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Background: Non-obese patients with diabetes mellitus (DM) are becoming more prevalent, but their cardiovascular risk (CV) especially when accompanied with cardio-renal-metabolic co-morbidities (hypertension, chronic kidney disease, hyperlipidemia) is not well characterised. The aim of the study was to assess the CV risk among patients with DM in relation to obesity and cardio-renal-metabolic co-morbidities. Materials and methods: This was a cohort study of all patients with DM without a history of major adverse cardiovascular event who were hospitalized for any reason in France in 2013 with at least 5 years of follow-up. They were categorized by the presence of obesity vs no obesity, as well as three cardio–renal–metabolic co-morbidities: hypertension, chronic kidney disease, hyperlipidemia. 'Extremely unhealthy' patients with DM were defined as those having all 3 co-morbidities. Results: There were 196,112 patients (mean age 65.7 (SD 13.7) years; 54.3% males) included into the analysis. During a mean follow-up of 4.69 ± 1.79 years, when adjusted for multiple covariates, the non-obese and 'extremely unhealthy' obese patients had the highest risk of CV death [aHR 1.40 (95% CI, 1.22–1.61) and 1.48 (95% CI, 1.25–1.75), respectively]. The 'extremely unhealthy' obese had the highest risk of MACE-HF [aHR 1.84 (95% CI, 1.72–1.97)] and new-onset AF [aHR 1.64 (95% CI, 1.47–1.83)]. Conclusion: Both non-obese and obese patients with DM with associated cardio-renal-metabolic co-morbidities are an 'extremely unhealthy' phenotype with the highest risk of CV death and CV events. [ABSTRACT FROM AUTHOR]

Degradation of vascular extracellular matrix is important in atherosclerosis. Cysteine protease legumain is upregulated in atherosclerotic plaques. We recently reported that plasma legumain levels are high in patients with complex coronary lesions. This study investigated the association between legumain levels and cardiovascular events in 372 patients undergoing coronary angiography. Patients with acute coronary syndrome were excluded. Of the 372 patients, 225 had coronary artery disease (CAD). During a mean follow-up of 7.0 ± 4.3 years, cardiovascular events occured in 62 patients. Compared with 310 patients without events, 62 with events tended to have higher prevalence of complex lesions (15% vs. 10%). Notably, patients with events had higher legumain levels (median 5.51 vs. 4.90 ng/mL, P < 0.01) than those without events. A Kaplan-Meier analysis showed lower event-free survival in patients with legumain > 5.0 ng/mL than in those with ≤ 5.0 ng/mL (P < 0.01). In multivariate Cox regression analysis, legumain level was an independent predictor of cardiovascular events. The hazard ratio for legumain > 5.0 ng/mL for cardiovascular events was 2.18 (95%CI = 1.27–3.77, P < 0.01). Only among 225 patients with CAD, patients with events had higher legumain levels (5.49 vs. 4.73 ng/mL) than without events (P < 0.02). Legumain level was also a predictor of cardiovascular events in patients with CAD. Thus, high plasma legumain levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography and those with stable CAD. [ABSTRACT FROM AUTHOR]

Endosialin, also known as tumor endothelial marker-1, is a transmembrane glycoprotein that plays a role in inflammation and tumor progression. Endosialin is upregulated in atherosclerotic lesions. To elucidate the association between blood endosialin levels and cardiovascular events, we measured plasma endosialin levels in 389 patients undergoing coronary angiography who were followed up for a mean follow-up of 6.4 ± 4.2 years for cardiovascular events (cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or need for coronary revascularization). Of the 389 patients, 223 had coronary artery disease (CAD). No significant difference was found in plasma endosialin levels between patients with and without CAD (median 0.92 vs. 0.92 ng/mL). During the follow-up, cardiovascular events occurred in 62 patients. Compared with patients without events, those with events had higher endosialin levels (1.12 vs. 0.89 ng/mL), and more often had endosialin level of > 1.1 ng/mL (53% vs. 31%) (P < 0.01). A Kaplan-Meier analysis showed lower event-free survival in patients with endosialin > 1.1 ng/mL than those with ≤ 1.1 ng/mL (P < 0.01). In a multivariate Cox regression analysis, endosialin > 1.1 ng/mL was an independent predictor of cardiovascular events (hazard ratio = 2.00; 95%CI = 1.21–3.32; P < 0.01). Thus, high plasma endosialin levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography. [ABSTRACT FROM AUTHOR]

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30 days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10 years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61–0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32–0.64) compared to azithromycin non-users (n = 2434, 72 ± 11 years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study. [ABSTRACT FROM AUTHOR]

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The current research focuses on the effects of nutritional supplementation and exercise on dialysis patients, but whether physical activity (PA) can reduce the risk of adverse outcomes for patients with different nutritional status is not clear. The maintenance hemodialysis (MHD) patients were recruited from April 2021 to April 2022. The information of PA was obtained from the international physical activity questionnaire (IPAQ). The outcomes were cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death. We used COX proportional risk model to estimate the association between PA and the outcomes of MHD patients. Patients are classified into two groups based on geriatric nutritional risk index (GNRI) and classified by age, and we used COX proportional risk model to estimate the association of PA and outcomes in subgroups. The isotemporal substitution model (ISM) was used to estimate the effects of replacing light physical activity (LPA) with moderate physical activity (MPA) or vigorous physical activity (VPA) on risk of cardiovascular events, tumors, and all-cause death in different subgroups. The effects of PA on ankle-brachial index (ABI) and body fat content were analyzed in different IPAQ groups. A total of 241 maintenance hemodialysis patients were included, 105 peoples developed cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death (43.6%). The median follow-up time was 12 months. MPA reduced the risk of outcome in MHD patients or high GNRI patients (40% vs 39%).In MHD patients who was under 65 years with high GNRI, MPA reduced cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death by 55%.PA reduced the risk of cardiovascular event by 65%, but did not reduce the risk of tumor or all-cause death. Replacing LPA with VPA did not improve clinical outcomes. It actually increases the risk of heart failure 0.4%. MPA reduced the risk of cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor, all-cause death in MHD patients under 65 years, while VPA had no health benefit. Trial registration: ChiCTR210050998. [ABSTRACT FROM AUTHOR]

Anthracyclines are associated with enhanced oxidative stress responsible for adverse events in patients with breast cancer. However, no study has investigated the potential anti-inflammatory role of statins in counteracting anthracycline toxicity. In this retrospective study utilizing a federated health network (TriNetX), patients with breast cancer (ICD code C50) treated with anthracyclines were categorized into two groups: statin users (for at least 6 months); and statin non-users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the risk of myocardial infarction, stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). We identified 3,701 statin users (68.8 ± 10.4 years) and 37,185 statin non-users (59.6 ± 12.8 years). After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.82, 95% CI 0.74–0.91) compared to statins non-users. Analyzing the risk for secondary outcomes, only the risk of stroke was significantly increased in statin users (HR 1.27, 95% CI 1.01–1.61), while no associations were found for the other cardiovascular events. The risk of all-cause death in statin users was the lowest during the first year after the anthracycline's initiation. No significant difference was found between lipophilic and hydrophilic statins. In patients with breast cancer treated with anthracyclines, statin use is associated with a reduced risk of all-cause death. Prospective studies are needed to investigate the potential beneficial effect of statin initiation in cancer patients without other indications. [ABSTRACT FROM AUTHOR]

Background: This work evaluated the effects of proton pump inhibitors (PPIs) on cardiovascular events (CVEs) and inflammatory factors in patients with upper gastrointestinal bleeding (UGIB) undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. Clinical data from these patients were analysis, intending to provide relevant theoretical evidence for clinical practice. Materials and methods: Data of 166 patients who underwent percutaneous coronary intervention and developed UGIB while on DAPT at The First People' Hospital of Linping District from April 2021 to April 2023 were retrospectively analyzed. The patients were rolled into two groups: those who received PPI treatment and those who did not, namely, PPI and non-PPI group, respectively. Furthermore, occurrence of CVEs and the levels of inflammatory factors of patients in all groups were statistically analyzed. Results: In patients with UGIB, melena is a common presentation. The incidence of CVE in the PPI group showed no statistically significant difference compared to the control group, and there was no significant variance observed in the distribution of CVE incidence among different PPIs. However, levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were significantly lower in the PPI group compared to the non-PPI group (P < 0.05). Conclusion: Melena was the most frequent clinical manifestation in UGIB patients. The use of PPIs did not increase the risk of CVEs, and different PPI drugs did not affect the occurrence of CVEs. Furthermore, PPIs lowered CRP and TNF-α levels in serum of these patients. [ABSTRACT FROM AUTHOR]

Background: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. Methods: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI). Results: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09–1.71), thrombotic events (HR 1.37, 95%CI 1.32–1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33–1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE. Conclusion: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis. [ABSTRACT FROM AUTHOR]

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score. A retrospective analysis was conducted of prospectively collected data of the ARPES and ITA.LI.CA databases. All patients received sorafenib for unresectable HCC from 2008 to 2018. Baseline information to calculate the ESC-2022 and CARDIOSOR scores and registration of evolutive events (including MACE) were available for all patients. The predictive ability of both scores was verified using competing risk regressions and tests for goodness of fit. This study included 843 patients (median follow-up 11.3 months). Thirty-four (4.0%) patients presented a MACE. The four-tier ESC-2022 classification showed a progressive risk increase for every class (cumulative risk 1.7%, 2.7%, 4.3%, and 15.0% in the low, medium, high, and high-risk tiers, respectively). The dichotomous CARDIOSOR scale identified a high-risk group with a fourfold increased risk of MACE (sHR 4.66, p = 0.010; cumulative risk 3.8% and 16.4%). ESC-2022 showed a better goodness of fit compared to the CARDIOSOR score [C-index 0.671 (0.583–0.758) vs 0.562 (0.501–0.634), p = 0.021], but this gap was eliminated using the linear version of CARDIOSOR. Both the ESC-2022 and CARDIOSOR scores discriminated patients at increased risk for MACE. The use of these scores in clinical practice should be encouraged, since therapeutic measures can mitigate the cardiovascular risk. [ABSTRACT FROM AUTHOR]

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort. [ABSTRACT FROM AUTHOR]

Purpose of Review: The population of older adults 60–79 years globally is projected to double from 800 million to 1.6 billion between 2015 and 2050, while adults ≥ 80 years were forecast to more than triple from 125 to 430 million. The risk for cardiovascular events doubles with each decade of aging and each 20 mmHg increase of systolic blood pressure. Thus, successful management of hypertension in older adults is critical in mitigating the projected global health and economic burden of cardiovascular disease. Recent Findings: Women live longer than men, yet with aging systolic blood pressure and prevalent hypertension increase more, and hypertension control decreases more than in men, i.e., hypertension in older adults is disproportionately a women's health issue. Among older adults who are healthy to mildly frail, the absolute benefit of hypertension control, including more intensive control, on cardiovascular events is greater in adults ≥ 80 than 60–79 years old. The absolute rate of serious adverse events during antihypertensive therapy is greater in adults ≥ 80 years older than 60–79 years, yet the excess adverse event rate with intensive versus standard care is only moderately increased. Among adults ≥ 80 years, benefits of more intensive therapy appear non-existent to reversed with moderate to marked frailty and when cognitive function is less than roughly the twenty-fifth percentile. Accordingly, assessment of functional and cognitive status is important in setting blood pressure targets in older adults. Summary: Given substantial absolute cardiovascular benefits of more intensive antihypertensive therapy in independent-living older adults, this group merits shared-decision making for hypertension targets. [ABSTRACT FROM AUTHOR]

Introduction: The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Methods: Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. Results: The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). Conclusion: This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk. [ABSTRACT FROM AUTHOR]

Background: There is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE). Methods: In a retrospective cohort of Medicare beneficiaries aged ≥ 65 years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users. Results: The study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63 years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832–1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45–0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58–0.78). Conclusion: HCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl Peptidase-4 (DPP-4) inhibitors do not suppress cardiovascular events in diabetic patients with a history of cardiovascular disease. However, the effect of DPP-4 inhibitors on cardiovascular events in Japanese diabetic patients is unclear. Therefore, we investigated whether DPP-4 inhibitors alter the incidence of cardiovascular events in Japanese diabetic patients without a history of cardiovascular events. Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study conducted from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. Patients who had had a cardiovascular event by the 2013 follow-up were excluded from the study. JPAD patients were divided into a DPP-4 group and a non-DPP-4 group based on whether they were taking DPP-4 inhibitors at the 2013 follow-up because few patients took DPP-4 inhibitors before 2013. We investigated the incidence of cardiovascular events consisting of coronary events, cerebrovascular events, heart failure requiring hospitalization, and aortic and peripheral vascular disease in 1099 JPAD patients until 2019. Results: During the observation period from 2013 to 2019, 37 (7%) first cardiovascular events occurred in the DPP-4 group (n = 518) and 66 (11%) in the non-DPP-4 group (n = 581). The incidence of cardiovascular events was significantly lower in the DPP-4 group than in the non-DPP-4 group (Log-Rank P = 0.0065). Cox proportional hazards model analysis revealed that the use of DPP-4 inhibitors (hazard ratio 0.65; 95% confidence interval 0.43–0.98; P = 0.038) was an independent factor after adjustment for age ≥ 65 years, hypertension, statin usage, and insulin usage. Conclusions: Our findings have demonstrated that the use of DPP-4 inhibitors may be associated with a reduced incidence of first cardiovascular events in Japanese diabetic patients. The results require confirmation in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Subclinical alterations in cardiac structure and function include a variety of abnormal phenotypes of established adverse prognostic significance such as left ventricular hypertrophy (LVH), alterations of LV geometry, left atrial (LA) enlargement, and aortic root (AR) dilatation. The excess cardiovascular (CV) risk associated with these phenotypes has been consistently demonstrated in different clinical settings such in patients with systemic hypertension, coronary heart disease, diabetes mellitus, chronic kidney disease, heart failure and in geneal population samples. The Pressioni Monitorate e Loro Associazioni (PAMELA), a longitudinal population-based study originally designed to assess the normality values, prognostic significance of office, home and 24-hour blood pressure, including among the many clinical and laboratory variables the collection of echocardiographic data, allowed to gather important information on the clinical prognostic significance of subclinical cardiac damage during a long follow-up period. This article summarizes the original findings provided by the PAMELA study on the clinical correlates and prognostic significance of echocardiographic markers of subclinical organa damage namely LVH, left atrial enlargement (LA) and AR dilatation at the community level. [ABSTRACT FROM AUTHOR]

Aim: The incidence of cardiovascular and renal events was investigated in patients with type 2 diabetes who were classified according to anemia and the components of dialysis-independent chronic kidney disease (CKD) in a prospective observational study. Methods: A population of 778 Japanese patients with type 2 diabetes was prospectively analyzed for 4 years. The outcomes were the incidence of cardiovascular events and renal events. Results: In all subjects, the incidence of cardiovascular and renal events was found to be 5% and 11%, respectively. Even after adjusting for a reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2), the incidence of cardiovascular events was significantly higher (hazard ratio [HR]: 5.73) in patients with anemia and albuminuria than in those without anemia and albuminuria. The incidence of renal events was significantly higher in patients with no anemia and albuminuria (HR: 2.93) and further in those with anemia and albuminuria (HR: 7.56) than in those without anemia and albuminuria even after adjusting for a reduced eGFR. Conclusion: Anemia combined with albuminuria is a risk factor for vascular events in patients with type 2 diabetes, regardless of the eGFR. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to provide an updated review on the active warming effects on major adverse cardiac events, 30-day all-cause mortality, and myocardial injury after noncardiac surgery. Method: We systematically searched MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, Web of Science, and Chinese BioMedical Literature Database. We included randomized controlled trials of adult population undergoing noncardiac surgeries that concentrate on the comparison of active warming methods and passive thermal management. Cochrane Collaboration's tool was applied for risk-of-bias assessment. We used trial sequential analysis to evaluate the possibility of false positive or negative results. Results: A total of 13,316 unique records were identified, of which only 19 with reported perioperative cardiovascular outcomes were included in the systematic review and nine of them were included in final meta-analysis. No statistically significant difference between active warming methods and routine care was found in major adverse cardiac events (RR 0.56, 95% confidence interval (CI) 0.14–2.21, I2 = 71%, number of events 59 vs. 70), 30-day all-cause mortality (RR 0.81, 95% CI 0.43–1.54, I2 = 0%, number of events 17 vs. 21), and myocardial injury after noncardiac surgery (RR 0.61, 95% CI 0.17–2.22, I2 = 79%, number of events 236 vs. 234). Trial sequential analysis suggests that current trials did not reach the minimum information size regarding the major cardiovascular events. Conclusions: Compared to routine perioperative care, we found that active warming methods are not necessary for cardiovascular prevention in patients undergoing noncardiac surgery. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with type 2 diabetes (T2D) are at high risk of experiencing atherosclerotic cardiovascular disease (ASCVD), which is associated with morbidity, mortality and healthcare resource utilisation. Clinical guidelines recommend the use of glucose-lowering medications with cardiovascular benefits in individuals with T2D and cardiovascular disease, but there is evidence that this is not reflected in clinical practice. We used linked national registry data from Sweden to compare outcomes in people with T2D and ASCVD against matched controls with T2D without ASCVD, over 5 years. Direct costs (inpatient, outpatient and selected drug costs), indirect costs resulting from work absence, early retirement, cardiovascular events and mortality were examined. Methods: Individuals with T2D who were at least 16 years old and were alive and resident in Sweden on 1 January 2012 were identified in an existing database. In four separate analyses, individuals with a record indicating ASCVD according to a broad definition, peripheral artery disease (PAD), stroke or myocardial infarction (MI) before 1 January 2012 were identified using diagnosis and/or procedure codes and propensity score matched 1:1 to controls with T2D and without ASCVD, using covariates for birth, sex and level of education in 2012. Follow-up continued until death, migration from Sweden or the end of the study period in 2016. Results: In total, 80,305 individuals with ASCVD, 15,397 individuals with PAD, 17,539 individuals with previous stroke and 25,729 individuals with previous MI were included. Total mean annual costs per person were €14,785 for PAD (2.7 × costs for controls), €11,397 for previous stroke (2.2 × controls), €10,730 for ASCVD (1.9 × controls) and €10,342 for previous MI (1.7 × controls). Indirect costs and costs of inpatient care were the major cost drivers. ASCVD, PAD, stroke and MI were all associated with an increased likelihood of early retirement, cardiovascular events and mortality. Conclusions: ASCVD is associated with considerable costs, morbidity and mortality in individuals with T2D. These results support structured assessment of ASCVD risk and broader implementation of guideline-recommended treatments in T2D healthcare. [ABSTRACT FROM AUTHOR]

Purpose: The ratio of low-density lipoprotein cholesterol (LDL-C)/apolipoprotein B (apo B) is associated with all-cause mortality and cardiovascular events in chronic kidney disease patients. The aim of this study was to investigate the association between the LDL-C/apo B ratio (LAR) and all-cause mortality and cardiovascular events in peritoneal dialysis (PD) patients. Methods: A total of 1199 incident PD patients were enrolled from November 1, 2005 to August 31, 2019. The LAR was used to divide the patients into two groups by X-Tile software and restricted cubic splines using 1.04 as the cutoff. The incidence of all-cause mortality and cardiovascular events at follow-up was compared according to LAR. Results: Of the 1199 patients, 58.0% were men, the mean age was 49.3 ± 14.5 years, 225 patients had a history of diabetes, and 117 patients had prior cardiovascular disease. During the follow-up period, 326 patients died, and 178 patients experienced cardiovascular events. After full adjustment, a low LAR was significantly associated with HRs for all-cause mortality of 1.37 (95% CI 1.02–1.84, P = 0.034) and for cardiovascular events of 1.61 (95% CI 1.10–2.36, P = 0.014). Conclusion: This study suggests that a low LAR is an independent risk factor for all-cause mortality and cardiovascular events in PD patients, indicating that the LAR may provide significant information when assessing all-cause mortality and cardiovascular risks. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D). Methods: A comprehensive search was conducted in six databases, from inception to January 27, 2022. Clinical trials that compared fibrate therapy with other lipid-lowering interventions or placebo were included. Outcomes of interest comprised cardiovascular (CV) events, complications of T2D, metabolic profile, and adverse events. Random-effects meta-analyses were performed to estimate mean differences (MD) and risk ratios (RR), alongside 95% confidence intervals (CI). Results: A total of 25 studies were included, six comparing fibrates against statins, 11 against placebo, and eight evaluating the combination of fibrates with statins. Overall risk of bias was rated as moderate, and most outcomes rendered low confidence per GRADE approach. Fibrates showed reduction of serum triglycerides (TGs) (MD −17.81, CI −33.92 to −1.69) and a marginal increase of high-density lipoprotein cholesterol (HDL-c) (MD: 1.60, CI 0.29 to 2.90) in adults with T2D, but no differences were found in CV events when compared to statin therapy (RR 0.99, CI 0.76 to 1.09). When used in combination with statins, no major differences were exhibited regarding lipid profile and CV outcomes. Adverse events were comparable between fibrate and statin monotherapies (e.g., RR of 1.03 for rhabdomyolysis, and 0.90 for gastrointestinal events). Conclusions: Fibrate therapy in patients with T2D results in a marginal improvement of TGs and HDL-c but without reducing the risk of CV events and mortality. Their use should be reserved for very specific scenarios after a deliberative dialogue between patients and clinicians regarding their benefits and harms. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of finerenone on cardiovascular events in Kidney Disease and/or Diabetes. Methods: The ClinicalTrials.gov, Medline, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to December 20, 2021 in order to identify randomized controlled trials that evaluated the effect of finerenone on cardiovascular events in Kidney Disease and/or Diabetes, without language restriction. This meta-analysis collected data from 7 randomized clinical trials that evaluated the effect of finrrenone in 15,618 patients with kidney disease and/or diabetes. Risk of bias was assessed by Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed by I2 statistic. The main endpoints included death from cardiovascular causes, death from any cause, incidence of myocardial infarction, rate of heart failure, hospitalization for any cause, rate of total advent events and study-drug-related adverse events. Results: A total of 7 randomized controlled trials involving 15,618 fulfilled the inclusion criteria. The outcomes of this meta-analysis presented that finerenone significantly reduced the death from any cause (95% CI 0.82–0.99; P = 0.031), risk of heart failure (95% CI 0.67–0.92; P = 0.002) among patients with kidney disease and/or diabetes when compared to control group. Besides, finerenone could not reduce the incidence of death from cardiovascular, myocardial infarction and hospitalization for any cause among patients with kidney disease and/or diabetes (p > 0.05). In terms of safety, finerenone shared the same risk of total advent events with placebo among patients with kidney disease and/or diabetes (p > 0.05). However, finerenone had higher risk of study-drug-related advent events than placebo among patients with kidney disease and/or diabetes (95% CI 1.27–1.48; P < 0.001). Conclusions: In patients with kidney disease and/or diabetes, treatment with finerenone resulted in lower risk of death from any cause and heart failure than placebo. However, the study-drug-related advent events also increased significantly at the same time. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular events (CVE) are the leading cause of death in peritoneal dialysis (PD) patients. The predictive value of cardiac valve calcification (CVC) for CVE in dialysis patients remains controversial. In particular, such studies are limited in PD patients. We aimed to examine the predictive role of CVC for CVE and cardiovascular mortality in PD patients. Methods: A retrospective analysis was performed on patients who initiated PD in our hospital. According to the result of echocardiography, patients were divided into CVC group and non-CVC group. The differences in baseline demographic characteristics, biochemical variables, comorbidities, and clinical outcomes between the two groups were compared. Kaplan–Meier method was used to obtain survival curves. The Cox regression model was used to evaluate the influence of CVC for cardiovascular outcomes. The inverse probability of treatment weighting (IPTW) was used to eliminate influence of the confounders in the groups. Results: 458 peritoneal dialysis patients were enrolled in this study. 77 patients were in CVC group and 381 patients in non-CVC group. The average follow-up time was (32 ± 21) months. At baseline, the absolute standardized difference (ASD) of age, BMI, history of CVE, diabetes, LVEF, LVMI, albumin, calcium, phosphorus, triglycerides, hsCRP, urine volume, Kt/V, statins and vitamin D intake rate were greater than 0.1 between the two groups. All of ASD dropped to less than 0.1 after IPTW, which meant that the balance had been reached between the two groups. Multivariable logistic analysis showed that advanced age, diabetes, and hyperphosphatemia were associated with CVC. The Kaplan–Meier survival curve showed the cumulative CVE-free survival rate and cardiovascular survival rate of CVC group were significantly lower than that of non-CVC group before and after IPTW (log-rank P < 0.05). After IPTW was used to eliminate the effect of confounders, multivariate Cox regression analysis still showed CVC was an independent risk factor for CVE (HR = 2.383, 95% CI 1.331~4.264, P = 0.003) and cardiovascular mortality (HR = 2.347, 95% CI 1.211~4.548, P = 0.012) in PD patients. Conclusion: The prevalence of CVC is high in peritoneal dialysis patients. CVC is an independent risk factor for CVE and cardiovascular mortality in peritoneal dialysis patients. [ABSTRACT FROM AUTHOR]

Introduction: Prior studies have found considerable disparities in prevalence and outcomes for patients with peripheral arterial disease (PAD). This study compared rates of diagnostic testing, treatment patterns, and outcomes after diagnosis of PAD among commercially insured Black and White patients in the United States. Methods: Optum's de-identified Clinformatics® Data Mart Database (1/2016–6/2021) were used to identify Black and White patients with PAD; first PAD diagnosis was deemed study index date. Baseline demographics, markers of disease severity, and healthcare costs were compared between cohorts. Patterns of medical management and rates of major adverse limb events (MALE; including acute or chronic limb ischemia, lower-limb amputation) and cardiovascular (CV) events (stroke, myocardial infarction) during the available follow-up period were described. Outcomes were compared between cohorts using multinomial logistic regression models, Kaplan–Meier survival analysis, and Cox proportional hazards models. Results: A total of 669,939 patients were identified, with 454,382 White patients and 96,162 Black patients. Black patients were younger on average (71.8 years vs. 74.2 years), but had higher comorbid burden, concomitant risk factors, and CV medication use at baseline. Prevalence of diagnostic testing, revascularization procedures, and medication use was numerically higher among Black patients. Black patients were also more likely than the White patients to receive medical therapy without a revascularization procedure [adjusted odds ratio with 95% confidence interval (CI) = 1.47 (1.44–1.49)]. However, Black patients with PAD had higher incidence of MALE and CV events than White patients [adjusted hazard ratio for composite event (95% CI) = 1.13, (1.11–1.15)]. Except myocardial infarction, the hazards of individual components of MALE and CV events were also significantly higher among Black patients with PAD. Conclusions: Results of this real-world study suggest that Black patients with PAD have higher disease severity at the time of diagnosis and are at increased risk of experiencing adverse outcomes following diagnosis. [ABSTRACT FROM AUTHOR]

High alkaline phosphatase (ALP) levels are reported to be associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Given the pathological link with CKD, a similar relationship may exist in patients with atrial fibrillation (AF). We retrospectively evaluated 1,719 patients with AF and normal hepatic function who were registered in the Shinken Database between November 2011 and March 2017. Study patients were divided into three groups according to ALP value tertiles with cut-offs of 175 and 227 IU/L (normal range: 95–350 IU/L). Each group's incidence rate was recorded, and the risks of cardiovascular events and each component for patients in the middle and high ALP tertiles were compared with those in the low tertile and evaluated using Cox regression models. The additional predictive value of the high ALP tertile over the existing risk scores for the components of cardiovascular events was evaluated via receiver operating characteristic (ROC) curve analysis. During the median follow-up of 731 days (IQR: 444–1095 days), 137 cardiovascular events occurred, with incidence rates of 2.94%, 3.44%, and 6.19%/person-year for the low, middle, and high ALP tertiles, respectively. Of these cardiovascular events, heart failure had the highest incidence rates (1.34%, 1.89%, and 4.29%/person-year for the low, middle, and high ALP tertiles, respectively) and the incidence rates of the other components of cardiovascular event were similar in each ALP groups. Multivariate Cox regression analysis yielded hazard ratios of 1.22 (95% confidence interval [CI] 0.70–1.96) and 1.62 (95% CI 1.06–2.48) for cardiovascular events and 1.66 (95% CI 0.87–3.15) and 2.50 (95% CI 1.39–4.48) for heart failure admission in the middle and high ALP tertiles, respectively. By ROC curve analysis for heart failure admission showed that the high ALP tertile lacked significant additive predictive value over the existing risk scores. High serum ALP levels, even those in the normal range, were significantly associated with an increased risk of cardiovascular events, especially heart failure admission in patients with AF. [ABSTRACT FROM AUTHOR]

Background: It is necessary to re-examine the optimal phosphate (P) and calcium (Ca) target values in the contemporary management of chronic kidney disease–mineral and bone disorder to reduce the risks of cardiovascular events in patients receiving hemodialysis. Methods: We performed a post-hoc analysis of the LANDMARK study. The outcomes were defined as cardiovascular events and all-cause death. Data from 2135 patients receiving hemodialysis at risk of vascular calcification were analyzed using a time-dependent Cox proportional hazard model adjusted for background factors. Results: On the hazard ratio (HR) curve, the ranges where the lower 95% confidence interval (CI) were below the minimum of HR (= 1.00) were as follows: P = 3.5–5.5 mg/dL; albumin-adjusted Ca < 9.1 mg/dL for cardiovascular events; and P = 3.6–5.3 mg/dL; albumin-adjusted Ca < 9.1 mg/dL for all-cause mortality. In stratified analysis, the HRs for cardiovascular events in P < 3.5 mg/dL and P ≥ 5.5 mg/dL were similar to that of P = 3.5–5.5 mg/dL (P ≥ 0.05), and albumin-adjusted Ca ≥ 9.1 mg/dL had higher HR than values < 9.1 mg/dL [1.30 (95% CI 1.00–1.68; P = 0.046)]. For all-cause mortality, the HR in P < 3.6 mg/dL was higher than that in P = 3.6–5.3 mg/dL [1.76 (95% CI 1.25–2.48; P = 0.001)], while the HRs between P ≥ 5.3 mg/dL and P = 3.6–5.3 mg/dL as well as those between albumin-adjusted Ca ≥ 9.1 and < 9.1 mg/dL were not significantly different (P ≥ 0.05). Conclusions: Managing albumin-adjusted Ca < 9.1 mg/dL may reduce the cardiovascular risk among patients undergoing hemodialysis. Hypophosphatemia < 3.6 mg/dL may be associated with mortality. [ABSTRACT FROM AUTHOR]

Background: This study assessed the association of pathological kidney lesions with cardiovascular events in biopsy-proven diabetic kidney disease (DKD) with type 2 diabetes.This multicenter, retrospective study involved 244 patients with no previous cardiovascular events before biopsy, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at biopsy (baseline), and ≥ 1 year of observation after biopsy. The outcomes were the first occurrence of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, coronary intervention, or non-fatal stroke), and non-cardiovascular deaths before cardiovascular events were considered competing events. The association between the severity of each pathological lesion and cardiovascular events was investigated.During follow-up (median: 6.4 years), 43 patients experienced cardiovascular events. The baseline clinical characteristics did not differ according to cardiovascular events. The cumulative incidence of cardiovascular events was higher in patients with mesangiolysis, global glomerulosclerosis ≥ 50%, moderate/severe interstitial inflammation, and moderate/severe arteriolar hyalinosis than in those having less advanced each lesion. Fine–Gray regression models revealed that global glomerulosclerosis ≥ 50% (subdistribution hazard ratio [SHR]: 3.85; 95% confidence interval [95% CI] 1.28–11.52), moderate/severe interstitial inflammation (SHR: 2.49; 95% CI 1.18–5.29), and moderate/severe arteriolar hyalinosis (SHR: 3.51; 95% CI 1.15–10.69) were linked to increased risk of cardiovascular events, after adjusting for clinical variables including RAAS inhibitors use at baseline. Adding the severity of these lesions to clinical variables improved the predictive value for cardiovascular events.In DKD with type 2 diabetes, advanced glomerulosclerosis, interstitial inflammation, and arteriolar hyalinosis were associated with cardiovascular events, adding predictive value to clinical features.Methods: This study assessed the association of pathological kidney lesions with cardiovascular events in biopsy-proven diabetic kidney disease (DKD) with type 2 diabetes.This multicenter, retrospective study involved 244 patients with no previous cardiovascular events before biopsy, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at biopsy (baseline), and ≥ 1 year of observation after biopsy. The outcomes were the first occurrence of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, coronary intervention, or non-fatal stroke), and non-cardiovascular deaths before cardiovascular events were considered competing events. The association between the severity of each pathological lesion and cardiovascular events was investigated.During follow-up (median: 6.4 years), 43 patients experienced cardiovascular events. The baseline clinical characteristics did not differ according to cardiovascular events. The cumulative incidence of cardiovascular events was higher in patients with mesangiolysis, global glomerulosclerosis ≥ 50%, moderate/severe interstitial inflammation, and moderate/severe arteriolar hyalinosis than in those having less advanced each lesion. Fine–Gray regression models revealed that global glomerulosclerosis ≥ 50% (subdistribution hazard ratio [SHR]: 3.85; 95% confidence interval [95% CI] 1.28–11.52), moderate/severe interstitial inflammation (SHR: 2.49; 95% CI 1.18–5.29), and moderate/severe arteriolar hyalinosis (SHR: 3.51; 95% CI 1.15–10.69) were linked to increased risk of cardiovascular events, after adjusting for clinical variables including RAAS inhibitors use at baseline. Adding the severity of these lesions to clinical variables improved the predictive value for cardiovascular events.In DKD with type 2 diabetes, advanced glomerulosclerosis, interstitial inflammation, and arteriolar hyalinosis were associated with cardiovascular events, adding predictive value to clinical features.Results: This study assessed the association of pathological kidney lesions with cardiovascular events in biopsy-proven diabetic kidney disease (DKD) with type 2 diabetes.This multicenter, retrospective study involved 244 patients with no previous cardiovascular events before biopsy, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at biopsy (baseline), and ≥ 1 year of observation after biopsy. The outcomes were the first occurrence of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, coronary intervention, or non-fatal stroke), and non-cardiovascular deaths before cardiovascular events were considered competing events. The association between the severity of each pathological lesion and cardiovascular events was investigated.During follow-up (median: 6.4 years), 43 patients experienced cardiovascular events. The baseline clinical characteristics did not differ according to cardiovascular events. The cumulative incidence of cardiovascular events was higher in patients with mesangiolysis, global glomerulosclerosis ≥ 50%, moderate/severe interstitial inflammation, and moderate/severe arteriolar hyalinosis than in those having less advanced each lesion. Fine–Gray regression models revealed that global glomerulosclerosis ≥ 50% (subdistribution hazard ratio [SHR]: 3.85; 95% confidence interval [95% CI] 1.28–11.52), moderate/severe interstitial inflammation (SHR: 2.49; 95% CI 1.18–5.29), and moderate/severe arteriolar hyalinosis (SHR: 3.51; 95% CI 1.15–10.69) were linked to increased risk of cardiovascular events, after adjusting for clinical variables including RAAS inhibitors use at baseline. Adding the severity of these lesions to clinical variables improved the predictive value for cardiovascular events.In DKD with type 2 diabetes, advanced glomerulosclerosis, interstitial inflammation, and arteriolar hyalinosis were associated with cardiovascular events, adding predictive value to clinical features.Conclusions: This study assessed the association of pathological kidney lesions with cardiovascular events in biopsy-proven diabetic kidney disease (DKD) with type 2 diabetes.This multicenter, retrospective study involved 244 patients with no previous cardiovascular events before biopsy, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 at biopsy (baseline), and ≥ 1 year of observation after biopsy. The outcomes were the first occurrence of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, coronary intervention, or non-fatal stroke), and non-cardiovascular deaths before cardiovascular events were considered competing events. The association between the severity of each pathological lesion and cardiovascular events was investigated.During follow-up (median: 6.4 years), 43 patients experienced cardiovascular events. The baseline clinical characteristics did not differ according to cardiovascular events. The cumulative incidence of cardiovascular events was higher in patients with mesangiolysis, global glomerulosclerosis ≥ 50%, moderate/severe interstitial inflammation, and moderate/severe arteriolar hyalinosis than in those having less advanced each lesion. Fine–Gray regression models revealed that global glomerulosclerosis ≥ 50% (subdistribution hazard ratio [SHR]: 3.85; 95% confidence interval [95% CI] 1.28–11.52), moderate/severe interstitial inflammation (SHR: 2.49; 95% CI 1.18–5.29), and moderate/severe arteriolar hyalinosis (SHR: 3.51; 95% CI 1.15–10.69) were linked to increased risk of cardiovascular events, after adjusting for clinical variables including RAAS inhibitors use at baseline. Adding the severity of these lesions to clinical variables improved the predictive value for cardiovascular events.In DKD with type 2 diabetes, advanced glomerulosclerosis, interstitial inflammation, and arteriolar hyalinosis were associated with cardiovascular events, adding predictive value to clinical features. [ABSTRACT FROM AUTHOR]

Excessive apoptosis and its insufficient clearance is characteristic of atherosclerotic plaques. Fortilin has potent antiapoptotic property and is abundantly expressed in atherosclerotic plaques. Fortilin-deficient mice had less atherosclerosis with more macrophage apoptosis. Recently, we reported that plasma fortilin levels were high in patients with coronary artery disease (CAD). However, its prognostic value has not been elucidated. We investigated plasma fortilin levels and major adverse cardiovascular events (MACE) in 404 patients (mean age 68 ± 12 years; 276 males) undergoing coronary angiography for suspected CAD. MACE was defined as cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or coronary revascularization. Of the 404 patients, 218 (54%) had CAD. Plasma fortilin levels were higher in patients with CAD than without CAD (median 74.9 vs. 70.9 pg/mL, p < 0.05). During a mean follow-up of 5.7 ± 4.2 years, MACE was observed in 59 (15%) patients. Notably, patients with MACE had higher fortilin levels (median 83.0 vs. 71.4 pg/mL) and more often had fortilin level > 80.0 pg/mL (54% vs. 36%) than those without MACE (p < 0.025). A Kaplan-Meier analysis showed lower event-free survival in patients with fortilin > 80.0 pg/mL than in those with ≤ 80.0 pg/mL (p < 0.001). In multivariate Cox proportional hazards analysis, fortilin level (> 80.0 pg/mL) was an independent predictor of MACE (hazard ratio: 2.29, 95%CI: 1.36–3.85, p < 0.002). Among the 218 patients with CAD, fortilin level was also a significant predictor of MACE (hazard ratio: 2.48; 95%CI: 1.34–4.61, p < 0.005). Thus, high plasma fortilin levels were found to be associated with cardiovascular events in patients with CAD as well as those undergoing coronary angiography. [ABSTRACT FROM AUTHOR]

Introduction: Comorbid diabetes, hypertension, and hyperlipidemia is associated with an adverse effect on cardiovascular (CV) outcomes. Adherence to concurrent anti-diabetics, anti-hypertensives, and lipid-lowering therapies is essential to achieve therapeutic benefits. Aim: The objective was to evaluate the association between adherence to concomitant oral antidiabetics, statins, and RAS antagonists (triple therapy) and CV outcomes, among elderly patients using marginal structural modeling (MSM). Methods: A retrospective study was conducted among patients on concurrent triple therapy from January 2016 until December 2019. Adherence to concurrent triple therapy was measured every 6 months using proportion of days covered (PDC) to determine the different adherence groups. CV outcomes were also measured every 6 months. A MSM controlling for baseline covariates and time-varying confounders affected by prior adherence was conducted to evaluate the association between adherence and CV outcomes. A sub-analysis was conducted among patients with prior CV events to evaluate the association between adherence to triple therapy and CV outcomes using MSMs. Results: The final cohort comprised of 7433 patients. The MSM model revealed no significant associations between adherence to triple/double therapies and cardiovascular outcomes. For sub-analysis, 471 patients with a prior CV event were identified. Results of the sub-analysis revealed no significant associations between adherence to triple/double therapies and CV outcomes among patients with prior CV events. Conclusion: Future studies should evaluate the association with longer follow-up periods. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of paclitaxal-coated balloon (PCB) versus conventional balloon (CB) on side branch (SB) lesion and cardiovascular outcomes in patients with de novo true bifurcation lesions. Methods: In total, 219 patients with de novo true bifurcation lesions were enrolled and divided into PCB group (102 cases) and CB group (117 cases) according to angioplasty strategy in SB. Drug-eluting stent (DES) was implanted in main vessel (MV) for each subject. All subjects underwent a 12-month follow-up for late lumen loss (LLL), restenosis, and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). MACEs included cardiac death, nonfatal myocardial infarction, and unstable angina requiring admission. Results: There were no differences in diameter, minimum lumen diameter (MLD), and stenosis for bifurcation lesions between the two groups before and immediately after PCI (P > 0.05). After 12-month follow-up, no differences occurred in MV-MLD and MV-LLL between the two groups (P > 0.05); SB-MLD in PCB group was higher than that in CB group (1.97 ± 0.36 mm vs. 1.80 ± 0.43 mm, P = 0.007); SB-LLL in PCB group was lower than that in CB group (0.11 ± 0.18 mm vs. 0.19 ± 0.25 mm, P = 0.024). Multivariate COX analyses indicated that PCB group had lower MACE risk than CB group (HR = 0.480, 95%CI 0.244–0.941, P = 0.033). Conclusion: PCB could decrease SB-LLL and MACE risk in patients with de novo true coronary bifurcation lesion 12 months after single-DES intervention. [ABSTRACT FROM AUTHOR]

Purpose of Review: Influenza infection is a significant, well-established cause of cardiovascular disease (CVD) and CV mortality. Influenza vaccination has been shown to reduce major adverse cardiovascular events (MACE) and CV mortality. Therefore, major society guidelines have given a strong recommendation for its use in patients with established CVD or high risk for CVD. Nevertheless, influenza vaccination remains underutilized. Historically, influenza vaccination is administered to stable outpatients. Until recently, the safety and efficacy of influenza vaccination among patients with acute myocardial infarction (MI) had not been established. Recent Findings: The recently published Influenza Vaccination after Myocardial Infarction (IAMI) trial showed that influenza vaccination within 72 h of hospitalization for MI led to a significant 28% reduction in MACE and a 41% reduction in CV mortality, without any excess in serious adverse events. Additionally, we newly performed an updated meta-analysis of randomized clinical trials (RCTs) including IAMI and the recent Influenza Vaccine to Prevent Adverse Vascular Events (IVVE) trial. In pooled analysis of 8 RCTs with a total of 14,420 patients, influenza vaccine, as compared with control/placebo, was associated with significantly lower risk of MACE at follow-up [RR 0.75 (95%CI 0.57–0.97), I2 56%]. Summary: The recent IAMI trial showed that influenza vaccination in patients with recent MI is safe and efficacious at reducing CV morbidity and mortality. Our updated meta-analysis confirms a 25% reduction in MACE. The influenza vaccine should be strongly encouraged in all patients with CVD and incorporated as an essential facet of post-MI care and secondary CVD prevention. [ABSTRACT FROM AUTHOR]

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan–Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036–2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is associated with an increased risk of heart failure (HF), stroke, and death. Although fibrillation cycle length (FCL) is used as a surrogate for atrial refractoriness, its impact on outcomes remains unclear. This study aimed to identify predictors of cardiovascular events, including FCL, in patients with long-standing persistent AF. Methods: The study included 190 consecutive patients with long-standing persistent AF (mean age 74 years, 74% male). Patients with valvular AF or hemodialysis-dependent end-stage renal disease and those on anti-arrhythmic drugs were excluded. The primary composite outcome was occurrence of cardiovascular events (myocardial infarction, HF), cerebrovascular events (stroke, transient ischemic attack), and all-cause death. FCL was calculated by fast Fourier transformation analysis of fibrillation waves in the surface electrocardiogram. Results: Over a median follow-up of 2.6 years, the primary outcome occurred in 31 patients (cardiovascular events, n = 18; cerebrovascular events, n = 8; all-cause death, n = 5). In multivariate analysis, longer FCL and history of HF were independent predictors of these outcomes. In a Cox proportional hazards model adjusted for age, sex, and history of HF, patients with an FCL > 160 ms (cut-off determined by receiver-operating characteristic curve analysis) were at increased risk of the outcome (hazard ratio 12.9; 95% confidence interval 4.99–44.10; p < 0.001). Conclusions: FCL was independently associated with cardiovascular outcomes in patients with long-standing persistent AF. [ABSTRACT FROM AUTHOR]

Background: In some stent implanted patients, cardiovascular events (CE) may occur. Acetylsalicylic acid (ASA) is routinely administered to these patients in order to prevent the occurrence of CE. CE may be related to gene variations which cause ASA resistance (AR). Therefore, it was aimed to investigate the relationship between COX-1, COX-2, CYP2C9 and CYP2C19 variations with CE due to AR. Materials and results: Seventy-four stent implanted patients, using 100 mg of ASA per day during five years were enrolled into the study. Following stent implantation, thirty-eight patients who had a CE within five years due to AR and 36 patients without CE were enrolled in patient and control group, respectively. AR was confirmed by platelet aggregation testing. After DNA isolation from blood; COX-1, COX-2, CYP2C19 and CYP2C9 variations were investigated with real-time polymerase chain reaction. At the end of this study, heterozygous genotype of COX-1 was found statistically high in patients whereas heterozygous genotype of CYP2C19*17 was found statistically high in controls. The presence of C and G allele in COX-1 and COX-2 were found statistically high in patients, respectively. The presence of T allele in CYP2C19*17 was found statistically high in controls. Heterozygous genotype of COX-1 variation was found statistically high in patients who have AR. Additionally heterozygous genotype of CYP2C19*17 was found statistically high in patients who have low thrombosis risk. Conclusions: COX-1 and COX-2 gene mutations may increase the risk of CE due to AR whereas CYP2C19*17 may have a protective effect in this process. [ABSTRACT FROM AUTHOR]

Purpose: Cardiovascular disease is the leading cause of death in maintenance hemodialysis (MHD) patients. The aim of this study is to investigate the predictive value of coronary artery calcification score (CACs) combined with bone mineral density (BMD) for the risk of cardiovascular diseases in MHD patients. Methods: From January 2017 to January 2019, we enrolled 112 MHD patients and 112 controls in Ningbo First Hospital, and retrospectively counted the cardiovascular events in the next 2 years after enrollment. According to the occurrence of cardiovascular events, the MHD patients were divided into CVD group and non-CVD group. The differences of vertebral BMD and CACs between the two groups were compared. ROC curve, Kaplan–Meier curve and Cox regression analyses were used for assess the predictive value of 2-year cardiovascular events in MHD patients. Results: Among 112 MHD patients, 49 (43.75%) patients had cardiovascular events. The results showed that the average value of BMD in MHD patients was significantly lower than that in the control group (99.88 ± 30.99 VS. 108.35 ± 23.98, P = 0.0231). The CACs in MHD patients were significantly higher than that in the control group (317.81 ± 211.53 VS. 190.03 ± 100.50, P < 0.001). The results between CVD group and the non-CVD group were to the same direction (BMD: 81.12 ± 31.28 VS. 114.48 ± 21.61, P < 0.001; CACs: 447.16 ± 234.11 VS. 217.21 ± 119.03, P < 0.001). Besides, CACs combined with BMD yield an AUC of 0.875 with a sensitivity of 79.60%, a specificity of 82.50%. Kaplan–Meier curve and Cox regression analyses indicated that CACs and BMD were independently associated with high risk of cardiovascular events in MHD patients. Conclusion: The combination of CACs and vertebral BMD could predict the occurrence of cardiovascular events in MHD patients to some extent. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high‐sensitivity C‐reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD). Methods: We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations. Results: 350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle–brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 > 220 ng/mL was a predictor of cardiovascular events, while the EF < 50% was a predictor for renal outcomes. For CKD patients with PCSK9 > 220 ng/mL and hsCRP > 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers. Conclusion: The results of this study show that PCSK9 > 220 ng/mL was predictor for cardiovascular events, while EF < 50% was predictor for CKD progression to ESRD. PCSK9 > 220 ng/mL and hsCRP > 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that sleep apnea hypopnea syndrome (SAHS) is an independent risk factor that contributes to certain cardiovascular events. However, there are studies arguing that patients with SAHS had lower peak troponin levels when suffering cardiovascular events compared to patients without SAHS, which indicates that there may potentially be a protective effect of SAHS. This meta-analysis aimed to assess the impact of SAHS on cardiovascular events. Methods: Databases were searched for studies that examined cardiac biomarkers or reported angiographic data when patients with SAHS experienced cardiovascular events. The data about peak cardiac biomarkers and angiographic coronary lesion were extracted and then used to compute the pooled standardized mean difference (SMD) and 95% confidence interval (95% CI). Results: Among 26 studies included in the meta-analysis, there was not a definite difference between the SAHS group and the control group for troponins (SMD, 0.05; 95% CI, [− 0.16, 0.26]), creatine kinase (SMD, − 0.08; 95% CI, [− 0.38, 0.22]), and CK-MB (SMD, − 0.11; 95% CI, [− 0.51, 0.29]). However, patients with SAHS revealed worse coronary lesion condition grading via both Gensini score (SMD, 0.63; 95% CI, [0.31, 0.95]) and SYNTAX score (SMD, 0.99; 95% CI, [0.31–1.67]). Conclusions: Ischemic preconditioning induced by the intermittent hypoxia at the early stage could generate a cardiac protection effect, which would then benefit SAHS patients encountering a major adverse cardiovascular event. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used. [ABSTRACT FROM AUTHOR]

Introduction: Cardio-cerebrovascular (CCV) disease contributes significantly to the global burden of disease, with dramatic consequences in terms of mortality and general health. Mitigate CCV risk factors is the key to reduce individual and population risk of CCV events. Evidence-based medicine and epidemiological investigations of risk factors are essential to optimize actions. Aim: To contribute to the knowledge of the burden of risk factors in determining CCV events in the individual patient and in the community. Methods: Clinical data and risk factors were collected through a longitudinal survey (1999) as part of a larger epidemiology and cardiovascular prevention project, namely the "VIP (Valle dell'Irno Prevention) Project". We assessed the incidence of major cardiovascular events (MACE) and for each risk factor we calculated: prevalence, absolute risk, odds ratio (OR), additional risk (AR) = risk of exposed to the risk factor − risk of non-exposed, population attributable risk (PAR) = additional risk * prevalence, population attributable risk fraction (PAF) = PAR/total incidence of the disease. Results: Comparing the MACE group with the non-MACE group, a statistically significant difference was found for the following: glomerular filtration rate (GFR), glucose and systolic blood pressure (SBP), BMI, diastolic blood pressure (DBP), cholesterol, triglycerides, creatinine and uric acid. GFR, glucose and SBP showed the highest OR. Age, creatinine, glycemia, SBP and uric acid were independent predictor of MACE. When calculating the PAF, the CCV risk factors with the greatest impact on MACE were: SBP (29.6%), triglyceridemia (19.4%) and metabolic syndrome (18.3%). Conclusion: The burden of risk factors on MACE changes substantially according to whether it is calculated in the single patient or in the population. It is crucial for physicians to take these differences into account when applying their own intervention to reduce CCV events. [ABSTRACT FROM AUTHOR]

Background: The impact of serum uric acid (SUA) on development of cardiovascular disease (CVD) in patients undergoing peritoneal dialysis (PD) remains controversial, especially the impact of hypouricemia (HUA) on CVD. The aim of our study was to investigate the influence of low-level SUA on cardiovascular (CV) events in PD patients. Methods: A retrospective cohort study was conducted.728 PD patients from February 1, 2010 to May 31, 2019 were enrolled. All demographic and laboratory data were collected at baseline and 6 months after PD treatment. The study cohort was divided into four groups according to SUA level (μmol/L) after 6 months of PD: Group1 (< 360), Group2 (360–420), Group3 (420–480), Group4 (≥ 480). The clinical characteristics of each group were analyzed. With Group2 as reference, logistic regression analysis was performed to investigate the correlation between SUA levels and risk of CV events in patients undergoing PD. Use Kaplan–Meier method to generate CV events risk graph. Results: 728 patients were enrolled in this study, including 403 (55.4%) males and 325 (44.6%) females, with an average age of 48.66 ± 13.98 years; of which 158 (21.7%) patients developed CV events. Multivariate COX regression showed that after adjusting for multiple clinical factors, Group1 (HR = 1.92, 95% CI 1.17–3.15, P = 0.01), Group3 (HR = 1.89, 95% CI 1.13–3.15, P = 0.015), and Group4 (HR = 2.38, 95% CI 1.35–4.19, P = 0.003) are all independent risk factors for developing CV events. The Kaplan–Meier risk curve of CV events showed that the risk of CV events in the Group1, Group3 and Group4 were significantly higher (Log-Rank = 12.67; P = 0.005). Restricted cubic spline (RCS) showed that SUA level is non-linearly associated with the risk of CV events, showing an U-shaped curve ( χ 4 2 =13.3 P = 0.01). Conclusions: Our study suggested that patients with SUA level less than 360 μmol/L also exhibited the higher risk for developing CV events, an U-shaped association between SUA level and risk of CV events in patients undergoing PD. Both SUA levels below 360 μmol/L and above 420 μmol/L were found to be significant risk factors for developing CV events in patients undergoing long-term PD. [ABSTRACT FROM AUTHOR]

Whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events (CVEs) independently from metabolic syndrome (MetS) is still matter of debate. Aim of the study was to investigate the risk of CVEs in a high-risk population of patients with non-valvular atrial fibrillation (AF) according to the presence of MetS and NAFLD. Prospective observational multicenter study including 1,735 patients with non-valvular AF treated with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). NAFLD was defined by a fatty liver index ≥ 60. We categorized patients in 4 groups: 0 = neither MetS or NAFLD (38.6%), 1 = NAFLD alone (12.4%), 2 = MetS alone (19.3%), 3 = both MetS and NAFLD (29.7%). Primary endpoint was a composite of CVEs. Mean age was 75.4 ± 9.4 years, and 41.4% of patients were women. During a mean follow-up of 34.1 ± 22.8 months (4,926.8 patient-years), 155 CVEs were recorded (incidence rate of 3.1%/year): 55 occurred in Group 0 (2.92%/year), 12 in Group 1 (2.17%/year), 45 in Group 2 (4.58%/year) and 43 in Group 3 (2.85%/year). Multivariable Cox regression analysis showed that use of DOACs, and female sex were inversely associated with CVEs, whilst age, heart failure, previous cardiac and cerebrovascular events, and group 2 (Group 2, Hazard Ratio 1.517, 95% Confidence Interval, 1.010–2.280) were directly associated with CVEs. In patients with AF, MetS increases the risk of CVEs. Patients with NAFLD alone have lower cardiovascular risk but may experience higher liver-related complications. [ABSTRACT FROM AUTHOR]

Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD. [ABSTRACT FROM AUTHOR]

Aims: Longitudinal studies of the association between sex and adverse clinical outcomes in patients with chronic kidney disease (CKD) are scarce. We assessed whether major outcomes may differ by sex among CKD patients. Methods: We analyzed a total of 1780 participants with non-dialysis CKD G1-5 from the KoreaN cohort study for Outcome in patients with Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of non-fatal cardiovascular events or all-cause mortality. Secondary outcomes included fatal and non-fatal cardiovascular events, all-cause mortality, and a composite kidney outcome of ≥ 50% decline in estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease. Results: There were 1088 (61%) men and 692 (39%) women in the study cohort. The proportion of smokers was significantly higher in men (24% vs. 3%). During 8430 person-years of follow-up, 201 primary outcome events occurred: 144 (13%) in men and 57 (8%) in women, with corresponding incidence rates of 2.9 and 1.7 per 100 person-years, respectively. In multivariable Cox models, men were associated with a 1.58-fold (95% CI 1.06–2.35) higher risk of composite outcome. Propensity score matching analysis revealed similar findings (HR 1.81; 95% CI 1.14–2.91). Risk of all-cause mortality was significantly higher in men of the matched cohort. However, there was no difference in the risk of CKD progression. In the subgroup with coronary artery calcium (CAC) measurements, men had a higher likelihood of CAC progression. Conclusions: In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes who had a recent myocardial infarction (MI) are at high risk of cardiovascular events. Therefore, risk assessment is important for treatment and shared decisions. We used data from EXAMINE trial to investigate whether a multi-proteomic approach would provide specific proteomic signatures and also improve the prognostic capacity for determining the risk of cardiovascular death, MI, stroke, heart failure [HF], all-cause death, and combinations of these outcomes. Methods: 93 circulating proteins (92 from the Olink® CVDII plus troponin) were assessed in 5131 patients. Cox, competing risks, and reclassification measures were applied. Results: The clinical model showed good discrimination and calibration for all outcomes. On top of the clinical model that included age, sex, smoking, diabetes duration, history of MI (prior to the index MI of inclusion), history of HF hospitalization, history of stroke, atrial fibrillation, hypertension, systolic blood pressure, statin therapy, estimated glomerular filtration rate, and study treatment (alogliptin or placebo), troponin and BNP added prognostic information to the composite of cardiovascular death, MI, or stroke (∆C-index + 5%) and cardiovascular death alone (∆C-index + 7%). Troponin, BNP, and TRAILR2 added prognostic information on all-cause death and the composite of cardiovascular death or HF hospitalization. HF hospitalization alone was improved by adding BNP and Gal-9. For MI, troponin, FGF23, and AMBP added prognostic value; whereas for stroke, only troponin added prognostic value (multi-proteomics improved C-index > 3% [p < 0.001] for all the studied outcomes). The addition of the final biomarker selection to the clinical model improved event reclassification (cNRI from + 23% to + 64%). Specifically, the addition of the biomarkers allowed a better classification of patients at low risk (as having "true" low risk) and patients and high risk (as having "true" high risk). These results were consistent for all the studied outcomes with even more marked differences in the fatal events. Conclusions: The addition of multi-proteomic biomarkers to a clinical model in this population with diabetes and a recent MI allowed a better risk prediction and event reclassification, potentially helping for better risk assessment and targeted treatment decisions. T2D type 2 diabetes, MI myocardial infarction, CV cardiovascular, HFH heart failure hospitalization, Δ delta, cNRI continuous net reclassification index, BNP brain natriuretic peptide, TRAILR2 trail receptor 2 (or death receptor 5), Gal-9 galectin-9, FGF23 fibroblast growth factor 23. [ABSTRACT FROM AUTHOR]

Purpose of Review: This reviews aims to evaluate the role of omega-3 for cardiovascular disease (CVD) risk reduction in mild-moderate hypertriglyceridemia. Recent Findings: Epidemiological and Mendelian randomization studies have demonstrated that hypertriglyceridemia is strongly correlated to CVD. Even in patients with optimal low-density lipoprotein cholesterol (LDL-C) levels, triglycerides remain an important predictor to lower residual cardiovascular risk. In addition to screening, lifestyle intervention, and LDL-C lowering with statins for hypercholesterolemia (and other agents if needed), additional pharmacological therapies may be indicated to lower residual CVD risk in patients with persistent elevated triglyceride levels. Low-dose combinations of eicosapentaenoic acid (EPA) and docosahexaenoic acid have failed to reduce CVD in primary prevention. A recent trial evaluating high-dose purified EPA (icosapent ethyl) in mild-moderate hypertriglyceridemic statin-treated patients with or at high-risk atherosclerotic CVD demonstrated a clear benefit on cardiovascular outcomes. Summary: The recent REDUCE-IT trial shed light on omega-3 therapy. High-dose icosapent ethyl, a highly purified ethyl ester of EPA, reduced the risk of CVD events in statin-treated hypertriglyceridemic patients at elevated cardiovascular risk. Therefore, omega-3 therapy using high-dose icosapent ethyl should be recommended in statin-treated high-risk patients at high residual CVD risk and mild to moderate elevation of triglycerides. While icosapent ethyl demonstrated a benefit in these patients, drug class effect cannot be assumed and further investigations are warranted to examine the effects of other omega-3 agents at high doses. [ABSTRACT FROM AUTHOR]

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Purpose: Previous studies have indicated that platelet indices are related to the pathogenesis of cardiovascular diseases (CVD). However, it is unclear which platelet-related indicators are associated with CVD events in patients with chronic kidney disease (CKD) without dialysis. Methods: We performed a single-center prospective cohort study involved 1391 CKD patients to explore the relationship between platelet indices and CVD events in CKD patients. A nomogram was generated to predict CVD-free survival after 3 and 5 years of follow-up in terms of the fitted Cox regression model. And the time-dependent receiver-operating characteristic (ROC) curves were applied to evaluate the prediction accuracy of platelet indices on CVD events. Results: During a median follow-up of 3.41 years, 211 (15.2%) patients experienced CVD events. Results showed that platelet counts (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), and platelet distribution width (PDW) among 5 platelet indices were significantly lower in advanced CKD stages. Cox regression model showed that PLT, PDW, and PCT were associated with CVD events. However, after multivariable-adjusted, low level of PLT, hazard ratio (HR) 0.994 and 95% confidence interval (95% CI 0.989–1.000, p = 0.04), and PDW, HR 0.936 (95% CI 0.878–0.998, p = 0.044) predicted CVD events. The area under the ROC curve (AUC) of platelet indices assessed by time-dependent ROC curve analysis showed that only PLT and PDW were significant for predicting CVD events for 5 years. Conclusions: We demonstrated that PLT and PDW among 5 platelet indices were independently associated with CVD events in patients with CKD. [ABSTRACT FROM AUTHOR]

The presence of carotid arterial plaque by ultrasound enhances cardiovascular risk stratification beyond traditional risk factors. However, plaque quantification techniques require further outcomes-based investigation. The purpose of this study was to evaluate the utility of a focused carotid ultrasound protocol and novel plaque grading system developed by the American Society of Echocardiography (ASE). A retrospective analysis of 514 outpatients who were referred for coronary angiography between 2011 and 2014 was performed using a province-sponsored health database. All participants prospectively received a focused carotid ultrasound. Maximum plaque height (MPH) of arterial carotid plaque was quantified, using the Grade II–III plaque definition of MPH ≥ 1.5 mm for stratification, according to recent ASE recommendations. Participants were followed for 1.33–5.11 years (average follow-up = 3.60 ± 1.65 years) to identify the occurrence of cardiovascular events. Major events (death, myocardial infarction [MI], stroke, and transient ischemic attack [TIA]) were correlated to MPH. Participants with MPH ≥ 1.5 mm were more likely to experience stable angina, coronary artery bypass grafting, and stress testing at both 1-year and total follow-up. After adjusting for cardiac risk factors, increased MPH was shown to be predictive for TIA (odds ratio [OR] = 1.33, 95% confidence interval (CI) = 1.01–1.75); p = 0.04), whereas the odds of non-ST-elevation MI (OR = 1.55, 95% CI = 0.99–2.43; p = 0.06) approached significance. Using Kaplan–Meier survival analysis, MPH ≥ 1.5 mm demonstrated good separation for the composite outcome of death, MI, stroke, and TIA over total follow-up (p = 0.02). This rapid, office-based quantification of MPH in carotid ultrasound may serve as a stratification tool for predicting major cardiovascular events. [ABSTRACT FROM AUTHOR]

Summary: Our 6-month study showed the usefulness of romosozumab for preventing fractures and its safety. It was effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP. Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with that from baseline of BMD after four to 6-month treatment. Introduction: Romosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody which increases bone formation and suppresses bone resorption. In this study, we analyzed the actual clinical effects, adverse effects, and the optimal way to evaluate the treatment. Methods: Romosozumab was administered as subcutaneous injection of 210 mg once every 4 weeks. We conducted pre-post study in 185 patients treated for 6 months. We focused on the incidence of new vertebral fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers. We evaluated BMD before romosozumab treatment and after 4 to 6 months and performed the serum analysis before romosozumab treatment, after 1, 3, and 6 months. Results: There was no new fracture during treatment, and there was no fatal adverse event including cardiovascular disease. Since percent changes from baseline of the spine and total hip BMD were 6.34% and 1.53% after 4- to 6-month treatment, the treatment was effective for spine osteoporosis. Tartrate-resistant acid phosphatase 5b (TRACP-5b) and intact type I procollagen N-terminal propeptide (iP1NP) had significant changes during romosozumab treatment (p < 0.05). Percent change from baseline of TRACP-5b and iP1NP after 1 month correlated with percent change from baseline of BMD after 4 to 6 months of treatment. Conclusion: Romosozumab is effective in preventing fractures and useful for increasing the spine BMD. Also, romosozumab is relatively safe to use. It is especially effective in patients with low baseline spine BMD, high TRACP-5b, and high iP1NP. [ABSTRACT FROM AUTHOR]