Posttraumatic stress disorder (PTSD) is characterized by a persistent maladaptive reaction after exposure to severe psychological trauma. Traumatic events that may precipitate PTSD include violent personal assaults, natural and human-made disasters, and exposure to military combat or warfare. There is a growing body of evidence for associations of PTSD with major risk factors for cardiovascular disease (CVD), such as hypertension and diabetes, as well as with major CVD outcomes, such as myocardial infarction and heart failure. However, it is unclear whether these associations are causal or confounded. Furthermore, the biological and behavioral mechanisms underlying these associations are poorly understood. Here, the available evidence on the association of PTSD with CVD from population, basic, and genomic research as well as from clinical and translational research are reviewed, seeking to identify major research gaps, barriers, and opportunities in knowledge acquisition and technology as well as research tools to support and accelerate critical research for near-term and longer-term translational research directions. Large-scale, well-designed prospective studies, capturing diverse and high-risk populations, are warranted that include uniform phenotyping of PTSD as well as broad assessment of biological and behavioral risk factors and CVD outcomes. Available evidence from functional brain imaging studies demonstrates that PTSD pathophysiology includes changes in specific anatomical brain regions and circuits, and studies of immune system function in individuals with PTSD suggest its association with enhanced immune inflammatory activity. However, establishment of animal models and human tissue biobanks is also warranted to elucidate the potential causal connection of PTSD-induced brain changes and/or inflammation with CVD pathophysiology. Emerging large-scale genome-wide association studies of PTSD will provide an opportunity to conduct mendelian randomization studies that test hypotheses regarding the presence, magnitude, and direction of causal associations between PTSD and CVD outcomes. By identifying research gaps in epidemiology and genomics, animal, and human translational research, opportunities to better justify and design future interventional trials are highlighted that may test whether treatment of PTSD or underlying neurobiological or immune dysregulation may improve or prevent CVD risk or outcomes.
Importance Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype.
Objective To evaluate the associations between hypoglycemia and CV outcomes.
Design, Setting, and Participants This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor. Participants were adults with T2D at high CV risk with or without high kidney risk. By design, participants in the CARMELINA trial had longer duration of T2D and had a higher CV risk than participants in the CAROLINA trial. Data analyses were conducted between June 2021 and June 2023.
Intervention Linagliptin or placebo in the CARMELINA trial, and linagliptin or glimepiride in the CAROLINA trial.
Main Outcomes and Measures The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3-point major adverse CV events [3P-MACE]). For the present analyses, hospitalization for heart failure (HF) was added. Hypoglycemia was defined as plasma glucose less than 54 mg/dL or severe hypoglycemia (episodes requiring the assistance of another person). Associations between the first hypoglycemic episode and subsequent CV events and between nonfatal CV events (MI, stroke, hospitalization for HF) and subsequent hypoglycemic episodes were assessed using multivariable Cox proportional hazards regression models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode.
Results In the CARMELINA trial (6979 patients; 4390 males [62.9%]; mean [SD] age, 65.9 [9.1] years), there was an association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (hazard ratio [HR], 1.23; 95% CI, 1.04-1.46) as well as between nonfatal CV events and subsequent hypoglycemia (HR, 1.39; 95% CI, 1.06-1.83). In the CAROLINA trial (6033 patients; 3619 males (60.0%); mean [SD] age, 64.0 [9.5] years), there was no association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (HR, 1.00; 95% CI, 0.76-1.32) and between nonfatal CV events and subsequent hypoglycemia (HR, 1.44; 95% CI, 0.96-2.16). In analyses of CV events occurring within 60 days after hypoglycemia, there was either no association or too few events to analyze.
Conclusions and Relevance This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events. The findings from the CARMELINA trial suggest that both hypoglycemia and CV events more likely identify patients at high risk for both.
Discussion
Results of these analyses of the CARMELINA and CAROLINA trials provide insights into the associations between hypoglycemia and CV or mortality outcomes in individuals with T2D, after adjustments for clinically relevant covariates. In patients with advanced T2D and established CV and/or kidney disease in the CARMELINA trial, hypoglycemia was associated with a 23% higher adjusted risk for subsequent 3P-MACE plus hospitalization for HF (adjusted HR, 1.23), while the reverse association was also observed where a nonfatal CV event was associated with a 39% higher adjusted risk of subsequent hypoglycemia (adjusted HR, 1.39). In patients with relatively early T2D and elevated CV risk in the CAROLINA trial, hypoglycemia was not associated with higher risk for subsequent 3P-MACE plus hospitalization for HF, and similarly, nonfatal CV events were not associated with a higher risk for subsequent hypoglycemia. In both trials, either there was no association between hypoglycemia and risk of subsequent 3P-MACE plus hospitalization for HF within 60 days of the hypoglycemic episodes or there were too few patients with events for meaningful assessment. In the CAROLINA trial, hypoglycemia was associated with higher risk for subsequent non-CV mortality but not for CV mortality.
These observations challenge, to some degree, the widely held viewpoint that hypoglycemia has a direct, causal association with CV events and mortality.1 First, within the 60 days after each hypoglycemia event, no evident risk increase for CV events was detected in either trial, as depicted in eFigures 1 to 16 in Supplement 1. Second, in the CAROLINA trial, there was an association between hypoglycemia and adjusted risk for non-CV death and consequently all-cause mortality, but not for CV death or any other key CV outcome. Third, while the CAROLINA trial demonstrated numerically fewer hypoglycemic events with linagliptin vs glimepiride, it did not demonstrate favorable association with any CV outcome. Thus, we speculated that both hypoglycemia and CV events occur in patients at highest risk for subsequent events, but most likely neither event causes the other. This hypothesis is not intended to undermine the importance of avoiding hypoglycemia with its myriad adverse consequences, including on patients’ quality of life.
To consider the causality of observed associations, we systematically applied the Bradford Hill criteria for causation, a series of 9 principles, in assessing the probability of causality.17 A key criterion is temporality; that is, the exposure precedes the event of interest. We analyzed the association between hypoglycemia and CV outcomes bidirectionally specifically to indirectly assess temporality; that is, if the association is bidirectional, it much more likely represents common vulnerability for each outcome rather than one causing the other. In the present study, the bidirectional associations of similar magnitude observed in the CARMELINA trial suggest that these 2 events (hypoglycemia and CV events) were associated in a temporally independent fashion. This association was complemented by the observed lack of increased risk for CV events within the 60-day risk interval after a hypoglycemia episode, as presented in eFigures 1 to 8 in Supplement 1. While such results did not exclude a causal association, taken together, they did suggest a low likelihood for causality.
Another key Bradford Hill principle is plausibility, defined as the presence of a biologically plausible mechanism that can link cause and effect. While much has been written about plausible ways that hypoglycemia might affect CV risk,1,5,18 in the present analyses, there was no apparent, biologically plausible mechanism that can explain how, for instance, an episode of hypoglycemia can increase the risk for MI a median of 6 to 23 months later. It is the absence of plausible causality that contributes to our interpretation of the observed higher risk for hypoglycemia events after nonfatal CV events in the CARMELINA trial as supporting an association most likely attributable to common vulnerability for both outcomes rather than one causing the other.
These observations add to prior results that challenged a causal association between hypoglycemia and CV risk. For example, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which randomized participants with T2D to standard vs more intensive glucose control and was terminated early due to excess mortality in the intensive strategy arm, hypoglycemia was associated with higher CV risk, yet no temporal association was observed.19 In the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial and in the Veterans Affairs Diabetes Trial (VADT), which randomized participants to treatment strategies similar to the ACCORD trial, no association between hypoglycemia and CV outcomes was observed.20,21 In the Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE),9 there was no association between hypoglycemia and subsequent risk for 3P-MACE, yet there was a significantly higher adjusted risk of all-cause mortality in those with hypoglycemia without temporal association, with a higher risk evident for up to 1 year after the hypoglycemic episode. Similar to observations in the present analyses, in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS), another DPP-4 inhibitor, severe hypoglycemia was associated with a higher crude risk of subsequent CV events, while CV events were associated with a higher crude risk of subsequent hypoglycemia, with only the latter association remaining after adjusting for relevant clinical characteristics.8 Additionally, bidirectional associations between severe hypoglycemia and CV events were found in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) of the GLP-1 receptor agonist, exenatide.22
The CARMELINA and CAROLINA trials were primarily analyzed separately, as opposed to pooling the data for analyses given the extreme heterogeneity of risks and outcomes between them (eTables 3-5 in Supplement 1). First, the trials had different comparators (placebo and sulfonylurea, respectively). Second, the trials had different durations (median [IQR] follow-up, 2.2 [1.6-3.0] years vs 6.3 [5.9-6.6] years, respectively). Third, the trials had different patient mixes. The CARMELINA trial enrolled patients at high CV risk enriched for chronic kidney disease; with a median (IQR) T2D duration of 13.6 (7.4-20.3) years; and who were intentionally recruited for being at or having high risk of kidney disease, which further amplified the risk for both CV events and hypoglycemia. In contrast, participants in the CAROLINA trial had lower CV risk, had a median (IQR) T2D duration of 6.3 (3.0-11.0) years, and included fewer patients with or at risk for kidney disease. Therefore, the results from the pooled analyses (eTables 1-2 in Supplement 1) should be interpreted cautiously due to the extreme differences between the trials that challenge the validity of such pooling of the data.
Strengths and Limitations
The strengths of this study include the use of large databases (including approximately 13 000 individuals) from trials that systematically captured hypoglycemic episodes as well as CV and mortality outcomes, with the CV outcomes centrally adjudicated. The study limitations are that hypoglycemia or CV events cannot be randomized, restricting the analyses to observational associations and making any causal inference challenging, and that all analyses presented were defined post hoc. Although statistical modeling adjusted for numerous covariates known to affect CV and mortality risk, some unknown degree of residual confounding inevitably persisted. Furthermore, given that most patients enrolled in each trial were of White or Asian race, the generalizability of the findings to other races is uncertain.
Conclusions
This secondary analysis found bidirectional adjusted associations between hypoglycemia and CV events in the CARMELINA trial, but no association in either direction in the CAROLINA trial. In both trials, there was no evident temporal association between hypoglycemic episodes and CV events. These findings support the theory that the observed associations between hypoglycemia and adverse CV events and mortality that have been iteratively reported most likely represent reverse confounding. The associations identify a phenotype of patients with T2D most susceptible to both hypoglycemia and CV events or mortality, in which case we speculated that hypoglycemia is a risk marker rather than a risk factor for CV events. Thus, while efforts to minimize hypoglycemia in patients with T2D are warranted due to its unpleasant symptoms, acute risk for serious adverse outcomes of severe hypoglycemia, and the overall burden of hypoglycemia on quality of life, avoiding hypoglycemia may not mitigate CV risk.
Side effects and adverse events related to COVID-19 vaccines continue to be identified.
COVID-19 vaccines may trigger Takotsubo cardiomyopathy. (Freepik)
Various vaccines have been rapidly developed and administered in response to the COVID-19 pandemic. However, accompanying the widespread vaccination efforts, there has been a notable increase in the occurrence of side effects and adverse events related to COVID-19 vaccines. Research has unveiled a potential association between COVID-19 vaccines and Takotsubo cardiomyopathy, with two fatalities among 16 patients.
The clinical presentation of Takotsubo cardiomyopathy resembles that of acute myocardial infarction, with common symptoms including acute chest pain and breathlessness. Its hallmark is impaired left ventricular function, typically occurring after intense emotional or physical stressors such as the death of a loved one, traumatic events, or severe illness. This condition, first identified by Japanese physician Dr. Hikaru Sato in 1990, is named “Takotsubo” due to the balloon-like bulging of the left ventricle, resembling the octopus-catching pot used in Japan.
Outside of Japan, Takotsubo cardiomyopathy is also referred to as stress cardiomyopathy, apical ballooning syndrome, or broken heart syndrome.
A Case Study
In August, a case report was published in the journal Cureus detailing the experience of a 59-year-old woman who developed Takotsubo cardiomyopathy after receiving a booster dose of the COVID-19 vaccine. The patient experienced persistent dyspnea for six hours, prompting her visit to the emergency department. According to the patient’s account, she had been experiencing intermittent chest pain for the past two days, described as a stabbing sensation that progressively intensified with each episode but did not radiate to other areas. Exertion worsened the pain, and there was no relief method. The patient had received the Moderna vaccine booster dose three days prior.
The patient did not have a fever and remained conscious, with a blood oxygen saturation of 89 percent and blood pressure at 150/90 mmHg. Crackling and rattling sounds known as crepitations were detected in her lungs. A COVID-19 polymerase chain reaction test yielded a negative result. The emergency electrocardiogram showed ST-segment elevation, a chest X-ray revealed pulmonary edema and an ultrasound indicated reduced left ventricular systolic function, with an estimated ejection fraction of 30 percent. Additionally, there was moderate hypokinesia (abnormally diminished motor activity) in the apex and anterior wall of the heart.
The patient continued to experience tachycardia and blood pressure fluctuations, leading to hemodynamic instability due to fluid overload and ultimately resulting in cardiac shock. The medical team administered intravenous injections of norepinephrine and dobutamine for treatment. As no other etiologies were identified, she was diagnosed with Takotsubo cardiomyopathy.
The patient showed improvement and was discharged on the sixth day but continued to experience persistent tachycardia, requiring treatment with metoprolol, a medication for the treatment of high blood pressure.
Before receiving the vaccine, the patient had a history of hyperlipidemia, hypothyroidism, and celiac disease. Additionally, she had smoked for five years but quit 15 years ago, and she had no history of alcohol consumption or drug abuse.
The researchers stated that the pathophysiology of COVID-19 vaccine-induced Takotsubo cardiomyopathy is not yet clear, but that “several theories have been proposed.” The immune response triggered by COVID-19 vaccines may, for some individuals, “result in an exaggerated inflammatory cascade, leading to endothelial dysfunction, microvascular dysfunction, and myocardial injury.” Vaccination may also stimulate the release of pro-inflammatory factors such as interleukin-6. Additionally, the stress response induced by COVID-19 vaccination could potentially “dysregulate the autonomic nervous system, contributing to the development of cardiac dysfunction.”
Takotsubo Cardiomyopathy Poses a Life-Threatening Risk
The association between COVID-19 vaccines and Takotsubo cardiomyopathy is not widely known, with only a few reported cases. On Dec. 11, a peer-reviewed study published in the journal Cureus consolidated and analyzed the evidence concerning COVID-19 vaccine-induced Takotsubo cardiomyopathy.
The researchers conducted a literature search and included 15 case reports involving a total of 16 patients. Among them, 14 individuals received mRNA vaccines (Pfizer, Moderna), while two received viral vector vaccines (AstraZeneca). Seven patients developed Takotsubo cardiomyopathy after the first dose and seven after the second dose.
All patients exhibited elevated cardiac troponin levels, abnormal electrocardiogram findings, and reduced left ventricular ejection fraction on echocardiograms. The most predominant symptom among patients was chest pain, followed by dyspnea and nausea. Eventually, 14 patients recovered and were discharged, while two of the patients died.
The researchers noted that 87.5 percent of patients recovered and were discharged, indicating that Takotsubo cardiomyopathy occurring after vaccination is mostly “transient and reversible.” However, the death of 2 of the patients highlights the “potentially life-threatening nature of this vaccine-related adverse event.”
The paper’s authors urge clinicians to consider the possibility of Takotsubo cardiomyopathy, especially among recipients of mRNA vaccines when presented with patients experiencing chest pain or dyspnea symptoms after vaccination.
The study also mentioned that vaccines developed for COVID-19 have various side effects, including pain and swelling at the injection site, fever, headache, myalgia (muscle pain), fatigue, and nausea.
Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. Atrial fibrillation detected after stroke is associated with a lower prevalence of risk factors, cardiovascular comorbidities, and atrial cardiomyopathy than atrial fibrillation known before stroke occurrence. These differences might explain why it is associated with a lower risk of recurrence of ischaemic stroke than known atrial fibrillation. Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.
Among patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease, angioplasty has been associated with frequent reintervention and adverse limb outcomes from restenosis. The effect of the use of drug-eluting resorbable scaffolds on these outcomes remains unknown.
METHODS
In this multicenter, randomized, controlled trial, 261 patients with CLTI and infrapopliteal artery disease were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting resorbable scaffold or angioplasty. The primary efficacy end point was freedom from the following events at 1 year: amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. The primary safety end point was freedom from major adverse limb events at 6 months and from perioperative death.
RESULTS
The primary efficacy end point was observed (i.e., no events occurred) in 135 of 173 patients in the scaffold group and 48 of 88 patients in the angioplasty group (Kaplan–Meier estimate, 74% vs. 44%; absolute difference, 30 percentage points; 95% confidence interval [CI], 15 to 46; one-sided P<0.001 for superiority). The primary safety end point was observed in 165 of 170 patients in the scaffold group and 90 of 90 patients in the angioplasty group (absolute difference, −3 percentage points; 95% CI, −6 to 0; one-sided P<0.001 for noninferiority). Serious adverse events related to the index procedure occurred in 2% of the patients in the scaffold group and 3% of those in the angioplasty group.
CONCLUSIONS
Among patients with CLTI due to infrapopliteal artery disease, the use of an everolimus-eluting resorbable scaffold was superior to angioplasty with respect to the primary efficacy end point.
Greater adherence to a healthful plant-based diet was linked to lower risks for CVD, cancer and mortality.
In contrast, adherence to an unhealthful plant-based diet had inverse associations.
Middle-aged adults with greater adherence to a healthful plant-based diet had significantly lower risks for CVD, cancer and mortality than those who had lower adherence, according to study results published in JAMA Network Open.
Alysha S. Thompson, MSci, a PhD researcher at Queen’s University Belfast, and colleagues wrote that, for both health and environmental reasons, plant-based diets have recently gained popularity. However, strict plant-based diets may be associated with health consequences like calcium deficiencies, they noted, and there is no comprehensive evaluation of diet quality in relation to risk for mortality and major chronic diseases.
Data derived from: Thompson AS, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.471.
“Previous population-based studies have shown that plant-based diets per se may not be associated with improved health but that their composition is crucial with respect to a reduction in chronic disease risk,” they wrote. “Only a healthful plant-based diet, characterized by low consumption of both animal foods and processed foods of plant origin (eg, refined grains, sugary drinks, snacks and desserts) has been associated with a lower risk of type 2 diabetes, CVD and total mortality.”
Thompson and colleagues conducted a prospective cohort study to evaluate the potential health benefits and risks associated with plant-based diets. They specifically wanted to see if adhering to a healthful plant-based diet (hPDI) vs. unhealthful plant-based diet (uPDI) was linked to mortality and major chronic diseases like cancer and CVD.
The researchers used data from 126,394 U.K. Biobank participants — 55.9% of whom were women and 91.3% of whom were white — and measured their adherence to plant-based diets with 24-hour dietary assessments.
Thompson and colleagues found that an hPDI might be beneficial for health, regardless of genetic predisposition and established chronic disease risk factors.
Greater adherence to the hPDI was linked to lower risks for:
cancer (HR = 0.93; 95% CI, 0.88-0.99);
CVD (HR = 0.92; 95% CI, 0.86-0.99);
ischemic stroke (HR = 0.84; 95% CI, 0.71-0.99);
myocardial infarction (HR = 0.86; 95% CI, 0.78-0.95); and
total mortality (HR = 0.84; 95% CI, 0.78-0.91).
Higher scores for the uPDI, however, were linked to higher risks for CVD, cancer and mortality.
The researchers noted that the associations did not show heterogeneity across strata of BMI, socioeconomic status, sex, smoking status or with polygenic risk scores.
“Importantly, we observed that inverse associations between the hPDI and CVD end points (total CVD, myocardial infarction, and stroke) were independent of genetic disease risk,” they wrote. “This finding is of particular public health relevance, as it suggests individual benefits of healthful PBDs irrespective of genetic predisposition for CVD.
At the same time, they added, “absolute risk reduction due to a healthful PBD may be greater among individuals with a stronger genetic predisposition for CVD, given their higher lifetime risk of CVD.”
Thompson and colleagues identified mechanisms that may underlie the associations between hPDI and lower risks for disease and mortality. Higher intake of unprocessed plant foods could reduce the risk for low-grade inflammation, impaired insulin sensitivity and obesity, they wrote, and these mechanisms could explain lower mortality risks because of both cancer and CVD.
“Similarly, plant constituents such as fiber may beneficially affect the composition and function of the large intestinal microbiome,” Thompson and colleagues wrote. “The fact that associations between hPDI and CVD revealed lower risks, especially of myocardial infarction and ischemic stroke compared with that for cancer in our study, suggests that additional CVD-specific mechanisms (eg, lower blood pressure or low-density lipoprotein cholesterol due to PBD6) further explain our findings.”
The Skeptical Cardiologist discusses the book’s lessons for patients
Earlier this year, the skeptical cardiologist wrote about the cardiovascular misadventures of the main character in Philip Roth’s novel Everyman.
I had initially intended this as a single blog post but very quickly realized there were more important points about cardiovascular disease management than could be contained in a 1,000-word post.
After Roth’s Everyman is rushed to the hospital to undergo an invasive coronary angiogram he likely didn’t need, he is then rushed off to undergo coronary bypass surgery he likely didn’t need. In 1998, at the age of 65, he undergoes renal artery stenting for high blood pressure, a procedure now considered of dubious value.
The First Unnecessary Carotid Surgery
One year after his renal artery stent, he had a left carotid endarterectomy (CEA) which he describes as “surgery for another major obstruction, this one in his left carotid artery, one of the two main arteries that stretch from the aorta to the base of the skull and supply blood to the brain, and that if left obstructed could cause a disabling stroke or even sudden death.”
He goes on to describe the procedure in some detail: “the incision was made in the neck, then the artery feeding the brain was clamped shut to stop the blood flowing through it. Then it was slit open and the plaque that was causing the blockage scraped out and removed.”
He is told “from a medical point of view, it was nothing extraordinary, or so he was led to believe by the agreeable surgeon, who assured him that a carotid endarterectomy was a common vascular surgical procedure and he would be back at his easel within a day or two.”
A lot has changed since Everyman had his CEA in 1999. My practice in the 90s was to strongly consider referring my patients with asymptomatic carotid obstructions >70% for CEA, but as medical treatments for atherosclerosis advanced, since 2010 studies began showing minimal benefit in reducing stroke for CEA.
In 2022, I am rarely sent a patient who has not had a stroke or transient ischemic attack for CEA.
A recent British paper noted, “the role of CEA in asymptomatic patients has been a source of considerable controversy, with some countries performing large numbers of CEA procedures in asymptomatic patients (e.g., the United States and Italy), while no CEAs are performed in asymptomatic patients in Denmark. Moreover, the latest Stroke Guidelines now advise against performing CEA in asymptomatic patients in Australia.”
This paper noted a 63% reduction in CEA performed in England on asymptomatic patients between 2011 and 2017.
The Choosing Wisely Project aims to identify low-value procedures and CEA in asymptomatic individuals with carotid stenosis >50% was in the top 5 for Australian/New Zealand Choosing Wisely Neurology Procedures. The recommendation: “Don’t routinely recommend surgery for a narrowed carotid artery (>50% stenosis) that has not caused symptoms.”
Everyman is asymptomatic. He has had no symptoms from the obstruction in his carotid artery. There is no mention of stroke symptoms in the book and it must be assumed that Everyman, like thousands of Americans, is getting an unwarranted routine annual carotid ultrasound, the noninvasive test which allows the identification of asymptomatic plaque build-up.
It is important to note that many guidelines mention that CEA only makes sense in the asymptomatic patient if the preoperative risks of stroke, death, and MI are less than 3%.
For a patient or referring physician to make an informed decision, therefore, they would need to know the surgical outcomes for the surgeon doing the procedure. In the real world, almost no one has this data.
The reason surgery for carotid blockages seems less helpful over the last 2 decades is similar to the reason that coronary artery stenting and bypass surgery is less helpful: improved medical control of atherosclerosis with lipid-lowering therapy, blood pressure control, and lifestyle changes including cigarette smoking cessation.
Unfortunately, we have no idea what medical therapy Everyman was getting. Given that statins were in widespread use by the mid-90s and given his history of coronary bypass surgery, he should have been on the most potent one available.
More Unnecessary Coronary Procedures
The year after his carotid artery surgery, Everyman “had an angiogram in which the doctor discovered that he’d had a silent heart attack on the posterior wall because of an obstructed graft.” Given that Everyman mentions no symptoms related to this and given the previous inappropriately aggressive test and procedure ordering of his doctors, I can only presume that this repeat invasive angiogram was done because of an abnormal stress test.
Cardiology guidelines now recommend against the routine performance of stress tests following stenting or bypass procedures which I have discussed in detail here. This practice was the norm 20 years ago and persists to this day. A major concern with these routine tests is downstream testing like invasive angiograms which follow false positive results.
When inappropriate invasive angiograms are performed, coronary blockages are often found and stents are frequently placed that don’t reduce the risk of heart attack or help symptoms. Sure enough, Everyman has a stent implanted in his left anterior descending coronary artery, one which was not involved with the posterior wall of the heart at all.
The next year he gets another coronary stent, this time in a bypass graft. A year later he gets three more coronary stents. Again, no symptoms mentioned, no benefit obtained, other than to the pocketbook of the stenting doctor.
A Final Carotid Ultrasound Followed by Lethal Carotid Surgery
As we reach page 156 of this 182-page novella, Roth writes “When he next went to the hospital for the annual checkup on his carotids, the sonogram revealed that the second carotid was now seriously obstructed and required surgery.”
As suspected, one of Everyman’s doctors has been ordering a routine annual carotid ultrasound. Often, significant asymptomatic carotid stenosis is identified in screening studies prior to coronary artery bypass grafting (CABG). There are no good randomized trials to guide management of such cases. Some carotid stenoses are operated on simultaneously with the CABG, some sequentially and in lesser degrees, like Everyman’s are managed medically.
Outside the U.S., international organizations are pretty unanimous in condemning the routine screening of asymptomatic patients with carotid ultrasound.
So, yes, Everyman was caught in the cycle of repetitive low-value annual carotid screening and it finally caught up with him.
Everyman requests general anesthesia “so as to make the surgery easier to bear than it had been under local anesthesia with the first operation.”
Roth writes “He went under feeling far from felled, anything but doomed, eager yet again to be fulfilled, but nonetheless, he never woke up. Cardiac arrest. He was no more, free from being, entering into nowhere without even knowing it. Just as he’d feared from the start.”
The fate of Everyman is not unique. How can today’s patients avoid or minimize this carousel of cardiovascular testing, invasive procedures, and potentially lethal operations?
Lesson For Patients
Decline low-value screenings like annual routine ECGs or screening carotid ultrasounds
Strongly consider obtaining a second opinion when an invasive vascular procedure or major operation is recommended to you, especially if you are free of symptoms
Ask your doctor why he is ordering imaging tests; how will the results change his treatment?
Remember that just because it seems logical to mechanically remove localized blockages in the arteries to our head or brain, the process of atherosclerosis which caused those blockages is diffuse and the optimal approach is most often a systemic medical one
Anthony C. Pearson, MD, is a noninvasive cardiologist and professor of medicine at St. Louis University School of Medicine.
Building civility, respect and inclusion into the cardiology workplace is essential, especially in an era where burnout is so high, a speaker said at the National Lipid Association Scientific Sessions.
Cardiology Today Editorial Board Member Laxmi Mehta, MD, FACC, FAHA, FNLA, professor of medicine, vice chair of wellness in the department of internal medicine and section director of preventive cardiology and women’s cardiovascular health at The Ohio State University, gave a presentation on how to define and identify physician burnout, how to relate contributors to burnout with discrimination and how to respond to microaggressions.
Mehta is professor of medicine, vice chair of wellness in the department of internal medicine and section director of preventive cardiology and women’s cardiovascular health at The Ohio State University.
Dealing with burnout
The signs of burnout include physical and emotional exhaustion manifested in chronic fatigue, insomnia, impaired concentration, reduced attention span, increased illness, loss of appetite, anxiety and depression; cynicism and detachment manifested in loss of enjoyment, pessimism, isolation and detachment; and ineffectiveness manifested in apathy, hopelessness, irritability, lack of productivity and poor performance, Mehta said.
In a 2019 American College of Cardiology survey, the prevalence of burnout among cardiologists was 26.8%, with 49.5% identifying themselves as stressed and only 23.7% saying they enjoyed work, she said.
Compared with those without burnout, those with it were less likely to be married, to feel satisfied with family life, to say they feel treated fairly at their job or valued in their profession and to say they feel their contributions matter, and more likely to say their family responsibilities hinder their ability to work, to be less satisfied with achieving professional goals, to be less satisfied with their financial compensation, to report experiencing discrimination and to recommend cardiology as a career, she said.
In a 2021 paper published in the Journal of the American College of Cardiology, 29% of cardiologists reported experiencing emotional harassment, 4% reported experiencing sexual harassment and 30% reported experiencing discrimination, while 79% reported adverse effects on professional activities as a result of these issues, Mehta said.
Addressing uncivil workplace behaviors
The four main components of uncivil workplace behaviors are bias, discrimination, bullying and harassment (BDBH), Mehta said, noting that components of programs that have successfully reduced them include subject-matter expertise; structures, resources and funds dedicated to addressing those issues; a strategic plan with comprehensive assessments; and organizational and leadership commitment to reducing BDBH.
“Individuals should ensure freedom from BDBH in their own personal behaviors and actions and assist others by practicing allyship and upstander behaviors, and by supporting institutional efforts,” Mehta said. “Individuals should work toward establishing a culture and climate of respect, including elimination of harassment and bullying. The workforce must have, and be able to use, the necessary skills and tools to achieve those goals.”
Moreover, she said, organizations should incorporate assessments of respect and civility into performance reviews, rewarding those who have worked toward reducing BDBH, should have robust training programs about BDBH and should have mechanisms for confidential reporting and investigation of incidents without retribution.
“The framework for a just culture matches the level of response to the degree of the behavioral problem,” she said.
Handling microaggressions
Microaggressions are common in the cardiology workplace, are often caused by implicit bias and “may have the same negative effect on individuals as overt racism and sexism,” Mehta said during the presentation.
“Microaggressions are more prevalent in environments where BDBH is also prevalent and where workforce diversity and inclusivity are low,” she said. “Long-term strategies for reducing microaggressions must include increasing organizational diversity, equity, inclusion and belonging.”
She said the best way to respond to microaggressions is to use the ACTION framework, which stands for Ask clarifying questions, Curiosity instead of judgment, Tell the facts you observed, Intention vs. impact, Own your thoughts/share your reactions and Next steps.
“For professional fulfillment, assessment is key,” she said. “Burnout is the metric and well-being is the goal. Cardiovascular organizations and individuals are responsible for ensuring a safe, supportive and respectful workplace environment.”
What might be the biggest clinical issues in cardiology in 2018? MedPage Todayasked a panel of leading cardiologists for their predictions.
“I think that the response to ORBITA will continue to resonate,” said Pamela Douglas, MD, director of the Multimodality Imaging Program at Duke Clinical Research Institute in Durham, North Carolina.
“I would say the biggest topic in the biomarker space is the launch of highly sensitive troponin assays in the United States — that’ll be a huge issue,” said James Januzzi, MD, director of the Cardiac Intensive Care Unit at Massachusetts General Hospital in Boston.
Kim Eagle, MD, director of the Frankel Cardiovascular Center at the University of Michigan in Ann Arbor, highlighted advances anticipated in several treatment areas:
Less invasive treatment for mitral valve failure
Expanding use of non-statin agents to lower cholesterol
Refinement of how we use newer anticoagulants
Faster, more effective arrhythmia ablation strategies
Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago, cautioned about the “weakness of our clairvoyance. Who would have ever considered the impact of ORBITA a year ago or the unique cardiac benefits of SGLT2-inhibitors 2 years ago?”
Still, he made the case “that the building momentum to incite meaningful discussions leading to changes in health policy – e.g., hospital readmission reduction program — that are less punitive and without unintended consequences can’t be ignored …
“The data that we and others have generated raise the question that overzealous application of an unproven policy based on a weak risk adjustment model may have indeed lowered readmissions but has done so with observed disproportionate penalties on those hospitals supporting care for the least advantaged and may have also been associated with an increased risk of death.
“These are not trivial issues — issues that are further amplified by the weekend [New York Times] story addressing the misdirected process to improve metrics in the VA health system (Oregon) leading to patients being precluded from hospitalization or being hospitalized under a hospice diagnosis. There must be a call to attention if two major regulatory systems are continuing to deploy policies without safeguards that would prevent unintended harm.
“We insist on nearly incontrovertible evidence to support the use of medical therapies and at least reasonable evidence to support the use of devices. Why do we not hold policy decisions to the same bar?” Yancy argued. “Perhaps 2018 will find the needed conversations initiated, less to impugn regulatory agencies and more to improve our processes, so that we remain true to that which is most central to our core as healthcare providers – ‘primum non nocere.'”
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