Dexamethasone is Associated With a Lower Risk of the Progression of Thoracic Aortic Calcification in Breast Cancer Survivors

Background and Purpose: Breast cancer survivors have an increased cardiovascular risk, and vascular calcification is the pathological basis of cardiovascular disease. Some factors that affect the progression of thoracic aortic calcification (TAC) in survivors are unclear, and this study aims to explore the relationship between dexamethasone or radiotherapy and the progression of TAC in survivors.Materials and Methods: This study included 189 female patients with breast cancer, and they were divided into the progression and non-progression TAC groups. Radiation or dexamethasone doses, and related laboratory parameters were collected.Results: The cumulative dose of dexamethasone was higher [40 (10–180) mg versus 180 (80–270) mg, p < 0.001], and the cycle was longer [4 (1–6) cycles versus 6 (4–8) cycles, p < 0.001] in the non-progression TAC group. The cumulative dose (r = −0.303, p < 0.001) and cycle (r = −0.357, p < 0.001) of dexamethasone were negatively correlated with the level of increased TAC Agatston scores in survivors. Logistic regression analysis showed that dexamethasone was a protective factor for the progression of TAC (p = 0.029, odds ratio = 0.263, 95% confidence interval = 0.08–0.872). However, there wasn’t significant relationship between radiotherapy, radiation dose, follow-up time and the progression of TAC (all p > 0.05). In addition, aorta volume was positively correlated with the level of increased TAC Agatston scores in intensity modulated radiation therapy (r = 0.460, p < 0.001).Conclusion: Dexamethasone is associated with a lower risk of the progression of TAC in breast cancer survivors, and there’s no correlation between radiotherapy and progression of TAC, but the aorta volume may be a predictor of the severity of progression of TAC.

Thoracic Aortic Calcification and Pre-Clinical Hypertension by New 2017 ACC/AHA Hypertension Guidelines

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm3), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference; all trends: p < 0.001). These differences remained consistent after being fully adjusted. Older age (>50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (<60 mL/min/1.73 m2) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.

Abstract P217: Associations Of Adipokine Levels With The Prevalence And Extent Of Valvular And Thoracic Aortic Calcification: The Multi-ethnic Study Of Atherosclerosis

Introduction: Extra-coronary calcification (ECC), a marker of systemic atherosclerosis, is an independent risk factor for incident cardiovascular disease (CVD). Adipokines participate in many cardiometabolic pathways and may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well established. We hypothesized that higher leptin and resistin levels and lower adiponectin levels would be associated with a greater extent of ECC. Methods: We performed a cross-sectional analysis of 1,955 community dwelling adults free of clinical CVD in the MESA cohort. Serum adipokine levels and a cardiac CT scan were obtained at exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin (per 1 SD of log transformed adipokine) with the prevalence and extent of ECC. Results: The mean age of participants was 62±10 years; 50% were women, 40% white, 13% Chinese, 21% Black and 26% Hispanic. In a model adjusted for demographics, we found 1) adiponectin was inversely associated with AVC prevalence and extent; 2) leptin was positively associated with MAC prevalence and extent; and 3) resistin was positively associated with ATAC prevalence and extent and with DTAC prevalence. After full adjustment for BMI and other CVD risk factors ( Table ), adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC or DTAC after full adjustment. Conclusion: In this diverse cohort free from clinical CVD, we found significant associations between selected adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis.

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P&lt;0.001), thoracic aortic calcification (P&lt;0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.