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| 12. |
- Young, WJ, et al.
(author)
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Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
- 2023
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 1411-
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Journal article (peer-reviewed)abstract
- The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
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| 16. |
- Newby, D, et al.
(author)
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Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus
- 2022
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In: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 10:5
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Journal article (peer-reviewed)abstract
- Type 2 diabetes is a risk factor for dementia and Parkinson’s disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas.Research design and methodsA new user comparator study design was conducted in patients ≥50 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer’s disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control.ResultsWe identified 96 140 and 16 451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4±8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70–0.94), 0.79 (0.63–1.00) and 0.91 (0.79–1.04). Stronger associations were observed in patients who were younger (<75 years old), Caucasian, and with moderate renal function.ConclusionsMetformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality.
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