Search

Objectives: To investigate whether frailty modifies the association of systolic blood pressure (SBP) with cardiovascular mortality and all-cause mortality in community-dwelling older adults. Design: A prospective cohort study. Setting: A population-based study of nationally representative older Chinese adults in a community setting. Participants: This study included participants aged 65 years or older from the Chinese Longitudinal Healthy Longevity Survey 2002–2014 and followed up to 2018. Measurements: Participants were divided into two groups according to a frailty index based on the accumulation of a 44-items deficits model. The association between SBP and mortality was analyzed using multivariable-adjusted Cox proportional hazards models. Results: Among 18,503 participants included, the mean age was 87.2 years and the overall median follow-up time was 42.7 months. We identified 7808 (42.2%) frail participants (mean frailty index=0.33), in which 7533 (96.5%) died during the follow-up. Effect modification by frailty was detected (P for interaction=0.032). Among frail participants, a U-shaped association was found with hazard ratios of 1.16 (95% CI, 1.02–1.32) for SBP < 100 mmHg, and 1.11 (95% CI, 1.00–1.24) for SBP ≥ 150 mmHg compared with SBP 120–130 mmHg. For non-frail older adults, a tendency toward higher risk among those with SBP ≥ 130 mmHg was observed. The analyses towards cardiovascular mortality showed similar results. Conclusion: Our results suggest the presence of effect modification by frailty indicating a possible negative effect for elevated SBP in non-frail older adults and a U-shaped relationship of SBP in frail older adults with respect to mortality even after adjusting for diastolic blood pressure. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic yield of prenatal whole exome sequencing (WES) for monogenic disorders in fetuses with structural malformations and normal results on cytogenetic testing, and to describe information on pathogenic variants that is provided by WES.Methods: Karyotyping, chromosomal microarray analysis (CMA) and WES were performed sequentially on stored samples from a cohort of 3949 pregnancies with fetal structural abnormalities detected on ultrasound and/or magnetic resonance imaging, referred between January 2011 and December 2015. Diagnostic rates of the three techniques were investigated overall, for phenotypic subgroups and for proband-only vs fetus-mother-father samples. Information on pathogenic variants was identified by WES.Results: Overall, 18.2% (720/3949) of fetuses had an abnormal karyotype. Pathogenic copy number variants were detected on CMA in 8.2% (138/1680) of fetuses that had a normal karyotype result. WES performed on a subgroup of 196 fetuses with normal CMA and karyotype results revealed the putative genetic variants responsible for the abnormal phenotypes in 47 cases (24%). The molecular diagnosis rates for fetus-mother-father and proband-only samples were 26.5% (13/49) and 23.1% (34/147), respectively. Variants of uncertain significance were detected in 12.8% (25/196) of fetuses, of which 22 were identified in the fetal proband-only group (15%; 22/147) and three in the fetus-mother-father group (6.1%; 3/49). The incidental finding rate was 6.1% (12/196).Conclusions: WES is a promising method for the identification of genetic variants that cause structural abnormalities in fetuses with normal results on karyotyping and CMA. This enhanced diagnostic yield has the potential to improve the clinical management of pregnancies and to inform better the reproductive decisions of affected families. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]