Effects Of Coronary Artery Disease Research Articles

Adenosine in Interventional Cardiology: Physiopathologic and Pharmacologic Effects in Coronary Artery Disease

This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine’s rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine’s involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine’s mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.

Exploring the effects of coronary artery disease as a preexisting comorbidity on mortality in hospitalized septic patients: a retrospective observation study

Abstract Background Sepsis has high prevalence and mortality rate, and it is imperative to identify populations at risk of poor sepsis outcomes. Septic patients with preexisting chronic comorbidities are shown to have worse sepsis outcomes. By identifying comorbidities with greater influence on sepsis progression, we can direct limited resources to septic patients with comorbidities and reduce health care costs. Chronic comorbidities can impact the risk of developing sepsis and having worse outcomes. Coronary artery disease (CAD) is a common comorbidity, especially in the elderly, and a leading cause of death globally. We wished to investigate the influence of CAD as a comorbidity on sepsis and hypothesized that preexisting CAD would increase mortality in hospitalized septic patients. Methods We conducted retrospective observational study using patient data from Freeman Health System in Joplin, MO. We analyzed patient records from Freeman Health System database from January 1, 2019, to June 30, 2020. Septic patients were identified using the International Classification of Diseases, Tenth Revision sepsis codes. To identify septic patients with preexisting CAD, we used International Classification of Diseases, Tenth Revision codes for CAD. We compared mortality rates for septic patients with and without CAD. Results Two-sample proportion test was conducted to test the difference in mortality between septic patients with and without preexisting CAD. The difference in mortality for the total population was −0.016 (P = 0.553). In the male and female subgroups, the differences in mortality were 0.0122 (P = 0.739) and −0.0511 (P = 0.208), respectively. The differences in mortality in patients aged 40 to 64 years and 65 years and older were −0.0077 (P = 0.870) and 0.0007 (P = 0.983), respectively. The statistical tests failed to find significant differences when comparing septic patients with and without preexisting CAD. There was no significant difference in the age and sex subgroups. Conclusions Our study showed that CAD alone was not associated with higher mortality due to sepsis in our population.

Effects of coronary artery disease in patients with permanent left bundle branch area pacing: A retrospective study

AimsMyocardial ischemia can affect traditional right ventricular (RV) pacing parameters, but it is unclear whether coronary artery disease (CAD) impact the pacing parameters and electrophysiological characteristics of left bundle branch area pacing (LBBaP) as a physiological pacing representative. MethodsPatients who underwent coronary angiography (CAG) after/before the LBBaP procedure and underwent percutaneous coronary intervention after LBBaP procedure were divided into CAD group and Non-CAD group according to visual CAG. Pacing parameters and electrophysiological characteristics were recorded at LBBaP implantation. Multivariate logistic regression analysis was implemented to evaluate the association between CAD and higher capture threshold. Sensitivity analyses were conducted to verify result stability. ResultsA total of 176 patients met inclusion criteria (115 Non-CAD patients and 61 CAD patients) with a mean age of 71.1 ± 9.0 years. Compared with the Non-CAD patients, CAD patients had the higher capture threshold (0.67 ± 0.22 V vs. 0.82 ± 0.28 V, P < 0.001) and lower R-wave amplitude (12.5 ± 4.8 mV vs. 10.1 ± 2.7 mV, P = 0.001). Moreover, CAD was independently associated with higher capture threshold (adjusted Odds ratio (OR) 3.418, 95% confidence interval (CI): 1.621–7.206, P = 0.001), which was further validated through sensitivity analyses. ConclusionPatients without CAD might have safer pacing parameters in the LBBaP procedure. Besides, CAD might be the risk factor of capture threshold increase during permanent LBBaP implantation.

Examining the effects of coronary artery disease- and mitochondrial biogenesis-related genes’ and microRNAs’ expression levels on metabolic disorders in epicardial adipose tissue

Background and aimsEpicardial adipose tissue (EAT) surrounds the heart and coronary arteries and is important for comprehending the pathogenesis of coronary artery disease (CAD). We aimed to evaluate the expressions of mitochondrial biogenesis- and CAD-related genes and miRNAs in EAT by comparing them to visceral adipose tissue (VAT) in CAD, diabetes, and obesity subgroups. MethodsIn this study, a total of 93 individuals were recruited, and EAT samples (63 CAD; 30 non-CAD) and VAT samples from 65 individuals (46 CAD; 19 non-CAD) were collected. For further analysis, the study population was divided according to obesity and diabetes status. PRKAA1, PPARGC1A, SIRT1, RELA, TNFA, and miR-155-5p, let-7g-5p, miR-1247-5p, miR-326 expression levels were examined. ResultsPRKAA1 and let-7g-5p were differentially expressed in EAT compared to VAT. TNFA expression was upregulated significantly in both tissues of CAD patients. In EAT, PRKAA1, PPARGC1A, and SIRT1 were downregulated with diabetes. Moreover, PPARGC1A expression is decreased under the condition of obesity in both tissues. EAT expressions of miR-1247-5p and miR-326 were downregulated with obesity, while miR-155-5p is decreased only in the VAT of obese. Also, miRNAs and genes were correlated with biochemical parameters and each other in EAT and VAT (p < 0.050). ConclusionsThe findings demonstrating distinct let-7g-5p and AMPKα1 mRNA expression between EAT and VAT underscores the importance of tissue-specific regulation in different clinical outcomes. In addition, the differential expressions of investigated genes and miRNAs highlight their responsiveness to obesity, DM, and CAD in adipose tissues.

Investigating the role of treatment adherence in predicting marital satisfaction among women with coronary artery disease: A cross-sectional study from Iran.

Despite the effect of coronary artery disease on sexual function and the relation between sexual function and marital satisfaction, few studies have investigated the effect of treatment adherence on marital satisfaction. The present study aims to investigate the role of treatment adherence in predicting marital satisfaction among women with coronary artery disease. In this cross-sectional study, 385 women with coronary artery disease in Bushehr-Iran, 2021, were selected using a convenient sampling method. The data were collected using the demographic form, Seyed Fatemi medication adherence scale, female sexual function index, and evaluation and nurturing relationship issues, communication, and happiness marital satisfaction scale. The data was analyzed using univariate and multivariate logistic regression tests. The mean (± standard deviation) age of the participants was 52.19 ± 12.15 years old. Considering the effect of demographic variables, treatment adherence (β = 0.164, P = 0.001) and sexual function (β = 0.156, P = 0.001) were positive predictors of marital satisfaction. Treatment adherence was a positive predictor of marital satisfaction. Healthcare providers should pay attention to the family consequences of non-adherence to treatment. Moreover, when counseling patients to adhere to the treatment, they should mention the physical benefits as well as psychological and family outcomes in order to motivate patients to follow their treatment.

Coronary Artery Disease as an Independent Predictor of Cardiovascular Mortality in COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is associated with increased risk of cardiovascular mortality. However, little is known about the combined effect of coronary artery disease (CAD) and COVID-19 on mortality. We aimed to investigate the incidence of cardiovascular and all-cause mortality in COVID-19 patients with CAD. This multicenter retrospective study identified 3,336 COVID-19 patients admitted between March and December 2020. Data points were manually reviewed in the patients' electronic health records. Multivariate logistic regression was used to assess whether CAD and its subtypes were associated with mortality. This study shows that CAD was not an independent predictor of all-cause mortality (odds ratio (OR): 1.512, 95% confidence interval (CI): 0.1529 - 14.95, P = 0.723). However, there was a significant increase in cardiovascular mortality in patients with CAD compared to those without (OR: 6.89, 95% CI: 2.706 - 17.53, P < 0.001). There was no significant difference in all-cause mortality in patients with left main artery and left anterior descending artery disease (OR: 1.29, 95% CI: 0.80 - 2.08, P = 0.29). However, CAD patients with a history of interventions (e.g., coronary stenting or coronary artery bypass graft) showed increased mortality compared to those solely treated by medical management (OR: 1.93, 95% CI: 1.12 - 3.33, P = 0.017). CAD is associated with a higher incidence of cardiovascular mortality but not all-cause mortality in COVID-19 patients. Overall, this study will help clinicians identify characteristics of COVID-19 patients with increased risk of mortality in the setting of CAD.

Effect of coronary artery disease on myocardial blood flow during passive heat stress

INTRODUCTION. Extreme heat is associated with a greater risk of cardiovascular mortality in older adults. However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. One possibility is that myocardial oxygen requirements during heat exposure surpass the capacity for myocardial oxygen delivery, thereby predisposing to myocardial ischemia. This may notably occur in individuals with coronary artery disease (CAD), because it reduces the capacity of the coronary arteries to dilate (i.e., coronary flow reserve). However, it is unknown to what extent myocardial blood flow (MBF) increases during heat exposure and whether this increase is altered by CAD. OBJECTIVE. This study tested the hypothesis that passive heat stress increases myocardial blood flow in older adults and that this increase is attenuated in older adults with CAD. METHODS. Healthy older adults (n=19, 68 ± 7 years) and older adults with CAD (n=12, 72 ± 6 years) were passively heated (water-perfused suit) until rectal temperature increased 1.5°C above baseline values. Myocardial blood flow was measured at baseline and at each 0.5°C increment in rectal temperature during heating by positron emission tomography following intravenous infusion of 82-Rubidium. Heart rate (ECG) and blood pressure (automated auscultation) were also measured to calculate rate pressure product (heart rate × systolic blood pressure). MBF reserve (MFR) was calculated by dividing the MBF at 1.5°C by baseline MBF. Adults with CAD were asked to withhold β-blockers, calcium channel blockers and nitroglycerin for 24h prior to the study. RESULTS. At a 1.5°C increase in core temperature, myocardial blood flow increased from 0.85 ± 0.20 to 1.51 ± 0.40 mL/min/g in healthy older adults and from 0.87 ± 0.19 to 1.37 ± 0.48 mL/min/g in adults with CAD. The change in myocardial blood flow at a 1.5°C increase in rectal temperature did not differ between groups (healthy: 0.66 ± 0.31 mL/g/min, CAD: 0.49 ± 0.42 mL/g/min, p=0.25. Furthermore, healthy adults and adults with CAD displayed a similar MFR at an increase in rectal temperature of 1.5°C (healthy: 1.8 ± 0.4 vs. CAD: 1.6 ± 0.6, p=0.25). CONCLUSION. These results demonstrate that passive heat stress increases myocardial blood flow nearly 1.6 times in older adults, and that this increase is not affected by CAD. These results will help determine if the increase in myocardial blood flow during passive heat exposure is sufficient to predispose to myocardial ischemia in individuals with low coronary flow reserve. Canadian Institutes for Health Research, Montreal Heart Institute Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effect of Coronary Artery Disease and Related Drugs on Sexual Activity in Turkish Society

The Effect of Coronary Artery Disease and Related Drugs on Sexual Activity in Turkish Society

Genetic variants associated with syncope implicate neural and autonomic processes.

Syncope is a common and clinically challenging condition. In this study, the genetics of syncope were investigated to seek knowledge about its pathophysiology and prognostic implications. This genome-wide association meta-analysis included 56 071 syncope cases and 890 790 controls from deCODE genetics (Iceland), UK Biobank (United Kingdom), and Copenhagen Hospital Biobank Cardiovascular Study/Danish Blood Donor Study (Denmark), with a follow-up assessment of variants in 22 412 cases and 286 003 controls from Intermountain (Utah, USA) and FinnGen (Finland). The study yielded 18 independent syncope variants, 17 of which were novel. One of the variants, p.Ser140Thr in PTPRN2, affected syncope only when maternally inherited. Another variant associated with a vasovagal reaction during blood donation and five others with heart rate and/or blood pressure regulation, with variable directions of effects. None of the 18 associations could be attributed to cardiovascular or other disorders. Annotation with regard to regulatory elements indicated that the syncope variants were preferentially located in neural-specific regulatory regions. Mendelian randomization analysis supported a causal effect of coronary artery disease on syncope. A polygenic score (PGS) for syncope captured genetic correlation with cardiovascular disorders, diabetes, depression, and shortened lifespan. However, a score based solely on the 18 syncope variants performed similarly to the PGS in detecting syncope risk but did not associate with other disorders. The results demonstrate that syncope has a distinct genetic architecture that implicates neural regulatory processes and a complex relationship with heart rate and blood pressure regulation. A shared genetic background with poor cardiovascular health was observed, supporting the importance of a thorough assessment of individuals presenting with syncope.

PET-MRI of Coronary Artery Disease.

Simultaneous positron emission tomography and magnetic resonance imaging (PET-MRI) combines the anatomical detail and tissue characterization of MRI with the functional information from PET. Within the coronary arteries, this hybrid technique can be used to identify biological activity combined with anatomically high-risk plaque features to better understand the processes underlying coronary atherosclerosis. Furthermore, the downstream effects of coronary artery disease on the myocardium can be characterized by providing information on myocardial perfusion, viability, and function. This review will describe the current capabilities of PET-MRI in coronary artery disease and discuss the limitations and future directions of this emerging technique. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Prevalence, risk factors, and clinical effect of coronary artery disease in patients with asymptomatic bilateral carotid stenosis

ObjectiveIn the present report, we have described the prevalence, risk factors, and clinical effects of coronary artery disease (CAD) for patients with asymptomatic bilateral carotid stenosis. MethodsWe conducted a single-center, retrospective cohort study of consecutive patients referred for bilateral carotid stenosis >70% (2014-2021). All the patients had undergone systematic coronary angiography. Depending on the anatomic and clinical characteristics, the patients had undergone combined carotid endarterectomy (CEA) plus coronary artery bypass grafting, coronary percutaneous intervention followed by CEA or carotid artery stenting (CAS), or staged bilateral CEA with cardiac best medical therapy. The cumulative 30-day stroke/myocardial infarction (MI) rate after cardiac and bilateral carotid interventions and long-term survival and freedom from cardiovascular mortality were assessed. ResultsA total of 167 patients with bilateral carotid stenosis >70% had undergone preoperative coronary angiography, identifying severe CAD in 108 patients (65.1%). Echocardiographic abnormalities (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.03-5.78; P = .04) and prior coronary intervention (OR, 11.94; 95% CI, 2.99-63.81; P = .001) were significantly associated with severe CAD. CAD was treatable in 91 patients (84%) and untreatable in 17 (16%). The cumulative MI rate was 4.8%; 5.6% for the patients with severe CAD and 1.7% for those without severe CAD (P = .262). The cumulative stroke rate was 1.8%; 1.8% for those with severe CAD and 1.7% for those without severe CAD (P = 1.00). The overall stroke/MI rate was 6.6%; 8.3% for those with severe CAD and 3.3% for patients without severe CAD (P = .33). Patients with severe CAD deemed untreatable for coronary bypass or percutaneous intervention had a higher risk of perioperative stroke/MI (OR, 1.24; 95% CI, 1.00-2.83; P = .04). At 10 years, overall survival was 67.1% (95% CI, 57%-79%), and freedom from cardiovascular mortality was 78.5% (95% CI, 69%-89%). Patients with untreatable CAD maintained a higher risk of 10-year mortality (hazard ratio, 5.5; 95% CI, 1.6-19.9; P < .01). ConclusionsIn the present study, the prevalence of CAD in patients with bilateral carotid stenosis was high, especially for those with abnormal echocardiographic findings. CAD was potentially treatable in 80% of patients, and staged or simultaneous CAD treatment was performed with an acceptable stroke/MI complication rate for these patients. The presence of untreatable CAD was associated with worsened early and long-term outcomes, questioning the benefit of carotid interventions for this subset of patients.

Cardiovascular responses to high-intensity stair climbing in individuals with coronary artery disease.

Exercise‐based cardiac rehabilitation leads to improvements in cardiovascular function in individuals with coronary artery disease. The cardiac effects of coronary artery disease (CAD) can be quantified using clinical echocardiographic measures, such as ejection fraction (EF). Measures of cardiovascular function typically only used in research settings can provide additional information and maybe more sensitive indices to assess changes after exercise‐based cardiac rehabilitation. These additional measures include endothelial function (measured by flow‐mediated dilation), left ventricular twist, myocardial performance index, and global longitudinal strain. To investigate the cardiovascular response to 12 week of either traditional moderate‐intensity (TRAD) or stair climbing‐based high‐intensity interval (STAIR) exercise‐based cardiac rehabilitation using both clinical and additional measures of cardiovascular function in individuals with CAD. Measurements were made at baseline (BL) and after supervised (4wk) and unsupervised (12 week) of training. This study was registered as a clinical trial at clinicaltrials.gov (NCT03235674). Participants were randomized into either TRAD (n = 9, 8M/1F) and STAIR (n = 9, 8M/1F). There was a training‐associated increase in one component of left ventricular twist: Cardiac apical rotation (TRAD: BL: 5.6 ± 3.3º, 4 week: 8.0 ± 3.9º, 12 week: 6.2 ± 5.1º and STAIR: BL: 5.1 ± 3.6º, 4 week: 7.4 ± 3.9º, 12 week: 7.8 ± 2.8º, p (time) = 0.03, η2 = 0.20; main effect) and post‐hoc analysis revealed a difference between BL and 4 week (p = 0.02). There were no changes in any other clinical or additional measures of cardiovascular function. The small increase in cardiac apical rotation observed after 4 weeks of training may indicate an early change in cardiac function. A larger overall training stimulus may be needed to elicit other cardiovascular function changes.

Effect of Coronary Artery Disease on COVID-19-Prognosis and Risk Assessment: A Systematic Review and Meta-Analysis.

Simple SummaryAs of October 2021, over 245 million people have been infected and nearly 5 million have died due to COVID-19. Atherosclerosis is a lipid-driven chronic inflammation of the arterial wall with coronary artery disease (CAD) that may lead to acute coronary syndrome (ACS), which remains the main cause of death in developed countries. We believe that due to CAD development factors affecting the vessel wall, the SARS-CoV-2 infection may precipitate further advancement of future thromboembolic events by a plaque erosion or rupture. Therefore, this metanalysis aims to unambiguously establish the role of the history of CAD in mortality and severity of COVID-19 disease.Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with pre-existing CAD were shown to have a more severe course of COVID-19, but this association has not been clarified. We performed a meta-analysis to determine the association between CAD and COVID-19 outcomes. We searched Scopus, Medline (PubMed), Web of Science, Embase, and Cochrane databases up to 2 November 2021. There were 62 studies with a total population of 49,286 patients included in the meta-analysis. CAD occurrence in survivor vs. non-survivor groups varied and amounted to 9.2% vs. 22.9%, respectively (OR = 0.33; 95%CI: 0.29 to 0.39; I2 = 70%; p < 0.001). CAD was also associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I2 = 72%; p < 0.001). The role of history of CAD in mortality and severe condition in COVID-19 presents itself as prominent—although a risk of bias in retrospective trials needs to be assessed, in case of our meta-analysis the statistically significant results when it comes to higher mortality among patients with CAD compared to non-CAD patients, a more severe condition observed in patients with CAD, and a visibly more frequent admission to intensive care unit in patients with CAD, it seems that an incidence of cardiovascular events plays a role in COVID-19 prognosis.

Coronary Artery Disease and Cancer: Treatment and Prognosis Regarding Gender Differences.

Simple SummaryCardiovascular disease and cancer are the leading causes of hospitalization and mortality in high-income countries. Studies of myocardial infarction show a disadvantage for the female sex in terms of survival and development of heart failure after myocardial infarction. The extent to which this also applies to the co-occurrence of coronary heart disease and cancer was investigated and analyzed here in large registry studies. Particular attention has been paid to the four most common cancers and hematologic diseases associated with coronary artery disease requiring treatment.Cardiovascular disease and cancer remain the leading causes of hospitalization and mortality in high-income countries. Survival after myocardial infarction has improved but there is still a difference in clinical outcome, mortality, and developing heart failure to the disadvantage of women with myocardial infarction. Most major cardiology trials and registries have excluded patients with cancer. As a result, there is only very limited information on the effects of coronary artery disease in cancer patients. In particular, the outcomes in women with cancer and coronary artery disease and its management remain empiric. We reviewed studies of over 27 million patients with coronary artery disease and cancer. Our review focused on the most important types of cancer (breast, colon, lung, prostate) and hematological malignancies with particular attention to sex-specific differences in treatment and prognosis.

Exercise-mediated adaptations in vascular function and structure: Beneficial effects in coronary artery disease.

Exercise exerts direct effects on the vasculature via the impact of hemodynamic forces on the endothelium, thereby leading to functional and structural adaptations that lower cardiovascular risk. The patterns of blood flow and endothelial shear stress during exercise lead to atheroprotective hemodynamic stimuli on the endothelium and contribute to adaptations in vascular function and structure. The structural adaptations observed in arterial lumen dimensions after prolonged exercise supplant the need for acute functional vasodilatation in case of an increase in endothelial shear stress due to repeated exercise bouts. In contrast, wall thickness is affected by rather systemic factors, such as transmural pressure modulated during exercise by generalized changes in blood pressure. Several mechanisms have been proposed to explain the exercise-induced benefits in patients with coronary artery disease (CAD). They include decreased progression of coronary plaques in CAD, recruitment of collaterals, enhanced blood rheological properties, improvement of vascular smooth muscle cell and endothelial function, and coronary blood flow. This review describes how exercise via alterations in hemodynamic factors influences vascular function and structure which contributes to cardiovascular risk reduction, and highlights which mechanisms are involved in the positive effects of exercise on CAD.

Dach1 Extends Artery Networks and Protects Against Cardiac Injury.

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Impact of initial very low-level low-density lipoprotein cholesterol on the prognosis of acute myocardial infarction patients.

Cholesterol control with statins has been shown to have beneficial effects in coronary artery disease. However, the relationship between initial very low low-density lipoprotein (LDL) cholesterol levels and long-term clinical outcomes in patients with acute myocardial infarction (AMI) remains unclear. A total of 8741 (mean age: 64.6 ± 12.7 years, men) consecutive AMI patients treated with drug-eluting stents were entered into the Korea Acute Myocardial Infarction Registry from November 2011 to December 2015. Patients were divided into six groups according to whether they were taking statins (on-statin group) or not (statin naive group) and depending on their LDL cholesterol level at admission (<70, 70-99, 100-129, 130-159, >160 mg/dl). Clinical outcomes at 24 months in patients with AMI were examined. The incidence of risk factors including hypertension, diabetes, coronary artery disease and heart failure was lower as LDL cholesterol increased, except in the on-statin group. Clinical outcomes, including total mortality at 24 months, showed better outcomes in those with high LDL cholesterol than those with low LDL cholesterol, except in the statin group. In the statin-naïve group, the higher the LDL cholesterol level, the higher the rate of 24-month survival. In a Cox regression model, initial low LDL cholesterol was an independent predictor of mortality at 24 months after adjusting for baseline confounding factors. At admission, a very low LDL cholesterol level (<70 mg/dL) in statin-naïve AMI patients undergoing percutaneous coronary intervention was independently associated with higher mortality at 24 months.

Smoking and heart failure: a Mendelian randomization and mediation analysis.

AimsWe performed a Mendelian randomization (MR) study to elucidate the associations of ever smoking, lifelong smoking duration, and smoking cessation with heart failure (HF) risk.Methods and resultsWe extracted genetic variants associated with smoking initiation, age at initiation of regular smoking, cigarettes per day, and smoking cessation from the genome‐wide association study and Sequencing Consortium of Alcohol and Nicotine use (1.2 million individuals), as well as a composite lifetime smoking index from the UK Biobank (462 690 individuals). The associations between smoking phenotypes and HF were explored in the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium (47 309 cases; 930 014 controls) employing inverse variance‐weighted meta‐analysis and multivariable MR. The mediation effects of coronary artery disease and atrial fibrillation on smoking–HF risk were explored using mediation analysis. The odds ratios (ORs) for HF were 1.28 [95% confidence interval (CI), 1.22–1.36; P = 1.5 × 10−18] for ever regular smokers compared with never smokers and 1.25 (95% CI, 1.09–1.44; P = 1.6 × 10−3) for current smokers vs. former smokers. Genetic liability to smoking more cigarettes per day (OR, 1.37; 95% CI, 1.20–1.58; P = 6.4 × 10−6) and a higher composite lifetime smoking index (OR, 1.49; 95% CI, 1.31–1.70; P = 2.5 × 10−9) were associated with a higher risk of HF. The results were robust and consistent in all sensitivity analyses and multivariable MR after adjusting for HF risk factors, and their associations were independent of coronary artery disease and atrial fibrillation.ConclusionsGenetic liability to ever smoking and a higher lifetime smoking burden are associated with a higher risk of HF.

Peripheral artery disease, lower limb revascularization, and amputation in diabetes patients with and without coronary artery disease: a cohort study from the Western Denmark Heart Registry

IntroductionPatients with diabetes have increased risk of lower limb revascularization and amputation due to higher risk of peripheral artery disease (PAD) and peripheral neuropathy. The additive effect of coronary artery...

Prevention of platelet aggregation and arterial thrombosis using a modified Shenzhu Guanxin Formula.

ObjectiveModified Shenzhu Guanxin Formula (mSGF) has beneficial effects in coronary artery disease. Previously, we found that mSGF inhibited platelet aggregation in rats. In the present study we further investigated the antiplatelet and antithrombotic activities of mSGF in rats.MethodsRats were orally administered mSGF (4.2, 8.4, or 16.8 g crude drug/kg), the adenosine 5′-diphosphate (ADP) receptor antagonist clopidogrel (7.875 mg/kg), or saline once a day for 7 days. The effects of mSGF on platelet aggregation were measured. Levels of cyclic adenosine monophosphate (cAMP) and phosphoinositide 3-kinase (PI3K) signaling were analyzed by ELISA and western blotting, respectively. The antithrombotic effect of mSGF was investigated using a FeCl3-induced carotid arterial thrombosis model and effects on bleeding time were assessed in a rat tail transection model.ResultsmSGF significantly inhibited ADP-induced platelet aggregation in a dose-dependent manner, elevated cAMP levels and inhibited phosphorylation of extracellular signal-regulated kinase (ERK) and PI3K/protein kinase B (Akt). Moreover, mSGF dose-dependently inhibited thrombosis in a FeCl3-induced carotid arterial thrombus model and had a significantly smaller effect on bleeding time compared with clopidogrel.ConclusionsmSGF represents a potent and safe antithrombotic agent whose antiplatelet activity is probably mediated through blockade of PI3K/Akt signaling and increased cAMP generation.