Smoking cessation and the risk of cardiovascular disease outcomes predicted from established risk scores: results of the Cardiovascular Risk Assessment among Smokers in Primary Care in Europe (CV-ASPIRE) study.

BACKGROUND: Smoking is a major risk factor for cardiovascular disease (CVD). This multicenter, cross-sectional survey was designed to estimate the cardiovascular (CV) risk attributable to smoking using risk assessment tools, to better understand patient behaviors and characteristics related to smoking, and characterize physician practice patterns. METHODS: 1,439 smokers were recruited from Europe during 2011. Smokers were ≥40 years old, smoked > 10 cigarettes/day and had recent measurements on blood pressure and lipids. CV risk was calculated using the SCORE system, Framingham risk equations, and Progetto CUORE model. The CV risk attributable to smoking was evaluated using a simulated control (hypothetical non-smoker) with identical characteristics as the enrolled smoker. Risks assessed included CV mortality, coronary heart disease (CHD), CVD and hard CHD. Demographics, comorbidities, primary reasons for consultation, behavior towards previous attempts to quit, and interest in smoking cessation was assessed. Dependence on nicotine was evaluated using the Fagerström Test for Nicotine Dependence. GP practice patterns were assessed through a questionnaire. RESULTS: The prediction models consistently demonstrated a high CV risk attributable to smoking. For instance, the SCORE model demonstrated that this study population of smokers have a 100% increased probability of death due to cardiovascular disease in the next 10-years compared to non-smokers. A considerable amount of patients would like to hear from their GP about the different alternatives available to support their quitting attempt. CONCLUSIONS: The findings of this study reinforce the importance of smoking as a significant predictor of long-term cardiovascular events. One of the best gains in health could be obtained by tackling the most important modifiable risk factors; these results suggest smoking is among the most important.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

A Narrative Review of the Role of Transthyretin in Health and Disease.

Transthyretin (TTR) is a tetrameric transport protein highly conserved through vertebrate evolution and synthesized in the liver, choroid plexus, and retinal pigment epithelium. TTR transports the thyroid hormone thyroxine and the retinol-binding protein (RBP) bound to retinol (vitamin A). Mutations in TTR are associated with inherited transthyretin amyloidosis (ATTRv), a progressive, debilitating disease that is ultimately fatal and is characterized by misfolding of TTR and aggregation as amyloid fibrils, predominantly leading to cardiomyopathy or polyneuropathy depending on the particular TTR mutation. Transthyretin amyloid cardiomyopathy can also occur as an age-related disease caused by misfolding of wild-type TTR. Apart from its transport role, little is known about possible additional physiological functions of TTR. Evidence from animal model systems in which TTR has been disrupted via gene knockout is adding to our cumulative understanding of TTR function. There is growing evidence that TTR may have a role in neuroprotection and promotion of neurite outgrowth in response to injury. Here, we review the literature describing potential roles of TTR in neurobiology and in the pathophysiology of diseases other than ATTR amyloidosis. A greater understanding of these processes may also contribute to further clarification of the pathology of ATTR and the effects of potential therapies for TTR-related conditions.