1vsQ5 , 1.43 to HR Q4vsQ5 , 1.20)., Conclusions: The association between neighborhood-level income and cardiovascular disease incidence varies by immigration status. Understanding the social and structural factors associated with residing in low-income neighborhoods can help with the development of prevention programs that improve health for all.

Background: Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long-term clinical outcomes after acute ischemic stroke., Methods and Results: We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all-cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log-corin was associated with a 21% (95% CI, 11-30), 16% (95% CI, 6-26), and 12% (95% CI, 3-21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all-cause mortality and cardiovascular events, as shown by C-statistics (all P <0.05)., Conclusions: Serum soluble corin was associated with decreased risks of long-term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.

Aims: There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 diabetes, diagnosed before age 18, and long‐term morbidity and mortality, and to investigate whether cognitive ability plays a role in long‐term morbidity and mortality risk. Methods: In a Swedish cohort, 120 men with type 1 diabetes and 469 without type 1 diabetes were followed between 18 and 77 years of age as regards morbidity and mortality outcomes, and impact of cognitive ability at military conscription for the outcomes. In Cox regression analyses and Kaplan‐Meier analyses with log‐rank tests, associations between diabetes and cognitive ability respectively, and outcomes (mortality, cardiovascular morbidity and diabetes complications) were investigated. Results: Men with type 1 diabetes suffered from dramatically higher mortality (HR 4.62, 95% CI: 3.56–5.60), cardiovascular mortality (HR 5.60, 95% CI: 3.27–9.57), and cardiovascular events (HR 3.97, 95% CI: 2.79–5.64) compared to men without diabetes. Higher cognitive ability at military conscription was associated with lower mortality in men without diabetes, but was not associated with any outcome in men with diabetes. Conclusions: In this historical cohort study with 60 years of follow‐up time and a less effective treatment of diabetes than today, mortality rates and cardiovascular outcomes were high for men with type 1 diabetes. Morbidity or mortality did not differ between those that had low to normal or high cognitive ability among men with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events. Objectives: The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol. Methods: A population‐based historical cohort of U.S. veterans receiving prescription NSAIDs (1,681,609) versus NSAIDs plus misoprostol (5972 misoprostol users) was followed for 5 years. In an intent‐to‐treat analysis, NSAID and NSAID plus misoprostol groups were compared using propensity score‐weighted Poisson regression models to estimate incident rate ratio (IRR) and Cox regression to estimate hazard ratio (HR). Results: The most prescribed NSAIDs were diclofenac and ibuprofen. The mean follow‐up was 35.2 ± 14.5 months. There were 439 total cardio‐renal events (5.62/1000 patient‐months) in the NSAID group and 419 patients (5.01/1000 patient‐months) in the NSAID plus misoprostol group (Hazard Ratio (HR): 0.89; 95% confidence interval [CI]: 0.78–1.019; p = 0.09). The risk of cardiovascular event was lower in the NSAID plus misoprostol group (HR: 0.56; 95% CI: 0.34–0.93; p < 0.0001). Cerebrovascular event rates were lower in the NSAID plus misoprostol group (HR: 0.74; 95% CI: 0.60–0.94, p < 0.0001) and for renal (HR: 0.67; 95% CI: 0.49–0.89, p < 0.0001) events. All‐cause mortality rate was not different between the two groups (HR: 1.05; 95% CI: 0.88–1.25, p = 0.61). Conclusion: Compared with NSAID use alone, the concomitant use of NSAID plus misoprostol is associated with a reduced risk of NSAID‐induced cardiovascular, cerebrovascular, and renal adverse events. These data support the development of a safer NSAID when combined with misoprostol. [ABSTRACT FROM AUTHOR]

The associations of blood pressure components with cardiovascular risks and death remain unclear, and the definition of wide pulse pressure (PP) is still controversial. Using data from 1257 participants without a history of cardiovascular disease, who were followed for 4.84 years, we performed multivariable Cox regression analyses to assess how systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP contribute to risks of cardiovascular events and all‐cause death. Among all participants, SBP and PP were significantly associated with the risks of cardiovascular events and all‐cause death (all p <.05). DBP was not significantly associated with the risk of all‐cause death; rather, it was only associated with a marginally significant 1% increased risk for cardiovascular events (p = 0.051). In participants aged < 65 years, DBP was significantly associated with a 3% increased risk for cardiovascular events (hazard ratio [HR]: 1.03, 95% confidence interval [95% CI]: 1.01–1.06). The association between PP and cardiovascular events appeared to be J‐shaped in comparison to participants with the lowest‐risk PP (50–60 mmHg), with adjusted HRs of 1.71 (95% CI: 1.03–2.85), 1.63 (95% CI: 1.00–2.68), and 2.13 (95% CI: 1.32–3.43) in the <50, 60.0–72.5, and ≥72.5 mmHg subgroups, respectively. The optimal cutoff points of a wide PP for predicting the risks of cardiovascular events and all‐cause death were 70.25 and 76.25 mmHg, respectively. SBP and PP had a greater effect on cardiovascular risk, whereas DBP independently influenced cardiovascular events in middle‐aged participants. Considerable PP alterations should be avoided in antihypertensive treatment. [ABSTRACT FROM AUTHOR]

Background: Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods: In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow‐up time was 6.4 years (interquartile range 3.7–9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow‐up, that is, living donor KT, deceased donor KT, or dialysis. Results: Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12–9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10‐year mortality in the dialysis group was 33.6 (95% CI, 10.0–113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion: Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT. [ABSTRACT FROM AUTHOR]

Study Objective: To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression. Design: Retrospective cohort study. Data Source: IBM MarketScan® commercial claims database and Medicare Supplemental claims database from 2007 to 2019. Patients Patients aged 18 years or older with stable treated hypertension and depression who newly initiate either serotonin norepinephrine reuptake inhibitors or SSRIs. Intervention: Serotonin norepinephrine reuptake inhibitors versus SSRIs. Measurements and Main Results: The primary outcomes were: (1) TI (first occurrence of antihypertensive regimen augmentation or dose escalation); (2) MACE (first occurrence of stroke or acute myocardial infarction). Baseline risk between the two groups was balanced via 1:1 propensity score (PS) matching. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). After 1:1 PS matching, we included 19,160 patients in the study cohort (mean age: 52 years, 62% females) of which 9580 initiated serotonin norepinephrine reuptake inhibitors and 9580 initiated SSRIs. Patients who initiated serotonin norepinephrine reuptake inhibitors had 15 MACE events (incidence rate per 1000 person‐years [IR], 3.9) and 1675 TI events (IR, 540.2), compared with 17 MACE events (IR, 4.0) and 1774 TI events (IR, 518.5) in the SSRI group. The risk of TI (aHR: 1.01, [95% CI: 0.94, 1.08]) and MACE (aHR: 0.98, [95% CI: 0.49, 1.96]) did not differ among patients initiated serotonin norepinephrine reuptake inhibitors versus SSRIs. Conclusions: Among patients with stable hypertension and depression, initiation of serotonin norepinephrine reuptake inhibitors had a similar risk of antihypertensive TI and MACE compared to initiation of SSRIs. Future study with a larger sample size is needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background and Aims: Continuous scoring systems were developed versus traditional dichotomous approaches to define metabolic syndrome. The current study was carried out to evaluate the ability of scoring systems to predict fatal and nonfatal cardiovascular events. Materials and Methods: The data of 5147 individuals aged 18 years or more obtained from a population‐based cohort study were analyzed. The occurrence of atherosclerotic cardiovascular disease (ASCVD) in the period of 7 years follow‐up was considered as the associated outcome. Joint Interim Statement (JIS) definition, as a traditional definition of metabolic syndrome (MetS), and two versions of MetS scoring systems, based on standardized regression weights from structural equation modeling (SEM) and simple method for quantifying metabolic syndrome (siMS) were considered as potential predictors. Results: The scoring systems, particularly, based on SEM, were observed to have a significant association with composite cardiovascular events (HR = 1.388 [95% CI = 1.153–1.670], p =.001 in men and HR = 1.307 [0.95% CI = 1.120–1.526] in women) in multiple Cox proportional hazard regression analyses, whereas the traditional definition of MetS did not show any significant association. While both two scoring systems showed acceptable predictive abilities for cardiovascular events in women (MetS score based on SEM: area of under curve [AUC] = 0.7438 [95% CI = 0.6195–0.7903] and siMS: AUC = 0.7207 [95% CI = 0.6676–0.7738]), the two systems were not acceptable for identifying risk in men. Conclusion: Unlike the dichotomous definition of MetS, the scoring systems showed an independent association with cardiovascular events. Scoring systems, particularly those based on SEM, may be useful for the prediction of cardiovascular events in women. [ABSTRACT FROM AUTHOR]

We propose a modified self‐controlled case series (SCCS) method to handle both event‐dependent exposures and high event‐related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID‐19 vaccines. Event‐dependence of vaccinations, and high event‐related mortality, are likely to arise in other SCCS studies of COVID‐19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular benefit from n‐3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear. Objectives: To assess changes in EPA and DHA serum concentrations during n‐3 PUFA supplementation and their association with incident cardiovascular events. Methods: In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all‐cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new‐onset atrial fibrillation (AF). Results: EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on‐treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high‐density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on‐treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75–0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07–1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66–1.06] for MACE and 1.39 [0.90–2.13] for AF). Conclusion: Greater on‐treatment increases in EPA were associated with lower risk of MACE and higher risk of new‐onset AF. These data suggest that the cardiovascular effects of increasing n‐3 PUFA levels through supplements are complex, involving both potential benefits and harm. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF). Methods: In this sub‐analysis of the HIJ‐PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut‐off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all‐cause death, non‐fatal myocardial infarction, non‐fatal stroke, and hospitalization for heart failure. Results: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut‐off point of 34 mL/m2. Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m2 group. Over a median follow‐up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m2 and LAVI ≥ 34 mL/m2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m2 (hazard ratio: 2.93; 95% confidence interval: 1.19–7.22; P =.014). The tendency was similar after adjusting for several confounders (P =.025). Conclusion: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events. Clinical trial registration: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742). [ABSTRACT FROM AUTHOR]

Background: Although living alone versus with others is a key social element for cardiovascular prevention in diabetes, evidence is lacking about whether the benefit of intensive glycemic and blood pressure (BP) control differs by living arrangements. We thus aim to investigate heterogeneity in the joint effect of intensive glycemic and BP control on cardiovascular events by living arrangements among participants with diabetes., Methods and Results: This study included 4731 participants with diabetes in the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial. They were randomized into 4 study arms, each with glycated hemoglobin target (intensive, <6.0% versus standard, 7.0-7.9%) and systolic BP target (intensive, <120 mm Hg versus standard <140 mm Hg). Cox proportional hazard models were used to estimate the joint effect of intensive glycemic and BP control on the composite cardiovascular outcome according to living arrangements. At a mean follow-up of 4.7 years, the cardiovascular outcome was observed in 445 (9.4%) participants. Among participants living with others, intensive treatment for both glycemia and BP showed decreased risk of cardiovascular events compared with standard treatment (hazard ratio [HR], 0.68 [95% CI, 0.51-0.92]). However, this association was not found among participants living alone (HR, 0.96 [95% CI, 0.58-1.59]). P for interaction between intensive glycemic and BP control was 0.53 among participants living with others and 0.009 among those living alone ( P value for 3-way interaction including living arrangements was 0.049)., Conclusions: We found benefits of combining intensive glycemic and BP control for cardiovascular outcomes among participants living with others but not among those living alone. Our study highlights the critical role of living arrangements in intensive care among patients with diabetes.

Background: The aim of this study was to assess how early-adulthood body mass index (BMI) and waist circumference (WC) relate to long-term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden., Methods and Results: A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF-optimal subgroup was also defined, with blood pressure<120/80 mm Hg, fasting glucose <100 mg/dL, total cholesterol <200, low-density lipoprotein cholesterol <130, and women with high-density lipoprotein cholesterol ≥50 mg/dL. Coronary artery calcification, carotid intima-media thickness, left ventricular mass, left ventricular ejection fraction, longitudinal peak systolic strain, and diastolic function were assessed in midlife. Cox regression was used to calculate hazard ratios of BMI and WC for all-cause death and CVD events. Logistic regression was used to estimate odds ratios for subclinical CVD. Over 33.9 years (median follow-up), 5.2% (n=105) died, and 2.6% (n=52) had CVD events. Each 1-SD BMI increase was associated with 27% (95% CI, 1.10-1.47), 24% (1.08-1.43), 42% (1.20-1.68), 28% (1.05-1.57), 51% (1.20-1.90), and 49% (1.10-2.02) higher odds of coronary artery calcification presence, increased carotid intima-media thickness, left ventricular hypertrophy, reduced left ventricular ejection fraction, low longitudinal peak systolic strain, and diastolic dysfunction, respectively, in the CVRF-low group. Generally, similar associations were found for WC and in the CVRF-optimal subgroup. No significant associations between BMI and WC with CVD and death were found., Conclusions: Elevations in BMI and WC among young low-risk individuals, even within the nonobesity range, are associated with midlife cardiovascular health.

Background: Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow-up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study., Methods and Results: The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack-years of smoking history. Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47-2.22]; with CVD: HR, 1.92 [95% CI, 1.51-2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events., Conclusions: COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Background: We aim to investigate prognostic effects of carotid strain (CS) and strain rate (CSR) in hypertension. Methods: We prospectively recruited 120 patients being treated for hypertension (65.8 ± 11.8 years, 58% male) in this observational study. Peak circumferential CS and peak CSR after ejection were identified using two‐dimensional speckle tracking ultrasound. Major cardiovascular events were any admission for stroke, acute coronary syndrome, and heart failure. Results: After a mean follow‐up period of 63.6 ± 14.5 months, 14 (12%) patients had cardiovascular events. Age (75.3 ± 9.2 vs 64.6 ± 11.6 years; p = 0.001), systolic blood pressure (131.8 ± 15.5 vs 143.1 ± 16.6 mm Hg; p = 0.021), diastolic blood pressure (74.6 ±11.4 vs 82.1 ± 12.2 mm Hg; p = 0.039), use of diuretics (71 vs 92%; p = 0.014), carotid CS (2.17 ± 1.02 vs 3.28 ± 1.14 %; p = 0.001), and CSR (.28 ±.17 vs.51 ±.18 1/s; p < 0.001) were significantly different between the patients who did and did not reach the end‐points. Multivariate Cox regression analysis controlling for age, systolic blood pressure, diastolic blood pressure, and use of diuretics showed that CS (HR.425, 95%CI.223–.811, p = 0.009) and CSR (HR.001, 95%CI.000–.072, p = 0.001) were independent predictors for cardiovascular events. Conclusion: In conclusions, decreased CS and CSR were associated with cardiovascular events in hypertension. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The relationship between glycated hemoglobin (HbA1c) and cardiovascular events in older adults was investigated using a Japanese administrative medical database. Materials and Methods: Anonymized medical data on patients with diabetes mellitus aged ≥65 years for the period from January 2010 to December 2019 were extracted from the EBM Provider database. The primary end‐point was a composite of cardiovascular events, whereas the other end‐points included severe hypoglycemia and fracture. The association between cardiovascular events and HbA1c at the index date (i.e., approximately 10 months after initial diabetes mellitus diagnosis) was evaluated using the Cox proportional hazards model. Results: Among the 3,186,751 patients in the database, 3,946 older adults with diabetes mellitus were eligible for inclusion and were subsequently grouped according to HbA1c quartiles at the index date. Cardiovascular events occurred in 142 patients. Patients with HbA1c in the highest quartile had significantly higher risk of hospitalization for cardiovascular disease than those with HbA1c in the lowest quartile (hazard ratio 1.948; 95% confidence interval 1.252–3.031, P = 0.003). However, the events risk was similar across subgroups with HbA1c <7.2%. The incidence of hypoglycemia and fracture was not significantly associated with the level of glycemic control. Conclusions: Among older adults with diabetes mellitus, those with poor glycemic control were at higher risk for cardiovascular events compared with those with better glycemic control. However, strict glycemic control had no effect on cardiovascular risk in patients with HbA1c <7.2%. [ABSTRACT FROM AUTHOR]

Aims: Whether to continue or stop mineralocorticoid receptor antagonists (MRA) after an episode of hyperkalaemia is a challenge in clinical practice. While stopping MRA may prevent recurrent hyperkalaemias, it deprives patients of their cardioprotection. We here assessed the association between stopping vs. continuing MRA therapy after hyperkalaemia and the subsequent risks of adverse health events. Methods and results: Observational study from the Stockholm CREAtinine Measurements (SCREAM) project 2006–2018. We identified patients initiating MRA and surviving a first‐detected episode of hyperkalaemia (plasma potassium >5.0 mmol/L). Using target trial emulation methods, we assessed the association between stopping vs. continuing MRA within 6 months after hyperkalaemia and subsequent outcomes. The primary outcome was the composite of hospital admission with heart failure, stroke, myocardial infarction, or death. The secondary outcome was occurrence of another hyperkalaemia event. Among 39 518 patients initiating MRA, we identified 7366 who developed hyperkalaemia. Median age was 76 years, 45% were women and 69% had a history of heart failure. Following hyperkalaemia, 2222 (30%) discontinued treatment. Compared with continuing MRA, stopping therapy was associated with a lower 2‐year risk of recurrent hyperkalaemia [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.72–0.79], but a higher risk of the primary outcome (HR 1.10, 95% CI 1.06–1.14). Similar results were observed in patients with heart failure, after censoring when treatment decision was changed, and across pre‐specified subgroups. Conclusions: Stopping MRA after an episode of hyperkalaemia was associated with reduced risk for recurrent hyperkalaemia, but higher risk of death or cardiovascular events. Recurrent hyperkalaemia was common in either strategy. [ABSTRACT FROM AUTHOR]

Background: The stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is particularly important. Remimazolam is a new type of benzodiazepine drug, with supposed advantages of rapid induction, rapid recovery, stable hemodynamics, and mild respiratory inhibition. Aim: To evaluate the effect of remimazolam anesthesia induction on hemodynamics in patients undergoing valve replacement surgery. Methods: This randomized, double-blind, controlled trial enrolled consecutive patients undergoing mitral valve replacement (MVR)/aortic valve replacement (AVR)/ double-valve replacement (DVR) surgery on cardiopulmonary bypass (CPB). The study was conducted according to the Consolidated Standards of Reporting Trials statement. Participants were randomly assigned to receive either remimazolam or propofol induction of 30 patients each. All patients, data collectors, and data analyzers were blinded to the group allocation. The primary outcomes were the fluctuations in hemodynamic parameters (the difference of maximum or minimum heart rate to baseline, ▲HR, the difference of maximum or minimum mean arterial pressure to baseline, ▲MAP), the occurrence of cardiovascular events (hypotension, severe bradycardia), and the cumulative norepinephrine doses used per patient, averaged per group during induction. The secondary outcomes were hemodynamic parameters (heart rate, HR, mean arterial pressure, MAP, bispectral index, BIS, plasma lactic acid, Lac, and blood glucose, Glu values). Results: A total of 60 patients with heart valve replacement were included in the final analysis, with 30 patients in each group. The ▲MAP was significantly lower in the remimazolam group than in the propofol group during induction (p < .05). The incidences of hypotension and the cumulative norepinephrine doses used per patient, averaged per group during induction were significantly lower in the remimazolam group than in the propofol group (p < .05). Conclusion: Remimazolam may be safe and effective for induction and may as an alternative to propofol during anesthesia induction in patients undergoing valve replacement surgery. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) usually rise from being asleep to awake, which is named the morning blood pressure surge (MBPS). Researches have reported that elevated MBPS was related with CV events, incident CKD in hypertensive patients. However, there have been no studies that have investigated the association between MBPS and renal or heart outcomes in patients with CKD and hypertension, in these patients, the MBPS is much lower because of high prevalence of night hypertension and reduced BP dipping. In this prospective two-center observational study, we enrolled patients with CKD and hypertension and the 24 h ambulatory blood pressure monitoring (ABPM) was conducted in all patients. Time to total mortality, CKD progression and CV events was recorded; Finally, a total of 304 patients were enrolled and 94 (30.9%) of them had elevated MBPS. After a follow-up for median 30 months, 23 (7.6%), 34 (11.2%), and 95 (31.3%) patients occurred death, CKD progression and new-onset CV events, respectively. The Cox regression analysis suggested the elevated MBPS was a strong predictor of CKD progression (HR 2.35, 95%CI 1.2 -4.63, p = .013), independent of morning BP, while no associations were found between elevated MBPS and CV events (HR 1.02, 95%CI 0.66 -1.57), as well as death (HR 1.08, 95%CI 0.46 -2.55). In conclusion, we provided the first evidence that elevated MBPS was an important risk factor of CKD progression in patients with CKD and hypertension. Appropriate evaluation and management of MBPS may be helpful to postpone CKD progression. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to assess the association between left ventricular mass index (LVMI) and cardiovascular events in patients with acute coronary syndrome (ACS) under standard ACS management. Methods and results: This study is the sub‐analysis of the HIJ‐PROPER study. A total of 299 patients who had echocardiographic LVMI data were included in the current analysis. The participants were divided into four groups according to the LVMI quartile [quartile 1 (Q1), 77 (25.8%); quartile 2 (Q2), 73 (24.4%); quartile 3 (Q3), 74 (24.7%); and quartile 4 (Q4), 75 (25.1%)]. The incidence of cardiovascular events was compared among the four groups. The primary endpoint was defined as the composite endpoint of all‐cause death, non‐fatal myocardial infarction, non‐fatal stroke, and hospitalization for heart failure. Mean LVMI in the four groups was 68.1±8.6, 86.2±3.8, 101.1±4.9, and 126.0±18.5 g/m2, respectively. The primary endpoint was noted in 4, 4, 7, and 14 patients in Q1, Q2, Q3, and Q4, corresponding to an incidence of 5.2%, 5.5%, 9.5%, and 18.7%, respectively (p = 0.03 for difference among four groups). The cumulative incidence of the primary endpoint was significantly higher in patients in Q4 than in those in Q1 and Q2 [hazard ratio (HR) 3.75; 95% confidence interval (CI), 1.23–11.4; p = 0.02 for Q4 vs Q1; HR 3.43; 95% CI, 1.13–10.4; p = 0.03 for Q4 vs Q2]. This tendency was noted even after adjusting for patient characteristics and echocardiography parameters (p = 0.039 for Q4 vs Q1). Conclusion: Elevated LVMI was associated with increased cardiovascular events in patients with ACS under standard management. Adequately powered studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

Background: The identification of novel predictors of poor outcome may help stratify cardiovascular risk. Aim was to evaluate the individual contribution of blood cell count parameters, as well as their clustering, on the risk of death and cardiovascular events over the long term in the population‐based Malmö Diet and Cancer Study cohort. Methods: In 30,447 individuals (age 57 ± 8 years), we assessed the incidence of all‐cause death (primary endpoint) and major adverse cardiovascular events (MACE, secondary outcome measure) according to absence or presence of one, two and three factors at baseline out of the following: anaemia, leukocytosis and thrombocytosis. Median follow‐up was 16 years. Results: The percentages of all‐cause death were 19.5% in individuals without factors, 21.3% in those with one factor, 27.4% with two and 46.4% with three (log‐rank test P <.001). The crude incidence of MACE was 28.0%, 29.2%, 35.5% and 57.1%, respectively (log‐rank test P <.001). At multivariate analysis, we found a stepwise increase in overall mortality with increasing number of prevalent factors (one factor: HR 1.23, 95% CI 1.14‐1.31, P <.001; two factors: 1.61, 1.37‐1.89, P <.001; three factors: 2.69, 1.44‐5.01, P =.002, vs no factor). Similar findings were observed for the incidence of MACE (one factor: adjusted HR 1.18, 95% CI 1.11‐1.24, P <.001; two factors: 1.52, 1.33‐1.76, P <.001; three factors: 2.03, 1.21‐3.67, P <.001, vs no factor). Conclusions: The easily assessable clustering of anaemia, leukocytosis and thrombocytosis heralds higher incidence of death and adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common cardiac rhythm disturbance and leads to morbidity and mortality. Peripheral artery disease (PAD) is associated with atherosclerotic risk factors and always classified as a vascular disease and deemed to be a bad complication of AF. In patients with AF, the risk and prognostic value of PAD have not been estimated comprehensively. Hypothesis: PAD is associated with all‐cause mortality, cardiovascular (CV) mortality, and other outcomes in patients with AF. Methods: We searched PubMed, Embase, and Cochrane Library databases for prospective studies published before April 2021 that provided outcomes data on PAD in confirmed patients with AF. Heterogeneity was estimated using the I2 statistic. The fixed‐effects model was used for low to moderate heterogeneity studies, and the random‐effects model was used for high heterogeneity studies. Results: Eight prospective studies (Newcastle‐Ottawa score range, 7–8) with 39 654 patients were enrolled. We found a significant association between PAD and all‐cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.25–1.62; p <.001), CV mortality (HR, 1.64; 95% CI, 1.32–2.05; p <.001) and MACE (HR, 1.75; 95% CI, 1.38–2.22; p <.001) in patients with AF. No significant relationship was found in major bleeding (HR, 1.22; 95% CI, 0.95–1.57; p = 0.118), myocardial infarction (MI) (HR, 2.07; 95% CI, 1.17–3.67; p =.038), and stroke (HR, 1.14; 95% CI, 0.87–1.50, p = 0.351). Conclusions: PAD is associated with an increased risk of all‐cause mortality, CV mortality, and MACE in patients with AF. However, no significant association was found with major bleeding, MI, and stroke. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of cardiovascular events among cancer patients with bone metastases is poorly understood. We examined rates of cardiovascular events among cancer patients with bone metastases and mortality following such events. Methods: Using Danish health registries, we identified all Danish cancer patients diagnosed with bone metastases (1994–2013) and followed them from bone metastasis diagnosis. We computed incidence rates (IR) per 100 person‐years and cumulative incidence for first‐time inpatient hospitalization or outpatient clinic visit for cardiovascular events, defined as myocardial infarction, ischemic stroke, or venous thromboembolism (VTE). We also analyzed all‐cause mortality rates including cardiovascular events as time‐varying exposure with adjustment for age, sex, and Charlson Comorbidity Index score. All analyses were performed overall and stratified by cancer type (prostate, breast, lung, and other). Results: We included 23,113 cancer patients with bone metastases. The cumulative incidence of cardiovascular events was 1.3% at 30 days, 3.7% at 1 year, and 5.2% at 5 years of follow‐up. The highest IR was observed for VTE, followed by ischemic stroke and myocardial infarction, both overall and by cancer types. Lung cancer patients with bone metastases had the highest incidence of cardiovascular events followed by prostate and breast cancer. Occurrence of any cardiovascular event was a strong predictor of death (5 years following the event, the adjusted hazard ratio was 1.8 [95% confidence interval: 1.7–1.9]). Conclusion: Cancer patients with bone metastases had a substantial risk of developing cardiovascular events, and these events were associated with a subsequent increased mortality. Our findings underscore the importance of continuous optimized prevention of and care for cardiovascular disease among cancer patients with bone metastases. [ABSTRACT FROM AUTHOR]