Rozh H. Al-Mashhadi, MD from the Aarhus University Hospital discusses Local Pressure Drives Low-Density Lipoprotein Accumulation and Coronary Atherosclerosis in Hypertensive Minipigs.
Link to Research -
There is a limited understanding of the mechanisms by which hypertension accelerates coronary artery disease. There are sometimes confusing humoral changes in patients with hypertension, and to date, no experimental models have allowed the isolated effect of pressure on atherosclerosis to be studied in a setting that recapitulates the dimensions and biomechanics of human coronary arteries.
This thesis aimed to examine and explore the fundamental mechanisms of the impact of pressure on coronary atherosclerosis.
Using inflatable suprarenal aortic cuffs, in the cephalad body portion of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9)D374Y Yucatan minipigs, we increased mean arterial pressure by >30 mm Hg for >1 year. Pressures at the caudal remained natural.
Cephalad hypertension accelerated coronary atherosclerosis to nearly 5-fold under hypercholesterolemic conditions in transgenic PCSK9D374Y mini pigs, with the consistent development of fibroatheromas that were sufficiently large to induce computed tomography angiography stenosis. This was caused by local pressure forces since there were no changes in lesion formation in vascular beds shielded from hypertension but subjected to the same humoral influences. The same experiment was performed to investigate the underlying mechanisms under normocholesterolemic conditions in wild-type mini-pigs. Hypertension with increased abundance of mechanical strength proteins and decreased levels of infiltrating plasma macromolecules induced clear changes in the arterial proteome. Increased smooth muscle cells and increased intimate accumulation of low-density lipoproteins in the coronary arteries were parallel to this.
Coronary atherosclerosis is facilitated by elevated pressure per se. Our data show that redesign of the artery to balance higher tensile forces in hypertension changes the movement of macromolecules and contributes to the increased intimate accumulation of lipoproteins of low density.
Prof. Giuseppe Tarantini, Chief of interventional Cardiology Unit - Associate Professor, University Medical school of Padua - GISE President speaks about Downstream or Upstream P2Y12 Receptor Blockers in NSTE-ACS: Primary Results of the DUBIUS Trial.
Link to Expert Analysis:
* In the case of various P2Y12 inhibitors, the available data on the clinical effect of pretreatment has been insufficient and heterogeneous.
* The DUBIUS (Downstream Vs Upstream Strategy for the Administration of P2Y12 Receptor Blockers in Non-ST Elevated Acute Coronary Syndromes With Initial Invasive Indication) trial found that both downstream and upstream oral P2Y12 inhibitor administration strategies were correlated with low rates of ischemic and bleeding events and a small numeric disparity between treatment groups.
* The widespread use of a radial method may have led to the low adverse event rates observed.
A brief introduction
In patients with non-ST-segment elevation acute coronary syndrome, dual antiplatelet therapy with aspirin and an oral P2Y12 inhibitor is the preferred treatment (NSTE-ACS). Ticagrelor and prasugrel, among P2Y12 inhibitors, are associated with better clinical results in patients with the acute coronary syndrome (ACS) than clopidogrel and are therefore favored unless contraindicated. 1 The timing of P2Y12 inhibitor administration has been a point of contention in recent years. 2 Their use prior to coronary angiography (also known as pretreatment) may minimize periprocedural ischemic events in patients undergoing percutaneous coronary intervention (PCI), but it may also increase the risk of significant bleeding. Furthermore, the available data on the clinical effects of pretreatment has been sparse and inconsistent across various P2Y12 inhibitors. 2
The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial) and CREDO (Clopidogrel for the Reduction of Events During Observation) trials on clopidogrel inspired the idea of starting dual antiplatelet therapy early in patients with NSTE-ACS. However, a significant percentage of CURE patients did not have coronary angiography, and the median time between enrollment and angiography for those who were treated invasively was several days. Patients for the CREDO trial were chosen after an angiography examination of their coronary anatomy.
In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 18,624 patients with ACS were randomly assigned to receive ticagrelor or clopidogrel. The PLATO study presented evidence in support of early initiation of ticagrelor therapy based on the observed early gain of ticagrelor over clopidogrel in terms of ischemic events (without a rise in the rate of overall significant bleeding). The research medications, however, were given before coronary angiography, and the study did not look into the issue of pretreatment.
In TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis In Myocardial Infarction 38), 13,608 patients with ACS were randomly assigned to receive prasugrel or clopidogrel. Prasugrel decreased the number of ischemic cases, but it came with a higher risk of significant bleeding. Patients in this study, however, were given prasugrel after coronary angiography if the need for PCI was verified.
Pretreatment with prasugrel was explicitly tested in the ACCOAST analysis (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction). Before coronary angiography, a total of 4,033 patients were randomized to receive prasugrel (pretreatment group) or a placebo (control group). Pretreatment with prasugrel was linked to a higher risk of major bleeding without a reduction in major ischemic incidents after 30 days.
In the ISAR-REACT 5 study (Intracoronary Stenting and Antithrombotic Regimen 5) 4,018 patients with ACS were randomly assigned to receive either ticagrelor or prasugrel.
3 The loading dose for the ticagrelor community was given as soon as possible after randomization. The loading dose was given as soon as possible in patients with ST-segment elevation ACS (41%) and after coronary anatomy was known in patients with NSTE-ACS in the prasugrel community. At one year, prasugrel substantially decreased ischemic events without raising the rate of serious bleeding. Because of the research nature, both the study drugs and the administration approach may have had a mixed impact on the observed outcomes.
Design of the DUBIUS Trial Study
The DUBIUS trial was a multicenter, randomized, adaptive, open-label trial that compared downstream and upstream oral P2Y12 inhibitor administration strategies in patients with NSTE-ACS who were undergoing invasive treatment.
4,5 patients were randomly allocated to receive ticagrelor or no ticagrelor before angiography (upstream group) (downstream group). All patients undergoing PCI were randomized to receive either ticagrelor or prasugrel in the downstream community.
In terms of net clinical gain on ischemic and haemorrhagic cases, the primary hypothesis was that the downstream administration strategy would be superior to the upstream administration strategy. At 30 days after randomization, the primary outcome was a combination of death from vascular causes (death from cardiovascular or cerebrovascular causes, and any death without another known cause), nonfatal myocardial infarction, or nonfatal stroke, and serious or fatal bleeding (BARC types 3, 4, and 5)
The DUBIUS Trial's Primary Findings
From December 2015 to May 2020, 1,449 patients were randomized from 30 Italian centers. The occurrence of the primary endpoint was measured at the second interim review. The steering committee agreed to halt enrollment for a futility scenario based on a predetermined stopping law. The research arms is well-balanced in terms of patient characteristics. Both groups had a median GRACE score of 122, and the downstream group had a median CRUSADE score of 22 and the upstream group had a median CRUSADE score of 21. More than 99 percent of patients had coronary angiography (median time: 23.3 hours), with the radial approach being the most common (94.5 percent of patients). In 72 percent of patients, PCI was used for revascularization, while coronary artery bypass graft was used in 6%. In 22% of patients, no revascularization was required.
The downstream and upstream classes had no variations in the rate of the primary endpoint (2.9 percent and 3.3 percent, respectively; absolute risk reduction –0.46; 95 percent confidence interval, –2.87 to 1.89). Significant or fatal bleedings were the most common adverse events, with no variations between categories. The timing of coronary angiography (within or after 24 hours of enrollment) and treatment with or without PCI had no effect on the results. In an exploratory study, the incidence of the primary endpoint did not vary substantially between patients treated with prasugrel and those treated with ticagrelor in the PCI subgroup of the downstream arm (4.1 percent and 3.1 percent, respectively; absolute risk reduction 0.9; 95 percent confidence interval, –3 to 5).
The DUBIUS trial is the first to investigate the effects of ticagrelor pretreatment in patients with NSTE-ACS. Owing to the unlikelihood of detecting an advantage of one approach over the other with continued enrollments, the DUBIUS trial was prematurely stopped after an interim review due to a futility scenario. The DUBIUS trial found that both a downstream treatment approach with an oral P2Y12 inhibitor (prasugrel or ticagrelor) and a ticagrelor-based pretreatment strategy were correlated with low rates of ischemic and bleeding incidents in patients with NSTE-ACS who are undergoing scheduled invasive treatment. Several factors, including early coronary angiography and revascularization, very high rates of radial approach, and widespread adoption of secondary prevention steps, may have led to the trial's low adverse event rates.
Summary In patients with NSTE-ACS receiving early invasive care, both downstream and upstream oral P2Y12 inhibitor administration methods were linked to a low incidence of ischemic and bleeding events, with little numeric difference between treatment classes. The widespread use of a radial method may have led to the low adverse event rates observed.
Carol Chiung-Hui Peng, MD from the University of Maryland Medical Center Midtown Campus, and Kashif Munir, MD from the University of Maryland School of Medicine, associate professor, and Medical Director of the University of Maryland Center for Diabetes and Endocrinology speak about Non‐vitamin K antagonist oral anticoagulants vs. warfarin for AFib patients: What the latest research tells us.
@UMMC @umms @UMmedschool
Link to Abstract:
Comparison of the risk of developing diabetes in patients with non-vitamin K antagonist oral anticoagulants (NOACs) treated with atrial fibrillation (AF) and warfarin.
Materials and Methods
Using Taiwan's National Health Insurance Research Database, we carried out a nationwide retrospective cohort analysis. Adult new-onset AF patients treated with NOACs or warfarin between 2012 and 2016 have been included. The NOAC cohort was further categorized into classes of dabigatran, rivaroxaban, and apixaban. Incident diabetes requiring treatment with antidiabetic medications was the primary outcome. Subdistribution hazard models of Fine and Gray were used to estimate the adjusted hazard ratio (aHR). For each head-to-head analysis, propensity score matching was conducted.
Our analysis included a total of 10,746 new-onset AF patients. NOACs were associated with a lower risk of developing diabetes than warfarin during the mean 2.4-year follow-up (aHR = 0.80, 95 percent confidence interval [CI]: 0.68-0.94, P = .007). Analyses of the subgroup indicated that dabigatran, rivaroxaban, and apixaban each had a decreased risk of diabetes. Stratified studies found that the lower risk of NOAC-related diabetes was specific for patients 65 years of age or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with strong adherence to medication (aHR = 0.70, 95% CI: 0.58-0.84, P < .001).
In patients with AF, taking NOAC was associated with a lower risk of developing diabetes compared to taking warfarin.
Paul W. Armstrong, MD from the Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada and the Merck speaks about the ACC 2021 Abstract - Coronary Artery Disease and Cardiovascular Outcomes in Heart Failure: Insights from the VerICiguaT Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA).
Link to Study:
The trial's purpose was to compare vericiguat to placebo in individuals with chronic heart failure (CHF) caused by a low ejection fraction (EF). Vericiguat boosts the activity of soluble guanylate cyclase. This may assist to enhance cardiac and vascular function by increasing the generation of cyclic guanosine monophosphate.
Design of the Research
* This is a randomized sample.
* Double-blind study
Vericiguat (n = 2,526) versus placebo (n = 2,524) were given to CHF patients. Vericiguat was begun at 2.5 mg per day, then raised to 5 mg, then 10 mg per day.
* The total number of students enrolled is 5,050.
* Follow-up period: 12 months
* The average patient is 68 years old.
* Females account for 24% of the total.
Criteria for inclusion:
* CHF; New York Heart Association class II-IV, left ventricular EF 45%, and heart failure treatment based on guidelines.
* A recent hospitalization for heart failure or the administration of an intravenous diuretic
* Natriuretic peptides elevated; N-terminal pro–B-type natriuretic peptide (NT-proBNP) 1000 pg/ml (1600 pg/ml if atrial fibrillation) or BNP 300 pg/ml (500 pg/ml if atrial fibrillation).
* Clinically stable (systolic blood pressure 100 mm Hg for 24 hours and no IV diuretics)
Criteria for exclusion:
* Nitrates with a lengthy half-life, phosphodiesterase type 5 inhibitors, and riociguat
* Awaiting a heart transplant, using continuous intravenous diuretics, or using a ventricular assist device now or in the future.
* Dialysis or chronic renal disease (evaluated glomerular filtration rate of 15 ml/min/1.73 m2)
* Severe pulmonary illness that necessitates the use of oxygen on a continual basis
* Hepatic insufficiency (severe)
* Cardiovascular comorbidities that can be treated
Other noteworthy features/characteristics include:
* The average EF is 29%.
* In 89 percent of cases, the target dosage of vericiguat was met.
The Most Important Findings:
Cardiovascular mortality or heart failure hospitalization occurred in 35.5 percent of the vericiguat group compared to 38.5 percent of the placebo group (hazard ratio [HR] 0.90, p = 0.019). The major outcome risk for vericiguat vs. placebo was 0.84% for those aged 75 years and 1.04% for those aged 75 years (p for interaction = 0.030).
Secondary effects include:
* Cardiovascular death: 16.4% in the vericiguat group vs. 17.5 percent in the placebo group (p = 0.27)
* Death from any cause: 20.3 percent in the vericiguat group vs. 21.2 percent in the placebo group (p = 0.38)
* Hospitalization for heart failure: 27.4 percent of the vericiguat group vs. 29.6 percent of the placebo group (p = 0.048).
* Serious adverse event: 32.8 percent of the vericiguat group versus 34.8 percent of the placebo group had a serious adverse event.
A new technique of boosting soluble guanylate cyclase activity with vericiguat proved successful in individuals with CHF who had recently decompensated. Vericiguat was shown to be more efficacious than placebo in lowering cardiovascular mortality and hospitalization for heart failure. There was a possibility of a greater advantage for those above the age of 75. Vericiguat did not appear to reduce all-cause mortality when compared to placebo. Vericiguat was well tolerated and did not need renal function or electrolyte monitoring. Vericiguat might be a potential therapy option for individuals who have recently had heart failure decompensation.
Carol Chiung-Hui Peng, MD and Kashif Munir, MD, Medical Director Of The University Of Maryland Center For Diabetes And Endrocrinology, University of Maryland Medical Center Midtown Campus, University of Maryland School of Medicine speaks about Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta‐Analysis.
Link To Abstract:
To evaluate the fracture risk associated with NOACs and warfarin, we performed a systematic review and meta-analysis.
Methods and Results:
From inception to May 19, 2020, we searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. We included studies that recorded measurements for any fracture in NOAC and warfarin users (regardless of major, secondary, tertiary, or safety outcomes). Two or more reviewers worked together to screen relevant papers, extract data, and evaluate accuracy. To synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin, data were retrieved. For data synthesis, random-effects models were used. There were 388 209 patients in 29 studies (5 cohort studies and 24 randomized controlled trials). Patients taking NOACs had a lower risk of fracture than those taking warfarin (pooled RR, 0.84; 95 percent CI, 0.77–0.91; P0.001), and there was little variability (I2=38.9%). NOACs were also linked to a lower risk of hip fracture than warfarin (pooled risk ratio, 0.89; 95 percent confidence interval, 0.81–0.98; P=0.023). There was also a nonsignificant trend of NOAC users having a lower risk of vertebral fracture (pooled RR, 0.74; 95 percent CI, 0.54–1.01; P=0.061). Specific NOACs dabigatran, rivaroxaban, and apixaban were found to be significantly associated with lower fracture risks in subgroup analyses. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were remarkably consistent, suggesting the validity of our findings.
NOACs are associated with a lower risk of bone fracture as compared to warfarin.
David Conen, MD from the Population Health Research Institute and McMaster University, discusses Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance.
Link To Study -
Atrial fibrillation (AF) is associated with an increased risk of death and cardiovascular complications and has been described as one of the 21st century cardiovascular epidemics.1 AF pathogenesis is complex, but many risk factors for AF have been described previously, explaining the attributable risk of about 50 percent of the population.1-4 Enhancing our understanding of risk factors. Indeed, only oral anticoagulation has so far been undeniably shown to boost difficult results once AF.5 has been established by a patient.
Excessive alcohol intake is a significant modifiable risk factor that predisposes to AF. 6,7 The development of AF has been related to both acute and increased habitual drinking. As is apparent in the Holiday Heart Syndrome, acute alcohol intake has a direct impact on the heart, contributing to atrial tachyarrhythmias.8,9 Chronic alcohol consumption is also associated with an elevated risk of AF.6,7 In the Women's Health Study, women who drank > 2 alcoholic drinks per day had a 60% higher risk of AF incident after the multivariable change, while lower amounts did n.
In this issue of the Journal, in a very broad dataset, Csengeri et al.10 discussed the relationship between alcohol consumption and incident AF. Five prospective community-based cohorts totaling 107,845 individuals free of AF at baseline were combined by Csengeri et al.10, of whom 5854 developed new-onset AF over a median follow-up of 13.9 years. From patient self-report, alcohol intake was determined at baseline, while incident AF was determined from hospitalization data through ICD codes or comorbidities reported on death certificates. The median age was 47.8 years, 48.3 percent were men and 3 g/day was the median intake of alcohol. Consumption of 1 alcoholic beverage (defined as 12 g of alcohol) per day was correlated with a 16 percent increased risk of incident AF in Cox regression models stratified by sex and cohort [hazard ratio 1.16, 95 percent confidence interval (CI) 1.11–1.22, P < 0.001]. Importantly, at very low alcohol consumption levels, there was a substantial association between alcohol and increased AF risk. Even an average 3 g/day intake was closely correlated with the risk of AF (HR 1.04, 95% CI 1.02-1.05). Adjustment for other AF risk factors has not substantially attenuated this relationship. It is important to remember, while not mentioned in the manuscript, that the absolute risk of AF was likely low in participants who drank low to moderate amounts of alcohol.
The authors found a J-shaped association between alcohol intake and heart failure events, with the lowest risk reported at alcohol levels of up to 20 g per day. The relationship between alcohol- and time-dependent heart failure (HF) was not important when evaluating the intermediate function of incident heart failure in developing AF from alcohol intake. Finally, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-I (hsTnI) were weakly associated with alcohol intake and the association between alcohol and AF for these biomarkers was not attenuated.
There are some strengths in the current study 10. Harmonization of the outcome and covariates across five cohorts allowed the authors to conduct standardized studies with very broad sample size and great power to define important associations between alcohol intake and AF, including the lower alcohol consumption range where the probability of AF incident is expected to be minimal. This research, therefore, offers strong evidence that even very low alcohol levels (i.e. < 1 drink per day) remain substantially correlated with an increased risk of new-onset AF.
There are drawbacks to the Csengeri et al.10 analysis. First, from hospitalization results, AF episodes were not adjudicated and relied on the international classification of diseases (ICD codes), which may have contributed to bias in misclassification. In addition, AF instances that did not result in hospital presentation or were listed on death certificates may not have been reported. Second, the link between binge drinking and incident AF could not be investigated in this review. Third, absolute risks of AF associated with low levels of alcohol intake were not reported in the study. This important problem must also be taken into account when considering the potentially beneficial associations with other cardiovascular outcomes of moderate alcohol intake.11-14 Finally, the research was not intended to shed more light on the mechanisms that link habitual alcohol consumption and AF production. Although the authors explored the potential role of NT-proBNP and hsTnI in this relationship, only a minority of patients had biomarker data available, and only at baseline. The effects of alcohol on atrial electrophysiology are likely to rely on many variables, including changes in atrial repolarization, vagal sound, and direct myocardial injury and fibrosis.9 More studies are required to investigate how alcohol affects atrial electrophysiology across these possible pathways.
In conclusion, the current Article10 makes a significant contribution to our understanding of the relationship between alcohol intake and AF incidence, especially with the lower alcohol consumption continuum. There was a substantial association between alcohol and AF, and even small amounts of alcohol were associated with an increased, albeit small, risk of AF incidence. Together with a recent randomized study showing that a decrease in alcohol intake resulted in a decrease in AF recurrence,15 these data indicate that reducing alcohol intake may be relevant for AF prevention and management. Importantly, any decrease in low-to-moderate alcohol consumption to potentially prevent AF needs to be balanced with the potentially beneficial association of low amounts of alcohol with other cardiovascular findings (Graphical abstract).11-14 More research is needed for the net clinical advantage of consuming low amounts of alcohol, preferably in adequately powered randomized studies. Until then, each person has to make their own best-educated decision as to whether it is worthwhile and healthy to consume up to 1 alcoholic drink per day.
Professor Murray Esler from the Baker Heart & Diabetes Institute discusses the Editorial - Reflections on the past four decades of mental stress research in autonomic cardiology.
Link to Full Article -
This commentary, with some observations and a description of my experience in the field of mental stress science, is my contribution to the celebration of the thirtieth anniversary of Clinical Autonomic Research, a journal that has become the benchmark publication for all those interested in the autonomic nervous system in recent years, regardless of their primary medical specialty, which in my case is the automobile.
In 1977, I returned to the Baker Medical Research Institute and the Alfred Hospital in Melbourne, Australia, after 4 years of postgraduate research and clinical training with Prof. Stevo Julius in the Hypertension Division of the University of Michigan Medical Center, where I worked as a clinical cardiologist and founded a laboratory for cardiovascular neuroscience.
I recall being struck by how the involvement of patients with myocardial infarction or ventricular arrhythmias was often precipitated by emotional turmoil in my early clinical practice in Melbourne. "I saw patients in whom armed robbery, robberies, and even an owner's racehorse winning by a "nose" had induced a heart attack. I was delighted to accept, in 1985, an invitation to participate in what I expected would be an influential national panel to discuss the relationship between mental stress and heart disease with this clinical exposure. However, I was not ready for the meeting chair's opening remark (whose name I will not say): "There is no proof that stress causes heart disease, nor will there ever be." I was saddened, but not discouraged, as this could not be true, of course. Where was his crystal ball? Even if the comment captured the pessimism that was prevalent in that era's cardiology.
Faced with this setback, by researching cardiac sympathetic responses to mental stress, I applied my newly developed noradrenaline spillover methodology to the stress-heart issue, tapping into research possibilities that are open to a cardiologist. I performed this study in a cardiac catheterization facility, using a tritiated noradrenaline infusion to measure the isotope dilution release of this catecholamine from sympathetic nerves, with sampling from the heart's coronary sinus. This was to make these measurements of noradrenaline release unique to the cardiac sympathetic nerves, all achieved during the study participants' exposure to laboratory mental stress (Fig. 1a). The applied stressor, as accepted by my institutional ethics committee, was 10 minutes of challenging mental arithmetic, only to surpass the arithmetic competence of the volunteer, and paced by a metronome. For the mathematically talented, an additional tweak was made by informing the individual that they were incorrect... when they were actually correct! In a standard experiment, we measured the secretion of adrenaline by the adrenal medulla, the release of noradrenaline from the sympathetic nerves and sympathetic nerves of the whole body, the concentrations of noradrenaline and adrenaline plasma sampled from the antecubital vein, and the firing of sympathetic outflow using microneurography in the innervation of the vasculature of the skeletal muscle in the leg.
Laura M. Stevens, Ph.D. from the Computational Bioscience Program, Department of Pharmacology (L.M.S.), University of Colorado Anschutz Medical School, Aurora and The American Heart Association discusses Association Between Coffee Intake and Incident Heart Failure Risk.
Link to Abstract -
Complex diseases with different phenotypes include coronary heart disease, heart failure (HF), and stroke. While several risk factors are well known for these diseases, researching as-yet unidentified risk factors will enhance risk evaluation and adherence to patients to preventive guidelines. In the FHS (Framingham Heart Study), CHS (Cardiovascular Heart Study), and ARIC (Atherosclerosis Risk in Communities) study, we investigated the diet domain to identify possible lifestyle and behavioral factors associated with coronary heart disease, HF, and stroke.
To classify possible risk factors associated with coronary heart disease, stroke, and HF in FHS, we used machine learning feature selection based on random forest analysis. Using univariable and multivariable Cox proportional hazards analysis optimized for known cardiovascular dangers, we assessed the importance of selected variables. Using CHS and ARIC, findings from FHS were then confirmed.
Multiple dietary and behavioral risk factors for cardiovascular disease outcomes were reported, including marital status, consumption of red meat, consumption of whole milk, and consumption of coffee. Among these dietary variables, the increase in coffee intake in FHS, ARIC, and CHS was associated with a decrease in the long-term risk of HF.
In all three studies, higher coffee intake was found to be associated with reduced HF risk. In order to better define the function, potential causality, and potential mechanism of coffee consumption as a potentially modifiable risk factor for HF, further research is warranted.
Giuseppina Caligiuri, MD, Ph.D. from the Laboratory for Vascular Translational Science, Université de Pari speaks about Coronary Stent CD31-mimetic Coating Favours Endothelialization And Reduces Local Inflammation And Neointimal Development In Vivo.
Link to Article:
The rapid endothelialization of bare-metal stents (BMS) is counterbalanced by neointimal growth caused by inflammation. Drug-eluting stents (DES) inhibit endothelialization thereby preventing leukocyte activation, slowing successful system penetration into arterial walls. We previously demonstrated that the vascular CD31 co-receptor is necessary for endothelial and leukocyte homeostasis as well as arterial healing. Furthermore, we have demonstrated that P8RI, a soluble synthetic peptide, acts as a CD31 agonist. The aim of this study was to see how a CD31-mimetic metal stent coating affected endothelial cell (EC) and blood element adherence in vitro, as well as strut coverage and neointimal growth in vivo.
Methods and Actual outcomes: We used two methods to coat Cobalt-Chromium discs and stents with a CD31-mimetic peptide: plasma amination and dip-coating, both of which achieved comparable results. In vitro, CD31-mimetic discs significantly decreased EC and blood platelet/leukocyte activation in primary human coronary arteries. At 7 and 28 days after implantation in pig coronary arteries, CD31-mimetic stent properties were compared to those of DES and BMS using coronarography and microscopy (n = 9 stents/group/time point). Only CD31-mimetic struts were completely endothelialized seven days after implantation, with no activated platelets or leukocytes. On day 28, neointima formation was substantially reduced over CD31-mimetic stents compared to BMS, appearing as a normal arterial media with no thrombosis, in contrast to DES.
Response: The CD31-mimetic coating promotes vascular homeostasis and arterial wall healing, avoiding stenosis and thrombosis within the stent. As a result, such coatings seem to increase the biocompatibility of metal stents.
Bart Meuris, prof. dr. from the University Hospitals Leuven Presentation on the HVS 2021 Abstract In-vivo Evaluation Of A Novel Surgical Heart Valve Prosthesis Designed To Be Durable, Anticoagulant-free And Silent.
Link to Abstract:
Reoperations of tissue valves or permanent anticoagulation of artificial valves are also drawbacks for heart valve prostheses. The Triflo valve, a tri-leaflet valve made of bio-inert materials with high resistance, was designed to overcome these limitations. In a chronic sheep model, we looked at protection and efficiency.
TECHNIQUES: The Triflo valve (size 21mm) was inserted in two models: in the aortic position for 90 days (n=7) and in the pulmonary position for 70 days (n=4). On-X valves (n=2) were used as a monitor in the pulmonary model. There was no more anticoagulant given after 7 days of low-molecular-weight heparin. Blood tests, echocardiography, acoustic measurements, fluoroscopy, and an autopsy were all performed.
The Triflo valve performed admirably during surgery. In the aortic analysis, there was one aborted surgery and one early death, all unrelated to the prosthesis. All of the other sheep (n=9) recovered well and continued in good clinical condition until they were slaughtered. We found low peak and mean gradients (8.1+/-2.7 and 4.8+/-1.9 mmHg, respectively), a large effective orifice area (2.3+/-0.2 cm2), no valvular regurgitation, and complete left ventricular activity in the aortic role. Both Triflo valves had a smooth surface at explantation, with no valve thrombosis. Thrombo-embolic (TE) damage was not found in any of the main organs. Both valve leaflet mobility was natural in the pulmonary role, and no TE-damage was observed in the lungs. Hematological parameters were stable, and no signs of hemolysis were present. In the pulmonary location, On-X valves performed well, but they produced slightly quieter acoustic signals (p0.05).
In both the aortic and pulmonary positions, the Triflo valve proved to be safe and reliable. These promising in-vivo effects, which include excellent hemodynamic activity and long-term operation even without anticoagulants, show that this valve is ready for human trials.
A. Michael Lincoff, MD, Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University speaks about Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design.
Link to Article:
CVD is a leading cause of morbidity and mortality in the United States. While it is widely accepted that obesity is a major risk factor for CVD, successful, long-term weight loss therapies and the effects of weight loss on lowering cardiovascular risk have remained elusive. Instead, drugs for managing lipids, hyperglycemia, blood pressure, heart disease, inflammation, and/or thrombosis have made progress in lowering CVD risk. Obesity has been linked to many of these problems, implying that sustained, successful weight loss may have a separate cardiovascular gain. GLP-1 receptor agonists (RAs) help people with diabetes lose weight, boost their glycemia, and reduce cardiovascular events. They can also have other cardioprotective effects. At a dosage of 2.4 mg subcutaneously (s.c.) once weekly, the GLP-1 RA semaglutide is in phase 3 trials as an obesity treatment. SELECT (Semaglutide Impact on Cardiac Disease and Stroke in Patients with Overweight or Obesity) is a randomized, double-blind, parallel-group study to see whether semaglutide 2.4 mg subcutaneously once weekly is better than placebo at preventing significant adverse cardiovascular events in patients with proven CVD and overweight or obesity but no diabetes when added to standard of care. SELECT is the first cardiovascular outcomes study to measure an antiobesity medication's superiority in reducing significant adverse cardiovascular conditions in this population. As a result, SELECT has the ability to advance novel approaches to lowering CVD risk while also addressing obesity.
Design and care of the overall sample
SELECT (NCT03574597, www.clinicaltrials.gov) is a randomized, double-blind, parallel-group, placebo-controlled study that compares semaglutide to placebo as an alternative to the standard of care for the prevention of major adverse cardiovascular events (MACE) in patients with existing CVD who are overweight or obese. Novo Nordisk is the main sponsor of the trial. Every participating center's institutional review board and ethics committee approved the trial protocol. Before any trial-related operation, all patients gave written informed consent.
Figure 1 portrays a high-level overview of SELECT's core design elements. Once-weekly subcutaneous (sc) semaglutide 2.4 mg or placebo is given to patients in a 1:1 ratio. Patients are started on a once-weekly dose of 0.24 mg, which is increased every four weeks (to doses of 0.5, 1.0, 1.7, and 2.4 mg/wk) before they hit the target dose of 2.4 mg after 16 weeks. To minimize the possibility of side effects, the procedure is versatile, allowing for prolonged escalation and treatment pauses if appropriate. The investigators will receive ongoing support from a Global Exert Panel, which is made up of local experts with experience in CVOTs and GLP-1RA use, and there will be a strong emphasis on educating and encouraging them during the trial. Since the most common side effects are gastrointestinal (nausea, vomiting, diarrhea, and constipation), manuals for clinicians and patients have been established and distributed. Overall, trial behavior places a heavy emphasis on maximizing trial product exposure. The management of cardiovascular risk factors is emphasized in the SELECT trial to ensure that patients meet international recommendations for quality of care. Investigators are given guidelines in the form of a standard-of-care document that is revised on a regular basis.
The patient is in touch with the investigator every 13th week during the trial to ensure retention and compliance, as well as to optimize care. During the first months of the study, site visits are more frequent to help the patient during the dose-escalation phase. Detailed tracking and recording of treatment pauses, missed visits, and possible loss of follow-up is done during the study. To ensure a high retention rate and ongoing support for investigators and patients involved in Pick, a number of mitigation steps have been introduced.
Numbers of people
Around 17,500 volunteers will be enrolled in the study from over 750 locations around the world, including locations on all six continents (Africa, Asia, Oceania, Europe, and North and South America). The first patient was randomized in November 2018, and the trial is planned to last 5 years, despite being event-driven. Patients must be at least 45 years old, have a BMI of 27 kg/m2, and have a history of CVD. Prior myocardial infarction (MI), prior ischemic or hemorrhagic stroke, symptomatic peripheral arterial disease (PAD) with an ankle-brachial index of less than 0.85 at rest, prior peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease are all examples of proven CVD. Patients with hemoglobin A1c (HbA1c) ≥48 mmol/mol (6.5%); with a history of type 1 or type 2 diabetes; or who had suffered MI, stroke, hospitalization for unstable angina pectoris, or a transient ischemic attack within 60 days of screening are excluded. The full eligibility requirements can be found in Table I. Patients who acquire diabetes during the study are held in the study and given concomitant diabetes medication (excluding other GLP-1 RAs) at the investigator's discretion.
Ramin Ebrahimi, MD, Department of Medicine, Cardiology Section, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California, and Department of Medicine, UCLA (University of California, Los Angeles) speaks about the Association of Posttraumatic Stress Disorder and Incident Ischemic Heart Disease in Women Veterans.
Link to Abstract:
Points to Remember:
Inquiry Is a history of posttraumatic stress disorder (PTSD) related to an increased risk of ischemic heart disease (IHD) in female veterans?
Findings: Those with PTSD had a 44 percent higher risk of developing incident IHD in this longitudinal cohort analysis of 398 769 women veterans, including 132 923 with PTSD matched 1:2 to 265 846 without PTSD. Various risk factors, including common and female-specific cardiovascular risk factors, as well as mental and physical health conditions, were taken into account using propensity score matching.
Meaning: These results indicate that among female veterans, PTSD is linked to an increased risk of experiencing incident IHD.
The significance of In primarily male populations or small group studies, posttraumatic stress disorder (PTSD) is linked to an increased risk of ischemic heart disease (IHD). Women veterans are an increasing but understudied demographic with high trauma exposure and specific cardiovascular risks, but there is little research on PTSD and IHD in this community.
The aim of this study was to see if PTSD is linked to incident IHD in female veterans.
Participants, Design, and Setting The a priori hypothesis that PTSD would be associated with a higher risk of IHD onset was tested in this retrospective, longitudinal cohort analysis of the national Veterans Health Administration (VHA) electronic medical records. Women veterans aged 18 and up, with or without PTSD, who were patients at the VHA between January 1, 2000, and December 31, 2017, were considered for the report. No VHA clinical experiences after the index visit, IHD diagnosis at or before the index visit, and IHD diagnosis within 90 days of the index visit were all exclusion criteria. Women veterans ever diagnosed with PTSD were compared in a 1:2 ratio to those never diagnosed with PTSD using propensity score matching based on age at index visit, number of previous visits, and prevalence of traditional and female-specific cardiovascular risk factors and mental and physical health conditions. From October 1, 2018, to October 30, 2020, data was analyzed.
PTSD diagnosis codes from inpatient or outpatient encounters, as specified by the International Classification of Diseases, Ninth Revision (ICD-9), or the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10).
Incident IHD, classified as new-onset coronary artery disease, angina, or myocardial infarction, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient experiences, and/or coronary procedures based on Current Procedural Terminology codes, are the main outcomes and measures.
The study included 398 769 women veterans, 132 923 of whom had PTSD, and 265 846 who had never been diagnosed with PTSD. The mean (SD) age at the start was 40.1 (12.2) years. 4381 women with PTSD (3.3%) and 5559 control persons (2.1%) developed incident IHD over a median follow-up of 4.9 (interquartile range, 2.1-9.2) years. In a Cox proportional hazards model, PTSD was linked to a higher risk of developing IHD (hazard ratio [HR], 1.44; 95 percent confidence interval [CI], 1.38-1.50). Secondary stratified tests revealed that women veterans with PTSD who were younger were at a higher risk of incident IHD. At baseline, effect sizes were highest for those under 40 years old (HR, 1.72; 95 percent CI, 1.55-1.93), and they decreased monotonically with age (HR for those 60 years old, 1.24; 95 percent CI, 1.12-1.38).
Conclusions and Consequences: This cohort study discovered that PTSD was linked to an increased risk of IHD in female veterans, which may have implications for assessing IHD risk in vulnerable people.
C. Michael Gibson, MD, CEO non-profit Baim / PERFUSE Research Institute, Harvard Professor, Cardiologist BIDMC, Founder & Chairman WikiDoc.org speaks about ACC 2021 Abstract - 1063-07 - Association Of Cholesterol Efflux Capacity With Adverse Cardiovascular Outcomes - A Meta Analysis
Link to Article:
The principal process by which macrophages remove cholesterol from atherosclerotic plaque is reverse cholesterol transport. A systematic literature review and meta-analysis were done to investigate the relationship between cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and poor cardiovascular (CV) events.
A literature study was conducted to gather papers that looked at the link between CEC and CV outcomes. Adverse CV events, a composite of incident atherosclerotic CV disease (acute coronary syndrome, stroke/transient ischemic attack, revascularization, or new atherosclerotic plaque), or all-cause death, were the main outcomes.
The following are the outcomes:
Twenty investigations yielded a total of 25,132 individuals. High CEC levels were linked with a 37 percent decreased risk of the main outcome when compared to low CEC levels (RR=0.63; 95 percent CI, 0.52-0.76; P0.00001; Figure A). A 20 percent decreased risk of unfavorable CV events was related with every SD rise in CEC (HR=0.80; 95 percent CI, 0.66-0.97; P=0.02). After controlling for CV risk factors, medicines, and HDL concentration, the link remained significant (HR=0.76; 95 percent CI, 0.63-0.91; P=0.004). There was a 5% risk decrease in unfavorable CV events for every 0.1 unit rise in CEC (RR=0.95; 95 percent CI, 0.91-0.99; Figure B).
Higher CEC is linked to less negative CV outcomes. These findings call for more research on CEC as a possible therapeutic target in order to enhance clinical outcomes.
Rohan Khera, MD, MS, Assistant Professor at Yale School of Medicine speaks about A phenomapping-derived tool to personalize the selection of anatomical vs. functional testing in evaluating chest pain (ASSIST).
Link to Lab's ASSIST:
Link to Article:
Coronary artery disease is often identified after anatomical or clinical examination is used to evaluate persistent chest pain. Personalized testing could be possible with a more detailed knowledge of patient phenotypes that benefit from either approach.
Methods and outcomes
We generated a topological representation of the sample population based on 57 pre-randomization variables using participant-level results from 9572 patients undergoing anatomical (n = 4734) vs. functional (n = 4838) research in the PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Cox regression models presented individual patient-centered hazard ratios for significant adverse cardiovascular outcomes within each patient's 5% topological neighbourhood and showed marked heterogeneity around the phenomap [median 1.11 (10th to 90th percentile: 0.52–2.61]], suggesting distinct phenotypic neighbourhoods favoring anatomical or functional research. We used an intense gradient boosting algorithm in 80% of the PROMISE population to estimate the personalized value of anatomical vs. functional tests using 12 model-derived, regularly collected variables and generated a decision support method called ASSIST based on this vulnerability phenomap (Anatomical vs. Stress teSting decIsion Support Tool). The testing strategy recommended by ASSIST was associated with a significantly lower incidence of each study's primary endpoint in both the remaining 20% of PROMISE and an external validation set consisting of patients from SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) undergoing anatomical-first vs. functional-first assessment (P = 0.0024 and P = 0.0321 for interaction, respectively) in both the remaining 20% of PROMISE and an external validation set consist
We suggest a new phenomapping-based decision support method to standardize the use of structural vs. functional research in the treatment of controlled chest pain, which has been tested in two broad and geographically disparate clinical trial populations.
Dino Mehic, MD from the Medical University of Vienna speaks about Elevated levels of tissue factor pathway inhibitor in patients with mild to moderate bleeding tendency.
Link to Abstract:
Points to Remember -
* TFPI levels are higher in patients with minor bleeding disorders, especially those that have BUC or PFDs.
* There were no genetic changes in the F5 gene that were related to increased TFPI levels.
High levels of tissue factor pathway inhibitor (TFPI) were recently discovered in two families with an unknown bleeding propensity, due to a longer TFPI half-life after binding to a factor V splice variant and variations in the F5 gene. The aim of this research was to look at the relationship between free TFPI and genetic alterations in the F5 gene in a well-characterized population of 620 patients with mild to moderate bleeding tendencies. Patients with leakage have higher TFPI values than stable controls (median [interquartile range], 8.2 [5.5-11.7] vs 7.8 [4.3-11.1]; P =.026). In comparison to stable samples, a higher percentage of patients had free TFPI ratios greater than or equal to the 95th percentile (odds ratio [OR] [95 percent confidence interval (CI)], 2.82 [0.98-8.13]). This was particularly noticeable in patients with no documented bleeding condition (bleeding of uncertain origin [BUC; n = 420]; OR [95 percent CI], 3.03 [1.02-8.98]) and platelet function defects (PFDs) (n = 121; OR [95 percent CI], 3.47 [1.09-11.08]). A rise in free TFPI was linked to a slight thrombin generation delay (longer lag time and time to peak), but not to changes in commonly used global clotting tests. In our patient cohort, we were unable to find any new or established genetic variants in the F5 gene that are linked to free TFPI levels, nor any effect of the single-nucleotide variant rs10800453 on free TFPI levels. Unexpected bleeding, which is more often multifactorial in the majority of patients, maybe caused or contributed by an excess of natural coagulation inhibitors such as TFPI.
Claudio de Lucia, MD, Ph.D. Center for Translational Medicine, Lewis Katz School of Medicine, Temple University speaks about G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure.
Link to Article:
The most common cause of heart failure (HF) is myocardial infarction (MI). In animal models, the G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy. The function of GRK5 in ischemic heart disease, on the other hand, is still unknown. In this research, we looked at whether myocardial GRK5 is essential after a heart attack in mice, as well as specific cardiac immune and inflammatory responses.
Methods and outcomes -
Cardiomyocyte-specific GRK5 overexpressing transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice, as well as cardiomyocyte-specific GRK5 knockout mice (GRK5cKO) and wild type (WT) mice, were all given a MI and their functional and structural changes, as well as their outcomes, were investigated. When compared to NLC post-MI mice, TgGRK5 post-MI mice had a lower cardiac function, a larger left ventricular dimension, and a lower survival rate. TgGRK5 mice had more cardiac hypertrophy and fibrosis, as well as fetal gene expression, after MI than NLC mice. GRK5 elevation developed immuno-regulators in TgGRK5 mice, which led to increased and long-lasting leukocyte recruitment into the injured heart, and eventually to chronic cardiac inflammation. At 4-days and 8-weeks post-MI, we observed a rise in pro-inflammatory neutrophils and macrophages, as well as neutrophils, macrophages, and T-lymphocytes in TgGRK5 hearts. In contrast to WT post-MI mice, GRK5cKO mice were protected from ischemic injury and showed reduced early immune cell recruitment (primarily monocytes) to the heart, increased contractility, and lower mortality. Surprisingly, cardiomyocyte-specific GRK2 transgenic mice did not exhibit the same phenotype as TgGRK5 mice and did not exhibit increased cardiac leukocyte migration or cytokine or chemokine output after MI.
Final thoughts -
In a murine model of post-ischemic HF, our findings show that myocyte GRK5 plays a critical and GRK-selective role in the control of leucocyte infiltration into the heart, cardiac function, and survival, indicating that GRK5 inhibition may be a therapeutic target for HF.
Sammy Zakaria, MD, MPH from Johns Hopkins University speaks about Acute Cardiac Effects of Severe Pre-Eclampsia.
Link to Article:
Background: Pre-eclampsia with severe features (PEC) is a pregnancy-related condition marked by severe hypertension and end-organ dysfunction, as well as short-term adverse cardiovascular events such as heart failure, pulmonary edema, and stroke.
The authors wanted to see how right ventricular (RV) systolic pressure (RVSP) and echocardiographic-derived diastolic, systolic, and speckle monitoring parameters changed over time in women with PEC.
The authors enrolled 63 women with PEC and 36 pregnant control patients in this prospective retrospective study.
The following are the outcomes:
As compared to the control cohort, the PEC cohort had a higher RVSP (31.0 7.9 mm Hg vs. 22.5 6.1 mm Hg; p 0.001) and a lower global RV longitudinal systolic strain (RVLSS) (19.6 3.2 percent vs. 23.8 2.9 percent [p 0.0001]). There were significant differences (p 0.001) in mitral septal e′ velocity (9.6 2.4 cm/s vs. 11.6 1.9 cm/s), septal E/e′ ratio (10.8 2.8 vs. 7.4 1.6), left atrial area size (20.1 3.8 cm2 vs. 17.3 2.9 cm2), and posterior and septal wall thickness for left-sided cardiac parameters (median [interquartile range]: 1.0 cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8 cm [0.7 to 0.9 cm]). PEC was seen in eight women (12.7%) with grade II diastolic dysfunction and six women (9.5%) with peripartum pulmonary edema.
When compared to healthy pregnant women, women with PEC have higher RVSP, higher rates of irregular diastolic activity, decreased global RVLSS, increased left-sided chamber remodeling, and higher rates of peripartum pulmonary edema.
Prof. Dr. Henner Hanssen from the University of Basel, Switzerland speaks about How To Prevent And Treat High Blood Pressure With Exercise.
Link to Consensus Document:
Treatment of hypertension and its symptoms is still a huge health-care problem. Hypertension is now responsible for about 25% of heart attacks in Europe, and by 2025, up to 60% of the population may have hypertension. Hypertension has become more common as a result of inactivity, but patients who exercise or partake in physical activity have a lower chance of stroke, myocardial infarction, and cardiovascular mortality. As a result, existing international recommendations on cardiovascular disease prevention include general advice to improve physical activity, but physiological responses vary depending on blood pressure (BP) level, and more personalized advice could be able to achieve larger BP reductions over a population. We conducted a comprehensive analysis of meta-analyses to see if there was enough data to provide a scientific Consensus Document outlining how to exercise medication could be tailored for blood pressure regulation. The paper summarizes the results of 34 meta-analyses on the effects of aerobic fitness exercise, dynamic strength training, and isometric resistance training on blood pressure in adults with hypertension, high-average blood pressure, and people with normal blood pressure. The meta-review found enough data, based on the approximate spectrum of exercise-induced BP reduction, the number of randomized controlled trials, and the consistency ranking, to suggest that form of exercise should be recommended based on initial BP level, but there are still significant research gaps. As a result, this evidence-based Consensus Document recommends that more studies be done to promote and develop more regular use of individual exercise prescriptions in order to improve lifestyle treatments for the prevention and treatment of hypertension.
Mads Hashiba Jensen, a Medical Student at the Department of Cardiology at Herlev og Gentofle Hospital and the University of Copenhagen a presentation on DANish Patients With Atrial Fibrillation and Sleep Apnea Prevalence by Night Owl (DANAPNO).
Link to Study:
Description of the Research -
A study to see whether NightOwl could be used to detect the prevalence of obstructive sleep apnea (OSA) in patients with atrial fibrillation (AF). The long-term goal is to use the system to test for OSA in AF patients undergoing ablation and/or AF patients undergoing cardioversion in a randomized clinical trial.
Patients with some form of AF who are referred to a nurse-run ambulatory for anticoagulation initiation will be required to participate. The ambulatory consists of four regular nurse-led tracks at Herlev-Gentofte University Hospital's Department of Cardiology. In a formal partnership, Herlev-Gentofte University Hospital's Department of Pulmonology offers work-up with cardio-respiratory monitoring investigation and clinical assessment of starting sleep apnea care in patients referred from the study. Those in attendance Participants will be recruited from the Thrombosis unit (Tromboseklinikken) at Herlev-GentofteHospital who have AF without established sleep apnea and a need for anticoagulation. As part of their routine check at the anticoagulation outpatient clinic at Herlev and Gentofte Hospital, participants will be contacted and invited to participate in the research project by a local investigator or a project nurse. Participants will be given verbal details about the research project as well as the appropriate time to discuss recruitment during the interview. The written participant information will be given to the participants before the verbal information, and it will be given to them by a researcher or a project nurse who is well-versed in the project. Before a written informed consent is received, the investigators will be given the details they need to find eligible participants. The written informed consent enables the researchers to access the participant's medical health records for the purposes of the study.
The analysis is cross-sectional in nature. A third visit will be scheduled for the first 20 participants and those with an apnea-hypopnea index (AHI)>15 who are included in the sample.
The participant borrows a NightOwl and receives system guidance during the initial visit, which includes a clinical assessment and a questionnaire about OSA symptoms.
In a home setting, NightOwlTM was used for four nights of recording.
A follow-up visit to discuss the findings of the home surveillance and the soft node questionnaire.
A fourth visit to the sleep apnea clinic will be scheduled for the first 20 patients, as well as all patients whose home test shows (AHI>15).
The research will take about 6 months from the time the first patient is enrolled until the last patient is enrolled.
Naveen L. Pereira, MD, Consultant for the Department of Cardiovascular Diseases and Professor of Medicine and Associate Professor of Pharmacology, Mayo Clinic College of Medicine speaks about ACC 2021 - Late-Breaking Clinic Science - Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y12 Inhibitor Therapy: A Meta-Analysis.
Link to Abstract:
The aim of this research was to compare the effects of ticagrelor or prasugrel versus clopidogrel treatment on clinical results in patients with coronary artery disease (CAD) who were primarily treated with percutaneous coronary intervention (PCI).
Background: The impact of CYP2C19 genotype on ticagrelor or prasugrel patient results relative to clopidogrel is unknown.
Methods: Experiments comparing the effects of CYP2C19 genotype on ischemic results during ticagrelor or prasugrel versus clopidogrel therapy were scanned through February 19, 2020. Results for CYP2C19 genotype status, clopidogrel, and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI are expected for study eligibility. The main focus of the study was on randomized controlled trials (RCTs). Non-RCTs are added to the main analysis as a supplementary analysis. Cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and extreme chronic ischemia were the main outcomes. To analyze the two-drug regimens and assess the relationship with the CYP2C19 genotype, a meta-analysis was performed.
Seven RCTs were found among the 1,335 studies found (15,949 patients, mean age 62 years; 77 percent had PCI, 98 percent had acute coronary syndromes). The probability of prejudice was poor, and statistical variability was small. When ticagrelor and prasugrel were linked to clopidogrel, there was a substantial decrease in ischemic incidents (relative risk: 0.70; 95 percent confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 0.70; 95 percent confidence interval: 0.59 to 0.83). (relative risk: 1.0; 95 percent confidence interval: 0.80 to 1.25). The association test on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), implying that the genotype of CYP2C19 altered the effect. Four further observational experiments were discovered, and when they were used in the study, the results were the same (p-value of the interaction test 0.001).
Conclusions: The role of ticagrelor or prasugrel in minimizing ischemic events in patients with CAD who specifically experience PCI is dependent on the existence of CYP2C19 loss-of-function carrier status when opposed to clopidogrel. These findings back up genetic tests before administering P2Y12 inhibitors.