Risk Of Cardiovascular Events Research Articles

Triglyceride-glucose related indices as predictors for major adverse cardiovascular events and overall mortality in type-2 diabetes mellitus patients

BACKGROUND Recent studies have indicated that triglyceride glucose (TyG)-waist height ratio (WHtR) and TyG-waist circumference (TyG-WC) are effective indicators for evaluating insulin resistance. However, research on the association in TyG-WHtR, TyG-WC, and the risk and prognosis of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) cases are limited. AIM To clarify the relation in TyG-WHtR, TyG-WC, and the risk of MACEs and overall mortality in T2DM patients. METHODS Information for this investigation was obtained from Action to Control Cardiovascular Risk in Diabetes (ACCORD)/ACCORD Follow-On (ACCORDION) study database. The Cox regression model was applied to assess the relation among TyG-WHtR, TyG-WC and future MACEs risk and overall mortality in T2DM cases. The RCS analysis was utilized to explore the nonlinear correlation. Subgroup and interaction analyses were conducted to prove the robustness. The receiver operating characteristic curves were applied to analysis the additional predicting value of TyG-WHtR and TyG-WC. RESULTS After full adjustment for confounding variables, the highest baseline TyG-WHtR cohort respectively exhibited a 1.353-fold and 1.420-fold higher risk for MACEs and overall mortality, than the lowest quartile group. Similarly, the highest baseline TyG-WC cohort showed a 1.314-fold and 1.480-fold higher risk for MACEs and overall mortality, respectively. Each 1 SD increase in TyG-WHtR was significantly related to an 11.7% increase in MACEs and a 14.9% enhance in overall mortality. Each 1 SD increase in TyG-WC corresponded to an 11.5% in MACEs and a 16.6% increase in overall mortality. Including these two indexes in conventional models significantly improved the predictive power for MACEs and overall mortality. CONCLUSION TyG-WHtR and TyG-WC were promising predictors of MACEs and overall mortality risk in T2DM cases.

Continuum of glucose and bone metabolism impairment across autonomous cortisol secretion: A cross-sectional study

BACKGROUND Autonomous cortisol secretion (ACS) is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events. AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system (CGMS) and dual-energy X-ray absorptiometry (DXA). METHODS Patients diagnosed with ACS, including Cushing syndrome, mild ACS (MACS), and nonfunctional adrenal incidentaloma (NFAI), were recruited for this study. Glucose variability and glycemic status were assessed using CGMS. Regional bone mineral content (BMC), bone mineral density (BMD), and bone area (BA) were evaluated using DXA. CGMS- and DXA-derived parameters were compared across the subgroups of ACS. Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion, measured by cortisol after 1 mg overnight dexamethasone suppression test (DST) or 24-hour urine free cortisol (24h UFC), and CGMS- or DXA-derived parameters. RESULTS A total of 64 patients with ACS were included in this study: 19 with Cushing syndrome, 11 with MACS, and 34 with NFAI. Glucose variability, time above range (TAR), and time in range (TIR) along with specific areal BMC, BMD, and BA, differed significantly between groups of Cushing syndrome and NFAI. A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC. By contrast, TIR, along with regional BMC, BMD, and BA, were negatively correlated with varying degrees of cortisol secretion. CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome. Prompt attention should be given to these patients with ACS, especially those with mild hormone secretion. Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.

Should Calcium Supplementation be Abandoned in Patients With Calcinosis Cutis?

Calcinosis cutis, characterized by the pathological deposition of insoluble calcium salts in the skin, is associated with several disease entities, particularly autoimmune conditions such as scleroderma and dermatomyositis. Lesions of calcinosis are often painful, prone to ulceration, and significantly impair quality of life. Despite the clinical impact, no effective treatments have been established to date, making prevention of this condition a critical priority. In this narrative review, we explore the evidence suggesting that calcium supplementation may contribute to skin calcification. Calcium supplements have been demonstrated to transiently elevate plasma calcium levels, potentially promoting dystrophic tissue calcification-a process that may be exacerbated in a context of magnesium and vitamin K2 deficiencies. Furthermore, calcium supplementation has been associated with an increased risk of adverse cardiovascular events; this concern is particularly relevant in patients with autoimmune diseases who already face elevated cardiovascular comorbidity. Notably, there is no robust evidence supporting the efficacy of calcium supplementation in preventing osteoporosis. Instead, sufficient dietary intake of calcium and protein, along with the supplementation of micronutrients critical for calcium homeostasis (magnesium, zinc, vitamin D3, and vitamin K2), should be considered as alternatives to calcium supplementation.

Association of ceramide risk scores with rheumatoid arthritis: a FINRISK population-based cohort study

ObjectivesThis study aimed to explore the association between lipid-based Cardiovascular Event Risk Tests (CERT1 and CERT2), including ceramides (Cer) and phosphatidylcholine (PC) lipid species, and rheumatoid arthritis (RA), an inflammatory...

Impact of diabetes on risk of major adverse cardiovascular events associated with lipoprotein(a) levels in patients with established atherosclerotic cardiovascular disease

Abstract Aims Lipoprotein(a) [Lp(a)] is an emerging risk factor for major adverse cardiovascular events (MACE). However, evidence on MACE risk according to Lp(a) level in atherosclerotic patients is insufficient, and more data is needed about whether type 2 diabetes (T2DM) additionally contributes to this risk. We aimed to investigate the association between Lp(a) and MACE in atherosclerotic patients and compare the magnitude of Lp(a)-MACE association in the patients with and without T2DM. Methods and results Using a retrospective cohort study of atherosclerotic patients with and without T2DM who were screened for Lp(a) between 1 January 2000 to 31 December 2020, we estimated the risk of MACE according to Lp(a) level stratified by quintiles and compared the difference in magnitude of Lp(a)-MACE association according to presence of T2DM with partial likelihood ratio test. The study included 25 826 patients with established atherosclerotic cardiovascular disease, of whom 7535 had T2DM (29.2%) and 18 291 did not (70.8%). During 160 174 person-years (PY) of follow-up, a total of 4836 MACE were observed. Compared to the lowest quintile (Q) of Lp(a) levels, multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for MACEs across Q2 to Q5 were 1.10 (95% CI: 0.94–1.30), 0.98 (95% CI: 0.83–1.16), and 1.25 (95% CI: 1.06–1.46), 1.29 (95% CI: 1.10–1.51) in patients with T2DM, and 0.99 (95% CI: 0.88–1.12), 1.10 (95% CI: 0.98–1.23), 1.01 (95% CI: 0.90–1.13), and 1.13 (95% CI: 1.01–1.27) for those without T2DM. The strength of Lp(a)-MACE association was stronger among the patients with T2DM (P < 0.001). Conclusion Among atherosclerotic patients with and without T2DM, elevated Lp(a) level was significantly associated with a higher risk of MACE. Compared to those without T2DM, the patients with T2DM showed an excess MACE risk, suggesting the need for clinical interventions concerning both Lp(a) level and glycemic control.

Gut microbiota: an emerging target connecting polycystic ovarian syndrome and insulin resistance

Polycystic ovary syndrome (PCOS) is a highly heterogeneous metabolic disorder, with oligomenorrhea and hirsutism as patients’ primary complaints. Hyperinsulinemia is a crucial pathophysiological mechanism in the development of PCOS, with 50-70% of patients exhibiting insulin resistance (IR). This condition not only exacerbates ovulatory dysfunction but also leads to various adverse metabolic outcomes, such as dyslipidemia and diabetes, and increases the risk of cardiovascular events both before and after menopause. Gut microbiota is a microbial community within the host that possesses significant metabolic potential and is shaped by external environmental factors, the neuro-immune network, and metabolism. Recent studies have shown that gut microbiota dysbiosis is closely related to the development and progression of PCOS. Despite the growing recognition of the potential role of gut microbiota in the pathogenesis and treatment of PCOS, its clinical application remains in its infancy. Currently, most clinical guidelines and expert consensus still emphasize traditional therapeutic approaches, such as hormonal treatments, lifestyle modifications, and insulin sensitizers. However, accumulating evidence suggests that gut microbiota may influence the metabolic and reproductive health of PCOS patients through various mechanisms. Therefore, understanding the role of gut microbiota between PCOS and IR is essential. This review describes the changes in the gut microbiota of IR-PCOS patients, examines the potential mechanisms by which the gut microbiota contributes to IR in PCOS patients, and updates the evidence supporting the gut microbiota as a potential metabolic regulatory target in IR-PCOS. In summary, gut microbiota dysbiosis may be involved in the development and progression of IR in PCOS patients, and improving gut microbiota may offer metabolic stability benefits.

Medication time of metformin and sulfonylureas and incidence of cardiovascular diseases and mortality in type 2 diabetes: a pooled cohort analysis

The effect of duration of medication with metformin and sulfonylurea (SUs) on cardiovascular diseases (CVD) and mortality events by duration of type 2 diabetes (DM) is unclear. This study aimed to investigate the effect of duration of treatment with metformin and SUs on CVD and mortality events based on DM duration in newly diagnosed DM patients. Data from three prospective cohorts of Tehran Lipid and Glucose Study (TLGS), Multi-Ethnic Study of Atherosclerosis (MESA), and Atherosclerosis Risk in Communities (ARIC) including 4108 newly diagnosed type 2 diabetes individuals (mean age, 59.4 ± 0.66 years) were pooled. Exposure was defined as the duration of metformin alone, SUs alone, and a combination of both since drug initiation. The Cox proportional hazards (CPH) model adjusted for confounders, including statin, aspirin, and anti-hypertensive, was used to estimate the hazard ratio (HR) (95% CI) for the outcomes. Cumulative exposure for metformin, SUs, aspirin, statin, and anti-hypertensive medication was calculated using the same method. The median follow-up was 20.33 ± 0.45 years. Cardiovascular events, all-cause mortality (ACM), and CVD mortality occurred in 767, 913, and 439 newly diagnosed DM patients, respectively. Metformin alone reduced the hazard of cardiovascular events, ACM, and CV-mortality by 7%, 4%, and 6%, respectively, for each year of use, respectively (p < 0.05); the corresponding values for SUs alone were 4%, 3%, and 4%, respectively (p < 0.05). The effect of metformin on reducing cardiovascular events, ACM, and CVD mortality continued until approximately 8, 10, and 5 years after the start of treatment, respectively, and then reached Plato. The effect of SUs on cardiovascular events, ACM, and CVD mortality continued to decline or reach Plato until approximately 6, 5, and 8 years after initiation of therapy and then was ineffective or reversed. The effect of the combination therapy on the reduction of cardiovascular events continued until 11 years after therapy initiation. Among newly diagnosed DM patients, metformin, with and without SUs, was associated with a reduced risk of cardiovascular events, ACM, and CVD mortality for up to about one decade. The combined effect of metformin + sulfonylurea was superior to the single effect of metformin or sulfonylurea alone. The combination therapy of Metformin and SUs can still be used with good safety, especially in the first years of diabetes diagnosis.

The Role of Olive Oil in Cardiometabolic Risk

Olive oil, the primary fat source in the Mediterranean diet (MedDiet), is rich in monounsaturated fatty acids (MUFA), especially oleic acid, which constitutes 70–80% of its composition. Extra-virgin olive oil (EVOO), produced by mechanically pressing olives, is the highest quality olive oil, with an intense flavor and acidity &lt;1%. In contrast, refined olive oil (ROO), a blend of virgin and refined oils, contains fewer antioxidants and anti-inflammatory compounds. EVOO’s health benefits stem largely from its MUFA content, which is linked to reduced risks of cardiovascular disease (CVD), neurodegenerative conditions, and certain cancers. Additionally, EVOO contains minor, but bioactive, components such as polyphenols, tocopherols, and phytosterols, contributing to its oxidative stability, sensory qualities, and health-promoting properties. These include polyphenols, like oleuropein, hydroxytyrosol, and tyrosol, which exhibit anti-inflammatory, cardioprotective, neuroprotective, and anticancer effects. Epidemiological studies suggest an inverse relationship between olive oil intake and CVD, with EVOO-enriched MedDiet interventions showing improved lipid profiles, reduced blood pressure, and lower cardiovascular event risk. The PREDIMED study highlights the significant role of EVOO in reducing cardiometabolic risk. This review explores the impact of EVOO’s chemical components within the MedDiet framework on metabolic variables influencing cardiometabolic health.

Cardiovascular Events During Treatment With Xanthine Oxidoreductase Inhibitors in Patients With Gout and Hyperuricemia in Japan - A JMDC Claims Database Study.

Studies have shown an increased risk of cardiovascular events during treatment with febuxostat vs. allopurinol, but comparative data with another xanthine oxidoreductase inhibitor (XORi), topiroxostat, are lacking. In this retrospective study we compared the incidence of cardiovascular/renal events in Japanese patients with newly diagnosed hyperuricemia and/or gout treated with allopurinol, febuxostat or topiroxostat. Data came from the JMDC Claims Database from September 2013-September 2019. Participants (n=24,112, age ≥20 years, ≥93% male) were diagnosed with hyperuricemia and/or gout and prescribed XORi treatment in the same month or the following month. Using a Poisson regression model, the adjusted risk (rate ratio [RR]; 95% confidence interval [CI]) of major adverse cardiovascular events was slightly lower with topiroxostat vs. allopurinol (0.63; 0.28-1.41) and febuxostat (0.64; 0.31-1.30). Adjusted risks (RR [95% CI]) for events during treatment with topiroxostat vs. febuxostat and allopurinol were 0.22 [0.10-0.48] and 0.26 [0.11-0.63], respectively, for heart failure, 0.43 [0.27-0.67] and 0.51 [0.31-0.86], respectively, for total cardiovascular events, and 0.46 [0.30-0.69] and 0.62 [0.39-0.98], respectively, for total cardiovascular + renal events. Adjusted risks of atrial fibrillation, heart failure, dialysis, total cardiovascular events, and total cardiovascular + renal events were significantly higher with febuxostat vs. allopurinol. Topiroxostat may provide a better tolerated option for the treatment of hyperuricemia and/or gout in Japanese patients with respect to cardiovascular events.

Early diagnosis of cardiovascular complications in obstructive sleep apnea syndrome and impact of CPAP administration

BackgroundObstructive sleep apnea syndrome (OSAS) is an epidemic disease. The correlation between OSAS and cardiovascular diseases has been explained in numerous approaches. Improving clinical outcome in OSA patients could be achieved with detailed echocardiographic screening using the speckle tracking technique to detect subclinical heart failure. This would raise awareness among OSA patients about the cardiological complications that can arise from OSA. For moderate to severe OSA, the treatment of choice is a continuous positive airway pressure (CPAP). However, there is still debate about whether or not CPAP decreases the risk of cardiovascular events including heart attacks and heart failures.AimPrimary aim: Detection of subclinical echocardiographic disorders in OSA patients through early detection approach and role of CPAP in improving these disorders. Secondary aim: Increase OSA complications awareness, CPAP tolerance for OSA patients, and primary prevention of all serious OSA hazardous.MethodsBetween November 2021 and November 2023, 115 patients suspected of OSA underwent diagnostic PSG, and new techniques of transthoracic echocardiography to early diagnosis of echocardiographic complications, and so 41 patients only had OSA with echocardiographic impairment, underwent 6 months of CPAP therapy, and then were assessed at Tanta University Hospitals’ Chest Medicine Department collaborated with the Cardiology Department of the Faculty of Medicine.ResultsAll the following parameters RV dilatation, RV speckle impairment, pulmonary hypertension, and diastolic dysfunction were the commonest cardiovascular abnormalities which mainly detected among OSA patients which improved after CPAP administration.ConclusionEarly detection of subclinical of echocardiographic OSA complication and early CPAP administration could be beneficial in primary prevention of OSA complications and increase CPAP adherence.

Relationship Between Dipper/Non-Dipper Pattern and Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Geriatric Patients with Hypertension

Objective: Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) are inflammatory markers associated with poor prognoses. Non-dipper hypertension (HT) is linked to a higher risk for cardiovascular events. This study aims to investigate the association between NLR and PLR in geriatric patients with dipper and non-dipper HT. Materials and Methods: A total of 124 geriatric patients with HT were included in the study. Based on ambulatory blood pressure monitoring, patients were categorized into two groups: non-dippers (n=62, Group 1) and dippers (n=62, Group 2). NLR and PLR were calculated by dividing the absolute neutrophil and platelet counts, respectively, by the absolute lymphocyte count. Results: There were no significant differences in sex, age, chronic conditions and smoking between the two groups (p&gt;0.005). The NLR was 1.96±0.66 in group 1 and 1.67±0.68 in group 2 (p:0.005). The PLR was 146±42.2 in group 1 and 115±34.2 in group 2 (p:0.001). The NLR and PLR were significantly higher in non-dippers compared to dippers (p

The Value of Clinical Variables and the Potential of Longitudinal Ultrasound Carotid Plaque Assessment in Major Adverse Cardiovascular Event Prediction After Uncomplicated Acute Coronary Syndrome

Due to the routine use of endovascular revascularization and improved medical therapy, the majority of acute coronary syndrome (ACS) cases now have an uncomplicated course. However, in spite of the currently accepted secondary prevention standards, the residual risk of remote major adverse cardiovascular events (MACEs) after ACS remains high. Ultrasound carotid/subclavian atherosclerotic plaque assessment may represent an alternative approach to estimate the MACE risk after ACS and to control the quality of secondary prevention. Aim: To find the most important clinical predictors of MACEs in contemporary patients with predominantly uncomplicated ACS treated according to the Guidelines, and to study the potential of the longitudinal assessment of quantitative and qualitative ultrasound carotid/subclavian atherosclerotic plaque characteristics for MACE prediction after ACS. Methods: Patients with ACS, obstructive coronary artery disease (CAD) confirmed by coronary angiography, and carotid/subclavian atherosclerotic plaque (AP) who underwent interventional treatment were prospectively enrolled. The exclusion criteria were as follows: death or significant bleeding at the time of index hospitalization; left ventricular ejection fraction (EF) &lt;30%; and statin intolerance. The clinical variables potentially affecting cardiovascular prognosis after ACS as well as the quantitative and qualitative AP characteristics at baseline and 6 months after the index hospitalization were studied as potential MACE predictors. Results: A total of 411 primary patients with predominantly uncomplicated ACS were included; AP was detected in 343 of them (83%). The follow-up period duration was 450 [269; 634] days. MACEs occurred in 38 patients (11.8%): seven—cardiac death, twenty-five—unstable angina/acute myocardial infarction, and six—acute ischemic stroke. In multivariate regression analyses, the most important baseline predictors of MACEs were diabetes (HR 2.22, 95% CI 1.08–4.57); the decrease in EF by every 5% from 60% (HR 1.22, 95% CI 1.03–1.46); the Charlson comorbidity index (HR 1.24, 95% CI 1.05–1.48); the non-prescription of beta-blockers at discharge (HR 3.24, 95% CI 1.32–7.97); and a baseline standardized AP gray scale median (GSM) &lt; 81 (HR 2.06, 95% CI 1.02–4.19). Among the predictors assessed at 6 months, after adjustment for other variables, only ≥ 3 uncorrected risk factors and standardized AP GSM &lt; 81 (cut-off value) at 6 months were significant (HR 3.11, 95% CI 1.17–8.25 and HR 3.77, 95% CI 1.43–9.92, respectively) (for all HRs above, all p-values &lt; 0.05; HR and 95% CI values varied minimally across regression models). The baseline quantitative carotid/subclavian AP characteristics and their 6-month longitudinal changes were not associated with MACEs. All predictors retained significance after the internal validation of the models, and models based on the baseline predictors also demonstrated good calibration; the latter were used to create MACE risk calculators. Conclusions: In typical contemporary patients with uncomplicated interventionally treated ACS, diabetes, decreased EF, Charlson comorbidity index, non-prescription of beta-blockers at discharge, and three or more uncontrolled risk factors after 6 months were the most important clinical predictors of MACEs. We also demonstrated that a lower value of AP GSM reflecting the plaque vulnerability, measured at baseline and after 6 months, was associated with an increased MACE risk; this effect was independent of clinical predictors and risk factor control. According to our knowledge, this is the first demonstration of the independent role of longitudinal carotid/subclavian AP GSM assessment in MACE prediction after ACS.

Glucagon-like peptide-1 receptor agonists to improve cardiorenal outcomes: data from FLOW and beyond.

Glucagon-like peptide-1 receptor agonists (GLP1RA), initially approved for glycemic control in type 2 diabetes mellitus (T2DM), have emerged as agents for weight loss, cardiovascular and kidney protection. This review summarizes the evidence supporting the benefits of these therapies on cardiorenal outcomes. Clinical trials have consistently demonstrated reductions in major adverse cardiovascular events with GLP1RA treatments. Recently, the FLOW trial revealed that semaglutide reduced the composite outcome of kidney failure, at least 50% decline in estimated glomerular filtration rate, kidney or cardiovascular mortality by 24% in patients with T2DM, thereby establishing GLP1RA as a pillar of therapy in this population. New evidence suggests favorable effects on kidney endpoints in nondiabetic individuals with overweight or obesity. Dedicated trials have also provided evidence for reduction in the risk for heart failure hospitalization and improvement in symptoms in individuals with heart failure with preserved ejection fraction. Subgroup analyses have suggested that GLP1RAs confer additive cardiorenal benefits irrespective of background medication use. There is increasing evidence that GLP1RA reduces the risk for cardiovascular events, chronic kidney disease progression, and heart failure hospitalizations. Further data on the effect of dual and triple GLP1-based therapies on cardiorenal outcomes is required.

Empagliflozin ameliorates renal and metabolic derangements in obese type 2 diabetic mice by blocking advanced glycation end product-receptor axis.

Although randomized clinical trials revealed that inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduced the risk of cardiovascular and renal events in patients with type 2 diabetes, the underlying molecular mechanisms remain to be elucidated. Since there is accumulating evidence that AGEs and their receptor (RAGE) play a crucial role in diabetes-related complications, we examined here whether empagliflozin ameliorates renal and metabolic derangements in db/db mice, an obese type 2 diabetes animal by blocking the AGE-RAGE axis. Eight-week-old db/db mice were fed a 0.045% empagliflozin diet (db/db + Empa) or normal diet (db/db) for 13weeks. The same week-old db/ + m mice were maintained on normal diet (db/ + m) used as a control. At baseline and 13weeks after intervention, biochemical analyses in the serum and urine were performed, and kidneys and adipose tissues were obtained for morphological, immunohistochemical, and reverse transcription-polymerase chain reaction analyses. Empagliflozin treatment for 13weeks significantly reduced AGEs, Nε-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), RAGE, NADPH oxidase-derived oxidative stress, inflammatory and fibrotic reactions in the kidneys of db/db mice of 21-week-old in association with attenuation of glomerular extracellular matrix accumulation, podocyte loss, proteinuria, and tubulointerstitial damage. Empagliflozin also reduced the AGE-RAGE-oxidative stress-induced inflammatory reactions in the adipose tissues of db/db mice, which was associated with restoration of adiponectin levels and decreased insulin resistance. Serum MG-H1 levels of control and db/db mice at 21weeks of age were significantly associated with proteinuria, tubulointerstitial damage, tissue AGEs levels, and serum monocyte chemoattractant protein-1 and adiponectin (inversely) values. Our present findings suggest that empagliflozin could ameliorate renal and metabolic derangements in type 2 diabetes animals by attenuating the AGE-RAGE axis.

Impact of SARS-CoV-2 infection therapies on the risk of venous thromboembolism and cardiovascular events from the SEMI-COVID-19 Registry

This study aimed to assess the impact of SARS-CoV-2 therapies on the risk of venous thromboembolism (VTE) and other cardiovascular events. A retrospective, multicenter, observational study included hospitalized patients in Spain due to acute SARS-CoV-2 infection from March 2020 to March 2022. A total of 184,324 hospitalized COVID-19 patients were included, with a mean age of 67.5 (± 16) years of whom 58.4% were male. Among the comorbidities, arterial hypertension was the most common, affecting 52.5% (9618 patients), followed by dyslipidemia in 39.5% (7237 patients), diabetes mellitus in 23.7% (1748 patients), and atrial fibrillation in 10.6% (1948 patients). The overall mortality rate was 17.4% (3183 patients) and 9.9% (1819 patients) required admission to an intensive care unit. Cardiovascular events occurred in 4.08% (748 patients), with VTE occurring in 2.78% (510 patients), myocardial infarction in 0.75% (137 patients), and ischemic stroke in 0.55% (101 patients). Among therapies, beta-lactams were used in 66.7% (12,228 patients), systemic corticosteroids in 56.9% (10,424 patients), and tocilizumab in 11.6% (2128 patients). Multivariate analysis revealed an independent association between VTE and the use of tocilizumab (adjusted OR 2.07; p < 0.01), corticosteroids (adjusted OR 1.44; p = 0.02), and macrolides (adjusted OR 0.58; p < 0.01). None of the therapies were associated with the risk of myocardial infarction or ischemic stroke. In this large national cohort, tocilizumab and corticosteroids exhibited an independent association for the risk of VTE, but not for myocardial infarction or ischemic stroke.

Metformin Use and Clinical Outcomes in Autosomal Dominant Polycystic Kidney Disease: A Nationwide Cohort Study

Background/Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder marked by bilateral renal cysts and extrarenal manifestations, ultimately resulting in renal failure. Emerging research indicates that metformin might influence the intracellular mechanisms of ADPKD, though its clinical significance remains uncertain. Methods: We applied the Taiwan National Health Insurance Database (NHIRD) to investigate the clinical impact of metformin utilization in ADPKD patients in real-world practice. The metformin user group was defined by more than 90 days of usage. To mitigate selection bias, we established a non-user group with a 1:2 ratio, matching for age, sex, and comorbidities by a propensity score matching method. Results: A total of 10,222 ADPKD cases were identified in the NHIRD between 2009 and 2018. After matching, the metformin user group was composed of 778 cases with a mean age of 59.5 ± 13.9 years, and the non-user group of 1546 cases with a mean age of 59.3 ± 14.4 years. The time from the index date to the outcome of ESKD in ADPKD was 5.3 ± 2.2 years in the metformin user group and 5.3 ± 2.3 years in the metformin non-user group, respectively. The metformin user group exhibited a significant reduction in the risk of end-stage kidney disease (ESKD), as indicated in the fully adjusted model (0.75, 95% CI 0.58–0.97, p = 0.03). A decreased risk of major adverse cardiovascular events (MACEs) was noted in metformin users, with an adjusted hazard ratio (HR) of 0.78 (95% CI 0.65–0.95, p = 0.01). Sensitivity analysis showed similar results by excluding late-stage CKD (CKD stage 5 or erythropoietin-stimulating agents use). Conclusions: Metformin usage in real-world practice showed lower hazards of ESKD and MACEs in patients with ADPKD, except for those with advanced CKD.

Exercise capacity in moderate aortic stenosis: a cardiopulmonary stress echocardiography study

BackgroundPatients with moderate aortic stenosis (AS) may experience symptoms and adverse outcomes. The aim of this study was to determine whether patients with moderate AS exhibited objective evidence of exercise limitation, compared with age and sex matched controls and if so, to determine which echocardiographic parameters predicted exercise ability.MethodsThis was a prospective case control study of patients with moderate AS (peak velocity (Vmax) 3.0–3.9 m/s, mean gradient (MG) 20-39mmHg, aortic valve area (AVA)1.1-1.5cm2 ) and left ventricular ejection fraction (LVEF) ≥ 55%. All patients underwent cardiopulmonary stress echocardiography.Results25 patients with moderate AS (Vmax 3.5 ± 0.2mmHg, mean gradient 28 ± 5mmHg, AVA 1.2 ± 0.1cm2, LVEF 61 ± 4%) were compared with 25 controls. % predicted oxygen uptake efficiency slope (OUES), % predicted O2 pulse and VO2 at anaerobic threshold (AT) were significantly lower in patients compared with controls (OUES 79 ± 15 vs. 89 ± 15%, p = 0.013). VO2 did not significantly differ between cases and controls.ConclusionObjective measures of exercise capacity including OUES, O2 pulse and VO2 at AT are significantly lower in patients with moderate AS compared with controls, suggesting that these parameters may be more useful than VO2 where patients may be unable to complete a maximal exercise test. Risk stratification using cardiopulmonary exercise echocardiography may help to identify patients with moderate AS who are at increased risk of cardiovascular events and should be considered for more intensive surveillance and intervention.Trial registrationClinical trial number MRC 0225 IRAS 207395.

Association of Serum Polyamines with Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease.

Emerging evidence indicates that serum polyamines, including putrescine, spermidine, and spermine, may serve as potential biomarkers for chronic kidney disease (CKD) and its progression. However, the association between serum polyamine levels, cardiovascular events, and mortality in CKD patients remains poorly understood. A retrospective cohort study was conducted, involving 297 adult patients with CKD at stages 1-5 from March 2015 to September 2018, with follow-up until May 2023. Serum polyamine levels were quantified using high-performance liquid chromatography and subsequently categorized into quartiles. The Kaplan-Meier curve was employed to assess the survival probabilities of CV events and overall mortality in relation to serum polyamine levels. The relationship between serum polyamines and the risk of CVD and overall mortality was explored using univariate and multivariate Cox regression analyses. Furthermore, we conducted a competing-risk analysis to investigate the link between serum polyamines and CV events, with mortality as the competing event. Over a median follow-up of 6.11 years, our findings revealed a negative correlation between putrescine levels and estimated glomerular filtration rate (eGFR), while spermidine and spermine levels were positively correlated with eGFR. The Kaplan-Meier curve demonstrated that serum polyamines were significantly associated with risk of CV events and all-cause mortality. Moreover, Cox regression analyses showed that, in multivariate Cox model, patients in the highest quartile of putrescine displayed a significantly higher risk of CV events (hazard ratio [HR] 6.972, 95% confidence interval [CI] 2.520-19.242, p＜0.001) compared to those in the lowest quartile. Conversely, higher levels of spermidine were associated with a lower risk of CV events (HR= 0.077, 95% CI 0.022-0.274, p＜0.001), and higher levels of spermine also appeared to reduce the risk of CV events (HR= 0.180, 95% CI 0.061-0.530, p=0.002). The relationship between serum polyamines and CVD remained robust in the competing risk models. Additionally, in the multivariate model, spermidine and spermine showed a significant protective effect on the risk of overall mortality; however, the protective effect was diminished upon the inclusion of eGFR as a covariate. Our study demonstrates significant disruption in serum polyamine levels among CKD patients, which correlates with eGFR. Altered polyamine levels are linked to an increased risk of CV events and overall mortality. Thus, serum polyamines may be considered valuable prognostic indicators for CKD patients.

Risk of Major Cardiovascular Events and All-Cause Death in Patients with Bronchiectasis and Associated Resistance to Antimicrobial Drugs.

To assess the impact of antimicrobial resistance (AMR) on major adverse cardiovascular event (MACE) risk in patients with bronchiectasis. This retrospective study utilized data from the TriNetX research network, analysing patients with bronchiectasis categorized by the presence or absence of AMR. Primary outcomes included the risk of MACE (myocardial infarction, stroke and systemic thromboembolism, and cardiac arrest) and all-cause death. Cox regression analysis with 1:1 propensity score matching (PSM) was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the primary outcomes. Subgroup analyses were conducted to validate results in clinically relevant subgroups. Prior to PSM, patients with AMR (n=6,543, 61.0±22.0 years, 55.8% female) were younger, more often male, and presented a higher prevalence of cardiovascular risk factors than those without AMR (n=154,685, 67.3±16.0 years, 59.4% female). After PSM, no significant differences were found between groups. However, AMR patients showed a higher risk of MACE (HR 1.29, 95% CI 1.17-1.41) and all-cause death (HR 1.49, 95% CI 1.38-1.61) compared to non-AMR patients. The MACE risk was notably elevated among AMR patients without prior cardiovascular events (HR 1.56, 95% CI 1.34-1.81). Similar MACE risks were observed in cystic fibrosis (HR 1.24, 95% CI 0.86-1.78) and non-cystic fibrosis subgroups (HR 1.28, 95% CI 1.16-1.41), with consistent findings across different AMR types. In patients with bronchiectasis, AMR is associated with an increased risk of MACE and all-cause death, suggesting that controlling AMR spread may confer broader health benefits, particularly in reducing cardiovascular risk.

Effect of erenumab versus other migraine preventive medications on cardiovascular and cerebrovascular outcomes: A United States claims database-based observational cohort study.

To estimate the real-world risk of cardiovascular events among patients with migraine treated with erenumab and other migraine preventive medications. Migraine preventive treatment with calcitonin gene-related peptide (CGRP) pathway inhibitors, such as erenumab and others, may theoretically result in cardiovascular effects due to a lack of compensatory vasodilation with CGRP pathway inhibition. In this retrospective observational cohort study, we estimated the unadjusted cumulative risk (CR) of new-onset hypertension, acute myocardial infarction (MI), or stroke among patients with migraine newly treated with erenumab, other anti-CGRP pathway monoclonal antibodies (mAbs), standard oral preventive medications, and onabotulinumtoxinA using data from the MarketScan® Commercial and Medicare Supplemental medical claims database. Comparative analyses to assess the relative risk (RR) of vascular events were gated on the comparability of treatment groups with respect to baseline demographics and clinical characteristics. Potential bias due to unmeasured confounding was evaluated via negative control outcome (NCO) analyses. Confounding based on measured covariates and differential informative censoring were addressed with inverse probability weights. A total of 108,019 new users of migraine preventive medications were included. Unadjusted CR (95% confidence interval [CI]) of hypertension at 12 months of treatment was: erenumab, 9.34% (8.79-9.89%); other anti-CGRP pathway mAbs, 9.42% (8.92-9.92%); standard oral preventive medications, 9.09% (8.77-9.41%); and onabotulinumtoxinA, 9.10% (8.39-9.81%). NCO analyses identified minimal concerns related to unmeasured confounding in erenumab versus other mAbs and erenumab versus onabotulinumtoxinA comparisons. Adjusted RRs (95% CIs) of acute MI and stroke, respectively, at 36 months of treatment were 1.02 (0.45-1.59) and 0.90 (0.56-1.25) for erenumab versus other mAbs and 0.87 (0.19-1.55) and 0.97 (0.42-1.52) for erenumab versus onabotulinumtoxinA. In this analysis of the MarketScan medical claims database, we found no difference in the risk of vascular events in patients treated with erenumab versus other anti-CGRP pathway mAbs or onabotulinumtoxinA.