Low vitamin K status, high sclerostin and mortality risk of stable coronary heart disease patients

Aim: We explored whether matrix Gla protein (MGP, natural calcification inhibitor) and sclerostin (glycoprotein responsible for osteoblast differentiation) interact in terms of mortality risk in coronary patients. Methods: 945 patients after myocardial infarction and/or coronary revascularization were followed in a prospective study. All-cause death, fatal or nonfatal cardiovascular events and heart failure hospitalizations were registered. Results: Either high desphospho-uncarboxylated MGP (dp-ucMGP) or high sclerostin were independently associated with 5-year all-cause/cardiovascular mortality. However, we observed an additional mortality risk in the coincidence of both factors. Concomitantly high dp-ucMGP (≥884 pmol/l) plus sclerostin (≥589 ng/l) were associated with increased all-cause mortality risk compared with ‘normal’ concentration s of both factors (HRR 3.71 [95% CI: 2.07–6.62, p < 0.0001]), or if only one biomarker has been increased. A similar pattern was observed for fatal, but not for nonfatal cardiovascular events. Conclusion: Concomitantly high MGP and sclerostin indicate increased mortality risk, which probably reflects their role in cardiovascular calcifications.

The role of cardiovascular calcifications in COVID-19

Background Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. Purpose The principal aim was to evaluate the association of coronary artery calcium (CAC) and total thoracic calcium on in-hospital mortality in COVID-19 patients. Then, to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by CAC. Methods 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included in the SCORE COVID-19 registry (calcium score for COVID-19 Risk Evaluation). At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. A specific sub analysis on CAC was performed stratifying the patients in three groups: (a) “clinical CAD” (prior revascularization history), (b) “subclinical CAD” (CAC &gt;0), (c) “No CAD” (CAC=0). In-hospital mortality was the primary endpoint, while a composite of myocardial infarction and cerebrovascular accident (MI/CVA) was the secondary one. Results Non-survivors compared to survivors had higher coronary artery [(487.7±565.3 vs 207.7±406.8, p&lt;0.001)], aortic valve [(322.4±390.9 vs 98.2±250.7 mm2, p&lt;0.001)] and thoracic aorta [(3786.7±4225.5 vs 1487.6±2973.1 mm2, p&lt;0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046 - 1.637, p=0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200 - 3.251, p=0.007) resulted to be independent predictors of in-hospital mortality. In the sub - analysis increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p&lt;0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p&lt;0.001) were observed from the No CAD to the clinical CAD groups. Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds ≤100, 101–400 and &gt;400, respectively, p&lt;0.001) Conclusion Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk. Cardiovascular calcifications may represent a bystander of an impaired vascular reserve, both microvascular and endothelial, but also a sign of vascular senescence. Therefore, it can be considered an index of biological frailty, likely more accurate than age and other risk factors. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Associations and outcomes of cardiovascular calcifications by computed tomography in atrial fibrillation patients

Background Coronary (CAC), mitral annular (MAC), aortic valve (AVC) and thoracic aortic (TAC) calcifications are known imaging biomarkers for cardiovascular risk in the general population. Despite this, their prognostic value are not well established in atrial fibrillation (AF) patients who have elevated risk for cardiovascular events. Purpose We assessed the associated factors and outcomes of cardiovascular calcifications detected by computed tomography (CT) in AF patients undergoing pulmonary vein isolation (PVI). Methods Consecutive AF patients enrolled in a prospective PVI registry during 2014–2018 with CT performed within 1-year of their procedure were reviewed for the presence of cardiovascular calcifications on CT. Risk factors and outcomes for each type of cardiovascular calcifications were analyzed in univariable and multivariable regression models. Results Amongst 3604 AF patients, there were 2238 (62.1%), 308 (8.6%), 572 (15.9%) and 1048 (29.1%) patients with CAC, MAC, AVC and TAC respectively. Factors independently associated with these cardiovascular calcifications are listed in Table 1. During mean follow-up of 2.8±1.6 years, there were 97 (2.7%) all-cause deaths, and 158 (4.4%) major adverse cardiovascular events (MACE). Forest plots of unadjusted and adjusted hazards ratios of cardiovascular calcifications at predicting these outcomes are shown in Figure 1. Conclusion Cardiovascular calcifications especially CAC are prevalent in AF patients, and share common risk factors with cardiovascular events, except for female being protective for CAC and AVC but having higher risk of MAC and TAC. Although all cardiovascular calcifications were associated with death and MACE in unadjusted analyses, only CAC remained so for both outcomes in adjusted analyses. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Heart Foundation of New Zealand Table 1 Figure 1

The hidden interplay between sex and COVID-19 mortality: the role of cardiovascular calcification

Recent clinical and demographical studies on COVID-19 patients have demonstrated that men experience worse outcomes than women. However, in most cases, the data were not stratified according to gender, limiting the understanding of the real impact of gender on outcomes. This study aimed to evaluate the disaggregated in-hospital outcomes and explore the possible interactions between gender and cardiovascular calcifications. Data was derived from the sCORE-COVID-19 registry, an Italian multicentre registry that enrolled COVID-19 patients who had undergone a chest computer tomography scan on admission. A total of 1683 hospitalized patients (mean age 67±14 years) were included. Men had a higher prevalence of cardiovascular comorbidities, a higher pneumonia extension, more coronary calcifications (63% vs.50.9%, p<0.001), and a higher coronary calcium score (391±847 vs. 171±479 mm3, p<0.001). Men experienced a significantly higher mortality rate (24.4% vs. 17%, p=0.001), but the death event tended to occur earlier in women (15±7 vs. 8±7 days, p= 0.07). Non-survivors had a higher coronary, thoracic aorta, and aortic valve calcium score. Female sex, a known independent predictor of a favorable outcome in SARS-CoV2 infection, was not protective in women with a coronary calcification volume greater than 100 mm3. There were significant differences in cardiovascular comorbidities and vascular calcifications between men and women with SARS-CoV2 pneumonia. The differences in outcomes can be at least partially explained by the different cardiovascular profiles. However, women with poor outcomes had the same coronary calcific burden as men. The presumed favorable female sex bias in COVID-19 must therefore be reviewed in the context of comorbidities, especially cardiovascular ones.

Cardiovascular calcifications in kidney transplant recipients

Vascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

IntroductionCardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECG-triggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk.Methods and analysisIn a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600).Ethics and disseminationThe Institutional Review Boards of the participating hospitals decided that the Medical Research Involving Human Subjects Act does not apply. Findings will be published in peer-reviewed journals and presented at conferences.Trial registration numberNCT03206333.