Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.

OBJECTIVE: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects. METHODS: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. RESULTS: Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. CONCLUSIONS: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

Genetic effects on carotid intima-media thickness: systematic assessment and meta-analyses of candidate gene polymorphisms studied in more than 5000 subjects.

BACKGROUND: Carotid intima-media thickness (CIMT) is highly heritable and associated with stroke and myocardial infarction, making it a promising quantitative intermediate phenotype for genetic studies of vascular disease. There have been many CIMT candidate gene association studies, but no systematic review to identify consistent, reliable findings. METHODS AND RESULTS: We comprehensively sought all published studies of association between CIMT and any genetic polymorphism. We obtained additional unpublished data and performed meta-analyses for the 5 most commonly studied genes (studied in at least 2 studies in a total of >5000 subjects). We used a 3-step meta-analysis method: meta-analysis of variance; genetic model selection; and random effects meta-analysis of the mean CIMT difference between genotypes. We performed subgroup analyses to investigate effects of ethnicity, vascular risk status, and study size. We accounted for potential reporting bias by assessing qualitatively the possible effects of including unavailable data. Polymorphisms in 3 of the 5 genes (apolipoprotein E, angiotensin I converting enzyme, and 5,10-methylenetetrahydrofolate reductase) had an apparent association with CIMT, but for all these, we found evidence of small study bias. Apolipoprotein E epsilon2/epsilon3/epsilon4 was the only polymorphism with a persistent, statistically significant but modest association when we restricted analysis to larger studies (>1000 subjects). CONCLUSIONS: Of the most extensively studied polymorphisms, apolipoprotein E epsilon2/epsilon3/epsilon4 is the only one so far with a convincing association with CIMT. Larger studies than have generally been performed so far may be needed to confirm the associations identified in future genome-wide association studies, and to investigate modification of effect according to characteristics such as ethnicity and vascular risk status.

Genetic determinants of white matter hyperintensities on brain scans: a systematic assessment of 19 candidate gene polymorphisms in 46 studies in 19,000 subjects.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are highly heritable and associated with small artery ischemic stroke, so they may be a useful trait for studying the genetics of small vessel disease. Many studies have attempted to find associations between polymorphisms in various candidate genes and WMH. We aimed to evaluate the evidence for these associations by performing a systematic review and series of meta-analyses. METHODS: We used a comprehensive search strategy to identify studies of the association between any genetic polymorphism and WMH. For all polymorphisms in genes studied in >2000 subjects we performed meta-analyses, calculating pooled odds ratios or standardized mean differences. RESULTS: We identified 46 studies of polymorphisms in 19 genes in approximately 19 000 subjects. Most genes were involved in lipid metabolism, control of vascular tone, or blood pressure regulation. Polymorphisms in the apolipoprotein E, angiotensin-converting enzyme, methylenetetrahydrofolate reductase, and angiotensinogen genes had been studied in >2000 subjects and were evaluated by meta-analysis. There was no evidence for an association between apolipoprotein E (epsilon 4+/-), methylenetetrahydrofolate reductase (677 cytosine/thymine polymorphism [C/T]), or angiotensinogen (Met235Thr) and WMH. For the angiotensin-converting enzyme insertion/deletion polymorphism (I/D) there appeared to be a significant association (OR, 1.95; 95% CI, 1.09-3.48), but this may be partly attributable to the small study (mainly publication) and other biases. CONCLUSIONS: No genetic polymorphism has yet shown convincing evidence for an association with WMH. Much larger studies will be needed to detect and confirm genetic associations with this promising trait in the era of genome-wide association studies.