Clinical impact of high platelet reactivity in patients with atrial fibrillation and concomitant percutaneous coronary intervention on dual or triple antithrombotic therapy.

High platelet reactivity (HPR) on clopidogrel is an established thrombotic risk factor after percutaneous coronary intervention (PCI). The introduction of more potent antiplatelet drugs has partially surpassed this issue. However, in the setting of concomitant atrial fibrillation (AF) and PCI clopidogrel is still the most adopted P2Y12 inhibitor. In the present study all consecutive patients with history of AF discharged from our cardiology ward with dual (DAT) or triple (TAT) antithrombotic therapy after a PCI from April 2018 to March 2021 were enrolled in an observational registry. For all subjects, blood serum samples were collected and tested for platelet reactivity by arachidonic acid and ADP (VerifyNow system) and genotyping of the CYP2C19*2 loss-of-function polymorphism. We recorded at 3 and 12-months follow-up: (1) major adverse cardiac and cerebrovascular events (MACCE), (2) major hemorrhagic or clinically relevant non-major bleeding and (3) all-cause mortality. A total of 147 patients were included (91, 62% on TAT). In 93.4% of patients, clopidogrel was chosen as P2Y12 inhibitor. P2Y12 dependent HPR resulted an independent predictor of MACCE both at 3 and 12 months (HR 2.93, 95% C.I. 1.03 to 7.56, p = 0.027 and HR 1.67, 95% C.I. 1.20 to 2.34, p = 0.003, respectively). At 3-months follow-up the presence of CYP2C19*2 polymorphism was independently associated with MACCE (HR 5.21, 95% C.I. 1.03 to 26.28, p = 0.045). In conclusion, in a real-world unselected population on TAT or DAT, the entity of platelet inhibition on P2Y12 inhibitor is a potent predictor of thrombotic risk, suggesting the clinical utility of this laboratory evaluation for a tailored antithrombotic therapy in this high-risk clinical scenario. The present analysis was performed in patients with AF undergoing PCI on dual or triple antithrombotic therapy. At 1 year follow-up MACCE incidence was consistent, and it was not different in different antithrombotic pattern groups. P2Y12 dependent HPR was a potent independent predictor of MACCE both at 3- and 12-months follow-up. In the first 3 months after stenting the carriage of CYP2C19*2 allele was similarly associated with MACCE. Abbreviation: DAT, dual antithrombotic therapy; HPR, high platelet reactivity; MACCE, major adverse cardiac and cerebrovascular events; PRU, P2Y12 reactive unit; TAT, triple antithrombotic therapy. Created with BioRender.com.

Peripheral arterial disease has a strong impact on cardiovascular outcome in patients with acute coronary syndromes: from the START Antiplatelet registry.

BACKGROUND: Peripheral arterial disease (PAD) was reported to increase the risk of new cardiovascular events in patients with acute coronary syndromes (ACS). However, most of the evidence comes from randomized clinical trials. We aimed to assess the impact of PAD on cardiovascular outcome and treatment decisions in ACS patients in a current real-life setting. METHODS: START-ANTIPLATELET is a multicenter registry enrolling ACS patient. Baseline clinical characteristics and treatment at discharge were recorded and follow-up was repeated at 6-months and 1-year. PAD was defined as intermittent claudication and/or previous revascularization. RESULTS: Among 1442 patients enrolled, 103 (7.1%) had PAD. PAD patients were older (71.8 ± 10.6vs66.2 ± 12.6 yrs., p < 0.0001), more frequently hypertensive (90.3vs68.6%, p< 0.0001), hypercholesterolemic (66vs52%, p= 0.037), diabetic (51.5vs24%, p= 0.0001), obese (28.2vs19.3%, p= 0.029) and with previous TIA (7.8vs2.8%, p= 0.005) or stroke (11.7vs3.1%, p< 0.0001). Clinical presentation and acute treatment were similar in non-PAD and PAD patients, but the latter were discharged significantly less frequently on dual antiplatelet therapy (DAPT) (68.9vs85%, p= 0.005). After a median follow-up time of 11.1 months, major cardio/cerebrovascular event-free survival [MACCE, including cardiovascular death, MI, TIA and stroke, target-vessel revascularization (TVR) and major arterial ischemic events] was significantly shorter (9.0vs11.2 months, p= 0.02; HR 3.2, 2.4-8.4) in PAD patients and net adverse cardiovascular events (NACE = MACCE plus major hemorrhages) were significantly more frequent (19.1%vs10.5%, p = 0.049). CONCLUSIONS: PAD identifies a subgroup of ACS patients at significantly increased cardiovascular risk, but these patients tend to be undertreated. Patients admitted for ACS should be screened for PAD and optimal medical therapy at discharge should be implemented.

Mediterranean, but not lacto-ovo-vegetarian, diet positively influence circulating progenitor cells for cardiovascular prevention: The CARDIVEG study.

AIM: To evaluate the possible association between dietary habits and progenitor cells using data obtained from a randomized crossover trial using two different diets, lacto-ovo-vegetarian (VD) and Mediterranean (MD), the CARDIVEG study. METHODS AND RESULTS: Eighty clinically healthy subjects with a low-to-moderate cardiovascular risk profile (61 F; 19 M; mean age: 50.7 ± 11.6 years) were randomly assigned to isocaloric VD and MD diets lasting three months each, and then crossed. The two diets showed no effects on endothelial progenitor cells and circulating endothelial cells but opposite effects on circulating progenitor cells. In fact, VD determined significant (p < 0.05) and negative changes on circulating progenitor cells, with an average geometric variation of -130 cells/106 events for CD34+/CD45-/dim, -80 cells/106 events for CD133+/CD45-/dim, and -84 cells/106 events for CD34+/CD133+/CD45-/dim while MD determined significant (p < 0.05) and positive changes for CD34+/CD45-/dim levels, with a geometric mean increase of +54 cells/106 events. No significant correlations were observed between changes in progenitor cells and changes in inflammatory parameters during the VD phase. On the other hand, during the MD phase negative correlations between changes of CD34+/CD45-/dim and interleukin-6 (R = -0.324; p = 0.004) as well as interleukin-8 (R = -0.228; p = 0.04) and monocyte chemotactic protein-1 (R = -0.277; p = 0.01), were observed. These correlations remained significant also after adjustment for confounding factors only for CD34+/CD45-/dim and interleukin-6 (ß = -0.282; p = 0.018) and monocyte chemotactic protein-1 (ß = -0.254; p = 0.031). CONCLUSIONS: MD, but not VD, reported a significant and positive effect on circulating progenitor cells in a group of subjects at low-to-moderate cardiovascular risk, probably acting through the modulation of inflammatory parameters.

Effects of a 3-month dietary intervention with a lacto-ovo-vegetarian diet on vitamin B12 levels in a group of omnivores: results from the CARDIVEG (Cardiovascular Prevention with Vegetarian Diet) study.

Previous studies have suggested that vegetarianism can result in a reduction of vitamin B12 circulating levels. The aim of the present study was to investigate the effects of a 3-month dietary intervention with a lacto-ovo-vegetarian diet (VD) on the levels of circulating vitamin B12 in a group of omnivores. We analysed fifty-four omnivorous subjects who followed a VD as a first dietary intervention within the CARDIVEG (Cardiovascular Prevention with Vegetarian Diet) study, a dietary intervention study. VD resulted in a significant reduction (P<0·001) of 51·2 % of vitamin B12 intake and in a significant reduction (P=0·005) of 6·2 % of the circulating levels of vitamin B12 (-24·5 pg/ml). Changes in vitamin B12 intake were significantly correlated with changes in circulating levels of vitamin B12 (R 0·61, P<0·001). Subgroup analyses showed that reduction in circulating vitamin B12 levels was more evident in participants who were younger, overweight, non-smokers and had hypercholesterolaemia. A logistic regression analysis showed that a reduction in vitamin B12 intake greater than the first quartile of the delta changes obtained in the study population (-28·5 %) conferred a significantly higher risk of experiencing a decrease in circulating vitamin B12 levels (OR 10·1; 95 % CI 1·3, 76·1). In conclusion, a 3-month VD period determined a significant reduction in circulating levels of vitamin B12, being significantly correlated with the reduction in vitamin B12 intake. Although a well-planned VD can provide adequate nutrition across all life stages, special care must be taken to ensure adequate vitamin B12 intake and to help prevent deficiency.

Comparison of five specific assays for determination of dabigatran plasma concentrations in patients enrolled in the START-Laboratory Register.

INTRODUCTION: Several specific assays are commercially available to determine dabigatran anticoagulant activity. Aims of this multicenter and multiplatform study were to compare five methods for dabigatran measurement and investigate their performances in the low concentration range. METHODS: Dabigatran levels were analyzed in 295 plasma samples from patients enrolled in the START-Laboratory Register by the following methods using dedicated calibrators and controls: STA-ECA II (Diagnostica Stago), standard and low range Hemoclot Thrombin Inhibitors (Hyphen BioMed), Direct Thrombin Inhibitor Assay (Instrumentation Laboratory), Direct Thrombin Inhibitor Assay (Siemens), Technoclot DTI (Technoclone). RESULTS: Methods showed variable agreement with the Hemoclot Thrombin Inhibitors assay used as reference test, with modest under- or overestimations (Bland-Altman bias from -17.3 to 4.0 ng/mL). Limits of detection and quantification varied depending on the assay (4-52 and 7-82 ng/mL, respectively). Between-run precision and accuracy were good for all methods for both quality control levels. Assay's repeatability assessed at very low dabigatran concentrations (from 10 to 60 ng/mL) was also acceptable, variability generally increased at lower drug levels. CONCLUSION: The five dabigatran-specific assays evaluated in this study provided reliable assessment of dabigatran plasma levels, although showing different performances.

Aging process, adherence to Mediterranean diet and nutritional status in a large cohort of nonagenarians: Effects on endothelial progenitor cells.

BACKGROUND AND AIM: Adherence to the Mediterranean Diet (MD) has been associated with a longer and better life. The aim of this study was to examine the effects of adherence to the MD, and of nutritional habits on endothelial progenitor (EPCs) and circulating progenitor (CPCs) cells in a cohort of nonagenarians enrolled within the Mugello Study, an epidemiological study aimed at investigating both clinically relevant geriatric items and various health issues, including those related to nutritional status. METHODS AND RESULTS: Four hundred twenty-one nonagenarians (306 F, 115 M, mean age: 93.1 ± 3.2 years) were evaluated. Adherence to MD was assessed through the Mediterranean Diet Score. Elderly subjects who were in the fourth quartile of the Mediterranean diet score showed significantly higher EPCs than subjects grouped into the other three quartiles. After adjustment for confounders, elderly subjects who were in the highest quartile of adherence to the MD score reported to have EPCs' levels significantly higher than those who reported lower values of adherence to the MD. Furthermore, by analyzing different food categories, it was reported that daily consumption of olive oil and a higher consumption of fruit and vegetables showed higher CPCs CD34+ and EPCs CD34+/KDR+ than subjects with not daily or lower consumption. CONCLUSION: Our results support the hypothesis that the adherence to MD, as well as a daily consumption of olive oil and fruit and vegetables, characteristics of MD, may protect against the development of endothelial dysfunction through increasing EPCs and CPCs in older age.

Erythrocyte oxidative stress is associated with cell deformability in patients with retinal vein occlusion.

Essentials Retinal vein occlusion (RVO), characterized by blood hyperviscosity, has an unclear pathogenesis. We aimed to find out if hemorheological profile is altered by oxidative stress in RVO patients. Red blood cell (RBC) oxidative stress is associated to whole blood viscosity and RBC deformability. Reactive oxygen species alter RBC membrane rigidity, playing a key role in RVO pathogenesis. SUMMARY: Background Retinal vein occlusion (RVO) is characterized by vision loss resulting from hypoperfusion and hypoxia of the retina. RVO pathogenesis is not yet fully understood, although blood hyperviscosity has been observed. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to microvascular perfusion and oxygen delivery. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Objectives To determine whether erythrocytes from RVO patients show signs of oxidative stress, and whether this condition can modify the hemorheologic profile in these patients. Patients and Methods We analyzed the entire hemorheologic profile and erythrocyte oxidative stress - reactive oxygen species (ROS) production and membrane lipid peroxidation - in 128 RVO patients and 128 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results In RVO patients, erythrocyte oxidative stress was present and positively correlated with whole blood viscosity and erythrocyte deformability. Multivariate linear regression analysis after adjustment for age, cardiovascular risk factors, medications, leukocyte number and mean corpuscular volume indicated that erythrocyte-derived ROS and erythrocyte lipid peroxidation were significantly and positively correlated with erythrocyte membrane viscosity and deformability. Moreover, in vitro experiments demonstrated that ROS have a key role in erythrocyte membrane fluidity. Conclusions Our findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of RVO, and pave the way to new therapeutic interventions.

Adherence to lifestyle modifications after a cardiac rehabilitation program and endothelial progenitor cells. A six-month follow-up study.

An increase of endothelial progenitor cells (EPCs) among acute myocardial infarction (AMI) patients participating in a cardiac rehabilitation (CR) program has been reported, but no data on the impact of adherence to lifestyle recommendations provided during a CR program on EPCs are available. It was our aim to investigate the effect of adherence to lifestyle recommendations on EPCs, inflammatory and functional parameters after six months of a CR program in AMI patients. In 110 AMI patients (90 male/20 female; mean age 57.9 ± 9.4 years) EPCs, high sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels, and cardiopulmonary testings were determined at the end of the CR (T1) and at a six-month follow-up (T2). At T2 we administered a questionnaire assessing dietary habits and physical activity. At T2, we observed a decrease of EPCs (p<0.05), of hsCRP (p=0.009) and of NT-ProBNP (p<0.0001). Patient population was divided into three categories by Healthy Lifestyle (HL) score (none/low, moderate and high adherence to lifestyle recommendations). We observed a significant association between adherence to lifestyle recommendations, increase in EPCs and exercise capacity between T1 and T2 (Δ EPCs p for trend <0.05; ΔWatt max p for trend=0.004). In a multivariate logistic regression analyses, being in the highest tertile of HL score affected the likelihood of an increase of EPC levels at T2 [OR (95% confidence interval): 3.36 (1.0-10.72) p=0.04]. In conclusion, adherence to lifestyle recommendations provided during a CR program positively influences EPC levels and exercise capacity.

Hipotiroidismo subclínico en mujeres infértiles / Subclinical Hypothyroidism in Infertile Women

Objetivo: Comparar la frecuencia de hipotiroidismo subclínico (HSC) entre mujeres con infertilidad primaria (IP) y secundaria (IS) asistidas en la consulta de ginecología de la Maternidad “Dr. Armando Castillo Plaza”, en Maracaibo, estado Zulia. Métodos: Investigación comparativa y aplicada, con diseño de tipo no experimental, contemporáneo transeccional y de campo en la cual se incluyeron 100 mujeres con infertilidad, separadas en dos grupos pareados en relación con el tipo de infertilidad, a las cuales se les determinó el perfil hormonal tiroideo: hormona estimuladora del tiroides (TSH), tiroxina libre (FT4) y triiodotiroxina libre (FT3). Resultados: No se evidenciaron diferencias estadísticas significativas entre las mujeres con IP o IS, en cuanto a edad, menarquía, sexarquía, número de parejas y tiempo de convivencia. En las mujeres con IP prevaleció el factor ovulatorio (50 %) seguido del tubo-peritoneal (34 %), mientras que entre las pacientes con IS el factor principal fue el tubo-peritoneal (38 %) seguido del ovulatorio (28 %); mostrando solamente el factor ovulatorio una diferencia significativa (p< 0,05). Se determinó que las pacientes con IP presentaron significativamente concentraciones más elevadas tanto de la TSH (3,14 ± 2,08 vs. 2,33 ± 1,59; p< 0,05) como de FT4 (1,19 ± 0,37 vs. 1,04 ± 0,25; p< 0,05); determinándose una prevalencia de HSC en mujeres infértiles del 17 %; siendo más frecuente y significativo en el grupo de mujeres con IP que en las pacientes con IS (26 % vs. 8 %; OR [IC95%]= 4,04 [1,26 -13,43]; p < 0,05), en tanto que según la severidad del HSC todos los casos detectados en ambos grupos se encontraban dentro del grado I. Conclusión: Existe una mayor prevalencia de HSC entre las mujeres con IP que en las pacientes con IS.

Objective: To compare the frequency of subclinical hypothyroidism (SCH) among women with primary (PI) and secondary infertility (SI) who presented for gynecology consultation at Maternity "Dr. Armando Castillo Plaza" in Maracaibo, Zulia state. Methods: Comparative and applied research with non-experimental, contemporary transactional and field design, including 100 women with infertility, separated into two groups matched for the type of infertility. Thyroid hormone profile: thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3) were measured in these women. Results: There were no statistically significant differences between women with PI or secondary SI, in terms of age, menarche, sexarche, number of partners and length of cohabitation. In women with PI the ovulatory factor prevailed (50 %) followed by the tube-peritoneal (34 %), while among patients with SI the main factor was the tube-peritoneal (38 %) followed by the ovulatory (28 %); only the ovulatory factor showed a significant difference (p < 0.05). PI patients had significantly higher concentrations of both TSH (3.14 ± 2.08 vs. 2.33 ± 1.59, p <0.05) and FT4 (1.19 ± 0, 37 vs. 1.04 ± 0.25, p < 0.05); the prevalence of SCH was determined at 17% in infertile women, being more frequent and significant in the PI group of women than in SI patients (26 % vs. 8 %, OR [95 % CI] = 4.04 [1.26-13.43], p < 0.05), while according to the severity of SCH all cases detected in both groups were within grade I. Conclusion: There is a higher prevalence of SCH in women with PI than in patients with SI.

Reticulated platelets predict cardiovascular death in acute coronary syndrome patients. Insights from the AMI-Florence 2 Study.

Reticulated platelets (RP) are newly-formed platelets with a greater mass, a residual amount of RNA and an increased prothrombotic potential. No studies investigating the association between RP and the risk of cardiovascular death in acute coronary syndrome (ACS) patients are available. In the frame of the AMI-Florence 2 study, we investigated RP in 229 (154 M/ 75 F) ACS patients (125 ST-elevation myocardial infarction [STEMI]; 104 Non-STEMI/Unstable Angina). RP were measured by using the Sysmex XE-2100 haematology analyzer and were expressed as the percentage of RP out of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (H-IPF). At one-year follow-up, 22 out of 229 patients (9.6%) died from cardiovascular causes. Higher values of IPF (p=0.05) and H-IPF (p=0.006) were detected in dead compared to alive patients. A receiver operating characteristics curve analysis identified IPF ≥3.3% and H-IPF ≥0.9% as optimal cut-off values to predict cardiovascular death. At the multivariate model adjusted for the Global Registry of Acute Coronary Events (GRACE) risk score, the association between RP and cardiovascular death remained significant for both IPF [OR (95%CI) : 4.15 (1.24-13.91) p=0.02] and H-IPF [OR (95%CI): H-IPF 5.03 (1.38-18.38) p=0.01]. In conclusion, RP are independent predictors of cardiovascular death and may be useful in improving risk stratification for ACS patients. Future prospective studies to evaluate the role of RP in determining cardiovascular events are warranted.

A interface da gestão em saúde e assistência domiciliar da Coordenadoria Regional de Saúde Sul do município de São Paulo

A regulamentação da modalidade de Assistência Domiciliar no SUS iniciou-se através da LEI Nº 10.424/02 do Ministério da Saúde (MS). Em 2002, os serviços de assistência domiciliar (UAD) foram implantados oficialmente pela SMS/PMSP

Conhecendo o idoso na Atenção Básica - Coordenadoria Regional de Saúde Sul de São Paulo

Desde 2006 o Ministério da Saúde e a Secretaria de Saúde do Município de São Paulo vem implementando ações para a Política Nacional de Saúde da Pessoa Idosa e, em 2008, implantou a Caderneta Nacional de Saúde da Pessoa Idosa com o objetivo de conhecer e monitorar os idosos usuários do SUS

Perfil dos usuários em Assistência Domiciliar no SUS – Coordenadoria Regional de Saúde Sul da cidade de São Paulo

A incidência de usuários com dependência para a realização das atividades de vida diária (AVD) é crescente e tem sido regulamentada pelo Ministério da Saúde desde 2002. Essa população deve ser atendida no ambiente domiciliar buscando melhor conforto e segurança. Na região sul do município de São Paulo, esse atendimento é realizado pela atenção básica, por equipes de assistência domiciliar (UAD) e unidades básicas de saúde (UBS/ESF) que acompanham os pacientes crônicos acamados estáveis, em domicílio, com suporte das UAD

A interface da gestão em saúde e assistência domiciliar da coordenadoria regional de saúde sul do município de São Paulo / The interface of health management and home care of the health region, south of São Paulo

A regulamentação da modalidade de Assistência Domiciliar no SUS iniciou-se através da LEI Nº 10.424/02 do Ministério da Saúde (MS). Em 2002, os serviços de assistência domiciliar (UAD) foram implantados oficialmente pela SMS/PMSP.

Perfil dos usuários em assistência domiciliar no SUS: coordenadoria regional de saúde sul da cidade de São Paulo / Profile of home care users in the SUS: regional health south of the city of Sao Paulo

A incidência de usuários com dependência para a realização das atividades de vida diária (AVD) é crescente e tem sido regulamentada pelo Ministério da Saúde desde 2002. Essa população deve ser atendida no ambiente domiciliar buscando melhor conforto e segurança. Na região sul do município de São Paulo, esse atendimento é realizado pela atenção básica, por equipes de assistência domiciliar (UAD) e unidades básicas de saúde (UBS/ESF) que acompanham os pacientes crônicos acamados estáveis, em domicílio, com suporte das UAD.

Conhecendo o idoso na atenção básica: coordenadoria regional de saúde sul de São Paulo / Knowing the elderly in primary care: health region, south of Sao Paulo

Desde 2006 o Ministério da Saúde e a Secretaria de Saúde do Município de São Paulo vem implementando ações para a Política Nacional de Saúde da Pessoa Idosa e, em 2008, implantou a Caderneta Nacional de Saúde da Pessoa Idosa com o objetivo de conhecer e monitorar os idosos usuários do SUS.

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome.

BACKGROUND AND AIM: Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n=247) or absence (n=883) of type 2 diabetes in ACS patients. METHODS AND RESULTS: We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p=0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [ß (SE)=0.17 (0.07), p=0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not -786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the -786C/894G/4a and -786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus. CONCLUSIONS: Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.

Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis.

Several polymorphisms in genes that encode platelet components (receptors or enzymes), or cytochrome P450 enzyme isoforms, involved in clopidogrel metabolism, have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Among them, a great deal of attention has been focused on the loss-of-function CYP2C19(*)2 (or 681 G > A) polymorphism. We performed a meta-analysis of all the prospective studies that have been published, which analyze the role of such a polymorphism in recurrent cardiovascular events in patients with coronary artery disease (CAD) being treated with clopidogrel. Studies were searched in MedLine, Embase, Web of Science, The Cochrane Systematic Review Database, Google Scholar and bibliographies of retrieved articles up to January 2010. The principal underlying hypothesis was that the presence of the (*)2 variant allele of the polymorphism would be associated with an increased risk of clinical recurrence. Data were available for a total of 8043 patients from seven cohort prospective studies, who were followed for a period of time ranging from 6 months to 8.3 years. The summary risk ratios (RRs) for the prospective cohort studies included showed a significant association between the CYP2C19(*)2 polymorphism and an increased risk of major adverse cardiovascular events in the follow-up (RR: 1.96 (1.14-3.37); P = 0.02). When studies evaluating stent thrombosis (n = 4) for a total of 4975 patients were considered, the presence of the variant allele was associated with an increased risk of stent thrombosis (RR: 3.82 (2.23-6.54); P = 0.0001). The current meta-analysis, carried out on nearly 8000 patients with CAD undergoing clopidogrel treatment, shows that the CYP2C19(*)2 polymorphism is associated with an increased risk of major adverse cardiovascular events and stent thrombosis.

High sensitivity C-reactive protein predicts the development of new carotid artery plaques in older persons.

BACKGROUND AND AIM: Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated. METHODS AND RESULTS: 486 "InCHIANTI" Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques. Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95%CI 1.5-1.9) and 1.9 (95%CI 1.2-3.1), respectively. Participants with high (>3 µg/mL) and moderate (≥1 and ≤3 µg/mL) CRP levels had a relative risk of 2.2 (95%CI 1.9-2.6) and 1.9 (95%CI 1.6-2.3) respectively, when compared with subjects with low (<1 µg/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significant predictors of the development of new carotid artery plaques. CONCLUSIONS: High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions.

Lower homocysteine levels in renal transplant recipients treated with everolimus: a possible link with a decreased cardiovascular risk?

Cardiovascular disease (CVD) is the main cause of morbidity and mortality in renal transplant recipients. The incidence of CVD in this setting is approximately 5-fold greater than in age- and and gender-matched subjects. This excess cardiovascular risk is not completely explained by traditional cardiac risk factors. It has been well documented that these patients show greatly increased prevalence of both fasting and postmethionine-loading hyperhomocysteinemia (hHcy) compared with the general population. An immunosuppressive therapy based on everolimus has been demonstrated to reduce the incidence major adverse coronary events at 4 years compared with azathioprine among heart transplant recipients. In contrast, scarce data are available on the impact of everolimus on emerging risk factors, such as homocysteine (Hcy), in renal transplant recipients. The aim of this study was to evaluate the possible impact of everolimus compared with other immunosuppressive regimes among 132 stable recipients, including 91 men and 41 women who were at least 1 year after transplant with stable renal function and no clinical evidence of acute or chronic renal graft rejections. We compared 31 subjects on everolimus immunosuppressive therapy (group A) versus 101 on immunosuppressive therapy based on cyclosporine, steroids, and mycophenolate. The Hcy levels were significantly lower among group A patients compared with group B: 16.5 +/- 5 micromol/L vs 21.2 +/- 11 micromol/L; P < .005. Hyper-Hcy, defined as Hcy levels >15 micromol/L, was diagnosed in 18 out of 31 patients (51%) of group A and in 82 out of 101 patients (81%) of group B. This preliminary study demonstrates a favorable impact of everolimus on a marker of atherothrombosis which is associated with a worse vascular prognosis.