<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03779217</url>
  </required_header>
  <id_info>
    <org_study_id>SecondUNI 17.12.2018</org_study_id>
    <nct_id>NCT03779217</nct_id>
  </id_info>
  <brief_title>Breast Disease and Cardiovascular Disease</brief_title>
  <official_title>BREast Density in Premenopausal Women is Predictive of CARdiovascular Outcomes at 10 Years of Follow-up: the BRECARD Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Campania &quot;Luigi Vanvitelli&quot;</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Campania &quot;Luigi Vanvitelli&quot;</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cardiovascular disease (CVD) occurs less frequently in women than in juvenile men.Frequently&#xD;
      the estrogen deficiency associated with the menopausal state affects cardiovascular outcomes.&#xD;
      In fact, in the post-menopausal state, even younger women may experience an increase in the&#xD;
      rate of ischemic heart disease (IHD). On the other hand, CVD may also occur in premenopausal&#xD;
      young women, due to not well known and/or not clearly investigated mechanisms. In addition,&#xD;
      pre-menopausal women with IHD show atypical symptoms and more frequently myocardial&#xD;
      infarction vs. angina pectoris. In detail, in these patients IHD is frequently due to&#xD;
      mono-vessel coronary heart disease, and to the presence of cardiovascular risk factors such&#xD;
      as hypertension, hyperlipidemia and type 2 diabetes. So, it is clear that all these&#xD;
      pro-atherogenic risk factors which lead to IHD in women, are significantly lower in the&#xD;
      pre-menopausal vs. post-menopausal patients. However, the causes leading to IHD and acute&#xD;
      coronary events in pre-menopausal women remain poorly understood and poorly investigated, and&#xD;
      these factors might be different from the traditional coronary risk factors evident in the&#xD;
      general population. In this context, recently some authors have shown that subcutaneous&#xD;
      abdominal fat affects cardiovascular performance at 1 year of follow-up in patients with&#xD;
      normoglycemia vs. pre-diabetic. Therefore, here authors can hypothesize that in a population&#xD;
      of female subjects, the fat tissue present in the mammary gland and the different degrees of&#xD;
      mammary adipocyte infiltration can somehow invalidate the number of cardiovascular events in&#xD;
      women of childbearing age. In detail, the different distribution of adipose tissue in the&#xD;
      mammary gland can influence the density of the breast, as studied by mammographic&#xD;
      examination, which is used to divide breast density into 4 different categories:&#xD;
&#xD;
        -  Category A: the breast is represented by 80% of adipose tissue and less than 20% by&#xD;
           fibro-glandular tissue.&#xD;
&#xD;
        -  Category B: the breast is represented by adipose tissue in the range of 50-75% and for&#xD;
           the rest by fibro-glandular tissue.&#xD;
&#xD;
        -  Category C: the breast is represented by fatty tissuein the range 25-50% and the rest is&#xD;
           from fibro-glandular tissue&#xD;
&#xD;
        -  Category D: the breast is represented by almost entirely fibro-glandular tissue.&#xD;
&#xD;
      Therefore, in the present study authors correlated the 4 different breast categories with CVD&#xD;
      and 10-year follow-up IHD in women of child-bearing age. In fact, according to authors'&#xD;
      opinion, a breast with higher fat density (category A) might influence the number of adverse&#xD;
      cardiovascular events at 10-year follow-up in asymptomatic women. Thus, pre-menopausal women&#xD;
      with breast tissue in category A (&quot;fatty breast&quot;) as compared to women with prevalence of&#xD;
      fibro-glandular tissue (&quot;non-fatty breast&quot;) may have a higher frequency of adverse cardiac&#xD;
      ischemic events at 10 years of follow-up.&#xD;
&#xD;
      On the other hand, the molecular pathways implied in worse CVD in these cohorts of women are&#xD;
      not fully investigated.&#xD;
&#xD;
      Furthermore, the authors aimed to investigate the expression of inflammatory cytokines and&#xD;
      sodium glucose transporter 2 (SGLT2) protein expression, as markers of over-inflammation, at&#xD;
      level of breast gland in these cohorts of women. Thus, these markers were analyzed in the&#xD;
      breast fat tissue excissed from the fatty vs. non-fatty breast women.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2, 2008</start_date>
  <completion_date type="Actual">February 2, 2021</completion_date>
  <primary_completion_date type="Actual">January 2, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>myocardial infarction</measure>
    <time_frame>10 years</time_frame>
    <description>Authors will evaluated for all follow up duration the number of myocardial infarction</description>
  </primary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">10000</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <condition>Ischemic Heart Disease</condition>
  <arm_group>
    <arm_group_label>group A</arm_group_label>
    <description>In this group there are women in that the mammography shows a breast represented by 80% of adipose tissue and less than 20% by fibro-glandular tissue.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group B</arm_group_label>
    <description>In this group there are women in that the mammography shows a breast represented by adipose tissue in the range of 50-75% and for the rest by fibro-glandular tissue</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group C</arm_group_label>
    <description>In this group there are women in that the mammography shows a breast represented by adipose tissue in the range 25-50% and the rest is from fibro-glandular tissue.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group D</arm_group_label>
    <description>In this group there are women in that the mammography shows a breast represented by almost entirely fibro-ghiandular tissue.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>screening mammography</intervention_name>
    <description>As indicated by international guidelines authors will perform screening mammography in all asymptomatic women.</description>
    <arm_group_label>group A</arm_group_label>
    <arm_group_label>group B</arm_group_label>
    <arm_group_label>group C</arm_group_label>
    <arm_group_label>group D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>mastoplasty and breast fat excission</intervention_name>
    <description>As indicated by guidelines, and in accordance to the breast surgery reduction criteria, the authors will practice a surgical intervention of mastoplasty. During the mastoplasty, authors will remove the breast fat tissue.</description>
    <arm_group_label>group A</arm_group_label>
    <arm_group_label>group B</arm_group_label>
    <arm_group_label>group C</arm_group_label>
    <arm_group_label>group D</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will include asymptomatic women without neoplastic breast disease and&#xD;
        other neoplastic diseases. These patients at enrollment did not have previous history of&#xD;
        cardiovascular and cerebrovascular adverse events. At enrollment all women did not have a&#xD;
        diagnosis of menopausal status.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with indication to receive a screening MiD, patients without breast cancer&#xD;
             diagnosis (previous or recent diagnosis), pre-menopausal status, without inflammatory&#xD;
             chronic disease and other neoplastic diseases. Patients without previous history of&#xD;
             cardiovascular and cerebrovascular adverse events. Patients with indication to receive&#xD;
             a breast reduction surgery (relief of physical pain and discomfort associated with&#xD;
             heavy, pendulous breasts; complain of chronic back and neck pain, headaches, shoulder&#xD;
             pain, deep bra-strap grooves, and rashes beneath both breasts; breast chronically&#xD;
             painful as well, evidence of upper extremity neuropathy and postural changes, along&#xD;
             with intertrigo, maceration, irritation, rashes, and other dermatologic&#xD;
             manifestations; difficulty with many forms of exercise and the inability to find&#xD;
             properly fitting clothe; patients that received a full package of supportive care,&#xD;
             advising on weight loss and managing pain, physiotherapy and assessment for thoracic /&#xD;
             shoulder girdle discomfort).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  aged &lt; 18 years, patients without indication to receive a screening MiD, patients with&#xD;
             breast cancer diagnosis (previous or recent diagnosis), menopausal status,&#xD;
             inflammatory chronic disease, other neoplastic diseases; previous history of&#xD;
             cardiovascular and cerebrovascular adverse events.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Raffaele Marfella</name>
      <address>
        <city>Naples</city>
        <zip>80138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>September 23, 2022</last_update_submitted>
  <last_update_submitted_qc>September 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Campania &quot;Luigi Vanvitelli&quot;</investigator_affiliation>
    <investigator_full_name>Celestino Sardu</investigator_full_name>
    <investigator_title>medical doctor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03779217
org study id: SecondUNI 17.12.2018
nct id: NCT03779217
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Cardiovascular disease (CVD) occurs less frequently in women than in juvenile men.Frequently
      the estrogen deficiency associated with the menopausal state affects cardiovascular outcomes.
      In fact, in the post-menopausal state, even younger women may experience an increase in the
      rate of ischemic heart disease (IHD). On the other hand, CVD may also occur in premenopausal
      young women, due to not well known and/or not clearly investigated mechanisms. In addition,
      pre-menopausal women with IHD show atypical symptoms and more frequently myocardial
      infarction vs. angina pectoris. In detail, in these patients IHD is frequently due to
      mono-vessel coronary heart disease, and to the presence of cardiovascular risk factors such
      as hypertension, hyperlipidemia and type 2 diabetes. So, it is clear that all these
      pro-atherogenic risk factors which lead to IHD in women, are significantly lower in the
      pre-menopausal vs. post-menopausal patients. However, the causes leading to IHD and acute
      coronary events in pre-menopausal women remain poorly understood and poorly investigated, and
      these factors might be different from the traditional coronary risk factors evident in the
      general population. In this context, recently some authors have shown that subcutaneous
      abdominal fat affects cardiovascular performance at 1 year of follow-up in patients with
      normoglycemia vs. pre-diabetic. Therefore, here authors can hypothesize that in a population
      of female subjects, the fat tissue present in the mammary gland and the different degrees of
      mammary adipocyte infiltration can somehow invalidate the number of cardiovascular events in
      women of childbearing age. In detail, the different distribution of adipose tissue in the
      mammary gland can influence the density of the breast, as studied by mammographic
      examination, which is used to divide breast density into 4 different categories:

        -  Category A: the breast is represented by 80% of adipose tissue and less than 20% by
           fibro-glandular tissue.

        -  Category B: the breast is represented by adipose tissue in the range of 50-75% and for
           the rest by fibro-glandular tissue.

        -  Category C: the breast is represented by fatty tissuein the range 25-50% and the rest is
           from fibro-glandular tissue

        -  Category D: the breast is represented by almost entirely fibro-glandular tissue.

      Therefore, in the present study authors correlated the 4 different breast categories with CVD
      and 10-year follow-up IHD in women of child-bearing age. In fact, according to authors'
      opinion, a breast with higher fat density (category A) might influence the number of adverse
      cardiovascular events at 10-year follow-up in asymptomatic women. Thus, pre-menopausal women
      with breast tissue in category A ("fatty breast") as compared to women with prevalence of
      fibro-glandular tissue ("non-fatty breast") may have a higher frequency of adverse cardiac
      ischemic events at 10 years of follow-up.

      On the other hand, the molecular pathways implied in worse CVD in these cohorts of women are
      not fully investigated.

      Furthermore, the authors aimed to investigate the expression of inflammatory cytokines and
      sodium glucose transporter 2 (SGLT2) protein expression, as markers of over-inflammation, at
      level of breast gland in these cohorts of women. Thus, these markers were analyzed in the
      breast fat tissue excissed from the fatty vs. non-fatty breast women.
observational model: Cohort
time perspective: Prospective
measure: myocardial infarction
time frame: 10 years
description: Authors will evaluated for all follow up duration the number of myocardial infarction
arm group label: group A
description: In this group there are women in that the mammography shows a breast represented by 80% of adipose tissue and less than 20% by fibro-glandular tissue.
arm group label: group B
description: In this group there are women in that the mammography shows a breast represented by adipose tissue in the range of 50-75% and for the rest by fibro-glandular tissue
arm group label: group C
description: In this group there are women in that the mammography shows a breast represented by adipose tissue in the range 25-50% and the rest is from fibro-glandular tissue.
arm group label: group D
description: In this group there are women in that the mammography shows a breast represented by almost entirely fibro-ghiandular tissue.
intervention type: Other
intervention name: screening mammography
description: As indicated by international guidelines authors will perform screening mammography in all asymptomatic women.
arm group label: group A
arm group label: group B
arm group label: group C
arm group label: group D
intervention type: Procedure
intervention name: mastoplasty and breast fat excission
description: As indicated by guidelines, and in accordance to the breast surgery reduction criteria, the authors will practice a surgical intervention of mastoplasty. During the mastoplasty, authors will remove the breast fat tissue.
arm group label: group A
arm group label: group B
arm group label: group C
arm group label: group D
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Campania "Luigi Vanvitelli"
investigator full name: Celestino Sardu
investigator title: medical doctor
mesh term: Cardiovascular Diseases
mesh term: Heart Diseases
mesh term: Myocardial Ischemia
mesh term: Coronary Artery Disease
sharing ipd: Undecided