Identifying the Patient at High Risk for Acute Coronary Syndrome: Plaque Rupture and “Immediate Risk”

11 Identifying the Patient at High Risk for Acute Coronary Syndrome


Plaque Rupture and “Immediate Risk”



John Paul Vavalle, Marschall S. Runge


Coronary heart disease, the clinical manifestation of coronary artery disease (CAD), is the number one killer of adults in the world and is estimated to retain this position over the next decade. In the United States alone, CAD is very prevalent. It has been estimated that as many as 100 million Americans have CAD. Among these, many have coronary heart disease, and there are approximately 12 million new cardiac events in the United States per year in individuals with CAD. Although many of those who die of coronary heart disease had been previously evaluated and treated, more than one half of patients with sudden cardiac death had no known history of coronary heart disease. Identifying such an individual involves determining the risk that an individual will have a cardiac event in the ensuing days or weeks—that is, determining the “immediate risk” of a cardiac event. Development of approaches to assign immediate risk is an area of extensive research.


It is, however, a daunting challenge, because there are no ideal screening tests to reliably define this population. A large portion of these individuals have coronary artery stenoses of less than 50% in transluminal disease, making detection by stress testing difficult. Furthermore, no reliable diagnostic tests exist to ascertain the risk of plaque rupture at a given site in a given individual.


Generally, screening strategies for coronary heart disease seek to identify those at risk before symptoms develop and lessen the burden of ischemic heart disease. Unfortunately, identifying the appropriate population to screen is difficult, and screening the entire population of individuals with CAD would be neither useful nor cost-effective. Without question, as medical technology and understanding of coronary disease expands—and concurrently national attention focuses more and more on the cost efficiency of health care—decisions about whom and how to screen will only become more complex. With a more detailed understanding of the cellular and molecular components of atherosclerosis and acute coronary syndrome, there is hope that novel screening tools with improved accuracy and specificity will be developed. This chapter focuses on the state of the art in detection of individuals at high risk and the promise for the future.



Etiology and Pathogenesis


The earliest evidence of CAD is present in many Americans during late adolescence, based on autopsy studies. Clinically detectable CAD develops over decades, often silently. Multiple risk factors contribute to the development of atherosclerosis: hypertension, diabetes mellitus, smoking, age, and hyperlipidemia (Fig. 11-1). Acute coronary syndromes occur following rupture of an atherosclerotic plaque and the development of a subocclusive or totally occlusive thrombus that may lead to unstable angina or acute myocardial infarction. Many triggers for plaque rupture have been proposed, ranging from hemodynamic stress to the presence of a generalized inflammatory state to neurohormonal influences. However, the precise factors that lead to the rupture of specific plaques in a given individual have yet to be defined.


image

Figure 11-1 Risk factors in coronary heart disease.


LDL-C, low-density lipoprotein cholesterol.


The principal problem with current methods of screening for CAD is that the majority of plaques that rupture and cause acute coronary syndrome are less than 70% in transluminal diameter and do not cause hemodynamically significant coronary obstruction until they rupture (Fig. 11-2). Thus, they are very difficult to detect with screening mechanisms that rely on reduced distal blood flow to cause changes detectable by the test (e.g., ischemic ECG changes, hypocontractility on echocardiogram, perfusion defects on nuclear scans). In fact, what many of these tests detect are narrowed, hemodynamically significant lesions that are stable and not prone to rupturing or causing acute coronary syndrome. Therefore, newer techniques to identify the vulnerable plaque prone to rupture are the focus of much research.


image

Figure 11-2 Steps in the progression of a stable plaque (Time A) to an unstable/ruptured plaque (Time C) are shown.



Clinical Presentation


Because only approximately 20% of acute coronary events are heralded by long-standing angina, the majority of patients are asymptomatic until their major cardiac event. In theory, identifying the immediate risk of asymptomatic patients at highest risk for CAD might allow risk reduction before their event.


There are many reasons why screening for CAD has become common clinical practice, ranging from better education of the public about the dangers of CAD (resulting in more patient-initiated requests for screening) to the possibility that a noninvasive assessment will preclude a need for cardiac catheterization. In addition, physicians are eager to detect early coronary disease in their patients deemed to be at risk, so that they may intervene before the onset of symptoms or a major cardiac event (Fig. 11-3).


image

Figure 11-3 Algorithm for differential diagnosis of acute coronary syndrome (ACS).


CAD, coronary artery disease; IVUS, intravascular ultrasound; MPI, myocardial perfusion imaging; OCT, optical coherence tomography.


An important group of patients who present for CAD screening are those who wish to be “cleared” to begin an exercise program. This has become standard for many structured-exercise programs. However, little evidence supports this as common clinical practice. Additionally, for the reasons described, potentially dangerous but hemodynamically insignificant coronary artery lesions are not detected by standard stress or stress-imaging studies.



Diagnostic Approach



Clinical Epidemiology


The basic idea behind screening is that earlier detection may lead to earlier and more robust implementation of preventive strategies and better health outcomes. However, this is only true if applied to the appropriate populations that should be screened. This concept is essential to understand, because screening inappropriate populations may actually lead to harm with the inherent risks of some tests and false-positive results.


It is important to understand Bayes’ theorem as it applies to medical screening tests. The post-test probability of CAD depends on the pre-test probability of disease and the sensitivity and specificity of the test being used. Testing at very low or very high pre-test probabilities may not actually change clinical decision making (see Chapter 1). In particular, for screening asymptomatic patients for CAD, patients with a very low pre-test probability are more likely to have a false-positive test result than a true-positive test result, especially if the test’s specificity is poor.



Risk Scores



Framingham Risk Score


There are many well-established risk factors for the development of CAD: age, smoking, hyperlipidemia, hypertension, male sex, diabetes, obesity, and physical inactivity, among others. Epidemiologic studies have allowed researchers to develop risk prediction calculators that determine the risk of coronary heart disease events based on the presence of these risk factors. One of the more commonly used risk calculators is based on the Framingham population. It provides an estimate of the 10-year risk of a cardiac event (see “National Cholesterol Education Program. Risk Assessment Tool for Estimating 10-Year Risk of Developing Hard CHD,” under “Additional Resources”).


Risk calculators such as the Framingham risk calculator can be used to group individuals into low-, medium-, or high-risk groups. Supplemental screening tests, as described below, may be used to further define future risk of CAD. While those in the high-risk group are most likely to have severe CAD, until it is possible to assess the potential for plaque rupture, screening these patients and uncovering CAD (see next section) while it is still asymptomatic may be of only limited benefit, since revascularization in asymptomatic patients does not confer the overall benefit of revascularization in symptomatic patients.



Screening Tests


Screening tests for CAD are used for many reasons: to diagnose CAD sufficient to cause myocardial ischemia in individuals (and who would benefit from revascularization), to determine if an individual is at high risk for vigorous activities or high-risk surgical procedures, or to determine whether known CAD in a patient with or without symptoms has progressed to a point requiring revascularization. Unfortunately, for the reasons discussed below, most conventional screening tests are not particularly effective for predicting the risk of plaque rupture in an asymptomatic or low-risk patient.



Electrocardiography—Resting ECG


The sensitivity of resting ECGs to detect CAD is low, yet resting-ECG abnormalities such as Q waves, ST-segment depression, bundle branch blocks, and left ventricular hypertrophy are indeed associated with worse outcomes. However, many people with normal coronary arteries have ECG changes, and a significant number of patients with CAD have normal ECGs. Furthermore, in patients who have a cardiac event who had an ECG in the year before that event, in the majority of instances the baseline resting ECG was normal.



Exercise Testing—Exercise ECG


Exercise-ECG testing has been widely adopted for screening for CAD in asymptomatic adults. Adding exercise to ECG monitoring increases the sensitivity of the test by unmasking ischemia not detectable at rest. A positive test is reflected by at least 1 mm of flat or down-sloping ST depression. Exercise-ECG testing can only be performed in those who can exercise and do not have underlying ECG abnormalities at rest that would prevent interpretation (left bundle branch block, ST depression at rest, or a paced ventricular rhythm) (Fig. 11-4).


image

Figure 11-4 The degrees of flow-limiting atherosclerosis and plaque rupture.


ECG, electrocardiogram; LDL, low-density lipoprotein cholesterol.


The Duke Treadmill Score is the most widely used validated treadmill score. Assessment of exercise time, millimeters of ST depression, and the presence or absence of angina provides a quantitative score that can be used to stratify patients into low-, moderate-, or high-risk groups. Importantly, in the development of the Duke Treadmill Score, asymptomatic patients were excluded. Thus, it is not appropriate to apply a Duke Treadmill Score to screening in asymptomatic patients.


Unfortunately, the sensitivity of exercise treadmill testing for the prediction of coronary heart disease events over the ensuing years is moderate. The ability of this test to detect severe CAD in middle-aged asymptomatic men is low. The majority of asymptomatic patients with an abnormal exercise stress test do not go on to have coronary heart disease events, and it is arguable whether there is a benefit to low- to medium-risk asymptomatic patients who undergo exercise stress testing. In studies of asymptomatic patients without risk factors, a positive result on exercise tolerance testing provided little additional predictive value. In contrast, the predictive value of exercise testing increases when the test is applied to those at higher risk who have a higher pre-test probability for disease.


Authors of a systematic review of the evidence for exercise tolerance testing to screen for CAD, performed for the U.S. Preventative Services Task Force, concluded that testing asymptomatic persons rarely detects previously unrecognized, clinically important coronary artery obstruction but does provide some additional prognostic information beyond that provided by traditional risk factors. However, the effect of this additional information on preventive or therapeutic strategies has not been studied.


As with other screening approaches, a major limitation of exercise stress testing is that ST-segment depression detects ischemia from obstructed coronary arteries while the majority of acute coronary events occur from the rupture and sudden occlusion of a previously nonobstructive plaque.



Stress Echocardiography


Echocardiographic imaging can be added to stress-ECG testing to improve both sensitivity and specificity. In this test, two-dimensional echocardiography is used to visualize regional wall motion abnormalities of hypocontractility that suggest ischemia. In addition to exercise stress, for individuals who cannot exercise, a pharmacologic stress agent such as dobutamine can be used as a means to increase heart rate and contractility. In patients who can exercise, however, a treadmill or bicycle exercise stress test is preferred over chemical stress.


An advantage of adding echocardiography is that it provides information on left ventricular and valvular function. The advantages over nuclear imaging include lower cost, avoidance of radiation exposure, and ease of testing. There are limited data on the use of this test to screen for CAD in the asymptomatic population.



Nuclear Imaging

Related posts:

  1. Angiogenesis and Atherosclerosis
  2. Left and Right Heart Catheterization
  3. Interventional Approaches for Peripheral Arterial Disease
  4. Aortic Regurgitation

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Jun 12, 2016 | Posted by in CARDIOLOGY | Comments Off on Identifying the Patient at High Risk for Acute Coronary Syndrome: Plaque Rupture and “Immediate Risk”

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