Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.

PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.

Importance: It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk. Objective: To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk. Design, Setting, and Participants: A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa. Interventions: Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins. Main Outcomes and Measures: The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. Results: When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%). Conclusions and Relevance: Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02104817.

Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

Prevalence and Predictors of Subclinical Micronutrient Deficiency in German Older Adults: Results from the Population-Based KORA-Age Study.

Subclinical micronutrient deficiency in older adults is associated with chronic age-related diseases and adverse functional outcomes. In Germany, the older population is at risk of insufficient micronutrient intake, but representative studies on micronutrient status in old and very old adults are scarce. This study's objectives were to estimate the prevalence of subclinical vitamin D, folate, vitamin B12 and iron deficiencies among older adults, aged 65 to 93, from the KORA-Age study in Augsburg, Germany (n = 1079), and to examine associated predictors, using multiple logistic regression. Serum concentrations of 25-hydroxyvitamin D (25OHD), folate, vitamin B12, and iron were analyzed. The prevalence of subclinical vitamin D and vitamin B12 deficiencies were high, with 52.0% and 27.3% of individuals having low 25OHD (<50 nmol/L) and low vitamin B12 concentrations (<221 pmol/L), respectively. Furthermore, 11.0% had low iron (men <11.6 µmol/L, women <9.0 µmol/L) and 8.7% had low folate levels (<13.6 nmol/L). Common predictors associated with subclinical micronutrient deficiency included very old age, physical inactivity, frailty and no/irregular use of supplements. Subclinical micronutrient deficiency is a public health concern among KORA-Age participants, especially for vitamins D and B12. The predictors identified provide further rationale for screening high-risk subgroups and developing targeted public health interventions to tackle prevailing micronutrient inadequacies among older adults.

Coffee consumption and NAFLD: a community based study on 1223 subjects.

BACKGROUND: Objective of the present cross-sectional study was to investigate the impact of caffeine consumption on fatty liver and serum alanine aminotransferase (ALT) concentrations in a random population sample. METHODS: All subjects (n = 1452; 789 women, 663 men; average age 42.3 ± 12.8 years) underwent ultrasonographic examination of the liver and completed a standardized questionnaire regarding personal and lifestyle data, in particular relating to coffee consumption and past medical history. In addition, anthropometric data were documented and laboratory examinations performed. Statistical interpretation of the data was performed descriptively and by means of bivariate and multivariate analysis. RESULTS: Data of the present study demonstrated a significant association between hepatic steatosis male gender (p < 0.0001), advanced age (p < 0.0001) and elevated body-mass index (BMI; p < 0.0001). No association between caffeine consumption and fatty liver was identified. An association between caffeine consumption and elevated serum ALT concentrations was not identified. CONCLUSIONS: The findings of the present study provide no evidence for an association between caffeine consumption and either the prevalence of hepatic steatosis or serum ALT concentrations.

Associations between calcium and vitamin D supplement use as well as their serum concentrations and subclinical cardiovascular disease phenotypes.

BACKGROUND: Supplementation of calcium (Ca) and vitamin D for the prevention of osteoporosis is frequently found in Western countries. Recent re-analyses of clinical trials observed a higher risk of myocardial infarction and stroke in subjects taking Ca (+vitamin D) supplements, although the underlying mechanisms are not clear. OBJECTIVE: Thus, we analyzed the associations between Ca and vitamin D supplementation as well as serum concentrations of Ca and 25-hydroxyvitamin D (25(OH)D) and subclinical cardiovascular disease (CVD) phenotypes, namely intima-media thickness, ankle-brachial-index (ABI), intermittent claudication, and atrial fibrillation (AF). DESIGN: Data of 1601 participants aged 50-81 years of the population-based cross-sectional Cooperative Health Research in the Region of Augsburg (KORA) F4 study in Germany were analyzed. Logistic and linear regression models were used to estimate odds ratios (OR) (95% confidence intervals (CI)) and ß-estimates (p-values), respectively. RESULTS: Regular Ca supplementation showed a significant positive association with the presence of AF after multivariable adjustment (OR = 3.89; 95% CI 1.28-11.81). Higher serum 25(OH)D concentrations were independently associated with a lower prevalence of asymptomatic peripheral arterial disease as assessed by ABI measurements (ß = 0.007; p = 0.01). No other significant associations between supplementation or serum concentrations of Ca or vitamin D and CVD phenotypes were identified. CONCLUSIONS: Although based on few cases the finding of a significant higher prevalence of AF in Ca supplement users hints at one possible mechanism that may contribute to an increased risk of myocardial infarction and stroke. The observed association between serum 25(OH)D and ABI supports results from other studies.

Vitamin E supplementation is associated with lower levels of C-reactive protein only in higher dosages and combined with other antioxidants: The Cooperative Health Research in the Region of Augsburg (KORA) F4 study.

The aim of the present study was to examine the association between intake of five common antioxidative nutrients from supplements and medications (vitamin E, vitamin C, carotenoids, Se, and Zn) and levels of high-sensitivity C-reactive protein (hs-CRP) in the general population. For this purpose, a total of 2924 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-8) were investigated cross-sectionally. Intake of dietary supplements and medication during the last 7 d was recorded in a personal interview, when participants were asked to show product packages of ingested preparations. Linear regression models were calculated; first, the exposure to regular nutrient intake was treated with a binary response (yes/no); then regularly ingested amounts were divided into quartiles to examine dose-response relationships. Effect of single v. combined supplementation of antioxidants was assessed through the inclusion of interaction terms into the models. Regular intake of any of the five investigated antioxidants per se was not associated with hs-CRP levels. However, dose-response analyses revealed that participants who regularly ingested more than 78 mg vitamin E/d, which corresponds to the upper quartile, had 22% lower hs-CRP levels (95% CI 0·63, 0·97) compared to those of persons who were not exposed to any vitamin E supplementation. Stratified analyses showed that this association was found only in persons who took vitamin E in combination with other antioxidants. The combined supplementation of vitamin E with other antioxidants could thus be a promising strategy for the prevention of inflammation-related diseases in the general population, if further studies could confirm that the proposed association is causal.

Objectively measured physical activity and vitamin D status in older people from Germany.

BACKGROUND: To analyse the seasonal relationship of objectively measured physical activity with vitamin D status in older persons from Southern Germany (latitude: 48.4°N). METHODS: Physical activity was assessed in 1193 community-dwelling individuals aged ≥65 years (58% men) over 1 week using a thigh-worn accelerometer. Furthermore, the 25-hydroxyvitamin D (25(OH)D) level was measured. Least-square means of 25(OH)D serum levels were calculated for quartiles of average daily walking duration stratified by season and adjusted for gender, age and body mass index. Participants with prescribed vitamin D supplements were excluded. RESULTS: Statistically significant linear associations between quartiles of walking duration with 25(OH)D serum levels were observed in all seasons but not in summer. Differences in 25(OH)D serum levels between the first and the last quartile were 3.42 ng/mL (p=0.002) in winter, 2.80 ng/mL (p=0.009) in spring, and 3.60 ng/mL (p<0.001) in the fall. The proportion of vitamin D insufficiency (<20 ng/mL) even in the highest quartile of walking duration was 45.3% in winter, 73.7% in spring, 17.4% in summer and 16.5% in the fall. CONCLUSIONS: Although a positive dose-response relationship was seen between walking duration and the 25(OH)D serum level for most seasons, vitamin D insufficiency was still very prevalent even in high-active persons during all seasons.

Seasonality of vitamin D status in older people in Southern Germany: implications for assessment.

BACKGROUND: from a clinical and public health perspective, it is important to understand the influence of seasonality on the serum vitamin D level to adequately assess and interpret an individual measurement. Therefore, the aim of this study was to analyse the effects of seasonal conditions on 25-hydroxyvitamin D (25(OH)D) serum levels in a population-based cohort of older people. METHODS: between March 2009 and April 2010 the 25(OH)D serum level was assessed in 1,418 community-dwelling individuals living in Germany aged ≥65 years (56.7% men) with no subscribed vitamin D supplementation. Least-square means of monthly 25(OH)D serum levels with 95% confidence intervals (CI) were estimated, adjusted for gender, age and body mass index. Additionally, the proportion of vitamin deficiency (<20 ng/ml), insufficiency (20-<30 ng/ml) and sufficiency (30 ng/ml or higher) were estimated for each month. Finally, mean values of daily total global solar radiation and daylight were calculated for each month. RESULTS: the minimum 25(OH)D serum level was observed in March with 15.4 ng/ml (SD = 6.56 ng/ml) and the maximum in August with 25.6 ng/ml (SD = 6.59 ng/ml). Compared with daylight and global solar radiation the progression over the year was similar but delayed by ∼2 months. The proportion of vitamin D deficiency, insufficiency and sufficiency were 78.8, 19.2 and 1.9% in March and 16.1, 63.4 and 20.5% in August, respectively. CONCLUSION: vitamin D insufficiency was very common in this cohort and showed a strong seasonal effect with lowest values in March.

Sfrp5 correlates with insulin resistance and oxidative stress.

BACKGROUND: Secreted frizzled-related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin-sensitising and anti-inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro-inflammatory antagonist wingless-type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee. MATERIAL AND METHODS: Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed. RESULTS: At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA-IR; r = 0·32, P < 0·05) and with the oxidative stress markers 8-isoprostane (r = 0·44, P < 0·01) and nitrotyrosine (r = 0·52, P < 0·001). Adiponectin showed inverse correlations with several indices of insulin resistance (e.g. HOMA-IR, Stumvoll index; all P < 0·05) and a direct correlation with the anti-atherogenic apolipoprotein A-I (r = 0·56, P < 0·001). Coffee did not affect serum concentrations of Sfrp5. Serum Wnt5a concentrations were below the detection limit (0·02 ng/mL) in 81% of the study participants. CONCLUSIONS: In contrast to obese mouse models, serum Sfrp5 was directly related to HOMA-IR and oxidative stress in humans, but not with apolipoproteins, and thus, associations differed from those found for circulating adiponectin. These differences between Sfrp5 and adiponectin might be explained by differences in the investigated species.

Low levels of serum 25-hydroxyvitamin D are associated with increased risk of myocardial infarction, especially in women: results from the MONICA/KORA Augsburg case-cohort study.

CONTEXT AND OBJECTIVE: A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system. Therefore, we thought to prospectively assess the association between serum 25-hydroxyvitamin D, the most commonly used index of vitamin D status, and incident coronary heart disease. DESIGN, SETTING, AND PATIENTS: We measured serum levels of 25[OH]D in 1783 healthy middle-aged subjects (964 men, 819 women) in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg studies. A total of 298 coronary heart disease cases were identified over a mean follow-up period of 11 yr. RESULTS: After adjustment for age, survey, and season of blood sampling, the hazard ratio (HR) and 95% confidence interval comparing tertile extremes of serum levels of 25[OH]D was 0.32 (0.16-0.65) (P for trend = 0.001) in women and 0.56 (0.38-0.82) (P for trend = 0.005) in men. Further adjustment for traditional cardiovascular risk factors slightly attenuated the association in women [HR 0.39 (0.18-0.84); P for trend = 0.013], whereas it became nonsignificant in men [HR 0.76 (0.49-1.17); P for trend = 0.215]. After additional adjustment for C-reactive protein, IL-6, soluble intercellular adhesion molecule-1, and interferon-γ-inducible protein-10, the association still remained significant in women [HR 0.42 (0.19-0.93); P for trend = 0.028], and it was further reduced in men [HR 0.84 (0.52-1.35); P for trend = 0.461]. CONCLUSION: Our findings suggest that higher vitamin D levels are associated with decreased risk of coronary heart disease. This effect is more pronounced in women than in men. Further clinical and experimental studies are needed to investigate the sex differences and whether vitamin D supplementation could contribute to the prevention of coronary heart disease.

Reduction of monocyte chemoattractant protein 1 and macrophage migration inhibitory factor by a polyphenol-rich extract in subjects with clustered cardiometabolic risk factors.

Inflammation is a hallmark of the metabolic syndrome, which also contributes to a pro-atherogenic state. NF-κB activation, a critical step in regulating inflammatory reactions, can be inhibited by polyphenol (PF) extracts, at least in vitro. In the present study, we set out to study whether a PF-rich extract could attenuate the chronic inflammatory state and/or an acute immune response in vivo in subjects with clustered metabolic risk factors. A commercially available, PF-rich extract (500 mg daily) or placebo was administered for 4 weeks to thirty-four subjects with two or more metabolic risk factors using a randomised, double-blind, cross-over design. During the final study visit, an acute inflammatory challenge (lipopolysaccharide (LPS) 1 ng/kg body weight) was administered to a random subgroup of subjects (PF-rich extract (n 12) and placebo (n 12)). The PF-rich extract modestly reduced the inflammatory chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage migration inhibitory factor (MIF) (MCP-1 - 6.5 % (PF, median 116 (interquartile range 97-136) pg/ml v. placebo, median 124 (interquartile range 105-153) pg/ml; P < 0.05); MIF - 10.8 % (PF, median 2512 (interquartile range 1898-3972) pg/ml v. placebo, median 2814.5 (interquartile range 2296-3852) pg/ml; P < 0.05); however, other measured markers of inflammation and cardiometabolic disease, such as C-reactive protein, IL-6, HDL-cholesterol, adiponectin and oxidised LDL, remained unaffected. Following the LPS challenge, we found a statistically significant 48 % reduction of MCP-1 production in the PF-rich extract group (n 12) v. placebo (n 12) over 6 h (PF 766 (sd 155) v. placebo 1466 (sd 989) ng/ml; P < 0.05, area under the curve). In conclusion, short-term oral administration of the PF-rich extract caused a modest anti-inflammatory effect in subjects with clustered metabolic risk factors. Further dose-ranging studies are needed to evaluate whether and to what extent PF-rich extracts can be used to reduce the pro-inflammatory state in subjects with metabolic diseases at increased cardiovascular risk.

Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial.

BACKGROUND: Coffee consumption is associated with a decreased risk of type 2 diabetes. Suggested mechanisms underlying the association have included attenuation of subclinical inflammation and a reduction in oxidative stress. OBJECTIVE: The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake, subclinical inflammation, oxidative stress, glucose, and lipid metabolism. DESIGN: Habitual coffee drinkers (n = 47) refrained for 1 mo from coffee drinking; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d (150 mL/cup). Blood samples were analyzed by gas chromatography-mass spectrometry, bead-based multiplex technology, enzyme-linked immunosorbent assay, or immunonephelometry. RESULTS: Coffee consumption led to an increase in coffee-derived compounds, mainly serum caffeine, chlorogenic acid, and caffeic acid metabolites. Significant changes were also observed for serum concentrations of interleukin-18, 8-isoprostane, and adiponectin (medians: -8%, -16%, and 6%, respectively; consumption of 8 compared with 0 cups coffee/d). Serum concentrations of total cholesterol, HDL cholesterol, and apolipoprotein A-I increased significantly by 12%, 7%, and 4%, respectively, whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8% and 9%, respectively (8 compared with 0 cups coffee/d). No changes were seen for markers of glucose metabolism in an oral-glucose-tolerance test. CONCLUSIONS: Coffee consumption appears to have beneficial effects on subclinical inflammation and HDL cholesterol, whereas no changes in glucose metabolism were found in our study. Furthermore, many coffee-derived methylxanthines and caffeic acid metabolites appear to be useful as biomarkers of coffee intake.

Vitamin C supplement use may protect against gallstones: an observational study on a randomly selected population.

BACKGROUND: Animal experiments have shown a protective effect of vitamin C on the formation of gallstones. Few data in humans suggest an association between reduced vitamin C intake and increased prevalence of gallstone disease. The aim of this study was to assess the possible association of regular vitamin C supplementation with gallstone prevalence. METHODS: An observational, population-based study of 2129 subjects aged 18-65 years randomly selected from the general population in southern Germany was conducted. Abdominal ultrasound examination, completion of a standardized questionnaire, compilation of anthropometric data and blood tests were used. Data were collected in November and December 2002. Data analysis was conducted between December 2005 and January 2006. RESULTS: Prevalence of gallstones in the study population was 7.8% (167/2129). Subjects reporting vitamin C supplementation showed a prevalence of 4.7% (11/232), whereas in subjects not reporting regular vitamin C supplementation, the prevalence was 8.2% (156/1897). Female gender, hereditary predisposition, increasing age and body-mass index (BMI) were associated with increased prevalence of gallstones. Logistic regression with backward elimination adjusted for these factors showed reduced gallstone prevalence for vitamin C supplementation (odds ratio, OR 0.34; 95% confidence interval, CI 0.14 to 0.81; P = 0.01), increased physical activity (OR 0.62; 95% CI, 0.42 to 0.94; P = 0.02), and higher total cholesterol (OR 0.65; 95% CI, 0.52 to 0.79; P < 0.001). CONCLUSION: Regular vitamin C supplementation and, to a lesser extent, increased physical activity and total cholesterol levels are associated with a reduced prevalence of gallstones. Regular vitamin C supplementation might exert a protective effect on the development of gallstones.

Varespladib methyl, an oral phospholipase A2 inhibitor for the potential treatment of coronary artery disease.

Varespladib methyl is an oral secretory phospholipase A2 inhibitor that is being developed by Anthera Pharmaceuticals Inc for the potential treatment of coronary artery disease, acute coronary syndrome and inflammation. Varespladib methyl is a prodrug that is rapidly metabolized to varespladib, and both compounds are able to potently inhibit the enzymes of the human secretory phospholipase groups IIa, V and X, which play a pivotal role in atherosclerotic disease and inflammation. Phase II clinical trials of varespladib methyl in patients with coronary artery disease, rheumatoid arthritis, asthma and ulcerative colitis revealed that the drug was well tolerated. Varespladib methyl did not demonstrate a good efficacy profile in patients with rheumatoid arthritis, asthma and ulcerative colitis, whereas in patients with coronary artery disease, varespladib methyl consistently reduced LDL-cholesterol levels (elevated LDL-cholesterol levels are a marker of increased cardiovascular risk). At the time of publication, phase II trials were ongoing in patients with acute coronary syndrome and in patients undergoing elective percutaneous coronary intervention, and a phase III trial in patients with acute coronary syndrome was planned. Varespladib methyl could represent a novel therapy for the treatment of cardiovascular disease, although the efficacy, safety profile and advantages of this drug compared with existing therapeutic options would need to be established in upcoming phase III trials.

The effect of marine n-3 fatty acids in different doses on plasma concentrations of Lp-PLA2 in healthy adults.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging independent risk factor for cardiovascular disease (CVD). Lp-PLA(2) can be modified by lipid lowering drugs, but it is unknown whether diet can reduce plasma levels of Lp-PLA(2). AIM OF THE STUDY: The aim of the trial was to study the effect of marine n-3 polyunsaturated fatty acids (PUFA) on plasma Lp-PLA(2) levels in healthy subjects. METHODS: Sixty healthy subjects were randomized to a moderate dose (2 g) of n-3 PUFA, a high dose (6.6 g) of n-3 PUFA or olive oil (control) daily for 12 weeks. Plasma Lp-PLA(2) was measured at baseline and after the interventions. RESULTS: Plasma Lp-PLA(2) levels were unchanged in all three groups before and after the supplements. Neither did the results differ between groups. There was no correlation between the content of n-3 PUFA in platelets or granulocytes or plasma Lp-PLA(2). CONCLUSION: Marine n-3 PUFA had no effect on plasma levels of Lp-PLA(2) in healthy adults and relatively young people.

Lipoprotein-associated phospholipase A2 concentrations in plasma are associated with the extent of coronary artery disease and correlate to adipose tissue levels of marine n-3 fatty acids.

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor for cardiovascular disease. In the present study, plasma levels of Lp-PLA(2) were measured in patients (n=301) admitted to elective coronary angiography because of suspected coronary artery disease (CAD). In a multiple linear regression analysis, the degree of CAD (0-, 1-, 2- or 3-vessel disease) and plasma LDL cholesterol significantly correlated to Lp-PLA(2) levels. Also the content of the marine n-3 fatty acid, eicosapentaenoic acid (EPA) in adipose tissue, a measure of long-term intake of seafood independently and inversely (r=-0.18, p<0.01) correlated with plasma levels of Lp-PLA(2). The results support the view that Lp-PLA(2) may relate to CAD and that intake of marine n-3 fatty acids might reduce plasma Lp-PLA(2) suggesting another mechanism by which n-3 fatty acids could reduce the risk of cardiovascular disease.