High Cardiovascular Risk Subjects Research Articles

Extra-media thickness and epicardial fat: Comparison of a novel carotid artery ultrasound index and a well-established cardiac magnetic resonance fat quantification method

Background and AimEpicardial and pericardial fat are well-established surrogate markers of cardiovascular diseases and complications. Extra-media thickness (EMT) is a novel ultrasound index corresponding to arterial adventitia and adipose tissue. We aimed to evaluate the association between carotid EMT and epicardial fat (EF) and pericardial fat (PF) and their relation to cardiovascular risk and metabolic syndrome (MS). Methods and ResultsOne hundred consecutive patients (age: 51.7 ± 15.4 years; males 70%) scheduled for cardiac magnetic resonance (CMR) were prospectively included in the study. Anthropometric parameters, CMR indices of EF and PF, both common carotid arteries EMT, and ultrasound indices of visceral and subcutaneous fat were measured in patients. In our study group, 53% of patients represented a very high cardiovascular risk, overweight or obesity was found in 68%, high body fat in 45%, and MS in 59% of individuals. Mean EMT (662 ± 129 μm) was significantly associated with EF area (r = 0.46; p < 0.001) and PF area (r = 0.3; p < 0.001). Among all fat indices, only EMT (MS+ 736 ± 140 μm vs. MS-658 ± 97 μm; p = 0.002) and EF area (MS+ 870 ± 451 mm2 vs. MS 668 ± 333 mm2; p = 0.02) were significantly increased in patients with MS compared with individuals without MS. Multivariable regression analysis also showed that mean EMT is independently associated with number of cardiovascular risk factors (b = 0.005; p < 0.001). Moreover, very high cardiovascular risk subjects showed significantly increased EMT/BMI (p < 0.001) and EF area/BMI (p = 0.03) ratios. However, there was no significant association between EMT/BMI and EF area/BMI values (p = ns). ConclusionsOur study showed the first findings on the relations between a novel ultrasound index EMT and EF assessed in a reference method of CMR. Carotid EMT may be a new surrogate marker, including both periarterial fat as a major component and arterial adventitia, which may provide additional data on cardiometabolic risk beyond that derived form a well-established EF alone.

Update on the management of severe hypertriglyceridemia--focus on free fatty acid forms of omega-3.

High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases, often associated with anomalies in other lipids or lipoproteins. Hypertriglyceridemia (HTG), particularly at very high levels, significantly increases also the risk of acute pancreatitis. Thus, interventions to lower TG levels are required to reduce the risk of pancreatitis and cardiovascular disease. Several strategies may be adopted for TG reduction, including lifestyle changes and pharmacological interventions. Among the available drugs, the most commonly used for HTG are fibrates, nicotinic acid, and omega-3 polyunsaturated fatty acids (usually a mixture of eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA). These last are available under different concentrated formulations containing high amounts of omega-3 fatty acids, including a mixture of EPA and DHA or pure EPA. The most recent formulation contains a free fatty acid (FFA) form of EPA and DHA, and exhibits a significantly higher bioavailability compared with the ethyl ester forms contained in the other formulations. This is due to the fact that the ethyl ester forms, to be absorbed, need to be hydrolyzed by the pancreatic enzymes that are secreted in response to fat intake, while the FFA do not. This higher bioavailability translates into a higher TG-lowering efficacy compared with the ethyl ester forms at equivalent doses. Omega-3 FFA are effective in reducing TG levels and other lipids in hypertriglyceridemic patients as well as in high cardiovascular risk patients treated with statins and residual HTG. Currently, omega-3 FFA formulation is under evaluation to establish whether, in high cardiovascular risk subjects, the addition of omega-3 to statin therapy may prevent or reduce major cardiovascular events.

Pro12Ala polymorphism of the PPARγ2 gene interacts with a mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial.

The gene variant Pro/Ala (rs1801282) in the PPARγ2 has been associated with lower cardiovascular risk and greater benefit from lifestyle interventions. This polymorphism also seems to be associated with longer lifespan, but no information on telomere length (TL) is available. Our aim was to study the association between the Ala allele and changes in TL in high cardiovascular risk subjects and the potential interaction with a Mediterranean dietary pattern. A total of 521 subjects (55-80 years) participating in the Prevención con Dieta Mediterránea randomized trial were genotyped. Changes in TL, measured by quantitative real-time polymerase chain reaction (PCR), were assessed over 5 years of a nutritional intervention, which promoted adherence to the Mediterranean diet (MeDiet). Interestingly, Ala carriers showed lower telomere shortening after 5 years compared with the Pro/Pro genotype (P=0.031). This association was modulated by MeDiet because those Ala carriers who reported better conformity to the MeDiet exhibited increased TL (P<0.001). Moreover, a reduction in carbohydrate intake (≤9.5 g/d) resulted in increased TL among Ala carriers. Notably, an apparent gene-diet interaction was found through the observed changes in the MUFA+PUFA/carbohydrates ratio: as this ratio increased, TL lengthening was detected to a greater extent in the Ala carriers compared with the Pro/Pro subjects (P for interaction <0.001). The Pro12Ala polymorphism is associated with TL homeostasis after 5 years follow-up in subjects at high cardiovascular risk. In addition, a higher adherence to the MeDiet pattern strengthens the prevention of telomere shortening among Ala carriers. www.controlled-trials.com; Unique Identifier: ISRCTN35739639.

Association between pneumococcal vaccination and cardiovascular outcomes: a systematic review and meta-analysis of cohort studies.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP) and CAP-related mortality in adults. Pneumococcal vaccination (PV) could protect subjects from cardiovascular events by reducing pneumonia severity or even preventing it. We sought to determine the ability of PV to protect from the risk of cardiovascular events. A comprehensive search of electronic databases was conducted up to March 2014. Cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CI) were included. Eleven studies were included (332,267 participants, mean follow-up 20.1 months). The pooled RRs for cardiovascular events and cardiovascular mortality were 0.86 (95% CI: 0.76-0.97) and 0.92 (95% CI: 0.86-0.98; fixed-effects), respectively, for subjects with PV versus without PV. Protective ability was more prominent in high cardiovascular risk populations and with older age. The protective role of PV was attenuated after 1 year (RR: 0.72; 95% CI: 0.59-0.88 vs RR: 1.03; 95% CI: 0.93-1.14; p = 0.002, for follow-up >1 year vs ≤1 year, respectively). It also increased as the presence of cardiovascular and pulmonary disease increased. Regarding myocardial infarction (MI) and cerebrovascular events, the protective role of PV was statistically significant only in the elderly (RR: 0.90; 95% CI: 0.817-0.999; fixed-effects and RR: 0.86; 95% CI: 0.75-0.99, respectively). PV is associated with decreased risk of cardiovascular events and mortality. This protective effect increases at older age and in high cardiovascular risk subjects and decreases as the time elapses from PV. PV decreases the risk of MI and cerebrovascular events in the elderly.

Effects of ezetimibe on endothelial progenitor cells and microparticles in high-risk patients.

Imbalance on endothelial turnover can predict cardiovascular outcomes. We aimed at evaluating the effects of lipid-modifying therapies on circulating endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and platelet microparticles (PMPs) in high cardiovascular risk subjects with elevated C-reactive protein (CRP). Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy, with LDL-cholesterol <100 mg/dL and CRP ≥ 2.0 mg/L were selected. After a 4-week run-in period with atorvastatin 10 mg, those with persistent CRP ≥ 2.0 mg/L were randomized to another 4-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or atorvastatin 40 mg/ezetimibe 10 mg. EPC (CD34(+)/CD133(+)/KDR(+)), EMP (CD51(+)), and PMP (CD42(+)/CD31(+)) were quantified by flow cytometry. Atorvastatin 40 mg and atorvastatin 40 mg/ezetimibe 10 mg reduced LDL-cholesterol (P < 0.001, paired T test, vs. baseline). Combined therapy, but not ezetimibe reduced CRP. CD34(+)/KDR(+) EPC were reduced after ezetimibe alone (P = 0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P = 0.016 vs. baseline, Wilcoxon test). In addition, ezetimibe increased CD51(+) EMP (P = 0.017 vs. baseline, Wilcoxon test). No correlations between these markers and LDL-cholesterol or CRP were observed. These results contribute to understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe alone.

The non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: A randomized clinical trial

RationaleModerate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients. ObjectiveTo compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors. MethodsIn this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored. ResultsThe number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions. ConclusionsThe non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects. Clinical trial registrationhttp://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245

Omega-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia

Epidemiological studies have established an association between high triglycerides (TG) plasma levels and increased cardiovascular risk. Increased TG levels, commonly coupled with low HDL-C levels, are common in high cardiovascular risk subjects including those with dyslipidemia, metabolic syndrome and type 2 diabetes. Management of hypertriglyceridemia (HTG) includes lifestyle modification for mild-to-moderate HTG and pharmacological therapies for the treatment of high and very high TG levels. Among drugs, fibrates, nicotinic acid and omega-3 polyunsaturated fatty acids may be considered. Omega-3 fatty acids reduce plasma TG levels by several mechanisms; beside the effects on TG, omega-3 can also influence the levels of other lipids and lipoproteins including HDL-C and LDL-C. Clinical trials have also shown that omega-3 fatty acid supplementation is effective also when added in combination with other lipid-lowering drugs. These findings suggest that omega-3 fatty acids may be usefully considered for the management of high TG levels.

Inhibition of the renin–angiotensin system for lowering coronary artery disease risk

The renin-angiotensin system when activated exerts proliferative and pro-inflammatory actions and thereby contributes to progression of atherosclerosis, including that occurring in the coronary arteries. It thus contributes as well to coronary artery disease (CAD). Several clinical trials have examined effects of renin-angiotensin system inhibition for primary and secondary prevention of coronary heart disease. These include important trials such as HOPE, EUROPA and PEACE using angiotensin converting enzyme inhibitors, VALIANT, OPTIMAAL and TRANSCEND using angiotensin receptor blockers, and the ongoing TOPCAT study in patients with preserved ejection fraction heart failure, many of who also have coronary artery disease. Data are unavailable as yet of effects of either direct renin inhibitors or the new angiotensin receptor/neprilysin inhibitor agents. Today, inhibition of the renin-angiotensin system is standard-of-care therapy for lowering cardiovascular risk in secondary prevention in high cardiovascular risk subjects.

Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene–diet interactions

Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing. THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial). The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity. THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.

Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption

BackgroundFat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood.ObjectiveTo investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake.MethodsAdherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed.ResultsFTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01–1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/−SE: −0.57+/−0.16 g/d per-score-allele; P = 0.001).ConclusionStatistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

BackgroundAlthough the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).MethodsCase-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.ResultsNeither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.ConclusionsThese novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.

Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method

Resveratrol exerts a variety of biological and pharmacological activities, which are observed despite its extremely low bioavailability and rapid clearance from the circulation due to extensive sulfation and glucuronidation in the intestine and liver. In order to more accurately quantify all known resveratrol metabolites, a sensitive and optimized analytical assay was developed and validated by pure standards. Methodology improvements aimed to the chromatographic detection of disulfates and sulfoglucuronides, improving resolution of sulfates, by using a buffered solution, with recovery values of resveratrol and its metabolites, even of sulfates, of 99%. The adapted methodology was then applied to a clinical study with high cardiovascular risk subjects, after the moderate consumption of red wine (RW) or dealcoholized red wine (DRW) for 28 days. Up to 21 resveratrol metabolites, including those formed by gut and microbial metabolism, were identified in 24-h urine samples. Interestingly, after long-term consumption of RW and DRW, resveratrol metabolite concentration significantly increased in urine with no differences between the two interventions, indicating that bioavailability and biotransformation of resveratrol is not affected by the alcoholic matrix of wine. In summary, we established a sensitive analytical assay for the quantification of a wide resveratrol metabolic profile in human urine, also regarding gut microbial-derived metabolites, which may also be applied to blood and tissue samples. The resveratrol metabolic pattern might therefore act as an excellent marker for the efficacy of resveratrol in clinical and epidemiological studies for the study of the beneficial effects of grape product consumption. In this sense, having a more precise concentration value of all the resveratrol metabolites in target tissues would finally lead to a better interpretation of the obtained results.

Relevant associations of the glucokinase regulatory protein/glucokinase gene variation with TAG concentrations in a high-cardiovascular risk population: modulation by the Mediterranean diet

The SNP rs1260326 (P446L) and rs1799884 (-30G>A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concentrations (PP: 1.34 (SD 0.05) mmol/l v. PL+LL: 1.54 (SD 0.03) mmol/l; P= 0.014) and LL carriers had lower glucose concentrations (PL+PP: 6.85 (SD 0.08) mmol/l v. LL: 6.40 (SD 0.16) mmol/l; P= 0.032) after multivariate adjustment. Conversely, homozygous subjects for the variant allele (A) in the GCK gene had significantly lower TAG (GG+GA: 1.48 (SD 0.03) mmol/l v. AA: 1.17 (SD 0.18) mmol/l; P= 0.033) and a higher risk of diabetes (OR 3.3, 95 % CI 1.2, 9.2). Combined effects for both SNP increased TAG concentrations by 37 % (P= 0.033). Adherence to the MD modulated the effects of GCKR polymorphism on TAG: subjects with genetic risk had lower TAG (L-allele carriers; PP: 1.48 (SD 0.14) mmol/l v. PL+LL: 1.51 (SD 0.08) mmol/l; P= 0.917) compared with those with a higher adherence. Analysis of the joint effects of the GCKR and individual food items identified significant associations (olive oil (P= 0.035), vegetables (P= 0.012), red meat (P= 0.017), butter (P= 0.039), sweetened carbonated beverages (P= 0.036) and nuts (P= 0.038)). In conclusion, we found that rs1260326 (GCKR) is significantly associated with higher TAG concentrations, but is modulated by adherence to the MD.

Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study

BackgroundA considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets, despite treatment with statins. Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L (N = 250), pretreated with atorvastatin 20 mg were randomized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks. The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment, time, time-by-treatment interaction, stratum, and time-by-stratum interaction. Percentage of subjects achieving LDL-C < 1.81 mmol/L, < 2.00 mmol/L, or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum. Tolerability was assessed.ResultsSwitching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP. Significantly more subjects achieved LDL-C < 1.81 mmol/L (29% vs. 5%), < 2.00 mmol/L (38% vs. 9%) or < 2.59 mmol/L (69% vs. 41%) after switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose (all p < 0.001). The overall safety profile appeared generally comparable between treatment groups.ConclusionsIn high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg. Both treatments were generally well-tolerated.Trial registrationRegistered at clinicaltrials.gov: NCT00782184

Reversibility of the endothelial dysfunction after CPAP therapy in OSAS patients

BackgroundThe obstructive sleep apnoea syndrome (OSAS) is a common airways disease which often involves cardiovascular structures, causing vessel inflammation as well as hypoxia, induced by difficulties in the passage of air through the upper airways. Aim of our research is to evaluate the effects of Continuous Positive Airway Pressure (CPAP) on the syndrome itself and the patients cardiovascular risk profile, practically adopting Flow-Mediated Vasodilation (FMD) technique to evaluate endothelial function. Methods and resultsWe enrolled 63 patients (49 males and 14 female, mean age: 54±10years) subdivided into four groups: high cardiovascular risk factors, no CPAP therapy, CPAP therapy started less- and more than 3months before. The patients underwent FMD of the brachial artery using a high resolution ultrasonograph connected to an image analysis system. The maximum recovery value was calculated as the ratio (maximum-baseline) of the change in diameter over the baseline value. Data obtained from this study demonstrate the significant reversibility of FMD in patients treated for more than 3months with CPAP therapy (Group 4). ConclusionsOur study shows the importance of administering CPAP therapy for more than 3months in patients suffering from OSAS to improve EF to a level equal to high cardiovascular risk subjects probably due to a recovery from the systemic hypoxia. Besides, our work points out the importance of FMD as a “clinical” tool able to point out any improvement or regression after therapies.

The rs1466113 Polymorphism in the Somatostatin Receptor 2 Gene Is Associated with Obesity and Food Intake in a Mediterranean Population

Background: A genome-wide association study identified rs1466113 (G>C) in the somatostatin receptor 2 (SSTR2) gene as one of the polymorphisms most significantly associated with body mass index (BMI). As replication is required, we examined the association between this polymorphism and anthropometric variables and food intake in a Mediterranean population. Methods: We studied 945 high cardiovascular-risk subjects (340 men and 605 women) aged 67 ± 6 years, participating in the PREDIMED-Valencia Study. Demographic, clinical, biochemical, dietary, genetic and anthropometric data were obtained. Results: We found recessive effects for the association between this polymorphism and anthropometric variables. Homozygous subjects for the C allele had significantly lower BMI than G-allele carriers (29.9 ± 4.5 in CC vs. 31.0 ± 4.9 in GG + GC; p = 0.035). Likewise, odds ratio for obesity was lower in CC subjects in comparison with G-allele carriers, even after adjustment for potential confounders (odds ratio: 0.60, 95% confidence interval: 0.38–0.94; p = 0.028). We also found significant differences in food (meats, dairy products and legumes) and nutrient (protein) intakes between CC- and G-allele carriers. Conclusion: The rs1466113 polymorphism in the SSTR2 gene is associated with anthropometric variables in the Mediterranean population replicating previous results in the Framingham study. We also observed differences in food intake between genotypes.

Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.

Prevalencia de sobrepeso y obesidad en población adulta de un área de Salud Urbana

To estimate prevalence of overweight and obesity in adults and to identify those individuals at high cardiovascular risk (subjects with type 2 diabetes or hypertension) in whom a nurse intervention might be beneficial in terms of life-style changes and reduction in body weight. A cross-sectional study on 2270 adults (18-80 years-old) from an urban Primary Health Care Centre. Medical history, social and demographic data, physical examination and blood tests were collected. The mean body mass index was 26.9±5.1kg/m(2) and was found to be higher in men. Thirty-eight percent of subjects were overweight and 22% were obese. Although the prevalence of obesity was identical in both sexes, women had higher prevalences of type ii and iii obesity than men, but overweight was more frequent in men. Among those older than fifty years-old, 84% were overweight or obese. One-hundred and fifty-six (7%) subjects had type 2 diabetes and 707 (31%) had hypertension, and 111 (5%) subjects with both diabetes and hypertension. BMI was higher (P<0.001) in patients who suffered from, hypertension (29.7±5.2), diabetes (28.5±4.6), and diabetes and hypertension (31.4±5.3), than in those who did not suffer from these diseases (25.4±4.3). Obesity and overweight is highly prevalent in the population studied and is higher in patients with diabetes and hypertension.

301 Metabolic syndrome and coronary heart disease

The value of metabolic syndrome (Mets) in the identification of high cardiovascular risk subjects remains questionable. We sought to examine the association among Mets and the occurrence of a coronary heart disease (CHD). Between 2006 and 2008, 540 patients were screened for the Mets according to the NCEP-ATP III definition. The mean age was 61 ± 12.3 years, 63.3% were men. Mets was diagnosed in 60% of the population. 276 had CHD confirmed by angiocoronarography (51,1%). Patients characteristics are presented in the table. CHD(+) (n=276) CHD(-) (n=264) P Age (years) 62 ± 10,2 60 ± 15,2 < 0,05 Men 75,4% 50,8% < 0,05 Smokers 48,9% 24,2% < 0,05 BMI (kg/m 2 ) 28,5 ± 4,6 28,3 ± 6,5 < 0,05 Waist (cm) 100,2 ± 12,6 98 ± 14 0,08 SBP (mmHg) 133 ± 20,2 132 ± 24,2 0,06 Diabetes 52,9% 23,1% < 0,05 Hypertension 52,8% 46% < 0,05 TG (mmol/l) 1,96 ± 1,1 1,63 ± 1 < 0,05 HDLc (mmol/l) 1,06 ± 0,5 1,2 ± 0,5 < 0,05 CHD (+) patients had a higher prevalence of metabolic syndrome: 74,6% versus 44,7% (p=0.05). Multivariate analyses revealed that only Mets was significantly associated with CHD (OR: 1.48 95% CI: 1.10-2.4, p=0.05). Our study indicates that MetS is highly prevalent and that it seems to be correlated to CHD.

A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes

The aim of this study was to analyze the effects of the rs9939609 (T/A) gene variant in fat mass and obesity-associated gene (FTO) on body weight changes after 3 years and its modification by a randomized nutritional intervention with a Mediterranean-style diet in a population of subjects at high cardiovascular risk. A substudy of PREDIMED, which is a randomized trial aimed at assessing the effect of the Mediterranean diet (MD) for primary cardiovascular disease prevention. There were three nutritional intervention groups: two of them with a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet. A total of 776 high cardiovascular risk subjects aged 55-80 years. Anthropometric measurements were recorded at baseline and at 3 years. The participants were genotyped by RT-PCR, followed by allelic discrimination. Homozygous subjects had the highest baseline body weight. The dominant model showed that subjects carrying the A allele had the lowest body weight gain (B=-0.685; P=0.022) after 3 years of nutritional intervention compared with nonmutated subjects (TT genotype) regardless of the nutritional intervention. Moreover, this effect was statistically significant in carriers of the A allele only among those allocated to the MD groups (B=-0.830; P=0.018), but it was not significant among those allocated to the control group (P for interaction=0.649). This study confirmed the association between body weight and the FTO rs9939609 polymorphism. Interestingly, our results showed that, although at baseline the A allele was associated with higher body weight, after 3 years of nutritional intervention with a Mediterranean-style-diet, A-allele carriers had lower body weight gain than wild type subjects. No interaction between nutritional intervention and the polymorphism was found.