11 research outputs found

    Familial aggregation of atrial fibrillation: a study in Danish twins

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    BACKGROUND: Heritability may play a role in non-familial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared to a dizygotic (DZ) twin in the same situation. METHODS AND RESULTS: A sample of 1137 same-sex twin pairs (356 MZ and 781 DZ pairs) where one or both members were diagnosed with AF were identified in The Danish Twin Registry. Concordance rates were twice as high for MZ pairs than for DZ pairs regardless of gender, 22.0% vs. 11.6% (p<0.0001). In a Cox regression of event free survival times, we compared the time span between occurrences of disease in MZ and DZ twins. The unaffected twin was included, when his or her twin-sibling (the index twin) was diagnosed with AF. After adjustment for age at entry, MZ twins had a significantly shorter event free survival time (hazard ratio: 2.0 (95% confidence interval (CI): 1.3 – 3.0)) thereby indicating a genetic component. Using biometric models, we estimated the heritability of AF to be 62 % (55 % – 68 %), due to additive genetics. There were no significant differences across genders. CONCLUSION: All the analyses of twin similarities in the present study indicate that genetic factors play a substantial role in the risk of AF for both genders. The recurrence risk for co-twins (12–22%) is clinically relevant and suggests that co-twins of AF-affected twins belong to a high-risk group for AF

    Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

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    BACKGROUND: Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. CONCLUSIONS: LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM
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