Tissue factor A-603G genotype associates with carotid intima-media thickness in subjects undergoing cardiovascular risk prevention

Tissue factor (TF), key initiator of coagulation, is also ascribed a non-haemostatic function in inflammation, cell migration and proliferation, suggesting a role of TF not only in thrombosis but also in atherosclerosis development. Polymorphisms in the TF gene promoter have been shown to modulate the expression of TF, and thereby potentially also its involvement in atherosclerosis and individual predisposition to atherosclerotic disease. Hence, this study was aimed at investigating associations between TF promoter polymorphisms and carotid intima-media thickness (IMT), a well-established surrogate marker of atherosclerotic disease. To this end, the TF A-603G polymorphism was analyzed in 316 subjects enrolled in a primary and secondary cardiovascular risk prevention programme, with measurements of carotid IMT by B-mode ultrasound. Also, the TF Ins-1208Del polymorphism was investigated in a limited number of subjects, which confirmed the previously reported complete concordance between the -603A and -1208Del alleles. The subjects were aged 60.2\ub18.4 years, 80% were male, and 78% were undergoing secondary prevention with a history of coronary, cerebrovascular, or peripheral atherosclerotic disease. Both mean and maximum carotid IMT (measured at the common carotid artery, carotid bifurcation, and internal carotid artery) differed significantly according to A-603G genotype, being highest in -603N A (n=93), intermediate in NG (n=161) and lowest in G/G (n=62) (mean IMT: A/A 1.31\ub10.36 mm, NG 1.27\ub10.33 mm, G/G 1.19\ub10.32 mm; max IMT: A/A 2.36\ub10.88 mm, NG 2.26\ub10.85 mm, 2.05\ub10.88 mm; both p<0.05; adjusted for age, gender, and statin treatment). In summary, a significant association between TF promoter genotype and carotid IMT was observed, perhaps mediated via alterations of TF expression levels in the circulation or within the carotid vessel wall. These findings support the hypothesis that TF plays a role in the atherosclerotic process, beyond its well-known role in haemostasis and thrombosis, thus further implicating TF not only in thrombotic complications of atherosclerotic disease, but also in plaque progression

Atorvastatin pretreatment diminishes the levels of myocardial ischemia markers early after CABG operation: an observational study

<p>Abstract</p> <p>Background</p> <p>Statin pretreatment has been associated with a decrease in myocardial ischemia markers after various procedures and cardiovascular events. This study examined the potential beneficial effects of preoperative atorvastatin treatment among patients undergoing on-pump CABG operation.</p> <p>Methods</p> <p>Twenty patients that had received atorvastatin treatment for at least 15 days prior to the operation and 20 patients who had not received any antihyperlipidemic agent prior to surgery were included in this study. CK-MB and troponin I levels were measured at baseline and 24 hours after the operation. Perioperative variables were also recorded.</p> <p>Results</p> <p>Twenty-four hours after the operation, troponin I and CK-MB levels were significantly lower in the atorvastatin group: for CK-MB levels, 12.9 ± 4.3 versus 18.7 ± 7.4 ng/ml, p = 0.004; for troponin I levels, 1.7 ± 0.3 versus 2.7 ± 0.7 ng/ml, p < 0.001. In addition, atorvastatin use was associated with a decrease in the duration of ICU stay.</p> <p>Conclusions</p> <p>Preoperative atorvastatin treatment results in significant reductions in the levels of myocardial injury markers early after on-pump CABG operation, suggesting a reduction in perioperative ischemia in this group of patients. Further studies are needed to elucidate the mechanisms of these potential benefits of statin pretreatment.</p

Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 +/- 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score.Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects

Tissue factor A-603G genotype associates with carotid intima-media thickness in subjects undergoing cardiovascular risk prevention

Tissue factor (TF), initiator of coagulation, is also ascribed a non-hemostatic function in atherosclerosis development. Polymorphisms in the TF gene promoter have been shown to modulate the expression of TF, and thus perhaps also its role in atherosclerosis. Hence, this study investigated associations between TF promoter genotype and carotid intima-media thickness (IMT), a well-established marker of atherosclerosis. The TF A-603G polymorphism and carotid IMT was analyzed in 324 patients undergoing primary and secondary cardiovascular risk prevention. Subjects were 60.5\ub18.4 years old, 80% were male, and 77% were undergoing secondary prevention with a history of atherosclerotic disease. Both mean and maximum carotid IMT (measured at the common carotid, bifurcation, and internal carotid) differed significantly according to A-603G genotype, being highest in -603A/A (n=95), intermediate in A/G (n = 164) and lowest in G/G (n = 65) (mean IMT: A/A 1.31\ub10.37 nm, A/G 1.28\ub10.33mm, G/G 1.22\ub10.35 mm; max IMT: A/A 2.35\ub10.91 mm, A/G 2.25\ub10.84mm, G/G 2.15+0.97 mm; both p<0.05; tested for tend; adjusted for age, gender, smoking habits, and anti-hypertensive treatment. In summary, a significant association between TF promoter genotype and carotid IMT was observed, maybe mediated via altered TF expression levels in the circulation or within the carotid vessel wall. These findings support a role of TF in the atherosclerotic process, beyond its role in hemostasis and thrombosis, thus implicating TF not only in thrombotic complications of atherosclerotic disease, but also in plaque progression

Different acute phase response to a standardized stimulus in patients with history of stable or unstable coronary heart disease

The basis of the relationship between inflammation and atherosclerosis are not fully understood. We speculated that the characteristics of the innate immune response may influence the development and expression of CHD. Thus, we compared the C-reactive protein (CRP) and serum amyloid A (SAA) responses to a standardized inflammatory stimulus in patients with history of stable or unstable CHD Methods: Adjuvanted influenza subcutaneous vaccination (lnflexal v\uae) was given to 60 adult male non-diabetic and non-current smoker patients with quiescent CHD and well controlled cardiovascular (CV) risk factors who had presented at onset of CHD as silent or inducible ischemia (group 1, n=26) or as acute coronary syndromes (group 2; n=34 ). CRP and SAA were determined by ELISA on plasma samples collected at baseline and 48 hours after vaccination, according to the results of a pilot time-course study performed in 5 healthy subjects. Results: The patients were immunocompetent and free of inflammatory conditions. Both groups were similar at baseline in terms of risk factor control, use of CV drugs including aspirin (1 00%) and statins (90%), and median [25-75th perc] CRP and SAA levels. Vaccination significantly augmented CRP in both groups (group 1: 0.47 [0.21-0.86] to 0.56 [0.32-1.17] \ub5g/ml, p=0.005; group 2: 0.64 [0.21-1.09] to 0.75 [0.33-1.48] \ub5g/ml, p=0.003), without significant differences between groups in terms of absolute or percent changes. Conversely, SAA did not change after vaccination in group 1 (14.4 [8.9-19.5] to 14.8 [10.3- 18.8] \ub5g/ml , p=0.88) whereas it augmented significantly in group 2 (16.9 [1 0.0-21.5] to 19.2 [11.3-29.1] \ub5g/ml , p=0.002), with significant differences between groups in terms of absolute and percent changes (p=0.015 and 0.019, respectively). Use of statins significantly interacted with changes induced by vaccination in CRP levels (p=0.05) but not in SAA levels (p=0.47). Conclusion: CHD patients with a history of stable or unstable disease respond differently to a defined standardized inflammatory stimulus (influenza vaccination) in terms of SAA changes, suggesting that individual features of the innate immune response may influence the clinical expression of CHD, presumably by determining attributes of atherosclerotic lesions. Lack of significant differences in terms of CRP changes may be related to interference by statins