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Cause ed epidemiologia analitica

  • Lorenzo Richiardi1

  1. Università di Torino

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Ricerca bibliografica periodo 02 giugno 2011 – 01 agosto 2011

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All’interno dell’area “Cause ed epidemiologia analitica” in questo numero saranno selezionati gli articoli relativi al tema: Malattie cardiovascolari.

Di ogni articolo è disponibile l'abstract. Per visualizzarlo basta cliccare sul titolo.

1. Zanon E, Iorio A, Rocino A, Artoni A, Santoro R, Tagliaferri A, Coppola A, Castaman G, Mannucci PM; the Italian Association of Hemophilia Centers. Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors. Haemophilia. 2011 Jul 14. doi: 10.1111/j.1365-2516.2011.02611.x. [Epub ahead of print]
Haemophilia Center, 2nd Chair Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, ON, Canada Haemophilia and Thrombosis Center, San Giovanni Bosco Hospital Department of Medicine and Medical Specialities, IRCCS Maggiore Hospital, University of Milan Haemophilia Center, Department of Oncology and Hematology, Pugliese Ciaccio Hospital Regional Reference of Inherited Bleeding Disorders, University Hospital of Parma, Medicine Centro di Coordinamento Regionale per le Emocoagulopatie - Department of Clinical and Experimental Medicine, Federico II University of Naples Department of Hematology, San Bortolo Hospital Department of Medicine and Medical Specialities, IRCCS Maggiore Hospital, University of Milan.

Abstract
Intracranial haemorrhage (ICH) is the most serious bleeding symptom in Summary. haemophiliacs, resulting in high rates of mortality and disabling sequelae. The Association of Italian Haemophilia Centres carried out a retrospective survey (1987-2008) of ICH occurring in haemophiliacs with the goals to establish: (i) incidence, location of bleeding, death rate and disabling sequels; (ii) risk factors for ICH; and (iii) treatment used during the acute phase of ICH and for recurrence prevention. A total of 112 ICH episodes had occurred in 88 patients (78 haemophilia A, 10 haemophilia B), 24 of whom experienced recurrences. The cumulative hazard of ICH for the whole cohort over the entire follow-up period was 26.7 per 1000 patients, and the annualized rate of ICH was 2.50 events per 1000 patients (95% CI 1.90-3.31). The risk of ICH was higher in the youngest children (24.4 per 1000, 95% CI 12.7-47.0 in the first year of age and 14.9, 95% CI 7.1-31.4 in the second year of age) and then progressively rose again after the age of 40. Univariate, bivariate (age-adjusted) and multivariate analysis investigating the effects of patient characteristics on ICH occurrence showed that haemophilia severity and inhibitor status were strongly associated with ICH [severe vs. mild, HR 3.96 (2.39-6.57); inhibitor vs. non-inhibitor 2.52 (1.46-4.35)]. HCV infection was also associated with the risk of ICH [HR 1.83 (1.25-2.69)]. Therapeutic suggestions based upon our experience to control ICH recurrence are provided.

2. Colivicchi F, Mocini D, Tubaro M, Aiello A, Clavario P, Santini M. Effect of Smoking Relapse on Outcome After Acute Coronary Syndromes. Am J Cardiol. 2011 Jul 7. [Epub ahead of print]
Cardiovascular Department, San Filippo Neri Hospital, Rome, Italy.

Abstract
The aim of the present study was to evaluate the smoking relapse rate among smokers who had become abstinent during admission for acute coronary syndromes. The association between smoking relapse and mortality was also analyzed. A cohort of 1,294 consecutive active smokers who had interrupted smoking after admission for acute coronary syndromes (1,018 men and 276 women, mean age 59.7 ± 12.3 years) was followed up for 12 months after the index admission. All patients received a brief in-hospital smoking cessation intervention consisting of repeated counseling sessions. During follow-up, 813 patients (62.8%) resumed regular smoking (median interval to relapse 19 days, interquartile range 9 to 76). Increasing age (hazard ratio [HR] 1.034 per year, 95% confidence interval [CI] 1.028 to 1.039, p = 0.001) and female gender (HR 1.23, 95% CI 1.09 to 1.42, p = 0.03) were independent predictors of smoking relapse. Patients enrolled in a cardiac rehabilitation program (HR 0.74, 95% CI 0.51 to 0.91, p = 0.02) and those with diabetes (HR 0.79, 95% CI 0.68 to 0.94, p = 0.03) were more likely to remain abstinent. During follow-up, 97 patients died (1-year probability of death 0.075, 95% CI 0.061 to 0.090). Multivariate analysis with the Cox proportional hazard regression method, including smoking relapse as a time-dependent covariate, demonstrated that, after adjustment for patient demographics, the clinical history features and variables related to the index event, the resumption of smoking was an independent predictor of total mortality (HR 3.1, 95% CI 1.3 to 5.7, p = 0.004). In conclusion, smoking relapse after acute coronary syndromes is associated with increased mortality, and counseling interventions should be integrated into the postdischarge support to reduce the negative effects of smoking resumption.

3. Bellasi A, Ferramosca E, Ratti C, Block G, Raggi P., Cardiac valve calcification is a marker of vascular disease in prevalent hemodialysis patients. J Nephrol. 2011 Jun 28. pii: 33250EC6-41F7-42B4-9281-1BB512F496B5. doi: 10.5301/JN.2011.8446. [Epub ahead of print]
Division of Nephrology, Malpighi Hospital, University of Bologna, Bologna - Italy.

Abstract
Background:
Vascular and valvular calcifications are a common finding in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. We investigated the hypothesis that calcification of the cardiac valves is a marker of coronary artery calcification (CAC) and thoracic aorta calcification (AoC) in hemodialysis (CKD-5) patients.
Methods:
This was a cross-sectional study of 145 maintenance CKD stage 5 (CKD-5) patients. All patients underwent electron beam tomography for quantification of CAC and AoC score via the Agatston score. The presence of calcification of the cardiac valves was assessed by standard bi-dimensional echocardiography.
Results:
Eighty-four of the study patients (58%) had echocardiographic evidence of valvular calcification. A significant and graded association between valvular calcification and CAC as well as AoC was detected. Patients with 1 or 2 calcified valves had a significantly greater likelihood of having a CAC score >1,000 (odds ratio [OR] = 5.94; 95% confidence interval [95% CI], 1.91-18.44; p=0.002; and OR=3.27; 95%CI, 1.36-7.88; p=0.007, respectively). Similarly, the presence of 1 or 2 calcified valves was associated with an eightfold and threefold increased probability of an AoC score greater than the third quartile, respectively.
Conclusions:
This cross-sectional analysis shows that calcification of the cardiac valves is closely associated with vascular calcification, an established marker of risk in prevalent hemodialysis patients.

4. Prugger C, Keil U, Wellmann J, de Bacquer D, de Backer G, Ambrosio GB, Reiner Z, Gaita D, Wood D, Kotseva K, Heidrich J; for the EUROASPIRE III Study Group. Blood pressure control and knowledge of target blood pressure in coronary patients across Europe: results from the EUROASPIRE III survey. J Hypertens. 2011 Aug;29(8):1641-1648.
aInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany bDepartment of Public Health, University of Ghent, Ghent, Belgium cDepartment of Internal Medicine, Venice City Hospital, Venice, Italy dDepartment of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia eInstitute of Cardiovascular Diseases, University of Medicine and Pharmacy of Timisoara, Timisoara, Romania fDepartment of Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, London, UK.

Abstract
BACKGROUND:
Blood pressure management is a key issue among patients with coronary heart disease (CHD). The present study aimed to identify particular patient groups that may need to be specifically targeted in secondary prevention of CHD.
METHODS:
EUROASPIRE III is a cross-sectional study conducted in 2006-2007 among patients up to 80 years of age hospitalized for CHD. Patients from 76 centres in 22 European regions were examined on average 15 months after hospitalization. Logistic regression analysis was applied to investigate factors associated with blood pressure control and knowledge of target blood pressure using the cut-point of less than 140/90 mmHg.
RESULTS:
Among 7649 patients using antihypertensive medication 50.4% achieved blood pressure control and 49.4% provided accurate knowledge of target blood pressure. Obese patients were less likely to show controlled blood pressure [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.65-0.80] and accurate knowledge of blood pressure target values (OR 0.80, 95% CI 0.72-0.90). Dyslipidaemia was negatively associated with blood pressure control and accurate target knowledge. Patients with diabetes mellitus less frequently achieved blood pressure control (OR 0.89, 95% CI 0.79-0.99). Accurate knowledge of target blood pressure was positively related to blood pressure control (OR 1.12, 95% CI 1.00-1.24). Patients who received advice by a health professional to reduce salt intake, to reduce weight, and to increase physical activity more frequently showed accurate knowledge of blood pressure target values.
CONCLUSION:
Blood pressure control and knowledge of target blood pressure are inappropriate in the European high-risk population of coronary patients. Particularly CHD patients with obesity, diabetes, and dyslipidaemia need better management and control of elevated blood pressure.

5. Cruciani M, Zanichelli V, Serpelloni G, Bosco O, Malena M, Mazzi R, Mengoli C, Parisi SG, Moyle G. ABACAVIR use and cardiovascular disease events: a meta-analysis of published and unpublished data. AIDS. 2011 Jun 29. [Epub ahead of print]
aCentre of Community Medicine & HIV Outpatient Clinic, Verona, Italy bDepartment of Histology, Microbiology and Medical Biotechnology, University of Padua, Padua, Italy cDepartment of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, United Kingdom.

Abstract
BACKGROUND:
The use of abacavir (ABC) has been associated with an increased risk of cardiovascular disease in some cohort studies. However, no excess risk of myocardial infarction (MI) with ABC therapy has been observed in individual randomized clinical trials (RCTs) and in the aggregated clinical trials database maintained by the manufacturer of ABC.
OBJECTIVE:
To combine all the evidence from RCTs by means of meta-analysis to estimate the effect of combined antiretroviral therapy (cART) containing ABC on MI and overall major cardiovascular events (CVE). METHODS:: Primary outcomes included MI, CVE, adverse events requiring discontinuation of treatment, and overall mortality. We used a conventional Mantel-Haenszel method, with risk ratio (RR) and 95 % confidence intervals (CI) or, in the presence of heterogeneity, a random-effect model.
RESULTS:
Data were from 28 primary RCTs (9,233 subjects) comparing ABC containing cART (4,376 subjects) to other regimens not-containing ABC (4,857 controls). MI data were available from 18 trials (31 episodes in 7,054 patients) and CVE data from 20 trials (79 episodes in 7,899 patients). Compared to the controls, ABC use did not increase significantly the occurrence of MI (RR, 0.73, 95 % CI, 0.39-1.35; p = 0.31), CVE (RR, 0.95; 95 % CI, 0.62-1.44; p = 0.80), overall mortality (RR, 1.20; 95 % CI, 0.63-2.27; p = 0.58), and adverse events requiring discontinuation of treatment (RR, 0.82, 95 % CI, 0.67-1.00; p = 0.05).
CONCLUSION:
This meta-analysis of RCTs does not support the hypothesis that ABC-containing cART regimens carry a greater risk of MI or major cardiovascular events relative to comparator cART.

6. Borghi C, Cosentino ER, Rinaldi ER, Brandolini C, Rimondi MC, Veronesi M, Cicero AF, Dormi A, Pirodda A. Tinnitus in elderly patients and prognosis of mild-to-moderate congestive heart failure: a cross-sectional study with a long-term extension of the clinical follow-up. BMC Med. 2011 Jun 29;9:80.
Department of Internal Medicine, Aging and Kidney Diseases, Internal Medicine Unit, Bologna, Italy. claudio.borghi@unibo.it.

Abstract
BACKGROUND:
The complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function.
METHODS:
In order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure.
RESULTS:
The presence of tinnitus was ascertained in 233 patients (24.3%; mean age 74.9 ± 6 years) and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; P = .027/P = .006), reduced LV ejection fraction (LVEF%; 43.6 ± 15 vs 47.9 ± 14%, P = .001), and increased BNP plasma levels (413.1 ± 480 vs 286.2 ± 357, P = .013) in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 (95% confidence interval (CI): 0.37 to 0.93, P <.002).
CONCLUSIONS:
Our preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF.

7. Palatini P, Mos L, Santonastaso M, Saladini F, Benetti E, Mormino P, Bortolazzi A, Cozzio S. Premenopausal women have increased risk of hypertensive target organ damage compared with men of similar age. Chiropr Man Therap. 2011 Jun 28;19(1):15.
Clinica Medica 4 - University of Padova , Padova, Italy .

Abstract
Background:
The impact of high blood pressure (BP) on target organs (TO) in premenopausal women is not well known. The purpose of this study was to describe gender differences in TO involvement in a cohort of young-to-middle-aged subjects screened for stage 1 hypertension and followed for 8.2 years.
Methods:
Participants were 175 women and 451 men with similar age (range 18-45 years). Ambulatory BP at entry was 127.5±12.5/83.7±7.2 mm Hg in women and 131.9±10.3/81.0±7.9 mm Hg in men. Ambulatory BP, albumin excretion rate (AER), and echocardiographic data (n=489) were obtained at entry, every 5 years, and before starting antihypertensive treatment.
Results:
Female gender was an independent predictor of final AER (p=0.01) and left ventricular mass index (LVMI) (p<0.001). At follow-up end, both microalbuminuria (13.7% vs. 6.2%, p=0.002) and left ventricular hypertrophy (LVH) (26.4% vs. 8.8%, p<0.0001) were more common among women than men. In a multivariable Cox analysis, after adjusting for age, lifestyle factors, body mass, ambulatory BP, heart rate, and parental hypertension, female gender was a significant predictor of time to development of microalbuminuria (p=0.002), with a hazard ratio (HR) of 3.06, (95% confidence interval [CI] 1.48-6.34) and of LVH (p=0.004), with an HR of 2.50 (1.33-4.70). Inclusion of systolic and diastolic BP changes over time in the models only marginally affected these associations, with HRs of 3.13 (1.50-6.55) and 3.43 (1.75-6.70), respectively.
Conclusions:
These data indicate that premenopausal women have an increased risk of hypertensive TO damage (TOD) and raise the question about whether early antihypertensive treatment should be considered in these patients.

8. Tripepi G, Mattace FR, Sijbrands E, Seck MS, Maas R, Boger R, Witteman J, Rapisarda F, Malatino L, Mallamaci F, Zoccali C. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am Soc Nephrol. 2011 Jul;6(7):1714-21. Epub 2011 Jun 3.
CNR-IBIM, Istituto di Biomedicina, Epidemiologia Clinica e Fisiopatologia, delle Malattie Renali e dell'Ipertensione Arteriosa, c/o Euroline di Ascrizzi Vincenzo, Via Vallone Petrara n. 55/57, 89124 Reggio Calabria, Italy. carmine.zoccali@tin.it.

Abstract
Background
Endothelial dysfunction as assessed by asymmetric dimethylarginine (ADMA) and inflammation has been consistently linked to atherosclerosis, death, and cardiovascular (CV) events in ESRD patients. Inflammation amplifies the effect of ADMA on the severity of atherosclerosis in ESRD patients, but it is still unknown whether inflammation and ADMA interact in the high risk of death and CV events in this population.
Design, setting, participants, & measurements
In a cohort of 225 hemodialysis patients, we investigated the interaction between inflammatory biomarkers (C-reactive protein and IL-6) and ADMA as predictors of death and CV events over an extended follow-up (13 years).
Results
During follow-up, 160 patients died, and 123 had CV events. With crude and multiple Cox regression analyses, an interaction was found between inflammation biomarkers and ADMA for explaining death and CV events in ESRD patients. The adjusted hazard ratios (HRs) for death (HR, 2.18; 95% confidence interval [CI], 1.34 to 3.54) and CV outcomes (HR, 2.59; 95% CI, 1.47 to 4.55) of patients with C-reactive protein and ADMA above the median were higher than expected in the absence of interaction under the additive model (1.15 and 1.97, respectively) and significantly higher than in patients with only one biomarker above the median. Data analyses carried out by stratifying patients according to IL-6 provided similar results.
Conclusions
These data support the hypothesis that inflammation amplifies the risk of death and CV events associated with high ADMA levels in ESRD. These analyses further emphasize the need for intervention studies to attenuate inflammation and high ADMA levels in this population.

9. Agnoli C, Krogh V, Grioni S, Sieri S, Palli D, Masala G, Sacerdote C, Vineis P, Tumino R, Frasca G, Pala V, Berrino F, Chiodini P, Mattiello A, Panico S. A priori-defined dietary patterns are associated with reduced risk of stroke in a large italian cohort. J Nutr. 2011 Aug;141(8):1552-8. Epub 2011 May 31.

Abstract
Stroke is a major cause of death. Several foods and nutrients have been linked to stroke, but their effects may be best investigated considering the entire diet. In the present EPICOR study, we investigated the association between stroke and adherence to 4 a priori-defined dietary patterns: Healthy Eating Index 2005 (HEI-2005), Dietary Approaches to Stop Hypertension (DASH), Greek Mediterranean Index, and Italian Mediterranean Index. We followed 40,681 volunteers and estimated the HR and 95%CI for stroke according to dietary pattern by using multivariate Cox models with adjustment for risk factors. During a mean follow-up of 7.9 y, 178 stroke cases were diagnosed (100 ischemic, 47 hemorrhagic). Scores of 3 dietary patterns (not HEI) were inversely associated with risk of all types of stroke, with the strongest association for the Italian Index [HR = 0.47 (95%CI = 0.30-0.75); third vs. first tertile]. All patterns were significantly inversely associated with ischemic stroke except the Greek Index, with the strongest association for the Italian Index [HR = 0.37 (95%CI = 0.19-0.70); third vs. first tertile]. Only the Italian Index tended to be inversely associated with hemorrhagic stroke [HR = 0.51 (95%CI = 0.22-1.20); P = 0.07)]. These epidemiological findings suggest that adherence to any one dietary pattern investigated would protect against at least one type of stroke. For our Italian population, a diet with a high score on the Italian Index was associated with the greatest risk reduction, probably because it was conceived to capture healthy eating in the context of foods typically available in Italy.

Breve commento a cura di Lorenzo Richiardi
EPICOR comprende i centri italiani coinvolti in EPIC: 47,000 volontari reclutati tra il 1993 ed il 1998 a Varese, Torino, Firenze, Napoli e Ragusa. In questo studio, gli autori hanno valutato l’associazione tra quattro pattern alimentari definiti a-priori ( i) in base alle linee guida americane del 2005 –HEI-2005-; ii) il punteggio DASH –Dietary Approaches to Stop Hypertension-; iii) la variante greca dell’indice di dieta mediterranea; iv) una variante italiana dell’indice di dieta mediterranea) ed il rischio di ictus. L’indice DASH e le due varianti dell’indice di dieta mediterranea erano inversamente associati con il rischio di ictus. L’associazione era più forte per la variante italiana dell’indice di dieta mediterranea, anche se le differenze tra i tre diversi indici non erano enormi.

10. Gambineri A, Tomassoni F, Munarini A, Stimson RH, Mioni R, Pagotto U, Chapman KE, Andrew R, Mantovani V, Pasquali R, Walker BR. A combination of polymorphisms in HSD11B1 associates with in vivo 11{beta}-HSD1 activity and metabolic syndrome in women with and without polycystic ovary syndrome. Eur J Endocrinol. 2011 Aug;165(2):283-92. Epub 2011 May 27.
Division of Endocrinology, Department of Clinical Medicine, Centre for Applied Biomedical Research (CRBA), S. Orsola-Malpighi Hospital, University of Bologna - Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, Italy Endocrinology Unit, Queen's Medical Research Institute, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK Division of Internal Medicine, Endocrine-Metabolic Laboratory, University of Padova, Padova, Italy.

Abstract
Objective Regeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) within liver and adipose tissue may be of pathophysiological importance in obesity and the metabolic syndrome. single nucleotide polymorphisms (SNPs) in HSD11B1, the gene encoding 11β-HSD1, have been associated with type 2 diabetes and hypertension in population-based cohort studies, and with hyperandrogenism in patients with the polycystic ovary syndrome (PCOS). However, the functional consequences of these SNPs for in vivo 11β-HSD1 expression and activity are unknown. Methods We explored associations of well-characterised hormonal and metabolic phenotypes with two common SNPs (rs846910 and rs12086634) in HSD11B1 in 600 women (300 with PCOS) and investigated 11β-HSD1 expression and activity in a nested study of 40 women from this cohort. Results HSD11B1 genotypes (as single SNPs and as the combination of the two minor allele SNPs) were not associated with PCOS. Women who were heterozygous for rs846910 A and homozygous for rs12086634 T (GA, TT genotype) had a higher risk of metabolic syndrome, regardless of the diagnosis of PCOS (odds ratio in the whole cohort=2.77 (95% confidence interval (CI) 1.16-6.67), P=0.023). In the nested cohort, women with the GA, TT genotype had higher HSD11B1 mRNA levels in adipose tissue, and higher rates of appearance of cortisol and d3-cortisol (16.1±0.7 nmol/min versus 12.1±1.1, P=0.044) during 9,11,12,12-2H4-cortisol (d4-cortisol) steady-state infusion. Conclusions We conclude that, in a population of Southern European Caucasian women with and without PCOS, alleles of HSD11B1 containing the two SNPs rs846910 A and rs12086634 T confer increased 11β-HSD1 expression and activity, which associates with the metabolic syndrome.

11. Taglieri N, Saia F, Rapezzi C, Marrozzini C, Bacchi Reggiani ML, Palmerini T, Ortolani P, Melandri G, Rosmini S, Cinti L, Alessi L, Vagnarelli F, Villani C, Branzi A, Marzocchi A. Prognostic significance of mean platelet volume on admission in an unselected cohort of patients with non ST-segment elevation acute coronary syndrome. Thromb Haemost. 2011 Jul 4;106(1):132-40. Epub 2011 May 26.
Nevio Taglieri, MD, Institute of Cardiology, Bologna University, St. Orsola/Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy, Tel.: +39 051 6364475, Fax: +39 051 6364477, E-mail: neviotaglieri@hotmail.it.

Abstract
Mean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5-8.0; Q3=8.1-8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06-1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06-1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06-1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.

12. Galluzzo S, Patti G, Dicuonzo G, Di Sciascio G, Tonini G, Ferraro E, Spoto C, Campanale R, Zoccoli A, Angeletti S. Association between NOD2/CARD15 polymorphisms and coronary artery disease: a case-control study. Hum Immunol. 2011 Aug;72(8):636-40. Epub 2011 Apr 29.
Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.

Abstract
Inflammation and immune response play an important role in the pathogenesis of atherosclerosis. In this prospective study we tested the hypothesis of whether polymorphic variations in the NOD2/CARD15 gene may influence the risk of developing clinically evident coronary artery disease (CAD). ARG702TRP, GLY908ARG, and Leu1007fsinsC NOD2/CARD15 polymorphisms were analyzed in 109 consecutive patients with angiographically documented CAD and in 109 age- and sex-matched healthy controls. The ARG702TRP, GLY908ARG, and Leu1007fsinsC polymorphisms were analyzed by polymerase chain reaction followed by restriction digestion. The prevalence of the Leu1007fsinsC polymorphism was significantly increased in CAD patients compared with controls (11.9% vs 1.8%; odds ratios (OR) 7.2, 95% confidence interval (95% CI) 1.5-32.9; p = 0.01), especially in those presenting with an acute coronary syndrome (OR 5.7; 95% CI 1.1-39.7; p = 0.034 vs stable angina). In CAD patients the frequency of GLY908ARG polymorphism was significantly lower (1.8% vs 6.4% in controls; OR 0.05, 95% CI 0.01-0.69; p = 0.031, at multivariable analysis) and the prevalence of the ARG702TRP polymorphism was higher compared with controls (10.1% vs 3.7%; OR 2.9, 95% CI 0.91-9.6; p = 0.07). We report in a Caucasian population that NOD2/CARD15 polymorphisms influence the development of clinically evident and angiographically documented coronary artery disease. In particular, the Leu1007fsinsC polymorphism was associated with an increased risk of clinically evident and angiographically documented coronary atherosclerosis and clinical destabilization of coronary plaques, whereas the GLY908ARG polymorphism demonstrated a protective effect on coronary atherogenesis. These correlations were independent of cardiovascular risk factors at multivariable analysis. These findings may contribute to the identification of a novel genetic approach for the stratification of cardiovascular risk profile.

13. Petoumenos K, Worm S, Reiss P, de Wit S, d'Arminio Monforte A, Sabin C, Friis-Møller N, Weber R, Mercie P, Pradier C, El-Sadr W, Kirk O, Lundgren J, Law M; for the D:A:D Study Group. Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study(*). HIV Med. 2011 Aug;12(7):412-421. doi: 10.1111/j.1468-1293.2010.00901.x. Epub 2011 Jan 20.
AHOD, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia Copenhagen HIV Programme (CHIP), Copenhagen University, Copenhagen, Denmark ATHENA, HIV Monitoring Foundation, Academic Medical Center, Amsterdam, The Netherlands Saint-Pierre Cohort, CHU Saint-Pierre Hospital, Brussels, Belgium Hospital San Paolo, University of Milan, Milan, Italy UCL Medical School, Royal Free Campus, London, UK Division of Infectious Diseases, University Hospital, Zurich, Switzerland INSERM E0338 & U593, ISPED, Université Victor Segalen Bordeaux 2, Bordeaux, France Nice Cohort, CHU Nice Hôpital de L'Archet, Nice, France Harlem Hospital and Columbia University, New York, NY, USA.

Abstract
OBJECTIVES:
The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection.
METHODS:
Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral 136 patients had smoking status reported, with treatment.
RESULTS:
A total of 27 totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality.
CONCLUSION:
The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients.

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