February 3rd, 2011
Lancet Papers Outline Worldwide Trends in Obesity, Hypertension, and Cholesterol
Larry Husten, PHD
Three papers published in the Lancet provide the most detailed view yet of worldwide trends over the last 3 decades in body-mass index (BMI), blood pressure, and cholesterol, and also include numerous details about different regions and countries. Here are a few highlights of the reports from the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group:
BMI:
- Worldwide, since 1980, mean BMI increased by 0.4 kg/m2 per decade for men and 0.5 kg/m2 per decade for women.
- More than half a billion people in the world are now obese.
- For both men and women, BMIs were highest in some Oceania countries.
- Among high-income countries, the U.S. had the highest mean BMI.
Cholesterol:
- Worldwide, in 2008, mean total cholesterol was 4.64 mmol/L for men and 4.76 mmol/L for women, nearly the same as it was in 1980.
- In high-income countries, total cholesterol fell since 1980, but remained highest when compared with other countries.
- Total cholesterol increased in east and southeast Asia and Pacific.
- The lowest cholesterol levels were found in sub-Saharan Africa.
Blood pressure:
- Worldwide, in 2008, mean systolic blood pressure (SBP) was 128.1 mm Hg in men and 124.4 mm Hg in women.
- Since 1980, global SBP decreased by 0.8 mm Hg per decade in men and 1.0 mm Hg per decade in women.
- For women, SBP declined the most in Western Europe and Australasia.
- For men, SBP fell the most in high-income North America.
- For both men and women, SBP rose in Oceania, east Africa, and south and southeast Asia.
- For women, SBP was highest in east and west African countries.
- For men, SBP was highest in Baltic and east and west African countries.
In an accompanying comment, Sonia Anand and Salim Yusuf write that “the forecast for cardiovascular disease burden in low-income and middle-income countries over the next few decades is dismal and comprises a population emergency that will cost tens of millions of preventable deaths, unless rapid and widespread actions are taken by governments and health-care systems worldwide.”
February 3rd, 2011
How to Question the Research Question
Harlan M. Krumholz, MD, SM
Another good paper for a journal club recently appeared in JAMA. What makes this one worth discussing is the research question the investigators posed and how they addressed it. Although this is not focused on cardiac care, the issues are germane to literature in our field and cardiac care certification is also spreading.
The article, titled “Association Between Stroke Center Hospitalization for Acute Ischemic Stroke and Mortality,” focuses on the New York State Stroke Center Designation program — a collaboration among the New York State Department of Health, the American Heart Association (AHA), and the New York State Quality Improvement Organization. Starting in 2004, the program allowed New York hospitals to apply for certification as a “stroke center” if they met a set of Brain Attack Coalition (BAC) criteria and passed an on-site review and inspection.
Findings and Conclusions
The researchers analyzed data from roughly 15,000 patients with acute ischemic stroke who were admitted to designated stroke centers and roughly 16,000 who were admitted to nondesignated sites in 2005 and 2006. They found that mortality rates were modestly better at the stroke centers than at the other centers (e.g., 30-day mortality, 10.1% vs. 12.5%; P<0.001). The authors’ conclusion: “Our study suggests that the implementation and establishment of a BAC-recommended stroke system of care was associated with improvement in some outcomes for patients with acute ischemic stroke.”
Interest in these systems is likely to grow. Indeed, an editorialist writing in JAMA uses the study results to support his final statement: “Through the collaborative work of many medical professionals, supportive hospital administrators, EMS personnel, and state legislatures, stroke centers have helped reduce death rates one stroke at a time.” And leaders in the AHA have published an assessment of these types of programs and concluded, “As a part of its commitment to promoting high-quality, evidence-based care for cardiovascular and stroke patients, it is recommended that the American Heart Association/American Stroke Association explore hospital certification programs to develop truly meaningful programs to facilitate improvements in and recognition for cardiovascular disease and stroke quality of care and outcomes.” The JAMA study was funded in part by an AHA grant.
Assessing the Study’s Purpose
In their abstract, the authors frame the context for their observational study this way: “Although stroke centers are widely accepted and supported, little is known about their effect on patient outcomes.” In the introduction to the article proper, they mention that there is relatively little information “on whether better care at stroke centers improves acute or long-term mortality.” Then, in contrast, is their stated objective: “to evaluate the association between admission to stroke centers for acute ischemic stroke and mortality.” (The italics in all three quotations are mine, for emphasis.)
The authors went to great lengths to take into account that hospitals may provide care for patients with different risk profiles (selection is an important issue because New York mandates that EMS transport patients suspected of having a stroke to a stroke center). Specifically, the authors employed an instrumental variable, which is often used in economic analyses, as a way to limit confounding. We can explore instrumental variables in another journal club; using one was a reasonable approach in this case, although the presumption is that patients go to the closest hospital. If the only stroke patients that go to a nondesignated hospital are those too ill to be transported a longer distance to a stroke center, the instrumental-variable analysis would be invalid.
That having been said, the bigger problem with this paper is not in the approach to differences in case mix among the hospitals that were studied. What’s hard to determine is whether the authors are interested in cause and effect (do stroke centers “improve” mortality?) or association (do designated stroke centers simply have better outcomes than centers without that designation?). This distinction — cause/effect versus association — is key to evaluating the study design and the appropriateness of the conclusions. The authors use the word “association” in their stated objective, but the language that they — and the editorialist — use around it points to an interest in the “effect” of stroke centers. So which is it?
Assessing Cause and Effect
A 2009 study by Lichtman and colleagues had shown that hospitals certified by the Joint Commission as a stroke center performed better (on mortality and readmission metrics) than noncertified hospitals — but that was the case both after and before the stroke-certification program began. In the conclusion of their abstract, Lichtman and her colleagues state, “Cross-sectional studies assessing the effects of stroke center certification need to account for these pre-existing differences.”
The newer JAMA study did not determine whether differences between the designated stroke centers and the other hospitals existed before the former received their designations. Without a before/after analysis, it’s impossible to determine whether the program had any effect. All one can safely claim is that during the period studied, patients admitted to the stroke centers had a modestly better survival rate than patients admitted to the other centers. Given that (1) more centers have received the designation since then, (2) the performance of the hospitals that are designated late might differ from that of hospitals that were designated early, and (3) the effect of joining is unknown — we cannot fairly assess whether the mortality finding persists today.
Despite this missing before/after analysis, the authors tried to prove cause and effect in another way. They compared the stroke centers and the non-stroke centers according to the outcomes of patients with GI hemorrhage and those with acute MI — and found no mortality difference for those conditions. At first glance, that sounds like proof that the stroke designation is what made the difference. The problem is that hospitals do not perform the same across all conditions and may be better at one type of care versus another. Indeed, you would expect centers that gravitate toward joining a stroke-center program to be those that are better at caring for stroke patients, not those that excel at care for GI hemorrhage or acute MI. The lack of mortality difference between designated stroke centers and nondesignated centers for patients with each of those conditions does not convince me at all that the association between stroke-center designation and mortality is causal.
A Better Approach
To determine whether the stroke-center designation itself mattered, the authors might have used a technique called “difference in differences.” It would have involved analyzing — for both the designated stroke centers and the nondesignated centers — the change in mortality rates from the period before to the period after the stroke-designation program was established. Comparing the changes over time between the two types of centers is where the nugget lies. If the designation program were effective, you would expect a greater diminution of mortality (i.e., a greater rate of improvement in outcomes) at the designated centers than at the nondesignated ones. But even that approach has limitations, given that the designated centers might have been improving at a faster rate all along.
Back to the Research Question
What, then, was the aim of the study? If it was to assist a patient in determining the best place to get care in 2007, then the authors probably showed that a stroke-center designation signaled a better-performing hospital, depending on your view of the instrumental-variable analysis. (The relevance to patients in 2011 is also not clear because of the potential difference between late designees and early designees). If instead the authors sought, as it appears, to prove the value of the stroke-center designation program in improving care, then they clearly fell far short.
In evaluating the value of research articles, start with the aim. Sometimes you need to examine how the authors frame and contextualize that aim — and also how they cast their conclusions — to figure out what they really intended to investigate. With that understanding in hand, you can proceed to assess whether the study design provides evidence that actually answers the research question the authors pose.
What are your thoughts about the consistency between the questions posed by researchers and the answers that their findings provide? Given the JAMA study just discussed, what would you do if you were a policymaker in New York?
February 2nd, 2011
CDC Details the Persistent Problem of Hypertension and Elevated LDL in the U.S.
Larry Husten, PHD
New data from the CDC show that in the years 2005 to 2008, 31% of adults in the U.S. had hypertension and 33.5% had high LDL cholesterol. The two reports are based on statistics gathered from the National Health and Nutrition Examination Survey (NHANES) and have been published online by Morbidity and Mortality Weekly Report.
Of the nearly one-third of adults who had hypertension, 70% received treatment but fewer than half (46%) had their blood pressure controlled. Of the one-third of adults who had high LDL levels, fewer than half (48.1%) received treatment and only one-third (33.2%) had their LDL controlled. For both hypertension and elevated LDL cholesterol, control was lowest in people with little access to regular medical care (received care less than twice in the previous year), who were uninsured, who were Mexican-American, or who had incomes below the poverty level. Significant increases in the treatment of people with both conditions were observed since the 1999 to 2002 period.
February 1st, 2011
New Guidelines Lend More Support for Carotid Stenting
Larry Husten, PHD
Newly issued guidelines provide increased support for carotid stenting as an alternative to carotid endarterectomy, but don’t favor widespread screening or the routine use of ultrasound to assess the risk for stroke. The Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease, developed by the AHA, the ACC, and multiple other organizations, is published online in Circulation, Stroke, and
Both stenting and endarterectomy are acceptable when blockages are greater than 50%, according to the guidelines, but medical therapy may be preferable for many patients. “The guidelines support carotid surgery as a tried-and-true treatment for most patients,” said Thomas G. Brott, co-chair of the writing committee, in a press release. “However, for patients who have a strong preference for less invasive treatments, carotid stenting offers a safe alternative. Because of the anatomy of their arteries or other individual considerations, some patients may be more appropriate for surgery and others for stenting.”
“The risks of these procedures have fallen considerably, but you need to make sure you have very experienced practitioners performing the latest techniques,” said Jonathan Halperin, the other co-chair.
Although widespread screening is not endorsed in the new guidelines, Halperin said that screening is reasonable in people with two or more risk factors for stroke.
January 31st, 2011
Learning to Network/Networking to Learn
John Ryan, MD
Last weekend, I attended a heart failure meeting in Florida. It was designed as a small meeting where fellows interested in heart failure got the opportunity to meet with heart failure faculty from across the country. The meeting provided various teaching seminars as well as one-on-one meetings and workshops. It was a unique experience that offered us fellows the chance to get career advice and research ideas.
This meeting was probably the closest I have ever come in my cardiology fellowship to actually network. Where career advancement is concerned, we fellows place most of our efforts into finding mentors and obtaining publications. But all of us are on the same trajectory — in a year or two, we will be looking for jobs or subspeciality fellowships. So how do we go about that?
- Should we be networking more to get more opportunities when we finish fellowship?
- If so, how, or where, could we do this? Are meetings like AHA are too oversized to offer this opportunity?
- Or are our research and clinical collaborations considered to be networking?
- Also, many of the smaller meetings have industry sponsorship. Some institutions do not let their fellows go to these meetings, even though they are among the most worthwhile. Is that the right approach?
Where do you set up the boundaries between education, collaboration, and networking? Is any gathering a networking opportunity?
January 31st, 2011
Women and Younger Patients May Be At Higher Risk For Sprint Fidelis Failure
Larry Husten, PHD
Women, younger patients, those with hypertrophic cardiomyopathy, and those with arrhythmogenic right ventricular dysplasia or channelopathies may be more likely to develop Sprint Fidelis lead failure. Robert Hauser and colleagues at the Minneapolis Heart Institute, the Mayo Clinic, and Beth Israel Deaconess Medical Center analyzed data from 1023 patients who received Fidelis leads and 1668 patients who received Quattro leads at their institutions. At 4 years, the lead survival rate was 87% for Fidelis compared with 98.7% for Quattro. No deaths or injuries were caused by the failures, but inappropriate shocks occurred in 42% of lead fractures. The study has been published online by
“We found that patients who were young and active with relatively normal pump function were at highest risk, as well as women compared with men,” said Hauser, in a press release. Hauser also expressed caution about Fidelis lead replacement: “Only in the hands of experienced operators should Fidelis lead replacement even be considered in these younger patients or women, who are expected to live with an ICD for a number of years.”
In an accompanying editorial, Avi Fischer writes that these data suggest “a relationship of lead failure to physical activity and better ventricular systolic function.” Lead replacement in these patients “should be considered at the time of elective generator replacement.”
January 28th, 2011
Justice Department Files New Suit Against Boston Scientific
Larry Husten, PHD
The U.S. Department of Justice has filed another suit against Boston Scientific. The government claims that Guidant (bought by Boston Scientific in 2006) sold the Ventak Prizm 2 and the Renewal 1 and 2 devices even after the company knew they were defective.
Earlier this month Boston Scientific was convicted and sentenced in a criminal case to pay more than $296 million for withholding information from the FDA about “catastrophic failures” in these devices. The suit filed yesterday is designed to recover Medicare payments for the devices.
January 28th, 2011
Does CRP Level Modify the Benefit of Statins? Paul Ridker Reacts to New Data
Paul Ridker, MD, MPH
CardioExchange welcomes Paul M. Ridker, a leading researcher on the value of C-reactive protein (CRP) concentration as a prognostic marker of cardiovascular risk, to respond to the latest data on CRP and statin therapy from the Heart Protection Study (HPS).
The New HPS Findings on CRP: The HPS investigators sought to determine whether statin therapy might be especially beneficial to patients with high CRP concentrations. They took the more than 20,000 HPS participants who had been randomized to receive simvastatin (40 mg/day) or placebo for a mean of 5 years and stratified them into 6 groups according to baseline CRP level, ranging from <1.25 mg/L to ≥8 mg/L.
The incidence of major vascular events — coronary death, MI, stroke, or revascularization — was significantly lower among simvastatin recipients than among placebo recipients (19.8% vs. 25.2%). The investigators found no evidence that incidence of that endpoint or its components varied according to baseline CRP concentration. Nor did relative risk reduction vary across four subgroups that were defined by high or low baseline levels of LDL cholesterol and CRP. Even patients with low baseline levels of both LDL-c and CRP benefited significantly from simvastatin.
Dr. Ridker’s Response:
First, although the HPS investigators report that baseline CRP does not modify the vascular benefits of statin therapy, it is important to remember that baseline LDL-c also did not modify the benefit of statin therapy in their study.
Second, the data presented clearly show that CRP levels track directly with absolute risk in the HPS. For example, within the placebo group, the baseline CRP level corresponded with the incidence of vascular events: 19% incidence among patients with low CRP, climbing to 31% among those with high CRP. Thus, although these data are not discussed at all in the article, they nonetheless confirm the ability of CRP to predict high risk.
Third, the HPS investigators elected not to address the core hypothesis that on-treatment levels of CRP correlate with the risk reduction attributable to statins, as has been shown in many prior statin trials. The authors make the claim that such an analysis should not be done, as it would be nonrandomized. Yet they go on to conclude that the benefits of statin therapy accrue solely to on-treatment LDL, an analysis that suffers equally from the same nonrandomized limitations.
Fourth, the well-conducted HPS was performed almost entirely among patients with a prior history of MI, stroke, peripheral artery disease, or diabetes. Therefore, the HPS cannot be interpreted as a primary-prevention trial. Primary prevention is the setting in which (1) CRP measurement has been shown to provide as much incremental information on vascular risk as does total or HDL cholesterol and (2) CRP testing is recommended to identify patient groups who benefit from statin therapy but otherwise would not qualify for treatment on the basis of LDL-c levels.
In the end, the only way to test the inflammatory hypothesis of atheroscerlosis is to directly randomize patients to targeted anti-inflammatory therapies. My research team and I hope to launch two such trials this year.
January 28th, 2011
She Doesn’t Mind that Her Heart Races … Do You?
Alfonso E. Sierra, MD and James Fang, MD
This latest installment in our case discussion series is submitted by Alfonso E. Sierra, MD. We encourage members to submit cases that they believe warrant discussion. Selected cases will be presented to the community, and case authors will receive a $100 Amazon gift card.
A 62-year-old woman comes in for a routine exam, with a history of sudden death on both sides of her family. Her paternal grandfather died suddenly in his 40s, her father in his mid-70s, and her maternal grandmother in her mid-90s; her maternal grandfather told her that many of his relatives also died suddenly at various ages. Her 60-year-old brother has angina and syncope and was found on an angiogram to be a candidate for angioplasty, which is pending.
The patient herself has no symptoms other than tachycardia during exercise, which has been happening for more than 35 years without any palpitations, pain, dyspnea, diaphoresis, or fainting. She notes that the episodes start suddenly, only during exercise, and that her heart rate often reaches 180 to 190 beats/minute. She usually feels her heart returns to its normal resting rate (86-89 beats/min) within a minute or so after she stops her workout. The occurrence of the tachycardia does not appear to be related to her clinical condition, the intensity or duration of the exercise, or the humidity or temperature of the room. The patient is curious about why it happens but is not concerned about it and is not eager to be treated if there is no need.
Her physical examination is normal, other than a resting pulse of 88. Her blood pressure is 108/62. She has been menopausal since her mid-50s and has no signs or symptoms of hypo- or hyperthyroidism. Her CRP and ESR levels are normal, as are her total and LDL cholesterol levels; her HDL is 66. Her resting ECG is normal for a woman her age.
Questions:
- Would you conduct any further tests to evaluate the nature/etiology of this patient’s exercise-induced tachycardia?
- Would you suggest any treatment to prevent the tachycardia during exercise?
- Would you advise her to restrict her activity in any way?
- Would her family history influence your treatment decision in any way?
Response
James Fang, MD
Most of the CardioExchange members who responded to this case indicated that they would evaluate this patient further before treating her symptoms or restricting her activity in any way. I agree. Although her symptoms and family history together are somewhat concerning, the gradual cool down and chronicity of her symptoms are reassuring, as are the normal results on her physical exam, EKG (most importantly, intervals), and basic laboratory tests. Furthermore, she has not experienced any syncope or presyncope.
Exploring family history is always important, and this patient’s is notable. Most genetic cardiovascular conditions are autosomal dominant, and her family history does appear to affect every generation, as would be anticipated with this mode of inheritance. However, in familial sudden death syndromes, the deaths usually occur by age 35 or 40. Most sudden deaths are caused by coronary artery disease (CAD), but the risk for ventricular fibrillation with CAD can be inherited as well (Circulation 1999; 99:1978). The ages of sudden death in this family would certainly be consistent with CAD.
An exercise test would be reasonable in this case, with particular attention to the patient’s QT interval during exercise and to the increases and declines in her heart rate. Her high resting heart rate may be due to lack of vagal tone, as is seen in patients who are deconditioned (e.g., those with impaired heart rate recovery). The exercise test would have only modest predictive value for CAD screening, but current guidelines recommend it over imaging as a first test (Circulation 2002; 106:1883). At this point, without a diagnosis, treating this patient or restricting her activity would be premature.
NEJM Journal Watch — Recent Cardiology Articles- Exercise as Medicine for Preventing Colon Cancer Recurrence
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- Is Routine Defibrillation Testing Necessary for Patients Undergoing Subcutaneous ICD Implantation?