Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. METHODS AND RESULTS: A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. CONCLUSIONS: Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Ultra-high-resolution mapping of ambient fine particulate matter to estimate human exposure in Beijing.

With the decreasing regional-transported levels, the health risk assessment derived from fine particulate matter (PM2.5) has become insufficient to reflect the contribution of local source heterogeneity to the exposure differences. Here, we combined the both ultra-high-resolution PM2.5 concentration with population distribution to provide the personal daily PM2.5 internal dose considering the indoor/outdoor exposure difference. A 30-m PM2.5 assimilating method was developed fusing multiple auxiliary predictors, achieving higher accuracy (R2 = 0.78-0.82) than the chemical transport model outputs without any post-simulation data-oriented enhancement (R2 = 0.31-0.64). Weekly difference was identified from hourly mobile signaling data in 30-m resolution population distribution. The population-weighted ambient PM2.5 concentrations range among districts but fail to reflect exposure differences. Derived from the indoor/outdoor ratio, the average indoor PM2.5 concentration was 26.5 µg/m3. The internal dose based on the assimilated indoor/outdoor PM2.5 concentration shows high exposure diversity among sub-groups, and the attributed mortality increased by 24.0% than the coarser unassimilated model.

Nonoptimum Temperatures Are More Closely Associated With Fatal Myocardial Infarction Than With Nonfatal Events.

BACKGROUND: Ambient temperatures trigger hospitalisation, mortality, and emergency department visits for myocardial infarction (MI). However, nonoptimum temperature-related risks of fatal and nonfatal MI have not yet been compared. METHODS: From 2007 to 2019, 416,894 MI events (233,071 fatal and 183,823 nonfatal) were identified in Beijing, China. A time-series analysis with a distributed-lag nonlinear model was used to compare the relative and population-attributable risks of fatal and nonfatal MI associated with nonoptimum temperatures. RESULTS: The reference was the optimum temperature of 24.3°C. For single-lag effects, cold (-5.2°C) and heat (29.6°C) effects had associations that persisted for more days for fatal MI than for nonfatal MI. For cumulative-lag effects over 0 to 21 days, cold effects were higher for fatal MI (relative risk [RR] 1.99, 95% confidence interval [CI] 1.68-2.35) than for nonfatal MI (RR 1.60, 95% CI 1.32-1.94) with a P value for difference in effect sizes of 0.048. In addition, heat effects were higher for fatal MI (RR 1.33, 95% CI 1.24-1.44) than for nonfatal MI (RR 0.99, 95% CI 0.91-1.08) with a P value for difference in effect sizes of 0.002. The attributable fraction of nonoptimum temperatures was higher for fatal MI (25.6%, 95% CI 19.7%-30.6%) than for nonfatal MI (19.1%, 95% CI 12.1%-25.0%). CONCLUSIONS: Fatal MI was more closely associated with nonoptimum temperatures than nonfatal MI, as evidenced by single-lag effects that have associations which persisted for more days, higher cumulative-lag effects, and higher attributable risks for fatal MI. Strategies are needed to mitigate the adverse effects of nonoptimum temperatures.

Associations between urban exposome and recurrence risk among survivors of acute myocardial infarction in Beijing, China.

Few previous studies have investigated the impacts of coexposure to multiple urban environmental factors on the prognosis of acute myocardial infarction (AMI) events. This study aimed to evaluate the associations between the urban exposome and AMI recurrence. We used data from 88,509 AMI patients from a large cohort obtained from the Beijing Cardiovascular Disease Surveillance System between 2013 and 2019. Twenty-six types of urban exposures were assessed within 300-m, 500-m, and 1000-m buffers of patients' home addresses in the baseline and cumulative average levels. We used the Cox proportional hazard model along with the Elastic Net (ENET) algorithm to estimate the hazard ratios (HRs) of recurrent AMI per interquartile range increase in each selected urban exposure. The increased risk of AMI recurrence was significantly associated with lower urban function diversity in the 500-m buffer, longer distance to subway stations and higher PM2.5 for both baseline and cumulative average exposure. The cumulative averages of two urban factors, including the distance to parks, and the density of fruit and vegetable shops in the 1000-m buffer, were also identified as significant factors affecting the risk of AMI recurrence. These findings can help improve the urban design for promoting human cardiovascular health.

Association of neighborhood physical activity facilities with incident cardiovascular disease.

BACKGROUND: The availability of physical activity (PA) facilities in neighborhoods is hypothesized to influence cardiovascular disease (CVD), but evidence from individual-level long-term cohort studies is limited. We aimed to assess the association between neighborhood exposure to PA facilities and CVD incidence. METHODS: A total of 4658 participants from the Chinese Multi-provincial Cohort Study without CVD at baseline (2007-2008) were followed for the incidence of CVD, coronary heart disease (CHD), and stroke. Availability of PA facilities was defined as both the presence and the density of PA facilities within a 500-m buffer zone around the participants' residential addresses. Time-dependent Cox regression models were performed to estimate the associations between the availability of PA facilities and risks of incident CVD, CHD, and stroke. RESULTS: During a median follow-up of 12.1 years, there were 518 CVD events, 188 CHD events, and 355 stroke events. Analyses with the presence indicator revealed significantly lower risks of CVD (hazard ratio [HR] 0.80, 95% confidence interval ([CI] 0.65-0.99) and stroke (HR 0.76, 95% CI 0.60-0.97) in participants with PA facilities in the 500-m buffer zone compared with participants with no nearby facilities in fully adjusted models. In analyses with the density indicator, exposure to 2 and ≥ 3 PA facilities was associated with 35% (HR 0.65, 95% CI 0.47-0.91) and 28% (HR 0.72, 95% CI 0.56-0.92) lower risks of CVD and 40% (HR 0.60, 95% CI 0.40-0.90) and 38% (HR 0.62, 95% CI 0.46-0.84) lower risks of stroke compared with those without any PA facilities in 500-m buffer, respectively. Effect modifications between presence of PA facilities and a history of hypertension for incident stroke (P = 0.049), and a history of diabetes for incident CVD (P = 0.013) and stroke (P = 0.009) were noted. CONCLUSIONS: Residing in neighborhoods with better availability of PA facilities was associated with a lower risk of incident CVD. Urban planning intervention policies that increase the availability of PA facilities could contribute to CVD prevention.

Geographic Variation in Mortality of Acute Myocardial Infarction and Association With Health Care Accessibility in Beijing, 2007 to 2018.

Background Little is known about geographic variation in acute myocardial infarction (AMI) mortality within fast-developing megacities and whether changes in health care accessibility correspond to changes in AMI mortality at the small-area level. Methods and Results We included data of 94 106 AMI deaths during 2007 to 2018 from the Beijing Cardiovascular Disease Surveillance System in this ecological study. We estimated AMI mortality for 307 townships during consecutive 3-year periods with a Bayesian spatial model. Township-level health care accessibility was measured using an enhanced 2-step floating catchment area method. Linear regression models were used to examine the association between health care accessibility and AMI mortality. During 2007 to 2018, median AMI mortality in townships declined from 86.3 (95% CI, 34.2-173.8) to 49.4 (95% CI, 30.5-73.7) per 100 000 population. The decrease in AMI mortality was larger in townships where health care accessibility increased more rapidly. Geographic inequality, defined as the ratio of the 90th to 10th percentile of mortality in townships, increased from 3.4 to 3.8. In total, 86.3% (265/307) of townships had an increase in health care accessibility. Each 10% increase in health care accessibility was associated with a -0.71% (95% CI, -1.08% to -0.33%) change in AMI mortality. Conclusions Geographic disparities in AMI mortality among Beijing townships are large and increasing. A relative increase in township-level health care accessibility is associated with a relative decrease in AMI mortality. Targeted improvement of health care accessibility in areas with high AMI mortality may help reduce AMI burden and improve its geographic inequality in megacities.

Using street view imagery to examine the association between urban neighborhood disorder and the long-term recurrence risk of patients discharged with acute myocardial infarction in central Beijing, China.

Background: To examine the association between urban neighborhood disorder and the recurrence risk of patients with acute myocardial infarction (AMI) in central Beijing, China. Methods: Recurrent AMI was identified by the Beijing Monitoring System for Cardiovascular Diseases through the end of 2019 for patients discharged with AMI between 2007 and 2017. Cox proportional hazards models were performed to estimate associations between neighborhood disorder and AMI recurrence. Results: Of 66,238 AMI patients, 11,872 had a recurrent event, and 3117 died from AMI during a median followup of 5.92 years. After covariate adjustment, AMI patients living in the high tertile of neighborhood disorder had a higher recurrence risk (hazard ratio [HR] 1.08, 95 % confidence interval [CI], 1.03-1.14) compared with those in the low tertile. A stronger association was noted for fatal recurrent AMI (HR 1.21, 95 % CI 1.10-1.34). The association was mainly observed in females (HR 1.04, 95 % CI: 1.02 to 1.06). Conclusions: Serious neighborhood disorder may contribute to higher recurrence risk, particularly fatal recurrence, among AMI patients. Policies to eliminate neighborhood disorders may play an important role in the secondary prevention of cardiovascular disease.

Synthesis of CuxO/Ag nanoparticles on exfoliated graphene: application for enhanced electrochemical detection of H2O2 in milk.

In this paper, a novel composite is constructed as a non-enzymatic hydrogen peroxide (H2O2) sensor by liquid-phase exfoliation method, which is composed of copper oxide, cuprous oxide and silver nanoparticles doped few-layer-graphene (CuxO/Ag@FLG). Its surface morphology and composition were characterized by scanning electron microscopy (SEM) and X-ray photo spectroscopy (XPS), and its H2O2 sensing performances include catalytic reduction and quantitative detection were studied with electrochemical methods. Our sensor had a high sensitivity of 174.5 µA mM-1 cm-2 (R2 = 0.9978) in an extremely wide range of concentrations from 10 µM to 100 mM, a fast response (about 5 s) and a low limit of detection (S/N = 3) of 2.13 µM. The sensor exhibits outstanding selectivity in the presence of various biological interference, such as dopamine, ascorbic acid, uric acid, citric acid, etc. In addition, the constructed sensor continued 95% current responsiveness after 1 month of storage further points to its long-term stability. Last but not least, it has a good recovery rate (90.12-102.00%) in milk sold on the open market, indicating that it has broad application possibilities in the food industry and biological medicine.

Driving Time to the Nearest Percutaneous Coronary Intervention-Capable Hospital and the Risk of Case Fatality in Patients with Acute Myocardial Infarction in Beijing.

Timely arrival at a hospital capable of percutaneous coronary intervention (PCI) is critical in treating acute myocardial infarction (AMI). We examined the association between driving time to the nearest PCI-capable hospital and case fatality among AMI patients. A total of 142,474 AMI events during 2013-2019 from the Beijing Cardiovascular Disease Surveillance System were included in this cross-sectional study. The driving time from the residential address to the nearest PCI-capable hospital was calculated. Logistic regression was used to estimate the risk of AMI death associated with driving time. In 2019, 54.5% of patients lived within a 15-min drive to a PCI-capable hospital, with a higher proportion in urban than peri-urban areas (71.2% vs. 31.8%, p < 0.001). Compared with patients who had driving times ≤15 min, the adjusted odds ratios (95% CI, p value) for AMI fatality risk associated with driving times 16-30, 31-45, and >45 min were 1.068 (95% CI 1.033-1.104, p < 0.001), 1.189 (95% CI 1.127-1.255, p < 0.001), and 1.436 (95% CI 1.334-1.544, p < 0.001), respectively. Despite the high accessibility to PCI-capable hospitals for AMI patients in Beijing, inequality between urban and peri-urban areas exists. A longer driving time is associated with an elevated AMI fatality risk. These findings may help guide the allocation of health resources.

Measuring Accessibility to Healthcare Using Taxi Trajectories Data: A Case Study of Acute Myocardial Infarction Cases in Beijing.

Several methods have been applied to measure healthcare accessibility, ie, the Euclidean distance, the network distance, and the transport time based on speed limits. However, these methods generally produce less accurate estimates than actual measurements. This research proposed a method to estimate historical healthcare accessibility more accurately by using taxi Global Positioning System (GPS) traces. The proposed method's advantages were evaluated vis a case study using acute myocardial infarction (AMI) cases in Beijing in 2008. Comparative analyses of the new measure and three conventionally used measures suggested that the median estimated transport time to the closest hospital with percutaneous coronary intervention (PCI) capability for AMI patients was 5.72 minutes by the taxi GPS trace-based measure, 2.42 minutes by the network distance-based measure, 2.28 minutes by the speed limit-based measure, 1.73 minutes by the Euclidean distance-based measure; and the estimated proportion of patients who lived within 5 minutes of a PCI-capable hospital was 38.17%, 89.20%, 92.52%, 95.05%, respectively. The three conventionally used measures underestimated the travel time cost and overestimated the percentage of patients with timely access to healthcare facilities. In addition, the new measure more accurately identifies the areas with low or high access to healthcare facilities. The taxi GPS trace-based accessibility measure provides a promising start for more accurately estimating accessibility to healthcare facilities, increasing the use of medical records in studying the effects of historical healthcare accessibility on health outcomes, and evaluating how accessibility to healthcare changes over time.

Reduced serum calcium is associated with a higher risk of retinopathy in non-diabetic individuals: The Chinese Multi-provincial Cohort Study.

Aims: As a common micro-vascular disease, retinopathy can also present in non-diabetic individuals and increase the risk of clinical cardiovascular disease. Understanding the relationship between serum calcium and retinopathy would contribute to etiological study and disease prevention. Methods: A total of 1836 participants (aged 55-84 years and diabetes-free) from the Chinese Multi-Provincial Cohort Study-Beijing Project in 2012 were included for analyzing the relation between serum calcium level and retinopathy prevalence. Of these, 1407 non-diabetic participants with data on serum calcium in both the 2007 and 2012 surveys were included for analyzing the association of five-year changes in serum calcium with retinopathy risk. The retinopathy was determined from retinal images by ophthalmologists and a computer-aided system using convolutional neural network (CNN). The association between serum calcium and retinopathy risk was assessed by multivariate logistic regression. Results: Among the 1836 participants (male, 42.5%), 330 (18.0%) had retinopathy determined by CNN. After multivariate adjustment, the odds ratio (OR) comparing the lowest quartiles (serum calcium < 2.38 mmol/L) to the highest quartiles (serum calcium ≥ 2.50 mmol/L) for the prevalence of retinopathy determined by CNN was 1.58 (95% confidence interval [CI]: 1.10 - 2.27). The findings were consistent with the result discerned by ophthalmologists, and either by CNN or ophthalmologists. These relationships are preserved even in those without metabolic risk factors, including hypertension, high hemoglobin A1c, high fasting blood glucose, or high low-density lipoprotein cholesterol. Over 5 years, participants with the sustainably low levels of serum calcium (OR: 1.58; 95%CI: 1.05 - 2.39) and those who experienced a decrease in serum calcium (OR: 1.56; 95%CI: 1.04 - 2.35) had an increased risk of retinopathy than those with the sustainably high level of serum calcium. Conclusions: Reduced serum calcium was independently associated with an increased risk of retinopathy in non-diabetic individuals. Moreover, reduction of serum calcium could further increase the risk of retinopathy even in the absence of hypertension, high glucose, or high cholesterol. This study suggested that maintaining a high level of serum calcium may be recommended for reducing the growing burden of retinopathy. Further large prospective studies will allow more detailed information.

Overall and gender-specific associations between marital status and out-of-hospital coronary death during acute coronary events: a cross-sectional study based on data linkage in Beijing, China.

OBJECTIVES: To assess overall and gender-specific associations between marital status and out-of-hospital coronary death (OHCD) compared with patients surviving to hospital admission. DESIGN: A cross-sectional study based on linkage of administrative health databases. SETTING: Beijing, China. PARTICIPANTS: From 2007 to 2019, 378 883 patients with acute coronary event were identified in the Beijing Monitoring System for Cardiovascular Diseases, a validated city-wide registration system based on individual linkage of vital registration and hospital discharge data. OUTCOME MEASURES: OHCD was defined as coronary death occurring before admission. Multilevel modified Poisson regression models were used to calculate the prevalence ratios (PR) and 95% CIs. RESULTS: Among 378 883 acute coronary events, OHCD accounted for 33.8%, with a higher proportion in women compared with men (41.5% vs 28.7%, p<0.001). Not being married was associated with a higher proportion of OHCD in both genders, with a stronger association in women (PR 2.18, 95% CI 2.10 to 2.26) than in men (PR 1.97, 95% CI 1.91 to 2.02; p for interaction <0.001). The associations of OHCD with never being married (PR 1.98, 95% CI 1.88 to 2.08) and being divorced (PR 2.54, 95% CI 2.42 to 2.67) were stronger in men than in women (never married: PR 0.98, 95% CI 0.82 to 1.16; divorced: PR 1.47, 95% CI 1.34 to 1.61) (p for interaction <0.001 for both). Being widowed was associated with a higher proportion of OHCD in both genders, with a stronger association in women (PR 2.26, 95% CI 2.17 to 2.35) compared with men (PR 1.89, 95% CI 1.84 to 1.95) (p for interaction <0.001). CONCLUSIONS: Not being married was independently associated with a higher proportion of OHCD and the associations differed by gender. Our study may aid the development of gender-specific public health interventions in high-risk populations characterised by marital status to reduce OHCD burden.

Corrigendum: Reduced serum calcium is associated with a higher risk of retinopathy in non-diabetic individuals: The Chinese Multi-provincial Cohort Study.

[This corrects the article DOI: 10.3389/fendo.2022.973078.].

Trends and Inequalities in the Incidence of Acute Myocardial Infarction among Beijing Townships, 2007-2018.

Acute myocardial infarction (AMI) poses a serious disease burden in China, but studies on small-area characteristics of AMI incidence are lacking. We therefore examined temporal trends and geographic variations in AMI incidence at the township level in Beijing. In this cross-sectional analysis, 259,830 AMI events during 2007-2018 from the Beijing Cardiovascular Disease Surveillance System were included. We estimated AMI incidence for 307 consistent townships during consecutive 3-year periods with a Bayesian spatial model. From 2007 to 2018, the median AMI incidence in townships increased from 216.3 to 231.6 per 100,000, with a greater relative increase in young and middle-aged males (35-49 years: 54.2%; 50-64 years: 33.2%). The most pronounced increases in the relative inequalities was observed among young residents (2.1 to 2.8 for males and 2.8 to 3.4 for females). Townships with high rates and larger relative increases were primarily located in Beijing's northeastern and southwestern peri-urban areas. However, large increases among young and middle-aged males were observed throughout peri-urban areas. AMI incidence and their changes over time varied substantially at the township level in Beijing, especially among young adults. Targeted mitigation strategies are required for high-risk populations and areas to reduce health disparities across Beijing.

Association of apolipoprotein Cs with new-onset type 2 diabetes mellitus: findings from the Chinese multi-provincial cohort study.

OBJECTIVES: Apolipoprotein Cs (apoCs), especially apoC-II and apoC-III, as the components of triglyceride-rich lipoproteins, play a key role in the pathophysiology of diabetes. However, prospective studies examining direct associations between apoCs and diabetes are not reproducible. The aim of this study was to evaluate the impact of apoCs on the risk of developing diabetes in a middle-aged population, and to explore possible mediators responsible for the relationship between apoCs and diabetes. DESIGN: Prospective cohort study. SETTING: Community-based study carried out in Beijing. METHODS: ApoCs were measured in 1085 participants aged 45-74 years and free of type 2 diabetes mellitus (T2DM) at baseline from the Chinese Multi-Provincial Cohort Study-Beijing Project. Multivariate logistic regression was performed to examine the association of apoCs with a 5-year risk of new-onset T2DM. The impacts of triglycerides, insulin and high-sensitivity C reactive protein (hs-CRP) on the association between apoC-III and the risk of T2DM were explored by a mediation test. RESULTS: During the 5 years of follow-up, 97 (8.9%) participants developed T2DM. ApoC-III was significantly associated with the risk of developing T2DM after multivariable adjustment (OR=1.40; 95% CI 1.07 to 1.82). This association was mainly mediated by triglyceride levels with a significant indirect effect (OR 1.61; 95% CI 1.19 to 2.18), followed by hs-CRP and insulin. CONCLUSIONS: Our findings demonstrated that higher serum apoC-III was independently associated with increased 5-year risk of new-onset T2DM in the Chinese population, and triglyceride plays a crucial role in mediating this relationship. More attention should be paid to preventive strategies of T2DM targeting apoC-III.

Association between body mass index, waist circumference, and age at natural menopause: a population-based cohort study in Chinese women.

The purpose of the study was to investigate whether premenopausal body mass index (BMI) and waist circumference (WC) influence age at menopause. A total of 2116 women aged 35-64 years from two communities of the CMCS Beijing cohort were recruited in 1992 and followed up to 2018. Of 1439 premenopausal women at baseline, 6 women data were missing. Finally, 1433 women were included for analysis. Overweight was defined as BMI 24-27.99 kg/m2. Central obesity was defined as WC ≥80 cm. Age at menopause was categorized as <45 years, 45-49 years, 50-51 years (reference), and >51 years. Multinomial logistic regression models were used to estimate relative odds ratios (RORs) and 95% confidence intervals (CIs). Compared to women with normal weight and normal WC, overweight women with normal WC had higher risk of menopause at >51 years (ROR 1.64, 95% CI 1.10-2.45; P = .01); and overweight women with central obesity had higher risk of menopause at not only >51 years (ROR 1.82, 95% CI 1.13-2.93; P = .01) but also <45 years (ROR 3.13, 95% CI 1.20-8.43; P = .02) and 45-49 years (ROR 2.76, 95% CI 1.71-4.46; P < .001). When overweight women combine with central obesity, the risk of early menopause will increase in some of them.

Combined effect of menopause and cardiovascular risk factors on death and cardiovascular disease: a cohort study.

BACKGROUND: Observational studies suggest that early menopause is associated with increased risk of death and cardiovascular disease (CVD); however, the results of these studies have been inconsistently. We aimed to assess the association of menopause with death and CVD and whether this association was modified by cardiovascular risk factors. METHODS: The study population was women age 35-64 years living in two communities of Beijing who were enrolled in the Chinese Multi-provincial Cohort Study in 1992. Participants were followed until first cardiovascular event, death, or the end of follow-up (2018). Self-reported age at menopause was recorded. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of death and CVD after adjusting for baseline covariates of age, family history of CVD, and white blood cell count, as well as time-varying covariates of menopause, use of oral estrogen, and conventional risk factors. Additionally, we assessed the combined effect of age at menopause and risk factors on the primary endpoint. RESULTS: Of 2104 eligible women, 124 died and 196 had a first CVD event (33 fatal CVD and 163 non-fatal CVD). Compared with women who experienced menopause at age 50-51 years, the risk of death was higher in women with menopause at age 45-49 years (HR 1.99, 95% CI 1.24-3.21; P = 0.005), and the risk of ischemic stroke was higher in women with menopause at age < 45 years (HR 2.16, 95% CI 1.04-4.51; P = 0.04) and at age 45-49 years (HR 2.05, 95% CI 1.15-3.63; P = 0.01). Women who had menopause before age 50 years and at least one elevated risk factor at baseline had a higher risk of death (HR 11.10, 95% CI 1.51-81.41; P = 0.02), CVD (HR 3.98, 95% CI 1.58-10.01; P = 0.003), ischemic CVD (HR 4.53, 95% CI 1.63-12.62; P = 0.004), coronary heart disease (HR 8.63, 95% CI 1.15-64.50; P = 0.04), and stroke (HR 2.92, 95% CI 1.03-8.29; P = 0.04) than those with menopause at age 50-51 years and optimal levels of all risk factors. CONCLUSIONS: Earlier menopause may predict death and ischemic stroke. Furthermore, there is a combined effect of earlier menopause and elevated risk factors on death and CVD.

Association of menopause with risk of carotid artery atherosclerosis.

OBJECTIVES: Observational studies suggest that the risk of cardiovascular disease increases during menopause; however, the menopause-related risk of subclinical atherosclerosis is unclear. The aim of the current study is to evaluate menopause and the risk of subclinical carotid atherosclerosis through a retrospective analysis of data from a population-based prospective cohort study. STUDY DESIGN: The study sample comprised 879 women in the Beijing community enrolled in the Chinese Multi-provincial Cohort Study at baseline study in 1992 and followed up to at least one carotid ultrasound examination at three on-site follow-up surveys. Age at menopause was categorized as <40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early menopause), 50-51 years (reference), and >51 years (relatively late menopause). Menopause staging at baseline was categorized as: reproductive, menopausal transition/perimenopause, early postmenopause, and late postmenopause. Menopause as a time-varying covariate was calculated using waiting time to menopause and menopause status at the last follow-up (2012). MAIN OUTCOME MEASURES: The main outcome measures included carotid plaque and intima-media thickening. Gray's test was performed to assess the equality of cumulative incidence functions between age groups at menopause and between menopause stages. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with menopause. RESULTS: Of the 879 women included (mean [SD] age at baseline, 48.6 [8.1] years), 573 (65.2%) developed carotid plaques and 430 (48.9%) developed intima-media thickening during follow-up. Menopause was significantly associated with risk of developing carotid plaques (HR 1.93, 95% CI 1.05-3.54; P = 0.03) after adjustment for age at baseline, age at menopause, use of oral estrogen due to menopause, and traditional cardiovascular risk factors at baseline. No significant association was found between age at menopause and risk of carotid atherosclerosis. CONCLUSION: Menopausal women, irrespective of age at menopause, had an increased risk of carotid plaque.

Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China: A nested case-control study.

OBJECTIVE: We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk. METHODS: We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models. RESULTS: A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P<0.05 & false discovery rate-adjusted Q<0.10). A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI, 0.84-0.93). Cross-validation and sensitivity analysis, excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls, or restriction to screen-endoscopic-detected or clinically diagnosed case-control triads, or using only bacterial data measured at the baseline, yielded AUCs>0.84. CONCLUSIONS: The oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.