Independent relevance of adiposity measures to coronary heart disease risk among 0.5 million adults in UK Biobank.

BACKGROUND: Evidence on body fat distribution shows opposing effects of waist circumference (WC) and hip circumference (HC) for coronary heart disease (CHD). We aimed to investigate the causality and the shape of such associations. METHODS: UK Biobank is a prospective cohort study of 0.5 million adults aged 40-69 years recruited between 2006 and 2010. Adjusted hazard ratios (HRs) for the associations of measured and genetically predicted body mass index (BMI), WC, HC and waist-to-hip ratio with incident CHD were obtained from Cox models. Mendelian randomization (MR) was used to assess causality. The analysis included 456 495 participants (26 225 first-ever CHD events) without prior CHD. RESULTS: All measures of adiposity demonstrated strong, positive and approximately log-linear associations with CHD risk over a median follow-up of 12.7 years. For HC, however, the association became inverse given the BMI and WC (HR per usual SD 0.95, 95% CI 0.93-0.97). Associations for BMI and WC remained independently positive after adjustment for other adiposity measures and were similar (1.14, 1.13-1.16 and 1.18, 1.15-1.20, respectively), with WC displaying stronger associations among women. Blood pressure, plasma lipids and dysglycaemia accounted for much of the observed excess risk. MR results were generally consistent with the observational, implying causality. CONCLUSIONS: Body fat distribution measures displayed similar associations with CHD risk as BMI except for HC, which was inversely associated with CHD risk (given WC and BMI). These findings suggest that different measures of body fat distribution likely influence CHD risk through both overlapping and independent mechanisms.

Lipoprotein Characteristics and Incident Coronary Heart Disease: Prospective Cohort of Nearly 90 000 Individuals in UK Biobank.

Background Associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear. Methods and Results UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very-low-density lipoproteins, intermediate-density lipoproteins, and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17-1.28), 1.16 (1.11-1.21), 1.20 (1.15-1.25), and 0.90 (0.86-0.95), respectively. Larger subclasses of very-low-density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high-density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration (r=0.99), but after adjustment for apolipoprotein B, concentrations of very-low-density lipoprotein and high-density lipoprotein particles remained strongly related to CHD risk. Conclusions This large-scale study reliably quantifies the associations of nuclear magnetic resonance-defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.

Predictive value of metabolic profiling in cardiovascular risk scores: analysis of 75 000 adults in UK Biobank.

BACKGROUND: Metabolic profiling (the extensive measurement of circulating metabolites across multiple biological pathways) is increasingly employed in clinical care. However, there is little evidence on the benefit of metabolic profiling as compared with established atherosclerotic cardiovascular disease (CVD) risk scores. METHODS: UK Biobank is a prospective study of 0.5 million participants, aged 40-69 at recruitment. Analyses were restricted to 74 780 participants with metabolic profiling (measured using nuclear magnetic resonance) and without CVD at baseline. Cox regression was used to compare model performance before and after addition of metabolites to QRISK3 (an established CVD risk score used in primary care in England); analyses derived three models, with metabolites selected by association significance or by employing two different machine learning approaches. RESULTS: We identified 5097 incident CVD events within the 10-year follow-up. Harrell's C-index of QRISK3 was 0.750 (95% CI 0.739 to 0.763) for women and 0.706 (95% CI 0.696 to 0.716) for men. Adding selected metabolites did not significantly improve measures of discrimination in women (Harrell's C-index of three models are 0.759 (0.747 to 0.772), 0.759 (0.746 to 0.770) and 0.759 (0.748 to 0.771), respectively) or men (0.710 (0.701 to 0.720), 0.710 (0.700 to 0.719) and 0.710 (0.701 to 0.719), respectively), and neither did it improve reclassification or calibration. CONCLUSION: This large-scale study applied both conventional and machine learning approaches to assess the potential benefit of metabolic profiling to well-established CVD risk scores. However, there was no evidence that metabolic profiling improved CVD risk prediction in this population.

Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank.

BACKGROUND: The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk. METHODS: UK Biobank is a prospective study of adults aged 40-69 in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures. RESULTS: During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09-1.20), 1.15 (1.10-1.21), 0.91 (0.87-0.94), and 1.04 (0.99-1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels. CONCLUSIONS: This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides.

Body Composition and Risk of Incident Heart Failure in 1 Million Adults: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background The aim of this systematic review was to quantify the associations between body composition measures and risk of incident heart failure (HF) and its subtypes in the general population. Methods and Results We searched Medline, Embase, and Global Health databases from each database inception to January 19, 2023 for prospective studies reporting on body composition and HF risk. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies. Fixed-effects models were used for meta-analysis. Thirty-five studies were included (ntotal=1 137 044; ncases=34 422). Summary relative risk (RR) per 5-kg/m2 higher body mass index was 1.42 (95% CI, 1.40-1.42; 𝜁2=0.02, I2=94.4%), 1.28 (95% CI, 1.26-1.31; 𝜁2=0.01, I2=75.8%) per 10-cm higher waist circumference, and 1.33 (95% CI, 1.28-1.37; 𝜁2=0.04, I2=94.9%) per 0.1-unit higher waist-hip ratio. Pooled estimates of the few studies that reported on regional fat suggested significant positive association between HF risk and both visceral fat (RR, 1.08 [95% CI, 1.04-1.12]) and pericardial fat (RR, 1.08 [95% CI, 1.06-1.10]). Among HF subtypes, associations were stronger for HF with preserved ejection fraction than HF with reduced ejection fraction. No study reported on lean mass. Conclusions Pooled data suggested strong associations between adiposity and HF. The association with adiposity is stronger for HF with preserved ejection fraction than HF with reduced ejection fraction, indicating that different mechanisms may be at play in etiopathogenesis of HF subtypes. Future studies are needed to investigate role of regional fat mass and lean mass in HF risk. Registration Information REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42020224584.

Incidence and Survival of Aortic Dissection in Urban China: Results from the National Insurance Claims for Epidemiological Research (NICER) Study.

BACKGROUND: Aortic dissection (AD) represents a significant mortality; however, there is rare epidemiologic information about the demography of AD in Chinese, especially its incidence rate. METHODS: A retrospective cohort study was established using the Urban Employee Basic Medical Insurance claims data covering 346.7 million residents from 23 provinces in China, 2015-2016. AD cases were then linked to database of the Urban Employee Basic Endowment Insurance for death information. Incidence rate was age- and sex-standardized to the 2010 China census population. The associations between AD and related factors were evaluated with Poisson regression models. Moreover, mortality and sex- and age-adjusted survival rate was estimated by Cox models. FINDINGS: 6084 adult AD cases were included in incidence analysis. Totally 4692(77.1%) were men and 5641(92.7%) were Han Chinese. The overall age- and sex-adjusted incidence rate of AD was 2.78(95%CI:2.59-2.98) per 100,000 person-years. In terms of geographic disparities, the crude incidence rate was significantly higher in Northwest China than South China (4.96[95%CI:4.17-5.75] vs. 2.04[95%CI:0.38-3.71] per 100,000 person-years; risk ratio: 2.67[95%CI: 2.34-3.04]). Moreover, survival analysis of 4518 AD patients with 683 recorded deaths during follow-up (median 2.2 years) showed that overall 3-year survival was 83.7%(95%CI:82.4-84.8). INTERPRETATION: This contemporary population-based cohort study provides a first comprehensive assessment of incidence of AD in urban Chinese adults. The distinct signatures of different incidence with respect to geographic variations may have important implications for clinical management of AD. FUNDING: Chinese Ministry of Science and Technology (2020YFC2003503, 2016YFC0903000), and National Natural Science Foundation of China (91846112, 81973132, 81961128006).

Body composition and risk of heart failure: protocol for a systematic review and meta-analysis.

INTRODUCTION: Although there is strong evidence of an association between general adiposity and incidence of heart failure, previous systematic reviews and meta-analyses have not reliably assessed the association of heart failure risk with other aspects of body composition (such as body fat distribution or lean mass), or between body composition and risk of heart failure subtypes. We aim to conduct a systematic review and meta-analysis of prospective studies to address these uncertainties, and inform efforts to prevent and treat heart failure. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I2 statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots. ETHICS AND DISSEMINATION: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media. PROSPERO REGISTRATION NUMBER: CRD42020224584.

Gestational Diabetes Mellitus: Predictive Value of Fetal Growth Measurements by Ultrasonography at 22-24 Weeks: A Retrospective Cohort Study of Medical Records.

Early intervention of gestational diabetes mellitus (GDM) is effective in reducing pregnancy disorders. Fetal growth, measured by routine ultrasound scan a few weeks earlier before GDM diagnosis, might be useful to identify women at high risk of GDM. In the study, generalized estimating equations were applied to examine the associations between ultrasonic indicators of abnormal fetal growth at 22-24 weeks and the risk of subsequent GDM diagnosis. Of 44,179 deliveries, 8324 (18.8%) were diagnosed with GDM between 24 and 28 weeks. At 22-24 weeks, fetal head circumference (HC) < 10th, fetal femur length (FL) < 10th, and estimated fetal weight (EFW) < 10th percentile were associated with 13% to 17% increased risks of maternal GDM diagnosis. Small fetal size appeared to be especially predictive of GDM among women who were parous. Fetal growth in the highest decile of abdominal circumference (AC), HC, FL and EFW was not associated with risk of subsequent GDM. The observed mean difference in fetal size across gestation by GDM was small; there was less than 1 mm difference for AC, HC, and FL, and less than 5 g for EFW before 24 weeks. Despite similar mean fetal growth among women who were and were not later diagnosed with GDM, mothers with fetuses in the lowest decile of HC, FL and EFW at 22-24 weeks tended to have higher risk of GDM.

Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013.

Importance: Previous studies have shown increasing prevalence of diabetes in China, which now has the world's largest diabetes epidemic. Objectives: To estimate the recent prevalence and to investigate the ethnic variation of diabetes and prediabetes in the Chinese adult population. Design, Setting, and Participants: A nationally representative cross-sectional survey in 2013 in mainland China, which consisted of 170 287 participants. Exposures: Fasting plasma glucose and hemoglobin A1c levels were measured for all participants. A 2-hour oral glucose tolerance test was conducted for all participants without diagnosed diabetes. Main Outcomes and Measures: Primary outcomes were total diabetes and prediabetes defined according to the 2010 American Diabetes Association criteria. Awareness and treatment were also evaluated. Hemoglobin A1c concentration of less than 7.0% among treated diabetes patients was considered adequate glycemic control. Minority ethnic groups in China with at least 1000 participants (Tibetan, Zhuang, Manchu, Uyghur, and Muslim) were compared with Han participants. Results: Among the Chinese adult population, the estimated standardized prevalence of total diagnosed and undiagnosed diabetes was 10.9% (95% CI, 10.4%-11.5%); that of diagnosed diabetes, 4.0% (95% CI, 3.6%-4.3%); and that of prediabetes, 35.7% (95% CI, 34.1%-37.4%). Among persons with diabetes, 36.5% (95% CI, 34.3%-38.6%) were aware of their diagnosis and 32.2% (95% CI, 30.1%-34.2%) were treated; 49.2% (95% CI, 46.9%-51.5%) of patients treated had adequate glycemic control. Tibetan and Muslim Chinese had significantly lower crude prevalence of diabetes than Han participants (14.7% [95% CI, 14.6%-14.9%] for Han, 4.3% [95% CI, 3.5%-5.0%] for Tibetan, and 10.6% [95% CI, 9.3%-11.9%] for Muslim; P < .001 for Tibetan and Muslim compared with Han). In the multivariable logistic models, the adjusted odds ratios compared with Han participants were 0.42 (95% CI, 0.35-0.50) for diabetes and 0.77 (95% CI, 0.71-0.84) for prediabetes for Tibetan Chinese and 0.73 (95% CI, 0.63-0.85) for diabetes and 0.78 (95% CI, 0.71-0.86) for prediabetes in Muslim Chinese. Conclusions and Relevance: Among adults in China, the estimated overall prevalence of diabetes was 10.9%, and that for prediabetes was 35.7%. Differences from previous estimates for 2010 may be due to an alternate method of measuring hemoglobin A1c.