Specific Cardiovascular Events Research Articles

A Meta-analysis of the Risk of Adverse Cardiovascular Events in Patients with Cancer Treated with Inhibitors of the PI3K/AKT/mTOR Signaling Pathway.

With the increasing of PI3K/AKT/mTOR (PAM) inhibitors in cancer therapy, there is a growing need to understand the incidence of cardiovascular events (CVAEs) associated with PAM inhibitors. A systematic search of all randomized clinical trials (RCTs) containing at least one PAM group in electronic databases such as PubMed, ClinicalTrials.gov registry, Embase, Medline, Cochrane Library, and major conferences was performed to extract available CVAEs. The cut-off date was January 31, 2024. Study heterogeneity was assessed using the I2 statistic. The risk of CVAEs associated with PAM inhibitors was calculated using Peto OR. The primary outcome was the incidence (95% CI) of PAM inhibitors cardiovascular adverse events in the total population and subgroups. The secondary outcome was the pooled risk of different CVAEs associated with PAM inhibitor exposure in the RCTs. 33 unique RCTs (n = 12,351) were included. The incidence of PAM inhibitors CVAEs of any grade in the intervention group was 48.2%, yielding a combined OR of 2.52 (95% CI 1.82-3.49). The incidence of severe adverse cardiovascular events (≥ grade 3) in the intervention group was estimated at 7.1%, yielding a combined Peto OR of 1.41 (95% CI 1.04-1.93). PAM inhibitors were associated with an increased risk of 5 CVAEs including peripheral edema, lymphoedema, hypercholesterolemia, hypertriglyceridaemia and hyperlipidemia, with higher risks for hypercholesterolemia (Peto OR: 3.27,95% CI 2.61-4.11, P < 0.01; I2 = 55.5%, P = 0.06) and hyperlipidemia (Peto OR: 3.53. 95% CI 1.70-7.32, P < 0.01; I2 = 19.3%, P = 0.29). This study identified an overall incidence of PAM inhibitors CVAEs and the increased risks associated with PAM inhibitor for five specific CVAEs, not confined to hypercholesterolemia and peripheral edema.

Spinal cord injury and risk of overall and type specific cardiovascular diseases: A meta-analysis.

Cardiovascular disease (CVD) is a growing concern among people with spinal cord injury (SCI). This meta-analysis aims to explore the risk of overall CVD and specific types of cardiovascular events among SCI patients. This meta-analysis is registered on PROSPERO (CRD CRD42024537888). The data sources comprised PubMed, Embase, the Cochrane Library, and reference lists of the included studies. The literature collection span is from database establishment until April 17, 2024. This meta-analysis encompassed observational studies investigating the association between SCI and the risk of overall types of CVD or specific CVD types. Risk of bias was evaluated utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Scale. Odds ratios (ORs) with 95% confidence intervals (CIs) were aggregated using a random-effects model. Our initial search generated 5357 relevant records form these international databases. This meta-analysis encompassed 9 observational studies involving 2,282,691 individuals, comprising 193,045 patients with SCI and 2,209,646 controls. We observed a 1.56-fold [OR = 1.56, 95% CI (1.43, 1.70), I2 = 91.3%, P < 0.001] rise in the risk of overall types of CVD among SCI patients, with a 1.82-fold increase in males and a 1.76-fold increase in females. SCI patients without comorbidities exhibited a 2.10-fold elevated risk of overall CVD types, while those with comorbidities had a 1.48-fold increased risk. Concerning specific CVD types, SCI patients showed a 1.58-fold [OR = 1.57, 95% CI (1.22, 2.03), I2 = 92.4%] higher risk of myocardial infarction, a 1.52-fold [OR = 1.52, 95% CI (1.07, 2.16), I2 = 88.7%] increase in atrial fibrillation, a 1.64-fold [OR = 1.64, 95% CI (1.22, 2.20), I2 = 95.5%] elevation in heart failure risk, and 2.38-fold [OR = 2.38, 95% CI (1.29, 4.40), I2 = 92.5%] increments in stroke risk. But there was no statistically significant difference in the risk of hypertension [OR = 1.54, 95% CI (0.98, 2.42), I2 = 96.6%]. The risk of overall CVD in SCI patients surpassed that of the non-SCI control group, with elevated risks of specific cardiovascular events like myocardial infarction, atrial fibrillation, heart failure, and stroke. Clinicians should prioritize awareness of CVD risks in SCI patients.

Association between HDL-C and intensive blood pressure control in patients with hypertension: A post-hoc analysis of SPRINT.

Previous studies in patients with hypertension have demonstrated that there is a U-shaped association between HDL-C (high-density lipoprotein cholesterol) and the risk of cardiovascular events in male patients with hypertension. However, to the best of our knowledge, the relationship between HDL-C and intensive blood pressure control in specific cardiovascular events has never been investigated. To fill this knowledge gap, the authors analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Systolic Blood Pressure Intervention Trial (SPRINT). The SPRINT evaluated the impact of intensive blood pressure control (systolic blood pressure<120mm Hg) versus standard blood pressure control (systolic blood pressure<140mm Hg). The Cox proportional risk regression was used to investigate the association between different HDL-C status and clinical outcomes. Additional stratified analyzes were performed to evaluate the robustness of sex difference. A total of 9323 participants (6016 [64.53%] males and 3307 [35.47%] females) with hypertension from the SPRINT research were included in the analysis. The median follow-up period was 3.26years. Our population was divided into five groups based on the HDL-C plasma levels: HDL-C<30mg/dL, HDL-C between 30 and 40mg/dL, HDL-C between 40 and 60mg/dL, HDL-C between 60 and 80mg/dL and HDL-C>80mg/dL. Sensitivity analyzes showed that in the SPRINT, women in the HDL-C high population had a higher risk of mortality from all causes than men. In this cohort study, results suggest that patients with HDL-C levels higher than 80mg/dL had lower risk of SPRINT primary outcome, cardiovascular death, and stroke, but this study tested association, not causation. HDL-C levels were associated with composite cardiovascular outcomes in male but not female patients. Our results demonstrated that in patients with hypertension, the association between HDL-C and risk of cardiovascular events is L-shaped.

Cardiovascular Events Among Women with Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

It is well documented that menopause is linked to an increased risk of cardiovascular (CV) events; however, the results of studies focusing on the association between premature ovarian insufficiency (POI) and the risk of CV events are controversial. The aim of this systematic review and meta-analysis was to assess the risk of CV events among women with POI compared to women with menopausal aged 50-54 years. A systematic literature search of PubMed (including Medline), Scopus, and Web of Science was conducted from 1990 to 2022 to retrieve observational studies published in English-language. The studies' quality was assessed using structured standard tools. Primary-outcome was the pooled risk of the composite outcome of CV events. We included 16 studies involving 40,549 women who suffered from POI and 1,016,633 women as controls. After adjustment for hormone therapy, the pooled risk of composite outcome of CV events and coronary heart disease, among women with the POI was significantly 1.3 (Pooled-adjusted hazard ratio (HR) = 1.35, 95% CI: 1.06-1.63, : 0%) and 1.4 (Pooled adjusted HR = 1.42, 95% CI: 1.17-1.66, : 0%) fold higher than women with menopausal age 50-54 years. There was no difference between the groups regarding the risk of stroke and death due to CV events between two groups. There was not sufficient data for pooled analysis of other specific CV events. In conclusion, POI is associated with an increased risk of CV events, particularly coronary heart disease. Our findings extend prior work with data supporting POI as a risk-enhancing factor for CV events. However, more studies are needed to confirmed these findings.

Effect of ertugliflozin on renal function and cardiovascular outcomes in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

The global prevalence of type 2 diabetes mellitus (T2DM) is growing yearly. The efficacy of ertugliflozin (ERT), a recently licensed anti-diabetic drug, has been widely reported. However, additional evidence-based data is required to ensure its safety. In particular, convincing evidence on the effects of ERT on renal function and cardiovascular outcomes is needed. We searched PubMed, Cochrane Library, Embase, and Web of Science for randomized placebo-controlled trials of ERT for T2DM published up to August 11, 2022. Cardiovascular events here mainly refer to acute myocardial infarction and angina pectoris (AP) (including stable AP and unstable AP). The estimated glomerular filtration rate (eGFR) was used to measure renal function. The pooled results are risk ratios (RRs) and 95% confidence intervals (CIs). Two participants worked independently to extract data. We searched 1516 documents and filtered the titles, abstracts, and full text, 45 papers were left. Seven trials met the inclusion criteria and were ultimately included in the meta-analysis. The meta-analysis found that ERT reduced eGFR by 0.60 mL·min-1·1.733 m-2 (95% CI: -1.02--0.17, P = .006) in patients with T2DM when used for no more than 52 weeks and these differences were statistically significant. Compared with placebo, ERT did not increase the risk of acute myocardial infarction (RR 1.00, 95% CI: 0.83-1.20, P = .333) and AP (RR 0.85, 95% CI: 0.69-1.05, P = .497). However, the fact that these differences were not statistically significant. This meta-analysis shows that ERT reduces eGFR over time in people with T2DM but is safe in the incidence of specific cardiovascular events.

164 HIGH HDL CHOLESTEROL INCREASES CARDIOVASCULAR RISK IN HYPERTENSIVE PATIENTS

Abstract Background Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. Methods To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. Results We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C&amp;lt;40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C&amp;gt;80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes (Figure 1). Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Conclusions Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients.

Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

COVID-19 Infection and Incidence of Myocarditis: A Multi-Site Population-Based Propensity Score-Matched Analysis.

BackgroundCardiovascular complications from COVID-19 include myocarditis, acute myocardial infarction, heart failure, and others. Population-level data is lacking about the relationship between COVID-19 and cardiovascular complications; therefore, we conducted a study to examine the incidence of myocarditis, acute myocardial infarction (AMI), heart failure (HF) after COVID-19 infection.MethodsRetrospective cohort study using de-identified data from 50 health systems across the United States. Cohort groups were created using patients ≥18 who were admitted to hospitals for respiratory illness with COVID-19 in 2020 and respiratory illness without COVID-19 for 2020 and 2019. There were 107,699 patients with COVID-19, 77,499 patients with respiratory illness in 2020, and 112,898 patients in 2019. The COVID-19 group was matched to each respiratory illness group by propensity score. Patients with prior specific cardiovascular events such as myocarditis, AMI, HF were excluded. The primary outcome was myocarditis, and secondary outcomes were AMI and HF.ResultsIn the COVID-19 group, 79 (0.12%) patients had new-onset myocarditis compared to 29 (0.04%) patients in the non-COVID-19 control (Pneumonia/flu) group Odd's Ratio (OR), (OR 2.73, CI 95%, 1.78-4.18). In the COVID-19 group, 1512 patients developed HF compared to 2,659 patients in the non-COVID-19 group (OR 0.49, CI 95%, 0.46-0.52). 1125 patients in COVID-19 group had AMI compared to 1243 patients in non-COVID-19 group (OR 0.87, CI 95%, 0.80-0.94).ConclusionCOVID-19 was associated with a 2-3-fold higher risk of myocarditis. Unexpectedly, lower rates of HF diagnosis reflect challenges faced due to the severity of lung disease leading to obscuring physical exam findings required for HF diagnosis and early mortality before a diagnosis of HF was made.

Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies.

Objective:To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents.Methods:Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out.Results:A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients.Conclusion:Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

Type 2 diabetes and different manifestations of pre-existing cardiovascular disease as predictors of specific cardiovascular events

Type 2 diabetes and different manifestations of pre-existing cardiovascular disease as predictors of specific cardiovascular events

Bariatric Surgery Lowers the Risk of Major Cardiovascular Events.

This study examines the impact of bariatric surgery on the risk of myocardial infarction, stroke, and a composite of cardiovascular outcomes in a large population cohort. Additionally, the impact of different bariatric surgery procedures on cardiovascular outcomes is assessed and compared. Bariatric surgery has been shown to improve comorbid conditions that are associated with cardiovascular disease and death. Few large studies have examined the impact of bariatric surgery on cardiovascular outcomes, and specifically compared the different bariatric procedures. A retrospective, observational, matched-cohort study was conducted in adult patients with obesity in New York state from 2006 to 2012. Patients were stratified into 2 groups, based on utilization of bariatric surgery. Patients were further subgrouped based on the types of primary bariatric surgery. The primary endpoint was the development of specific cardiovascular events - myocardial infarction (MI), and stroke; as well as a composite of both events. A total of 328,807 patients, including 60,445 who had undergone bariatric surgery, and 268,362 matched nonsurgical controls were the study cohort for comparing surgical and nonsurgical patients. The risk of composite cardiovascular events decreased in the surgical group [hazards ratio (HR) = 0.48, 95% confidence intervals (CI): 0.45-0.51], as did the risk of MI (HR = 0.39, 95% CI: 0.35-0.42), and stroke (HR = 0.55, 95% CI: 0.51-0.59). Among the surgical cohort, sleeve gastrectomy patients had a higher risk of developing MI, stroke, and any type of cardiovascular event than gastric bypass patients. Bariatric surgery is associated with decreased risk of significant cardiovascular events compared to nonsurgical controls. In this exploratory analysis, gastric bypass was associated with a lower risk of all cardiovascular events than sleeve gastrectomy.

Multi-proteomic approach to predict specific cardiovascular events in patients with diabetes and myocardial infarction: findings from the EXAMINE trial.

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. 93 circulating proteins (92 from the Olink® CVDII plus troponin) were assessed in 5131 patients. Cox, competing risks, and reclassification measures were applied. The clinical model showed good discrimination and calibration for all outcomes. On top of theclinical 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. 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.

Oral Bisphosphonate use Reduces Cardiovascular Events in a Cohort of Danish Patients Referred for Bone Mineral Density.

The cardiovascular (CV) safety of oral bisphosphonates (oBPs) is uncertain. Determine the risk of CV events in oBP users referred for bone mineral density (BMD) testing compared with matched controls. Cohort study. Danish national prescription registry enriched with local hospital data from Odense. Individuals aged ≥45 years referred for BMD testing. oBP. Hospitalization for any CV event. Secondary study outcomes were specific CV events. Negative (inguinal hernia surgery and ingrown toenail) and positive (fragility fracture) control outcomes assessed systemic bias. Cox proportional hazards models were fitted to estimate hazard ratio (HR) and 95% confidence intervals. There were 2565 oBP users (82.6% women) and 4568 (82.3% women) propensity score-matched controls. Alendronate accounted for 96% of oBP prescription. A total of 406 (15.8%) CV events occurred in oBP users (rate = 73.48 [66.67-80.98]); rate = events divided by person-time; and 837 (18.3%) events in controls (rate = 104.73 [97.87-112.07]) with an adjusted HR of 0.68 (95% CI 0.60-0.77). Additional adjustment for BMD did not attenuate estimates (HR 0.67; 95% CI 0.58-0.78]. Similar results were seen for secondary outcomes where risk reductions were seen regarding atrial fibrillation, stroke, heart failure, and aneurysms. Positive and negative control outcome analyses identified minimal residual confounding. Oral BP users experienced a 33% reduced risk of CV events. This observational real-world study adds to a growing body of evidence for cardioprotection by oBP that warrants testing in a randomized setting.

Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions.

Cardiovascular diseases (CVD) represent one of the biggest causes of death globally, and their prevalence, aetiology, and outcome are related to genetic, metabolic, and environmental factors, among which sex- and age-dependent differences may play a key role. Among CVD risk factors, platelet hyperactivity deserves particular mention, as it is involved in the pathophysiology of main cardiovascular events (including stroke, myocardial infarction, and peripheral vascular injury) and is closely related to sex/age differences. Several determinants (e.g., hormonal status and traditional cardiovascular risk factors), together with platelet-related factors (e.g., plasma membrane composition, receptor signaling, and platelet-derived microparticles) can elucidate sex-related disparity in platelet functionality and CVD onset and outcome, especially in relation to efficacy of current primary and secondary interventional strategies. Here, we examined the state of the art concerning sex differences in platelet biology and their relationship with specific cardiovascular events and responses to common antiplatelet therapies. Moreover, as healthy nutrition is widely recognized to play a key role in CVD, we also focused our attention on specific dietary components (especially polyunsaturated fatty acids and flavonoids) and patterns (such as Mediterranean diet), which also emerged to impact platelet functions in a sex-dependent manner. These results highlight that full understanding of gender-related differences will be useful for designing personalized strategies, in order to prevent and/or treat platelet-mediated vascular damage.

Correlation of Inhaled Long-Acting Bronchodilators With Adverse Cardiovascular Outcomes in Patients With Stable COPD: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

A majority of existing studies have focused on the efficacy of inhaled long-acting bronchodilators (ILABs), such as long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs), and LABAs combined with LAMAs in treating chronic obstructive pulmonary disease (COPD). The current meta-analysis aimed to investigate the correlation of ILABs with specific cardiovascular adverse events (CAEs). Five electronic databases, including PubMed, Embase, Cochrane Library, Scopus, and Web of Science were systematically retrieved. Finally, 16 randomized controlled trials were enrolled into the current meta-analysis. Typically, the efficacy of 3 major classes of drugs (LABAs, LAMAs, and LABAs combined with LAMAs), and 7 specific drugs (including formoterol, glycopyrrolate, indacaterol, olodaterol, Salmeterol, tiotropium, and vilanterol) for 4 CAEs, including myocardial infarction, cardiac failure (CF), ischemic heart disease (IHD), and stroke in stable COPD patients, was examined. All the pooled results were analyzed through the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). The direct meta-analysis results suggested that LABAs could increase the risk of CF in patients with stable COPD compared with placebo controls (OR 1.70, 95% CI, 1.00-2.90). In addition, network meta-analysis results indicated that LAMAs combined with LABAs would result in an increased risk of CF in patients with stable COPD (OR 2.31, 95% CI, 1.10-5.09). According to the ILABs specific drug analysis, formoterol may potentially have protective effects on IHD compared with placebo controls (OR 0.45, 95% CI, 0.18-1.00). In conclusion, among these 3 kinds of ILABs, including LAMAs, LABAs, and LABAs/LAMAs, for stable COPD patients, LAMAs and LABAs are associated with the least possibility to induce myocardial infarction and stroke, respectively. However, the application of LABAs will probably increase the risk of CF; they should be used with caution for stable COPD patients with CF. In addition, in specific-drug analysis, the use of formoterol can reduce the risk of treatment-related IHD. Nevertheless, more studies on different drug doses are needed in the future to further validate this conclusion.

2209-PUB: Type 2 Diabetes and Different Manifestations of Preexisting Cardiovascular Disease as Predictors of Specific Cardiovascular Events

Coronary artery disease (CAD) and peripheral artery disease (PAD) confer an increased risk of cardiovascular events that is particularly high when type 2 diabetes (T2DM) is present in addition to cardiovascular disease (CVD). Here, we aimed at investigating the impact of T2DM and of the manifestation of pre-existing cardiovascular disease (PAD vs. CAD) as predictors of specific cardiovascular events. We prospectively recorded cardiovascular events over 10 years in 1777 patients with established CVD, including 1312 patients with CAD, of whom 29.3% had T2DM and 465 patients with PAD, of whom 43.9% had T2DM. T2DM after multivariate adjustment significantly predicted cardiovascular mortality (n=102; HR 1.77 [1.33-2.36]; p&amp;lt;0.001), myocardial infarction (n=74; HR 1.50 [1.10-2.04]; p=0.010), ischemic stroke (n=54; HR 1.69 [1.16-2.46]; p=0.007), and revascularization of non-coronary arteries (n=134; HR 1.66 [1.29-2.13]; p&amp;lt;0.001) independently from the manifestation of CVD. The presence of PAD versus that of CAD after adjustment for conventional cardiovascular risk factors including T2DM predicted myocardial infarction (HR 2.33 [1.61-3.37]; p&amp;lt;0.001) and revascularization of non-coronary arteries (HR 7.48 [5.51-10.16]; p&amp;lt;0.001). Neither T2DM nor the presence of PAD vs. that of CAD was significantly associated with percutaneous coronary interventions (n=246) or coronary artery bypass graftings (n=94) in our cohort. We conclude that both T2DM and the manifestation of pre-existing CVD predict cardiovascular events in patients with established CVD. Disclosure C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. B. Larcher: None. A. Mader: None. S. Sternbauer: None. M. Schindewolf: None. I. Baumgartner: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.

Relationship of inhaled long-acting bronchodilators with cardiovascular outcomes among patients with stable COPD: a meta-analysis and systematic review of 43 randomized trials.

Background: Long-acting muscarinic antagonists (LAMAs) and long-acting β2–agonists (LABAs) are the mainstay of maintenance therapy for chronic obstructive pulmonary disease (COPD). Although previous studies have supported inhaled long-acting bronchodilators (ILABs) for overall cardiovascular safety, the risk of specific cardiovascular outcomes such as arrhythmia, heart failure and stroke is still unknown.Materials and methods: We systematically searched from PubMed, the Embase database and the Cochrane Library for published studies on ILABs and COPD, from its inception to November 10, 2018, with no language restrictions. The RRs and corresponding 95% CIs were pooled to evaluate ILAB/placebo.Results: Finally, 43 randomized controlled trials were included. Compared with placebo, ILABs do not increase the risk of overall and specific cardiovascular adverse events (AEs); on the contrary, they can reduce the incidence of hypertension (RR 0.73, 95% CI 0.55–0.98;I219.9%; P= 0.221). However, when stratified according to the specific agents of ILABs, olodaterol might reduce the risk of overall cardiovascular adverse events (OCAEs) (RR 0.65, 95% CI 0.49–0.88;I227.5%; P= 0.000), and the protective effect of lowing blood pressure disappeared. Similarly, the use of inhaled LABA might increase the risk of cardiac failure (RR 1.71, 95% CI 1.04–2.84;I20%; P= 0.538), but this risk disappeared when stratified according to the specific agents of LABA. Besides, formoterol might decrease the risk of cardiac ischemia (RR 0.53, 95% CI 0.32–0.91; I20%; P= 0.676).Conclusions: Overall, the use of ILABs was not associated with overall cardiovascular AEs in patients with stable COPD. When stratified according to the specific agents of LABA, olodaterol might reduce the risk of OCAE; and formoterol might decrease the risk of cardiac ischemia. LABA might reduce the incidence of hypertension, but might increase the risk of heart failure. Therefore, COPD patients with a history of heart failure should use it with caution.

Associations between childhood maltreatment and risk of myocardial infarction in adulthood: Results from the National Epidemiologic Survey on alcohol and Related Conditions

ObjectiveAlthough childhood maltreatment has been reported to be associated with the incidence of cardiovascular diseases, its association with specific major cardiovascular events remains unclear. This study aimed to examine the relationship between different types of childhood maltreatment (CM) and myocardial infarction (MI) occurrence in a nationally representative sample. MethodsWe used data from the National Epidemiologic Survey of Alcohol and Related Conditions, a nationally representative US sample of adults aged 20 years and older (N = 34, 653). Logistic regression models were constructed to investigate the associations between five types of CMs including physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse and the risk of MI adjusting for sociodemographic variables. ResultsAfter adjusting for sociodemographic variables, childhood sexual abuse was significantly associated with increased odds of MI occurrence (adjusted odds ratio [aOR] = 1.85, 95%CI = 1.24–2.76, p = 0.003). Additionally, childhood physical abuse was significantly associated with increased odds of MI occurrence in men (aOR = 2.45, 95%CI = 1.35–4.44, p = 0.004) but this association was not observed in women (aOR = 0.72, 95%CI = 0.32–1.66, p = 0.440). Compared to those who did not experience CM, those who experienced more than three types of CMs showed increased odds of MI occurrence (adjusted OR = 2.08–3.05, all p < 0.05). ConclusionsUsing data from a nationally representative US sample of adults, we found significant positive associations between CM and odds of MI occurrence in adulthood. Future longitudinal prospective studies are needed to confirm our findings.

Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study

Background and aimsThe lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease. MethodsThe CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs. ResultsCathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05–1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07–1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events. ConclusionsCathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.

Abstract 075: Does the Benefit From Treating to Blood Pressure Targets Vary With Age?

Hypertension guidelines differ regarding how blood pressure targets vary with age. Crucial to this debate is how the benefit of treatment might vary with age. Therefore, a systematic search was conducted for trials randomizing treatment in the more intensive arm to systolic blood pressure (SBP) targets generally recommended, i.e., 140 mmHg or less. Meta-analysis examined the effects of age on risk reduction. Sixteen trials met criteria with SBP targets of 120-140 mmHg. Relative to high targets, low targets reduced risk for cardiovascular events (CVEs), 0.86 (95% CI 0.75,0.98), P=0.019, but treatment benefit differed among trials. This heterogeneity was explained by patient age. Relative to high targets, low targets reduced risk in older patients (mean ages 74+): 0.77 (0.61,0.97), P=0.025, but not in younger patients (mean ages 55-67): 0.90 (0.78,1.03), P=0.121, even though the latter had much greater statistical power. Risk reduction from low targets was greater in older patients than in younger patients: Relative risk in older patients versus relative risk in patients 16 years younger (2 standard deviations of age) = 0.78 (95% CI 0.63,0.98), P=0.036 (see Figure). Although generally not statistically significant, similar patterns were seen for specific CVEs and total mortality. Risks for adverse effects also tended to decrease with age. The number needed to treat to low targets to prevent 1 CVE in 10 years for 2 typical populations declined with age from 45 to 14 and from 110 to 13. In conclusion, for both relative risk and absolute risk, treating to SBP targets of 120-140 mmHg was more beneficial in older patients than in younger patients with no age-related increase in adverse effects.