Risk Of Serious Cardiovascular Events Research Articles

Cardiovascular screening of elderly athletes.

The permanently growing interest in amateur and professional sports activities among young, middle-aged and elderly athletes raises serious concerns about athletes' health, the safety of physical training, and the sports-related risk of sudden cardiac death and other cardiovascular complications during exercise. In recent years there has been an increasing number of cases of sudden cardiac death during physical effort. At present, life expectancy in the most developed countries grows rapidly and the number of people >65 years dramatically increases. Moreover, biological age of the population is lower. Subsequently, relevant increase in the number of elderly athletes involved in various types of sports activities has been reported in many countries. It was also demonstrated that physical activity has strong beneficial effect on cognitive functions, psychomotor performance and thus exercise capacity, which is very important for the elderly people in their everyday routine activities. Nonetheless, it should be remembered that participation in amateur and professional sports activities may be associated with risk of serious cardiovascular events in the elderly athletes often suffering from various civilization diseases. It is also reported that the number of elderly people after interventional cardiology procedures, open heart surgery and cancer treatment (chemotherapy, radiotherapy), who wish to participate in various sports activities, systematically grows. The authors of the paper conduct a literature review on cardiovascular risk assessment in the elderly athletes including the contemporary cardiology diagnostic methods and diagnostic schemes to prevent sudden cardiac death and other cardiovascular events during exercise. The controversies over efficacy of particular diagnostic tools to detect cardiovascular diseases in the elderly athletes and worldwide epidemiologic data concerning risk of sudden cardiac death during physical exercise have been also presented. Here, the authors have derived suggestions for establishment of comprehensive diagnostic schemes to prevent sudden cardiac death during sports activities. Med Pr Work Health Saf. 2024;75(3):233-241.

Nalmefene, an opioid receptor modulator, aggravates atherosclerotic plaque formation in apolipoprotein E knockout mice by enhancing oxidized low-density lipoprotein uptake in macrophages

Nalmefene, an antagonist of mu- and delta-opioid receptors and a partial agonist of kappa-opioid receptors, has shown promise in reducing alcohol consumption among patients with alcohol dependence. Opioid receptors play pivotal roles in various physiological processes, including those related to peripheral inflammatory diseases such as colitis and arthritis, as well as functions in the immune system and phagocytosis. Atherosclerosis, a chronic inflammatory disease, progresses through the phagocytosis and uptake of oxidized low-density lipoprotein (oxLDL) by macrophages in atherosclerotic plaques. Despite this knowledge, it remains unclear whether nalmefene influences the formation of atherosclerotic plaques and increases the risk of serious cardiovascular events. This study aims to elucidate the impact of nalmefene on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and peritoneal macrophages in vitro.In this experiment, 8-week-old male ApoE KO mice were fed a high-fat diet intraperitoneally administered either vehicle (saline) or nalmefene (1 mg and 3 mg kg−1 day−1) for 21 days. Oil red O-staining and immunohistochemistry with an anti-MOMA2 (monocyte/macrophage) antibody showed that a dose-dependent increase in atherosclerotic plaque formation and augmentation of macrophage-rich plaque formation in ApoE-KO mice. Further investigations focused on the effects of nalmefene on the expression of scavenger receptor CD36 in RAW264.7 cells, conducted through western blotting analysis. Nalmefene demonstrated a significant increase in CD36 protein expression in RAW264.7 cells. To explore the impact on oxidized LDL uptake in peritoneal macrophages, cells were treated with nalmefene (300 μg/mL) for 24 h, followed by the addition of DiI-labeled oxLDL (DiI-oxLDL) for 4 h. Nalmefene significantly enhanced DiI-oxLDL uptake in macrophages. Additionally, treatment with nalmefene (300 μg/mL) for 24 h decreased the mRNA expression of mu-, delta-, and kappa-opioid receptors in RAW264.7 cells.In conclusion, nalmefene may augment oxLDL uptake by macrophages through increased CD36 expression and decreased opioid receptor, thereby contributing to atherosclerotic plaque formation and vulnerability. Consequently, the use of nalmefene may be associated with an elevated risk of cardiovascular events.

Understanding the Gaps in the Reporting of COPD Exacerbations by Patients: A Review.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function, poor quality of life, loss of exercise capacity, risk of serious cardiovascular events, hospitalization, and death. However, patients underreport exacerbations, and evidence suggests that unreported exacerbations have similar negative health implications for patients as those that are reported. Whilst there is guidance for physicians to identify patients who are at risk of exacerbations, they do not help patients recognise and report them. Newly developed tools, such as the COPD Exacerbation Recognition Tool (CERT) have been designed to achieve this objective. This review focuses on the underreporting of COPD exacerbations by patients, the factors associated with this, the consequences of underreporting, and potential solutions.

Circulating miR-129-3p in combination with clinical factors predicts vascular calcification in hemodialysis patients.

Vascular calcification (VC) commonly occurs and seriously increases the risk of cardiovascular events and mortality in patients with hemodialysis. For optimizing individual management, we will develop a diagnostic multivariable prediction model for evaluating the probability of VC. The study was conducted in four steps. First, identification of miRNAs regulating osteogenic differentiation of vascular smooth muscle cells (VSMCs) in calcified condition. Second, observing the role of miR-129-3p on VC in vitro and the association between circulating miR-129-3p and VC in hemodialysis patients. Third, collecting all indicators related to VC as candidate variables, screening predictors from the candidate variables by Lasso regression, developing the prediction model by logistic regression and showing it as a nomogram in training cohort. Last, verifying predictive performance of the model in validation cohort. In cell experiments, miR-129-3p was found to attenuate vascular calcification, and in human, serum miR-129-3p exhibited a negative correlation with vascular calcification, suggesting that miR-129-3p could be one of the candidate predictor variables. Regression analysis demonstrated that miR-129-3p, age, dialysis duration and smoking were valid factors to establish the prediction model and nomogram for VC. The area under receiver operating characteristic curve of the model was 0.8698. The calibration curve showed that predicted probability of the model was in good agreement with actual probability and decision curve analysis indicated better net benefit of the model. Furthermore, internal validation through bootstrap process and external validation by another independent cohort confirmed the stability of the model. We build a diagnostic prediction model and present it as an intuitive tool based on miR-129-3p and clinical indicators to evaluate the probability of VC in hemodialysis patients, facilitating risk stratification and effective decision, which may be of great importance for reducing the risk of serious cardiovascular events.

Fatal Coronary Artery Anomaly Concealed in Young Athletes with Exertional Syncope

Background. Syncope is a common symptom in children, many of which are benign and do not require treatment. Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital malformation but can be a risk for serious cardiovascular events, including sudden death as well as cardiogenic syncope. Case Report. We describe the case of a 14-year-old boy who suffered an initial syncope and afebrile seizure during a soccer game. A detailed medical history and imaging studies led to the diagnosis of the anomalous aortic origin of the left main coronary artery with an intramural course (AAOLCA-IM). Conclusion. Symptomatic AAOLCA-IM has the highest risk of sudden death among AAOCA, and surgical repair may be performed. Onset during exercise or preceding chest symptoms are suspicious signs of cardiogenic syncope and should be considered for cardiovascular imaging evaluation.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: diagnostic and therapeutic aspects. Review

The increase in the prevalence of non‑alcoholic fatty liver disease (NAFLD) occurs in parallel with the global epidemic of obesity and type 2 diabetes mellitus (T2DM) in the world. T2DM is an independent risk factor for the development of NAFLD. At the same time, researchers found that patients diagnosed with NAFLD have a two‑fold increased risk of developing T2DM. NAFLD is encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NASH is an aggressive form of NAFLD, associated with an increased risk of liver and non‑liver‑related mortality. Liver‑biopsy remains the gold standard for diagnosis, but the majority of patients liver damage can be diagnosed accurately by noninvasive methods.
 The presence of NAFLD in a patient with T2DM makes it difficult to achieve adequate glycemic control, deepens the manifestations of insulin resistance and atherogenic dyslipidemia, increases the risk of serious cardiovascular events and chronic kidney disease. Lifestyle modification and treatment of concomitant T2DM should be undertaken in all patients with NAFLD. To reduce the severity of liver steatosis, weight reduction by 3—5% is necessary, to reduce the inflammatory‑necrotic process, a more significant reduction may be required — up to 10% within 6—12 months. Physical activity increases the sensitivity of insulin receptors, and in combination with diet leads to a significantly significant improvement in biochemical and histological indicators in patients with NAFLD. Early identification and management of patients with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. Pharmacological therapy should be administered to patients with NASH purposed on the fibrosis inhibition, especially in case of the established predictors of high risk of disease progression (age >50 years, metabolic syndrome, T2DM, or increase in the activity of alanine aminotransferase), as well as to the patients with active NASH with high inflammatory activity.
 At the congress of the European Association for the Study of the Liver (EASL), which took place in Vienna on June 21—24, 2023, a new classification and nomenclature of NAFLD was adopted. It was proposed to replace the term «non‑alcoholic fatty liver disease» to the term «metabolic dysfunction‑associated steatotic liver disease» (MASLD). This diagnosis is established in patients with confirmed steatosis of the liver and one of five cardiometabolic risk factors: obesity, T2DM, insulin resistance, hyperlipidemia, atherosclerosis. The concept of «non‑alcoholic steatohepatitis» (NASH) has been changed to the concept of «metabolic dysfunction‑ associated steatohepatitis» (MASH). Coordination of the views of international and domestic experts in the field of studying this pathology will be important for clinical practice and scientific research.

Novel third-generation tyrosine kinase inhibitor for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a case study.

Although Philadelphia chromosome-positive acute leukemia (Ph + -ALL) has been revolutionized with tyrosine kinase inhibitors (TKIs), resistance and mutation are universal events during treatment with first-generation and second-generation TKIs. The present third-generation TKI has a dose-dependent, increased risk of serious cardiovascular events and the sensitivity is poor for patients with ≥2 mutations accompanied by the T315I mutation. Thus, novel and well-tolerated TKIs should be explored. This study analyzes the efficacy and advert effects of olverembatinib, a novel third TKI, in the treatment of newly diagnosed adult Ph + -ALL in induction therapy. Four adult patients with newly diagnosed Ph + -ALL were treated with olverembatinib as the first-line treatment. For induction therapy, these patients received 40 mg of oral olverembatinib quaque omni die for 28 days, 1 mg/kg/d of prednisone for 14 days, then tapered and stopped at 28 days and vindesine 4 mg/d at days 1, 8 and 15. After induction therapy, these patients received median or high-dose of cytarabine and methotrexate combined with oral olverembatinib as consolidation therapy. Then the allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. All patients reached complete remission with a complete cytogenetic response after induction therapy. Two patients reached major molecular remission and one with complete molecular remission. Before allo-HSCT, all the patients achieved complete molecular remission. All the patients have survived disease-free for 3-6 months. No severe advert effects were observed. It is well-tolerated and effective for olverembatinib in the treatment of newly diagnosed adult patients with Ph + -ALL. A prospective study should be performed to further testify the role.

Comparison of Risk of Serious Cardiovascular Events after Hemorrhagic versus Ischemic Stroke: A Population-Based Study

Patients with ischemic stroke are considered a very high risk population for subsequent cardiovascular events and guidelines recommend intensive preventive strategies. However, there is no clear recommendation that patients with hemorrhagic stroke should also be regarded as a very high cardiovascular risk population. To compare the risk of subsequent cardiovascular morbidity/mortality between patients with incident hemorrhagic and ischemic stroke. Patients aged ≥18 years with incident hemorrhagic or ischemic stroke between 1998 and 2017 and no prior history of serious vascular event were identified from UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics data. The cohort included 32,091 patients with an overall follow-up of 381,237 person-years (median: 11.8 years). After adjusting for potential confounders, patients with incident hemorrhagic stroke had no significantly different risk of subsequent cardiovascular morbidity compared with patients with incident ischemic stroke-coronary heart disease (CHD; hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.32), recurrent stroke (HR: 0.92, 95% CI: 0.83-1.02), peripheral vascular disease (PVD; HR: 1.15, 95% CI:0.56-2.38), or heart failure (HR: 1.03, 95% CI: 0.61-1.74). Patients with incident hemorrhagic stroke had significantly higher risk of subsequent cardiovascular disease (CVD)-related mortality (HR: 2.35, 95% CI: 2.04-2.72) and all-cause mortality (HR: 2.16, 95% CI: 1.94-2.41). Propensity-score matched analysis of 1,039 patients with hemorrhagic stroke and 1,039 with ischemic stroke showed similar risk in subsequent cardiovascular morbidity-CHD (stratified HR [sHR]: 0.92, 95% CI: 0.55-1.54), recurrent stroke (sHR: 0.93, 95% CI: 0.82-1.02), PVD (sHR: 1.04 95% CI: 0.45-2.41), or heart failure (sHR: 0.71, 95% CI: 0.39-1.27). The risk of subsequent cardiovascular events is similar between patients with incident hemorrhagic and ischemic stroke. Patients with previous hemorrhagic stroke should be regarded as a population at very high risk for subsequent CVD.

Characteristics of adverse event reporting of Xeljanz/Xeljanz XR, Olumiant, and Rinvoq to the US Food and Drug Administration.

BACKGROUND: On September 9, 2021, the US Food and Drug Administration (FDA) issued a drug safety communication and required revisions to the Boxed Warning for Xeljanz/Xeljanz XR (tofacitinib), Olumiant (baricitinib), and Rinvoq (upadacitinib) to include information about the risk of serious heart-related events, cancer, blood clots, and death. The Boxed Warning was based on a large safety randomized clinical trial of tofacitinib, but neither baricitinib nor upadacitinib has been studied in similar large safety clinical trials. OBJECTIVE: To evaluate characteristics of adverse event (AE) reporting of tofacitinib/XR, baricitinib, and upadacitinib to the FDA. METHODS: We analyzed the public FDA's Adverse Event Reporting System data to examine reported AEs that were related to any of the 3 drugs between January 1, 2019, and September 30, 2021. Both brand and generic names of these drugs were used to identify these AEs. Frequencies of AE reports were evaluated by patient demographics (age and sex), type of reporter, reporter region, seriousness, and reactions related to death, cardiovascular, cancer, and blood clots. Chi-square tests were used to compare the proportion of characteristics of AEs between these drugs at P < 0.05. RESULTS: We identified 56,833 AE reports of tofacitinib/XR, 2,318 reports of baricitinib, and 5,359 reports of upadacitinib. Higher proportions of patients reporting AEs for tofacitinib/XR were older and female than for baricitinib and upadacitinib. Higher proportions of tofacitinib/XR and baricitinib AEs were reported by health professionals than for upadacitinib. Higher proportions of upadacitinib AEs were in the United States and more serious than those of tofacitinib/XR and baricitinib AEs (all group and paired comparisons at P < 0.05). Regarding reactions, baricitinib AEs had highest proportions of death (7.2%) and cancer-related (4.1%) events, whereas tofacitinib/XR AEs had the highest proportions of cardiovascular-related (14.1%) and blood clot-related (14.8%) events. CONCLUSIONS: Although baricitinib and upadacitinib are in the same drug class as tofacitinib/XR, their risk of serious cardiovascular events, cancer, blood clots, and death might not be similar. Findings from this hypothesis-generating study suggest that there may be differential AEs between Janus kinase inhibitors, and therefore, future research for robust comparative safety is warranted.

Effects of GLP-1RAs on cardiovascular outcomes in patients with type 2 diabetes mellitus: review of real-world data on target populations from diabetes registry in Russian Federation

RATIONALE. Over the past 20 years the prevalence of type 2 diabetes in Russia has more than doubled and reached 4.43 million people in 2020, while the growth rate keeps increasing. Most patients with T2DM are at a higher risk of developing major adverse cardiovascular events (MACE) associated with significant mortality. There is a strong evidence base that the drugs belonging to GLP-1RA class contribute to reducing the risk of cardiovascular events and renal outcomes. At the same time, the current prescribing rates of these treatments in Russia are quite low - only about 0.1% of patients are prescribed GLP-1RAs, according to Diabetes Registry data.AIM. Review the results of several randomized clinical trials (RCTs) concerning effects of GLP-1RA treatments on prevention of primary and secondary cardiovascular events and estimate the number of diabetic target population.MATERIALS AND METHODS. We examined the data from clinical trials on GLP-1RA treatments registered in Russia and used in routine clinical practice (ELIXA, EXSCEL, LEADER, SUSTAIN-6 and REWIND) and data from two meta-analyzes published as of December 1, 2020. The task was to evaluate the inclusion criteria, patient profile, and the clinical efficacy and safety profiles of the studied therapies. Also, the analysis of clinical information from the Diabetes Registry (DR) was performed to estimate the number of target T2DM patients meeting RCTs inclusion criteria that could benefit from prescribing of GLP-1RAs.RESULTS. The reviewed clinical trials demonstrated a statistically significant reduction (p &lt;0.05) in the risk of serious cardiovascular events in patients treated with Liraglutide [RR 0.87 (95% CI, 0.78-0.97)], Semagltuide [OP 0.74 (95% CI 0.58-0.95)] and Dulaglutide [RR 0.88 (95% CI 0.79-0.99)]. Meta-analyzes utilizing data from 6 RCTs with the total number of 56,004 T2DM patients, also, confirmed a statistically significant reduction in the risk of developing MACE (by 12%) in the studied population, and a 17% reduction in the risk of combined renal outcomes [RR 0.83 (95% CI 0.78-0.89), p &lt;0.0001]. The DR patient population that met the RCTs inclusion criteria amounted to 538.6 thous. subjects in case of REWIND and 432.4 thous. in case of LEADER and SUSTAIN-6. The key differences between FDR patients and patients engaged in RCTs included gender and age characteristics. The DR patients were generally older and the bulk of them were women, which has to do with overall Russian demographic trends. The proportion of DR patients with established CVD was 26%, which closely matched the profile of patients from REWIND study (31.5%). According to DR data, the number of patients in whom the treatment was intensified following prescription of basal insulin was 7612 per year, which is close to a potential cohort eligible for alternative treatment with GLP-1RAs.CONCLUSION. All the drugs belonging to GLP-1RA class are clinically effective in reducing the risk of cardiovascular and renal outcomes, while demonstrating a favorable safety profile including with respect to lower risk of developing hypoglycemia. The decreased risk of complications was recorded both in patients with existing cardiovascular risks and patients with established CVD. Of all GLP-1RA treatments available in Russia at this point, the greatest clinical effectiveness is achieved by Liraglutide, Semaglutide and Dulaglutide. The estimated patient population from DR, meeting RCTs inclusion criteria and matching RCTs patient profile was over 500, 000 people with the largest number of patients meeting the REWIND criteria. The target population of patients with T2DM who may potentially benefit from the administration of GLP-1RAs is over 500, 000 people. Out of that number at least 7.5 thousand are patients, whose treatment is intensified following prescription of basal insulin (with an aim of improving glycemic control, but without consideration of cardiovascular risks).Currently, if we take the real world clinical setting in Russia, the number of patients receiving GLP-1RA treatments is substantially lower than the estimated figures (less than 1%), which requires reconsideration of the approach toward their prescribing as is recommended by state-of-the-art clinical guidelines prioritizing prevention of cardiovascular risks.

Hypertensive Retinopathy and Risk of Serious Cardiovascular Events: Five Years Prospective Cohort Study in Primary Care

Introduction: Poorly controlled hypertension causes damage to the retinal microcirculation, which is predictive and associated to risk of stroke. Studies have shown that retinal microvascular changes can be reliably documented by retinal photographs. This study aims at examine the associative risk and incident of hypertensive retinopathy related serious cardiovascular events in primary care. Methodology: This is a prospective cohort study involving hypertensive patients in one regional primary care clinic of Hong Kong. Eligible digital retinal photographs of hypertensive patients done in the period Jan 1, 2011 to Dec 31, 2012 were graded based on Wong & Mitchell criteria. Consecutive subjects with hypertensive retinopathy (HTR) and without HTR (Non-HTR) were allocated to cohort and control group respectively until ceiling of 138. All patients will be followed prospectively for five years to exam the incidence of serious cardiovascular events. The relative risk of hypertensive retinopathy related serious cardiovascular events were investigated. Results: The cohort group patients are younger (mean age 57.3 versus 61.0, P<0.01), and have higher proportion of comorbid hyperlipidaemia (P=0.02). There are no statistical difference in sex, smoking status, duration of hypertension (HT), number of anti-hypertensive medication taking and mean blood pressure. At five year, both groups have no cardiovascular related mortality. Cohort group has 13 events of cardiovascular disease (incidence rate 9.42%), while control group has 5 events (incidence rate 3.62%). The five year realative risk (RR) of HTR for serious cardiovascular events is 2.77 (95% CI: 0.96-7.98, P=0.051), while five year RR of HTR for stroke is 9.56 (95% CI 1.19-76.5, P=0.010). With logistic regression analyasis, HTR is independent risk factor for stroke, with RR 8.55 (p=0.047). Conclusion: Hypertensive retinopathy is the independent predictive risk factor for stroke. The sensitivity and specificity of HT patients with HTR in predicting stroke in 5 years is 90.0% and 51.5% respectively.

Obstructive Sleep Apnea Screened by Overnight Pulse Oximetry and Higher Risk of Serious Cardiovascular Events: Prospective Cohort Study in the Primary Care

Introduction: Obstructive sleep apnea (OSA) is a condition characterized by sleep disordered breathing which results in health impairment and other related injuries. Cardiovascular and neurocognitive morbidities and increased risk of motor vehicle accidents have been demonstrated in patients with untreated OSA. Overnight pulse oximetry is a good screening tool for OSA. There is no study to examine the prospective outcome of patients with screening positive OSA in the primary care setting. Methodology: This is a prospective cohort study involving consecutive patients whom had performed OSA screening by overnight pulse oximetry in a primary care clinic of Hong Kong from year 2011 to year 2012. One hundred and eighty consecutive OSA screening positive patients were the cohort group while 180 consecutive OSA screening negative patients were the control group. The five year incidence of serious cardiovascular complications and associated predictive factors were examined. Results: Both of cohort and control group patients were followed prospectively for 5 years. There was higher proportion of male (68.3% versus 45.0%, p<0.001) and obesity (58.3% versus 41.1%, p=0.001) patients in the cohort group. There was no statistical difference in concomitant chronic disease or difference in mean blood pressure and Epworth Sleepiness Scale (ESS) score among two groups. At five year follow up, there was no cardiovascular related mortality among two groups. The five year relative risk (RR) of screening positive OSA versus screening negative for serious cardiovascular event is 3.03 (95% CI, 1.16-7.86; p=0.018). By stratification, the relative risk for stroke is 1.69 (95% CI, 0.40-7.16; p=0.475), while for coronary artery disease (CAD) is 4.24 (95%CI, 1.18-15.29; p=0.017). Conclusion: Overnight pulse oximetry screening positive obstructive sleep apnea is the independent risk factor for coronary artery disease.

Avaliação da Problemática da Doença Renal Crónica (Não Diálise) em Portugal: Abordagens para a Intervenção Precoce e Redução da Progressão

Chronic kidney disease is a global public health problem and is associated with an increased risk of serious cardiovascular events and mortality. Since Portugal is one of the European countries with the highest incidence of this pathology, we emphasize the importance of promoting the increase of notoriety of this problem with the health authorities, the health professionals and the scientific community. We present a few recommendations that we consider relevant for the better management of this problematic in our country, namely the promotion of communication between different medical specialties, healthcare organization, and we mention others that may play an important role in the future pharmacotherapy approach, such as sodium–glucose cotransporter 2 inhibitors to reduce morbidity and mortality of this population.

Sclerostin Downregulation Globally by Naturally Occurring Genetic Variants, or Locally in Atherosclerotic Plaques, Does Not Associate With Cardiovascular Events in Humans.

ABSTRACTInhibition of sclerostin increases bone formation and decreases bone resorption, leading to increased bone mass, bone mineral density, and bone strength and reduced fracture risk. In a clinical study of the sclerostin antibody romosozumab versus alendronate in postmenopausal women (ARCH), an imbalance in adjudicated serious cardiovascular (CV) adverse events driven by an increase in myocardial infarction (MI) and stroke was observed. To explore whether there was a potential mechanistic plausibility that sclerostin expression, or its inhibition, in atherosclerotic (AS) plaques may have contributed to this imbalance, sclerostin was immunostained in human plaques to determine whether it was detected in regions relevant to plaque stability in 94 carotid and 50 femoral AS plaques surgically collected from older female patients (mean age 69.6 ± 10.4 years). Sclerostin staining was absent in most plaques (67%), and when detected, it was of reduced intensity compared with normal aorta and was located in deeper regions of the plaque/wall but was not observed in areas considered relevant to plaque stability (fibrous cap and endothelium). Additionally, genetic variants associated with lifelong reduced sclerostin expression were explored for associations with phenotypes including those related to bone physiology and CV risk factors/events in a population‐based phenomewide association study (PheWAS). Natural genetic modulation of sclerostin by variants with a significant positive effect on bone physiology showed no association with lifetime risk of MI or stroke. These data do not support a causal association between the presence of sclerostin, or its inhibition, in the vasculature and increased risk of serious cardiovascular events. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6-8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial 'Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients' (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. METHODS: MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. SUMMARY: While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

Foreword

The extensive collection of bacteria cohabiting within the host collaborates with human functions and metabolisms in both health and disease. The fine equilibrium of commensals is tightly controlled and an imbalance (“dysbiosis”) in the gut microbiota can play different roles in human disease. The development of new genome sequencing techniques has allowed a better understanding of the role of human gut microbiota. This led to the identification of numerous metabolites produced in the gut, which have been suggested to play a role in human disease. Among these, trimethylamine oxide (TMAO) appears to be of particular importance as a risk factor and potentially as a causative agent of various pathologies, most remarkably cardiovascular and disease and other associated conditions. Mechanistic links are yet to be established, however, increased levels of TMAO have been shown to augment the risk of developing renal failure, metabolic syndrome, diabetes mellitus, heart failure, hypertension, atherosclerosis, and dyslipidemia ultimately leading to increased risk of serious cardiovascular events. This article reviews the potential impact of TMAO in human cardiovascular disease.

Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial.

OBJECTIVETo determine the risk factors for severe hypoglycemia and the association between severe hypoglycemia and serious cardiovascular adverse events and cardiovascular and all-cause mortality in the Veterans Affairs Diabetes Trial (VADT).RESEARCH DESIGN AND METHODSThis post hoc analysis of data from the VADT included 1,791 military veterans (age 60.5 ± 9.0 years) with suboptimally controlled type 2 diabetes (HbA1c 9.4 ± 2.0%) of 11.5 ± 7.5 years disease duration with or without known cardiovascular disease and additional cardiovascular risk factors. Participants were randomized to intensive (HbA1c <7.0%) versus standard (HbA1c <8.5%) glucose control.RESULTSThe rate of severe hypoglycemia in the intensive treatment group was 10.3 per 100 patient-years compared with 3.7 per 100 patient-years in the standard treatment group (P < 0.001). In multivariable analysis, insulin use at baseline (P = 0.02), proteinuria (P = 0.009), and autonomic neuropathy (P = 0.01) were independent risk factors for severe hypoglycemia, and higher BMI was protective (P = 0.017). Severe hypoglycemia within the past 3 months was associated with an increased risk of serious cardiovascular events (P = 0.032), cardiovascular mortality (P = 0.012), and total mortality (P = 0.024). However, there was a relatively greater increased risk for total mortality in the standard group compared with the intensive group (P = 0.019). The association between severe hypoglycemia and cardiovascular events increased significantly as overall cardiovascular risk increased (P = 0.012).CONCLUSIONSSevere hypoglycemic episodes within the previous 3 months were associated with increased risk for major cardiovascular events and cardiovascular and all-cause mortality regardless of glycemic treatment group assignment. Standard therapy further increased the risk for all-cause mortality after severe hypoglycemia.

CHANGES OF PULSE WAVE VELOCITY AND THE EFFECTIVENESS OF BLOOD PRESSURE CONTROL IN PATIENTS WITH HYPERTENSION AND MORBID OBESITY AFTER BARIATRIC SURGERY

Objective: Research objective was studying of pulse wave velocity (PWV) changes and the effectiveness of blood pressure (BP) control in obese patients after bariatric treatment. Design and method: It were surveyed 22 untreated patients (11 males) with morbid obesity. The body mass index before the surgery was 47.6 ± 2.14 kg/m2. Hypertension was detected in 20 (90.9%) patients: grade 1 was established in 9 (40.9%), grade 2 - in 8 (36.4%) and grade 3 - in 3 (13.6%) patients. According to target organ damage stage I hypertension was established in 4 (18.2%), stage II in 16 (72.7%) patients. Low cardiovascular (CV) risk was established in 1 (4.55%) patient, moderate CV risk in 1 (4.55%) patient, high CV risk in 16 (72.7%) patients, very high CV risk in 4 (18.2%) patients. The combined antihypertensive therapy was prescribed to all patients with hypertension and obese before surgery to reach normal BP values. As a result 2-component therapy was prescribed to 6 (27,3%) patients, 3-component therapy - to 8 (36,4%), 4-component therapy - to 5 (22,7%), 5-component therapy - to 1 (4,55%) patient. The effectiveness of the prescribed antihypertensive therapy was evaluated using office BP measurement. BP control in all patients was repeated after bariatric treatment. Results: Systolic BP level significantly decreased from 152,60 ± 5,71 mm Hg to 121,70 ± 3,02 mmHg (p < 0,001) after bariatric surgery. Diastolic BP also declined during estimated period from 86,20 ± 3,13 to 69,0 ± 2,92 mm Hg (p < 0,001). PWV levels decreased from 8,66 ± 0,27 to 7,14 ± 0,46 (p < 0,005). Significant positive results achieved after bariatric treatment allowed 5 (22.7%) patients first to reduce dosages, and subsequently to stop taking antihypertensive therapy in order to achieve normotension, and 15 (68.2%) patients - significantly to reduce dosages and quantity of taken drugs. Conclusions: Weight loss as a result of surgical treatment of obesity significantly improves BP control and PWV level in patients with morbid obesity, allows to reduce doses and the number of taken medications, to achieve not only long-term weight loss, but also to reduce the risk of serious CV events. This category of patients requires careful further dynamic monitoring by a multidisciplinary team of specialists.

Smoking Cessation Pharmacotherapies Are Not Hazardous to Heart

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessSmoking Cessation Pharmacotherapies Are Not Hazardous to HeartNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:17 May 2018https://doi.org/10.1176/appi.pn.2018.5b7AbstractVarenicline, bupropion, and the nicotine patch pose no more risks of heart attacks, strokes, or other major cardiovascular complications than placebo, even among smokers with psychiatric illness.The single biggest step smokers can take to reduce their risks of serious health risks and premature death is to quit. Most guidelines agree that the best approach to quitting is counseling coupled with pharmacotherapy such as varenicline, bupropion, or nicotine replacement. Despite the proven efficacy of smoking cessation medications, however, some clinicians remain hesitant to prescribe them due to concerns over possible side effects of the medications, including cardiovascular safety.iStock/MiljaPhotoA study published April 9 in JAMA Internal Medicine concluded that relative to placebo, smoking cessation medications pose no risk of serious cardiovascular events in most smokers, including those who have a psychiatric disorder.These findings are the latest to come from the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES)—a large clinical trial that enrolled over 8,000 smokers from 140 clinical centers across the world. The trial was initially designed to assess the potential risk of psychiatric side effects in smokers taking varenicline or bupropion (and as reported in 2016, these medications posed no increased neuropsychiatric risks). The study was later extended so the investigators could monitor long-term cardiovascular risks as well.As lead EAGLES investigator Neal Benowitz, M.D., a professor of medicine at the University of California, San Francisco, explained, the cardiovascular concerns over varenicline and bupropion stem from their mechanisms of action. Varenicline binds to nicotine receptors that stimulate blood flow; bupropion is an amphetamine-like compound that can increase blood pressure and heart rate.No formal studies had identified any cardiovascular problems with these cessation medications, but the anecdotal evidence was enough that drug regulatory agencies in the United States and Europe requested that the manufacturers of varenicline (Pfizer) and bupropion (GlaxoSmithKline) conduct a large study that hopefully would provide some definitive answers.The 8,058 EAGLES participants (including 4,116 with a psychiatric disorder) were randomly assigned to receive either varenicline (1 mg twice daily), bupropion (150 mg twice daily), a nicotine patch (an active control group), or placebo pills (passive control) for 12 weeks. The participants were then followed for an additional 40 weeks. About 4,600 participants remained enrolled in the study at the end of the 52 weeks; of these, 26 participants experienced a major cardiovascular event (defined as a heart-related death, nonfatal heart attack, or nonfatal stroke), and 21 others had some cardiovascular complication such as peripheral cardiovascular disease or the need for bypass surgery. There were no differences in the frequency of a cardiovascular event among any of the four treatment groups, nor was there any indication that adverse outcomes were more frequent in participants with a psychiatric disorder.Benowitz acknowledged that since the total number of cardiovascular events was so small, a very slight cardiovascular risk in one of the treatments might go unnoticed. Even if that were the case, though, that risk would be far outweighed by all the health benefits of smoking cessation, he said. “We hope that this study will reassure physicians that if a smoker comes into their clinic looking to quit, medication-assisted therapy is still the recommended approach,” he said. One caveat of the study Benowitz noted is that none of the participants had any unstable cardiovascular or psychiatric problems, such as uncontrolled blood pressure, a recent heart attack, or an active substance use disorder (other than smoking). These populations would require some special considerations. Bupropion, for example, should be avoided in people with a history or risk of seizures, eating disorders, or unstable blood pressure, while varenicline is cleared by the kidneys and should not be used in people with kidney disease.As noted above, EAGLES was funded by Pfizer and GlaxoSmithKline, at the behest of the Food and Drug Administration and European Medicines Agency. ■“Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial” can be accessed here. ISSUES NewArchived

Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers

Quitting smoking is enhanced by the use of pharmacotherapies, but concerns have been raised regarding the cardiovascular safety of such medications. To compare the relative cardiovascular safety risk of smoking cessation treatments. A double-blind, randomized, triple-dummy, placebo- and active-controlled trial (Evaluating Adverse Events in a Global Smoking Cessation Study [EAGLES]) and its nontreatment extension trial was conducted at 140 multinational centers. Smokers, with or without established psychiatric diagnoses, who received at least 1 dose of study medication (n = 8058), as well as a subset of those who completed 12 weeks of treatment plus 12 weeks of follow up and agreed to be followed up for an additional 28 weeks (n = 4595), were included. Varenicline, 1 mg twice daily; bupropion hydrochloride, 150 mg twice daily; and nicotine replacement therapy, 21-mg/d patch with tapering. The primary end point was the time to development of a major adverse cardiovascular event (MACE: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) during treatment; secondary end points were the occurrence of MACE and other pertinent cardiovascular events (MACE+: MACE or new-onset or worsening peripheral vascular disease requiring intervention, coronary revascularization, or hospitalization for unstable angina). Of the 8058 participants, 3553 (44.1%) were male (mean [SD] age, 46.5 [12.3] years). The incidence of cardiovascular events during treatment and follow-up was low (<0.5% for MACE; <0.8% for MACE+) and did not differ significantly by treatment. No significant treatment differences were observed in time to cardiovascular events, blood pressure, or heart rate. There was no significant difference in time to onset of MACE for either varenicline or bupropion treatment vs placebo (varenicline: hazard ratio, 0.29; 95% CI, 0.05-1.68 and bupropion: hazard ratio, 0.50; 95% CI, 0.10-2.50). No evidence that the use of smoking cessation pharmacotherapies increased the risk of serious cardiovascular adverse events during or after treatment was observed. The findings of EAGLES and its extension trial provide further evidence that smoking cessation medications do not increase the risk of serious cardiovascular events in the general population of smokers. clinicaltrials.gov Identifier: NCT01574703.