Atherosclerotic disease, including coronary heart disease (CHD), is one of the chronic inflammatory conditions, and an imbalance between pro-inflammatory and anti-inflammatory cytokines plays a role in the process of atherosclerosis. Interleukin (IL)-27, one of the IL-12 family members, is recognized to play a dual role in regulating immune responses with both pro-inflammatory and anti-inflammatory properties. IL-27 is secreted from monocytes, T cells, and endothelial cells, and its expression is upregulated in atherosclerotic plaques. We previously reported that no significant difference was observed in plasma IL-27 levels between patients with stable CHD and those without it. However, the prognostic value of IL-27 levels has not been fully elucidated. We studied the relation of plasma IL-27 levels to cardiovascular events in 402 patients undergoing elective coronary angiography for suspected CHD. We defined cardiovascular events as cardiovascular death, myocardial infarction, unstable angina, stroke, or coronary revascularization. Of the 402 study patients, CHD was present in 209 (52%) patients. Plasma IL-27 levels were not markedly different between patients with CHD and those without it (median 0.23 vs. 0.23 ng/mL). During a follow-up of 7.6 ± 4.5 years, cardiovascular events were observed in 70 patients (17%). In comparison to the 332 patients with no event, the 70 patients who had cardiovascular events showed significantly higher IL-27 levels (median 0.29 vs. 0.22 ng/mL) and more frequently had an IL-27 level of >0.25 ng/mL (59% vs. 40%) (p < 0.01). The Kaplan–Meier analysis demonstrated a lower event-free survival rate in patients with an IL-27 level >0.25 ng/mL than in those with an IL-27 level ≤0.25 ng/mL (p < 0.02). The multivariate Cox proportional hazards regression analysis showed that IL-27 level (>0.25 ng/mL) was a significant predictor for cardiovascular events (hazard ratio: 1.82; 95%CI: 1.13–2.93, p < 0.02), independent of CHD. Thus, high IL-27 levels in plasma were related to an increased risk of further cardiovascular events in patients who underwent elective coronary angiography.

Several cohort studies have reported that the Japanese diet is associated with reduced cardiovascular disease mortality. However, the results were not always consistent, and most of those studies conducted dietary surveys around 1990. We investigated the association between the Japanese diet and coronary artery disease (CAD) in 802 patients undergoing coronary angiography. The Japanese diet score was defined as the sum of scores of the intakes of fish, soy products, vegetables, seaweed, fruits, and green tea. CAD was found in 511 patients, of whom 173 had myocardial infarction (MI). Intakes of fish, soy products, vegetables, seaweed, fruits, and green tea were lower in patients with CAD, especially in those with MI, than in those without CAD. As a result, the Japanese diet score was significantly lower in patients with CAD than in those without CAD (p < 0.001). To clarify the association between the Japanese diet and CAD, the 802 study patients were divided into three tertiles by the Japanese diet score. The proportion of CAD decreased with the Japanese diet score, reaching 72% in patients at T1 (lowest score), 63% at T2, and 55% at T3 (highest) (p < 0.05). The proportion of MI also decreased with the Japanese diet score, reaching 25% at T1, 24% at T2, and 15% at T3 (p < 0.05). In a multivariate analysis, compared with T1, the adjusted odds ratios for CAD and MI were 0.41 (95% confidence interval [CI]: 0.26–0.63) and 0.61 (95% CI: 0.38–0.99) for T3, respectively. Thus, the Japanese diet was found to be inversely associated with CAD in Japanese patients undergoing coronary angiography.

Excessive apoptosis is known to be a common feature of atherosclerotic lesions. Fortilin is recognized to have potent antiapoptotic properties. An increased fortilin expression was demonstrated in atherosclerotic lesions, and fortilin knockout mice developed less atherosclerosis. However, no study has reported blood fortilin levels in patients with coronary artery disease (CAD). We investigated plasma fortilin levels in 384 patients undergoing coronary angiography. CAD severity was evaluated as the numbers of stenotic vessels and segments. CAD was found in 208 patients (one-vessel (1VD), n = 86; two-vessel (2VD), n = 68; and three-vessel disease (3VD), n = 54). Plasma C-reactive protein (CRP) levels were higher in patients with CAD than without CAD (median 0.60 vs. 0.45 mg/L, p < 0.01). Notably, fortilin levels were higher in patients with CAD than without CAD (75.1 vs. 69.7 pg/mL, p < 0.02). A stepwise increase in fortilin was found according to the number of stenotic vessels: 69.7 in CAD(−), 71.1 in 1VD, 75.7 in 2VD, and 84.7 pg/mL in 3VD (p < 0.01). Fortilin levels also correlated with the number of stenotic segments (r = 0.16) and CRP levels (r = 0.24) (p < 0.01). In a multivariate analysis, fortilin levels were independently associated with 3VD. The odds ratio for 3VD was 1.93 (95%CI = 1.01–3.71) for a high fortilin level (>70.0 pg/mL). Thus, plasma fortilin levels in patients with CAD, especially those with 3VD, were found to be high and to be associated with the severity of CAD.

TGF-β is recognized as playing a protective role against atherosclerosis. Endoglin is a receptor for TGF-β, and its expression is upregulated in atherosclerotic plaques. Endoglin is secreted from the cell membrane into the circulation as a soluble form (sEng). We previously reported that plasma sEng levels were low in patients with coronary artery disease (CAD). However, the prognostic value of sEng levels has not been clarified. We investigated the association between plasma sEng levels and cardiovascular events in 403 patients who had an elective coronary angiography and were then followed up. Cardiovascular events were defined as cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or coronary revascularization. Of the 403 patients, 209 (52%) had CAD. Plasma sEng levels were lower in patients with CAD than in those without CAD (median 4.26 vs. 4.41 ng/mL, p < 0.025). During a mean follow-up period of 7.5 ± 4.5 years, cardiovascular events occurred in 79 patients. Compared with 324 patients without events, 79 with events had lower sEng levels (3.95 vs. 4.39 ng/mL) and more often had an sEng level < 3.9 ng/mL (47% vs. 28%) (p < 0.02). A Kaplan–Meier analysis showed lower event-free survival in patients with sEng < 3.9 ng/mL than in those with ≥3.9 ng/mL (p < 0.02). In a multivariate Cox proportional hazards analysis, the sEng level (<3.9 ng/mL) was an independent predictor of cardiovascular events (hazard ratio: 1.59; 95%CI: 1.01–2.49). Furthermore, only among the 209 patients with CAD, the sEng level was also a predictor of further cardiovascular events (hazard ratio: 2.07; 95%CI: 1.24–3.45). Thus, low plasma sEng levels were found to be associated with an increased risk of cardiovascular events in patients with CAD and patients undergoing coronary angiography.

Vinculin and talin-1, which are cytoskeletal proteins affecting focal adhesions, were reported to be down-expressed in atherosclerotic lesions. Recently, we reported high concentrations of plasma talin-1 in patients with coronary artery disease (CAD). However, blood vinculin concentrations in CAD patients have not been clarified. Plasma vinculin concentrations as well as talin-1 were studied in 327 patients in whom coronary angiography was performed. CAD was proven in 177 patients (1-vessel, n = 79; 2-vessel, n = 57; 3-vessel disease, n = 41). However, vinculin concentrations were not markedly different between the CAD(-) and CAD groups (median 122.5 vs. 119.6 pg/mL, p = 0.325) or among patients with CAD(-), 1-, 2-, and 3-vessel diseases (122.5, 112.8, 107.9, and 137.2 pg/mL, p = 0.202). In contrast, talin-1 concentrations were higher in CAD than the CAD(-) group (0.29 vs. 0.23 ng/mL, p = 0.006) and increased stepwise in the number of stenotic vessels: 0.23 in CAD(-), 0.28 in 1-vessel, 0.29 in 2-vessel, and 0.33 ng/mL in 3-vessel disease (p = 0.043). No correlation was observed between vinculin and talin-1 concentrations. In multivariate analysis, vinculin concentrations were not a factor for CAD. In conclusion, plasma vinculin concentrations in patients with CAD were not high and were not associated with the presence or severity of CAD.