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Cause ed epidemiologia analitica

  • Lorenzo Richiardi1

  1. Università di Torino

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Ricerca bibliografica periodo 15 ottobre 2010 – 15 gennaio 2011

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

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Database: Pubmed/MEDline
Stringa: ("italy"[MeSH Terms] OR "italy"[All Fields]) AND ("2010/10/15"[PDat] : "2011/01/31"[PDat]) AND (“Case-Control” [All fields] OR “Cohort”[all fileds] OR “Cross-sectional”[All fields]) AND ("risk"[All Fields] OR "association"[all fields] OR "epidemiologic factors"[MeSH Terms]) and (“odds ratios”[all fields] OR “odds ratio”[all fields] OR “ORs”[all fields] OR “rate ratio”[all fileds] OR “rate ratios”[all fileds] OR “RR”[all fileds] OR “RRs” [all fileds] OR “risk ratio”[all fields] OR “risk ratios”[all fields] OR “prevalence ratio*” [all fields] OR “prevalence ratios” [all fields] OR “hazard ratio” [all fields] OR “hazard ratios” [all fields] OR “HR”[all fields] OR “HRs”[all fields]) NOT "Clinical Trials as Topic"[Mesh] NOT "Sensitivity and Specificity"[Mesh] NOT "Comorbidity"[Mesh] NOT "Predictive Value of Tests"[Mesh] NOT "Prognosis"[Mesh] NOT "Review"[publication type] NOT "Population Surveillance"[Mesh]

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1. Floud S, Vigna-Taglianti F, Hansell A, Blangiardo M, Houthuijs D, Breugelmans O, Cadum E, Babisch W, Selander J, Pershagen G, Antoniotti MC, Pisani S, Dimakopoulou K, Haralabidis AS, Velonakis V, Jarup L; on behalf of the HYENA study team.Medication use in relation to noise from aircraft and road traffic in six European countries: results of the HYENA study. Occup Environ Med. 2010 Nov 16. [Epub ahead of print]
MRC-HPA Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Abstract
ObjectivesStudies on the health effects of aircraft and road traffic noise exposure suggest excess risks of hypertension, cardiovascular disease and the use of sedatives and hypnotics. Our aim was to assess the use of medication in relation to noise from aircraft and road traffic.
Methods This cross-sectional study measured the use of prescribed antihypertensives, antacids, anxiolytics, hypnotics, antidepressants and antasthmatics in 4,861 persons living near seven airports in six European countries (UK, Germany, the Netherlands, Sweden, Italy, and Greece). Exposure was assessed using models with 1dB resolution (5dB for UK road traffic noise) and spatial resolution of 250×250m for aircraft and 10×10m for road traffic noise. Data were analysed using multilevel logistic regression, adjusting for potential confounders.
Results We found marked differences between countries in the effect of aircraft noise on antihypertensive use; for night-time aircraft noise, a 10dB increase in exposure was associated with ORs of 1.34 (95% CI 1.14 to1.57) for the UK and 1.19 (1.02 to 1.38) for the Netherlands but no significant associations were found for other countries. For day-time aircraft noise, excess risks were found for the UK (OR 1.35; CI: 1.13 to 1.60) but a risk deficit for Italy (OR 0.82; CI: 0.71 to 0.96). There was an excess risk of taking anxiolytic medication in relation to aircraft noise (OR 1.28; CI: 1.04 to 1.57 for daytime and OR 1.27; CI: 1.01 to 1.59 for night-time) which held across countries. We also found an association between exposure to 24hr road traffic noise and the use of antacids by men (OR 1.39; CI 1.11 to 1.74).
Conclusion Our results suggest an effect of aircraft noise on the use of antihypertensive medication, but this effect did not hold for all countries. Results were more consistent across countries for the increased use of anxiolytics in relation to aircraft noise.
PMID: 21084328 [PubMed - as supplied by publisher]

Breve commento a cura di Lorenzo Richiardi
L’articolo riporta i risultati dell’analisi sull’uso di diversi classi di farmaci, tra cui farmaci anti-ipertensivi, ansiolitici e ipnotici nell’ambito dello studio HYENA su popolazioni residenti in prossimità di aeroporti. HYENA e’ uno studio trasversale multicentrico europeo che comprende anche la popolazione residente vicino all’aeroporto di Malpensa. E’ stata trovata un’associazione tra esposizione a rumore e farmaci ipertensivi, anche se con una forte eterogeneità tra i diversi paesi partecipanti

2. Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, Sparrow D, Vokonas P, Schwartz J Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology. 2010 Nov;21(6):819-28.
Center of Molecular and Genetic Epidemiology, Università degli Studi di Milano & IRCCS Ca', Granda Policlinico Maggiore Hospital Foundation, Milan, Italy. abaccare@hsph.harvard.edu
Abstract
BACKGROUND: Epigenetic features such as DNA hypomethylation have been associated with conditions related to cardiovascular risk. We evaluated whether lower blood DNA methylation in heavily methylated repetitive sequences predicts the risk of ischemic heart disease and stroke.
METHODS: We quantified blood DNA methylation of Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements through PCR-pyrosequencing in 712 elderly individuals from the Boston-area Normative Aging Study. We estimated risk-factor adjusted relative risks (RRs) for ischemic heart disease and stroke at baseline (242 prevalent cases), and during follow-up (44 new cases; median follow-up, 63 months), as well as subsequent mortality from ischemic heart disease (86 deaths; median follow-up, 75 months).
RESULTS
: Blood LINE-1 hypomethylation was associated with baseline ischemic heart disease (RR = 2.1 [95% confidence interval = 1.2-4.0] for lowest vs. highest methylation quartile) and for stroke (2.5 [0.9-7.5]). Among participants free of baseline disease, individuals with methylation below the median also had higher risk of developing ischemic heart disease (4.0 [1.8-8.9]) or stroke (5.7 [0.8-39.5]). In the entire cohort, persons with methylation below the median had higher mortality from ischemic heart disease (3.3 [1.3-8.4]) and stroke (2.8 [0.6-14.3]). Total mortality was also increased (2.0 [1.2-3.3]). These results were confirmed in additional regression models using LINE-1 methylation as a continuous variable.
CONCLUSIONS
: Subjects with prevalent IHD and stroke exhibited lower LINE-1 methylation. In longitudinal analyses, persons with lower LINE-1 methylation were at higher risk for incident ischemic heart disease and stroke, and for total mortality. PMID: 20805753 [PubMed - in process]

Breve commento a cura di Lorenzo Richiardi
Lo studio è stato condotto in collaborazione tra ricercatori italiani e ricercatori di americani su una popolazione residente nell’area di Boston. Viene analizzata l’associazione tra metilazione globale misurata sulle sequenze LINE-1 e malattie cardiovascolari sia in maniera trasversale sia in maniera prospettica con un follow-up mediano di 5 anni. I risultati indicano un importante aumento di rischio cardiovascolare in associazione con l’ipometilazione globale. Notevole il confronto tra la magnitudine dell’effetto dell’ipometilazione e la magnitudine degli altri rischi cardiovascolari.

3. Del Rio D, Agnoli C, Pellegrini N, Krogh V, Brighenti F, Mazzeo T, Masala G, Bendinelli B, Berrino F, Sieri S, Tumino R, Rollo PC, Gallo V, Sacerdote C, Mattiello A, Chiodini P, Panico S. Total antioxidant capacity of the diet is associated with lower risk of ischemic stroke in a large Italian cohort. J Nutr. 2011 Jan;141(1):118-23. Epub 2010 Nov 24.
Department of Public Health, University of Parma, Parma 43125, Italy.
Abstract
Experimental studies suggest that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke. Consuming a diet with a high total antioxidant capacity (TAC) has been related to reduced inflammation and increased circulating antioxidants in cross-sectional and randomized intervention studies. This study investigates the relation between dietary TAC and risk of ischemic and hemorrhagic stroke in 41,620 men and women not previously diagnosed with stroke or myocardial infarction, representing the Italian segment of the European Prospective Investigation into Cancer and Nutrition. Controlling for potential confounders, a diet rich in TAC was associated with a reduction in HR for all types of stroke, but this association was only marginally significant (P-trend = 0.054). When only ischemic stroke cases were considered, data suggest a stronger inverse association with dietary TAC, with HR = 0.41 (95% CI = 0.23-0.74). Regarding single antioxidants, data from subanalyses on stroke types suggest that vitamin C is significantly associated with a decreased risk of ischemic stroke [HR = 0.58 (95% CI = 0.34-0.99)], whereas vitamin E was associated with increased HR of hemorrhagic stroke in the highest tertile of intake [HR = 2.94 (95% CI = 1.13-7.62)]. In conclusion, our findings suggest that antioxidants may play a role in reducing the risk of cerebral infarction but not hemorrhagic stroke. However, a high intake of vitamin E could be positively associated to the risk of brain hemorrhagic events; therefore, more focused investigations about this observation are needed. PMID: 21106923 [PubMed - indexed for MEDLINE]
4. Manetti M, Allanore Y, Revillod L, Fatini C, Guiducci S, Cuomo G, Bonino C, Riccieri V, Bazzichi L, Liakouli V, Cipriani P, Giacomelli R, Abbate R, Bombardieri S, Valesini G, Montecucco C, Valentini G, Ibba-Manneschi L, Matucci-Cerinic M. A genetic variation located in the promoter region of the UPAR (CD87) gene is associated with the vascular complications of systemic sclerosis. Arthritis Rheum. 2011 Jan;63(1):247-56. doi: 10.1002/art.30101.
University of Florence and Excellence Centre for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, Florence, Italy. mirkomanetti@yahoo.it
Abstract
OBJECTIVE: The UPAR gene encodes a pleiotropic receptor (urokinase-type plasminogen activator receptor [uPAR]) involved in fibrosis, immunity, angiogenesis, and vascular remodeling. Previous studies have implicated uPAR in systemic sclerosis (SSc) vasculopathy and impaired angiogenesis. We undertook this study to investigate whether UPAR gene promoter polymorphisms might be associated with SSc phenotypes in the European Caucasian population.
METHODS
: We studied a total population of 1,339 individuals. The Italian discovery cohort comprised 388 SSc patients and 391 healthy controls. The French replication cohort consisted of 344 SSc patients and 216 healthy controls. The UPAR rs344781 and rs4251805 single-nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay.
RESULTS
: In the Italian cohort, the rs344781 G allele was associated with SSc-related digital ulceration (odds ratio [OR] 1.39), pulmonary arterial hypertension (PAH) (OR 1.81), anticentromere antibody (ACA) positivity (OR 1.45), and limited cutaneous SSc (lcSSc) (OR 1.37). The rs344781 GG genotype was associated with SSc-related (OR 3.79), ACA-positive SSc (OR 2.17), and lcSSc (OR 1.96). Allelic and genotypic associations with SSc-related digital ulceration and ACA-positive SSc were replicated in the French sample. Combined analyses showed an association of the rs344781 G allele and GG genotype with SSc-related digital ulceration (allele OR 1.41, genotype OR 2.15), SSc-related PAH (allele OR 1.65, genotype OR 3.16), ACA-positive SSc (allele OR 1.47, genotype OR 2.40), and lcSSc (allele OR 1.34, genotype OR 1.77). In a multivariate logistic regression analysis model including the above associated phenotypes of SSc patients, the rs344781 GG genotype remained an independent risk factor for SSc-related digital ulceration (OR 1.96) and SSc-related PAH (OR 2.68).
CONCLUSION
: The UPAR rs344781 gene variant is associated with the SSc vascular phenotype. PMID: 20967855 [PubMed - indexed for MEDLINE]
5. Guella I, Asselta R, Ardissino D, Merlini PA, Peyvandi F, Kathiresan S, Mannucci PM, Tubaro M, Duga S. Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. J Lipid Res. 2010 Nov;51(11):3342-9. Epub 2010 Aug 10.
Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milan, Italy.
Abstract
The R46L variant in the proprotein-convertase subtilisin-kexin type 9 (PCSK9) gene was associated with reduced levels of LDL and total cholesterol and with a lower risk of coronary artery disease. We investigated the association of R46L with myocardial infarction (MI) in 1,880 Italian patients with premature MI and 1,880 controls. A trend toward a protective effect of the L46 allele was observed [odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.49-1.13; P = 0.17], although the association with MI was not significant. This is probably due to the combined effect of the low frequency of R46L among Italians and of the young age of the analyzed cohort for whom the impact of coronary atherosclerosis is less important. This hypothesis was indirectly confirmed by the significant association found after including 1,056 additional older controls (OR = 0.67, 95%CI = 0.46-0.97; P = 0.036). LDL cholesterol was significantly lower in L46 carriers (116.2 ± 34.7 mg/dl) than in noncarriers (137.4 ± 47.3 mg/dl; P = 0.00022); a similar reduction was observed for total cholesterol (191.7 ± 37.7 vs. 211.7 ± 49 mg/dl; P = 0.00019). Analysis of 23 additional polymorphisms in the PCSK9 region identified another single nucleotide polymorphism (SNP) (rs11206510) associated with cholesterol levels. We confirmed that the L46 allele not only decreases LDL cholesterol but also protects against MI. Moreover, we replicated the association of total and LDL cholesterol with the SNP rs11206510. PMCID: PMC2952575 [Available on 2011/11/1]. PMID: 20699424 [PubMed - indexed for MEDLINE]
6. Vitale C, Iellamo F, Volterrani M, Lombardi M, Fini M, Banach M, Rosano GM. Heart rate control in an unselected consecutive population of outpatients with stable coronary artery disease: Analysis of the CARDIf Study Cohort. Angiology. 2010 Nov;61(8):763-7. Epub 2010 May 12.
Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Roma, Italy. cristiana.vitale@sanraffaele.it
Abstract
BACKGROUND: Despite increasing pharmacological and mechanical treatment options, coronary artery disease (CAD) continues to be associated with considerablemortality and morbidity. The detrimental effects of elevated heart rate (HR) on cardiac morbidity and mortality are well established. Although β-blockers represent the mainstay of treatment of patients with CAD and heart failure (HF), according to current guidelines, these drugs are most often undertitrated for various reasons despite the lack of real contraindications. This observational, cross-sectional, multicenter survey was designed to assess which clinical variables influence HR and whether HR is adequately controlled; and the rate of administration of β-blockers in patients with chronic CAD attending outpatient clinics.
METHODS
: Over 6 months 2226 (of 2362 screened) outpatients with stable CAD and resting HR > 60 beats/min (bpm) were enrolled. Left ventricular systolic function was not a criterion of inclusion. Each patient had a full clinical examination and the past medical history, angina, or HF-related symptoms were evaluated. In each patient, the demographics and cardiovascular risk factors were assessed; weight, height, and body mass index (BMI) was calculated; sitting blood pressure and a HR by a 12-lead electrocardiogram was obtained.
RESULTS: Overall, 45.4% of patients with CAD were not under β-blocker therapy. Male patients featured a significantly lower HR than females, corrected from β-blockers use. In multiple regression analysis, which also included the use/nonuse of β-blockers as independent variable, not using β-blockers, female sex (OR 2.55), New York Heart Association (NYHA) classes I and II (OR 1.62 vs classes III-IV), smoking (OR 0.89), and increased BMI (OR 0.14) were all independent determinants of resting HR, with the lack of β-blockade therapy (OR 3.35) being the main determinant of the magnitude of HR increase. Heart rate in patients under β-blocker therapy was significantly less than in untreated patients (73.6 ± 10.0 vs 77.1 ± 10.4, P < .0001), although it often did not reach target values of <70 bpm. Among patients with HF symptoms, 56.6% were under β-blocker therapy. In patients free of symptoms of HF, HR was significantly less in those receiving a β-blocker (72.3 ± 10 vs 76.7 ± 11 bpm, P < .0001).
CONCLUSION
: This survey demonstrates that HR is poorly controlled in a broadly representative cohort of outpatients with CAD, even in those on β-blocker therapy, mainly because of undertitration of therapy-almost half of the patients with CAD and elevated resting HR are not on β-blockers. This might be related to absolute or relative controindications and to haemodynamic and chronotropic intolerance to beta-blockers. PMID: 20462892 [PubMed - indexed for MEDLINE]
7. 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 Jan 20. doi: 10.1111/j.1468-1293.2010.00901.x. [Epub ahead of print]
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 ecreased withincreasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV- ositive patients. PMID: 21251183 [PubMed - as supplied by publisher]
8. The contribution of major risk factors and job strain to occupational class differences in coronary heart disease incidence: the MONICA Brianza and PAMELA population-based cohorts. Occup Environ Med. 2010 Dec 30. [Epub ahead of print]
Dipartimento di Medicina Sperimentale, Università degli Studi dell'Insubria, Varese, Italy.
Abstract
Objectives We investigated the contribution of major coronary heart disease (CHD) risk factors and job strain to occupational class differences in CHD incidence in a pooled-cohort prospective study in northern Italy.
Methods
2964 men aged 25-74 from four northern Italian population-based cohorts were investigated at baseline and followed for first fatal or non-fatal CHD event (171 events). Standardised procedures were used for baseline risk factor measurements, follow-up and validation of CHD events. Four occupational classes were derived from the Erikson-Goldthorpe-Portocarero social class scheme: higher and lower professionals and administrators, non-manual workers, skilled and unskilled manual workers, and the self-employed. HRs were estimated with Cox models.
Results
Among CHD-free subjects, with non-manual workers as the reference group, age-adjusted excess risks were found for professionals and administrators (+84%, p=0.02), the self-employed (+72%, p=0.04) and manual workers (+63%, p=0.04). The relationship was consistent across different CHD diagnostic categories. Adjusting for major risk factors only slightly reduced the reported excess risks. In a sub-sample of currently employed subjects, adjusting for major risk factors, sport physical activity and job strain reduced the excess risk for manual workers (relative change = -71.4%) but did not substantially modify the excess risks of professionals and administrators and the self-employed.
Conclusions
In our study, we found higher CHD incidence rates for manual workers, professionals and administrators, and the self-employed, compared to non-manual workers. When the entire spectrum of job categories is considered, the job strain model helped explain the CHD excess risk for manual workers but not for other occupational classes. PMID: 21193567 [PubMed - as supplied by publisher]
9. Bendinelli B, Masala G, Saieva C, Salvini S, Calonico C, Sacerdote C, Agnoli C, Grioni S, Frasca G, Mattiello A, Chiodini P, Tumino R, Vineis P, Palli D, Panico S. Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: the EPICOR Study. Am J Clin Nutr. 2011 Feb;93(2):275-83. Epub 2010 Dec 22.
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy.
Abstract
BACKGROUND: Many observational studies support the recommendation to eat sufficient amounts of fruit and vegetables as part of a healthy diet.
OBJECTIVE
: The present study aimed to investigate the association between consumption of fruit, vegetables, and olive oil and the incidence of coronary heart disease (CHD) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts in northern (Turin and Varese), central (Florence), and southern (Naples and Ragusa) Italy.
DESIGN
: Baseline dietary, anthropometric, and lifestyle characteristics were collected. Major events of CHD (fatal and nonfatal myocardial infarction and coronary revascularization) were identified through a review of clinical records. Analyses were stratified by center and adjusted for hypertension, smoking, education, menopause, physical activity, anthropometric measures, nonalcohol energy, alcohol, total meat, vegetables in analyses for fruit, and fruit in analyses for vegetables.
RESULTS
: During a mean follow-up of 7.85 y, 144 major CHD events were identified. A strong reduction in CHD risk among women in the highest quartile of consumption of leafy vegetables (hazard ratio: 0.54; 95% CI: 0.33, 0.90; P for trend = 0.03) and olive oil (hazard ratio: 0.56; 95% CI: 0.31, 0.99; P for trend = 0.04) was found. In contrast, no association emerged between fruit consumption and CHD risk.
CONCLUSION
: An inverse association between increasing consumption of leafy vegetables and olive oil and CHD risk emerged in this large cohort of Italian women. PMID: 21177799 [PubMed - in process]
10. Tosetto A, Prati P, Baracchini C, Manara R, Rodeghiero F. Association of plasma fibrinogen, C-reactive protein and G-455>A polymorphism with early atherosclerosis in the VITA Project cohort. Thromb Haemost. 2010 Dec 6;105(2). [Epub ahead of print]
Francesco Rodeghiero, Department of Hematology, S. Bortolo Hospital, via Rodolfi, 36100 Vicenza, Italy, E-mail: rodeghiero@hemato.ven.it.
Abstract
While increased fibrinogen is associated with vascular events, only few data are available on its association with preclinical atherosclerosis. We aimed at evaluating the association between fibrinogen levels, fibrinogen polymorphism G-455>A and C-reactive protein and preclinical atherosclerosis in a population-based, cross-sectional study. A cohort of 2,580 subjects was enrolled. Fibrinogen was measured at time of original enrolment and at time of the second visit, when ultrasound examination of both left and right common carotid arteries was performed, together with evaluation of C-reactive protein (CRP) and of the fibrinogen G-455>A polymorphism. CRP and fibrinogen levels at baseline were the two variables mostly influencing fibrinogen levels at the follow-up visit (p<0.0001). Carriers of the H2H2 genotype of the G-455>A polymorphism had increased fibrinogen levels, particularly in association with increased CRP levels. Increased fibrinogen levels were independently associated with presence of carotid plaques, particularly in those subjects having a persistent increase of fibrinogen (odds ratio 1.98, 95% confidence interval 1.47-2.67). An association between the H2H2 genotype and presence of carotid plaques was observed only in a subgroup of subjects with CRP > 0.5 mg/dl. A persistent increase of plasma fibrinogen is associated with an increased risk of early atherosclerosis. PMID: 21136015 [PubMed - as supplied by publisher]
11. De Caterina R, Talmud PJ, Merlini PA, Foco L, Pastorino R, Altshuler D, Mauri F, Peyvandi F, Lina D, Kathiresan S, Bernardinelli L, Ardissino D; on behalf of the Gruppo Italiano Aterosclerosi. Strong association of the APOA5-1131T>C gene variant and early-onset acute myocardial infarction. Atherosclerosis. 2011 Feb;214(2):397-403. Epub 2010 Nov 16.
Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University-Chieti and Fondazione "G. Monasterio", Pisa, Italy.
Abstract
BACKGROUND: Epidemiological studies support the role for a strong genetic component in the occurrence of early-onset myocardial infarction (MI), although the specific genetic variants responsible for familial clustering remain largely unknown.
METHODS: The Italian study of early-onset MI is a nationwide case-control study involving 1864 case patients <45 years old who were hospitalized for a first MI, and age/sex/place of origin-matched controls (n=1864). We investigated the association between early-onset MI, lipid levels and 20 single nucleotide polymorphisms (SNPs) in the candidate genes ADIPOQ, APOA5, ALOX5AP, CYBA, IL6, LPL, PECAM1, PLA2G2A and PLA2G7, chosen because of previously reported associations with Coronary Heart Disease (CHD) or with CHD risk factors.
RESULTS
: Of all the SNPs investigated, APOA5-1131T>C [(rs662799), minor allele frequency 0.084 (95% confidence interval (CI) 0.07-0.09)] alone showed a statistically significant association with risk of early-onset MI (p=6.7×10(-5)), after Bonferroni correction, with a per C allele odds ratio of 1.44 (95% CI 1.23-1.69). In controls, APOA5-1131T>C was significantly associated with raised plasma triglyceride levels (p=0.001), compared with non-carriers, the per C allele increase being 11.4% (95% CI 4-19%), equivalent to 0.15mmol/L (95% CI 0.11-0.20mmol/L). In cases, the association with early MI risk remained statistically significant after adjustment for triglycerides (p=0.006).
CONCLUSIONS: The APOA5-1131C allele, associated with higher fasting triglyceride levels, strongly affects the risk for early-onset MI, even after adjusting for triglycerides. This raises the possibility that APOA5-1131T>C may affect the risk of early MI over and above effects mediated by triglycerides. PMID: 21130994 [PubMed - as supplied by publisher]
12. Cipriani V, Mannucci PM, Ardissino D, Ferrario M, Corsini G, Merlini PA, Notarangelo F, Lina D, Bernardinelli L. Familial aggregation of early-onset myocardial infarction. Eur J Intern Med. 2010 Dec;21(6):511-5. Epub 2010 Aug 25.
Department of Applied Health Sciences, Division of Epidemiology and Medical Statistics, University of Pavia, via Bassi 21, 27100, Pavia, Italy. v.cipriani@ucl.ac.uk
Abstract
BACKGROUND: An inherited predisposition is an important factor in the etiology of myocardial infarction (MI) at a young age. However, the extent of the risk for early-onset MI in relatives of young patients is still unclear, due to the paucity of family history data. Hence familial aggregation of early-onset MI was investigated in a cohort of relatives of Italian patients who had survived MI who occurred at the age of 45 or earlier.
METHODS
: In the framework of a case-control study, lifetime data and early-onset MI status for 11,696 relatives of cases and 8897 relatives of controls were collected using a standardized questionnaire.
RESULTS
: Occurrence of early-onset MI in females was very uncommon (Kaplan-Meier risk=0.6%, 95% confidence interval (CI): 0.38-0.82%, for female case relatives), and significantly lower than that for male case relatives (5.0%, 95% CI: 4.41-5.56%). The hazard ratio (HR) for case relatives was approximately 3-fold greater than that for control aunts (taken as reference category). Risk for early-onset MI to siblings (HR=1.7, 95% CI: 1.33-2.18) was significantly different from that to parents (HR=0.9, 95% CI: 0.71-1.16). The familial risk ratio λ(R) was 2.6 (95% CI: 2.30-2.89) for case relatives, using control parents as reference population for early-onset MI risk estimates (i.e. 37 per 100,000 in fathers and 7 per 100,000 in mothers).
CONCLUSION: We evaluated the risk of early-onset MI by category of relatives, obtaining evidence for familial aggregation of the disease in this Italian sample and providing figures for genetic counselling and planning genetic epidemiological studies. PMID: 21111936 [PubMed - in process]
13. Corona G, Monami M, Rastrelli G, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M .Is Metabolic Syndrome a Useless Category in Subjects with High Cardiovascular Risk? Results from a Cohort Study in Men with Erectile Dysfunction. J Sex Med. 2010 Nov 22. doi: 10.1111/j.1743-6109.2010.02126.x. [Epub ahead of print]
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy Diabetes Section Geriatric Unit, Department of Critical Care, University of Florence, Florence, Italy Epidemiological Unit, Azienda Sanitaria Locale 10, Florence, Italy Endocrinology Unit, Azienda Usl di Bologna, Maggiore-Bellaria Hospital, Bologna, Italy.
Abstract
Introduction. Although several studies have demonstrated that MetS is associated with a two-fold increase in the risk of cardiovascular (CV) diseases, this risk does not appear to be greater than the sum of risks associated with each of its To determine the association of men with ED and individual components.
Aim.
individual components of MetS and their subsequent relationship to CV risk, and, more specifically whether the sum of the MetS components is greater than the We longitudinally studied individual components in predicting CV risk.
Methods.
12.8; range 17-88 years) patients ± a consecutive series of 1,687 (mean age 52.9 attending our clinic for ED and evaluated different clinical and biochemical Information on major adverse CV event (MACE) parameters.
Main Outcome Measures.
One hundred was obtained through the City of Florence Registry Office.
Results. Thirty-nine MACE, 15 of which were fatal, occurred during a mean follow-up of 2.6 years. Subjects with MetS at baseline showed a higher incidence of MACE ± 4.3 1.77), after adjusting for age, however, the association = (hazard ratio [HR] disappeared in an alternative Cox model, adjusting both for age and for 0.408). The two most = 1,525 [0,564-4,123]; P = individual MetS components (HR predictive MetS components of CV risk were low high-density lipoprotein (HDL) cholesterol and high triglycerides. Exploring possible interactions between individual components of MetS and their effect on CV risk using two alternative approaches indicates that the effect of MetS components on CV risk is additive, but not synergistic. Among subjects with hypertension, after adjusting for age, elevated glycemia, and low HDL cholesterol confer relevant additional risk, whilein subjects with high triglycerides, hyperglycemia increased the risk of incident. With regards to CV risk, the MetS construct seems to add MACE.
Conclusions.
little or nothing to the careful assessment of its components. Thus, there is no reason to recommend the use of MetS as a diagnostic category in patients with ED.
14. Martinelli I, Bucciarelli P, De Stefano V, Passamonti SM, Menegatti M, Tormene D, Tosetto A, Mannucci PM. Effect of prothrombin 19911 A>G polymorphism on the risk of cerebral sinus-venous thrombosis. Eur J Neurol. 2010 Dec;17(12):1482-5.
A. Bianchi Bonomi Haemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. martin@policlinico.mi.it
Abstract
BACKGROUND AND PURPOSE: The A>G polymorphism at position 19911 of the prothrombin gene is associated with a mildly increased risk of venous thromboembolism, alone or in association with such common thrombophilia mutations as factor V Leiden and prothrombin 20210 GA. Its role in cerebral sinus-venous thrombosis (CSVT) is not known.
METHODS
: The presence of prothrombin 19911 A>G was investigated in a case–control study of 107 patients with cerebral thrombosis and factor V Leiden (n = 25), prothrombin 20210 GA (n = 47), without known thrombophilia (n = 35) and 842 healthy individuals with the corresponding coagulation profile.
RESULTS: Prothrombin 19911 A>G did not increase the risk of CSVT in carriers of factor V Leiden (adjusted odds ratio 1.6, 95%CI 0.6–4.7), prothrombin 20210 GA (odds ratio 1.1, 95%CI 0.6–2.2), nor in patients without known thrombophilia (odds ratio 1.3, 95%CI 0.5–3.1).
CONCLUSIONS
: Prothrombin 19911 A>G polymorphism does not appear to be a risk factor for CSVT, alone or in association with factor V Leiden or prothrombin 20210GA. PMID: 20482605 [PubMed - in process]
15. Perissinotto E, Buja A, Maggi S, Enzi G, Manzato E, Scafato E, Mastrangelo G, Frigo AC, Coin A, Crepaldi G, Sergi G; ILSA Working Group. Alcohol consumption and cardiovascular risk factors in older lifelong wine drinkers: the Italian Longitudinal Study on Aging. Nutr Metab Cardiovasc Dis. 2010 Nov;20(9):647-55. Epub 2009 Aug 19.
Collaborators: Scafato E, Farchi G, Galluzzo L, Gandin C, Di Carlo A, Baldereschi M, Crepaldi G, Maggi S, Minicucci N, Noale M, Capurso A, Panza F, Solfrizzi V, Lepore V, Livrea P, Motta L, Carnazzo G, Motta M, Bentivegna P, Bonaiuto S, Cruciani G, Postacchini D, Inzitari D, Amaducci L, Gandolfo C, Conti M, Canal N, Franceschi M, Scarlato G, Candelise L, Scapini E, Rengo F, Abete P, Cacciatore F, Enzi G, Battistin L, Sergi G, Grigoletto F, Perissinotto E, Carbonin P. Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy. egle.perissinotto@unipd.it
Abstract
BACKGROUND AND AIMS: A protective effect of moderate alcohol consumption on the cardiovascular system has consistently been reported, but limited evidence has been produced on the association of alcohol with metabolic factors in the elderly. The aim of this study was to investigate the association between different levels of current alcohol consumption and cardiovascular risk factors in a representative sample of elderly Italian men, mainly wine drinkers.
METHODS AND RESULTS
: This is a cross-sectional multi-centre study on a population-based sample of Italian men aged 65-84 years, drawn from the Italian Longitudinal Study on Aging (ILSA) cohort. The analyses included 1896 men. Almost all the drinkers (98%) drank wine as a lifelong habit. Adjusted ORs for risk levels for cardiovascular factors (BMI, waist circumference, fibrinogen, α2 protein, white blood cells, HDL cholesterol, Apo A-I, total cholesterol, Apo B-I, triglycerides, LDL, glycated hemoglobin, insulin, fasting plasma glucose, HOMA IR, systolic and diastolic blood pressure) were estimated, comparing drinkers with teetotalers using multivariate logistic regression models. We found alcohol consumption in older age associated with healthier hematological values of fibrinogen, HDL cholesterol, Apo A-I lipoprotein and insulin, but it was also associated with a worse hematological picture of total, LDL cholesterol levels, and systolic pressure.
CONCLUSION
: Our results indicated in elderly moderate wine drinkers a noticeably safe metabolic, inflammatory and glycemic profile that might balance higher blood pressure, leading to a net benefit. These findings however need to be placed in relation to the known adverse social and health effects of heavy drinking. PMID: 19695851 [PubMed - in process]