Change in the association between coffee intake and ischemic heart disease in an international ecological study from 1990 to 2018.

In previous observational studies, the association between coffee intake and risk of cardiovascular disease has reversed from positive to negative over time. This long-term international ecological study examined whether the association between coffee intake and mortality and incidence rates of ischemic heart disease (IHD) changed between 1990 and 2018 using multiple coherent data. We obtained data on coffee intake per capita, IHD mortality and incidence rates per 100,000 population, and socioeconomic and lifestyle indicators for each country from various publicly available databases. We integrated and analyzed data from 147 countries with populations of ≥ 1 million. We employed a linear mixed model analysis to assess the association between coffee intake and IHD mortality and incidence rates by year. The mean global coffee intake increased (p < 0.001), whereas IHD mortality (p < 0.001) and incidence (p = 0.073) decreased. In all models, the interaction between coffee intake and year showed a significant inverse association for IHD mortality and incidence rates (p < 0.001 for all). The country-level association between coffee intake and IHD mortality and incidence rates between 1990 and 2018 was stronger in the negative direction.

Regular egg consumption at breakfast by Japanese woman university students improves daily nutrient intakes: open-labeled observations.

BACKGROUND AND OBJECTIVES: Eggs, an important source of high-quality protein, contain a variety of key nutrients and antioxidants. Here we conducted an intervention study to evaluate whether the additional consumption of one egg per day would affect the daily nutritional intakes and blood antioxidant status in Japanese woman university students. METHODS AND STUDY DESIGN: For 4 weeks, the 14 subjects were provided a nutritious breakfast including one boiled egg, and they were asked to keep a daily dietary record. RESULTS: The subjects' daily energy intake during the intervention did not differ compared to the baseline, whereas the protein energy ratio and cholesterol intake were significantly increased. The subjects' consumption of confectionery during the intervention was significantly decreased compared to the pre-trial period. The total score of adherence to the food-based Japanese dietary guidelines for a healthy diet during the intervention was higher than that at baseline. The analysis of fasting blood samples showed that the subjects' serum lipids levels were not altered, whereas their malondialdehyde modified low-density lipoprotein (MDA-LDL) levels and the oxidative susceptibility of LDL were significantly reduced after the intervention. More importantly, serum folic acid levels were significantly increased. CONCLUSIONS: Our results suggest that regular egg consumption at breakfast can help improve the daily nutritional status and dietary habits and also ameliorate certain indices of antioxidant status in young women.

Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease.

AIM: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated. METHODS: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening. RESULTS: CAD was found in 224 patients (1-vessel [1-VD], n=92; 2-vessel [2-VD], n=65; 3-vessel disease [3-VD], n=67). No significant difference was found in the FGF-21 levels between 224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21 levels in 4 groups of CAD(-), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0 pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference did not reach statistical significance. PAD was found in 38 patients. Compared to the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%), especially 3-VD (P＜0.001). FGF-21 levels were lower in patients with PAD than in those without PAD (0.0 vs. 30.7 pg/mL, P＜0.02). In multivariate analysis, the FGF-21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD was 2.13 (95%CI=1.01-4.49) for a low FGF-21 level (＜15.6 pg/mL). CONCLUSION: No significant difference was found in the FGF-21 levels between patients with and without CAD. However, FGF-21 levels were low in patients with PAD, and were a factor for PAD independent of atherosclerotic risk factors.

Plasma interleukin-27 levels in patients with coronary artery disease.

Interleukin (IL)-27, one of cytokines in the IL-12 family, is considered to have both pro- and anti-inflammatory properties. However, blood IL-27 levels in coronary artery disease (CAD) have not been fully elucidated yet. This cross-sectional study was done to elucidate the association between blood IL-27 levels and CAD.We investigated plasma IL-27 and high-sensitivity C-reactive protein (hsCRP) levels in 274 consecutive patients who underwent elective coronary angiography for suspected CAD. CAD was present in 177 patients [30 acute coronary syndrome (ACS) and 147 stable CAD]. Compared with 97 patients without CAD, 177 patients with CAD had higher IL-27 (median 0.26 vs 0.22 ng/mL, P < .05) and higher hsCRP (0.98 vs 0.41 mg/L, P < .001) levels. However, there was no significant difference in IL-27 levels among 3 groups of ACS, stable CAD, and CAD(-) (0.26, 0.25, and 0.22 ng/mL), whereas hsCRP levels were significantly higher in ACS and stable CAD than in CAD(-) (2.09, 0.91 vs 0.41 mg/L, P < .001) and were highest in ACS. IL-27 levels tended to increase with the number of >50% stenotic coronary vessels: 0.22 in CAD(-), 0.22 in 1-vessel disease, 0.31 in 2-vessel disease, and 0.27 ng/mL in 3-vessel disease (P < .05). A stepwise increase in hsCRP levels was also found: 0.41 in CAD(-), 0.75 in 1-vessel, 1.05 in 2-vessel, and 1.85 mg/L in 3-vessel disease (P < .001). Plasma hsCRP levels significantly (r = 0.35), but IL-27 levels weakly (r = 0.15), correlated with the number of stenotic coronary segments. In multivariate analysis, both IL-27 and hsCRP levels were independent factors associated with CAD. However, hsCRP, but not IL-27, was also a factor for ACS.While plasma IL-27 levels were high in patients with CAD, these levels were an independent factor for only CAD, not ACS, and weakly correlated with the severity of CAD. Our results suggest that IL-27 is unlikely to be a good biomarker reflecting the severity of CAD or the presence of ACS, or to play a major role in the progression of CAD.

Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations.

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.

The Effect of the Consumption of Egg on Serum Lipids and Antioxidant Status in Healthy Subjects.

The egg is a nutrient-dense food and contains a number of antioxidants. The consumption of eggs has been considered to improve the balance of diets, although its impact on serum cholesterol levels has been a matter of concern in many countries. Here, we conducted a pilot study to investigate whether daily additional consumption of an egg might affect serum lipid profiles and also antioxidant status in healthy subjects. Fourteen male subjects were provided with breakfasts including a boiled egg for 4 wk. At the end of intervention, serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were unchanged, despite the significant increase in the intake of dietary cholesterol. In contrast, a significant increase in high-density lipoprotein cholesterol (HDL-C) and a reduction of the LDL-C/HDL-C ratio were observed. Interestingly, the malondialdehyde modified-LDL (MDA-LDL)/LDL-C ratio and the oxidizability of LDL were significantly reduced. Serum total antioxidant capacity value after the intervention period was higher than at baseline. These data indicate that consuming one egg per day for 4 wk as breakfast in addition to a normal diet does not affect serum lipids, and suggests that it may improve serum antioxidant status in healthy males.

Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro.

The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 µg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression.

Green tea catechins prevent low-density lipoprotein oxidation via their accumulation in low-density lipoprotein particles in humans.

Green tea is rich in polyphenols, including catechins which have antioxidant activities and are considered to have beneficial effects on cardiovascular health. In the present study, we investigated the effects of green tea catechins on low-density lipoprotein (LDL) oxidation in vitro and in human studies to test the hypothesis that catechins are incorporated into LDL particles and exert antioxidant properties. In a randomized, placebo-controlled, double-blind, crossover trial, 19 healthy men ingested green tea extract (GTE) in the form of capsules at a dose of 1 g total catechin, of which most (>99%) was the gallated type. At 1 hour after ingestion, marked increases of the plasma concentrations of (-)-epigallocatechin gallate and (-)-epicatechin gallate were observed. Accordingly, the plasma total antioxidant capacity was increased, and the LDL oxidizability was significantly reduced by the ingestion of GTE. We found that gallated catechins were incorporated into LDL particles in nonconjugated forms after the incubation of GTE with plasma in vitro. Moreover, the catechin-incorporated LDL was highly resistant to radical-induced oxidation in vitro. An additional human study with 5 healthy women confirmed that GTE intake sufficiently increased the concentration of gallated catechins, mainly in nonconjugated forms in LDL particles, and reduced the oxidizability of LDL. In conclusion, green tea catechins are rapidly incorporated into LDL particles and play a role in reducing LDL oxidation in humans, which suggests that taking green tea catechins is effective in reducing atherosclerosis risk associated with oxidative stress.

Estimated Dietary Polyphenol Intake and Major Food and Beverage Sources among Elderly Japanese.

Estimating polyphenol intake contributes to the understanding of polyphenols' health benefits. However, information about human polyphenol intake is scarce, especially in the elderly. This study aimed to estimate the dietary intake and major sources of polyphenols and to determine whether there is any relationship between polyphenol intake and micronutrient intake in healthy elderly Japanese. First, 610 subjects (569 men, 41 women; aged 67.3 ± 6.1 years) completed food frequency questionnaires. We then calculated their total polyphenol intake using our polyphenol content database. Their average total polyphenol intake was 1492 ± 665 mg/day, the greatest part of which was provided by beverages (79.1%). The daily polyphenol intake differed largely among individuals (183-4854 mg/day), also attributable mostly to beverage consumption. Coffee (43.2%) and green tea (26.6%) were the major sources of total polyphenol; the top 20 food items accounted for >90%. The polyphenol intake did not strongly correlate with the intake of any micronutrient, suggesting that polyphenols may exert health benefits independently of nutritional intake. The polyphenol intake in this elderly population was slightly higher than previous data in Japanese adults, and beverages such as coffee and green tea contributed highly to the intake.

Polyphenol Intake from Beverages in Japan over an 18-Year Period (1996-2013): Trends by Year, Age, Gender and Season.

An association between the dietary intake of polyphenols and human health has been shown in many epidemiological studies. Since beverages are rich sources of polyphenols, we aimed to evaluate the polyphenol intake from beverages in Japanese individuals with a focus on differences according to year, age, gender and season. More than 10,000 Japanese male and female subjects aged 1-99 y old participated in this survey every year from 1996 to 2013, and their beverage consumption and amount of polyphenol intake were calculated. Polyphenol intake from beverages in Japan showed no tendency to increase or decrease over the 18-y period, and the major sources of polyphenols in Japanese daily life were coffee and green tea. Polyphenol intake was larger in participants with higher age up to 59 y old in both male and female subjects. There was a slight difference in polyphenol intake by gender, with adult males consuming more polyphenols than adult females. Polyphenols were consumed slightly more in the winter than the summer, although the seasonal difference in polyphenol intake was not large. Our results suggest that polyphenol intake from beverages is influenced by age rather than gender or season in Japan, and may not have changed over time, at least over the 18-y period beginning in 1996 in Japan.