Comparison of Prognostic Usefulness of Coronary Artery Calcium in Men Versus Women (Results from a Meta- and Pooled Analysis Estimating All-Cause Mortality and Coronary Heart Disease Death or Myocardial Infarction)

doi:10.1016/j.amjcard.2007.03.037

The American Journal of Cardiology

Volume 100, Issue 3, 1 August 2007, Pages 409-414

https://doi.org/10.1016/j.amjcard.2007.03.037 Get rights and content

Women with coronary heart disease (CHD) have higher mortality compared with men. Atherosclerotic imaging risk markers are associated with higher mortality and relative risk of CHD events in women compared with men. However, data on the predictive accuracy of coronary artery calcium (CAC) in women are scarce. We performed a systematic review of the published literature from 2003 to 2006 on the prognostic value of CAC in women and men. Two investigators reviewed Medline for prospective registries on annual rates of CHD death or myocardial infarction (MI) by CAC results. Three studies in 6,481 women and 13,697 men reported results by gender. We also analyzed 2 observational registries for annual all-cause death rates by CAC scores in women (n = 17,779) and men (n = 17,850). Summary relative risk ratios and 95% confidence intervals were calculated using a random effects model. For all-cause mortality, rates were 0.1% to 1.6% per year for women and 0.1% to 2.6% for men with CAC scores from 0 to 10 to ≥1,000, respectively (p <0.0001). For CHD death or MI, annual rates were 0.2% to 1.3% in women and 0.3% to 2.4% for men with low- to high-risk CAC scores. For women with a CAC score of 0, annual CHD death or MI rates were 0.16%, similar to that of men (p = 0.55). Summary relative risk ratios increased 4.9-fold (p = 0.006), 5.5-fold (p = 0.002), and 8.7-fold (p <0.0001) for mild-, moderate-, and high-risk CAC scores, respectively. A comparative analysis of gender differences showed no significant differences between women and men for mild- to high-risk CAC scores (p = 0.66), suggesting an equivalent ability to risk stratify by gender. In conclusion, this meta- and pooled analysis revealed that CAC screening is equally accurate in stratifying risk in women and men.

Section snippets

Methods

For this report, we calculated clinical outcomes for CAC scores in women versus men using pooled analysis and meta-analysis. For the pooled analysis, we calculated all-cause mortality rates for women and men by their CAC scores. For the meta-analysis, we calculated CHD death or MI rates for women and men by their CAC scores.

A systematic search of Medline for English-language articles included the terms “coronary calcium” and “prognosis.” Published articles were limited to those reported from

Results

Women from the pooled datasets1, 15 were on average 54 years of age with nearly 1/3 being hypertensive or hyperlipidemic (Table 1). Approximately 5% of women were diabetic and nearly 1 in 5 women was a current smoker. Men were older with nearly 1/2 of all patients having measurable CAC. Cumulative mortalities were 1.7% for women and 2.6% for men at 10 years. For women, all-cause death rates were 0.1%, 0.3%, 0.5%, 0.8%, and 1.6% for CAC scores of 0 to 10, 11 to 100, 101 to 399, 400 to 999, and

Discussion

The present results support the notion that there is a strong predictive relation between CAC and incident CHD in asymptomatic women and men. A large dataset of 17,778 women and 17,850 men showed a high degree of risk discrimination for all-cause death by extent of CAC.1, 15 Available meta-analytic evidence in 6,481 women and 13,697 men followed for the occurrence of CHD death or MI showed a similar ability to stratify risk in men and women.3, 6, 8 These data coincide with previous evidence

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Cited by (88)

The power of zero calcium in 82-Rubidium PET irrespective of sex and age
2023, Journal of Nuclear Cardiology
Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings.
Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients.
Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P < 0.001). Abnormal PET was significantly less frequent in ZCS patients (2.6% vs 27.6%, P < 0.001). Sensitivity/negative predictive value (NPV) of ZCS to detect/exclude abnormal PET and ≥ 10% ischemia were 96.8% (95%-CI 95.0%-97.9%)/97.4% (95.9%-98.3%) and 98.9% (96.7%-99.6%)/99.6% (98.7%-99.9%), respectively. Radiation and cost reduction were estimated to be 23% and 22%, respectively.
ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.
Major Global Coronary Artery Calcium Guidelines
2023, JACC: Cardiovascular Imaging
This review summarizes the framework behind global guidelines of coronary artery calcium (CAC) in atherosclerotic cardiovascular disease risk assessment, for applications in both the clinical setting and preventive therapy. By comparing similarities and differences in recommendations, this review identifies most notable common features for the application of CAC presented by different cardiovascular societies across the world. Guidelines included from North America are as follows: 1) the 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease; and 2) the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for Prevention of Adult Cardiovascular Disease. The authors also included European guidelines: 1) the 2019 European Society for Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias; and 2) the 2016 National Institute for Health and Care Excellence Clinical Guidelines. In this comparison, the authors also discuss: 1) the Cardiac Society of Australia and New Zealand Guidelines on CAC; 2) the Chinese Society of Cardiology Guidelines; and 3) the Japanese Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. Last, they include statements made by specialty societies including the National Lipid Association, Society of Cardiovascular Computed Tomography, and U.S. Preventive Services Task Force. Utilizing an in-depth review of clinical evidence, these guidelines emphasize the importance of CAC in the primary and secondary prevention of atherosclerotic cardiovascular disease. International guidelines all empower a dynamic clinician-patient relationship and advocate for individualized discussions regarding disease management and pharmacotherapy treatment. Some differences in precise coronary artery calcium score intervals, risk cut points, treatment thresholds, and stratifiers of specific patient subgroups do exist. However, international guidelines employ more similarities than differences from both a clinical and functional perspective. Understanding the parallels among international coronary artery calcium guidelines is essential for clinicians to correctly adjudicate personalized statin and aspirin therapy and further medical management.
Coronary artery calcium and atherosclerotic cardiovascular disease risk in women with early menopause: The Multi-Ethnic Study of Atherosclerosis (MESA)
2022, American Journal of Preventive Cardiology
We aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM).
To examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at <45 years of age.
The cohort was 64.1 ± 9.1 years old and 28.0% experienced EM. There were 291 ASCVD events over 12.5 ± 3.6 year follow-up with a higher event rate among those with EM compared to those without EM of 13.6 vs. 9.0 per 1,000 year follow-up (p < 0.01). Women with EM had a slightly lower prevalence of CAC = 0 (55.1%) than women without EM (59.7%) (p = 0.04) despite no difference in mean age. Among women with CAC = 0, the cumulative incidence of ASCVD at 10 years was low-to-borderline for women with (5.4%) and without EM (3.2%) (p = 0.06). However, women with EM had a significantly higher 15-year risk with an adjusted HR of 1.96 (95% CI: 1.26–3.04). In multivariable Cox models, women with CAC ≥ 1 had progressively increased ASCVD risk that did not significantly differ by EM status.
In MESA, >50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM.
This study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0.
The Future of Cardiac Molecular Imaging
2020, Seminars in Nuclear Medicine
Molecular imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) serves numerous applications in clinical cardiology and research. Similar to other medical imaging technologies, this area has undergone and continues to experience rapid changes resulting from technological and medical advances. These have immediate impacts on diagnosis, treatment planning, and patient care, as well as supplying innovative tools for fundamental and translational research. A broad shift toward hybrid PET systems and incorporation of advanced computational tools has been accompanied by mechanism-specific, targeted radiopharmaceuticals that seek to address long-standing limitations in cardiac imaging. While this review addresses some of the still-emerging clinical uses of established radiopharmaceuticals, it too highlights newer imaging probes, applications, and imaging techniques and instrumentation on the horizon. We highlight molecular imaging advances in inflammatory and infiltrative myocardial conditions, heart metabolism, vascular and valvular diseases, neurohormonal dysregulation, and transformational technical advances such as the rise of artificial intelligence and theranostic approaches to cardiovascular disease.
Prognostic value of coronary artery calcium score in symptomatic individuals: A meta-analysis of 34,000 subjects
2020, International Journal of Cardiology
Citation Excerpt :
In that study, patients with positive CAC scores had a hazard ratio of 2.04 as compared with patients without any CAC. Another study found no significant differences between men and women for mild- to high-risk CAC scores, suggesting an equivalent ability to stratify CVD risk by gender [32]. The data in the studies we included did not allow us to stratify by gender.
Coronary artery calcium (CAC) scanning has evolved into an important subclinical prediction method for cardiovascular diseases in asymptomatic subjects. However, the prognostic implication of CAC scanning in symptomatic individuals is less clear.
To assess the prognostic utility of CAC in predicting risk of major adverse cardiac events (MACE) in stable patients with suspected CAD.
We did a systematic electronic literature search for studies presenting original data in CAC score, and reporting cardiovascular events in stable, symptomatic patients as primary outcome. Primary outcome of the meta-analysis was the occurrence of MACE, a composite of late coronary revascularization, hospitalization for unstable angina or heart failure, nonfatal myocardial infarction, and cardiac death or all-cause mortality. Using random effects models, we pooled relative risk ratios of CAC for MACE, and adjusted hazard ratios (HR) of the associations between different CAC strata (CAC 0–100,100–400, and ≥ 400, versus CAC = 0) and incident MACE.
We included 19 observational studies (n = 34,041). In total, 1601 events were analyzed, of which 158 in patients with CAC = 0. The pooled relative risk ratio was 5.71 (95%-CI: 3.98;8.19) for subjects with CAC > 0. The pooled estimate of adjusted HRs demonstrated increasing, positive associations, with the strongest association for CAC > 400 (HR: 4.88; 95%-CI: 2.44;9.27).
This meta-analysis demonstrated that increased levels of CAC are strongly and independently associated with increased risk for MACE in stable, symptomatic patients with suspected CAD, showing increasing risk with greater CAC scores. Application of CAC scanning as a prediction method could be useful for a considerable number of such patients.
Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers
2019, JACC: Cardiovascular Imaging
The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening.
CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry.
We performed a nested case–control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality.
CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease.
CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

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Coronary artery diseaseComparison of Prognostic Usefulness of Coronary Artery Calcium in Men Versus Women (Results from a Meta- and Pooled Analysis Estimating All-Cause Mortality and Coronary Heart Disease Death or Myocardial Infarction)

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality

Radiology

Gender-based differences in the prognostic value of coronary calcification

J Womens Health (Larchmt)

Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals

JAMA

Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults

Circulation

Coronary artery disease
Comparison of Prognostic Usefulness of Coronary Artery Calcium in Men Versus Women (Results from a Meta- and Pooled Analysis Estimating All-Cause Mortality and Coronary Heart Disease Death or Myocardial Infarction)