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BACKGROUND Mid-life hypertension is associated with cognitive decline and dementia in later life. Reducing high blood pressure (BP) with antihypertensive agents is a well-researched strategy to prevent dementia and mild cognitive impairment (MCI). However, there is still limited direct evidence to support the approach, and particularly for the treatment of the very old and those with existing MCI. METHODS This review presents an overview of the current evidence for the relationship between MCI and hypertension, and of the potential pathophysiological mechanisms related to cognitive decline and incidence dementia in relation to aging. RESULTS Although observational data are near consistent in showing an association between mid-life hypertension and MCI and/or dementia, the evidence in relation to hypertension in younger adults and the very old (age >80 years) is much more limited. Most of the commonly available antihypertensive agents appear to provide beneficial effects in reducing the risk dementia, but there is limited evidence to support such treatment in those with existing MCI. CONCLUSIONS Further studies are needed to determine the optimal levels of BP control across different age groups, especially in adults with MCI, and which class(es) of antihypertensive agents and duration of treatment best preserve cognitive function in those at risk of, or with established, MCI. [ABSTRACT FROM AUTHOR]

Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n  = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of −50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes. [ABSTRACT FROM AUTHOR]

Background Sex and gender differences in chronic kidney disease (CKD), including epidemiology and response to treatment, remain poorly understood. This study aimed to investigate how women are represented in CKD clinical trials and whether sex- and gender-disaggregated outcomes were reported. Methods Clinical trials on CKD were identified from ClinicalTrials.gov. Randomised, phase 3/4 trials with ≥100 participants were selected to quantify women's representation among participants by computing the participation:prevalence ratio (PPR) and investigating whether sex-disaggregated analyses had been performed. Results In total, 192 CKD trials registered on ClinicalTrials.gov and published between 1995 and 2022 were included. Overall, women accounted for 66 875 (45%) of the 147 136 participants. Women's participation in clinical trials was lower than their representation in the underlying CKD population globally (55%). The PPR was 0.75 (95% confidence interval 0.72–0.78), with no significant variation irrespective of mean age, CKD stage, dialysis, location, type of intervention or funding agency. A total of 39 (20%) trials reported sex-disaggregated efficacy outcomes and none reported sex-disaggregated safety outcomes. Conclusion Women's participation in CKD clinical trials was lower than their representation in the underlying CKD population. Sex-disaggregated efficacy and safety outcomes were rarely reported. Improving women's enrolment into clinical trials is crucial to enable sex- and gender-disaggregated analysis and thus identify potential differences in treatment response between women and men. [ABSTRACT FROM AUTHOR]

Aims Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia. Methods and results Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk. Conclusion The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia. Classification of evidence Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo. [ABSTRACT FROM AUTHOR]

Key Features The Zahedan Adult Cohort Study (ZACS) was established to investigate the incidence of non-communicable diseases and their risk factors in Zahedan, and is the first cohort study in the Baluch and Sistani ethnic groups. Importantly, cardiovascular disease, cancers and chronic respiratory disease have been the main drivers of reducing premature avertable mortality from NCDs.[3] Moreover, evidence shows that premature mortality among drug users, chronic kidney disease, acute glomerulonephritis and diabetes increases. Therefore, identifying risk factors for NCDs at the local and national levels is essential for policy makers to decide on effective policies for reducing the burden of NCDs in Iran.[9] Cohort studies are the best type of research to identify and quantify the relationship between exposure and outcome. The ZACS outcomes of interest are death, non-communicable diseases and changes in risk factors or protective factors. [Extracted from the article]

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of 'the comparison of high-dose HDF with high-flux HD' (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease. [ABSTRACT FROM AUTHOR]

Background: It is commonly assumed that high oestradiol levels in women are cardioprotective. We assessed the association between oestradiol and the risk of incident myocardial infarction (MI) in women.Methods: We used data from 263 295 female UK Biobank participants [mean age 56.2; standard deviation (SD) 8.0 years] without previous cardiovascular disease (CVD). Associations of oestradiol with age and other cardiovascular risk factors were assessed. Cox proportional hazards models estimated crude, ag- and multiple-adjusted hazard ratios (HR) for MI associated with oestradiol levels.Results: After a mean follow-up of 9 years, 2206 incident cases of MI had been recorded, including 230 events among the 57 204 women (mean age 48) with detectable oestradiol levels. In the unadjusted analyses, a unit higher in log-transformed oestradiol was associated with an HR [95% confidence interval (CI) for MI of 0.73 (0.58; 0.92)]. After adjusting for age, this HR became 0.94 (0.75; 1.17), and after further adjusting for classical CVD risk factors, it was 1.05 (0.83; 1.31. Results were similar in subgroup analyses defined by age, menopausal status, socioeconomic status, contraceptive pill use and the use of hormone replacement therapy. The multivariable-adjusted HR for the 171 431 women (mean age 59) with undetectable levels of oestradiol, compared with those with detectable levels, was 0.97 (0.92; 1.02).Conclusions: Higher levels of oestradiol were not associated with a decreased risk of MI. The presumed cardioprotective effects of oestradiol seem to be largely confounded by age and further confounded by other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

There is a causal relationship between dietary salt intake and blood pressure. A reduction in salt intake from the current world average of ∼10 g/day to the WHO recommended level of <5 g/day, lowers blood pressure and reduces the risk of cardiovascular disease and all-cause mortality. However, a few cohort studies have claimed that there is a J-shaped relationship between salt intake and cardiovascular risk, i.e. both high and low salt intakes are associated with an increased risk. These cohort studies have several methodological problems, including reverse causality, and inaccurate and biased estimation of salt intake, e.g. from a single spot urine sample with formulas. Recent studies have shown that the formulas used to estimate salt intake from spot urine cause a spurious J-curve. Research with inappropriate methodology should not be used to refute the robust evidence on the enormous benefits of population-wide reduction in salt intake. Several countries, e.g. Finland, the UK, have successfully reduced salt intake, which has resulted in falls in population blood pressure and deaths from stroke and ischaemic heart disease. Every country should develop and implement a coherent, workable strategy to reduce salt intake. Even a modest reduction in salt intake across the whole population will lead to a major improvement in public health, along with huge cost-savings to the healthcare service. [ABSTRACT FROM AUTHOR]

Background Several studies have investigated the effect of socioeconomic deprivation on cardiovascular disease (CVD) and diabetes; less is known about its effect on chronic kidney disease (CKD). We aimed to measure the association between deprivation, CKD Stages 4–5 and end-stage renal disease (ESRD) in a general population sample. Methods This observational study examined 1 405 016 participants from the English Clinical Practice Research Datalink (2000–14), linked to hospital discharge data and death certification. Deprivation was assessed according to the participant's postcode. Cox models were used to estimate hazard ratios (HRs) for CKD Stages 4–5 and ESRD, adjusting for age and sex, and additionally for smoking status, body mass index, diabetes, systolic blood pressure, prior CVD and estimated glomerular filtration rate (eGFR) at baseline. Results During 7.5 years of median follow-up, 11 490 individuals developed CKD Stages 4–5 and 1068 initiated ESRD. After adjustment for age and sex, the HRs and confidence interval (CI) comparing those in the 20% most deprived of the population to the 20% least deprived were 1.76 (95% CI 1.68–1.84) and 1.82 (95% CI 1.56–2.12) for CKD Stages 4–5 and ESRD, respectively. Further adjustment for known risk factors and eGFR substantially attenuated these HRs. Adding our results to all known cohort studies produced a pooled relative risk of 1.61 (95% CI 1.42–1.83) for ESRD, for comparisons between highest to lowest categories of deprivation. Conclusion Socioeconomic deprivation is independently associated with an increased hazard of CKD Stages 4–5 and ESRD, but in large part may be mediated by known risk factors. [ABSTRACT FROM AUTHOR]

Aims Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. Methods and results We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n  = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n  = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83–0.84) and 0.64–0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment. Conclusion Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients. [ABSTRACT FROM AUTHOR]

Background There is strong evidence of an association between socioeconomic status (SES) and end-stage renal disease (ESRD). However, the association of SES with the risk of chronic kidney disease (CKD) and the rate of change in kidney function is unclear. Methods A cohort of 14 086 participants with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline in the Atherosclerosis Risk in Communities study (1987–89) were studied. The association of annual household income, educational attainment and neighborhood deprivation with incident ESRD, incident CKD and change in eGFR using four measurements over ∼23 years was assessed. Results A total of 432 participants developed ESRD and 3510 developed CKD over a median follow-up time of ∼23 years. After adjustment for demographics and baseline eGFR, the hazard ratio (HR) for incident ESRD compared with the high-income group was 1.56 [95% confidence interval (CI) 1.22–1.99 in the medium-income group and 2.30 (95% CI 1.75–3.02) in the low-income group (P-trend < 0.001), and for CKD was 1.10 (95% CI 1.01–1.20) in the medium-income group and 1.30 (95% CI 1.17–1.44) in the low-income group (P-trend < 0.001). After full adjustments, the HR for ESRD was 1.33 (95% CI 1.03–1.70) in the medium-income group and 1.50 (95% CI 1.14–1.98) in the low-income group (P-trend = 0.003) and for CKD was 1.01 (95% CI 0.92–1.10) in the medium-income group and 1.04 (95% CI 0.93–1.16) in the low-income group (P-trend = 0.50). The eGFR decline was 5% and 15% steeper in the medium- and low-income groups, respectively, after full adjustment (P-trend < 0.001). Results were similar, with lower educational attainment and higher neighborhood deprivation being associated with adverse outcomes. Conclusions SES (annual household income, educational attainment or neighborhood deprivation) was associated not only with ESRD risk but also with eGFR decline, although the association with CKD appeared weaker. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity is associated with an increased risk of major chronic diseases, although uncertainty exists about which chronic diseases, themselves, might contribute to physical inactivity. The objective of this study was to compare the physical activity of those with chronic diseases to healthy individuals using an objective measure of physical activity.Methods: We conducted a cross-sectional analysis of data from 96 706 participants aged 40 years or older from the UK Biobank prospective cohort study (2006-10). Diagnoses were identified through ICD 9 and 10 coding within hospital admission records and a cancer registry linked to UK Biobank participants. We extracted summary physical activity information from participants who wore a wrist-worn triaxial accelerometer for 7 days. Statistical analyses included computation of adjusted geometric means and means using general linear models.Results: Participants with chronic disease undertook 9% or 61 minutes (95% confidence interval: 57.8-64.8) less moderate activity and 11% or 3 minutes (95% confidence interval: 2.7-3.3) less vigorous activity per week than individuals without chronic disease. Participants in every chronic-disease subgroup undertook less physical activity than those without chronic disease. Sixty-seven diagnoses within these subgroups were associated with lower moderate activity.Conclusions: The cross-sectional association of physical activity with chronic disease is broad. Given the substantial health benefits of being physically active, clinicians and policymakers should be aware that their patients with any chronic disease are at greater health risk from other diseases than anticipated because of their physical inactivity. [ABSTRACT FROM AUTHOR]

Background: Accurate assessment of surgical‐site infection (SSI) is crucial for surveillance and research. Self‐reporting patient measures are needed because current SSI tools are limited for assessing patients after leaving hospital. The Bluebelle Wound Healing Questionnaire (WHQ) was developed for patient or observer completion; this study tested its acceptability, scale structure, reliability and validity in patients with closed primary wounds after abdominal surgery. Methods: Patients completed the WHQ (self‐assessment) within 30 days after leaving hospital and returned it by post. Healthcare professionals completed the WHQ (observer assessment) by telephone or face‐to‐face. Questionnaire response rates and patient acceptability were assessed. Factor analysis and Cronbach's α examined scale structure and internal consistency. Test–retest and self‐ versus observer reliability assessments were performed. Sensitivity and specificity for SSI discrimination against a face‐to‐face reference diagnosis (using Centers for Disease Control and Prevention criteria) were examined. Results: Some 561 of 792 self‐assessments (70·8 per cent) and 597 of 791 observer assessments (75·5 per cent) were completed, with few missing data or problems reported. Data supported a single‐scale structure with strong internal consistency (α greater than 0·8). Reliability between test–retest and self‐ versus observer assessments was good (κ 0·6 or above for the majority of items). Sensitivity and specificity for SSI discrimination was high (area under the receiver operating characteristic (ROC) curve 0·91). Conclusion: The Bluebelle WHQ is acceptable, reliable and valid with a single‐scale structure for postdischarge patient or observer assessment of SSI in closed primary wounds. Simple and valid [ABSTRACT FROM AUTHOR]

Background: The capacity of spot urine samples for detecting changes in population sodium and potassium excretion is unclear.Methods: Changes in urinary sodium and potassium excretion, over a 6-month to 2-year interval, were measured from 24-h urine samples and estimated from spot urine samples using several published methods in 3270 Chinese. Additional estimates were made by multiplying individual spot sodium and potassium concentrations by a single estimated 24-h urine volume derived from external data.Results: The measured difference in 24-h urinary excretion between intervention and control groups was -0.35 g (95% CI: -0.68 to -0.02; P = 0.039) for sodium and 0.66 g (95% CI: 0.52 to 0.80; P < 0.001) for potassium, based upon 24-h urine samples. The corresponding estimates of sodium differences for the Tanaka (-0.06 g), Kawasaki (-0.09 g), Intersalt without potassium (-0.09 g) and Intersalt with potassium (-0.14 g) equations were all smaller and identified no reduction in sodium excretion (all P > 0.10). The estimates were -0.65 g for sodium and 1.11 g for potassium using individual spot urine concentrations and an externally derived standard urine volume (both P < 0.01).Conclusions: The published equations were unable to detect the differences in sodium excretion measured by 24-h urine samples. A method based upon spot urine electrolyte concentrations and a standard urine volume may offer an alternative approach to measuring differences in sodium and potassium excretion between population groups without requiring 24-h urine, but will need further investigation. [ABSTRACT FROM AUTHOR]

Aims To test two related hypotheses that elevated blood pressure (BP) is a risk factor for aortic valve stenosis (AS) or regurgitation (AR). Methods and results In this cohort study of 5.4 million UK patients with no known cardiovascular disease or aortic valve disease at baseline, we investigated the relationship between BP and risk of incident AS and AR using multivariable-adjusted Cox regression models. Over a median follow-up of 9.2 years, 20 680 patients (0.38%) were diagnosed with AS and 6440 (0.12%) patients with AR. Systolic BP (SBP) was continuously related to the risk of AS and AR with no evidence of a nadir down to 115 mmHg. Each 20 mmHg increment in SBP was associated with a 41% higher risk of AS (hazard ratio 1.41, 95% confidence interval 1.38–1.45) and a 38% higher risk of AR (1.38, 1.31–1.45). Associations were stronger in younger patients but with no strong evidence for interaction by gender or body mass index. Each 10 mmHg increment in diastolic BP was associated with a 24% higher risk of AS (1.24, 1.19–1.29) but not AR (1.04, 0.97–1.11). Each 15 mmHg increment in pulse pressure was associated with a 46% greater risk of AS (1.46, 1.42–1.50) and a 53% higher risk of AR (1.53, 1.45–1.62). Conclusion Long-term exposure to elevated BP across its whole spectrum was associated with increased risk of AS and AR. The possible causal nature of the observed associations warrants further investigation. [ABSTRACT FROM AUTHOR]

Previous studies of predominantly Western populations have reported inconsistent associations between age at menarche and risk of diabetes. We examined this relationship among Chinese women, who generally experience menarche at a later age than Western women. In 2004-2008, China Kadoorie Biobank recruited 302, 632 women aged 30-79 years from 10 areas across China, and recorded 5, 391 incident cases of diabetes during 7 years of follow-up among 270, 345 women without baseline diabetes, cardiovascular disease or cancer. Cox regression models yielded adjusted hazard ratios for incident diabetes associated with age at menarche. Overall, the mean age at menarche was 15.4 years, and decreased across successive generations. Age at menarche was linearly and inversely associated with incident diabetes, with adjusted hazard ratio of 0.96 (95% confidence interval (CI): 0.94, 0.97) per year delay. Hazard ratios were greater in younger generations (for women born in the 1960s-1970s, hazard ratio (HR) = 0.93, 95% CI: 0.90, 0.97; for women born in the 1950s, HR = 0.95, 95% CI: 0.93, 0.98; and for women born in the 1920s-1940s, HR = 0.97, 95% CI: 0.95, 0.99). Further adjustment for adulthood body mass index significantly attenuated the association (HR = 0.99, 95% CI: 0.97, 1.00), especially among those born before 1950 (HR = 1.00, 95%CI: 0.97, 1.02). Much of the inverse association between age at menarche and incident diabetes was mediated through increased adiposity associated with early menarche, especially in older generations. [ABSTRACT FROM AUTHOR]

Background: Spot urine samples are easier to collect than 24-h urine samples and have been used with estimating equations to derive the mean daily salt intake of a population. Whether equations using data from spot urine samples can also be used to estimate change in mean daily population salt intake over time is unknown. We compared estimates of change in mean daily population salt intake based upon 24-h urine collections with estimates derived using equations based on spot urine samples.Methods: Paired and unpaired 24-h urine samples and spot urine samples were collected from individuals in two Australian populations, in 2011 and 2014. Estimates of change in daily mean population salt intake between 2011 and 2014 were obtained directly from the 24-h urine samples and by applying established estimating equations (Kawasaki, Tanaka, Mage, Toft, INTERSALT) to the data from spot urine samples. Differences between 2011 and 2014 were calculated using mixed models.Results: A total of 1000 participants provided a 24-h urine sample and a spot urine sample in 2011, and 1012 did so in 2014 (paired samples n = 870; unpaired samples n = 1142). The participants were community-dwelling individuals living in the State of Victoria or the town of Lithgow in the State of New South Wales, Australia, with a mean age of 55 years in 2011. The mean (95% confidence interval) difference in population salt intake between 2011 and 2014 determined from the 24-h urine samples was -0.48g/day (-0.74 to -0.21; P < 0.001). The corresponding result estimated from the spot urine samples was -0.24 g/day (-0.42 to -0.06; P = 0.01) using the Tanaka equation, -0.42 g/day (-0.70 to -0.13; p = 0.004) using the Kawasaki equation, -0.51 g/day (-1.00 to -0.01; P = 0.046) using the Mage equation, -0.26 g/day (-0.42 to -0.10; P = 0.001) using the Toft equation, -0.20 g/day (-0.32 to -0.09; P = 0.001) using the INTERSALT equation and -0.27 g/day (-0.39 to -0.15; P < 0.001) using the INTERSALT equation with potassium. There was no evidence that the changes detected by the 24-h collections and estimating equations were different (all P > 0.058). Separate analysis of the unpaired and paired data showed that detection of change by the estimating equations was observed only in the paired data.Conclusions: All the estimating equations based upon spot urine samples identified a similar change in daily salt intake to that detected by the 24-h urine samples. Methods based upon spot urine samples may provide an approach to measuring change in mean population salt intake, although further investigation in larger and more diverse population groups is required. [ABSTRACT FROM AUTHOR]

Background: Adiposity is increasing rapidly in China but little is known about the relevance to it of women's reproductive factors, which differ inter-generationally and from that in the West. We assess associations of adiposity with life-course reproductive factors in Chinese women.Methods: In 2004-08, the nationwide China Kadoorie Biobank recruited 303 000 women aged 30-79 (mean 50) years from 10 diverse regions. Multivariable linear regression was used to examine associations of reproductive factors (e.g. age at menarche/first birth/menopause, parity, breastfeeding and reproductive years) with measures of general [e.g. body mass index (BMI)] and central [e.g. waist circumference (WC)] adiposity in adulthood.Results: Overall, the mean BMI was 23.7 (standard deviation 3.3) kg/m 2 , mean age at menarche was 15 (2) years and nearly all had given birth (99%) and breastfed children (98%). Adiposity was associated inversely with age at menarche and at first birth, with 0.19 and 0.05 kg/m 2 lower BMI and 0.38 and 0.12 cm lower WC per 1-year delay respectively ( P  < 0.001). Among 128 259 post-menopausal women, adiposity was associated positively with age at menopause and reproductive years, with 0.05 and 0.07 kg/m 2 higher BMI and 0.12 and 0.17 cm higher WC per 1-year increase, respectively ( P  < 0.001). The proportion with overweight/obesity had similar associations with these reproductive factors. Adiposity had a non-linear positive association with parity, but no association with breastfeeding duration.Conclusion: Among Chinese women, earlier age at menarche and at first birth, later age at menopause and longer reproductive years were independently associated with increased adiposity late in life. [ABSTRACT FROM AUTHOR]

Background: Women's parity has been associated with risk of cardiovascular disease (CVD). It is unclear, however, whether it reflects biological effects of childbearing or uncontrolled socio-economic and lifestyle factors associated with childrearing. We assessed the association between number of children and incident CVD outcomes separately in women and men.Methods: In 2004-08, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30-79 years from 10 diverse regions. During 7 years of follow-up, 24 432 incident cases of coronary heart disease (CHD) and 35 736 of stroke were recorded among 489 762 individuals without prior CVD. Multivariable Cox regression models were used to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD and stroke associated with number of children.Results: Overall, 98% of all participants had children and the mean number of children declined progressively from four in older participants to one or two in younger participants. Compared with childless women, women with children had an increased risk of CHD, but not of stroke [HR (95% CI): 1.14 (1.00; 1.30) and 1.03 (0.92; 1.16)]. Corresponding results for men were 1.20 (1.06; 1.35) and 1.13 (1.03; 1.24), respectively. In individuals with children, there was a log-linear association between number of children and CVD outcomes; in women, each additional child was associated with adjusted HRs of 1.02 (1.01; 1.04) for CHD and 1.02 (1.01; 1.03) for stroke, similar in magnitude to that in men [1.03 (1.01; 1.04) for CHD and 1.02 (1.01; 1.03) for stroke].Conclusion: In Chinese adults, the association between the number of children and risk of CHD and stroke was similar between men and women, suggesting that factors associated with parenthood and childrearing are more likely to affect the risk of CVD outcomes than factors associated with childbearing. [ABSTRACT FROM AUTHOR]

Background: Although elevated blood pressure is associated with an increased risk of atrial fibrillation (AF), it is unclear if this association varies by individual characteristics. Furthermore, the associations between AF and a range of different vascular events are yet to be reliably quantified.Methods: Using linked electronic health records, we examined the time to first diagnosis of AF and time to first diagnosis of nine vascular events in a cohort of 4.3 million adults, aged 30 to 90 years, in the UK.Results: : A 20-mmHg higher usual systolic blood pressure was associated with a higher risk of AF [hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.19, 1.22]. The strength of the association declined with increasing age, from an HR of 1.91 (CI 1.75, 2.09) at age 30-40 to an HR of 1.01 (CI 0.97, 1.04) at age 80-90 years. AF without antithrombotic use at baseline was associated with a greater risk of any vascular event than AF with antithrombotic usage ( P interaction < 0.0001). AF without baseline antithrombotic usage was associated with an increased risk of ischaemic heart disease (HR 2.52, CI 2.23, 2.84), heart failure (HR 3.80, CI 3.50, 4.12), ischaemic stroke (HR 2.72, CI 2.19, 3.38), unspecified stroke (HR 2.59, CI 2.25, 2.99), haemorrhagic stroke, chronic kidney disease, peripheral arterial disease and vascular dementia, but not aortic aneurysm.Conclusions: The association between elevated blood pressure and AF attenuates with increasing age. AF without antithrombotic usage is associated with an increased risk of eight vascular events. [ABSTRACT FROM AUTHOR]

Background. Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. Methods. Individual participant datawere used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. Results. After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m² body surface area (BSA) per session], with amultivariable-adjusted HRof 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. Conclusions. This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA. [ABSTRACT FROM AUTHOR]

Initially submitted February 11, 2015; accepted for publication April 23, 2015. Married couples might be an appropriate target for obesity prevention interventions. In the present study, we aimed to evaluate whether an individual's risk of obesity is associated with spousal risk of obesity and whether an individual's change in body mass index (BMI; weight in kilograms divided by height in meters squared) is associated with spousal BMI change. We analyzed data from 3,889 spouse pairs in the Atherosclerosis Risk in Communities Study cohort who were sampled at ages 45-65 years from 1986 to 1989 and followed for up to 25 years. We estimated hazard ratios for incident obesity by whether spouses remained nonobese, became obese, remained obese, or became nonobese. We estimated the association of participants' BMI changes with concurrent spousal BMI changes using linear mixed models. Analyses were stratified by sex. At baseline, 22.6% of men and 24.7% of women were obese. Nonobese participants whose spouses became obese were more likely to become obese themselves (for men, hazard ratio = 1.78, 95% confidence interval: 1.30, 2.43; for women, hazard ratio = 1.89, 95% confidence interval: 1.39, 2.57). With each 1-unit increase in spousal BMI change, women's BMI change increased by 0.15 (95% confidence interval: 0.13, 0.18) and men's BMI change increased by 0.10 (95% confidence interval: 0.09, 0.12). Having a spouse become obese nearly doubles one's risk of becoming obese. Future research should consider exploring the efficacy of obesity prevention interventions in couples. [ABSTRACT FROM AUTHOR]

Background: Estimating equations based on spot urine samples have been identified as a possible alternative approach to 24-h urine collections for determining mean population salt intake. This review compares estimates of mean population salt intake based upon spot and 24-h urine samples. Methods: We systematically searched for all studies that reported estimates of daily salt intake based upon both spot and 24-h urine samples for the same population. The associations between the two were quantified and compared overall and in subsets of studies. Results: A total of 538 records were identified, 108 were assessed as full text and 29 were included. The included studies involved 10 414 participants from 34 countries and made 71 comparisons available for the primary analysis. Overall average population salt intake estimated from 24-h urine samples was 9.3 g/day compared with 9.0 g/day estimated from the spot urine samples. Estimates based upon spot urine samples had excellent sensitivity (97%) and specificity (100%) at classifying mean population salt intake as above or below the World Health Organization maximum target of 5 g/day. Compared with the 24-h samples, estimates based upon spot urine overestimated intake at lower levels of consumption and underestimated intake at higher levels of consumption. Conclusions: Estimates of mean population salt intake based upon spot urine samples can provide countries with a good indication of mean population salt intake and whether action on salt consumption is required. [ABSTRACT FROM AUTHOR]

Background: Theoretical links between seasonal lack of sunlight, hypovitaminosis D and excess cardiovascular disease and death prompted our adding novel to conventional cohort analyses.Methods: We tested three postulates on 13,224 Scottish Heart Health Extended Cohort participants, assayed for 25-hydroxyvitamin D (25OHD) and followed for 22 years. (i) Endpoints enumerated by month of occurrence mirror annual seasonal oscillation in 25OHD. (ii) Endpoint seasonality is increased in people with below median 25OHD. (iii) Low 25OHD predicts endpoints independently of major risk factors.Results: Baseline median 25OHD level was 36.4 (other quartiles 26.7, 51.7) nmol/l. The March trough was half the August peak, both well after seasonal solstices. (i) There was no demonstrable monthly variation in First Cardiovascular Event (n = 3307). Peaks and troughs for All Death and Cardiovascular Death (n = 2987, 1350) were near the solstices, earlier than extremes of 25OHD. (ii) Endpoint variability showed no difference between those above and below median 25OHD. (iii) Cox model hazard ratios (HR), by decreasing 25OHD, increased modestly and nonspecifically for all endpoints examined, with no threshold, the gradients diminishing by ∼ : 60% following multiple adjustment. For Cardiovascular Disease, HR, by 20 (∼ SD) nmol/l decrease, =1.224 (1.175, 1.275) adjusted for age and sex; additionally adjusted for family history, deprivation index, smoking, systolic blood pressure, total and HDL cholesterol, =1.093 (1.048, 1.139); All Deaths = 1.238 (1.048, 1.139) and 1.098 (1.050, 1.149). 25OHD made no independent contribution to cardiovascular discrimination and reclassification.Conclusions: Our analyses challenge vitamin D's alleged role as major prime mover in cardiovascular disease and mortality. [ABSTRACT FROM AUTHOR]

Aims Our aim was to test the prediction and clinical applicability of high-sensitivity assayed troponin I for incident cardiovascular events in a general middle-aged European population. Methods and results High-sensitivity assayed troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340) with 2171 cardiovascular events (including acute coronary heart disease and probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by the high-sensitivity method was associated with future cardiovascular risk after full adjustment such as that individuals in the fourth category had 2.5 times the risk compared with those without detectable troponin I (P < 0.0001). These associations remained significant even for those individuals in whom levels of contemporary-sensitivity troponin I measures were not detectable. Addition of troponin I levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (P < 0.0001) and net reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in men is suggested to detect individuals at high risk for future cardiovascular events. Conclusion Troponin I, measured with a high-sensitivity assay, is an independent predictor of cardiovascular events and might support selection of at risk individuals. [ABSTRACT FROM PUBLISHER]

The Chronic Kidney Disease Prognosis Consortium (CKD-PC) was established in 2009 to provide comprehensive evidence about the prognostic impact of two key kidney measures that are used to define and stage CKD, estimated glomerular filtration rate (eGFR) and albuminuria, on mortality and kidney outcomes. CKD-PC currently consists of 46 cohorts with data on these kidney measures and outcomes from >2 million participants spanning across 40 countries/regions all over the world. CKD-PC published four meta-analysis articles in 2010-11, providing key evidence for an international consensus on the definition and staging of CKD and an update for CKD clinical practice guidelines. The consortium continues to work on more detailed analysis (subgroups, different eGFR equations, other exposures and outcomes, and risk prediction). CKD-PC preferably collects individual participant data but also applies a novel distributed analysis model, in which each cohort runs statistical analysis locally and shares only analysed outputs for meta-analyses. This distributed model allows inclusion of cohorts which cannot share individual participant level data. According to agreement with cohorts, CKD-PC will not share data with third parties, but is open to including further eligible cohorts. Each cohort can opt in/out for each topic. CKD-PC has established a productive and effective collaboration, allowing flexible participation and complex meta-analyses for studying CKD. [ABSTRACT FROM AUTHOR]

Several observational studies published over the last 10-15 years show unequivocally that there is an association between certain forms of cancer and type 2 diabetes…in a post-hoc analysis of a randomized intervention trial in type 2 diabetes patients, the ADVANCE study…there was a lack of association of kidney failure and overall and case specific cancer risk in the type 2 diabetes patients.Background Diabetes and chronic kidney disease (CKD) are both associated with an increased risk of cancer but it is unclear whether diabetes complicated by CKD further augments an individual's cancer risk. The aim of our study was to determine the association of CKD [defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min] with the overall and site-specific risks of incident cancers among individuals with Type 2 diabetes. Methods Cox proportional hazard regression models and competing risk analyses were used to examine the univariate and multivariate adjusted associations between reduced kidney function and the overall and site-specific risks of cancer in participants enrolled in the Action in Diabetes and Vascular disease: Preterax and Diamicron MR controlled evaluation (ADVANCE) trial. Results Over a median follow-up of 5.0 years, 700 malignant neoplasms occurred in the 11 140 (6.4%) participants. There was no increase in overall cancer risk [adjusted hazard ratio: 1.07 (95% confidence interval: 0.89–1.29, P = 0.50)] or site-specific cancer risk for individuals with CKD (defined as eGFR < 60 mL/min) compared to those without CKD at baseline. These results were robust to multiple methods and thresholds used to estimate CKD. Conclusions Mild to moderate CKD does not increase the risk of cancer in people with Type 2 diabetes. ADVANCE is registered with ClincalTrial.gov (number NCT00145925). [ABSTRACT FROM AUTHOR]

Aims Dietary fats are routinely considered key determinants of cardiovascular risk, yet the scientific basis of this association has never been demonstrated using objective measures of fat intakes in a large prospective study in a general population. Methods and results Adipose tissue was taken from 3944 participants, predominantly aged 40–59 years, in Scotland, 1984–87. Percentages of individual fatty acids were measured using gas chromatography. Over a median of 19.5 years, 870 incident cardiovascular disease (CVD) events occurred. Hazard ratios (HRs) were obtained from Cox models and the additional prognostic value, accounting for variables in the Framingham and ASSIGN CVD risk scores, were assessed using discrimination indices. Adjusting for age, sex, total and HDL-cholesterol, systolic blood pressure, smoking, hypertensive medication use, diabetes, socio-economic status and family history, the percentage of monounsaturated adipose tissue fatty acids had a positive log-linear relationship with incident CVD: the HR comparing risk between the fourth and first quartiles was 1.29 (95% confidence interval: 1.05, 1.59). n-3 polyunsaturated fat showed the reverse trend, the corresponding result being 0.77 (0.63, 0.94). These two composite variables improved the classification of incident CVD events by 1.0 and 6.4%, respectively, with only the latter being significant at the 5% level. Conclusions A diet which is proportionately rich in polyunsaturated fat, as opposed to other fats, is expected to decrease the risk of CVD independently of the effects of common CVD risk factors, including social deprivation. Taking account of such diets improves the classification of future CVD events. [ABSTRACT FROM PUBLISHER]

Aims Individuals with diabetes and chronic kidney disease (CKD) are at high risk for cardiovascular disease. In these analyses of the ADVANCE trial, we assessed the effects of a fixed combination of perindopril–indapamide on renal and cardiovascular outcomes in patients with type 2 diabetes according to baseline CKD stage. Methods and results Patients with type 2 diabetes were randomized to perindopril–indapamide (4 mg/1.25 mg) or placebo. Treatment effects on cardiovascular (cardiovascular death, myocardial infarction, or stroke) and renal outcomes were compared in subgroups defined by baseline Kidney Disease Outcome Quality Initiative CKD stage. Homogeneity in treatment effect was tested by adding interaction terms to the relevant Cox models. The study included 10 640 participants with known CKD status, of whom 6125 did not have CKD, 2482 were classified as CKD stage 1 or 2, and 2033 as CKD stage ≥3. The relative treatment effects on major cardiovascular events were similar across all stages of CKD, with no heterogeneity in the magnitude of the effects for any outcome. In contrast, the absolute treatment effects approximately doubled in those with CKD stage ≥3 when compared to those with no CKD. For every 1000 patients with CKD stage ≥3 treated for 5 years, active treatment prevented 12 cardiovascular events when compared with six events per 1000 patients with no CKD. Conclusion The treatment benefits of a routine administration of a fixed combination of perindopril–indapamide to patients with type 2 diabetes on cardiovascular and renal outcomes, and death, are consistent across all stages of CKD at baseline. Absolute risk reductions are larger in patients with CKD highlighting the importance of blood pressure-lowering in this population. [ABSTRACT FROM PUBLISHER]

Aims To assess the additional discriminative value of adding each of five inflammatory biomarkers to the ASSIGN risk score, which includes social deprivation. Methods and results In this study, 1319 men and women aged 25–64 in the fourth Glasgow MONICA study were followed-up for cardiovascular endpoints. Baseline C-reactive protein, fibrinogen, IL-6, IL-18, and TNFα were related to risk of CVD. The discriminative value of adding each to the ASSIGN score was assessed using area under the receiver operating characteristic (AUC) and relative integrated percentage improvement in classification (RIDI). During a median of 10.5 years, 151 CVD events occurred. After adjusting for ASSIGN variables, each inflammatory marker except IL-18 had a significant (P < 0.05) association with CVD risk. The AUC using ASSIGN [0.799 (95% CI 0.790–0.809)] was improved by the inclusion of C-reactive protein and TNFα [0.805 (95% CI 0.795–0.815); P < 0.03], but not by other combinations. C-reactive protein and TNFα yielded a significant RIDI (IL-6 almost so). C-reactive protein and TNFα together improved the classification of risk by 11% (95% CI, 3–19%) when added to the ASSIGN variables. Conclusion Some inflammatory biomarkers add moderate discriminative information to the ASSIGN CVD risk score. The clinical utility of this information, cost-effectiveness, and optimization should be assessed in future studies. [ABSTRACT FROM PUBLISHER]

Background: In Caucasian populations, adult height is inversely associated with cardiovascular disease (CVD) risk and positively related to some cancers. However, there are few data from Asian populations and from women. We sought to determine the sex- and region-specific associations between height and cardiovascular outcomes, and deaths due to cancer, respiratory and injury in populations from the Asia-Pacific region.Methods: Thirty-nine studies from the Asia Pacific Cohort Studies Collaboration database were included. We used Cox proportional hazard regression models to estimate the associations between height and pre-specified outcomes.Results: A total of 510,800 participants with 21,623 deaths were included. Amongst men, inverse linear associations were observed between height and coronary heart disease (CHD), stroke, CVD, injury and total mortality. The hazard ratios [95% confidence intervals, (CI)] for a 1-SD (= 6 cm) increment in height ranged from 0.85 (0.80-0.91) for injury to 0.97 (0.95-0.98) for total mortality. Similar trends were found between height and CHD, haemorrhagic stroke and CVD in women. A positive linear association was observed between height and cancer mortality. For each standard deviation greater height, the risk of cancer was increased by 5% (2-8%) and 9% (5-14%) in men and women, respectively. No regional difference was observed between Asian and Australasian cohorts. Adjusting for markers of education did not alter the results.Conclusions: The opposing relationships of height with CVD and cancer suggest that care is required in setting national policies on childhood nutrition lest they have unintended consequences on the incidence of major non-communicable diseases. [ABSTRACT FROM AUTHOR]

In this paper, data obtained between 1984 and 1993 from 11,629 men and women as part of the Scottish Heart Health Study (Scotland, United Kingdom) were used to investigate the relation between antioxidant vitamin and fiber intakes and both incident coronary heart disease (CHD) (649 events) and all-causes mortality (591 deaths). All age-adjusted mean intakes tended to be higher in the group that experiecned no event. For men, increased fiber intake was associated with decreased risk of CHD even after adjustment for a host of other major coronary risk factors; hazard ratios relative to the lowest quarter were 0.68, 0.70, and 0.64 by increasing quarter. This relation was alos observed for mortality (hazard ratios of 0.62, 0.66, and 0.62). Evidence was found that higher intakes of the antioxidants were also beneficial, although the associations were weaker. For women, fiber was the only obviously influential dietary factor, with hazard ratios of 0.94, 0.60, and 0.56 for CHD and 1.25, 0.82, and 0.65 for mortality. These results suggest that the current public health drive to increase the consumption of foods rich in antioxidant vitamins and (particularly) fiber will impact on both CHD risk and the general health of the population. Am J Epidemiol 1999; 150:1073-80. [ABSTRACT FROM PUBLISHER]

Aims To evaluate the role of plasma lipids in recurrent vascular events, including stroke, among individuals with established cerebrovascular disease. [ABSTRACT FROM PUBLISHER]

Missing values, common in epidemiologic studies, are a major issue in obtaining valid estimates. Simulation studies have suggested that multiple imputation is an attractive method for imputing missing values, but it is relatively complex and requires specialized software. For each of 28 studies in the Asia Pacific Cohort Studies Collaboration, a comparison of eight imputation procedures (unconditional and conditional mean, multiple hot deck, expectation maximization, and four different approaches to multiple imputation) and the naive, complete participant analysis are presented in this paper. Criteria used for comparison were the mean and standard deviation of total cholesterol and the estimated coronary mortality hazard ratio for a one-unit increase in cholesterol. Further sensitivity analyses allowed for systematic over- or underestimation of cholesterol. For 22 studies for which less than 10% of the values for cholesterol were missing, and for the pooled Asia Pacific Cohort Studies Collaboration, all methods gave similar results. For studies with roughly 10–60% missing values, clear differences existed between the methods, in which case past research suggests that multiple imputation is the method of choice. For two studies with over 60% missing values, no imputation method seemed to be satisfactory. [ABSTRACT FROM AUTHOR]

Background: Vascular mortality is increasing in economically developing countries such as Thailand but reliable data about the determinants of these changes are few.Methods: In 1985, male and female employees of the Electricity Generating Authority of Thailand took part in a cardiovascular risk factor survey. In 1997, a follow-up survey was conducted and causes of death were determined for those subjects known to have died. Changes in levels of vascular risk factors over 12 years, and the associations of baseline risk factors with vascular mortality, were calculated.Results: The 1985 survey recruited 3499 volunteers (average age 43 years) of whom 23% were female. In 1997, vital status was determined for 3318 (95%) and 2967 (85%) of the study participants were resurveyed. Mean levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index, total cholesterol and high density lipoprotein (HDL) cholesterol all increased over the 12-year follow-up period. Over the same time, the prevalence of diabetes also rose but the proportion of current smokers decreased. Vascular diseases were the most frequent cause of death during follow-up (n = 46), were positively associated with baseline age, SBP, DBP, smoking, diabetes, male sex, and total cholesterol, and were negatively associated with HDL cholesterol.Conclusions: Levels of most vascular risk factors worsened over the 12-year period between 1985 and 1997. The associations between baseline risk factor levels and vascular mortality were consistent with those observed in other populations. Interventions that control vascular risk factors have the potential to avert much premature vascular disease in Thailand. [ABSTRACT FROM AUTHOR]

Woodward M (Cardiovascular Epidemiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK), Smith WCS and Tunstall-Pedoe H. Bias from missing values: Sex differences in implication of failed venepuncture for the Scottish Heart Health Study. 1991; : 379–383. Missing values are common in epidemiological data, and yet their possible effect on the results of the investigation is seldom quantified despite the fact that they are a likely source of bias. This paper describes a simple method, based on odds ratios, for assessing whether missing values are likely to cause bias, and for quantifying the magnitude of any such bias. The method is applied to the Scottish Heart Health Study, a study of risk factors for coronary heart disease amongst 10 359 men and women. It is found that, although no bias is apparent in the male subjects, females with missing blood samples are twice as likely to have a history of myocardial infarction than other women. Missing blood samples are shown to be associated with increased body mass index and difficult peripheral veins. The bias caused by the missing female blood samples is considerable, with estimated errors of between 4% and 12% in the mean values of total cholesterol, HDL-cholesterol, triglycerides, creatinine, uric acid and fibrinogen. [ABSTRACT FROM PUBLISHER]

Background: Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21HD) can affect the in utero development of the genital anatomy of people with the 46XX karyotype. Health professionals engage parents in decision-making regarding managing genitals with this difference, including genital surgery options and patient communication. Aim: We sought to investigate parental communication with their daughters regarding clitoral size variation related to neonatal CAH. Methods: Semistructured in-person interviews of 24 parents of chromosomal XX children with clitoral size variation attributable to a neonatal CAH diagnosis comprised 3 management categories: (1) clitoral reduction surgery (RS) (7 parents, 9 children), (2) clitoral concealment surgery (CS) (8 parents, 8 children), and no surgery on or around the clitoris (NS) (9 parents, 7 children). Outcomes: Four representative themes, Obvious Choice, Still Different, Parental Burden, and Ignorance Is Bliss, were common across all 3 treatment groups. Results: For most parents, none of the 3 options of genital appearance alteration via clitoral reduction, clitoral concealment surgery, or avoidance of clitoral surgery ameliorated concerns, with most parents expressing an aversion to educating their child on the topic of genital differences, past treatment, or future function. Clinical Implications: Reliance on surgical treatment pathways to manage this psychosocial concern is ineffective in alleviating parental uncertainty without the application of psychosocial interventions. Strengths and Limitations: This was a qualitative study but was limited to parents of children with a specific genital difference, without direct exploration of parental values regarding the clitoris or the application of adequate psychosocial care. Conclusion: Healthcare services must have an impact on parental ability to engage in essential communication with their children in cases such as clitoral size variation related to neonatal CAH. Improved communication skills allow parents to engage in more genuine decision-making and adapt to enduring genital reality, including possible future sexual challenges for their adult child, without resorting to burdensome strategies focused on attempts to perpetuate a benevolent ignorance. [ABSTRACT FROM AUTHOR]