Pharmacodynamic effects of adjunctive high dose atorvastatin on double dose clopidogrel in patients with high on-treatment platelet reactivity depending on diabetes mellitus status.

Diabetes mellitus (DM) is associated with impaired platelet response to clopidogrel. In patients with high on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel, high-dose atorvastatin enhances the pharmacodynamic (PD) effects of double-dose clopidogrel. It is unknown if similar effects are achieved in patients with DM. This study compare the PD effects of high-dose atorvastatin associated with double dose clopidogrel in HTPR patients with and without DM undergoing elective percutaneous coronary intervention (PCI). This is a post hoc analysis of a prospective randomized PD study that compared double-dose (150 mg) clopidogrel associated with high-dose (80 mg) atorvastatin to double-dose clopidogrel alone in statin naïve patients with HTPR undergoing elective PCI. In this analysis, patients were divided in two groups according to DM (n = 27) and non-DM (n = 49) status. Platelet reactivity was evaluated immediately before PCI and at 30 days using the VerifyNow P2Y12 assay. HTPR was defined as P2Y12 reaction units (PRU) ≥235. Administering high-dose atorvastatin in addition to high-dose clipodogrel, the 30 days absolute PRU changes (106 ± 75 vs 100 ± 42, p = 0.7) and optimal response rates (83 vs 84%; p = 0.9) were similar in DM and non-DM patients. The baseline variables significantly associated with 30-day optimal response to high-dose clopidogrel were: atorvastatin treatment (OR = 7.5 [95% CI 1.19-47]; p = 0.032) in DM patients; PRU values (OR = 0.9 [95% CI 0.95-0.99]; p = 0.031) and creatinine clearance (OR = 1.07 [95% CI 1.008-1.13]; p = 0.025) in non-DM patients. High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in DM patients with HTPR undergoing elective PCI.

High-dose atorvastatin on the pharmacodynamic effects of double-dose clopidogrel in patients undergoing percutaneous coronary interventions: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study.

OBJECTIVES: The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic (PD) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease (CAD) and high-on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel before percutaneous coronary intervention (PCI). BACKGROUND: Patients with HTPR are at increased risk of adverse cardiovascular events after PCI. High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms, including antithrombotic effects. METHODS: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study was a randomized PD study of high-dose (80 mg) atorvastatin in addition to double-dose (150 mg) clopidogrel (atorvastatin group, n = 38) versus double-dose clopidogrel alone (control group, n = 38) in patients with HTPR. HTPR was defined as P2Y(12) reaction units (PRU) ≥235 by the VerifyNow P2Y12 assay. Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days. RESULTS: Patients randomized to atorvastatin had lower PRU values (188 ± 48 vs. 223 ± 53 PRU, p < 0.01; primary endpoint) and HTPR rates (16% vs. 42%, p < 0.01) at 30 days than patients in the control group. Statin treatment (odds ratio [OR]: 3.8, p = 0.011), baseline PRU <298 (OR: 10.7, p = 0.0001), noncarrier status of CYP2C19*2 loss-of-function allele (OR: 2.9, p = 0.043), and age (OR: 0.94, p = 0.032) were variables significantly associated with optimal PD response (PRU <235) at 30 days. No correlations were found between PRU and lipid fractions. CONCLUSIONS: High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ACHIDO]; NCT01335048).

Effects of a 1-year dietary intervention with n-3 polyunsaturated fatty acid-enriched olive oil on non-alcoholic fatty liver disease patients: a preliminary study.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a worldwide diffuse condition due to alimentary, environment and genetic factors. The aim of our preliminary study was to evaluate the effectiveness of long-term consumption of food enriched with n-3 polyunsaturated fatty acids (PUFA) in patients with NAFLD. METHODS: Eleven patients were enrolled; six (four males, two females) were planned for oral administration of 6.5 ml olive oil enriched with n-3 PUFA for 12 months, while five (four males, one female) were used as controls. RESULTS: Consumption of olive oil enriched with n-3 PUFA demonstrated a significant improvement of liver echo-texture and of the Doppler Perfusion Index after 12 months (after: 0.19 ± 0.02 vs. pre: 0.15 ± 0.03; P < 0.05), whereas no significant changes were seen at the end of follow-up in controls. Moreover, patients who consumed the olive oil enriched with n-3 PUFA showed a significant amelioration of liver enzymes, and of triglycerides (post: 132.8 ± 63.7 vs. pre: 164.5 ± 85.5 mg/dl; P = 0.04) in a general linear model adjusted for age and gender. Interestingly, patients reported to have a significant increase of adiponectin levels (post: 1,487.9 ± 96.7 vs. pre: 1,143 ± 24.8 µg/ml; P = 0.04). CONCLUSION: The results of this preliminary study showed that long-term consumption of olive oil enriched with n-3 PUFA in patients with NAFLD is able to decrease circulating liver enzymes and triglycerides, with a significant improvement of adiponectin levels.

Effects of short-term consumption of bread obtained by an old Italian grain variety on lipid, inflammatory, and hemorheological variables: an intervention study.

The aim of this study was to evaluate the influence of short-term dietary intake of bread obtained by a selected variety of old grain grown in Tuscany, Italy on some parameters related to the atherosclerotic process. Twenty healthy subjects (median age, 39.5 years) followed for 10 weeks a diet containing bread (150 g/day) made from the test grain (test period) and for the same period a diet containing commercially available bread of the same quantity (control period). Lipid, inflammatory, and hemorheological profiles before and after dietary intervention were evaluated. The test period showed a significant (P < .05) improvement of total cholesterol (pre-intervention, 211.2 +/- 10.8 mg/dL; post-intervention, 196.5 +/- 9.8 mg/dL) and low-density lipoprotein-cholesterol levels (pre-intervention, 137.5 +/- 8.1 mg/dL; post-intervention, 119.5 +/- 7.5 mg/dL), whereas no significant changes during the control period were observed. With regard to inflammatory and hemorheological parameters, the test period showed a significant decrease in some of the parameters investigated (interleukin-8 [pre-intervention vs. post-intervention, 67.4 +/- 10.7 vs. 43.9 +/- 4.1 pg/mL], whole blood viscosity at high [4.36 +/- 0.03 vs. 4.32 +/- 0.03 mPa x s, respectively] and low [26.1 +/- 0.4 vs. 24.8 +/- 0.5 mPa x s, respectively] shear rates, and erythrocyte filtration [8.4 +/- 0.7% vs. 9.1 +/- 0.6%, respectively]) relative to the control period, which showed no significant changes. Short-term dietary intake of whole grain bread obtained from an old grain variety seems to impose a favorable status with regard to lower circulating levels of markers of atherosclerosis.

Emerging drugs for acute myocardial infarction.

IMPORTANCE OF THE FIELD: The present review is aimed at going over the pharmacological profile (and the clinical impact) of the emerging drugs involved in the management of patients with ST-elevation myocardial infarction (STEMI) in order to provide the cardiologists who deal with these patients in the early phase with the most recent evidence on this topic. AREAS COVERED IN THIS REVIEW: Anticoagulant and antiplatelet drugs are the main cornerstones of therapy in the treatment of STEMI patients undergoing primary percutaneous coronary intervention (PCI). The main issues that clinicians have to deal with are represented by balancing thrombotic and bleeding risks. In tailoring therapy, variables such as age, sex and previous disease should be taken into account, as well as ongoing complications (such as acute renal failure) that could affect hemostasis. Despite the well-established clinical benefits of antiplatelet agents, questions remain, mainly surrounding potential for variable platelet response, which are strictly related to non-genetic (i.e., diet, drug-drug interaction, clinical factors such as obesity, diabetes mellitus, and inflammation) and genetic determinants. WHAT THE READER WILL GAIN: In their daily practice, cardiologists cannot abstract from the knowledge and updating on the ongoing research fields as well as the newly developed drugs, which they should frame in the very patient in the attempt to the develop a personalized medical strategy. These include also the pharmacological option(s) in the treatment of the reperfusion injury, the metabolic aspects and the stem cell therapy. TAKE HOME MASSAGE: In our opinion, the goal of ongoing research on the pharmacological approach to STEMI patients is a personalized medical strategy that relies on critical clinicians who merge newly developed acquisitions on this topic and a more complete, systemic and critical approach to the patient.

Coffee consumption and risk of coronary heart disease: a meta-analysis.

BACKGROUND AND AIMS: During the past three decades the relationship between habitual coffee drinking and coronary heart disease (CHD) has been assessed in numerous studies, with conflicting results. The aim of this study was to systematically examine the data published on the association between habitual coffee consumption and risk of CHD. METHODS AND RESULTS: Thirteen case-control and 10 cohort studies were included. Case-control studies incorporated 9487 cases of CHD and 27,747 controls, and cohort studies included a total of 403,631 participants that were followed for between 3 and 44 years. The summary of odds ratios (OR) for the case-control studies showed statistically significant associations between coffee consumption and CHD for the highest intake group (>4 cups/day), OR 1.83 (95% CI 1.49-2.24; P<0.0001), and for the second highest category (3-4 cups/day), OR 1.33 (95% CI 1.04-1.71; P<0.0001), while no significant association emerged for low daily coffee intake (< or =2 cups/day), OR 1.03 (95% CI 0.87-1.21; P=0.45). The analysis of long-term follow-up cohort studies did not show any association between the consumption of coffee and CHD, with a relative risk (RR) of 1.16 (95% CI 0.95-1.41; P=0.14) for the highest category, and 1.05 (95% CI 0.90-1.22; P=0.57) and 1.04 (95% CI 0.90-1.19; P=0.60) for the second and third highest categories, respectively. These results did not differ substantially when controlling for region of origin, fatal and non-fatal events, year of publication, and number of years of follow-up. CONCLUSIONS: Despite a significant association between high consumption of coffee and CHD reported among case-control studies, no significant association between daily coffee consumption and CHD emerged from long-term follow-up prospective cohort studies.

Low adherence of a clinically healthy Italian population to nutritional recommendations for primary prevention of chronic diseases.

BACKGROUND AND AIM: Several data demonstrated that dietary habits significantly affect the health state of the population. During recent years all the major scientific associations have provided nutritional recommendations for primary prevention of chronic diseases but few data are available about prevalence of adherence to these recommendations in an otherwise healthy population. The aims of this study were to evaluate dietary habits, and to assess the adherence of the general population to the recommendations for correct nutritional behaviour. METHODS AND RESULTS: Dietary habits, anthropometric and biochemical parameters were evaluated in a population of 932 (367 M; 565 F) clinically healthy subjects living in Florence, enrolled in an epidemiologic study conducted between 2002 and 2004. By comparing the dietary pattern with the nutritional guidelines, the study population reported a hyperproteic and hyperlipidic nutritional pattern, with a considerably low contribution from polyunsaturated fats (PUFA). A low fibre intake is shown in both genders. In addition, food consumption pattern showed an increased consumption of some foods such as meat, both fresh and processed, and a low intake of some "healthy" foods like fruit and vegetables. CONCLUSIONS: We found several nutritional flaws in the dietary habits of a clinically healthy Italian population. In particular, we reported a high intake of animal protein and total fats with a very low contribution from PUFA.

Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients.

BACKGROUND: We previously demonstrated among renal-transplant recipients (RTRs) a high prevalence of hyperhomocysteinemia, which might account for their elevated cardiovascular risk. The purpose of our study was to document, in hyperhomocysteinemic RTRs, the effect of vitamin supplementation on carotid intima-media thickness (cIMT), which is an early sign of atherosclerosis. METHODS: A total of 56 stable hyperhomocysteinemic RTRs were randomly assigned to vitamin supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin B(12) 400 microg) (group A) or placebo treatment (group B) for 6 months. All subjects underwent cardiovascular risk-factor assessment, including fasting homocysteine (Hcy) levels assay, and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries, at time of enrollment and after 6 months. RESULTS: Fasting Hcy levels markedly decreased in group A after treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas no significant changes were observed in group B (20.5 [17-37.6] micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group A, cIMT significantly decreased after treatment (0.95+/-0.20 mm vs. 0.64+/-0.17 mm; P<0.0001). All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was -32.2+/-12.9%. Patients with methylenetetrahydrofolate reductase (MTHFR) C677T +/+ genotype, with higher Hcy levels, had the major percentage of decrease of Hcy with respect to the other genotypes (mean decrease: MTHFR +/+ 74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/- 56.3+/-8.6%). In hyperhomocysteinemic patients without vitamin supplementation (group B) we documented a significant increase in cIMT after 6 months (0.71+/-0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we observed an increase in cIMT, and in 9 of 28 the cIMT was unmodified. The mean percentage of cIMT increase was + 23.3+/-21.1%. CONCLUSIONS: Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs.