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  • Change in albuminuria and risk of renal and cardiovascular outcomes: natural variation should be taken into account

    16 October 2018

    Introduction Changes in urinary albumin-to-creatinine ratio (UACR) may affect the risk of advanced chronic kidney disease (CKD). How much the effect depends upon natural variation and the time period for the change is unknown. Methods English Clinical Practice Research Datalink records (2000-2015), with linkage to secondary care and death certification, were used to identify prospective cohorts with at least two measures of UACR within 1, 2 and 3 years. Adjusted Cox regression assessed the separate relevance of baseline UACR and UACR change to the risk of developing CKD stage 4-5 and end-stage renal disease (ESRD). Associations were compared before and after accounting for the effects of natural regression to the mean (RtM). Results 212,810 individuals had baseline UACR measurements; 22% had a UACR ≥3.4, and 3% had UACR ≥33.9, mg/mmol. During a median 4.0 years follow-up, 5976 developed CKD stage 4-5 and 1076 developed ESRD. There were strong associations between baseline UACR and CKD stage 4-5 or ESRD risk, which doubled in strength after accounting for RtM. Over 3 years, the hazard ratios, HRs (95%CIs) for CKD stage 4-5, relative to stable UACR, were 0.62 (0.50-0.77) for at least a halving of UACR and 2.68 (2.29-3.14) for at least a doubling. Associations were weaker for shorter exposure windows (and for cardiovascular disease or death), but strengthened after allowing for RtM. Conclusion Baseline values and medium term increases in albuminuria are both associated with substantially increased risk of developing advanced CKD. Standard analyses, not allowing for RtM, may underestimate these associations.

  • Cardiovascular Outcomes Reported in Hemodialysis Trials

    16 October 2018

    © 2018 American College of Cardiology Foundation Patients on long-term hemodialysis are at very high risk for cardiovascular disease but are usually excluded from clinical trials conducted in the general population or in at-risk populations. There are no universally agreed cardiovascular outcomes for trials conducted specifically in the hemodialysis population. In this review, we highlight that trials reporting cardiovascular outcomes in hemodialysis patients are usually of short duration (median 3 to 6 months) and are small (59% of trials have <100 participants). Overall, the cardiovascular outcomes are very heterogeneous and may not reflect outcomes that are meaningful to patients and clinicians in supporting decision making, as they are often surrogates of uncertain clinical importance. Composite outcomes used in different trials rarely share the same components. In a field in which a single trial is often insufficiently powered to fully assess the clinical and economic impact of interventions, differences in outcome reporting across trials make the task of meta-analysis and interpretation of all the available evidence challenging. Core outcome sets are now being established across many specialties in health care to prevent these problems. Through the global Standardized Outcomes in Nephrology–Hemodialysis initiative, cardiovascular disease was identified as a critically important core domain to be reported in all trials in hemodialysis. Informed by the current state of reporting of cardiovascular outcomes, a core outcome measure for cardiovascular disease is currently being established with involvement of patients, caregivers, and health professionals. Consistent reporting of cardiovascular outcomes that are critically important to hemodialysis patients and clinicians will strengthen the evidence base to inform care in this very high-risk population.

  • Self-Rated Health Status and Risk of Incident Stroke in 0.5 Million Chinese Adults: The China Kadoorie Biobank Study.

    11 December 2018

    BACKGROUND AND PURPOSE: Self-rated health (SRH) is a consistent and strong predictor of all-cause and cardiovascular mortality in various populations. However, the associations between SRH measures and risk of first-ever or recurrent stroke were rarely explored. We thus aim to prospectively investigate the associations between SRH measures and risk of total and subtypes of stroke in Chinese population. METHODS: A total of 494,113 participants from the China Kadoorie Biobank without prior heart diseases or cancer (486,541 without stroke and 7,572 with stroke) were followed from baseline (2004 to 2008) until December 31, 2013. General and age-comparative SRH were obtained from baseline questionnaires. First-ever stroke or recurrent events were ascertained through linkage to disease registry system and health insurance data. RESULTS: We identified 27,662 first-ever stroke and 2,909 recurrent events during an average of 7.0 years of follow-up. Compared with excellent general SRH, the hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever stroke associated with good, fair, and poor general SRH were 1.04 (1.00 to 1.08), 1.19 (1.15 to 1.23), and 1.49 (1.42 to 1.56) in the multivariate model, respectively. Compared with better age-comparative SRH, the HRs (95% CIs) of same and worse age-comparative SRH were 1.13 (1.10 to 1.17) and 1.51 (1.45 to 1.58), respectively. The relations of SRH measures with ischemic stroke, hemorrhagic stroke, and recurrent stroke were similar to that with total first-ever stroke. However, the magnitude of associations was much stronger for fatal stroke than for non-fatal stroke. CONCLUSIONS: This large-scale prospective cohort suggests that self-perceived health status is associated with incident stroke, regardless of stroke subtype.

  • Chronic hepatitis B virus infection and risk of chronic kidney disease: a population-based prospective cohort study of 0.5 million Chinese adults.

    11 December 2018

    BACKGROUND: Existing evidence remains inconclusive as to the association between chronic hepatitis B virus (HBV) infection and the risk of chronic kidney disease (CKD). We prospectively examined the association between chronic HBV infection and CKD risk, and the joint associations of HBV infection with established risk factors of several lifestyle factors and prevalent diseases on CKD risk. METHODS: Participants from the China Kadoorie Biobank were enrolled during 2004-2008 and followed up until 31 December 2015. After excluding participants with previously diagnosed CKD, cancer, heart disease, and stroke at baseline, the present study included 469,459 participants. Hepatitis B surface antigen (HBsAg) was qualitatively tested at baseline. Incident CKD cases were identified mainly through the health insurance system and disease and death registries. RESULTS: During a median follow-up of 9.1 years (4.2 million person-years), we documented 4555 incident cases of CKD. Cox regression yielded multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with HBsAg-negative participants, the multivariable-adjusted HR (95% CI) for CKD was 1.37 (1.18, 1.60) for HBsAg-positive participants. The association was stronger in men (HR = 1.77; 95% CI: 1.43, 2.20) than in women (HR = 1.10; 95% CI: 0.88, 1.36). HBsAg-positive participants, with or without hepatitis or cirrhosis, whether or not under treatment, all showed increased risk of developing CKD. We observed positive additive interactions of HBsAg positivity with smoking, physical inactivity, or diabetes on CKD risk. Compared with HBsAg-negative participants who were nonsmokers, more physically active, or did not have diabetes at baseline, the greatest CKD risk for HBsAg-positive participants was for those who were smokers (HR = 1.85; 95% CI: 1.44, 2.38), physically inactive (HR = 1.91; 95% CI: 1.52, 2.40), or diabetic (HR = 6.11; 95% CI: 4.47, 8.36). CONCLUSIONS: In countries with a high endemicity of HBV infection, kidney damage associated with chronic HBV infection should be a non-negligible concern. Our findings also highlight the importance of health advice on quitting smoking, increasing physical activity, improving glucose control, and early screening for CKD in people with chronic HBV infection.

  • Association between multiple comorbidities and self-rated health status in middle-aged and elderly Chinese: the China Kadoorie Biobank study.

    11 December 2018

    BACKGROUND: Understanding the correlates of self-rated health (SRH) can help public health professionals prioritize health-promotion and disease-prevention interventions. This study aimed to investigate the association between multiple comorbidities and global SRH and age-comparative SRH. METHODS: A total of 512,891 participants aged 30-79 years old were recruited into the China Kadoorie Biobank study from ten regions between 2004 and 2008. Multivariate logistic regression models were used to estimate the odds ratios (ORs) for the associations between comorbidities (including diabetes, hypertension, coronary heart disease, rheumatic heart disease, stroke, tuberculosis, emphysema/bronchitis, asthma, cirrhosis/chronic hepatitis, peptic ulcer, gallbladder disease, kidney disease, fracture, rheumatic arthritis, psychiatric disorders, depressive symptoms, neurasthenia, head injury and cancer) and SRH. Population attributable risks (PARs) were used to estimate the contribution of multiple comorbidities to poor global SRH and worse age-comparative SRH. RESULTS: After adjusting for covariates, suffering from various diseases increased the chance of reporting a poor global SRH [OR (95% CI) ranged from 1.10 (1.07, 1.13) for fracture to 3.21 (2.68, 3.83) for rheumatic heart disease] and a worse age-comparative SRH [OR (95% CI) ranged from 1.18 (1.13, 1.23) for fracture to 7.56 (6.93, 8.25) for stroke]. From the population perspective, 20.23% of poor global SRH and 45.12% of worse age-comparative SRH could attributed to the cardiometabolic diseases, with hypertension (7.84% for poor global SRH and 13.79% for worse age-comparative SRH), diabetes (4.35% for poor global SRH and 10.71% for worse age-comparative SRH), coronary heart disease (4.44% for poor global SRH and 9.51% for worse age-comparative SRH) and stroke (3.20% for poor global SRH and 10.19% for worse age-comparative SRH) making the largest contribution. CONCLUSIONS: Various diseases were major determinants of global and age-comparative SRH, and cardiometabolic diseases had the strongest impact on both global SRH and age-comparative SRH at the population level. Prevention measures concentrated on these conditions would greatly reduce the total burden of poor SRH and its consequences such as poor quality of life and use of health care services.

  • [Prospective study on the effect of BMI and waist circumference on diabetes of adults in Zhejiang province].

    16 October 2018

    Objective: To explore the effect of BMI and waist circumference on diabetes of adults. Methods: After excluding participants with heart disease, stroke, cancer and diabetes at baseline study, 53 916 people aged 30-79 in the China Kadoorie Biobank (CKB) study from Tongxiang city of Zhejiang province were recruited. Cox regression model was used to estimate the hazards ratios (HR) for the associations of baseline BMI and waist circumference with incident diabetes. Results: Among 391 512 person-years of the follow-up program between 2004 and 2013 (median 7.26 years), a total of 944 men and 1 643 women were diagnosed as having diabetes. Compared to those with normal weight, after adjusting for known or potential factors, HR of both overweight and obesity in men for incident diabetes appeared as 2.72 (95%CI: 2.47-2.99) and 6.27 (95%CI: 5.33-7.36), respectively. The corresponding figures in women were 2.19 (95%CI: 2.04-2.36) and 3.78 (95%CI: 3.36-4.26). Compared to those with normal waist circumference, after adjusting for known or potential factors, HR of Ⅰgrade andⅡgrade in men for diabetes were 2.56 (95%CI: 2.22-2.95) and 4.66 (95%CI: 4.14-5.24), respectively. The corresponding figures in women were 1.99 (95%CI: 1.80-2.21) and 3.16 (95%CI: 2.90-3.44), respectively. Conclusions: Overweight, obesity and central obesity were all associated with the increased incident of diabetes. Strategies on diabetes prevention should include not only losing weight, but reducing waist circumference as well.

  • Authors' Reply.

    16 October 2018