Impact of chronic stable angina on health status



by J. F. Beltrame, Australia

John F. BELTRAME, BSc,
BMBS, PhD, FRACP, FESC,
FACC, FCSANZ, FAHA
Discipline of Medicine
University of Adelaide
Adelaide
Cardiology Unit, The Queen
Elizabeth Hospital Campus
Central Adelaide Local
Health Network, Adelaide
Basil Hetzel Institute for
Translational Health
Research, Adelaide
Lyell McEwin Health Service
Northern Adelaide Local
Health Network, Adelaide
AUSTRALIA

Angina is associated with reduced physical limitations and a poorer quality of life. The more frequent the angina, the greater the impairment in physical limitation and quality of life. While enquiring about the frequency of angina provides some insights into the disability associated with the disorder, it is important to understand the full impact of the condition on the patient’s life. Unfortunately, clinicians may not be completely aware of the angina burden experienced by their patients, as alluded to in the CADENCE study (Coronary Artery Disease in gENeral practice). The objective of this review is to discuss the impact of stable angina on the health status of patients, with a focus on the existing gap between the patient’s experience and the clinician’s perception of the disability associated with angina and how this gap could potentially be bridged.

Stable angina – a different emphasis in the CAD spectrum

Coronary artery disease (CAD) may clinically manifest as an acute or chronic coronary syndrome, with the latter more often referred to as “chronic stable angina” or simply “stable angina.” Whereas acute coronary syndromes constitute a significant proportion of in-hospital clinical activity and therefore attract considerable medical attention, stable angina is disseminated within the community and comes to medical attention in the general practitioner’s or specialist’s clinic. Indeed, in developed countries the estimated prevalence of stable angina is 5% in the male population and 4% in the female population.1 Furthermore, the incidence of newly diagnosed cases in these developed communities is 49/100 000 males and 28/100 000 females.1 Hence stable angina is a significant medical problem within the community, although it receives less attention than the more acute state. The principal objectives in the management of CAD, which are applicable to both acute and chronic forms of the disease, include prevention of cardiac events (death and myocardial infarction) and improvement of health status (Figure 1, page 12).

Health status is the impact of the CAD process on the patient’s lifestyle and includes the associated symptoms, functional limitations, and impairment on quality of life (Figure 2, page 12). Since coronary atherosclerosis is the most common underlying pathophysiological process for both the acute and chronic forms of CAD, the available therapies are similar. As shown in Figure 1, these include (i) revascularization therapies—coronary artery bypass grafting and percutaneous coronary interventions, (ii) cardioprotective therapies—such as anti-platelet agents, statins, and angiotensin-converting enzyme (ACE) inhibitors, and (iii) anti-ischemic therapies—including nitrates, β-blockers, and calcium channel blockers.

Figure 1. Coronary artery disease spectrum and management.

Figure 2. Health status in coronary
artery disease (CAD).

Although the treatment goals and available therapies in the acute and chronic forms of CAD are similar, the difference in prognosis between these clinical manifestations influences the emphasis placed on their respective clinical management. In acute coronary syndromes, there is a high risk of death within the first 30 days of presentation (between 2% and 10% at 30 days),2 primarily due to platelet activation/thrombus generation as a result of plaque disruption. In this context, antiplatelet agents, statins, and ACE inhibitors have been shown to be effective in reducing cardiac events. Similarly, early revascularization strategies have been shown not only to reduce cardiac events, but also to have an impact on health status, often improving symptoms. The use of anti-ischemic agents in acute coronary syndrome (ACS) has received less attention in contemporary clinical practice, but postinfarct angina that is not amenable to revascularization therapies is often managed with conventional antianginal therapies (nitrates, β-blockers, and calcium channel blockers).

In contrast to ACS, where the 1-year mortality rate ranges between 8% and 10%,2 patients with stable angina have an annual mortality risk of 1.2% to 2.4% per year,3 and the condition has a chronic course so the treatment goals are focused toward improving health status. This does not diminish the essential role of cardioprotective agents, which should be utilized in all patients with stable angina. However, the role of revascularization therapies is less imperative in patients with stable angina since their impact in the prevention of cardiac events in these patients is limited.4 Furthermore, revascularization therapy provides only a small incremental benefit over optimal medical therapy (cardioprotective and anti-ischemic therapies) in controlling angina symptoms in patients with stable angina.

In summary, acute and chronic CAD syndromes have a common therapeutic armamentarium to target the underlying CAD; however, the relatively lower risk of cardiac events in stable angina results in some of these therapies being less effective and therefore having a less central focus in the management of these patients. Moreover, due to the chronic nature of stable angina, improving patient health status should be a central focus.

The importance of health status in stable angina

The consideration of health status in stable angina provides a more global and patient-orientated focus in clinical man- agement. As summarized in Figure 2, health status comprises of three components: symptoms, functional limitations, and quality of life. These components are interrelated and together provide a holistic perspective.

Symptoms
Angina is the hallmark symptom of stable angina and the clinical manifestation of myocardial ischemia. The American College of Physicians’ criteria for angina include (i) substernal chest discomfort with a characteristic quality and duration, (ii) provoked by exertion or emotional stress, and (iii) promptly relieved by rest or short-acting nitrates.5 If all three criteria are met, the symptom is considered as “definite angina,” whereas with only two criteria it is labeled as “probable angina.” If only one criterion is met, then it is considered as “noncardiac chest pain.”

In addition to confirming the presence of angina symptoms, clinical assessment should focus on quantitating the extent of the symptoms, in particular angina frequency (number of episodes over time) and the frequency of short-acting nitrate consumption to alleviate the chest pain. This latter measure provides a robust method of assessing the number of angina episodes that sufficiently concern the patient to seek treatment. Together these measures provide insights into the extent of the symptoms experienced by a patient with stable angina.

Anginal symptoms have an impact not only on a patient’s health status, but also on the clinical outcome.6 The CLARIFY Registry (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is a large international registry that has recruited over 32 000 stable angina patients with a 2-year follow-up for clinical outcomes. In a prospective analysis of this registry, Steg et al7 demonstrated that stable angina patients with anginal symptoms (with or without evidence of ischemia) were at higher risk of cardiac events than those without angina (silent ischemia), underscoring the importance of angina as a predictor of cardiac events. Furthermore, in a study of over 5500 outpatients with stable angina, the severity of angina frequency was associated with the risk of an ACS admission over the following 12 months and a trend toward increased all-cause mortality.8 Whether reducing angina frequency protects against cardiac events requires further evaluation, since there is only limited data available addressing this question.

Functional limitations
As outlined above, a fundamental characteristic of angina is its relationship with physical exertion, and thus it would be expected to impact on a patient’s physical limitations. The extent to which a patient is physically limited by angina can be quantitated by estimating how far he/she can walk before stopping because of chest pain. However, a more pragmatic approach is to determine which activities of daily living are impaired by the angina symptoms.

Physical limitation due to angina has been shown to be an independent determinant of all-cause mortality among patients with stable angina.8,9 In a study of over 8000 outpatients with stable angina followed for an average of 2 years, the extent of physical limitation was found to be related to all-cause mortality when compared with patients who had no limitations; ie, a hazard ratio of 1.27 (95% confidence interval [CI], 0.98-1.64) with mild limitation, of 1.61 (95% CI, 1.27-2.05) with moderate limitation, and of 2.55 (95% CI, 1.97-3.30) with severe limitation.9 This again reflects the clinical importance of health status in stable angina.

In addition to physical limitations, patients with stable angina may be emotionally or socially limited by their condition. Emotional limitations may manifest as anxiety disorders, with excessive worry relating to the CAD diagnosis. Social limitations may also occur with patients avoiding activities such as shopping or visiting friends since it precipitates angina. Hence the functional limitations resulting from stable angina are multidimensional and should be considered in the clinical assessment of patients.

Health-related quality of life
In health status assessment, quality of life needs to be specifically evaluated in relation to the impact of stable angina; hence health-related quality of life (HRQoL) is a better outcome measure. Importantly, HRQoL is the “patients’ perception” of how the disease process impacts on their lifestyle and not the “clinician’s perception.” For example, a patient who experiences angina when walking 100 meters may be perceived by a clinician as having a significant impairment in his/her quality of life, yet the patient may perceive this as no significant impairment since he/she is content with being angina-free in undertaking the gardening. In contrast, an elderly patient experiencing angina only when playing competition table tennis may be perceived as only a mild impairment by a clinician, but this may be devastating for the patient. As with the other components of health status, HRQoL is associated with all-cause mortality.8,10 In a methodical review of the impact of health status domains on all-cause mortality in stable angina patients, Spertus et al8 demonstrated that physical limitation was the strongest determinant, followed by angina frequency, with HRQoL having a smaller impact.

The key determinants of global HRQoL include depression and anxiety.11 Depression in patients with stable angina has been strongly associated with an impaired HRQoL, as demonstrated in multiple studies.11-13 Women are more often affected by depression,14,15 and studies have demonstrated that women with stable angina have a poorer HRQoL than their male counterparts.16 However, Norris et al demonstrated that women with stable angina still have a poorer HRQoL, even following adjustment for depression, which suggests that there is an inherent sex difference in HRQoL among patients with stable angina.17

Assessment of health status in stable angina

With an understanding that health status has three key components (angina symptoms, functional limitations, and HRQoL) and that these components are each related to mortality in patients with stable angina, the importance of evaluating health status in patients is clear, especially considering the chronic nature of the disorder. The assessment of health status is best achieved by utilizing established health status assessment instruments that are typically completed by the patient. However, lessons learned from the application of these questionnaires should also be translated into routine clinical assessment.

Health status instruments
These questionnaires can be either generic or disease-specific.18 Generic health status instruments allow comparison across disease states since the questions are not specific for any one condition. Commonly utilized generic instruments include the Medical Outcomes Short Form-3619 (SF-36 or its shorter version the SF-12), EuroQoL (EQ-5D),20 World Health Organization Quality of Life assessment (WHOQOL),21 Nottingham Health Profile,22 and McMaster Health Index Questionnaire.23 In contrast, disease-specific instruments for coronary artery disease have been developed and provide a more specific assessment in relation to stable angina. The McNew Scale is an example of a disease-specific coronary artery disease questionnaire,24 but the most commonly used instrument is the Seattle Angina Questionnaire (SAQ),25 which has been well validated and is available in multiple languages.

Considering that depression is a major determinant of HRQoL and may impact on the components of health status, it would be prudent to specifically assess depression in patients with stable angina. Multiple instruments for the assessment of depression have been used in patients with stable angina. These include the Patient Health Questionnaire (PHQ-9),26,27 the Center for Epidemiologic Studies Depression Scale (CES-D),28 the Hospital Anxiety and Depression Scale (HADS),27 the Beck Depression Inventory (BDI),29,30 and the Cardiac Depression Scale (CDS).31

Many of these instruments involve extensive questioning and are thus of limited benefit as screening tools in clinical practice; consequently, there is no consensus as to which one of them is the optimal instrument for depression screening of CAD patients.32 However, shorter versions of these questionnaires (especially the PHQ-2 and the CDS) have been recommended as routine screening tools in cardiac patients.33

Clinical assessment
The traditional clinical measure of health status in patients with stable angina is the Canadian Cardiovascular Society Classification (CCSC).34 This simple, 4-scale grading system, classifies angina on the basis of its impact on physical activity. This includes Class I – only strenuous effort precipitates angina, Class II – ordinary activities only slightly limited by angina, Class III – ordinary activities markedly limited by angina, Class IV – unable to perform any physical activity because of angina. Although easily administered, it has a number of limitations including (i) the physician’s interpretation of the patient’s symptoms, (ii) it is unclear, and thus variable, how angina-free patients are classified, (iii) it does not record many components of health status including angina frequency, emotional impairments, social impairments, and quality of life. Hence there is a need for improved clinical assessment of health status.

An important lesson from previous health status studies of stable angina is directly questioning and documenting the patient’s symptoms and functional limitations. The CADENCE study (Coronary Artery Disease in gENeral practice) recruited 207 primary care practitioners, who each assessed between 10 and 15 consecutive stable angina patients (n=2031) in relation to their clinical status and also asked them to complete an SAQ.35 Although the clinicians perceived that 80% of their patients had “optimally controlled” angina, only 52% of patients reported being “angina-free” and only 47% claimed their “enjoyment in life” was not limited by their angina. These clinician-patient discrepancies in health status assessment are not limited to primary care practitioners, since similar discrepancies were observed in cardiology outpatients.36

These discrepancies underscore the need for patient-related outcome measures in clinical practice. Ultimately, no matter how astute clinicians are, only the patients themselves can detail the frequency of their angina attacks and their impact on their functioning and lifestyle. Even when the clinician attempts to closely detail these health status attributes, discrepancies may occur either as a result of clinician misperception or patient anxiety and recall. Thus the routine use of abridged versions of the disease-specific instruments, such as the SAQ-7,37 may be the most effective approach to assess patient health status. This approach of incorporating health status assessment into clinical evaluation of CAD patients has been adopted by ICHOM (International Consortium for Health Outcome Measurement), as reflected in their CAD Standards.38

An observation evident from patient assessment of health status that has clinical utility is the relationship between angina frequency and functional status/quality of life. As summarized in Figure 3, the CADENCE study35 demonstrated that there was a linear relationship between angina frequency and physical limitation as assessed by the SAQ. Moreover, this linear relationship was also evident between angina frequency and quality of life. Thus, as would be intuitively expected, the more angina symptoms a patient experiences, the more physical limitations he/she incurs and the greater the impact on quality of life. Thus, quantifying the frequency of angina at each clinical visit may provide the clinician with insights into other aspects of the patient’s health status.

Figure 3. Relationship between angina frequency,
physical limitation, and quality of life in patients
with stable angina.
Abbreviations: mth, month; SAQ, Seattle Angina Questionnaire;
wk, week.
Based on data from reference 35: Beltrame et al. Arch
Intern Med. 2009;169:1491-1499.

Implications in stable angina management

In the preceding sections discussions have focused upon (i) the differences between ACS and stable angina despite their sharing a common underlying atherosclerotic process, and the need to especially focus on health status in stable angina given the low risk of cardiac events; (ii) the key components of health status including angina symptoms, functional limitations, and quality of life; and (iii) the assessment of health status in stable angina utilizing both clinical approaches and disease-specific instruments such as the SAQ. The question that now arises is how we utilize this knowledge in the management of our stable angina patients and whether we can improve their health status?

Impact of CAD therapies on health status
Available conventional therapies for stable angina include cardioprotective, antianginal, and revascularization therapies (Figure 1). The cardioprotective therapies are essential to reduce cardiovascular events but also, surprisingly, have an impact on health status. For example, statins have been shown to improve depression in patients with CAD,39 and thus improve health status. By design, antianginal therapies improve symptoms and are therefore expected to have flow-on benefits for functional capacity, quality of life, and thus health status. Indeed, health status is now routinely assessed in the development of new antianginal agents. For example, ranolazine has been shown to reduce angina frequency and improve physical functioning in patients with stable angina.40

Revascularization therapies improve health status in patients with stable angina, but their incremental benefit over optimal medical (cardioprotective and antianginal) therapy is limited. This is exemplified by the COURAGE trial (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) where the benefits in health status of percutaneous coronary intervention (PCI) disappeared within 36 months41; an effect that has also been observed in “real life” registry data.42

Therapeutic appropriateness
Considering the limited impact of revascularization on cardiac events and health status, the appropriateness of these procedures needs to be carefully considered in patients with stable angina. This is reflected in the appropriate use criteria for revascularization,43 where the procedure has limited justification in patients who have few symptoms, or when noninvasive investigations suggest a low cardiac risk and minimal medical therapy has been prescribed. Future iterations of these criteria may incorporate baseline health status assessment, considering this is the primary goal of therapy.

Precision medicine
Stable angina is potentially a prime example of implementing precision medicine, where health care is customized to the individual patient. This should involve both a holistic approach and the patient’s involvement in shared decision making. Treatment should not be disease-focused, but should consider the whole patient. Hence the treatment of depression should be considered equally as important as the treatment of the anginal symptoms, since both have a significant impact on health status. Shared decision making is especially important in deciding when to embark upon revascularization therapy. For example, should PCI be considered for uncomplicated single-vessel disease when two antianginal medications have failed or should it only be considered when triple therapy + ranolazine has failed? Involving patients in these relatively arbitrary decisions will provide the opinion of the key person in the therapeutic paradigm since patients are best placed to balance the decision in relation to their overall health status.

Concluding remarks

Stable angina is a chronic disease that impacts on health status, and thus its management should particularly focus on improving health status in addition to minimizing the risk of cardiac events. The assessment of health status needs to be routine in clinical practice, and therapies that improve symptoms, functional limitations, and quality of life should be utilized. This will be optimized with a precision medicine approach involving shared decision making with the patient. ■

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