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Authors' Interview: Drs. Blankstein & Nasir:
Predictors of Coronary Heart Disease Events Among Asymptomatic Persons With Low Low-Density Lipoprotein Cholesterol
MESA (Multi-Ethnic Study of Atherosclerosis)
Authors Interview:
Response by Dr. Ron Blankstein (Brigham and Women’s Hospital / Harvard Medical School) and Dr. Khurram Nasir (Yale University)
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Publication:
Authors Interview: Drs. Blankstein & Nasir
Predictors of Coronary Heart Disease Events Among Asymptomatic Persons With Low Low-Density Lipoprotein Cholesterol: MESA (Multi-Ethnic Study of
Atherosclerosis)
Ron Blankstein, MD, Matthew J. Budoff, MD, Leslee J. Shaw, PhD, David C. Goff, Jr, MD, PhD, Joseph F. Polak, MD, MPH, Joao Lima, MD, Roger S. Blumenthal, MD and Khurram Nasir, MD, MPH
J Am Coll Cardiol, 2011; 58:364-374, doi:10.1016/j.jacc.2011.01.055
Non-invasive Cardiovascular Imaging Program, Department of Medicine (Cardiovascular Division) and Radiology, Brigham and Women's Hospital, Boston, Massachusetts
Division of Cardiology, Harbor-UCLA Medical Center, Los Angeles, California
Emory University School of Medicine, Atlanta, Georgia
Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina
|Department of Radiology, Tufts-New England Medical Center, Boston, Massachusetts
Departments of Medicine and Radiology, Johns Hopkins University, Baltimore, Maryland
Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, Maryland
Section of Cardiovascular Medicine, Yale University, New Haven, Connecticut
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What are the main findings of the study?
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Reply: Although current treatment guidelines focus on lowering LDL cholesterol as the primary goal of therapy, it is known that even among individuals with low LDL cholesterol levels, some will still experience coronary heart disease events and may benefit from more aggressive pharmacologic and lifestyle therapies. Our study shows that among individuals with no known CAD and low LDL cholesterol, both traditional risk factors -- namely older age, male gender, hypertension, diabetes, and low HDL cholesterol -- and imaging biomarkers such coronary artery calcifications, and to a lesser extent carotid intima-media-thickness -- can be used to identify patients who have increased risk of future events.
An important finding in ours study is that even after accounting for all traditional clinical risk factors, the presence and severity of coronary artery calcifications (which is a direct marker of pre-clinical coronary atherosclerosis) can be used to substantially enhance risk assessment. For instance, even after accounting for clinical risk factors, the presence of even a mild amount of coronary artery calcifications imparted nearly a 3 fold increase in risk, a level of risk which was similar (or higher) to the risk associated with having any other clinical risk factor. Strikingly, in those individuals who had severe coronary artery calcifications (i.e. CAC score >400), the risk was increased approximately 9 folds. However, as importantly, the absence of CAC was associated with a very low event rate, even when multiple other risk factors were present.
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Were any of the findings unexpected?
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Reply:While many of the risk factors identified in our study have been previously studied, the relevance of these risk factors among individuals with baseline low LDL-C is less established. Thus, it could have been suggested that some risk factors may be less important in a population that already has low LDL cholesterol. However, the predictive ability of traditional risk factors, and especially imaging biomarkers, was striking. Nevertheless, an unexpected finding – given the fact that our population was similar to participants of the JUPITER study --- is that in our study hsCRP was not associated with an increased risk of future events. Interestingly, the presence (and severity) of coronary artery calcifications emerged as the strongest predictor of future events. We found that even in individuals who had no clinical risk factors, the presence of severe coronary artery calcifications was associated with a substantially elevated risk. On the other hand, among individuals with multiple risk factors, the absence of coronary artery calcification was associated with a very low event rate.
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What should clinicians and patients take away from this study?
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Reply: When establishing the role for more aggressive lifestyle or pharmacologic interventions, it is not merely enough to assess LDL cholesterol levels. Even among individuals with low LDL cholesterol, the presence of hypertension, low HDL cholesterol, and diabetes are all associated with an increased risk of future coronary heart disease events. Among individuals in whom more aggressive therapies are being considered, the use of coronary artery calcium scoring may offer further risk stratification. While our results cannot be used to recommend widespread use of CAC screening, selective use of this test, particularly when clinicians are “on the fence” if to treat a given individual may be effective and provide improved risk assessment for an individual patient.
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What recommendations do you have for nephrology health care providers as a result of your study?
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Reply: We would make the following 4 recommendations:
1. All patients, especially if they have any risk factors, should be encouraged to follow a healthy lifestyle by avoiding tobacco, exercising, achieving an optimal weight, and adhering to a heart healthy diet.
2. Treatment decisions for individual patients should be individualized based on risk, cost of treatment, and patient preferences. In individuals in whom the role of pharmacotherapy is being contemplated, or among those who are reluctant to start pharmacotherapy, consider obtaining a coronary artery calcium score. We would only recommend a CAC score in selected cases, if it has the potential to impact future therapies.
3. Based on our study, individuals who have no coronary artery calcification have a very low event rate and thus pharmacotherapy may be deferred. On the other hand, those with moderate or severe coronary artery calcifications have a substantially higher event and thus are more likely to benefit from treatment.
4. While our study (and others) have clearly demonstrated that even after considering all baseline clinical factors, CAC can be used to identify individuals who have a higher risk of events, a large-scale randomized trial is needed in order to determine whether the use of coronary artery calcium scoring is associated with improved outcomes.
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Abstract: |
Objectives: Our aim was to identify risk factors for coronary heart disease (CHD) events among asymptomatic persons with low ( 130 mg/dl) low-density lipoprotein cholesterol (LDL-C).
Background: Even among persons with low LDL-C, some will still experience CHD events and may benefit from more aggressive pharmacologic and lifestyle therapies.
Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort of 6,814 participants free of clinical cardiovascular disease. Of 5,627 participants who were not receiving any baseline lipid-lowering therapies, 3,714 (66%) had LDL-C  130 mg/dl and were included in the present study. Unadjusted and adjusted hazard ratios were calculated to assess the association of traditional risk factors and biomarkers with CHD events.
To determine if subclinical atherosclerosis markers provided additional information beyond traditional risk factors, coronary artery calcium (CAC) and carotid intima media thickness were each separately added to the multivariable model.
Results: During a median follow-up of 5.4 years, 120 (3.2%) CHD events were observed. In unadjusted analysis, age, male sex, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and subclinical atherosclerosis markers (CAC >0; carotid intima media thickness  1 mm) predicted CHD events. Independent predictors of CHD events included age, male sex, hypertension, diabetes, and low HDL-C. After accounting for all traditional risk factors, the predictive value of CAC was attenuated but remained highly significant. The relationship of all independent clinical predictors remained robust even after accounting for elevated CAC.
Conclusions: Among persons with low LDL-C, older age, male sex, hypertension, diabetes, and low HDL-C are associated with adverse CHD events. Even after accounting for all such variables, the presence of CAC provided incremental prognostic value. These results may serve as a basis for deciding which patients with low LDL-C may be considered for more aggressive therapies.
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Featured Angina| Acute Coronary Syndrome and Heart Disease Interviews
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Highlights of Article by Dr. Erik Hess et of Mayo Clinic ;CIRCOUTCOMES 2012
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Chest pain is the 2nd most common reason patients come to EDs across the United States
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Initial testing – including information obtained from the history, physical exam, electrocardiogram, and cardiac troponin – identifies > 98% of heart attacks
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To avoid missing a diagnosis of heart attack or pre-heart attack symptoms, emergency physicians often admit patients to observation units or to the hospital for extensive diagnostic testing, including stress testing
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This results in false positive test results, unnecessary exposure to radiation, and unnecessary downstream procedures such as stent placement in arteries of the heart
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Decision aids are evidence-based tools designed to educate and engage patients in decisions regarding their care
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We hypothesized that patients who were educated regarding their future risk for a heart attack and engaged in the decision of whether to be admitted to the observation unit for stress testing or to follow-up with a Mayo Clinic heart doctor in the next 72 hours would have greater knowledge about their short-term risk for heart attack, be more aware of the management options, and choose less intensive approaches to evaluation
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We randomly assigned 204 patients who came to the ED with chest pain and were being considered for observation unit admission to the decision aid or to usual care
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Decision aid patients:
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Had greater knowledge regarding their short-term risk for a heart attack
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Less frequently decided to be admitted to the observation unit for stress testing
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Had 4 times greater engagement in the decision making process
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Had no adverse events within 30 days of the ED visit
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Take home points
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Patients want to be educated and engaged in decisions regarding their care
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Once properly informed and engaged in treatment decisions, patients often choose less intensive treatment options
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Integrated health systems like the Mayo Clinic in which physicians collaboratively work together to provide ER patients ready access to outpatient follow-up have potential to improve the value of Emergency care
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Glucose, Insulin and Potassium (“GIK”) TO MINIMIZE IMPACT OF HEART ATTACKS BEFORE PATIENTS GET TO THE HOSPITAL
Study puts life-saving drugs in the hands of paramedics, decreasing rate of cardiac arrest and death from heart attacks
CHICAGO (March 27, 2012) — Paramedics can potentially reduce someone’s chances of having a cardiac arrest or dying by 50 percent by immediately administering a mixture of glucose, insulin and potassium (“GIK”) to people having a heart attack, according to research presented today at the American College of Cardiology’s 61st Annual Scientific Session. The Scientific Session, the premier cardiovascular medical meeting, brings cardiovascular professionals together to further advances in the field.
The study showed that patients who received GIK immediately after being diagnosed with acute coronary syndrome — which indicates a possible heart attack is either in progress or on the way — were 50 percent less likely to have cardiac arrest (a condition in which the heart suddenly stops beating) or die than those who received a placebo, although the treatment did not prevent the heart attack from occurring. The reduction in in-hospital cardiac arrest or death was a “secondary endpoint”, so statistically was not definitive, but was consistent with how GIK seems to work in experimental models of heart attack.
The effect was also present for patients with ST-elevation heart attacks, which require immediate treatment. For those patients, immediate GIK was associated with a 60 percent reduction in in-hospital cardiac arrest or death.
“When started immediately in the home or on the way to the hospital — even before the diagnosis is completely established — GIK appears not completely prevent any heart attack from occurring, but appeared in this trial to reduce the size of heart attacks and to reduce by half the risk of having a cardiac arrest or dying,” said Harry P. Selker, MD, MSPH, executive director of the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, who led the study with Joni Beshansky, RN, MPH, co-principal investigator and project director. “Acute coronary syndromes represent the largest cause of death in this country. GIK is a very inexpensive treatment that appears to have promise in reducing those deaths and morbidity.”
The cost of the treatment is about $50.
“Because the trial is the first to show GIK could be effective when used by paramedics in real-world community settings, it could have important implications for the treatment of heart attacks,” Dr. Selker said. Previous clinical trials have shown no consistent effect, likely because the GIK was given too late to help. This study, the “IMMEDIATE Trial,” was the first to test the effectiveness of administering GIK at the very first signs of a threatening heart attack, in the community, rather than waiting hours until the diagnosis was well-established at a hospital, as done in previous clinical trials.
“We wanted to do something that is effective and can be used anywhere,” said Dr. Selker. “We’ve done a lot of studies of acute cardiac care in emergency departments and hospitals, but more people die of heart attacks outside the hospital than inside the hospital. Hundreds of thousands of people per year are dying out in the community; we wanted to direct our attention to those patients.”
The researchers trained paramedics in 36 Emergency Medical Services systems in 13 cities across the country to administer GIK after determining that a patient was likely having a threatened or already established heart attack using electrocardiograph-based ACI-TIPI (acute cardiac ischemia time-insensitive predictive instrument) and thrombolytic predictive instrument decision support that prints patient-specific predictions on the top of an electrocardiogram. The paramedics used these predictions to decide if a patient would likely benefit from treatment. There were 911 patients randomized to receive either the GIK treatment or a placebo.
Administering GIK immediately also reduced the severity of the damage to the heart tissue from the heart attack. On average, 2 percent of the heart tissue was destroyed by the heart attack in people receiving GIK, compared with 10 percent in those who received the placebo. Although a significant proportion of suspected heart attacks are later determined to be false alarms (23 percent in this study), administering GIK does not appear to cause any harmful effects in such patients.
The research team will follow up with study participants at six and 12 months to evaluate the longer-term benefit of the GIK treatment.
This study was funded by the NIH’s National Heart, Lung and Blood Institute.
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Angina | Heart Disease Resourses
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Chronic Chest Pain
Part of the award winning public television series Healthy head
/Healthy Mind. It's one of the scariest medical symptoms for people who are generally healthy: a tightening, painful feeling in the chest known as Angina. In some cases this chest pain can be a serious warning that requires immediate treatment. But for the millions of people with chronic, stable angina the discomfort is something that can be readily managed with a variety of treatments. In this program we take a look at what generally causes angina, what can be done to prevent it and how it can be effectively treated with lifestyle changes, innovative drug therapies and medical procedures.
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Amazon.com Editorial Review:
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Be prepared for the unexpected.
When sudden cardiac arrest (SCA) strikes, the electrical system of the heart short circuits, causing the heart to quiver rather than pump in a normal rhythm. It typically results in the abnormal heart rhythm know as ventricular fibrillation (VF). It usually happens without warning and the majority of people have no previously recognized symptoms of heart disease. And it most often happens at home. For the best chance of survival from SCA caused by VF, a defibrillator should be used within 5 minutes. Yet, less than 1 in 20 people survive largely because a defibrillator does not arrive in time.
Just as seat belts or airbags do not save every life in a traffic accident, a defibrillator will not save every person who suffers a sudden cardiac arrest. Yet many lives could be saved if more people could be reached more quickly.
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