High plasma concentrations of vanin-1 in patients with coronary artery disease.

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.

Association between high plasma levels of legumain and cardiovascular events in patients undergoing coronary angiography.

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.

High plasma levels of endosialin and cardiovascular events in patients undergoing coronary angiography.

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.

Japanese carotenoid database with α- and ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, lycopene, and fucoxanthin and intake in adult women.

Carotenoid intake is associated with low mortality and cancer risks; data on non-provitamin carotenoid intake is limited especially in Asians. We aimed to estimate carotenoid intake in Japanese adult women. Carotenoid content database comprises 196 food items, including 39 fruits, 87 vegetables and mushrooms, and 11 seaweeds, and was established using data from the literature and analyses of foods available in Japan. We surveyed the intake of these foods in Japanese women aged 21-56 years (n=109). Total intake of 7 carotenoids (mean±SD [range]) was 7,450±3,840 (1,160-21,300) µg/day; α-carotene, ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, lycopene, and fucoxanthin represented 4.3%, 23%, 3.4%, 15%, 2.0%, 39%, and 13% of total intake, respectively. Lutein intake was 1,132±686 (294-3,490) µg/day; its best sources were spinach, cucumber, chicken egg, green onion, and Chinese chives, representing 51% of total intake. Lutein can be obtained from a variety of sources. Thus, lutein intake levels did not vary widely among individuals and very few individuals consumed insufficient levels of lutein. Intake of zeaxanthin, lycopene, and fucoxanthin was 149±93 (2-479), 2,890±2,970 (0-17,100), and 980±1,230 (0-5,660) µg/day, respectively. Their intake required rich sources including chicken egg for zeaxanthin (52%); tomato products for lycopene (98%), and wakame seaweed for fucoxanthin (76%). The carotenoid content database including all food items consumed in Japan will be helpful for further investigations on carotenoid intake and its health benefits.

High Plasma Levels of Fortilin in Patients with Coronary Artery Disease.

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.

The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases.

Atherosclerotic disease, such as coronary artery disease (CAD), is known to be a chronic inflammatory disease, as well as an age-related disease. Excessive oxidative stress produced by reactive oxygen species (ROS) contributes to the pathogenesis of atherosclerosis. Sestrin2 is an anti-oxidant protein that is induced by various stresses such as hypoxia, DNA damage, and oxidative stress. Sestrin2 is also suggested to be associated with aging. Sestrin2 is expressed and secreted mainly by macrophages, endothelial cells, and cardiomyocytes. Sestrin2 plays an important role in suppressing the production and accumulation of ROS, thus protecting cells from oxidative damage. Since sestrin2 is reported to have anti-oxidant and anti-inflammatory properties, it may play a protective role against the progression of atherosclerosis and may be a potential therapeutic target for the amelioration of atherosclerosis. Regarding the association between blood sestrin2 levels and atherosclerotic disease, the blood sestrin2 levels in patients with CAD or carotid atherosclerosis were reported to be high. High blood sestrin2 levels in patients with such atherosclerotic disease may reflect a compensatory response to increased oxidative stress and may help protect against the progression of atherosclerosis. This review describes the protective role of sestrin2 against the progression of atherosclerotic and cardiac diseases.

Association between Plasma Follistatin-like Protein 1 Levels and the Presence and Severity of Coronary Artery Disease.

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein known for its role in inflammation. However, plasma FSTL1 levels in patients with coronary artery disease (CAD) have not been fully elucidated. Thus, in this study, we investigated the plasma FSTL1 levels of 350 patients who underwent elective coronary angiography. The severity of CAD was represented as the numbers of > 50% stenotic vessels and segments and the severity score. CAD was detected in 196 patients, of whom 84 had 1-vessel disease (1-VD), 62 had 2-VD, and 50 had 3-VD. Plasma high-sensitivity C-reactive protein (hsCRP) levels were higher in patients with CAD than in those without CAD (median 0.56 versus 0.44 mg/L, P < 0.01). Notably, plasma FSTL1 levels were higher in patients with CAD than in those without CAD (median 4.05 versus 3.47 ng/mL, P < 0.02). A stepwise increase in FSTL1 levels was found depending on the number of > 50% stenotic vessels: 3.47 in CAD (-), 3.74 in 1-VD, 4.42 in 2-VD, and 4.65 ng/mL in 3-VD (P < 0.05). FSTL1 levels also correlated with the number of > 50% stenotic segments and the severity score (r = 0.14 and r = 0.15, respectively, P < 0.005) and hsCRP levels (r = 0.10, P < 0.05). In the multivariate analysis, FSTL1 levels were an independent factor associated with CAD. The odds ratio for CAD was 1.61 (95% CI = 1.01-2.58) for high FSTL1 level of > 3.6 ng/mL (P < 0.05). In conclusion, plasma FSTL1 levels in patients with CAD were found to be high and associated with the presence and severity of CAD, thus, suggesting that FSTL1 may play a role in the progression of coronary atherosclerosis.

Correction to: Dietary intake of total polyphenols and the risk of all-cause and specific-cause mortality in Japanese adults: the Takayama study.

The original version of this article unfortunately contained a mistake.

Dietary intake of total polyphenols and the risk of all-cause and specific-cause mortality in Japanese adults: the Takayama study.

PURPOSE: Several epidemiological studies have demonstrated the health benefits of polyphenols, but the associations between polyphenol intake and mortality including total and major causes of death remain unclear. We investigated the associations between subjects' total polyphenol intake and their mortality from all causes, cardiovascular disease (CVD), cancer, and other causes of death in a population-based cohort study in Japan. METHODS: A total of 29,079 residents of Takayama City, Japan were analyzed. Their dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire (FFQ) in 1992. Mortality was ascertained over the subsequent 16 years. The dietary polyphenol intake was calculated by matching the subjects' food consumption data with our original polyphenol content database. RESULTS: A total of 5339 deaths occurred during the follow-up. After multivariable adjustment, the highest quartile of total polyphenol intake compared with the lowest quartile was significantly associated with a lower risk of all-cause mortality (HR: 0.93, 95% CI: 0.82-0.99, p trend = 0.003). The subjects in the highest quartile showed significantly lower CVD mortality compared to those in the lowest quartile, and among the types of CVD mortality, a strong inverse association was observed for stroke mortality. Inverse associations were also observed for mortality from other causes, specifically digestive disease. The total polyphenol intake was not significantly associated with the risk of cancer mortality. CONCLUSIONS: The results of this prospective study indicate that dietary total polyphenol intake in Japanese is inversely associated with all-cause mortality and mortality from cardiovascular and digestive diseases.

Associations between plasma nesfatin-1 levels and the presence and severity of coronary artery disease.

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.

The Protective Role of Heme Oxygenase-1 in Atherosclerotic Diseases.

Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate ferrous iron, carbon monoxide (CO), and biliverdin, which is subsequently converted to bilirubin. These products have anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-thrombotic properties. Although HO-1 is expressed at low levels in most tissues under basal conditions, it is highly inducible in response to various pathophysiological stresses/stimuli. HO-1 induction is thus thought to be an adaptive defense system that functions to protect cells and tissues against injury in many disease settings. In atherosclerosis, HO-1 may play a protective role against the progression of atherosclerosis, mainly due to the degradation of pro-oxidant heme, the generation of anti-oxidants biliverdin and bilirubin and the production of vasodilator CO. In animal models, a lack of HO-1 was shown to accelerate atherosclerosis, whereas HO-1 induction reduced atherosclerosis. It was also reported that HO-1 induction improved the cardiac function and postinfarction survival in animal models of heart failure or myocardial infarction. Recently, we and others examined blood HO-1 levels in patients with atherosclerotic diseases, e.g., coronary artery disease (CAD) and peripheral artery disease (PAD). Taken together, these findings to date support the notion that HO-1 plays a protective role against the progression of atherosclerotic diseases. This review summarizes the roles of HO-1 in atherosclerosis and focuses on the clinical studies that examined the relationships between HO-1 levels and atherosclerotic diseases.

Plasma Heme Oxygenase-1 Levels and Carotid Atherosclerosis.

Background and Purpose- Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to generate carbon monoxide, biliverdin, and iron. Because these products have antiatherogenic properties, HO-1 may play a protective role against atherosclerosis. However, plasma HO-1 levels in patients with carotid atherosclerosis have not been reported. Methods- We investigated plasma HO-1 levels by ELISA in 136 subjects (age, 66±9 years) undergoing carotid ultrasonography. Results- Of the 136 study subjects, carotid plaque was found in 61 subjects (45%). Compared with 75 subjects without plaque, 61 with plaque were older and predominantly male ( P<0.05). Plasma HO-1 levels were higher in subjects with plaque than in those without plaque (median, 0.56 versus 0.44 ng/mL; P<0.05). The percentage of subjects with HO-1 level >0.50 ng/mL was higher in subjects with plaque than without plaque (66% versus 44%; P<0.025). In multivariate analysis, HO-1 level was a significant factor for carotid plaque independent of atherosclerotic risk factors. Odds ratio for plaque was 2.33 (95% CI, 1.15-4.75) for HO-1 level >0.50 ng/mL. Conclusions- Plasma HO-1 levels were high in subjects with carotid plaques, probably reflecting a protective response against carotid atherosclerosis.

Plasma Soluble Endoglin Levels Are Inversely Associated With the Severity of Coronary Atherosclerosis-Brief Report.

OBJECTIVE: Transforming growth factor-ß inhibits migration and proliferation of endothelial and smooth muscle cells. Endoglin is a transmembrane receptor for transforming growth factor-ß1 and transforming growth factor-ß3. Endoglin is released into blood as a soluble form (soluble endoglin [sEng]), but plasma sEng levels in patients with coronary artery disease (CAD) have not been elucidated. APPROACH AND RESULTS: We measured plasma sEng levels in 244 patients undergoing coronary angiography. The severity of coronary atherosclerosis was evaluated as the numbers of >50% stenotic vessels and segments. CAD was found in 147 patients, of whom 55 had 1-vessel, 42 had 2-vessel, and 50 had 3-vessel disease. Compared with 97 patients without CAD, 147 with CAD had lower sEng levels (median 4.04 versus 4.37 ng/mL; P<0.005). A stepwise decrease in sEng levels was found based on the number of stenotic vessels: 4.37 in CAD(-), 4.23 in 1-vessel, 4.13 in 2-vessel, and 3.74 ng/mL in 3-vessel disease (P<0.005). sEng levels inversely correlated with the number of stenotic segments (r=-0.25; P<0.001). In multivariate analysis, sEng was an independent factor for 3-vessel disease and CAD. Odds ratios for CAD and 3-vessel disease were 0.97 (95% confidence interval, 0.95-0.99; P<0.02) and 0.96 (95% confidence interval, 0.93-0.99; P<0.01) for a 0.1 ng/mL increase in sEng levels, respectively. CONCLUSIONS: Plasma sEng levels were low in patients with CAD, especially 3-vessel disease, and were inversely associated with the severity of coronary atherosclerosis.

Serum gamma-glutamyltransferase is inversely associated with dietary total and coffee-derived polyphenol intakes in apparently healthy Japanese men.

PURPOSE: Serum γ-glutamyltransferase (GGT) has been proposed as a marker of oxidative stress. Here, we examined the association between serum GGT and the dietary intake of polyphenols, which have antioxidant properties. METHODS: A cross-sectional survey including 7960 apparently healthy Japanese men (aged 22-86 years) who participated in health checkups was conducted in Shizuoka, Japan. We analyzed these subjects' clinical serum parameters and lifestyle factors, including dietary polyphenol intake, which was evaluated by a self-administered questionnaire and by matching the subjects' food consumption data with our original polyphenol content database. RESULTS: The average intake of polyphenols was 1157 ± 471 mg/day, and green tea was the largest source of polyphenols at 40%, followed by coffee at 36%. Dividing the population according to quintiles of total polyphenol intake, the difference in polyphenol intake from coffee between the groups was much greater than the difference in polyphenol intake from green tea. The analysis of the association between polyphenol intake and biological parameters showed a significant negative association between polyphenol intake and the levels of systolic and diastolic blood pressure (SBP and DBP), GGT, and alanine aminotransferase (ALT) after adjusting for age, smoking habit, energy intake and alcohol intake. The GGT levels were inversely associated with the polyphenol intake from coffee, but not with that from green tea. Multivariable linear regression analyses demonstrated that the subjects' GGT levels were negatively and independently associated with their polyphenol intake. CONCLUSIONS: The intake of total polyphenol including coffee as a major contributor is inversely associated with the serum GGT concentration in Japanese males.

Potential Anti-Atherosclerotic Properties of Astaxanthin.

Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed.

Association between Plasma Interleukin-27 Levels and Cardiovascular Events in Patients Undergoing Coronary Angiography.

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.

Consumption of polyphenol-rich juar tea increases endothelium-bound extracellular superoxide dismutase levels in men with metabolic syndrome: link with LDL oxidizability.

Endothelium-bound extracellular superoxide dismutase (eEC-SOD), a major antioxidative enzyme in the vasculature, is involved in anti-atherogenesis by inhibiting low-density lipoprotein (LDL) oxidation. The objective was to investigate whether the polyphenol-rich juar tea had beneficial effects on LDL oxidation and eEC-SOD levels in patients with metabolic syndrome (MetS). A total of 20 men with MetS participated in a randomized cross-over trial, comparing consumption of five cups/day of juar tea with that of a polyphenol-poor tea, barley tea, for 4 weeks. Although there was no change in LDL oxidizability after consumption of either tea, juar tea significantly increased eEC-SOD levels by 16% (p < 0.05), whereas barley tea significantly decreased levels by 15% (p < 0.05). It is noteworthy that the changes in eEC-SOD were positively associated with those in LDL oxidizability after tea consumption (r(2) = 0.11, p < 0.05). Tea polyphenols may provide anti-atherosclerotic effects by inhibiting LDL oxidation through EC-SOD bound to the endothelium.

Association between the Japanese Diet and Coronary Artery Disease in Patients Undergoing 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.

Low Plasma Levels of Soluble Endoglin and Cardiovascular Events in Patients Undergoing Coronary Angiography.

TGF-ß is recognized as playing a protective role against atherosclerosis. Endoglin is a receptor for TGF-ß, 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.

Effects of acute strawberry consumption on serum levels of vitamin C and folic acid, the antioxidant potential of LDL and blood glucose response: a randomised cross-over controlled trial.

Strawberry contains many bioactive compounds such as vitamin C and polyphenols as well as folate, a vitamin that is especially important for women of childbearing age. We investigated the effects of the acute consumption of strawberry on the serum levels of vitamin C and folate, and on the antioxidant potential of low-density lipoprotein (LDL). In a randomised, placebo-controlled, double-blind, crossover study, twenty-three healthy female volunteers (age 22⋅5 ± 1⋅4 years) ingested 500 g of a strawberry purée beverage or a sugar content-matched placebo beverage. Blood samples were collected at fasting and at 0⋅5, 1, 2 and 4 h post-ingestion. The serum concentrations of vitamin C and folate were significantly elevated from 0⋅5 to 4 h after the strawberry beverage ingestion (P < 0⋅001); the levels peaked at 2 h, with peak levels of 15⋅0 ± 2⋅5 µg/ml for vitamin C and 14⋅4 ± 7⋅0 ng/ml for folate. Notably, at 1 h after the strawberry beverage ingestion, the LDL oxidation lag time was significantly prolonged (P < 0⋅05), suggesting that the antioxidant potential of LDL was increased. After the ingestion of either beverage, the serum levels of glucose and insulin reached a peak at 0⋅5 h and then quickly returned to baseline levels. These results suggest that strawberries are a useful source of vitamin C and folate and may help enhance the antioxidant potential of LDL in healthy young women.