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Role of Noninvasive Testing in the Clinical Evaluation of Women With Suspected Coronary Artery Disease

27 August 2012
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Cardiovascular disease

Introduction

Cardiovascular disease is the leading cause of mortality for women in the United States . Although US men have experienced a decline in CAD deaths, the number of coronary deaths in women, >240 000 annually, has remained stable or has increased. CAD, which increases with advancing age, also is a substantial cause of morbidity and disability for US women. Women, in particular young women (<55 years), have a worse prognosis from acute MI than their male counterparts, with a greater recurrence of MI and higher mortality. Furthermore, women have less favorable near-term outcomes after myocardial revascularization procedures than do their male peers. An effective diagnostic strategy is critical in women at risk because up to 40% of initial cardiac events are fatal.

A consistent body of evidence documents that women are less likely than age-matched men to have obstructive CAD; in particular, triple-vessel or left main CAD is more common in men, even though more women than men die from CAD. The high prevalence of nonobstructive CAD and single-vessel disease in women results in an observed decreased diagnostic accuracy and higher false-positive rate for noninvasive testing in women versus men. Physicians may choose from a wide range of diagnostic modalities, but the accuracy and limitations of stress testing in women patients remains an area of significant confusion.

Role of CT Measurements of Coronary Calcification in the Diagnosis and Risk Assessment of Women With Suspected CAD
Coronary CT detects and quantifies the amount of coronary artery calcium (CAC), a marker of atherosclerotic disease burden, via either electron beam tomography (EBT) or multidetector CT (MDCT). However some limitations remain for MDCT (including slower speed of the acquisition [EBT 50 to 100 ms, MDCT 200 to 330 ms], higher radiation dose [EBT dose 0.7 mSv, MDCT dose 1.5 to 1.8 mSv], and possibly greater interscan variability of measurement [EBT 11% to 16%, MDCT 23% to 35%]).

Calcification does not occur in a normal vessel wall, thus signifying the presence of atherosclerosis; however, it is not specific for luminal obstruction. CAC scores approximate the total atherosclerotic plaque burden. Data specific to symptomatic women include a report on a cohort including 539 women (mean age 60±16 years) undergoing clinically indicated angiography. Among the 220 (41%) women with a normal coronary arteriogram, none had detectable CAC, yielding a negative predictive value of 100%. In contrast, women with moderate (100) or higher (400) CAC scores had a greater prevalence of obstructive coronary disease.

Sex and age distributions of the presence and severity of CAC have been published. For women, the prevalence of CAC is low premenopausally, but in general, across age deciles, prevalence lags by 10 years when compared with their male counterparts.

Risk Assessment

The greatest potential for CAC detection could be as a marker for CAD prognosis in asymptomatic women, beyond the prognostic information supplied by conventional coronary risk factors. Since the 2000 ACC/AHA expert consensus document on EBT noted inconclusive risk-stratification evidence on CAC scanning, a number of studies primarily composed of men have reported that the presence and severity of CAC has independent and incremental value when added to clinical or historical data in the estimation of death or nonfatal MI. Included among these is one study estimating total mortality that is notable for the inclusion of a large number of women. In a cohort of 10 377 asymptomatic individuals (including >4000 women) undergoing CAC measurement with EBT (with a mean follow-up of 5.0 years), the extent of CAC was an independent and incremental estimator of all-cause mortality over and above an estimate of the FRS determined by patient history without measurement of lipids or glucose. For women, risk-adjusted relative risk ratios for all-cause mortality were elevated 2.5-, 3.7-, 6.3-, and 12.3-fold for calcium scores of 11 to 100, 101 to 400, 401 to 1000, and >1000, respectively (P<0.0001), as compared with a score of 10. Importantly, for a given CAC score, mortality rates in this study were 3- to 5-fold higher for women than they were for men.

Thus, in 2000, the ACC/AHA issued a joint statement that advocated the use of CAC testing as a screening procedure for CAD risk in selected clinically referred individuals with intermediate clinical risk. Since then, on the basis of the evolving literature, other guidelines and expert consensus documents have extended this recommendation to suggest its use, or the use of other tests of atherosclerosis burden, in clinically selected intermediate-CAD risk patients (eg, those with a 10% to 20% Framinghamc 10-year risk estimate) to refine clinical risk prediction and to select patients for altered targets for lipid-lowering therapies. Consistent with these statements, the recent US Preventive Services Task Force recommends against EBT scanning for either the presence of severe coronary artery stenosis or for prediction of CAD events in adults at low risk for CAD events.

Summary

Given the evolving literature since the last ACC/AHA Expert Consensus statement, current data indicate that CAD risk stratification is possible in women. Specifically, low CAC scores are associated with a low adverse event risk, and high CAC scores are associated with a worse event-free survival. Additional high-quality data are needed from larger cohorts that specifically address CAD outcomes in women to more precisely establish female-specific CAC risk cut points and to more precisely quantify the incremental prognostic value beyond the measurement of conventional coronary risk factors. Until then, consistent with recent consensus statements, CAC testing for CAD risk detection should be limited to clinically selected women at intermediate risk.

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