Sylvain Pagé

Sex-related discordance between aortic valve calcification and hemodynamic severity of aortic stenosis : is valvular fibrosis the explanation?

Rationale: Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification loads than men for the same AS hemodynamic severity. Objective: We, thus, aimed to assess sex differences in aortic valve fibrocalcific remodeling. Methods and Results: One hundred and twenty-five patients underwent Doppler echocardiography and multidetector computed tomography within 3 months before aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed, and fibrosis degree was determined. Sixty-four men and 39 women were frequency matched for age, body mass index, hypertension, renal disease, diabetes mellitus, and AS severity. Mean age (75±9 years), mean gradient (41±18 mm Hg), and indexed aortic valve area (0.41±0.12 cm2/m2) were similar between men and women (all P≥0.18). Median aortic valve calcification (1973 [1124–3490] Agatston units) and mean valve weight (2.36±0.99 g) were lower in women compared with men (both P<0.0001). Aortic valve calcification density correlated better with valve weight in men (r2=0.57; P<0.0001) than in women (r2=0.26; P=0.0008). After adjustment for age, body mass index, aortic valve calcification density, and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (P=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (P=0.01), and Masson trichrome staining revealed a greater proportion of dense connective tissue (P=0.02) in women compared with men. Conclusions: In this series of patients with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared with men. These findings suggest that the pathophysiology of AS and thus potential targets for drug development may be different according to sex.

Angiotensin Receptor Blockers Are Associated with Reduced Fibrosis and Interleukin-6 Expression in Calcific Aortic Valve Disease

Background: Calcific aortic valve disease (CAVD) is a chronic disorder characterized by the mineralization of the aortic valve and involving fibrosis. Objectives: In this work we sought to determine if the fibrotic component of the remodeling process of CAVD was related to the use of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). Methods: In 477 patients with CAVD, the aortic valve was examined by histology. A semiquantitative score of fibrosis was generated and associations with clinical/cardiometabolic variables examined. In a subset of 103 patients the aortic valve was available to study the infiltration by inflammatory cells and expression of interleukin-6 (IL-6) by quantitative real-time PCR. Results: The fibrosis score of the aortic valve was independently related to the hemodynamic severity of CAVD measured by echocardiography. The fibrotic score of the aortic valve was also related to the expression of IL-6. The use of ARBs but not of ACEi was associated with a lower fibrosis score of the aortic valve even after correction for covariates. In addition, patients under ARBs had lower aortic valve inflammation and expression of IL-6. Conclusions: These findings suggest that ARBs may alter the fibrotic process of the aortic valve in CAVD, possibly by lowering tissue inflammation.

Lipoprotein lipase in aortic valve stenosis is associated with lipid retention and remodelling

Calcific aortic valve disease (CAVD) is a chronic disorder characterized by a fibrocalcific remodelling. It is suspected that lipid retention within the aortic valve may be one important mechanism participating to aortic valve remodelling. Lipoprotein lipase (LPL) is implicated in lipid metabolism and may play a role in lipid retention within the aortic valve.

What the Cardiologist Should Know About Cardiac Involvement in Behçet Disease

Behçet disease (BD) is a chronic multisystem inflammatory vasculitis affecting mainly young adults and is characterized by a remitting-relapsing course. In North America, the prevalence is 5.2 per 100,000 population. It is believed that cardiac involvement is one of the most severe complications in patients with BD despite its sporadic occurrence, being greatly correlated with mortality.

Transcriptomic Microenvironment of Lung Adenocarcinoma

Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers. Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity. Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant. Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor. Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389–96. ©2016 AACR.