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  • Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study.

    16 October 2018

    BACKGROUND: The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. METHODS: 512 891 adults (59% women) aged 30-79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. FINDINGS: During a median follow-up of 9 years (IQR 8-10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40-79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120-180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28-1·34]) and ischaemic stroke (1·30 [1·29-1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65-1·71]). HRs for vascular disease were twice as steep at ages 40-49 years than at ages 70-79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35-1·44]) and diabetes (1·14 [1·12-1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually. INTERPRETATION: Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality. FUNDING: UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.

  • Author Correction: Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel.

    14 March 2019

    Since the publication of this paper, the authors noticed that James E. East was assigned to the incorrect affiliation. The affiliation information is provided correctly, above.

  • Microbial Interactions in the Cystic Fibrosis Airway.

    16 October 2018

    Interactions in the airway ecology of cystic fibrosis may alter organism persistence and clinical outcomes. Better understanding of such interactions could guide clinical decisions. We fitted logistic regression models using generalized estimating equations to longitudinal two-year patient cohorts in the Cystic Fibrosis Foundation Patient Registry, 2003-2011 to study associations between airway organisms present in each calendar year and their presence in the subsequent year. Models were adjusted for clinical characteristics and multiple observations per patient and tested for sensitivity to cystic fibrosis-specific treatments. The study included 28,042 patients aged six and older from 257 accredited US Care Centers and Affiliates with sputum cultures for at least two consecutive years for methicillin-sensitive Staphylococcus aureus, methicillin-resistant S aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Candida and Aspergillus species. We analyzed 99.8% of 538,458 sputum cultures from the patients during the study period. Methicillin-sensitive S aureus was negatively associated with subsequent P aeruginosa. P aeruginosa was negatively associated with subsequent B cepacia complex, A xylosoxidans, and S maltophilia. B cepacia complex was negatively associated with future presence of all studied bacteria and Aspergillus species. P aeruginosa, B cepacia complex and S maltophilia were each reciprocally and positively associated with Aspergillus species. Independent of patient characteristics, studied organisms interact and alter outcomes of treatment decisions, sometimes in unexpected ways. By inhibiting P aeruginosa, methicillin-sensitive S aureus may delay lung disease progression. P aeruginosa and B cepacia complex may inhibit other organisms by decreasing airway biodiversity, potentially worsening lung disease.

  • An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded RCT recruitment.

    16 October 2018

    To explore how the concept of randomisation is described by clinicians and understood by patients in randomised clinical trials (RCTs), and how it contributes to patient understanding and recruitment.Qualitative analysis of seventy-three audio recordings of recruitment consultations from five, multi-centre, UK based RCTs with identified or anticipated recruitment difficulties.One in ten appointments did not include any mention of randomisation. Most included a description of the method or process of allocation. Descriptions often drew on gambling-related metaphors or similies, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was 'best for them'. Descriptions of the rationale for randomisation were rarely present, and often only came about as a consequence of patients questioning the reason for a random allocation.The methods and processes of randomisation were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomisation was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations, and instead focus on clearer descriptions of the rationale and method of randomisation to ensure patients are better informed about randomisation and RCT participation.

  • Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis.

    14 March 2019

    BACKGROUND: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. METHODS AND RESULTS: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. CONCLUSIONS: Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

  • Cardiovascular risk factors and frailty in a cross-sectional study of older people: implications for prevention.

    16 October 2018

    to examine the associations of cardiovascular disease (CVD) and cardiovascular risk factors with frailty.a cross-sectional study.the Irish Longitudinal Study on Ageing (TILDA).frailty measures were obtained on 5,618 participants and a subset of 4,330 participants with no prior history of CVD.cardiovascular risk factors were combined in three composite CVD risk scores (Systematic Coronary Risk Evaluation [SCORE], Ideal Cardiovascular Health [ICH] and Cardiovascular Health Metrics [CHM]).a frailty index (40-items) was used to screen for frailty.the associations of CVD risk factors with frailty were examined using logistic regression.overall, 16.4% of participants had frailty (7.6% at 50-59 years to 42.5% at 80+ years), and the prevalence was higher in those with versus those without prior CVD (43.0% vs. 10.7%). Among those without prior CVD, mean levels of CVD risk factors were closely correlated with higher frailty index scores. Combined CVD risk factors, assessed using SCORE, were linearly and positively associated with frailty. Compared to low-to-moderate SCOREs, the odds ratio (OR) (95% confidence interval, CI) of frailty for those with very high risk was 3.18 (2.38-4.25). Conversely, ICH was linearly and inversely associated with frailty, with an OR for optimal health of 0.29 (0.21-0.40) compared with inadequate health.the concordant positive associations of SCORE and inverse associations of ICH and CHM with frailty highlight the potential importance of optimum levels of CVD risk factors for prevention of disability in frail older people.

  • PCSK9 inhibition: ready for prime time in CKD?

    16 October 2018

    Lowering LDL cholesterol reduces the risk of atherosclerotic vascular disease in a wide range of patients with chronic kidney disease, with no evidence of a threshold below which further reductions no longer reduce risk. Statins safely lower LDL cholesterol, but novel inhibitors of proprotein convertase subtilisin kexin 9 (PCSK9) provide additional reductions which may reduce atherosclerotic vascular disease yet further in this high risk population.

  • Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data.

    5 December 2018

    Purpose Incidental cardiac irradiation can cause cardiac injury, but little is known about the effect of radiation on specific cardiac segments. Methods For 456 women who received breast cancer radiotherapy between 1958 and 2001 and then later experienced a major coronary event, information was obtained on the radiotherapy regimen they received and on the location of their cardiac injury. For 414 women, all with documented location of left ventricular (LV) injury, doses to five LV segments were estimated. For 133 women, all with documented location of coronary artery disease with ≥ 70% stenosis, doses to six coronary artery segments were estimated. For each segment, numbers of women with left-sided and right-sided breast cancer were compared. Results Of women with LV injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left v right, 1.42; 95% CI, 1.17 to 1.73), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy; left minus right dose difference, 7.7 Gy). For individual LV segments, the ratios of women with left- versus right-sided radiotherapy were as follows: inferior, 0.94 (95% CI, 0.70 to 1.25); lateral, 1.42 (95% CI, 1.04 to 1.95); septal, 2.09 (95% CI, 1.37 to 3.19); anterior, 1.85 (95% CI, 1.39 to 2.46); and apex, 4.64 (95% CI, 2.42 to 8.90); corresponding left-minus-right dose differences for these segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy, respectively ( Ptrend < .001). For women with coronary artery disease, the ratios of women with left- versus right-radiotherapy for individual coronary artery segments were as follows: right coronary artery proximal, 0.48 (95% CI, 0.26 to 0.91); right coronary artery mid or distal, 1.69 (95% CI, 0.85 to 3.36); circumflex proximal, 1.46 (95% CI, 0.72 to 2.96); circumflex distal, 1.11 (95% CI, 0.45 to 2.73); left anterior descending proximal, 1.89 (95% CI, 1.07 to 3.34); and left anterior descending mid or distal, 2.33 (95% CI, 1.19 to 4.59); corresponding left-minus-right dose differences for these segements were -5.0, -2.5, 1.6, 3.5, 9.5, and 38.8 Gy ( Ptrend = .002). Conclusion For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized.