Abstract
Aims
In recent years, microcalcifications identified in routine mammograms were found to be associated with cardiometabolic disease in women. Here, we aimed to systematically evaluate the association of microcalcifications and other mammographic features with cardiometabolic disease risk and mortality in a large screening cohort and to understand a potential genetic contribution.
Methods and results
This study included 57 867 women from a prospective mammographic screening cohort in Sweden (KARMA) and 49 583 sisters. Cardiometabolic disease diagnoses and mortality and medication were extracted by linkage to Swedish population registries with virtually no missing data. In the cardiometabolic phenome-wide association study, we found that a higher number of microcalcifications were associated with increased risk for multiple cardiometabolic diseases, particularly in women with pre-existing cardiometabolic diseases. In contrast, dense breasts were associated with a lower incidence of cardiometabolic diseases. Importantly, we observed similar associations in sisters of KARMA women, indicating a potential genetic overlap between mammographic features and cardiometabolic traits. Finally, we observed that the presence of microcalcifications was associated with increased cardiometabolic mortality in women with pre-existing cardiometabolic diseases (hazard ratio and 95% confidence interval: 1.79 [1.24–2.58], P = 0.002) while we did not find such effects in women without cardiometabolic diseases.
Conclusions
We found that mammographic features are associated with cardiometabolic risk and mortality. Our results strengthen the notion that a combination of mammographic features and other breast cancer risk factors could be a novel and affordable tool to assess cardiometabolic health in women attending mammographic screening.
In recent years, microcalcifications identified in routine mammograms were found to be associated with cardiometabolic disease in women. Here, we aimed to systematically evaluate the association of microcalcifications and other mammographic features with cardiometabolic disease risk and mortality in a large screening cohort and to understand a potential genetic contribution.
Methods and results
This study included 57 867 women from a prospective mammographic screening cohort in Sweden (KARMA) and 49 583 sisters. Cardiometabolic disease diagnoses and mortality and medication were extracted by linkage to Swedish population registries with virtually no missing data. In the cardiometabolic phenome-wide association study, we found that a higher number of microcalcifications were associated with increased risk for multiple cardiometabolic diseases, particularly in women with pre-existing cardiometabolic diseases. In contrast, dense breasts were associated with a lower incidence of cardiometabolic diseases. Importantly, we observed similar associations in sisters of KARMA women, indicating a potential genetic overlap between mammographic features and cardiometabolic traits. Finally, we observed that the presence of microcalcifications was associated with increased cardiometabolic mortality in women with pre-existing cardiometabolic diseases (hazard ratio and 95% confidence interval: 1.79 [1.24–2.58], P = 0.002) while we did not find such effects in women without cardiometabolic diseases.
Conclusions
We found that mammographic features are associated with cardiometabolic risk and mortality. Our results strengthen the notion that a combination of mammographic features and other breast cancer risk factors could be a novel and affordable tool to assess cardiometabolic health in women attending mammographic screening.
| Original language | English |
|---|---|
| Pages (from-to) | 3361–3370 |
| Number of pages | 10 |
| Journal | European Heart Journal |
| Volume | 42 |
| Issue number | 34 |
| DOIs | |
| Publication status | Published - 2 Aug 2021 |
Bibliographical note
Open Access via the OUP Open Access AgreementAcknowledgements: The authors thank all the participants in the KARMA study and personnel for their devoted work during data collection. They also would like to acknowledge Jose ́ Tapia for helping in data management.
Funding: This work was supported by “Ma ̈rit and Hans Rausing’s Initiative Against Breast Cancer” and was financed by the Swedish Research Council (Grant 2018-02547 to K.C.), the Swedish Cancer Society (Grant 19 0266 and 19 0267 to K.C.), FORTE (Grant 2016-00081 to K.C.), and the Karolinska Institutet’s Research Foundation (Grant 2018-02146 to F.G.). F.G. was a Leopoldina Postdoctoral Fellow (Grant No. LPDS 2018-06) funded by the Academy of Sciences Leopoldina. H.Y. was supported by Start-up Fund for high-level talents of Fujian Medical University (Grant .No. XRCZX2020007) and Start-up Fund for Scientific Research, Fujian Medical University (Grant No. 2019QH1002). The funding agency had no role in the study design, data collection, analyses, and data interoperation, in writing the manuscript, or in the decision to submit the manuscript for publication.
Data Availability Statement
Data availabilityAccess to phenotypes, biospecimen and genotypes from the KARMA study can be requested from https://karmastudy.org/contact/data-ac cess/
Keywords
- Mammographic screening
- Cardiometabolic diseases
- Ageing
- BMI
- Microcalcifications
- Breast cancer genetics
Access to Document
- Grassman_etal_EHJ_Mammographic_features_are_VOR
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