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on behalf of IGIGI InvestigatorsObjectives-To investigate the role of interleukin-1␤ (IL-1␤) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. Methods and Results-A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the Ϫ511C/T IL-1␤ polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (Pϭ0.0020 in MI; Pϭ0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1␤ and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1␤ during cell stimulation resulted in a marked reduction of tissue factor activity expression. Key Words: risk factors Ⅲ genetics Ⅲ stroke Ⅲ myocardial infarction Ⅲ inflammation Ⅲ coagulation I ncreased levels of inflammatory markers are associated with ischemic vascular disease. [1][2][3][4] Inflammation has a relevant role in the initiation and progression of atherosclerosis; 5 however, it can also play a primary role in thrombosis development by activating the coagulation process. 6 Interleukin-1␤ (IL-1␤), a proinflammatory cytokine, stimulates the synthesis of tissue factor (TF) from monocytes and endothelial cells. 7,8 TF triggers activation of the coagulation cascade toward thrombus formation. 9 Inflammatory responses show a high interindividual variability and have been associated with polymorphisms in IL-1␤ gene; 10,11 the latter have also been related to the risk of several chronic inflammatory diseases. 11,12 We hypothesized that IL-1␤ gene polymorphisms might modulate the inflammation-triggered pathway of thrombus formation and the risk of ischemic arterial disease such as myocardial infarction (MI) and ischemic stroke. Patients with early-onset disease represent a subset of individuals in whom the impact of genes is more expressed and can be more easily identified. [13][14][15] Therefore, we investigated whether the risk of MI and ischemic stroke at young age is associated with polymorphisms in IL-1␤ gene and whether these polymorphisms can influence thrombosis by modulating the IL-1␤-mediated TF activation in response to inflammation. Conclusions--511C/T IL- Methods Study Population Patients With MIBetween May 1995 and July 2002, 430 patients Ͻ45 (males) or Ͻ50 (females) years of age admitted to cardiology centers (see the list in the Appendix) with a first episode of MI were consecutively included into the study. Acute MI was defined as resting chest pain lasting Ͼ30 minutes accompanied by ST-segment...

Background Consumption of ultra-processed food (UPF) is gaining growing attention in relation to disease/mortality risk, but less is known on the main nutritional factors or biological mechanisms potentially underlying such associations. Objectives We aimed to assess the association between UPF and mortality risk in a large sample of the Italian adult population and test which nutritional factors were on the pathway of this relation. Established risk factors for cardiovascular disease (CVD) were analyzed as potential biological mechanisms linking UPF to mortality. Methods Longitudinal analysis was conducted on 22,475 men and women (mean ± SD age: 55 ± 12 y) recruited in the Moli-sani Study (2005–2010, Italy) and followed for 8.2 y. Food intake was assessed using a semiquantitative FFQ. UPF was defined using the NOVA classification according to degree of processing, and UPF intakes were categorized as quartiles of the ratio (%) of UPF (g/d) to total food consumed (g/d). Results Individuals reporting the highest intake of UPF (Q4, >14.6% of total food), as opposed to the lowest (Q1, UPF < 6.6%), experienced increased risks of CVD mortality (HR: 1.58; 95% CI: 1.23, 2.03), death from ischemic heart disease (IHD)/cerebrovascular disease (HR: 1.52; 95% CI: 1.10, 2.09), and all-cause mortality (HR: 1.26; 95% CI: 1.09, 1.46). High sugar content explained 36.3% of the relation of UPF with IHD/cerebrovascular mortality, whereas other nutritional factors (e.g., saturated fats) were unlikely to be on the pathway. Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality, and 12.0% for that of UPF with CVD mortality. Conclusions A high proportion of UPF in the diet was associated with increased risk of CVD and all-cause mortality, partly through its high dietary content of sugar. Some established biomarkers of CVD risk were likely to be on the pathway of such associations. These findings should serve as an incentive for limiting consumption of UPF, and encouraging natural or minimally processed foods, as several national nutritional policies recommend.