Global Risk Assessment - Clinical Tree

Introduction

This chapter is focused on tools for risk assessment in patients with stable coronary heart disease. In general, patients with stable ischemic heart disease have a good prognosis. However, these data summarize the population average, and the clinician is able to significantly refine the estimate of risk for the individual using methods described in this chapter.The central goal of risk assessment is to guide therapeutic decision-making and, in some cases, additional diagnostic evaluation. These diagnostic and prognostic assessments, although overlapping, are not identical. The prognostic assessment is valuable because the risk of recurrent events is strongly linked to the potential absolute and relative benefits of specific therapeutic interventions. In patients with stable coronary heart disease, an estimate of risk is similarly pivotal in management such as in identifying candidates for coronary angiography and revascularization. In this chapter we will review individual prognostic markers that are associated with adverse outcomes in stable coronary artery disease (CAD). We will also review multivariable models that incorporate multiple markers to quantitatively estimate risk and examine current approaches to match therapies to individual risk of an adverse outcome.

Prognosis Overall and in Subgroups

The assessment of cardiovascular disease risk and the prevention of recurrent events in patients with established CAD represent an opportunity for major public health gain. Aligning diagnostic studies and therapeutic interventions with clinical risk is a cornerstone of secondary prevention. Previous epidemiologic studies have demonstrated that established CAD is a major risk factor for incident events. For example, data from the Framingham Study, obtained before the widespread use of aggressive medication and modification of risk factors, revealed an average annual mortality rate of 4% in patients with stable CAD. Current therapies and management have improved the prognosis of the disease substantially, with an annual mortality rate of 1% to 3% and a rate of major ischemic events of 1% to 2%. In contemporary clinical trials, patients with stable CAD have an annual rate of major cardiovascular events of 1.2–2.4% per annum.

However, substantial heterogeneity in overall risk exists amongst patients with stable CAD with baseline cardiovascular risk factors, functional characteristics, and coronary anatomy each playing an important role. For example, in the international Reduction for Continued Health (REACH) Registry—which included asymptomatic adults with risk factors, patients with stable atherosclerosis, and individuals with prior ischemic events—large variations in cardiovascular risk between subgroups of patients were observed. Patients with a prior history of ischemic events at baseline had the highest rate of subsequent ischemic events (18.3%); patients with stable coronary, cerebrovascular, or peripheral artery disease had a lower risk (12.2%); and patients without established atherothrombosis but with risk factors only had the lowest risk (9.1%) during 4-year follow-up.

As might be expected, conventional risk factors for the development of CAD —hypertension, diabetes, smoking, hypercholesterolemia, obesity, and family history —each retain their prognostic value in the context of established CAD. The prognosis for patients with stable CAD is also worsened in patients with reduced left ventricular ejection fraction, by the severity and intensity of angina pectoris, with the presence of dyspnea, and by the presence of three-vessel disease or left main disease. The estimation of the long-term risk of adverse outcomes is crucial to effectively apply measures of secondary prevention and prevent overtreatment of patients at low risk of an adverse outcome, or under-treatment of patients at high risk of an adverse outcome.

Individual prognostic markers that are associated with adverse outcomes in stable CAD are summarized in Box 17.1 .

BOX 17.1

Risk Stratification Based on Noninvasive Testing

Modified from Fihn SD, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation . 2012;e354–471.

High Risk (> 3% Annual Risk for Death or Myocardial Infarction)

1.
Severe resting left ventricular dysfunction (LVEF < 35%) not readily explained by noncoronary causes
2.
Resting perfusion abnormalities involving ≥ 10% of the myocardium without previous known MI
3.
High-risk stress findings on the ECG, including
- ≥ 2 mm ST-segment depression at low workload or persisting into recovery
- Exercise-induced ST-segment elevation
- Exercise-induced VT/VF
4.
Severe stress-induced LV dysfunction (peak exercise LVEF < 45% or drop in LVEF with stress ≥ 10%)
5.
Stress-induced perfusion abnormalities encumbering ≥ 10% myocardium or stress segmental scores indicating multiple vascular territories with abnormalities
6.
Stress-induced LV dilation
7.
Inducible wall motion abnormality (involving more than two segments or two coronary beds)
8.
Wall motion abnormality developing at low dose of dobutamine (≤ 10 mg/kg per min) or at a low heart rate (< 120 beats/min)
9.
Multivessel obstructive CAD (≥ 70% stenosis) or left main stenosis (≥ 50% stenosis) on CCTA

Intermediate Risk (1–3% Annual Risk for Death or Myocardial Infarction)

1.
Mild to moderate resting LV dysfunction (LVEF of 35–49%) not readily explained by noncoronary causes
2.
Resting perfusion abnormalities involving 5–9.9% of the myocardium in patients without a history or previous evidence of MI
3.
ST-segment depression of ≥ 1 mm occurring with exertional symptoms
4.
Stress-induced perfusion abnormalities encumbering 5–9.9% of the myocardium or stress segmental scores (in multiple segments) indicating one vascular territory with abnormalities but without LV dilation
5.
Small wall motion abnormality involving one to two segments and only one coronary bed
6.
One-vessel CAD with ≥ 70% stenosis or moderate CAD stenosis (50–69% stenosis) in two or more arteries on CCTA

Low Risk (< 1% Annual Risk for Death or Myocardial Infarction)

1.
Low-risk treadmill score (score ≥ 5) or no new ST-segment changes or exercise-induced chest pain symptoms when achieving maximal levels of exercise
2.
Normal or small myocardial perfusion defect at rest or with stress encumbering < 5% of the myocardium ^∗

∗ Although the published data are limited, patients with these findings will probably not be at low risk in the presence of either a high-risk treadmill score or severe resting LV dysfunction (LVEF < 35%).
3.
Normal stress or no change in limited resting wall motion abnormalities during stress
4.
No coronary stenosis > 50% on CCTA

CAC , Coronary artery calcium; CAD , coronary artery disease; CCTA , coronary computed tomography angiography; ECG , electrocardiogram; LV , left ventricular; LVEF , left ventricular ejection fraction; MI , myocardial infarction; VF , ventricular fibrillation; VT , ventricular tachycardia.

Prognosis in Subgroups

Coronary Artery Spasm

Although the pathophysiology is incompletely understood, known triggers for coronary vasospasm include smoking, electrolyte disturbances (potassium, magnesium), cocaine use, cold stimulation, autoimmune diseases, hyperventilation, or insulin resistance. The symptoms vary from silent myocardial ischemia to angina and even myocardial infarction. Long-term survival is usually good as long as patients are on calcium antagonists and avoid smoking. The incidence of cardiac death among patients with coronary artery spasm is up to 10% during 3 years of follow-up. The prognosis of vasospastic angina depends on the extent of underlying CAD and on disease activity (frequency and duration of spastic episodes), the amount of myocardium at risk, and the presence of severe ventricular tachyarrhythmias or advanced atrioventricular block during ischemia. The prognosis of vasospasm may be better in Japanese patients than patients of European ancestry, potentially due to differences in baseline characteristics, ascertainment of individuals of less severe disease, and fewer patients of Japanese ancestry having multivessel coronary spasm and/or reduced left ventricular function.

Women

Cardiovascular disease remains the leading cause of death in women and is responsible for 42% of premature deaths in women under the age of 75 years. Although coronary heart disease develops 5–10 years later in women than in men and women have historically been at lower risk for CAD, more recent data indicate that the prevalence of cardiac events in men is decreasing, whereas women are experiencing an increase in cardiac events, including myocardial infarction. Women have been underrepresented in cardiovascular clinical trials to date, representing 30% of participants in trials conducted since 2006, thus diminishing the quality of the evidence base available to guide therapy.The increasing recognition of heart disease in women is likely to stimulate key additional research in coming years. The considerable decline in mortality from CAD is mainly caused by population-level improvements in risk factors and by improvements in primary and secondary prevention.

Although the risk factors for CAD in women and men are similar, their distribution differs over time and between regions. Smoking seems to be associated with a higher relative risk of CAD in women than men, and the prevalence of hypertension increases more with age in women than men, resulting in higher rates of stroke, hypertrophy of the left ventricle, and diastolic heart failure. Diabetes is associated with a higher risk of CAD in women than in men. Previously, circulating estrogens were believed to have a beneficial effect on the risk of CAD, but exogenous hormone administration has not led to a similar effect.

Women and men of every age presenting with stable angina have increased coronary mortality relative to the general population, and several studies have indicated gender-related bias in care of both acute and chronic CAD. However, in a large international prospective population (CLARIFY) of outpatients with stable CAD, the rates for cardiovascular clinical outcomes were similar between men and women at 1-year follow-up.

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