Overall dietary variety and adherence to the Mediterranean diet show additive protective effects against coronary heart disease.

Abstract Background and aim Along with the increasing evidence of the cardioprotective effects of the Mediterranean Diet (MD), the scientific interest and advocacy of dietary variety as a potentially healthy eating habit gradually faded, until its complete oblivion in the latest European cardiovascular prevention guidelines. Our study aims to investigate whether dietary variety adds to the "Mediterranean-ness" of the diet in protecting against coronary heart disease (CHD). Methods and results In this case–control Italian study, data on eating habits were collected from 178 patients with CHD and 155 healthy controls, primarily males, frequency matched for age and gender, using the Food Frequency Questionnaire (FFQ) of the European Prospective Investigation into Cancer and Nutrition. Adherence to MD was estimated from FFQ by the Mediterranean Diet Score (MDS), an index developed by Trichopoulou (2003) ranging from 0 to 9, with higher scores indicating a stricter adherence. Overall dietary variety was computed from FFQ as a count of single food items consumed at least once a month. Associations between MDS or overall dietary variety and coronary status were evaluated by logistic regression models adjusted for BMI, physical activity, smoking, education, and caloric intake; the Odds Ratio (OR) for CHD for each 1.5-point increase in MDS was 0.76 [IC 95% 0.59; 0.98], whereas the OR for CHD for each 15-item increase in dietary variety was 0.62 [IC 95% 0.46; 0.84]. Remarkably, adherence to MD and overall dietary variety were independently associated with a significantly reduced chance of CHD. Conclusion Dietary Mediterranean-ness and overall dietary variety exhibit additive cardioprotective effects

Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: evidence from PHYLLIS randomised double blind trial

Objective To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring

Association Between Uric Acid, Carotid Intima-Media Thickness, and Cardiovascular Events:Prospective Results From the IMPROVE Study

Background The association between elevated serum uric acid (SUA), cardiovascular disease (CVD) risk, and carotid atherosclerosis has long been explored, and contrasting results have been reported. Therefore, the role of SUA as an independent risk factor for vascular events (VEs) and carotid atherosclerosis deserves further attention. We investigated the relationship between SUA, incident VEs, carotid intima-media thickness (cIMT), and cIMT progression in subjects at moderate-to-high CVD risk. Methods and Results In the IMPROVE (IMT-Progression as Predictors of VEs) study, 3686 participants (median age 64 years; 48% men) with >= 3 vascular risk factors, free from VEs at baseline, were grouped according to SUA quartiles (division points: 244-284-328 mu mol/L in women, 295-336-385 mu mol/L in men). Carotid-IMT and its 15-month progression, along with incident VEs, were recorded. A U-shaped association between SUA and VEs was observed in men, with 2.4-fold (P = 0.004) and 2.5-fold (P = 0.002) increased CVD risk in the first and fourth SUA quartiles as compared with the second. Adjusted hazard ratios (HRs) for cerebro-VEs in men were the highest (first and fourth quartile versus second: HR, 5.3, P = 0.010 and HR, 4.4, P = 0.023, respectively). SUA level was independently associated with cIMT progression in men (beta = 0.068, P = 0.014). No significant association between SUA levels, CVD end points, and cIMT progression were found in women. Conclusions Both low and high SUA levels are associated with an increased risk of VEs in men at moderate-to-high CVD risk but not in women. Only elevated SUA levels predict cIMT progression and at a lesser but not significant extent in women

Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease

IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E−5 and chromosome 14, rs4902762, BETA = 0.12, P = 5.76E−6) and one for eosinophil count (rs72797327, BETA = −0.10, P = 1.41E−6). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P = 0.2763, I2 = 24, I2 − P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = −0.10, P = 8.64E−6 and rs11739623 (r2 = 0.96 with rs72797327) BETA = −0.23, P = 1.74E−29, respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels

Causal relevance of blood lipid fractions in the development of carotid atherosclerosis: Mendelian randomization analysis.

BACKGROUND: Carotid intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with risk of coronary heart disease events. Statins reduce progression of CIMT and coronary heart disease risk in proportion to the reduction in low-density lipoprotein cholesterol. However, interventions targeting triglycerides (TGs) or high-density lipoprotein cholesterol (HDL-C) have produced inconsistent effects on CIMT and coronary heart disease risk, making it uncertain whether such agents are ineffective for coronary heart disease prevention or whether CIMT is an inadequate marker of HDL-C or TG-mediated effects. We aimed to determine the causal association among the 3 major blood lipid fractions and common CIMT using mendelian randomization analysis. METHODS AND RESULTS: Genetic scores specific for low-density lipoprotein cholesterol, HDL-C, and TGs were derived based on single nucleotide polymorphisms from a gene-centric array in ≈5000 individuals (Cardiochip scores) and from a genome-wide association meta-analysis in >100 000 individuals (Global Lipids Genetic Consortium scores). These were used as instruments in a mendelian randomization analysis in 2 prospective cohort studies. A genetically predicted 1 mmol/L higher low-density lipoprotein cholesterol concentration was associated with a higher common CIMT by 0.03 mm (95% confidence interval, 0.01-0.04) and 0.04 mm (95% confidence interval, 0.02-0.06) based on the Cardiochip and Global Lipids Genetic Consortium scores, respectively. HDL-C and TGs were not causally associated with CIMT. CONCLUSIONS: Our findings confirm a causal relationship between low-density lipoprotein cholesterol and CIMT but not with HDL-C and TGs. At present, the suitability of CIMT as a surrogate marker in trials of cardiovascular therapies targeting HDL-C and TGs is questionable and requires further study

Untargeted metabolomics to go beyond the canonical effect of acetylsalicylic acid

15openInternationalItalian coauthor/editorGiven to its ability to irreversibly acetylate the platelet cyclooxygenase-1 enzyme, acetylsalicylic acid (ASA) is successfully employed for the prevention of cardiovascular disease. Recently, an antitumoral effect of ASA in colorectal cancer has been increasingly documented. However, the molecular and metabolic mechanisms by which ASA exerts such effect is largely unknown. Using a new, untargeted liquid chromatography–mass spectrometry approach, we have analyzed urine samples from seven healthy participants that each ingested 100 mg of ASA once daily for 1 week. Of the 2007 features detected, 25 metabolites differing after ASA ingestion (nominal p 1) were identified, and pathway analysis revealed low levels of glutamine and of metabolites involved in histidine and purine metabolisms. Likewise, consistent with an altered fatty acid β-oxidation process, a decrease in several short- and medium-chain acyl-carnitines was observed. An abnormal β-oxidation and a lower than normal glutamine availability suggests reduced synthesis of acetyl-Co-A, as they are events linked to one another and experimentally related to ASA antiproliferative effects. While giving an example of how untargeted metabolomics allows us to explore new clinical applications of drugs, the present data provide a direction to be pursued to test the therapeutic effects of ASA—e.g., the antitumoral effect—beyond cardiovascular protectionopenDi Minno, Alessandro; Porro, Benedetta; Turnu, Linda; Manega, Chiara Maria; Eligini, Sonia; Barbieri, Simone; Chiesa, Mattia; Poggio, Paolo; Squellerio, Isabella; Anesi, Andrea; Fiorelli, Susanna; Caruso, Donatella; Veglia, Fabrizio; Cavalca, Viviana; Tremoli, ElenaDi Minno, A.; Porro, B.; Turnu, L.; Manega, C.M.; Eligini, S.; Barbieri, S.; Chiesa, M.; Poggio, P.; Squellerio, I.; Anesi, A.; Fiorelli, S.; Caruso, D.; Veglia, F.; Cavalca, V.; Tremoli, E

Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression:results from a European longitudinal multicentre study

BACKGROUND/AIM: The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption. METHODS: Between 2002-2004, 1772 men and 1931 women aged 54-79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 - 5 g/d), low (> 5 to  ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women,  > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude. RESULTS: Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMTmean[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMTmean[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMTmean[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMTmean[- 0.009(95% - 0.016; - 0.002)] and ICA-IMTmax[- 0.016(95%: - 0.032; - 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT. CONCLUSION: In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders

The α2-adrenergic receptor pathway modulating depression influences the risk of arterial thrombosis associated with BDNFVal66Met polymorphism

Depression is associated with thrombotic risk and arterial events, its proper management is strongly recommended in coronary artery disease (CAD) patients. We have previously shown that the Brain-Derived Neurotrophic Factor (BDNF)Val66Met polymorphism, related to depression, is associated with arterial thrombosis in mice, and with an increased risk of acute myocardial infarction in humans. Herein, expanding the previous findings on BDNFVal66Met polymorphism, we show that desipramine, a norepinephrine reuptake-inhibitor, rescues behavioral impairments, reduces the arterial thrombosis risk, abolishes pathological coagulation and platelet hyper-reactivity, normalizes leukocyte, platelet, and bone marrow megakaryocyte number and restores physiological norepinephrine levels in homozygous knock-in BDNF Val66Met (BDNFMet/Met) mice. The in vitro data confirm the enhanced procoagulant activity and the alpha(2A)-adrenergic receptor (alpha(2A)-ADR) overexpression found in BDNFMet/Met mice and we provide evidence that, in presence of Met variant, norepinephrine is crucial to up-regulate procoagulant activity and to enhance platelet generation. The alpha(2)-ADR antagonist rauwolscine rescues the prothrombotic phenotype in BDNFMet/Met mice and reduces procoagulant activity and platelet generation in cells transfected with BDNFMet plasmid or exposed to pro-BDNFMet peptide. Finally, we show that homozygous BDNFMet/Met CAD patients have hyper-reactive platelets overexpressing abundant alpha(2A)-ADR. The great proplatelet release from their megakaryocytes well reflects their higher circulating platelet number compared to BDNFval/val patients. These data reveal an unprecedented described role of Met allele in the dysregulation of norepinephrine/alpha(2A)-ADR pathway that may explain the predisposition to arterial thrombosis. Overall, the development of alpha(2A)-ADR inhibitors might represent a pharmacological treatment for depression-associated thrombotic conditions in this specific subgroup of CAD patients

Shorter Survival of SDF1-3′A/3′A Homozygotes Linked to CD4+ T Cell Decrease in Advanced Human Immunodeficiency Virus Type 1 Infection

The SDF-1 3′A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3′A/3′A genotype and accelerated disease progression was evident among seroconverters (n = 319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4+ T cell counts <200 was observed. The relative hazards for SDF1-3′A/3′A homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16 (P = .0047), for time from diagnosis according to the 1993 Centers for Disease Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43 (P = .0001), for time from CD4+ T cells <200 to death. Because no difference in survival was observed after diagnosis according to AIDS-'87, the association of the SDF1-3′A/3′A genotype with the accelerated progression of late-stage HIV-1 disease appears to be explained for the most part by the loss of CD4+ T lymphocyte

Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants

The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54-79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point >= 75th), and (2) C-IMT progression (binary, cut-point>zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06-1.47), CC-IMTmean (OR:1.22;1.04-1.44) and ICA-IMTmean (OR:1.26;1.07-1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis