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Excessive apoptosis and its insufficient clearance is characteristic of atherosclerotic plaques. Fortilin has potent antiapoptotic property and is abundantly expressed in atherosclerotic plaques. Fortilin-deficient mice had less atherosclerosis with more macrophage apoptosis. Recently, we reported that plasma fortilin levels were high in patients with coronary artery disease (CAD). However, its prognostic value has not been elucidated. We investigated plasma fortilin levels and major adverse cardiovascular events (MACE) in 404 patients (mean age 68 ± 12 years; 276 males) undergoing coronary angiography for suspected CAD. MACE was defined as cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or coronary revascularization. Of the 404 patients, 218 (54%) had CAD. Plasma fortilin levels were higher in patients with CAD than without CAD (median 74.9 vs. 70.9 pg/mL, p < 0.05). During a mean follow-up of 5.7 ± 4.2 years, MACE was observed in 59 (15%) patients. Notably, patients with MACE had higher fortilin levels (median 83.0 vs. 71.4 pg/mL) and more often had fortilin level > 80.0 pg/mL (54% vs. 36%) than those without MACE (p < 0.025). A Kaplan-Meier analysis showed lower event-free survival in patients with fortilin > 80.0 pg/mL than in those with ≤ 80.0 pg/mL (p < 0.001). In multivariate Cox proportional hazards analysis, fortilin level (> 80.0 pg/mL) was an independent predictor of MACE (hazard ratio: 2.29, 95%CI: 1.36-3.85, p < 0.002). Among the 218 patients with CAD, fortilin level was also a significant predictor of MACE (hazard ratio: 2.48; 95%CI: 1.34-4.61, p < 0.005). Thus, high plasma fortilin levels were found to be associated with cardiovascular events in patients with CAD as well as those undergoing coronary angiography., Competing Interests: Declarations. Conflict of interest: Our study has no conflicts of interest to disclose., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Degradation of vascular extracellular matrix is important in atherosclerosis. Cysteine protease legumain is upregulated in atherosclerotic plaques. We recently reported that plasma legumain levels are high in patients with complex coronary lesions. This study investigated the association between legumain levels and cardiovascular events in 372 patients undergoing coronary angiography. Patients with acute coronary syndrome were excluded. Of the 372 patients, 225 had coronary artery disease (CAD). During a mean follow-up of 7.0 ± 4.3 years, cardiovascular events occured in 62 patients. Compared with 310 patients without events, 62 with events tended to have higher prevalence of complex lesions (15% vs. 10%). Notably, patients with events had higher legumain levels (median 5.51 vs. 4.90 ng/mL, P < 0.01) than those without events. A Kaplan-Meier analysis showed lower event-free survival in patients with legumain > 5.0 ng/mL than in those with ≤ 5.0 ng/mL (P < 0.01). In multivariate Cox regression analysis, legumain level was an independent predictor of cardiovascular events. The hazard ratio for legumain > 5.0 ng/mL for cardiovascular events was 2.18 (95%CI = 1.27-3.77, P < 0.01). Only among 225 patients with CAD, patients with events had higher legumain levels (5.49 vs. 4.73 ng/mL) than without events (P < 0.02). Legumain level was also a predictor of cardiovascular events in patients with CAD. Thus, high plasma legumain levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography and those with stable CAD., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Endosialin, also known as tumor endothelial marker-1, is a transmembrane glycoprotein that plays a role in inflammation and tumor progression. Endosialin is upregulated in atherosclerotic lesions. To elucidate the association between blood endosialin levels and cardiovascular events, we measured plasma endosialin levels in 389 patients undergoing coronary angiography who were followed up for a mean follow-up of 6.4 ± 4.2 years for cardiovascular events (cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or need for coronary revascularization). Of the 389 patients, 223 had coronary artery disease (CAD). No significant difference was found in plasma endosialin levels between patients with and without CAD (median 0.92 vs. 0.92 ng/mL). During the follow-up, cardiovascular events occurred in 62 patients. Compared with patients without events, those with events had higher endosialin levels (1.12 vs. 0.89 ng/mL), and more often had endosialin level of > 1.1 ng/mL (53% vs. 31%) (P < 0.01). A Kaplan-Meier analysis showed lower event-free survival in patients with endosialin > 1.1 ng/mL than those with ≤ 1.1 ng/mL (P < 0.01). In a multivariate Cox regression analysis, endosialin > 1.1 ng/mL was an independent predictor of cardiovascular events (hazard ratio = 2.00; 95%CI = 1.21-3.32; P < 0.01). Thus, high plasma endosialin levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Vanin-1 is a pantetheinase that hydrolyzes pantetheine to pantothenic acid and cysteamine. Vanin-1 has become recognized to be associated with oxidative stress and inflammation. In animal models, vanin-1 was reported to accelerate atherosclerosis. However, no study has reported blood vanin-1 concentrations in patients with coronary artery disease (CAD). We investigated plasma vanin-1 concentrations in 388 patients undergoing elective coronary angiography for suspected CAD. Patients with acute coronary syndrome were excluded. Of the 388 study patients, CAD was found in 207 patients [1-vessel (1-VD), n = 88; 2-vessel (2-VD), n = 66; and 3-vessel disease (3-VD), n = 53]. Plasma vanin-1 concentrations were higher in patients with CAD than in those without CAD (median 0.59 vs. 0.46 ng/mL, P < 0.005). Vanin-1 concentrations in patients without CAD and those with 1-VD, 2-VD, and 3-VD were 0.46, 0.58, 0.57, and 0.61 ng/mL, respectively, and were highest in 3-VD (P < 0.05). A high vainin-1 concentration (> 0.48 ng/mL) was found in 46% of patients without CAD, 61% of 1-VD, 65% of 2-VD, and 66% of 3-VD (P < 0.01). Vanin-1 concentrations significantly correlated with the number of stenotic coronary segments (r = 0.14, P < 0.02). In the multivariate analysis, vanin-1 concentration was a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.63 (95%CI = 1.04-2.55) for the high vanin-1 concentration of > 0.48 ng/mL. Thus, plasma vanin-1 concentrations in patients with CAD were found to be high and to be associated with the presence and severity of CAD., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events., (© 2021. Springer Japan KK, part of Springer Nature.)

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8 months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71-1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49-0.94) and had a CHA 2 DS 2 -VASc score  < 3 (HR 0.66 [vs. CHA 2 DS 2 -VASc score ≥ 3], 95% CI 0.43-0.98]). The 2-year risk reduction achieved by ablation may be small among Japanese patients, but AF ablation may benefit those with paroxysmal AF and a CHA 2 DS 2 -VASc score < 3.

Nesfatin-1 is a recently identified anorexigenic peptide mainly secreted from the brain and adipose tissue. Although nesfatin-1 may have pro-inflammatory and apoptotic properties, the association between plasma nesfatin-1 levels and coronary artery disease (CAD) has not been clarified yet. We investigated plasma nesfatin-1 levels in 302 patients undergoing elective coronary angiography. Of the 302 study patients, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, and 56 had 3-vessel disease. Compared with 130 patients without CAD, 172 with CAD had higher plasma nesfatin-1 levels (median 0.21 vs. 0.17 ng/mL, P < 0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of > 50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-vessel, 0.21 in 2-vessel, and 0.22 ng/mL in 3-vessel disease (P < 0.05). A high nesfatin-1 level (> 0.19 ng/mL) was found in 43% of patients with CAD(-), 55% of those with 1-vessel, 55% of those with 2-vessel, and 68% of those with 3-vessel disease (P < 0.05). Nesfatin-1 levels significantly correlated with the number of > 50% stenotic coronary segments (r = 0.14, P < 0.02). In multivariate analysis, plasma nesfatin-1 levels were a significant factor for CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.71 (95% CI 1.01-2.91) for high nesfatin-1 level of > 0.19 ng/mL (P < 0.05). Thus, plasma nesfatin-1 levels were found to be high in patients with CAD and were associated with CAD independent of atherosclerotic risk factors, suggesting that high nesfatin-1 levels in patients with CAD may play a role in the development of coronary atherosclerosis.