Table of Contents
- Key Points
- Why This Research Matters
- Understanding Coronary Artery Calcium and ASCVD
- How This Review Was Conducted
- Key Findings: How Men and Women Differ
- The Danger of Non-Calcified Plaque in Women
- Sex-Specific CAC Patterns and Mortality Risk
- Clinical Implications: The Case for Sex-Adjusted Scoring
- Limitations of This Review
- Recommendations for Patients and Providers
- Frequently Asked Questions
- Source Information
Key Points
- Heart disease is the leading cause of death for women, but women's plaque is often less calcified and more lipid-rich than men's.
- A low coronary artery calcium score does not rule out dangerous non-calcified plaque, especially in women.
- Women's plaque is more prone to erosion, which can trigger heart attacks even without heavy calcification.
- Specific CAC patterns in women—multiple lesions, larger size, greater volume, and progression—raise cardiovascular mortality risk.
- The review recommends sex-adjusted CAC scoring to better risk stratify patients, particularly those at intermediate risk.
Why This Research Matters
Cardiovascular disease (CVD) is often thought of as a "man's disease," but it is the leading cause of death for women as well. For decades, research and clinical practice treated heart disease in men and women as essentially the same condition. This review challenges that assumption.
The authors—Allison Bigeh, Chandana Shekar, and Martha Gulati from the University of Arizona—set out to summarize the known differences in plaque depositions, coronary artery calcium scoring, and the role of CAC in predicting atherosclerotic cardiovascular disease mortality in men and women.
Why does this matter? If women tend to accumulate different types of plaque in different patterns than men, then a one-size-fits-all approach to heart risk screening could be missing women at the highest risk. Understanding these sex differences is a critical step toward more accurate risk prediction and, ultimately, saving more lives.
Understanding Coronary Artery Calcium and ASCVD
Before diving into the findings, it helps to understand the basic terminology. Atherosclerotic cardiovascular disease (ASCVD) is the medical term for the buildup of plaque—a waxy substance made of cholesterol, fat, calcium, and other materials—inside the walls of the arteries. Over time, this plaque can harden, narrow the arteries, and restrict blood flow to the heart. If a plaque ruptures or erodes, it can trigger a blood clot that causes a heart attack or stroke.
Coronary artery calcium (CAC) scoring is a test that uses a computed tomography (CT) scan to measure the amount of calcified (hardened) plaque in the coronary arteries—the blood vessels that supply the heart muscle. The test produces a score that helps doctors estimate a person's burden of atherosclerosis.
CAC scoring has emerged as a particularly useful tool because it is noninvasive, quick, and provides a direct measurement of plaque, unlike blood tests that only infer risk. The review notes that CAC scoring is now widely used for ASCVD risk stratification, meaning it helps doctors place patients into low, intermediate, or high risk categories for future heart events. A patient with a CAC score of zero, for example, has a very low short-term risk of a heart attack, while higher scores correspond to greater risk.
How This Review Was Conducted
This article is a narrative review published on February 12, 2020, in Current Cardiology Reports (Volume 22, Issue 4, Article number 21; DOI: 10.1007/s11886-020-1267-9). The authors, affiliated with the University of Arizona, reviewed the recent body of scientific literature on sex differences in plaque deposition, CAC scoring, and cardiovascular mortality.
Rather than conducting a new clinical trial with new patients, the authors synthesized findings from multiple existing studies that examined how plaque composition and calcium distribution differ between men and women. They specifically focused on studies that linked CAC patterns to long-term cardiovascular outcomes, including death from heart disease. The goal was to identify evidence-based recommendations for improving risk stratification, particularly for women.
Key Findings: How Men and Women Differ
The review highlights a striking paradox in cardiovascular risk between the sexes. On the surface, men appear to have more plaque: studies consistently show that men have higher overall CAC burdens than women, even when age and other risk factors are similar. However, this apparent protection in women is misleading.
Here are the core findings in plain language:
- Men have higher calcium scores overall. When researchers sum up all the calcified plaque in the coronary arteries, men typically come out with higher numbers than women at any given age.
- Women's plaque is different in composition. Compared to men, women have coronary plaque that is more lipid-rich (high in fats), more dense, and less calcified. In other words, women's plaque is softer and oilier—and not as easily detected on a calcium scan.
- Women face a plaque erosion risk. The review reports that women are more likely to develop plaque erosions—a condition where the surface of the plaque wears away, exposing the inner contents to the bloodstream. This erosion can trigger a blood clot and a heart attack even when the plaque itself is not heavily calcified.
- Non-calcified plaque carries greater event risk. The soft, non-calcified plaque that dominates in women poses a higher immediate risk for cardiovascular events compared to stable, heavily calcified plaque.
This contrast means that a woman with a "normal" or low CAC score could still be carrying a substantial burden of dangerous, non-calcified plaque that the scan simply does not capture well. The authors emphasize that the pathophysiology—the underlying disease process—of ASCVD is genuinely different in women when compared to men, and that risk assessment tools need to account for these biological differences.
The Danger of Non-Calcified Plaque in Women
Let's look more closely at why plaque composition matters for survival. Calcified plaque is essentially scar tissue with calcium—it is stable and less likely to suddenly rupture. Non-calcified plaque, by contrast, is a fragile, fatty deposit with a thin fibrous cap that can break open or erode, exposing its contents to the blood.
The review notes that women are more likely than men to experience plaque erosion as the mechanism of a heart attack. In plaque erosion, the protective layer of cells on the artery wall is lost, and a clot forms over the exposed surface. This type of blockage is often less severe in terms of physical narrowing, yet it can still cause a major heart attack—sometimes even a fatal one.
Because women's plaque is more lipid-rich and less calcified, a standard CAC scan—which specifically measures calcium—can underestimate the true atherosclerotic burden in a woman's arteries. This is one of the most concerning gaps in current clinical practice. A woman could have a low CAC score yet still face substantial risk from soft plaque that is not visible on the calcium scan.
The authors also emphasize that this is not just a theoretical concern. Multiple studies have now shown that the pathophysiology and associated risks of ASCVD differ between women and men, and that these differences manifest in measurable ways: different plaque composition, different distribution patterns, and different outcomes.
Sex-Specific CAC Patterns and Mortality Risk
Even within the calcium that is detectable, the review identifies specific distribution patterns in women that are linked to increased cardiovascular mortality. These are important details because they suggest that the location and arrangement of calcium matter, not just the total score.
Several studies identified the following CAC characteristics in women as markers of elevated mortality risk:
- Number of lesions involved: Women with calcium deposits scattered across multiple coronary artery segments have a higher risk of dying from cardiovascular disease, even if the total calcium score is modest.
- CAC volume: The total volume of calcium in the arteries, a measurement related to but distinct from the traditional Agatston score, is another predictor of mortality in women.
- Lesion size: As individual calcium deposits grow larger, the risk of cardiovascular death increases for women.
- Increasing lesion size and number over time: The review specifically warns that progression in both the size and number of CAC lesions carries increased mortality risk for women.
These findings point to a critical clinical message: for women, it is not enough to look at a single total CAC score and conclude "low risk." The pattern of calcium distribution matters, and increasing plaque burden across multiple lesions should raise a red flag for providers.
Clinical Implications: The Case for Sex-Adjusted Scoring
So what should change in clinical practice? The review makes a clear recommendation: the current approach to CAC scoring should be adjusted to account for sex differences.
The evidence reviewed favors the use of sex-adjusted CAC cutoffs for women. Because women generally have lower overall CAC burdens than men—even when their actual risk is similar or higher—using the same numerical thresholds for both sexes can misclassify women. A CAC score that would be considered "moderately elevated" in a man might actually represent a much greater relative burden in a woman, simply because women's arteries tend to be smaller and their baseline calcium levels lower.
The authors suggest that revised, sex-specific scoring systems would help to better risk stratify patients, especially those deemed intermediate risk—the gray zone where treatment decisions are most difficult. Intermediate-risk patients are those whose 10-year risk of a heart event falls in the middle range (roughly 5% to 20%), and doctors often struggle with whether to prescribe cholesterol-lowering medications or other aggressive therapies for them. A more accurate, sex-adjusted CAC score could help push these decisions in the right direction.
Beyond the score itself, the review urges providers to recognize the specific CAC patterns that signal elevated mortality risk in women:
- Increasing lesion size
- Increasing number of lesions
- Greater CAC volume
- The presence of non-calcified plaque (which may require additional imaging beyond CAC scoring)
By being aware of these patterns, providers can identify high-risk women earlier and intervene with preventive therapies—such as statins, blood pressure control, and lifestyle changes—potentially reducing cardiovascular deaths.
Limitations of This Review
It's important to acknowledge the limitations of this article. First, it is a narrative review, not a meta-analysis or a new prospective study. The authors synthesized findings from existing research, but the abstract does not specify the exact number of studies reviewed, the combined patient population, or the follow-up durations across studies. This means the strength of the conclusions depends on the quality of the underlying studies.
Second, while the review makes a strong case for sex-adjusted CAC scoring, it does not present a specific new scoring algorithm or validated numerical cutoffs for women. The recommendation is directional—"we should recalibrate"—rather than prescriptive.
Third, the review focuses on CAC and plaque characteristics but does not delve into other important risk factors—such as diabetes, hypertension, smoking, or inflammatory markers—that also interact with sex to influence cardiovascular outcomes. The relationship between CAC and mortality is powerful, but it does not tell the whole story.
Finally, because much of the underlying data comes from observational studies, it cannot fully prove cause and effect. The association between certain CAC patterns and increased mortality in women is well documented, but the degree to which aggressive risk-factor modification would alter those outcomes requires interventional trials.
Recommendations for Patients and Providers
What can patients take away from this research? Here are practical recommendations based on the review's conclusions:
- Know that a "normal" calcium score is not a guarantee. Especially for women, a low CAC score does not rule out the presence of dangerous non-calcified plaque. If you have symptoms or strong risk factors, talk to your doctor about whether additional testing—such as a coronary CT angiography or stress testing—is warranted.
- Ask about your calcium pattern, not just your score. If you have had a CAC scan, ask your provider about the number of lesions, the volume of calcium, and whether the plaque appears calcified or non-calcified. These details matter, particularly for women.
- If you are intermediate risk, advocate for further evaluation. The review specifically suggests that sex-adjusted CAC scoring can help risk stratify intermediate-risk patients. If you fall into this category, ask whether a CAC scan—and a sex-aware interpretation of it—would help clarify your treatment plan.
- Do not ignore cardiac symptoms because you are "low risk." Women experience heart attacks differently and often with less typical symptoms. The review's findings reinforce that women's plaque behaves differently—it is more prone to erosion—so symptoms like chest tightness, unusual fatigue, or shortness of breath deserve prompt medical attention.
- Focus on prevention regardless of your score. A healthy diet, regular physical activity, blood pressure control, cholesterol management, and smoking cessation remain the foundation of cardiovascular risk reduction for both men and women. A calcium score is a risk marker, not a destiny.
For providers, the review's message is clear: be aware that CAC scoring was largely developed and validated with male-predominant populations, and apply sex-specific interpretation. Look beyond the total score to lesion number, size, and volume. Consider additional imaging when a woman's clinical risk seems higher than her CAC score suggests. And incorporate the knowledge that women's plaque is more lipid-rich and erosion-prone into clinical counseling.
Frequently Asked Questions
What is a coronary artery calcium (CAC) score?
A CAC score is a number from a CT scan that measures calcified plaque in the heart's arteries. Higher scores generally mean more hardened plaque and higher risk of future heart problems. A score of zero indicates very low short-term risk, but the review notes that non-calcified plaque can still be present.
Why might a woman have a low calcium score but still be at risk?
Women tend to have more lipid-rich, non-calcified plaque that is softer and less visible on standard calcium scans. So a low CAC score may underestimate a woman's true plaque burden. This type of plaque is more prone to erosion, which can trigger a heart attack even without heavy calcification.
How does plaque differ between men and women?
Men generally have higher total calcium scores. Women's plaque is more lipid-rich, dense, and less calcified, making it softer and more fragile. Women are also more likely to experience plaque erosion, where the plaque surface wears away, which can cause blood clots and heart attacks.
What CAC patterns in women signal higher cardiovascular mortality risk?
The review identifies several patterns: calcium deposits scattered across multiple coronary segments, larger individual lesions, increasing lesion size and number over time, and greater total calcium volume. These markers were linked to higher risk of dying from cardiovascular disease in women, even with modest total scores.
Should calcium score thresholds be different for women?
Yes. The authors recommend sex-adjusted CAC cutoffs because women generally have lower overall calcium levels than men, even when actual risk is similar or higher. Using the same numerical thresholds for both sexes can misclassify women, especially those in the intermediate-risk category.
If I have symptoms but a low calcium score, should I seek more testing?
The review suggests a low calcium score does not rule out dangerous non-calcified plaque, especially in women. If you have symptoms like chest tightness, unusual fatigue, or shortness of breath, or have strong risk factors, discuss with your doctor whether additional imaging such as coronary CT angiography or stress testing is warranted.
What should I ask my doctor after a CAC scan?
Ask about the pattern of calcium, not just the total score. Inquire about the number of lesions, the volume of calcium, and whether plaque appears calcified or non-calcified. These details matter particularly for women, and a sex-aware interpretation can help clarify your actual risk and treatment plan.
Should I get a second opinion if my calcium score is low but I'm a woman with heart symptoms?
Yes, a second opinion can be valuable. A low coronary artery calcium score does not rule out dangerous non-calcified plaque, especially in women, whose plaque is often softer and less visible on standard scans. If you have symptoms or strong risk factors, a specialist can review your imaging and assess plaque pattern, including lesion number, size, and volume, which may signal higher risk. Diagnostic Detectives Network provides independent expert second opinions.
Source Information
Original Article Title: Sex Differences in Coronary Artery Calcium and Long-term CV Mortality - PubMed
DOI: 10.1007/s11886-020-1267-9
Authors: Allison Bigeh, Chandana Shekar, and Martha Gulati
Journal: Current Cardiology Reports, Volume 22, Issue 4, Article 21
Publication Date: February 12, 2020
DOI: 10.1007/s11886-020-1267-9
PMID: 32052199
This patient-friendly article is based on peer-reviewed research. The original abstract is indexed on PubMed, a service of the U.S. National Library of Medicine and the National Institutes of Health. The original article is available in full text from Springer. It is provided for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider with questions about your heart health.
