[How to overcome barriers to implementation of prevention and management strategies of atherosclerotic cardiovascular disease through lipid-lowering therapy]. / Come superare le barriere all'implementazione delle strategie di prevenzione e cura della malattia cardiovascolare aterosclerotica mediante terapia ipolipemizzante.

Atherosclerotic cardiovascular diseases remain the main cause of mortality worldwide, due to a poor control of modifiable risk factors for atherosclerosis. High levels of low-density lipoprotein cholesterol represent the most relevant actor in the development of atherosclerotic cardiovascular diseases, as well as the main target of prevention strategies. Although lipid-lowering treatments were shown to be effective for cardiovascular prevention, several barriers (e.g. clinician reluctance to prescribe an intensive treatment, poor adherence of patients to therapy, high pharmacotherapy burden of high-risk patients and the fear for adverse events potentially associated with statins) still prevent therapy optimization. Such issues will be addressed in this review article, taking into account possible strategies for their solution, through an integrated approach including both management interventions and a larger use of the available pharmacologic options.

Hemostatic system in Takotsubo patients at long-term follow-up: A hidden activation?

BACKGROUND: Takotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients. METHODS: We assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit. RESULTS: Compared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase. CONCLUSIONS: The long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Atherogenic Dyslipidemias: Unmet Needs and the Therapeutic Potential of Emerging and Novel Approaches and Drugs.

Innovative lipid-modifying agents are valuable resources to improve the control of atherogenic dyslipidemias and reduce the lipid-related residual cardiovascular risk of patients with intolerance or who are not fully responsive to a consolidated standard of care (statins plus ezetimibe). Moreover, some of the upcoming compounds potently affect lipid targets that are thus far considered "unmodifiable". The present paper is a viewpoint aimed at presenting the incremental metabolic and cardiovascular benefits of the emerging lipid-modulating agents and real-life barriers, hindering their prescription by physicians and their assumption by patients, which need to be worked out for a more diffuse and appropriate drug utilization.

LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals.

AIMS: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. DATA SYNTHESIS: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. CONCLUSIONS: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.

Impact of Prior Statin Therapy on In-Hospital Outcome of STEMI Patients Treated with Primary Percutaneous Coronary Intervention.

Background: Prior statin therapy has a cardioprotective effect in patients undergoing elective or urgent percutaneous coronary intervention (PCI). However, data on patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI are still controversial. We retrospectively evaluated the effect of prior statin therapy on in-hospital clinical outcomes in consecutive STEMI patients undergoing primary PCI. Methods: A total of 1790 patients (mean age 67 ± 11 years, 1354 men) were included. At admission, all patients were interrogated about prior (>6 months) statin therapy. The primary endpoint of the study was the composite of in-hospital mortality, acute pulmonary edema, and cardiogenic shock in patients with or without prior statin therapy. Results: A total of 427 patients (24%) were on prior statin therapy. The incidence of the primary endpoint was similar in patients with or without prior statin therapy (15% vs. 16%; p = 0.38). However, at multivariate analysis, prior statin therapy was associated with a lower risk of the primary endpoint, after adjustment for major prognostic predictors (odds ratio 0.61 [95% CI 0.39−0.96]; p = 0.03). Conclusions: This study demonstrated that prior statin therapy is associated with a better in-hospital clinical outcome in patients with STEMI undergoing primary PCI compared to those without prior statin therapy.

Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes.

The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75 g of glucose during OGTT results in a systemic state of inflammation and oxidative stress. Therefore, we evaluated the effect of OGTT on oxidative stress and L-arginine/Nitric Oxide (L-Arg/NO) metabolic pathway in RBCs obtained from patients with prediabetes. Blood samples were collected from all participants before (T0) and at 10 (T1), 20 (T2), 30 (T3), 60 (T4), 90 (T5), 120 (T6), 150 (T7), and 180 (T8) minutes after glucose loading. Results showed a significant increase in oxidative stress status characterized by a rise in the GSSG/GSH ratio at T4 and T6 that increased in parallel with a reduction of NO production in RBCs. In addition, in this time frame, increased exposure of phosphatidylserine on RBCs membrane was observed. These metabolic modifications were rescued at T8, together with an increase in activated RBC NO synthase expression. These findings provide a possible explanation of the phenomena occurring after glucose loading and suggest that, even in the early stages of diabetes, it may be important to avoid acute variations in glycemia in order to prevent diabetic complications.

Psychological Characteristics of Patients with Takotsubo Syndrome and Patients with Acute Coronary Syndrome: An Explorative Study toward a Better Personalized Care.

During an acute cardiac event, Takotsubo Syndrome (TTS) and Acute Coronary Syndrome (ACS) apparently share very similar clinical characteristics. Since only a few inconsistent studies have evaluated the psychological features that characterize these different patients, the aim of the present explorative research was to investigate if post-recovery TTS and ACS patients present different psychological profiles. We also investigated whether the occurrence of acute psychological stressful episodes that had occurred prior to the cardiac event could be found in either syndrome. Twenty TTS and twenty ACS female patients were recruited. All patients completed self-report questionnaires about anxiety and depressive symptoms, perceived stress, type-D personality and post-traumatic symptoms. Results showed that only three subscales of health anxiety (i.e., Fear of Death/Diseases, Interference and Reassurance) significantly differed between the two groups, while no differences were found in the other psychological measurements. Moreover, personality traits seem to not be associated with the impact of the cardiac traumatic event. Finally, only TTS patients reported the presence of a significant emotional trigger preceding the acute cardiac event. In conclusion, post-recovery TTS patients differ from ACS patients in their level of concern about their health and in their need of reassurance and information only, probably as a result of the different clinical characteristics of the two illnesses.

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.

Persistent long-term platelet activation and endothelial perturbation in women with Takotsubo syndrome.

BACKGROUND: Takotsubo (TTS) syndrome is an acute cardiac condition characterized by transient and reversible left ventricle dysfunction that mainly affects postmenopausal women. Catecholamine burst is the most accredited mechanism underpinning TTS onset and leading to endothelial dysfunction and platelet activation. Even if the use of low dose acetylsalycilic acid (ASA) in this clinical setting is based on both clinical presentation and unfavorable long-term prognosis, its efficacy has been recently challenged. AIM: This study was designed to assess endothelial function, residual thromboxane formation and platelet aggregation in TTS women on low-dose ASA treatment at long-term follow-up. METHODS: Twenty-eight females with previously diagnosis of TTS syndrome were enrolled. Data were compared to those obtained from 23 coronary artery disease (CAD) women with a history of acute myocardial infarction, and 26 control subjects with no TTS or clinically evident CAD. Psychological and clinical profile were assessed in all study groups at the enrollment. Main metabolites involved in L-arginine/nitric oxide pathway, urinary prostacyclin, serum and urine thromboxane metabolites were measured by LCMS/MS methods. Thrombomodulin levels were quantified using an ELISA kit, and platelet aggregation, carried out on platelet rich-plasma, was induced by ADP or by epinephrine (EPI), norepinephrine (NORE) and TRAP-6, alone or in association with ADP and evaluated by Born's method. RESULTS: In TTS women an endothelial derangement, characterized by reduced citrulline production and increased thrombomodulin concentration, with no perturbation in prostacyclin levels, was evidenced. In addition, despite ASA treatment, TTS displayed a higher residual thromboxane formation, in parallel with an enhanced platelet response to compared to CAD. CONCLUSIONS: Our study highlighted the presence of endothelial perturbation in TTS patients even at long-term from the index event. The residual thromboxane production and platelet aggregation still leave open the question about the use of low dose ASA in this clinical setting.

Moving Safely to Phase 2 of the COVID-19 Pandemic: What Is More Pressing, Dates or Data?

An in-depth analysis of gathered data collected in several countries on the pre-infectious characteristics of patients who have developed severe forms of COVID-19 disease could be the basis for developing tools to estimate individual risk and tailor protective measures for a safer route through the Phase 2 of the pandemic.

Relationship between Influenza Vaccination Coverage Rate and COVID-19 Outbreak: An Italian Ecological Study.

Background: The lack of specific vaccines or drugs against coronavirus disease 2019 (COVID-19) warrants studies focusing on alternative clinical approaches to reduce the spread of this pandemic disease. In this study, we investigated whether anti-influenza vaccination plays a role in minimizing the diffusion of COVID-19 in the Italian population aged 65 and over. Methods: Four COVID-19 outcomes were used: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, hospitalizations for COVID-19 symptoms, admissions to intensive care units for reasons related to SARS-CoV-2, and deaths attributable to COVID-19. Results: At univariate analyses, the influenza vaccination coverage rates correlated negatively with all COVID-19 outcomes (Beta ranging from -134 to -0.61; all p < 0.01). At multivariable analyses, influenza vaccination coverage rates correlated independently with SARS-CoV-2 seroprevalence (Beta (95% C.I.): -130 (-198, -62); p = 0.001), hospitalizations for COVID-19 symptoms (Beta (95% C.I.): -4.16 (-6.27, -2.05); p = 0.001), admission to intensive care units for reasons related to SARS-CoV-2 (Beta (95% C.I.): -0.58 (-1.05, -0.12); p = 0.017), and number of deaths attributable to COVID-19 (Beta (95% C.I.): -3.29 (-5.66, -0.93); p = 0.010). The R2 observed in the unadjusted analysis increased from 82% to 159% for all the considered outcomes after multivariable analyses. Conclusions: In the Italian population, the coverage rate of the influenza vaccination in people aged 65 and over is associated with a reduced spread and a less severe clinical expression of COVID-19. This finding warrants ad hoc studies to investigate the role of influenza vaccination in preventing the spread of COVID-19.

Impact of BDNF Val66Met Polymorphism on Myocardial Infarction: Exploring the Macrophage Phenotype.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family, well known for its role in the homeostasis of the cardiovascular system. Recently, the human BDNF Val66Met single nucleotide polymorphism has been associated with the increased propensity for arterial thrombosis related to acute myocardial infarction (AMI). Using cardiac magnetic resonance imaging and immunohistochemistry analyses, we showed that homozygous mice carrying the human BDNF Val66Met polymorphism (BDNFMet/Met) undergoing left anterior descending (LAD) coronary artery ligation display an adverse cardiac remodeling compared to wild-type (BDNFVal/Val). Interestingly, we observed a persistent presence of pro-inflammatory M1-like macrophages and a reduced accumulation of reparative-like phenotype macrophages (M2-like) in the infarcted heart of mutant mice. Further qPCR analyses showed that BDNFMet/Met peritoneal macrophages are more pro-inflammatory and have a higher migratory ability compared to BDNFVal/Val ones. Finally, macrophages differentiated from circulating monocytes isolated from BDNFMet/Met patients with coronary heart disease displayed the same pro-inflammatory characteristics of the murine ones. In conclusion, the BDNF Val66Met polymorphism predisposes to adverse cardiac remodeling after myocardial infarction in a mouse model and affects macrophage phenotype in both humans and mice. These results provide a new cellular mechanism by which this human BDNF genetic variant could influence cardiovascular disease.

Gene-expression profiles of abdominal perivascular adipose tissue distinguish aortic occlusive from stenotic atherosclerotic lesions and denote different pathogenetic pathways.

Perivascular adipose tissue (PVAT) helps regulate arterial homeostasis and plays a role in the pathogenesis of large vessel diseases. In this study, we investigated whether the PVAT of aortic occlusive lesions shows specific gene-expression patterns related to pathophysiology. By a genome-wide approach, we investigated the PVAT transcriptome in patients with aortoiliac occlusive disease. We compared the adipose layer surrounding the distal aorta (atherosclerotic lesion) with the proximal aorta (plaque-free segment), both within and between patients with complete aortoiliac occlusion (Oc) and low-grade aortic stenosis (St). We found that PVAT of the distal versus proximal aorta within both Oc- and St-patients lacks specific, locally restricted gene-expression patterns. Conversely, singular gene-expression profiles distinguished the PVAT between Oc- and St-patients. Functional enrichment analysis revealed that these signatures were associated with pathways related to metabolism of cholesterol, vessel tone regulation, and remodeling, including TGF-ß and SMAD signaling. We finally observed that gene-expression profiles in omental-visceral or subcutaneous fat differentiated between Oc- and St-patients, suggesting that the overall adipose component associates with a different atherosclerosis burden. Our work points out the role of PVAT and, likely, other adipose tissues play in the pathophysiological mechanisms underlying atherosclerotic disease, including the abdominal aortic occlusive forms.

Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm.

Objective- Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of large vessel diseases, including abdominal aortic aneurysm (AAA). Herein, we tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA, indicating specific dysfunctions associated with the disease. Approach and Results- Using a paired sample design to limit the effects of interindividual variation, we performed a microarray-based investigation of the PVAT transcriptome in 30 patients with AAA, comparing the adipose layer of the dilated abdominal aorta with that of the not-dilated aortic neck in each patient. Furthermore, we used a state-of-the-art data mining procedure to remove the effect of confounders produced by high-throughput gene expression techniques. We found substantial differences in PVAT gene expression clearly distinguishing the dilated from the not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. Comparisons with other adipose depots (omental or subcutaneous fat) confirmed that gene expression changes are locally restricted. We dissected putative mechanisms associated with AAA PVAT dysfunction through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans, and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of the not-dilated aorta. Conclusions- Our results support a possible function of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. Interfering with these disease-specific pathways would clarify their precise role in AAA pathogenesis.

[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.

Exploring the Barriers to and Facilitators of Using Evidence-Based Drugs in the Secondary Prevention of Cardiovascular Diseases: Findings From a Multistakeholder, Qualitative Analysis.

BACKGROUND: Health-system barriers and facilitators associated with cardiovascular medication adherence have seldom been studied, particularly in low- and middle-income countries where uptake rates are poorest. OBJECTIVES: This study sought to explore the major obstacles and facilitators to the use of evidence-supported medications for secondary prevention of cardiovascular disease using qualitative analysis in 2 diverse countries across multiple levels of their health care systems. METHODS: A qualitative descriptive study approach was implemented in Hamilton, Ontario, Canada, and Delhi, India. A purposeful sample (n = 69) of 23 patients, 10 physicians, 2 nurse practitioners, 5 Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy physicians, 11 pharmacists, 3 nurses, 4 hospital administrators, 1 social worker, 3 nongovernmental organization workers, 2 pharmaceutical company representatives, and 5 policy makers participated in interviews in Hamilton, Ontario, Canada (n = 21), and Delhi, India (n = 48). All interviews were digitally recorded and transcribed followed by directed content analysis to summarize and categorize the interviews. RESULTS: Themes that emerged across the stakeholder groups included: medication counseling; monitoring adherence; medication availability; medication affordability and drug coverage; time restrictions; and task shifting. The depth of verbal medication counseling provided varied substantially between countries, with prescribers in India unable to convey relevant information about drug treatments due to time constraint and high patient load. Canadian patients reported drug affordability as a common issue and very few patients were familiar with government subsidized drug programs. In India, patients purchased medications out-of-pocket from private, community pharmacies to avoid long commutes, lost wages, and unavailability of medications from hospitals formularies. Task shifting medication-refilling and titration to nonphysician health workers was accepted and supported by physicians in Canada but not in India, where many of the physicians considered a high level of clinical expertise a precondition to carry out these tasks skillfully. CONCLUSIONS: Our findings reveal context-specific, health system factors that affect the patient's choice or ability to initiate and/or continue cardiovascular medication. Strategies to optimize cardiovascular drug use should be targeted and relevant to the health care system.

Assessing Free-Radical-Mediated DNA Damage during Cardiac Surgery: 8-Oxo-7,8-dihydro-2'-deoxyguanosine as a Putative Biomarker.

Coronary artery bypass grafting (CABG), one of the most common cardiac surgical procedures, is characterized by a burst of oxidative stress. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), produced following DNA repairing, is used as an indicator of oxidative DNA damage in humans. The effect of CABG on oxidative-induced DNA damage, evaluated through the measurement of urinary 8-oxodG by a developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in 52 coronary artery disease (CAD) patients, was assessed before (T0), five days (T1), and six months (T2) after CABG procedure. These results were compared with those obtained in 40 subjects with cardiovascular risk factors and without overt cardiovascular disease (CTR). Baseline (T0) 8-oxodG was higher in CAD than in CTR (p = 0.035). A significant burst was detected at T1 (p = 0.019), while at T2, 8-oxodG levels were significantly lower than those measured at T0 (p < 0.0001) and comparable to those found in CTR (p = 0.73). A similar trend was observed for urinary 8-iso-prostaglandin F2α (8-isoPGF2α ), a reliable marker of oxidative stress. In the whole population baseline, 8-oxodG significantly correlated with 8-isoPGF2α levels (r = 0.323, p = 0.002). These data argue for CABG procedure in CAD patients as inducing a short-term increase in oxidative DNA damage, as revealed by 8-oxodG concentrations, and a long-term return of such metabolite toward physiological levels.