Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease.

BACKGROUND: Classical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD. METHOD: Two hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0-1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE). RESULTS: The median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1-9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181-0.312) and CACS (0.243, CI: 0.172-0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates). CONCLUSION: Our results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.

Neutrophil-to-lymphocyte ratio as a prognostic biomarker in patients with peripheral artery disease: A systematic review and meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a simple and routinely obtained parameter reflecting systemic inflammation, including in peripheral artery disease (PAD). METHODS: This systematic review aimed to assess the role of NLR as a prognostic biomarker in patients with PAD. A systematic search was conducted across PubMed, ScienceDirect, Web of Science, Scopus, ProQuest, EBSCO, and Cochrane. Random-effects meta-analysis was used to pool risk ratios, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A bivariate model was used to generate summary receiver operating characteristics with the corresponding area under the curve (AUC). RESULTS: This review included 5243 patients with PAD from nine eligible studies. High NLR corresponded to at least a twofold increased risk of all-cause mortality (ACM), major adverse limb events (MALE), and major adverse cardiovascular events (MACE). NLR's performance was good for predicting 1-year ACM (AUC 0.71 [95% CI: 0.59-0.79], sensitivity 58.2% [95% CI: 45.3-71.0], specificity 72.6% [95% CI: 65.6-79.62], PPV 41.0% [95% CI: 31.2-50.7], NPV 82.7% [95% CI: 74.1-91.3]) and 1-year MALE (AUC 0.78 [95% CI: 0.75-0.80], sensitivity 65.4% [95% CI: 41.6-89.2], specificity 77.7% [95% CI: 71.0-84.3], PPV 53.7% [95% CI: 47.3-60.1], NPV 83.91% [95% CI: 73.2-94.6]). However, these values tended to decrease as the follow-up duration extended, except for the pooled specificities, which exhibited the opposite pattern. CONCLUSION: NLR emerges as a simple and cost-effective prognostic biomarker with decent performance for poor outcomes in patients with PAD (PROSPERO Registration No.: CRD42023486607).

Major Adverse Cardiovascular Events Following Coronary Artery Stenting by History of Hypertensive Disorder of Pregnancy.

BACKGROUND: A history of hypertensive disorders of pregnancy is associated with at least twice the risk of incident ischemic heart disease. Whether the long-term outcome following treatment with coronary artery stenting is associated to the history of hypertensive disorders of pregnancy is unknown. METHODS AND RESULTS: We included 8364 women (age ≤65 years) undergoing first coronary artery stenting 2006 to 2022 following their first delivery in 1973 or later, linking nationwide data on percutaneous coronary intervention and delivery history. In total, 1122 women (13.4%) had a history of hypertensive disorders of pregnancy. The main outcome, a major adverse cardiovascular event, was defined as any incident myocardial infarction, ischemic heart disease, cardiac arrest, arrhythmias, angina pectoris, heart failure, cerebral infarction, or sudden death. During a median follow-up time of 5 years, 258 women with a history of hypertensive disorders of pregnancy had a major adverse cardiovascular event, compared with 1465 women without a history of hypertensive disorders of pregnancy (23% versus 20.2%, P=0.028 for log-rank test). Estimates adjusted for patient- and procedural characteristics in proportional hazards regression models suggested that the hazard rate increased only after 4-8 years of follow-up (hazard ratio [HR], 1.36 [95% CI, 1.05-1.78]) and was primarily driven by women with history of gestational hypertension (HR, 2.15 [95% CI, 1.49-3.11]). CONCLUSIONS: Women with a history of hypertensive disorders of pregnancy have an increased risk of a major adverse cardiovascular event following coronary artery stenting compared with other parous women. A history of hypertensive disorders of pregnancy warrants further attention in the secondary prevention setting of coronary artery disease.

Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.

BACKGROUND: To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. METHODS AND RESULTS: A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%). CONCLUSIONS: Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.

Single-inhaler triple versus LABA-ICS therapy for COPD: Comparative safety in real-world clinical practice.

BACKGROUND: Recent treatment guidelines for chronic obstructive pulmonary disease (COPD) have replaced the long-acting beta2-agonist and inhaled corticosteroid (LABA-ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA-LABA-ICS). Yet, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS. RESEARCH QUESTION: Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting? STUDY DESIGN AND METHODS: We identified a cohort of COPD patients, 40 years or older, treated during 2017-2021, from the United Kingdom's Clinical Practice Research Datalink. Among LAMA-naïve patients, initiators of single-inhaler triple therapy were matched 1:1 to LABA-ICS users on time-conditional propensity scores. They were compared on the incidence of major adverse cardiovascular events (MACE), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over one year. RESULTS: The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACE was 11.3 per 100 per year with triple therapy compared with 8.7 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACE with triple therapy was 1.28 (95% CI: 1.05-1.55), relative to LABA-ICS, though the increase was mainly in the first four months (HR 1.41; 95%CI: 1.14-1.74). The HR of all-cause death was 1.31 (95% CI: 1.06-1.62), while for acute myocardial infarction and stroke hospitalization it was 1.00 (95% CI: 0.56-1.79) and 1.06 (95% CI: 0.48-2.36), respectively, with triple therapy, relative to LABA-ICS. INTERPRETATION: In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACE compared with similar patients treated with a LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first four months after treatment initiation.

Associations of Plasma Erythritol with Dietary Factors, Cardiometabolic, Inflammatory, and Gut Health Markers in People with and without HIV: A Cross-Sectional Study.

BACKGROUND: Recently, elevated levels of plasma erythritol have been associated with major adverse cardiovascular events (MACE). It is known that people with HIV (PWH) have a higher cardiovascular disease burden. Whether PWH have higher levels of plasma erythritol has not been evaluated. This study aimed to assess if blood erythritol levels are elevated in PWH and to examine relationships between erythritol and dietary, cardiometabolic, inflammatory, and gut health markers. METHODS: Plasma erythritol levels were measured using frozen samples from 162 participants, including 109 PWH and 53 people without HIV (PWoH) in a parent study. General linear models were used to assess the linear relationship between characteristics, cardiovascular measures, markers of body composition, inflammation, and gut integrity with plasma erythritol. Logistic regression was used to assess risk factors associated with PWH, and cumulative logit models were used to investigate which factors were associated with having the highest plasma erythritol levels among PWH. RESULTS: Compared to PWoH, PWH had higher plasma erythritol levels (p = 0.03). Every 10% increase in VLDL (p = 0.01), visceral adipose tissue (p < 0.0001), or TNFrI (p = 0.01) was associated with an approximately 1% increase in plasma erythritol. Among PWH, HgbA1c (p = 0.003), TNFrI (p = 0.002), and IFAB-P (p = 0.004) were associated with having the highest tertile of plasma erythritol (≥3.6 µM). Compared to PWoH, PWH were more than two times as likely (p = 0.03) to have plasma erythritol ≥ 3.6 µM. CONCLUSIONS: We identified positive associations between plasma erythritol levels and several factors, including HIV status, BMI, adipose tissue, TNFr1, HbA1c, and VLDL. These results underscore the importance of further investigating the role of elevated plasma erythritol levels in people with HIV, particularly in light of their increased vulnerability to cardiovascular and metabolic diseases.

Comparison of Efficacy of Atorvastatin and Rosuvastatin in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Acute coronary syndrome (ACS) remains a leading cause of morbidity and mortality worldwide. Statins, particularly atorvastatin, and rosuvastatin, are crucial in managing cholesterol levels and reducing cardiovascular risk in ACS patients. However, direct comparative studies between these two statins are limited. This meta-analysis aimed to compare the efficacy of atorvastatin and rosuvastatin in reducing major adverse cardiovascular events (MACE) and all-cause mortality in patients with ACS. A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Scopus for studies published up to July 2024. Randomized controlled trials and observational studies directly comparing atorvastatin and rosuvastatin in ACS patients were included. The primary outcomes were the incidence of MACE and all-cause mortality. Six studies involving 4195 patients were included in the meta-analysis. Pooled analysis showed no statistically significant difference between atorvastatin and rosuvastatin in reducing MACE [risk ratio (RR): 0.91, 95% confidence interval (CI): 0.68 to 1.22, p-value: 0.54] or all-cause mortality (RR: 0.94, 95% CI: 0.52 to 1.70, p-value: 0.83). No significant heterogeneity was observed among the studies (I-square: 0% for both outcomes). This meta-analysis suggests that atorvastatin and rosuvastatin have comparable efficacy in reducing MACE and all-cause mortality in ACS patients. These findings provide clinicians with flexibility in choosing between these statins based on individual patient factors. However, further large-scale randomized controlled trials are needed to confirm these results and explore potential differences in specific patient subgroups.

The role of hemoglobin A1c as a predictor of major adverse cardiovascular events in patients with type 2 diabetes mellitus after percutaneous coronary intervention: a case-cohort study.

BACKGROUND: Few studies have investigated the potential predictive value of glycosylated hemoglobin A (HbA1c) and clinical outcomes in diabetic patients after percutaneous coronary intervention (PCI), and the results of the reports have often been inconclusive and contradictory. We have organized a study to investigate the relationship between HbA1c and the occurrence of major adverse cardiovascular events (MACE) in diabetic patients after PCI. METHODS: This case-cohort study was conducted on 563 diabetic patients who underwent PCI. All studied patients had an HbA1c level measured within 24 h before angioplasty. All patients were followed for six months regarding the occurrence of MACE, and the HbA1c level was measured again at the end of the sixth month of follow-up. In the case of MACE, the subjects were considered the case group, and other non-MACE patients were included in the control group. RESULTS: 505 patients remained in the study at the end of follow-up. MACE occurred in 23 (4.6%) patients during the first month and in 57 (11.3%) patients by the end of the sixth month. Baseline HbA1c was an independent predictor of MACE and mortality at the end of month-6 (P = 0.008 and 0.001, respectively). CONCLUSIONS: The level of HbA1c at the time of admission has a significant predictive value for the occurrence of MACE in diabetic patients who undergo PCI. However, post-PCI glycemic control may not effectively reduce the risk of MACE in this population. CLINICAL TRIAL REGISTRATION: Not applicable.

Impact of admission glucose and 30-day major adverse cardiovascular events on patients with chest pain in an emergency setting: insights from the China EMPACT registry.

Objective: Although the association between admission glucose (AG) and major adverse cardiac events (MACE) is well-documented, its relationship with 30-day MACE in patients presenting with cardiac chest pain remains unclarified. In light of this, this study aims to examine the correlation between AG levels and the incidence of MACE in patients with chest pain in an emergency setting. Materials and methods: We consecutively enrolled patients who presented to the emergency department for chest pain symptoms within 24 h from the EMPACT cohort in Eastern China (clinicaltrials.gov, Identifier: NCT02536677). The primary outcome was 30-day MACE, including all-cause death, recurrent myocardial infarction, urgent target vessel revascularization, stroke, cardiogenic shock, and cardiac arrest (CA). The associations of AG levels with 30-day MACE were analyzed using Kaplan-Meier analysis and Cox regression models. Results: Among 1,705 patients who were included in this study, 154 (9.03%) patients met the primary outcome at 30 days. The average age of the patients was 65.23 ± 12.66 years, with 1,028 (60.29%) being male and 500 (29.33%) having diabetes. The median AG levels were 7.60 mmol/L (interquartile range: 6.30-10.20). Kaplan-Meier survival analysis revealed significant differences in the 30-day MACE risk (P < 0.001 according to the log-rank test). We found that the highest AG level (Q4) was associated with increased MACE risk compared with the lowest AG level [adjusted hazard radio (aHR): 2.14; 95% confidence interval (CI): 1.2-3.815; P = 0.010]. In addition, Q4 level was also associated with increased all-cause death risk (aHR: 3.825; 95% CI: 1.613-9.07; P = 0.002) and increased CA risk (aHR: 3.14; 95% CI: 1.251-7.884; P = 0.015). Conclusions: An elevated AG level significantly correlates with a higher incidence of 30-day MACE in patients with acute chest pain. The findings reveal the importance of managing AG levels to potentially reduce the risk of adverse cardiac events.

Influence of Metformin Discontinuation on Readmission Rate in Patients With Acute Heart Failure.

Background: The consequences of discontinuing metformin in patients with heart failure have not been determined. Knowing that acute exacerbation of chronic heart failure contributes to substantial increases in major adverse cardiovascular events (MACE), we proposed a retrospective study to examine whether discontinuing metformin in patients hospitalized with heart failure impacts mortality and readmission rates. Methods: We conducted a retrospective analysis of patients admitted with a diagnosis of acute heart failure to hospitals in the HCA Healthcare System from 2020 to 2022. Included patients had a prior diagnosis of diabetes mellitus, acute heart failure, and were taking metformin prior to admission. After applying our exclusion criteria, a total of 7740 patients remained. The primary outcomes were 30-, 60-, and 90-day readmission rates and secondary outcomes were mortality and length of stay. Results: Patients who were discharged without a prescription for metformin (NONDIS-MET) were 4.489 (95% CI 3.673-5.488, p < 0.0001) times more likely to have a MACE outcome in 30 days compared to patients who received a discharge order for metformin (DIS-MET). The findings were similar for 60-day and 90-day readmission rates, with NONDIS-MET patients 3.457 (95% CI 2.893-4.131, p < 0.0001) and 2.992 (95% CI 2.534-3.533 p < 0.0001) times more likely to have a MACE outcome than MET patients, respectively. However, when metformin was continued during the patients' hospital stay (CONT-MET) there was no significant association with MACE outcomes, readmission, or mortality rates. Conclusion: We found that diabetic patients admitted with acute heart failure exacerbations had a higher incidence of major adverse cardiac events and were more likely to be readmitted when they were not prescribed metformin after discharge. Our findings agree with prior work showing the cardioprotective effects of metformin; however, continuing metformin during hospital admission did not affect our patients adverse outcomes.

The Predictive Value of Global Longitudinal and Circumferential Strains in Hypertensive Patients: 10-Year Follow-Up.

Background: The aim of the current study was to investigate the predictive value of a multidirectional LV strain on adverse outcomes in a large population of uncomplicated hypertensive patients who were followed for a mean period of 10 years. Methods: This retrospective study included 591 recently diagnosed hypertensive patients who underwent clinically indicated echocardiography between January 2010 and December 2014 and were followed for a mean period of 10 years. Global longitudinal, circumferential and radial strains (GLS, GCS and GRS) were measured by 2D speckle tracking imaging. The primary outcome was a MACE occurrence defined by all-cause mortality, cardiovascular mortality, myocardial infarction, coronary artery by-pass, coronary stent implantation, stroke, development of heart failure and the occurrence of atrial fibrillation during follow-up. Results: Our results showed that GLS, GCS and GRS were significantly lower in patients who experienced MACE. Age, male gender, systolic blood pressure, left ventricular hypertrophy (LVH) and left atrial enlargement (LAE) were associated with MACE occurrence. Reduced GLS [OR 1.15; 95%CI: 1.01-1.30] and reduced GCS [OR 1.1; 95%CI: 1.02-1.22] were related with MACE independently of clinical characteristics, LV systolic and diastolic function, as well as LVH. Reduced GRS was not independently associated with adverse outcomes. Conclusions: Reduced GLS and GCS were independently associated with adverse outcomes during 10-year follow-up in patients who were recently diagnosed and uncomplicated hypertensive patients at the baseline.

The Relationship Between Right Ventricular Longitudinal Strain and Adverse Outcome in Hypertensive Patients: 10-year Follow-up.

INTRODUCTION: Previous studies showed the importance of right ventricular (RV) remodeling in patients with arterial hypertension and RV longitudinal strain was recognized as very sensitive parameter for detection of subtle cardiac impairment. However, its clinical importance in arterial hypertension has not been established so far. AIM: The present study aimed to evaluate the association between RV longitudinal strain (global and free-wall) on adverse outcomes measured by MACE in the large group of hypertensive patients who were followed for mean period of 10 years. METHODS: This retrospective study finally included 544 hypertensive patients who underwent full echocardiographic examination including 2D speckle tracking imaging. between January 2010 and December 2014. MACE was considered as the primary outcome and it was defined by all-cause mortality, cardiovascular mortality, myocardial infarction, coronary artery by-pass, coronary stent implantation, stroke, development of heart failure, and occurrence of atrial fibrillation during follow-up. RESULTS: Patients who experienced MACE were older than those who did not. There was no difference in demographic and clinical parameters between MACE and non-MACE patients. There was no difference in RV diameter, but MACE patients had higher RV wall thickness. RV systolic function parameters were similar between the two groups. RV global and free-wall longitudinal strain were significantly lower in MACE patients (-22.3 ± 3.6 vs. -24.7 ± 3.9%, p < 0.001 and - 25.8 ± 4.2 vs. -28.1 ± 4.5%, p < 0.001; respectively). Reduced RV GLS [OR 1.10; 95%: 1.02-1.20] and reduced RV free-wall longitudinal strain [OR 1,21; 95%CI: 1.05-1.39] were independently of clinical and echocardiographic parameters related with adverse outcome measured by MACE. CONCLUSION: RV GLS and RV free-wall longitudinal strain were independently related with adverse outcomes during 10-year follow-up in initially uncomplicated hypertensive patients.

Predictive value of miR-636 in patients with acute myocardial infarction undergoing percutaneous coronary intervention and its bioinformatics analysis.

BACKGROUND: MicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI). Percutaneous coronary intervention (PCI) is currently the most direct and effective procedure to treat AMI, but the occurrence of postoperative cardiovascular events (MACE) affects patients' quality of life. The objective of this study was to identify a new biomarker that could provide a theoretical basis for the prevention of MACE in patients with AMI undergoing PCI. METHODS: 142 AMI patients who underwent PCI and 130 healthy volunteers were selected as study subjects. Detection of miR-636 expression level by fluorescence quantitative PCR. ROC, Kaplan-Meier and Cox regression analyses were applied to evaluate the diagnostic and prognostic value of miR-636 for AMI. The miR-636 target genes were predicted and enriched for GO function and KEGG pathway. RESULTS: MiR-636 expression levels were elevated in patients with AMI. ROC curve analysis showed that miR-636 had a feasible diagnostic value in distinguishing AMI patients from healthy controls miR-636 expression levels were elevated in patients who developed MACEs. ROC results showed that miR-636 had significant diagnostic value in differentiating AMI patients with and without MACEs after PCI treatment. GO and KEGG enrichment analyses showed that miR-636 may transmit information to vesicles formed by the cell membrane. CONCLUSIONS: MiR-636 expression serves as a biomarker for diagnosing AMI and predicting the occurrence of MACE after PCI.

Vitiligo is associated with an increased risk of cardiovascular diseases: a large-scale, propensity-matched, US-based retrospective study.

BACKGROUND: Vitiligo is an autoimmune disease, characterized by specific destruction of melanocytes. While associations with numerous comorbid conditions, which potentially increase the risk of cardiovascular diseases have been described, data on the risk for cardiovascular disease is inconclusive. To address this relevant knowledge gap, this study aims to identify the risk of cardiovascular disease in vitiligo. METHODS: The US Collaborative Network was accessed using the TriNetX platform, allowing retrospective data retrieval from electronic health records (EHRs) from 57 US based health care organizations (HCOs). Patients with vitiligo and controls were identified by their respective ICD10 codes. Risk of onset of several cardiovascular diseases was determined in patients within 15 years after diagnoses. FINDINGS: A total of 94 diagnoses with a prevalence of ≥1% in both cohorts, which consisted of 96,581 individuals per group after propensity-score-matching, were identified. Of those, 54 displayed an increased risk in vitiligo. None of the cardiovascular diseases investigated were associated with a decreased risk in patients with vitiligo. Specifically, cerebral infarction occurred in 1.3% of patients with vitiligo, and 1.0% in controls. This difference translated into a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.11-1.32, padj < 0.001). Venous thromboembolism was recorded in 1.34% of cases and 1.02% of controls without vitiligo, resulting in an increased HR of 1.27 (95% CI 1.171-1.38, padj < 0.001). Further, major adverse cardiovascular events (MACE) as a composite endpoint was evaluated. The risk for MACE was increased following a vitiligo diagnosis (HR 1.28, 95% CI 1.22-1.35, padj < 0.001), which persisted in both sensitivity analyses. INTERPRETATION: Patients with vitiligo display an increased risk of onset of cardiovascular diseases as compared to healthy individuals. Thus, vitiligo might require more precise monitoring and systemic treatment. FUNDING: This research was supported by the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein, by the Excellence Cluster Precision Medicine in Chronic Inflammation (DFG, EXC 2167), and by DFG Individual Grant LU 877/25-1.

Body weight variability as a predictor of cardiovascular outcomes in type 1 diabetes: A nationwide cohort study.

AIM: Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition. MATERIALS AND METHODS: Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow-up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all-cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome. RESULTS: Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24-1.62). In addition, high BWV was significantly associated with a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.28-1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06-1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20-2.01). BWV showed a quasi-linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant. CONCLUSIONS: High BWV is associated with an increased risk of CVD and all-cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it.

Colchicine for secondary prevention of ischaemic stroke and atherosclerotic events: a meta-analysis of randomised trials.

Background: Guidelines recommend low-dose colchicine for secondary prevention in cardiovascular disease, but uncertainty remains concerning its efficacy for stroke, efficacy in key subgroups and about uncommon but serious safety outcomes. Methods: In this trial-level meta-analysis, we searched bibliographic databases and trial registries form inception to May 16, 2024. We included randomised trials of colchicine for secondary prevention of ischaemic stroke and major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, coronary revascularisation, or cardiovascular death). Secondary outcomes were serious safety outcomes and mortality. A fixed-effect inverse-variance model was used to generate a pooled estimate of relative risk (RR) with 95% confidence intervals (CI). This study is registered with PROSPERO, CRD42024540320. Findings: Six trials involving 14,934 patients with prior stroke or coronary disease were included. In all patients, colchicine compared with placebo or no colchicine reduced the risk for ischaemic stroke by 27% (132 [1.8%] events versus 186 [2.5%] events, RR 0.73 [95% CI 0.58-0.90]) and MACE by 27% (505 [6.8%] events versus 693 [9.4%] events, with RR 0.73 [0.65-0.81]). Efficacy was consistent in key subgroups (females versus males, age below versus above 70, with versus without diabetes, statin versus non-statin users). Colchicine was not associated with an increase in serious safety outcomes: hospitalisation for pneumonia (109 [1.5%] versus 106 [1.5%], RR 0.99 [0.76-1.30]), cancer (247 [3.5%] versus 255 [3.6%], RR 0.97 [0.82-1.15]), and gastro-intestinal events (153 [2.1%] versus 135 [1.9%]), RR 1.15 [0.91-1.44]. There was no difference in all-cause death (201 [2.7%] versus 181 [2.4%], RR 1.09 [0.89-1.33]), cardiovascular death (70 [0.9%] versus 80 [1.1%], RR 0.89 [0.65-1.23]), or non-cardiovascular death (131 [1.8%] versus 101 [1.4%], RR 1.26 [0.98-1.64]). Interpretation: In patients with prior stroke or coronary disease, colchicine reduced ischaemic stroke and MACE, with consistent treatment effect in key subgroups, and did not increase serious safety events or death. Funding: There was no funding source for this study.

Prognosis of Zero Coronary Artery Calcium Score in Symptomatic Patients of South Asian Descent - an Experience from a Tertiary Care Center in Pakistan.

Introduction: The absence of CAC in asymptomatic individuals is associated with a very low incidence of cardiovascular events. Of symptomatic patients, 1-2% with zero CAC score have non-calcified coronary artery atherosclerosis, and at least one third of cardiovascular events occur in individuals with zero CAC. South Asians (SA) have proportionally higher case fatality rates for CVD, relatively younger age of presentation, and accelerated rate of atherosclerosis when compared with other ethnic groups. Methods: All consecutive patients who underwent a CTCA to evaluate angina or angina-equivalent symptoms during the study duration were enrolled retrospectively. Patients with prior myocardial infarction, history of revascularization, and congenital heart disease were excluded. MACE was defined as the total of cardiac death, non-fatal myocardial infarction, and/or non-elective revascularization. Results: A total of 534 patients were enrolled after final exclusion. The mean age was 53 years ± 11. Males constituted 68.4% of the study population. Dyslipidemia was the most common co-morbid condition identified (50%), followed by diabetes (18.4%) and hypertension (3.6%). At least 28.8% of patients with zero CAC scores had the presence of coronary artery disease (soft plaque) of any degree. Obstructive CAD (>50%) was present in 5.8% of patients. Follow-up was available for 61.4% of patients. On a mean follow-up of 96.6 months ± 49.8 (range 21-194 months), all-cause MACE was observed in 8.8% of patients. The most common MACE was angina (3.96%) and all-cause mortality (3%). The baseline characteristics and MACE did not differ in patients with and without obstructive CAD. The baseline characteristics did not differ significantly between patients with and without MACE. Conclusion: The incidence of soft plaque in this SA cohort is higher than that reported in international studies. However, in symptomatic SA, a CAC score of zero carries a good long-term prognosis, irrespective of the degree of CAD.

Intensive early and sustained lowering of non-high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry.

BACKGROUND AND AIMS: Non-HDL-C provides an estimate of lipid-associated risk and is a secondary treatment target after myocardial infarction (MI). The aim was to study the relationship between non-HDL-C levels after MI and risk of adverse outcomes. METHODS: From the SWEDEHEART registry, 56 262 patients with MI were included. Outcomes were major adverse cardiovascular event (MACE: death, MI, and ischaemic stroke), death, and non-fatal MI. Non-HDL-C was assessed at admission, 2 months, and 1 year. Target achievement (<2.2 mmol/L) of non-HDL-C, timing thereof, and outcomes were assessed. RESULTS: During median follow-up of 5.4 years, 9549 had MACE, 5427 died, and 3946 had MI. Long-term hazard ratio (HR) for MACE in the lowest vs. the highest quartile of achieved non-HDL-C at 1 year was 0.76 [95% confidence interval (CI) 0.71-0.81]. Short-term results were consistent also when assessing non-HDL-C levels at 2 months, including early events up to 1 year (HR 0.80, 95% CI 0.68-0.92). Similar results were observed for all outcomes. Patients achieving both early and sustained targets had lowest risk of outcomes (HR 0.80, 95% CI 0.74-0.86) vs. patients achieving target early or late (HR for both 0.86, 95% CI 0.79-0.93). CONCLUSIONS: The lowest achieved levels both at 2 months and at 1 year of non-HDL-C were associated with better outcome. The lowest risk was observed when target was achieved within 2 months of MI and sustained thereafter. These findings challenge the current stepwise approach for cholesterol lowering after MI, which inevitably results in delaying goal attainment and possible harm.

Cardiovascular Effectiveness and Safety of Antidiabetic Drugs in Patients with Type 2 Diabetes and Peripheral Artery Disease: Systematic Review.

Peripheral artery disease (PAD) is an atherosclerotic condition commonly complicating type 2 diabetes (T2D), leading to poor quality of life and increased risk of major adverse lower-limb (MALE) and cardiovascular (CV) events (MACE). Therapeutic management of PAD in T2D patients is much more arduous, often due to bilateral, multi-vessel, and distal vascular involvement, in addition to increased systemic polyvascular atherosclerotic burden. On the other hand, the pathophysiological link between PAD and T2D is very complex, involving mechanisms such as endothelial dysfunction and increased subclinical inflammation in addition to chronic hyperglycemia. Therefore, the clinical approach should not ignore vascular protection with the aim of reducing limb and overall CV events besides a mere glucose-lowering effect. However, the choice of the best medications in this setting is challenging due to low-grade evidence or lacking targeted studies in PAD patients. The present review highlighted the strong relationship between T2D and PAD, focusing on the best treatment strategy to reduce CV risk and prevent PAD occurrence and worsening in patients with T2D. The Medline databases were searched for studies including T2D and PAD up to June 2024 and reporting the CV effectiveness and safety of the most used glucose-lowering agents, with no restriction on PAD definition, study design, or country. The main outcomes considered were MACE-including nonfatal acute myocardial infarction, nonfatal stroke, and CV death-and MALE-defined as lower-limb complications, amputations, or need for revascularization. To the best of our current knowledge, GLP-1 receptor agonists and SGLT2 inhibitors represent the best choice to reduce CV risk in T2D and PAD settings, but a personalized approach should be considered. GLP-1 receptor agonists should be preferred in subjects with prevalent atherosclerotic burden and a history of previous MALE, while SGLT2 inhibitors should be used in those with heart failure if overall CV benefits outweigh the risk of lower-limb complications.