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Association of citrullination with the progression of aortic stenosis.

ABSTRACT: Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of citrullinated proteins. At baseline, 241 (35.5%) subjects with AV degeneration had a higher rate of anti-CCP antibody positivity (42.7% versus 34.6%, p = 0.035) than those without AV degeneration. Out of the 331 (48.8%) subjects who underwent echocardiographic follow-up, progression of AS was observed in 34 (10.3%) patients, with a higher incidence in the high-positive group compared to the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p = 0.041). On multivariable analysis, high anti-CCP antibody positivity was independently associated with progression to AS (odds ratio: 2.312; 95% confidence interval: 1.006-5.310; p = 0.048). Furthermore, immunohistochemistry and Western blotting revealed increased citrullination in diseased AV compared to normal AV tissue. This study demonstrated that a high positive anti-CCP antibody result is associated with AV degeneration and may be an independent factor for AS progression.

SUBMITTER: Kim AR

PROVIDER: S-EPMC10235071 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Association of citrullination with the progression of aortic stenosis.

Kim Ah-Ram AR Ji Eunhye E Lee Sahmin S Hong Seokchan S Kim Dae-Hee DH Song Jong-Min JM Kang Duk-Hyun DH Song Jae-Kwan JK

Scientific reports 20230601 1

Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of ci ...[more]

PMID: 37264066

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Project description:AimsIn patients with aortic stenosis (AS), the coronary flow reserve decreases even in the absence of epicardial coronary artery stenosis. Systolic coronary flow reversal (SFR) reflecting reduced coronary microcirculation, often seen in patients with severe AS, has a potential negative impact on the pathogenesis of cardiac dysfunction. However, there are limited data on the relationship between the severity of AS and SFR, as well as on the benefits of transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the relationship between the severity of AS and efficacy of TAVI in improving SFR.Methods and resultsConsecutive patients with AS who had undergone TAVI using transoesophageal echocardiography (TEE) from November 2020 to February 2022 were prospectively enrolled. Coronary flow in the left anterior descending artery as well as the aortic valve peak velocities, and the mean aortic valve pressure gradients (AVPGs), indicating the severity of AS, were measured using intraprocedural TEE before and after TAVI. The following parameters were measured as coronary flow: systolic and diastolic peak velocity (cm/s) and systolic and diastolic velocity-time integral (VTI) (cm). SFR was defined as the presence of a reversal coronary flow component in systole. The enrolled patients were classified into two groups according to the presence or absence of SFR before TAVI. A total of 25 patients were included: 13 had SFR and 12 who had no SFR, before TAVI. Patients with SFR had significantly higher aortic valve peak velocities (451.1 ± 45.9 vs. 372.1 ± 52.1 cm/s; P < 0.001) and mean AVPGs (49.2 ± 14.5 vs. 30.3 ± 11.6 mmHg; P = 0.002) than those without. The optimal binary cut-off aortic valve peak velocity values and the mean AVPG associated with the presence of SFR before TAVI were >410.0 cm/s (specificity, 75.0%; sensitivity, 92.3%) and >37.4 mmHg (specificity, 83.3%; sensitivity, 92.3%), respectively. After TAVI, SFR immediately disappeared in 11 of 13 patients with SFR (84.6%). Overall, the systolic coronary VTI significantly increased after TAVI (2.0 ± 4.7 vs. 6.4 ± 3.2 cm, P < 0.001), and this increase was greater in patients with SFR than in those without SFR before TAVI (interaction P = 0.035).ConclusionsSFR was found to be associated with the severity of AS and with a greater increase in systolic coronary flow immediately after TAVI.

Project description:BACKGROUND:Previous studies reported that middle-aged patients with atherogenic lipoprotein-lipid profile exhibit faster progression of aortic valve stenosis (AS). The ratio of apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) reflects the balance between atherogenic and anti-atherogenic lipoproteins. The aim of this study was to examine the association between apoB/apoA-I ratio and AS hemodynamic progression and to determine whether this association varies according to age. METHODS AND RESULTS:A total of 159 patients (66±13 years, 73% men) with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. Hemodynamic progression of AS was determined by the change in peak aortic jet velocity (Vpeak) measured by Doppler-echocardiography between baseline and 2-year follow-up. Patients in the top tertile of apoB/apoA-I ratio (≥0.62) had a faster progression rate of AS compared with those in the bottom/mid tertiles (Vpeak progression: 0.30 [0.09-0.49] versus 0.16 [0.01-0.36] m/s, P=0.02). There was a significant interaction (P=0.007) between apoB/apoA-I ratio and age. Among younger patients (ie, aged <70 years; median value of the cohort), those in the top tertile of apoB/apoA-I ratio had a 3.4-fold faster AS progression compared with those in the bottom/mid tertiles (Vpeak progression: 0.34 [0.13-0.69] versus 0.10 [-0.03-0.31] m/s, P=0.002), whereas there was no significant difference between tertiles in the subgroup of older patients (P=0.83). After comprehensive adjustment, higher apoB/apoA-I ratio was significantly associated with faster AS progression in the subset of younger patients (all, standardized β≥0.36; P≤0.01). CONCLUSIONS:Higher apoB/apoA-I ratio is significantly associated with faster hemodynamic progression of AS in the younger patients. These findings suggest that atherogenic lipid factors may play a crucial role in the pathogenesis of AS in younger patients, but may be are less important in older patients. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT01679431.

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Association of citrullination with the progression of aortic stenosis.

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Association of citrullination with the progression of aortic stenosis.

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