Syllabus: Coronary Artery Calcifications in Women: CT Scoring
By Leo P. Lawler, MD, FRCR
Introduction
Coronary artery disease remains one of the leading causes of mortality and morbidity for women in the western world. In recent decades there has been significant progress in the therapies aimed at the limitation of ischaemic insults and the salvage of function in infarcted myocardial tissues. Most people accept that it is preferable to arrest the atherosclerotic process before it gets to this point of vascular compromise. Fifty percent of those who suffer a myocardial infarction (MI) have no prior history of cardiac disease and conventional risk factors fail to predict one third of those who subsequently suffer a cardiac event. Coronary calcium is specific for atherosclerotic plaque and can be detected with high sensitivity and accurately quantified by computed tomography (CT) to help predict future cardiac events related to coronary artery disease. This article will discuss the evolution of coronary artery calcium imaging as it pertains to atherosclerotic heart disease in women.
Women and coronary artery disease
Many of the theories and therapies of coronary artery disease may be applied equally to men and women. However one must bear in mind that gender differences in pathophysiology may influence the distribution of disease among the sexes, its detection and the response to therapy. The leading cause of death in U.S. women is cardiovascular disease with 500,000 dying annually and 250,000 of these deaths are ascribed to myocardial infarction (MI) . Between 35 and 64 years of age only 0.2% of women will have experienced a non-fatal myocardial infarction but by age 70, 15-20% of women will have experienced a manifestation of coronary artery disease . The average age for female MI is 10 years later than for men but after age 60 one in four of each group will die of such a cardiac event. The rate of decline of MI mortality is falling less for women and they undergo less evaluation and treatment than men with similar or less symptoms. It has been suggested women may not have benefited from all the recent advances in detection and management of coronary artery disease [1, 6].
Diet, weight, activity, diabetes, hypertension and dyslipedaemia behave as similar modifiable risk factors in both sexes. Relative estrogen deficiency is a risk factor specific to women. Post-menopausal women lose a protective effect from circulating estrogens and an up to 50 percent reduction in the risk of coronary artery disease has been recognized in healthy post-menopausal women with of oral estrogen replacement . Smoking is one of the leading identifiable risk factors for CAD and is more hazardous to women but their cessation has been less than men with women more likely switch to 'low yield' brands rather than stop altogether. Smoking is higher in female adolescents and is increasing among young and disadvantaged females.
The significance of cornary artery calcification
Coronary arteries become calcified in an active and regulated process only in those areas that are atherosclerotic. The amount of calcium present correlates highly with histomorphometric measurements of calcium crystals deposited . Calcification is present in 50% of those 40-49 years and 80% of those 60-69 years though the numbers are higher in symptomatic individuals. Crystalline calcium is deposited in fatty streaks and in greater quantity in older people and those with advanced lesions. In a non-linear way the amount of calcium correlates with the amount of atherosclerosis. Though there may be a correlation with vessel lumen compromise or plaque instability the exact relationship is hard to define . Conversely the absence of coronary calcification can reliably exclude the presence of significant atherosclerotic disease and vessel narrowing though it does not exclude the presence of fatty streaks or non-calcified plaque. Fallavollita showed a 95% negative predictive value for significant atherosclerotic disease with a CT demonstrating no calcium and the predictive values are similar in men and women. Coronary artery calcification may be present in small lesions and its population prevalence is higher than the expected incidence of coronary artery disease implying there may be a threshold quantity that represents clinical significance.
The CT detection of coronary artery calcification
Chest radiographs and fluoroscopy have been explored as easy and inexpensive modalities to detect coronary calcium but both are insensitive for detection and inaccurate in quantification. CT, not surprisingly, has been shown to be highly sensitive and specific in detection of coronary calcium.
CT must have temporal resolution values that approximate the 40ms R-R interval of the cardiac cycle to accurately image and quantify coronary artery calcium without motion artifact. We cannot, as yet, image the motionless heart but the accepted gold standard at present is electron beam CT (EBCT) with a temporal resolution of 100ms. Most of the current principles of imaging and clinical application of scoring relate to the original EBCT work which was shown to be reproducible . However EBCT is expensive and limited in availability making it of less utility for common clinical use and an unlikely candidate for future population screening. Single detector sequential CT scanning with a gantry rotation time of 1 second lacks the temporal resolution required. With the advent of slip ring technology single, dual and multi-detector row helical scanners with partial reconstruction algorithms can now give up to 500ms gantry rotation times and temporal resolution of up to 250ms. Prospective or retrospective gating is used to image the heart in the phase of end-diastole with least motion. We know that we can obtain reproducible results with these non-EBCT methods [13-16] but since much of the data to date relates to EBCT the exact meaning of these measurements for clinical use is still a matter of debate. It is hoped that with the constant progress in helical scanning technology we may have a widely available tool for routine coronary calcium imaging but standardize protocols and techniques remain elusive.
The CT quantification of coronary artery calcium
Plaque histomorphometry , severity , progression and response to therapy may be indexed to attenuation value [8, 11] but quantification of this calcium is no simple matter. The actual coronary artery calcium score has evolved from the original description by Agatston et al. . After the images are sent to a workstation regions of interest are drawn over foci of high density, deemed to be in the coronary arteries. A calcification is defined as a focus with a Houndsfield unit measurement over 130 and occupying over 1mm2 or three pixels. The density is assigned a value based on an arbitrary severity scale and is multiplied by the total area involved. The final score for the epicardial coronary arteries is tabulated based on a summation of all the regions of interest over all the vessels. Scoring mechanisms have been refined and modified and conversion equations for different types of scanners have been developed. Some authors have suggested other methods such as volume measurements may be superior for calcium quantification. Consensus on the actual scoring methods has yet to be obtained and this is compounded by rapidly changing CT scanners and techniques.
What do CT coronary calcium scores mean?
As previously mentioned it is believed there is a threshold of calcium and score that is of clinical significance. The scores are thought to identify those at higher than expected risk for future coronary events . Though many practice with a philosophy that a threshold score around 100 is of significance others believe ranges of values should be ultilized. Similarly it is likely that similar scores in different patient populations based on age and gender may have different significance. For example a lower score in a young woman may imply severe disease whereas a similar value in an older man may not reach significance. Further studies are required to interpret the significance of score changes over time to assess progression or response to therapy.
Women tend to have low scores or negative scans before the menopause. Under 50 years of age scores over 10 are extremely uncommon but are seen in 25% of such men. In women 50-59 years old their scores remain significantly lower than men. From 60-69 women have scores equivalent to men 10 years younger. A study of women 60-76 years showed that the absence of coronary calcium was predictive of angiographically normal arteries with sensitivity 61%, specificity 100% and 85% accuracy . In general terms high scores are predictive of moderate risk over the next 2-5 years of a morbid cardiovascular event and low scores imply low risk of such an event in a similar time period .
The roles suggested for coronary artery calcium scoring at present include management of acute chest pain syndrome, screening of asymptomatic patients for risk factor assessment and follow-up of disease progression after risk factor modification. For the patient in the emergency room with chest pain high calclium scores do predict the likelihood of significant stenosis and these patients have a four fold risk of death of infarction compared to those free of calcium . However scoring is not recommended instead of conventional methods of stress testing or nuclear imaging. The absence of coronary calcium on CT has a high negative predictive value for significant luminal narrowing and it has been suggested as a useful tool for triage of the patient with atypical chest pain and low pre-test probability for the presence of disease. In screening of low-risk asymptomatic patients the role of coronary calcium scoring is not defined but it may be considered in association with conventional risk factors. Ususpected high calcium scores may precipitate either more aggressive risk factor modification or more directed pharmacologic therapies such as cholesterol lowering medication.
Conclusion
Coronary artery calcium scoring will be with us for the foreseeable future. It clearly bears a relationship to the pathophysiology of coronary artery disease and its sequelae and it is likely that CT will continue to be the easiest way to detect and quantify it. There are many implications for women’s cardiovascular health and for the practice of radiology. However before it is embraced uniformly in patient care there are questions still to be answered. Which scanner and what scoring method is to be the universal standard ? Is population screening to be recommended? What are the ethical and clinical guidelines for patients who self-refer for scoring? What are the issues relating to radiation exposure and the discovery of incidental findings such as lung nodules? How are the professional and financial interests of radiologists and cardiologists to be reconciled? The final, consensus driven application of this tool has yet to be defined for its potentially large contribution to be realized.
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