October 27th, 2014
Case: When an “Inappropriate” Stress Test Might Be Appropriate
Jean-Pierre Usdin, MD and James Fang, MD
A 58-year-old male gynecologist with well-treated hypertension and no symptoms wants to start exercising and asks his cardiologist to give him a stress test. He is a nonsmoker, has a normal BMI, and does not take aspirin. He has never had a coronary angiogram. The patient’s cardiologist asks him to discontinue his acebutolol, which he takes for the hypertension, so that he can undergo an “unmasked” exercise stress test. The patient discontinues the medication on the morning of the test.
The stress test results are normal, and the patient feels reassured. He recovers for a few minutes, showers, and is sent home with a green light to exercise. Before he even exits the hospital, however, he begins to experience chest heaviness, nausea, and sweating.
He returns to the cardiology department, where he is found to have low blood pressure and a slow heart rate, initially thought to be a delayed vasovagal response to the stress test. However, an ECG shows an ST-segment-elevation MI in the inferior leads. Prompt catheterization reveals a huge thrombus in the right coronary artery.
The patient undergoes immediate, successful primary PCI and stent placement, and he is admitted to the CCU. On day 3, he is discharged in good condition with prescriptions for aspirin, prasugrel, acebutolol, and atorvastatin.
Questions:
- Could the exercise stress test have caused this patient’s MI (by provoking a rupture in a plaque that is presumed to be stable but turns out not to be), or was the MI inevitable — and more likely to be fatal if it had happened outside the hospital?
- Would it have made any difference if the patient had been on aspirin or hadn’t stopped his beta-blocker?
- Would the patient-requested stress test have been considered “inappropriate” in this case, even though it helped to prevent a potentially fatal event? (See the recent CardioExchange discussion on this topic.)
- Should people at high risk for ACS events take aspirin before exercising? What about healthy individuals and athletes (e.g., marathon runners) who are about to engage in intense activity?
Response:
November 3, 2014
1. Could the exercise stress test have caused this patient’s MI (by provoking a rupture in a plaque that is presumed to be stable but turns out not to be), or was the MI inevitable — and more likely to be fatal if it had happened outside the hospital?
MI is a known but rare complication of exercise stress testing (the risk is likely less than 1 in 1000, according to multiple large series). Possible mechanisms include increased shear stress at the point of modest plaques, increased thrombogenic milieu related to the increased adrenergic environment, and previously asymptomatic high-grade lesions leading to supply-and-demand mismatch. But it is at best speculative to suggest that the stress test “caused” the MI. It is also difficult to say the MI was “inevitable,” but no doubt the patient was at risk given his CV risk factor(s). Having an MI in a medical environment can expedite diagnosis and therapy, although paradoxically hospitalized patients often have greater door-to-balloon times because the MI may not be recognized.
2. Would it have made any difference if the patient had been on aspirin or hadn’t stopped his beta-blocker?
Aspirin and beta-blockade may have had some effect, in the context of the pathophysiology of STEMI, but it appears that the patient had underlying CAD. Withholding the beta-blocker to improve the sensitivity of the test helps only to identify flow-limiting lesions and would not improve the accuracy of diagnosing less severe coronary atherosclerosis.
3. Would the patient-requested stress test have been considered “inappropriate” in this case, even though it helped to prevent a potentially fatal event? (See the recent CardioExchange discussion on this topic.)
I do not believe that this stress test was “inappropriate” because this scenario is a guideline-recognized indication — i.e., testing sedentary people before initiating a rigorous exercise program. Interestingly, concomitant imaging does not appear to have been ordered.
4. Should people at high risk for ACS events take aspirin before exercising? What about healthy individuals and athletes (e.g., marathon runners) who are about to engage in intense activity?
I’m not aware of any evidence that aspirin use before exercise in patients at high risk for ACS reduces that risk, but it is an interesting hypothesis. I suspect, however, that it would take a large study to show any benefit, given that event rates would probably be low.
Follow-Up:
November 7, 2014
This acute event happened 2 months ago. This patient, who decided to switch his cardiologist to the one who did the primary PCI, started a 2-week cardiac rehabilitation program at the end of September (3 weeks after the acute MI). He is now doing well on a medication regimen of aspirin 75 mg, prasugrel 10 mg, rosuvastatin 10 mg, ramipril 10 mg, and nebivolol 5 mg.
October 26th, 2014
Genetic Study Suggests Possible Causal Role for LDL in Aortic Valve Disease
Larry Husten, PHD
Although LDL is an important risk factor for aortic valve disease, the precise role it plays has been uncertain. Lipid-lowering therapy in people with established aortic valve disease has not been shown to be beneficial. Now, however, a new genetic study published in JAMA suggests that LDL cholesterol may in fact cause an increase in aortic valve calcium and aortic valve stenosis. This may mean that LDL-lowering therapy could prove beneficial when given earlier in the disease process.
Researchers in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium used Mendelian randomization to assess in nearly 7,000 people the association of a genetic risk score with the presence of aortic valve calcium. They found a strong association between the genetic risk score for LDL and the presence of aortic valve calcium.
The researchers also analyzed data from more than 28,000 participants in the the Malmö Diet and Cancer Study (MDCS). The genetic risk score for LDL was significantly associated with the incidence of aortic stenosis as ascertained from national registries.
“Our findings link a genetically mediated increase in plasma LDL-C with early subclinical valve disease, as measured by aortic valve calcium, and incident clinical aortic stenosis, providing supportive evidence for a causal role of LDL-C in the development of aortic stenosis,” write the authors. The authors speculate that LDL lowering may not be effective in established valve disease “once valve calcification and remodeling are well established…” But, they write, “our results suggest that early lipid lowering, prior to the development of even mild forms of aortic stenosis, may be required to prevent aortic valve disease.”
October 23rd, 2014
The Survival Benefits of Physical Activity: Moderate vs. Vigorous Intensity
Harlan M. Krumholz, MD, SM
CardioExchange’s Harlan M. Krumholz interviews Eric J. Shiroma about his research group’s study of the relative survival benefits of moderate- versus vigorous-intensity physical activity. The study is published in the Journal of the American Heart Association.
Krumholz: Please summarize your findings for our readers.
Shiroma: We found that physical activity is inversely associated with both all-cause mortality and cardiovascular disease mortality in both men and women. This supports the current U.S. federal guidelines recommending at least 150 minutes of moderate-, 75 minutes of vigorous-intensity physical activity, or an equivalent combination. In examining the relative benefits of moderate- compared with vigorous-intensity physical activity, we found that men (but not women) experienced a slight additional all-cause mortality benefit when a greater proportion of their activity was vigorous in intensity. However, for cardiovascular disease mortality, moderate-intensity and vigorous-intensity activity conferred similar benefits in both men and women.
Krumholz: Some studies have suggested that more exercise above a certain level is not better, but in your study, more exercise conferred lower risk. How do you reconcile your findings with those that suggest a plateau?
Shiroma: With respect to the dose-response curve of physical-activity volume (at any intensity above moderate) and mortality, there is a leveling off at the highest volumes. Notably, this leveling off does not mean a lack of reduced risk compared with being sedentary; it just means little additional benefit compared with other high levels. In our study, we observed a similar trend among men but did not see a leveling off among women, possibly because not as many women as men in our study engaged in the highest level of physical-activity volume (>10 hours per week). Therefore, low statistical power (and even some selection bias) may have been factors.
Krumholz: We are limited by observational studies in this field, with their limitations. Are you concerned by confounding in these types of studies?
Shiroma: Residual confounding is always a concern in observational studies, but we were able to control for many of the usual confounders, such as age, diet, smoking status, and alcohol consumption. In addition, when comparing the unadjusted or age-only estimates with the fully adjusted models, we did not observe large differences in the estimates, suggesting that confounding did not account for the observed effect. It is possible, however, that questionnaire use resulted in misclassification of what is moderate- versus vigorous-intensity physical activity. A more objective assessment of intensity may provide further insight into this relationship.
Krumholz: Should we be making recommendations about exercise as strongly and precisely as we recommend drugs that have been tested in randomized controlled trials?
Shiroma: A plethora of data supports the value of physical activity in maintaining good health. Questions remain about the optimum intensity and patterning of physical activity, but consistent evidence shows the overall benefits of increasing the volume of physical activity. However, any medical recommendation should be tailored to the individual patient’s fitness levels and injury risk. Randomized controlled trials may help to define some of the nuances of physical activity as a “prescription,” but that should not detract from the overall message about its value.
Krumholz: What are your recommendations about exercise for longevity?
Shiroma: The guidelines recommend regular physical activity (150 minutes moderate, 75 vigorous, or a combination) to reduce the risk for premature mortality. Our study supports those recommendations, and we conclude specifically that moderate-intensity physical activity, which may be more appropriate and easier to promote in a more sedentary population, confers benefits similar to those of a more vigorous-intensity program.
JOIN THE DISCUSSION
Given the findings from Dr. Shiroma’s study, share your thoughts about the relative benefits of moderate- versus vigorous-intensity exercise.
October 21st, 2014
Study Behind the Green Coffee Bean Diet Craze Retracted
Larry Husten, PHD
The “scientific” paper that helped ignite the green coffee bean diet craze has been retracted. The details of the retraction and the full background of the story were fully reported by Ivan Oransky on Retraction Watch.
The paper, published in Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, purported to report the substantial weight loss findings of a randomized, double-blind, placebo-controlled crossover study of green coffee bean extract. The article has been viewed or downloaded by more than three-quarters of a million people since its publication in January 2012.
Following the paper’s publication, Dr. Oz featured the product on his television show. According to Scott Gavura, writing in the Science-Based Medicine blog, Oz used the terms “magic,” “staggering,” “unprecedented,” “cure,” and “miracle pill” to describe the product, which then became an international bestseller.
The statement of retraction provides few details:
The sponsors of the study cannot assure the validity of the data so we, Joe Vinson and Bryan Burnham [two of the three authors], are retracting the paper.
Vinson and Burnham are a chemist and a psychologist at the University of Scranton in Pennsylvania. But more details about the affair are provided by the Federal Trade Commission (FTC), which last month reached a $3.5 million settlement with Applied Food Sciences, Inc. (AFS), the company that sponsored the study and that markets the extract.
In its press release, the FTC said that “the study was so hopelessly flawed that no reliable conclusions could be drawn from it.” According to the FTC, AFS hired researchers in India to perform the clinical trial. AFS “knew or should have known that this botched study didn’t prove anything. In publicizing the results, it helped fuel the green coffee phenomenon.”
According to the FTC:
…the study’s lead investigator repeatedly altered the weights and other key measurements of the subjects, changed the length of the trial, and misstated which subjects were taking the placebo or GCA [Green Coffee Antioxidant] during the trial. When the lead investigator was unable to get the study published, the FTC says that AFS hired researchers Joe Vinson and Bryan Burnham at the University of Scranton to rewrite it. Despite receiving conflicting data, Vinson, Burnham, and AFS never verified the authenticity of the information used in the study, according to the complaint.
Despite the study’s flaws, AFS used it to falsely claim that GCA caused consumers to lose 17.7 pounds, 10.5 percent of body weight, and 16 percent of body fat with or without diet and exercise, in 22 weeks, the complaint alleges.
Although AFS played no part in featuring its study on The Dr. Oz Show, it took advantage of the publicity afterwards by issuing a press release highlighting the show. The release claimed that study subjects lost weight “without diet or exercise,” even though subjects in the study were instructed to restrict their diet and increase their exercise, the FTC contends.
October 20th, 2014
Are Women Who Live Near Roadways at Greater Risk for Sudden Cardiac Death?
Jaime E Hart, Sc.D and Harlan M. Krumholz, MD, SM
CardioExchange’s Harlan M. Krumholz interviews Jaime E. Hart about her research group’s study of the relation between residential proximity to roadways and sudden cardiac death in women. The study is published in Circulation.
Krumholz: Please describe your main findings for our readers.
Hart: Among 107,130 women in the Nurses’ Health Study, women living within 50 meters of a major roadway had a 38% greater risk for sudden cardiac death (SCD) and a 24% greater risk for fatal coronary heart disease, compared with women living at least 500 meters away. The findings persisted after adjustment for multiple traditional cardiovascular risk factors.
Krumholz: During a period of 26 years, the SCD rate was 0.5%, or 0.02% per year. Does the fact that living near a roadway was associated with almost a 40% increased risk have any practical importance?
Hart: This is an excellent point. For any given individual, the risk for SCD, even with residential exposure to a major roadway, is very low. However, this level of increased risk is important on a population level.
Krumholz: Given that property near roadways may be less expensive, could the risk be related to socioeconomic factors?
Hart: Residual confounding by socioeconomic status is always a concern in studies of roadway proximity. However, women in this cohort tend to be of middle to upper SES, as they all had to be nurses at enrollment. We also adjusted our analyses for a number of individual-level and census-tract–level measures of SES, so there isn’t likely to be substantial residual confounding.
Krumholz: What do you think people should do as a result of this research?
Hart: First, wait for confirmation in other studies. Although the findings are consistent with the literature suggesting that roadway proximity is associated with increased risk for several adverse cardiovascular outcomes, our specific results need to be confirmed in other populations. An important next step is to identify what specific exposures, such as noise or air pollution, may underlie these findings.
JOIN THE DISCUSSION
Share your thoughts on the findings from Dr. Hart’s study.
October 20th, 2014
Selections from Richard Lehman’s Literature Review: October 20th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
Lancet 18 October 2014 Vol 384
The Safety of Addition of Nitrous Oxide to General Anesthesia in At-Risk Patients Having Major Non-Cardiac Surgery (pg. 1446): If you are about to undergo surgery and your anaesthetist wishes to use nitrous oxide, let not your heart be troubled. In a randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery, nitrous oxide did not increase the risk of death or cardiovascular complications. In fact, you might want to try some at sub-anaesthetic doses just for pleasure. The first person to do this was the intrepid young Cornishman Humphry Davy in 1799, when he worked with Dr Beddoes at the Pneumatic Institute in Bath. You may experience “sublime emotion connected with highly vivid ideas,” according to Davy’s electrifying account of his extensive experiments on himself and others, which you can read page by page.
October 20th, 2014
Are We Conducting Too Many Cardiac Stress Tests with Imaging?
Joseph A. Ladapo, MD, PhD
CardioExchange’s Harlan M. Krumholz interviews Joseph A. Ladapo, lead investigator of a study about the use (and overuse) of cardiac stress testing in the United States. The article is published in the Annals of Internal Medicine and has been covered as a news story here on CardioExchange.
Krumholz: Please summarize your main findings .
Ladapo: We found that the use of cardiac stress testing in the U.S. has risen briskly during the past two decades; the use of imaging has grown particularly rapidly. The growth in cardiac stress testing can largely be explained by population and provider characteristics, but the use of imaging cannot. Notably, nearly one third of cardiac stress tests with imaging were probably inappropriate, because they were performed in patients who rarely benefit from imaging. Those tests — about 1 million each year — are associated with roughly half a billion dollars in annual healthcare costs and lead to about 500 people developing cancer in their lifetime because of radiation they received during that cardiac stress test.
Krumholz: How convinced are you that 1 million stress tests were inappropriate during the past two decades?
Ladapo: Using the 2014 ACCF/AHA Multimodality Appropriate Use Criteria, we estimate that probably about 1 million inappropriate stress tests with imaging are performed each year. We used liberal criteria to classify tests as appropriate, which we describe in detail in our supplementary appendix. For example, we considered the test appropriate if a patient had ischemic equivalents, CHD-risk equivalents (e.g., diabetes or peripheral artery disease), more than 2 CHD risk factors (e.g., a male smoker 50 years old), or a history of heart failure. We categorized the remaining tests as rarely appropriate because they were largely performed in low-risk patients. It’s likely that we actually underestimate the number of inappropriate stress tests.
Krumholz: What do you think ought to be done to improve testing?
Ladapo: This is clearly an area where more intensive testing is being used in patients for whom there is marginal value. I think the Choosing Wisely campaign will help reduce rates of inappropriate testing, along with the efforts of the ACCF/AHA. Clinical decision support for physicians would also be beneficial. Training medical residents and fellows about appropriate use of testing is an important step in helping to break the cycle. I think much of what we’re seeing in physician behavior is ecological, related to habit and familiar patterns.
Krumholz: Do you feel confident about your cancer estimate (harm) as a result of this screening?
Ladapo: We based our cancer estimates on excellent research from Dr. Rebecca Smith-Bindman and others at UCSF. Substantial uncertainty certainly exists in the research that has attempted to quantify the health harms from medical radiation, but we did our best to reflect what was supported in the scientific literature.
Krumholz: Is this an example of harm that cardiology has done inadvertently?
Ladapo: This is not just a “cardiology issue.” Primary care physicians order many of these tests. We have some work that shows that, in fact, PCPs are more likely to order an inappropriate cardiac stress test than cardiologists are. But it is definitely a big issue. We have an opportunity to reduce healthcare costs and the incidence of cancer by more appropriately selecting patients who benefit from imaging.
JOIN THE DISCUSSION
In light of Dr. Ladapo’s findings, share your observations about the inappropriate use of cardiac stress tests with imaging in clinical practice.
October 15th, 2014
Another Diet Myth Exploded: Gradual Weight Loss No Better Than Rapid Weight Loss
Larry Husten, PHD
Once again, a popular weight loss myth has been exploded. It has been widely believed that weight loss, which is nearly always difficult to maintain, is even less likely to be sustained if it’s the product of a rapid weight-loss regimen. This belief is even enshrined in current guidelines. Now a study published in The Lancet Diabetes & Endocrinology provides no support for this view. Instead, the study suggests that although long-term weight loss remains elusive regardless of the diet, short-term weight loss is actually greater with rapid weight loss.
Australian researchers randomized 200 obese adults to either a 12-week rapid weight loss diet (with Optifast) or a 36-week gradual diet. Participants who lost at least 12.5% of their weight then participated in the second phase of the study, in which they were placed on a 144-week maintenance diet.
In the first phase of the study, 50% of people on the gradual diet and 81% of people on the rapid diet achieved the 12.5% weight loss goal. Both groups struggled considerably in the second phase: 71.2% in the gradual diet group and 70.5% in the rapid diet group regained most of the weight they had shed in the first phase. In both groups, patients who successfully completed phase 1 lost a little over 14 kilograms in the first phase but then gained back all but 4 kg in the second phase.
In an accompanying comment, Corby Martin and Kishore Gadde write that the study shows that “a slow and steady approach does not win the race, and the myth that rapid weight loss is associated with rapid weight regain is no more true than Aesop’s fable.” They cite a number of potential short-term advantages of very low calories diets and note that these diets are now well formulated and provide adequate protein and essential micronutrients. They are “safe if used under expert supervision,” the write.
“Across the world, guidelines recommend gradual weight loss for the treatment of obesity, reflecting the widely held belief that fast weight loss is more quickly regained,” said the first author of the paper, Katrina Purcell, of the University of Melbourne, in a press release. “However, our results show that achieving a weight loss target of 12.5% is more likely, and drop-out is lower, if losing weight is done quickly.”
(Editor’s note: The senior author of the paper served as an adviser to Opitfast’s manufacturer from 2005 to 2010.)
October 14th, 2014
Inappropriate Cardiac Stress Tests May Cost Half a Billion Dollars a Year
Larry Husten, PHD
Inappropriate cardiac stress tests may cost the U.S. healthcare system as much as half a billion dollars each year, according to a new study published in the Annals of Internal Medicine.
Joseph Ladapo and colleagues set out to analyze long-term trends in the use of cardiac stress testing in the U.S. Using data from national surveys, they found that from the years 1993-1995 to 2008-2010, the use of cardiac stress tests more than doubled, from 1.6 million to 3.8 million procedures each year. This represented an increase in the rate of procedures from 28 to 45 per 10,000 visits to the doctor.
The overall growth in these tests was largely explained by changes in the patient population. But the growth in cardiac stress tests with imaging — far more expensive than a simple treadmill test — was not explained by these changes. Use of these imaging tests — most often a nuclear stress test, which involves exposure to radiation — have exploded in popularity and are far more expensive than the much simpler treadmill test.
The investigators calculated that from 2005-2010, 30% of imaging stress tests were performed without an appropriate reason, and these tests cost $494 million annually. The radiation received by patients during these inappropriate procedures could lead to 491 patients developing cancer later in life. By contrast, inappropriate stress testing without imaging cost only $7.7 million each year.
In recent years, there has been a slight decrease in the use of these tests as medical guidelines have stated emphatically that these procedures are inappropriate in patients without chest pain or other significant symptoms.
The cost of inappropriate testing “reduces society’s ability to provide other health services or expand access to care for uninsured and underserved populations.” the authors write. “Our results therefore support and further refine concerns voiced by professional societies and insurers about use.”
Note: Comments on this news story are closed, but please join the discussion about this topic over at Harlan Krumholz’s interview with Joseph Ladapo, lead author of this study.
October 13th, 2014
Medicare Reimbursement for Lung Cancer Screening Provokes Debate
Larry Husten, PHD
Although 160,000 people in the U.S. die each year from lung cancer, accounting for more than a quarter of all cancer deaths, screening for lung cancer remains controversial. Based on results from the National Lung Screening Trial (NLST) in 2011, the U.S. Preventive Services Task Force (USPSTF) issued a B recommendation in favor of low-dose CT screening for high-risk current and former smokers. Due to a provision in the Affordable Care Act, private insurance is now mandated. More recently, the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) concluded that there is only low to intermediate confidence that “there is adequate evidence to determine if the benefits outweigh the harms.” The Centers for Medicare and Medicaid Services (CMS) is expected to issue a final decision on national coverage in 2015.
In a special communication published in JAMA Internal Medicine, Douglas Wood writes that the NLST clearly established that the benefits of screening were greater than the risks: “the balance was not close, with a substantial improvement in lung cancer mortality among screened patients.” He argues that the “unintended consequences of screening… can be reasonably mitigated by well-constructed policies and disciplined control within screening programs.” Guidelines from professional societies will help ensure the safe and effective implementation of screening programs, he writes.
Wood further notes that 70% of lung cancer is found in the Medicare population — people who are 65 years or older. “CMS should cover low-dose CT,” he writes, “thus avoiding the situation of at-risk patients being screened up to age 64 through private insurers and then abruptly ceasing screening at exactly the ages when their risk for developing lung cancer is increasing.”
Steven Woolf, Russell Harris, and Doug Campos-Outcalt take the opposite perspective in a competing special communication. The 16% mortality reduction in NLST translated into an absolute reduction of only 0.3% from 21 to 18 deaths from lung cancer per 1000 people. Although the trial prevented 83 deaths among the 26,722 participants, “on the other side of the ledger, the screening caused 16 iatrogenic deaths from diagnostic workups, which included 10,246 imaging studies, 322 percutaneous biopsies, 671 bronchoscopies, 713 surgical procedures, and 228 complications (86 classified as major).”
Woolf et al also warn that “the lure of a vast consumer market of current and former smokers and mandated insurance coverage might entice a groundswell of companies and health systems” seeking to profit from the coverage with little commitment to “accuracy, minimizing radiation exposure, and responsible referrals.”
In an Editor’s Note, Robert Steinbrook expresses concern about the scope of the intensive lobbying effort before the final CMS decision. By June 2014, 45 U.S. senators and 134 House Representatives had written in support of reimbursement for low-dose CT scans. The final CMS decision should be “based on medical evidence, not lobbying or politics,” writes Steinbrook.
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