The impact of the 2019 ESC/EAS dyslipidaemia guidelines on real-world initial lipid-lowering therapy in patients with acute myocardial infarction.

This study aimed to investigate the impact of the latest guidelines on the real-world clinical practice of initial lipid-lowering therapy, especially on the use of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in China. All adult patients diagnosed with acute myocardial infarction in our hospital between August 31, 2018, and August 31, 2020, were divided into the following 2 groups: those patients treated before the latest guideline release, and those patients treated after the release. A propensity score-matched method was used, and logistic regression was used to assess the association with intensive statin, ezetimibe and PCSK9 inhibitor usage together with treatment results between the 2 groups. A total of 325 patients were enrolled in this study, including 141 patients who were admitted before the release of the latest guideline and 184 patients who were admitted after the release. After a median follow-up time of 8.20 months, the mean low-density lipoprotein cholesterol was 1.87 ±â€…0.59 mmol/L (1.87 ±â€…0.55 in the before group vs 1.88 ±â€…0.62 in the after group, P = .829). After propensity score matching, the initial usage of intensive statin therapy was decreased after guideline release without statistical significance (17.00% vs 28.00%, P = .090), whereas the usage of ezetimibe and PCSK9 inhibitors was increased (19.00% vs 8.00%, P = .039; and 10.00% vs 3.00%, P = .085, respectively). In logistic regression models, the release of the guideline was associated with a statistically significantly increased use of ezetimibe (odds ratio [OR]: 1.91; 95% confidence interval [CI]: 1.21, 3.02; P = .005), a marginally decreased use of intensive statins (OR: 0.68; 95% CI: 0.45, 1.03; P = .069) and a marginally increased use of PCSK9 inhibitors (OR: 1.31; 95% CI: 0.98, 1.76; P = .068). In this single-center, real-world data analysis, after the release of the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines, an increasing number of patients with a recent acute myocardial infarction were initially receiving ezetimibe and PCSK9 inhibitors.

Sorafenib reduces the production of epoxyeicosatrienoic acids and leads to cardiac injury by inhibiting CYP2J in rats.

Sorafenib, an important cancer drug in clinical practice, has caused heart problems such as hypertension, myocardial infarction, and thrombosis. Although some mechanisms of sorafenib-induced cardiotoxicity have been proposed, there is still more research needed to reach a well-established definition of the causes of cardiotoxicity of sorafenib. In this report, we demonstrate that sorafenib is a potent inhibitor of the CYP2J enzyme. Sorafenib significantly inhibited the production of epoxyeicosatrienoic acids (EETs) in rat cardiac microsomes. The in vivo experimental results also showed that after the administration of sorafenib, the levels of 11,12-EET and 14,15-EET in rat plasma were significantly reduced, which was similar to the results of CYP2J gene knockout. Sorafenib decreased the levels of EETs, leading to abnormal expression of mitochondrial fusion and fission factors in heart tissue. In addition, the expression of mitochondrial energy metabolism factors (Pgc-1α, Pgc-1ß, Ampk, and Sirt1) and cardiac mechanism factors (Scn5a and Prkag2) was significantly reduced, increasing the risk of arrhythmia and heart failure. Meanwhile, the increase in injury markers Anp, CK, and CK-MB further confirmed the cardiotoxicity of sorafenib. This study is of great significance for understanding the cardiotoxicity of sorafenib, and is also a model for studying the cardiotoxicity of other drugs that inhibit CYP2J activity.

Paclitaxel-induced acute myocardial infarction: a case report and literature review.

BACKGROUND: Paclitaxel is a chemotherapeutic agent commonly used for ovarian, lung, breast carcinoma, and Kaposi's sarcoma. Its common side effects include hypersensitivity reaction, bone marrow suppression, and peripheral neuropathy. However, a rare and life-threatening side effect is paclitaxel-induced myocardial infarction. CASE PRESENTATION: A 71-year-old man with type 2 diabetes mellitus, hypertension, heavy smoking history, previous coronary artery disease with percutaneous coronary intervention (PCI) in left anterior descending artery (LAD), and non-small lung cancer presented with non-ST elevation myocardial infarction during infusion of paclitaxel infusion. Coronary angiogram showed de novo three vessel disease with 70% stenosis in ostial to distal left main artery (LM) and 80% in-stent re-stenosis in proximal to mid left anterior descending artery. CONCLUSIONS: Physicians should be keeping this in mind when dealing with patients on paclitaxel, especially if they have previous risk factors for coronary artery disease.

Cardioprotective effects of p-coumaric acid on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance in isoproterenol-induced experimental myocardial infarction.

Cardiovascular diseases cause a large number of deaths throughout the world. No research was conducted earlier on p-coumaric acid's effect on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance. Hence, we appraised the above-said parameters in isoproterenol-induced myocardial infarcted rats. This investigation included 24 male albino Wistar rats in 4 groups. Normal control Group 1, p-coumaric acid (8 mg/kg body weight) alone treated Group 2, Isoproterenol (100 mg/kg body weight) induced myocardial infarcted Group 3, p-coumaric acid (8 mg/kg body weight) pretreated isoproterenol (100 mg/kg body weight) induced Group 4. After 1 day of the last dose of isoproterenol injection (day 10), rats were killed and blood and heart were taken and inflammatory markers, lipid peroxidation, nonenzymatic antioxidants, ion pumps, and electrolytes were measured. The heart rate, serum cardiac troponin-T, serum/plasma inflammatory markers, and heart proinflammatory cytokines were raised in isoproterenol-induced rats. Isoproterenol also enhanced plasma lipid peroxidation, lessened plasma nonenzymatic antioxidants, and altered heart ion pumps and serum and heart electrolytes. In this study, p-coumaric acid pretreatment orally for 7 days to isoproterenol-induced myocardial infarcted rats prevented changes in the above-cited parameters. p-Coumaric acid's anti-tachycardial, anti-inflammatory, anti-ion pump dysfunction and anti-electrolyte imbalance properties are the mechanisms for these cardioprotective effects.

Remote intensive management to improve antiplatelet adherence in acute myocardial infarction: a secondary analysis of the randomized controlled IMMACULATE trial.

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.

The association of tadalafil exposure with lower rates of major adverse cardiovascular events and mortality in a general population of men with erectile dysfunction.

BACKGROUND: Tadalafil is a long-acting phosphodiesterase-5 inhibitor (PDE-5i) indicated for erectile dysfunction (ED). HYPOTHESIS: Our hypothesis was that tadalafil will reduce the risk of major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, coronary revascularization, unstable angina, heart failure, stroke) and all-cause death in men with ED. METHODS: A retrospective observational cohort study was conducted in a large US commercial insurance claims database in men with a diagnosis of ED without prior MACE within 1 year. The exposed group (n = 8156) had ≥1 claim for tadalafil; the unexposed group (n = 21 012) had no claims for any PDE-5i. RESULTS: Primary outcome was MACE; secondary outcome was all-cause death. Groups were matched for cardiovascular risk factors, including preventive therapy. Over a mean follow-up of 37 months for the exposed group and 29 months for the unexposed group, adjusted rates of MACE were 19% lower in men exposed to tadalafil versus those unexposed to any PDE-5i (hazard ratio [HR] = 0.81; 95% confidence intervals [CI] = 0.70-0.94; p = .007). Tadalafil exposure was associated with lower adjusted rates of coronary revascularization (HR = 0.69; 95% CI = 0.52-0.90; p = .006); unstable angina (HR = 0.55; 95% CI = 0.37-0.81; p = .003); and cardiovascular-related mortality (HR = 0.45; CI = 0.22-0.93; p = .032). Overall mortality rate was 44% lower in men exposed to tadalafil (HR = 0.56; CI = 0.43-0.74; p < .001). Men in the highest quartile of tadalafil exposure had the lowest rates of MACE (HR: 0.40; 95% CI: 0.28-0.58; p < .001) compared to lowest exposure quartile. CONCLUSION: In men with ED, exposure to tadalafil was associated with significant and clinically meaningful lower rates of MACE and overall mortality.

Risk of Stroke and Myocardial Infarction Among Initiators of Triptans.

Importance: Triptans are contraindicated in patients with ischemic heart disease or previous myocardial infarction, and caution is advised when prescribing these drugs to patients with vascular risk factors. However, controlled observational studies have either shown no association or an apparent lower risk, possibly owing to a channeling of triptans to individuals at low risk of cardiovascular outcomes, and it remains unclear whether avoiding triptan treatment for these patients is meaningful. Objective: To establish whether an association between triptans and ischemic events could be demonstrated using a self-controlled design because this type of design is robust to the previously mentioned type of confounding. Design, Setting, and Participants: All people in nationwide Danish registries who were initiating triptans and all the ischemic events that they experienced were identified. A case-crossover design was used to estimate odds ratios (OR) for associations between first-ever triptan use and ischemic outcomes, comparing triptan exposure in the 2-week period up to the event with four 2-week reference periods. Data were obtained for the period January 1995 to August 2022. Included from the population of Denmark were individuals redeeming a prescription for any triptan and experiencing at least 1 of 3 predefined ischemic outcomes. No one was excluded. Exposure: Initiation of any triptan. Main Outcomes and Measures: Acute myocardial infarction, ischemic stroke, or nonspecified stroke. Results: Identified were a total of 429 612 individuals (median [IQR] age, 38 [28-48] years; 325 687 female [75.8%]) who redeemed a first prescription for a triptan in the study period. Of these patients, 11 (0.003%) had a myocardial infarction with the first triptan prescription in either a focal or referent window (odds ratio [OR], 3.3; 95% CI, 1.0-10.9), 18 (0.004%) had ischemic stroke (OR, 3.2; 95% CI, 1.3-8.1), and 35 (0.008%) had ischemic/nonspecified stroke (OR, 3.0; 95% CI, 1.5-5.9). Case patients had a median age of approximately 60 years and had a high-risk cardiovascular profile. Conclusions and Relevance: Results of this case-crossover study suggest that triptan initiation was associated with higher risk of ischemic stroke and myocardial infarction. For the individual patient with low background cardiovascular risk, the risk of an ischemic event after triptan initiation was very low.

Proton Pump Inhibitor Use and the Risk of Cardiovascular Complications and Death in Older Adults with Diabetes: A Population-Based Cohort Study.

BACKGROUND: The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing. METHODS: Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population. RESULTS: A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08-1.20), MI (HR 1.36, 95% CI 1.31-1.41) and total mortality (HR 1.24, 95% CI 1.22-1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort. CONCLUSIONS: Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.

Effect of six month's treatment with omega-3 acid ethyl esters on long-term outcomes after acute myocardial infarction: The OMEGA-REMODEL randomized clinical trial.

BACKGROUND: Omega-3 polyunsaturated fatty acids (O3-FA) have been shown to reduce inflammation and adverse cardiac remodeling after acute myocardial infarction (AMI). However, the impact of O3-FA on long-term clinical outcomes remains uncertain. AIMS: To investigate the impact of O3-FA on adverse cardiac events in long-term follow up post AMI in a pilot-study. METHODS: Consecutive patients with AMI were randomized 1:1 to receive 6 months of O3-FA (4 g/daily) or placebo in the prospective, multicenter OMEGA-REMODEL trial. Primary endpoint was a composite of major adverse cardiovascular events (MACE) encompassing all-cause death, heart failure hospitalizations, recurrent acute coronary syndrome, and late coronary artery bypass graft (CABG). RESULTS: A total of 358 patients (62.8% male; 48.1 ± 16.1 years) were followed for a median of 6.6 (IQR: 5.0-9.1) years. Among those receiving O3-FA (n = 180), MACE occurred in 65 (36.1%) compared to 62 (34.8%) of 178 assigned to placebo. By intention-to-treat analysis, O3-FA treatment assignment did not reduce MACE (HR = 1.014; 95%CI = 0.716-1.436; p = 0.938), or its individual components. However, patients with a positive response to O3-FA treatment (n = 43), defined as an increase in the red blood cell omega-3 index (O3I) ≥5% after 6 months of treatment, had lower annualized MACE rates compared to those without (2.9% (95%CI = 1.2-5.1) vs 7.1% (95%CI = 5.7-8.9); p = 0.001). This treatment benefit persisted after adjustment for baseline characteristics (HRadjusted = 0.460; 95%CI = 0.218-0.970; p = 0.041). CONCLUSION: In long-term follow-up of the OMEGA-REMODEL randomized trial, O3-FA did not reduce MACE after AMI by intention to treat principle, however, patients who achieved a ≥ 5% increase of O3I subsequent to treatment had favorable outcomes.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and mild/moderate chronic kidney disease.

AIM: To determine the comparative effectiveness regarding major cardiovascular events of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). MATERIALS AND METHODS: We assembled a cohort of commercially insured adult patients with T2DM in the United States (derived from Optum Clinformatics DataMart 2003-2021) who were new users of GLP-1 receptor agonists or SGLT-2 inhibitors. We compared risks of non-fatal myocardial infarction or stroke in patients with and without CKD, and further categorized by CKD stage: stages G1 or G2 [estimated glomerular filtration rate (eGFR) ≥60 ml/min] and A2 (urine albumin to creatinine ratio 30 to <300 mg/g) or A3 (urine albumin to creatinine ratio ≥300 mg/g), stage G3a (eGFR 45 to <60 ml/min/1.73 m2 ) and stage G3b (eGFR 30 to <45 ml/min/1.73 m2 ). We used proportional hazards regression after inverse probability of treatment weighting to compute hazard ratios and 95% confidence intervals. RESULTS: After accounting for the probability of treatment, patients with T2DM and CKD treated with SGLT-2 inhibitors experienced a 14% lower risk of non-fatal myocardial infarction or stroke (hazard ratio 0.86, 95% confidence interval 0.78-0.94) relative to those treated with GLP-1 receptor agonists. CONCLUSIONS: Recognizing the potential for residual confounding, selection bias and immortal time bias, commercially insured patients in the United States with T2DM and CKD treated with SGLT-2 inhibitors experienced significantly lower risks of non-fatal myocardial infarction or stroke relative to those treated with GLP-1 receptor agonists.

Inhibition of Pyruvate kinase M2 (PKM2) by shikonin attenuates isoproterenol-induced acute myocardial infarction via reduction in inflammation, hypoxia, apoptosis, and fibrosis.

Myocardial infarction (MI) is a major cause of mortality and disability globally. MI results from acute or chronic myocardial ischemia characterized by an imbalance of oxygen demand and supply, leading to irreversible myocardial injury. Despite several significant efforts in the understanding of MI, the therapy of MI is not satisfactory due to its complicated pathophysiology. Recently, therapeutic potential of targeting pyruvate kinase M2 (PKM2) has been postulated in several cardiovascular diseases. PKM2 gene knockout and expression studies implicated the role of PKM2 in MI. However, the effects of pharmacological interventions targeting PKM2 have not been investigated in MI. Therefore, in the present study, effect of PKM2 inhibitor has been investigated in the MI along with elucidation of possible mechanism(s). MI in rats was induced by administrations of isoproterenol (ISO) at a dose of 100 mg/kg s.c. for two consecutives days at 24-h interval. At the same time, shikonin (PKM2 inhibitor) was administered at 2 and 4 mg/kg in ISO-induced MI rats. After the shikonin treatment, the ventricular functions were measured using a PV-loop system. Plasma MI injury markers, cardiac histology, and immunoblotting were performed to elucidate the molecular mechanism. Treatment of shikonin 2 and 4 mg/kg ameliorated cardiac injury, reduced infarct size, biochemical alterations, ventricular dysfunction, and cardiac fibrosis in ISO-induced MI. Expression of PKM2 in the ventricle was reduced while PKM1 expression increased in the shikonin treated group, indicating PKM2 inhibition restores PKM1 expression. In addition, PKM splicing protein (hnRNPA2B1 & PTBP1), HIF-1α, and caspase-3 expression were reduced after shikonin treatment. Our findings suggest that pharmacological inhibition of PKM2 with shikonin could be a potential therapeutic strategy to treat MI.

Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis.

PURPOSE: Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed. MATERIALS AND METHODS: To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death. RESULTS: After matching, 10,511 men who experienced an any increase in Hct after initiating TTh and an equal number of controls who did have an increase in Hct were included. Compared to controls who did not have an increase in Hct after starting TTh, the men who had an increase in subsequent Hct had a significantly increased risk of MACE compared to men with no change in Hct. CONCLUSIONS: We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh.

Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: A SEER-medicare study.

BACKGROUND: Triple-negative breast cancer (TNBC) is more aggressive as compared to other subtypes of breast cancer with characteristic metastatic patterns and a poor prognosis. The standard of care for early-stage TNBC is historically anthracycline and taxane-based chemotherapy (ATAX). Despite the effectiveness of this regimen, anthracyclines carry a small but important risk of cardiotoxicity, which is specifically a concern in the older population. This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with ATAX compared to taxane-based chemotherapy (TAX). METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women aged 66 and older with TNBC diagnosed between 2010 and 2015 (N = 2215). We compared patient and clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs), Kaplan-Meier survival curves were generated to estimate three-year overall survival (OS) and cancer specific survival (CSS). Cox proportional hazards models were used to analyze OS and CSS while controlling for patient and tumor characteristics. MACE was defined as acute myocardial infarction, heart failure, potentially fatal arrhythmia, and cerebral vascular incidence. Few patients experienced a cardiac death and therefore this was excluded in the analysis. RESULTS: Of the 2215 patients in our cohort, most patients (n = 1334; 60.26%) received TAX compared to ATAX (n = 881; 39.78%). Patients who received ATAX were not statistically significantly more likely than those who received TAX to experience acute myocardial infarction, cerebral vascular accident (CVA), or potentially fatal arrhythmia when controlling for traditional risk factors. Among patients who experienced MACE, there was no difference in OS or CSS in patients who received TAX vs ATAX. Patients who received ATAX were less likely to develop heart failure than those who received TAX (OR 0.63, 95% CI [0.45-0.88], p < 0.01). Patients who developed MACE and who were > 76 years old had worse OS compared to those who experienced MACE and were age 66-75 years old (HR 1.67, 95% CI [1.07-2.62], p = 0.02). CONCLUSION: Among older women with TNBC, receipt of adjuvant chemotherapy with ATAX was not associated with increased risk of major adverse cardiac events. For those who experienced a cardiac event, there was no difference in survival amongst those who received TAX vs ATAX. Other factors including additional chemotherapy toxicities should be investigated as a potential etiology for the inferior OS previously observed with ATAX vs TAX in older women with node negative or 1-3 positive lymph nodes.

Disentangling impacts of multiple pollutants on acute cardiovascular events in New York city: A case-crossover analysis.

BACKGROUND: Ambient air pollution contributes to an estimated 6.67 million deaths annually, and has been linked to cardiovascular disease (CVD), the leading cause of death. Short-term increases in air pollution have been associated with increased risk of CVD event, though relatively few studies have directly compared effects of multiple pollutants using fine-scale spatio-temporal data, thoroughly adjusting for co-pollutants and temperature, in an exhaustive citywide hospitals dataset, towards identifying key pollution sources within the urban environment to most reduce, and reduce disparities in, the leading cause of death worldwide. OBJECTIVES: We aimed to examine multiple pollutants against multiple CVD diagnoses, across lag days, in models adjusted for co-pollutants and meteorology, and inherently adjusted by design for non-time-varying individual and aggregate-level covariates, using fine-scale space-time exposure estimates, in an exhaustive dataset of emergency department visits and hospitalizations across an entire city, thereby capturing the full population-at-risk. METHODS: We used conditional logistic regression in a case-crossover design - inherently controlling for all confounders not varying within case month - to examine associations between spatio-temporal nitrogen dioxide (NO2), fine particulate matter (PM2.5), sulfur dioxide (SO2), and ozone (O3) in New York City, 2005-2011, on individual risk of acute CVD event (n = 837,523), by sub-diagnosis [ischemic heart disease (IHD), heart failure (HF), stroke, ischemic stroke, acute myocardial infarction]. RESULTS: We found significant same-day associations between NO2 and risk of overall CVD, IHD, and HF - and between PM2.5 and overall CVD or HF event risk - robust to all adjustments and multiple comparisons. Results were comparable by sex and race - though median age at CVD was 10 years younger for Black New Yorkers than White New Yorkers. Associations for NO2 were comparable for adults younger or older than 69 years, though PM2.5 associations were stronger among older adults. DISCUSSION: Our results indicate immediate, robust effects of combustion-related pollution on CVD risk, by sub-diagnosis. Though acute impacts differed minimally by age, sex, or race, the much younger age-at-event for Black New Yorkers calls attention to cumulative social susceptibility.

The role of aspirin, statins, colchicine, and IL-1 inhibitors in prevention of cardiovascular events: a systematic integrative review.

CONTEXT: Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse cardiovascular events (CVEs). Specifically, identifying drugs that can reduce the progression of CVD and serious adverse events is much needed. Drugs that work by reducing platelet aggregation, blocking cholesterol formation (3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase inhibitors), and/or blocking inflammation pathways (mainly interleukin-1b [IL-1b]) have been linked to preventing adverse CVEs, including acetylsalicylic acid (ASA, aspirin), statins, colchicine, and IL-1 inhibitors (interleukin-1 receptor antagonists). This systematic review aims to provide insight into utilizing these four agents for the primary and/or secondary prevention of CVD. OBJECTIVES: In this systematic review, we opted to review the efficacy of aspirin, statins, colchicine, and IL-1 inhibitors in the primary and secondary prevention of CVE to provide clinical practitioners with evidence-based practice approaches and determine any unmet needs in their utilization. METHODS: Between October 1 and 12, 2021, a search was conducted and completed on five databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Biomedical Reference Collection: Comprehensive. A total of 13 researchers (V.A., A.H., S.B., V.G., D.C., C.C., C.B., C.A., S.K., J.H., A.K., S.F., and S.E.) were involved in the search and screening of the articles. Search terms included "aspirin, statins, colchicine, IL-1 inhibitors, and primary, secondary, myocardial infarction (MI)." Inclusion criteria included clinical study design, English language articles, all genders older than 50 years old, and established patient history of CVD, including MI. In addition, articles were excluded if they were animal models, in vitro studies, pharmacokinetic studies, systematic reviews, literature reviews, and studies exploring therapies other than those listed in the inclusion criteria. First, five individuals independently sorted through abstracts or articles based on the inclusion and exclusion criteria. Then, a team of 13 individuals sorted through full-text articles of selected abstracts based on the same criteria. A separate researcher resolved conflicts between the team. RESULTS: A total of 725 articles were identified from all databases, from which 256 duplicated articles were removed. Thus, a total of 469 articles abstracts were screened, of which 425 articles either did not meet the inclusion criteria or met the exclusion criteria. A total of 42 articles were retrieved and assessed for full-text review, from which 15 articles were retrieved for analysis. CONCLUSIONS: Statins may prevent primary CVEs based on their role in preventing cholesterol formation. Aspirin, canakinumab, and colchicine may be helpful in the secondary prevention of CVEs due to their blocking of various steps in the inflammation pathway leading to CVD. Future research should primarily focus on the use of canakinumab and colchicine in preventing CVD due to the limited number of studies on these drugs.

The Detrimental Effect of Pre-Treatment with Ivermectin on Myocardial Ischemia.

INTRODUCTION: Ivermectin (IVM) is a broad-spectrum anti-parasitic agent with potential antibacterial, antiviral, and anti-cancer effects. There are limited studies on the effects of IVM on cardiovascular diseases, so the present study sought to determine the effects of pre-treatment with IVM on myocardial ischemia in both ex vivo and in vivo. METHODS: In the ex vivo part, two groups of control and treated rats with IVM (0.2 mg/kg) were examined for cardiac function and arrhythmias by isolated heart perfusion. In the in vivo part, four groups, namely, control, IVM, Iso (MI), and Iso + IVM 0.2 mg/kg were used. Subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used for the induction of myocardial infarction (MI) in male Wistar rats. Then electrocardiogram, hemodynamic factors, cardiac hypertrophy, and malondialdehyde (MDA) levels were investigated. RESULTS: The ex vivo results showed that administration of IVM induces cardiac arrhythmia and decreases the left ventricular maximal rate of pressure increase (contractility) and maximal rate of pressure decline (relaxation). The isoproterenol-induced MI model used as an in vivo model showed that cardiac hypertrophy were increased with no improvement in the hemodynamic and electrocardiogram pattern in the IVM-treated group in comparison to MI (Iso) group. However, the MDA level was lower in the IVM-treated group. CONCLUSION: IVM pre-treatment demonstrates detrimental effects in cardiac ischemia through exacerbation of cardiac arrhythmia, myocardial dysfunction, and increased cardiac hypertrophy. Therefore, the use of IVM in ischemic heart patients should be done with great caution.

Chitosan-sodium alginate-polyethylene glycol-Ally isothiocyante nanocomposites ameliorates isoproterenol-induced myocardial infarction in rats.

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1ß and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.

Effect of sodium-glucose cotransporter-2 inhibitors on myocardial infarction incidence: A systematic review and meta-analysis of randomized controlled trials and cohort studies.

AIM: To assess whether sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce myocardial infarction (MI) incidence in patients with or without type 2 diabetes. METHODS: PubMed, Embase, Web of Science, the Cochrane library, and https://ClinicalTrials.gov were searched up to 7 May 2022. Randomized controlled trials (RCTs) and cohort studies reporting the effects of SGLT2 inhibitor treatment on MI incidence were included. Relative risks (RRs) with a 95% confidence interval (CI) for MI incidence were extracted and pooled. Subgroup analysis and meta-regression were performed to explore the heterogeneity. RESULTS: This meta-analysis included 54 RCTs and 32 cohort studies, with data from six SGLT2 inhibitors and 3 394 423 individuals. In the overall analysis, SGLT2 inhibitors significantly reduced MI incidence in RCTs (RR 0.9, 95% CI 0.84-0.96) and cohort studies (RR 0.89, 95% CI 0.83-0.94). In RCTs, the results of the subgroup analysis revealed no significant alterations in outcomes based on different SGLT2 inhibitor types, control drug types, cardiovascular disease (CVD) status and sources of outcome extraction (p for interaction >0.05). In cohort studies, the presence or absence of CVD led to similar effects of SGLT2 inhibitors on decreasing MI incidence (p for interaction = 0.179). However, variations in results were observed based on the type of control group in cohort studies (p for interaction = 0.036). Meta-regression results did not reveal an association between baseline cardiovascular risk factors, follow-up length, or MI incidence. CONCLUSIONS: In both RCTs and cohort studies, SGLT2 inhibitors reduced MI incidence. The cardioprotective effects of SGLT2 inhibitors were observed in patients with and without a history of CVD.