Uptake and effectiveness of a primary cardiovascular prevention program in an underserved multiethnic urban community.

BACKGROUND AND AIMS: Cardiometabolic risk is increased among disadvantaged people and ethnic minorities. Paradoxically, their uptake of primary cardiovascular prevention is relatively low. New strategies are needed to tackle this public health problem. Aims of this study were to assess the uptake (as well as its determinants) and effectiveness of a primary cardiovascular prevention program for communities devised to facilitate access of disadvantaged and inclusion of ethnic minorities in addition to providing a state-of-the-art interdisciplinary personalized care. METHODS AND RESULTS: Single center, hospital-based, open study. All the residents in an underserved multiethnic urban community aged 40-65 years (n = 1646, 43.6% immigrants) were proactively invited by post mail to participate in a cardiovascular prevention program and different approaches were adopted to promote accessibility and inclusiveness. Program uptake was 23% and individual features independently associated with program uptake were status of immigrant (OR [CI 95%]: 3.6 [2.6-5.1]), higher educational level (3.6 [2.8-4.7]), and female gender (1.6 [1.2-2.1]). Retention was 82% at 6 months and 69% at 12 months. A predefined outcome of global cardiovascular risk improvement at 12 months in subjects with glycaemia >126 mg/dl, LDL-C >115 mg/dl, systolic blood pressure ≥140 mmHg or BMI >28 at baseline was reached in 35%, 33%, 37% and 7% of the patients, respectively. 20% of smokers quitted and significant favorable changes were reported in diet quality, anxiety, depression and physical activity. CONCLUSION: Access inequalities to effective prevention may be counteracted, but increasing global uptake requires further upstream sensitization and awareness actions. REGISTERED IN CLINICALTRIALS.GOV: NCT03129165.

Long-term secondary cardiovascular prevention programme in patients subjected to coronary artery bypass surgery.

AIMS: Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case-control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG). METHODS AND RESULTS: Programme participants (henceforth 'cases') were men and women aged <75 years subjected to CABG between 2002 and 2014, living within 100 km of the hospital. Key programme actions included optimization of treatments according to the most updated European preventive guidelines, surveillance of therapy adherence, and customized lifestyle counselling. Controls were analogous patients not involved in the programme because living farther than 100 km away, matched 1:1 with cases for gender, age at CABG, and year of CABG. Both groups (n = 1248) underwent usual periodic cardiology follow-up at our centre. Data on symptomatic or silent CHD recurrences were obtained from the hospital electronic health records. Cox analysis (adjusted for baseline differences between groups) shows that programme participation was associated with a significantly lower incidence throughout 5 years post-CABG of symptomatic [hazard ratio (95% confidence interval): 0.59 (0.38-0.94)] and silent [0.53 (0.31-0.89)] coronary recurrences. CONCLUSION: In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.

Effects of Mediterranean Diet or Low-Fat Diet on Blood Fatty Acids in Patients with Coronary Heart Disease. A Randomized Intervention Study.

The Mediterranean diet (MD) prevents cardiovascular disease by different putative mechanisms, including modifications in the blood fatty acid (FA) profile. Polytherapy for secondary cardiovascular prevention might mask the effect of MD on the FA profile. This study was aimed to assess whether MD, in comparison with a low-fat diet (LFD), favorably modifies the blood FA profile in patients with coronary heart disease (CHD) on polytherapy. One hundred and twenty patients with a recent history of coronary stenting, randomized to MD or to LFD, completed 3 months of this open-label dietary intervention study. Diet Mediterranean-ness was evaluated using the Mediterranean Diet Adherence Screener (MeDAS) score. Both diets significantly reduced saturated FA (p < 0.01). Putative favorable changes in total n-3 FA (p = 0.03) and eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA; p = 0.04) were significantly larger with MD than with LFD. At 3 months, in the whole cohort, the MeDAS score correlated inversely with palmitic acid (R = -0.21, p = 0.02), and with palmitoleic acid (R = -0.32, p = 0.007), and positively with total n-3 FA (R = 0.19, p = 0.03), EPA (R = 0.28, p = 0.002), and EPA + DHA (R = 0.21, p = 0.02). In CHD patients on polytherapy, both MD and LFD shift FA blood composition towards a healthier profile, with a more favorable effect of MD on omega-3 levels.

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

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.

[Barriers and facilitators for physical activity in sedentary people residing in a disadvantaged Italian neighbourhood]. / Barriere e facilitatori per l'attività fisica in soggetti sedentari residenti in un quartiere svantaggiato italiano.

OBJECTIVES: to explore which factors have a personal significance of barrier or facilitator for physical activity (PA) in sedentary subjects living in a peripheral, multiethnic, and economically disadvantaged Italian neighbourhood. DESIGN: qualitative, descriptive phenomenological study. SETTING AND PARTICIPANTS: the study was carried out in Ponte Lambro, a neighbourhood in the South-eastern outskirts of Milan (Lombardy Region, Northern Italy). Among the first 260 participants in a primary cardiovascular prevention programme (called ProSALUTE) targeted to this community, 63 subjects were categorized as sedentary. Out of these, 45 were selected through purposive sampling and 24 of them participated in this study. MAIN OUTCOME MEASURES: • qualitative content analysis of semi-structured interviews conducted through motivational interviewing; • analysis of values acquired by personal value cards. RESULTS: the factors emerged throughout the interviews were external (social support, environment, and tools) and individual (health status, self-confidence, reliance on the beneficial effects of PA, psychological issues). Barriers or facilitators were recognized in each of these factors according to the expressed significance. The most frequently chosen personal values (health, family, delight, strength and autonomy) were concordant with the contents of the interviews. CONCLUSION: distinctive barriers and facilitators to PA are identifiable among the significances expressed by residents in a disadvantaged neighbourhood. These barriers and facilitators may be the targets of socio-environmental or personal interventions aimed to promote an active life-style.

Update of green tea interactions with cardiovascular drugs and putative mechanisms.

Many patients treated with cardiovascular (CV) drugs drink green tea (GT), either as a cultural tradition or persuaded of its putative beneficial effects for health. Yet, GT may affect the pharmacokinetics and pharmacodynamics of CV compounds. Novel GT-CV drug interactions were reported for rosuvastatin, sildenafil and tacrolimus. Putative mechanisms involve inhibitory effects of GT catechins at the intestinal level on influx transporters OATP1A2 or OATP2B1 for rosuvastatin, on CYP3A for sildenafil and on both CYP3A and the efflux transporter p-glycoprotein for tacrolimus. These interactions, which add to those previously described with simvastatin, nadolol and warfarin, might lead, in some cases, to reduced drug efficacy or risk of drug toxicity. Oddly, available data on GT interaction with CV compounds with a narrow therapeutic index, such as warfarin and tacrolimus, derive from single case reports. Conversely, GT interactions with simvastatin, rosuvastatin, nadolol and sildenafil were documented through pharmacokinetic studies. In these, the effect of GT or GT derivatives on drug exposure was mild to moderate, but a high inter-individual variability was observed. Further investigations, including studies on the effect of the dose and the time of GT intake are necessary to understand more in depth the clinical relevance of GT-CV drug interactions.

Overview of green tea interaction with cardiovascular drugs.

Sensitive to the massive diffusion of purported metabolic and cardiovascular positive effects of green tea and catechincontaining extracts, many consumers of cardiovascular drugs assume these products as a "natural" and presumably innocuous adjunctive way to increase their overall health. However, green tea may interfere with the oral bioavailability or activity of cardiovascular drugs by various mechanisms, potentially leading to reduced drug efficacy or increased drug toxicity. Available data about interactions between green tea and cardiovascular drugs in humans, updated in this review, are limited so far to warfarin, simvastatin and nadolol, and suggest that the average effects are mild to modest. Nevertheless, in cases of unexpected drug response or intolerance, it is warranted to consider a possible green tea-drug interaction, especially in people who assume large volumes of green tea and/or catechin-enriched products with the conviction that "more-is-better".

Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats.

Effects of green tea extract (GTE) on the activity of cytochrome P450 (CYP) enzymes and pharmacokinetics of simvastatin (SIM) were investigated in rats. Inhibitory effects of GTE on CYP3A activity were investigated in rat hepatic microsomes (RHM) using midazolam (MDZ) 1'-hydroxylation as a probe reaction. SD female rats received a single oral dose of GTE (400 mg/kg) or troleandomycin (TAO, a CYP3A selective inhibitor, 500 mg/kg), followed 30 min later by SIM (20 mg/kg). Plasma concentrations of SIM and its active metabolite, simvastatin acid, were determined up to 6 h after the SIM administration using LC/MS/MS. In RHM, GTE inhibited MDZ 1'-hydroxylation with IC50 and K(i)(app) values of 12.5 and 18.8 µg/mL, respectively, in a noncompetitive manner. Area under plasma concentration-time curves for SIM in the GTE and TAO groups were increased by 3.4- and 10.2-fold, respectively, compared with the control. The maximum concentrations of SIM were higher in the GTE (3.3-fold) and TAO (9.5-fold) groups. GTE alters the pharmacokinetics of SIM, probably by inhibiting intestinal CYP3A.

Effects of green tea catechins on cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A activities in human liver and intestinal microsomes.

The effects of green tea catechins on the main drug-metabolizing enzymatic system, cytochrome P450 (CYP), have not been fully elucidated. The objective of the present study was to evaluate the effects of green tea extract (GTE, total catechins 86.5%, w/w) and (-)-epigallocatechin-3-gallate (EGCG) on the activities of CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A in vitro, using pooled human liver and intestinal microsomes. Bupropion hydroxylation, amodiaquine N-deethylation, (S)-mephenytoin 4'-hydroxylation, dextromethorphan O-demethylation and midazolam 1'-hydroxylation were assessed in the presence or absence of various concentrations of GTE and EGCG to test their effects on CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A activities, respectively. Each metabolite was quantified using UPLC/ESI-MS, and the inhibition kinetics of GTE and EGCG on CYP enzymes was analyzed. In human liver microsomes, IC50 values of GTE were 5.9, 4.5, 48.7, 25.1 and 13.8 µg/mL, for CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A, respectively. ECGC also inhibited these CYP isoforms with properties similar to those of GTE, and produced competitive inhibitions against CYP2B6 and CYP2C8, and noncompetitive inhibition against CYP3A. In human intestinal microsomes, IC50 values of GTE and EGCG for CYP3A were 18.4 µg/mL and 31.1 µM, respectively. EGCG moderately inhibited CYP3A activity in a noncompetitive manner. These results suggest that green tea catechins cause clinically relevant interactions with substrates for CYP2B6 and CYP2C8 in addition to CYP3A.

Development of rapid and simultaneous quantitative method for green tea catechins on the bioanalytical study using UPLC/ESI-MS.

A rapid and quantitative analytical method for the simultaneous determination of green tea catechins using ultra-performance liquid chromatography/electrospray ionization-mass spectrometry was developed. Total analytical run time was 3.5 min for the detection of (-)-epicatechin (EC), (-)-epicatechin-3-O-gallate (ECG), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-O-gallate (EGCG) and myricetin as the internal standard (IS) in rat plasma. The calibration curves were linear over the range of 10-5000 ng/mL for all the catechins. The inter- and intra-day precision (relative standard deviation) and accuracy (percentage deviation) of the method were both lower than 10%. The average extraction recoveries in plasma ranged from 68.5 to 86.5%, and the lower limits of quantification of EC, EGC, ECG and EGCG were 10 ng/mL with a signal-to-noise ratio of >10. The assay developed was successfully applied to a pharmacokinetic study of catechins following intravenous and intragastric administrations of green tea extract in rats. Plasma concentrations of four catechins were detected up to 5-24 h after administration, and the pharmacokinetic parameters of catechins were in agreement with previous studies. From these findings, taken together with the high productivity and precision, the developed method could be a reliable and reproducible tool for the evaluation of pharmacokinetic properties of catechins.