Two-year impact of COVID-19 pandemic on hospitalized patients with skin diseases in China.

To investigate the clinical characteristics of skin disorders among hospitalized patients before and during the coronavirus disease 2019 (COVID-19) pandemic, a retrospective study was conducted based on hospitalized patients with skin diseases from Xiangya Hospital of Central South University, the largest hospital in the south-central region of China, between January 1, 2018, and December 31, 2021. A total of 3039 hospitalized patients were enrolled in the study, including 1681 patients in the prepandemic group and 1358 patients in the pandemic group. The total number of hospitalized patients in the pandemic group decreased by 19.2%, with an increased proportion of patients over 60 years of age (39.8% vs. 35.8%). Moreover, compared with the prepandemic group, there were decreases in the occurrence of most skin diseases in the pandemic group, but the proportions of keratinolytic carcinoma (6.6% vs. 5.2%), dermatitis (24.0% vs. 18.9%), and psoriasis (18.0% vs. 14.8%) were higher in the pandemic group. In addition, longer hospital stays (ß = 0.07, SE = 0.02, P = 1.35 × 10-3 ) and higher hospital costs (ß = 0.06, SE = 0.03, p = 0.031) were found in the pandemic group through general linear models, even after the corresponding adjustment. In summary, the COVID-19 pandemic has had a lasting impact on patients with skin diseases, with fewer hospitalized patients, increased proportions of older patients, longer hospital stays, and increased hospital costs. These findings will facilitate better preparation for the most effective response to future pandemics.

Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies.

BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen. RESULTS: Hair arsenic (µg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum ß-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of ß-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (ß = -0.98, p = 0.04). CONCLUSION: Arsenic exposure is associated with pruritus, and ß-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.

WHO cardiovascular disease risk prediction model performance in 10 regions, China.

Objective: To validate the World Health Organization (WHO) non-laboratory-based cardiovascular disease risk prediction model in regions of China. Methods: We performed an external validation of the WHO model for East Asia using the data set of China Kadoorie Biobank, an ongoing cohort study with 512 725 participants recruited from 10 regions of China from 2004-2008. We also recalculated the recalibration parameters for the WHO model in each region and evaluated the predictive performance of the model before and after recalibration. We assessed discrimination performance by Harrell's C index. Findings: We included 412 225 participants aged 40-79 years. During a median follow-up of 11 years, 58 035 and 41 262 incident cardiovascular disease cases were recorded in women and men, respectively. Harrell's C of the WHO model was 0.682 in women and 0.700 in men but varied among regions. The WHO model underestimated the 10-year cardiovascular disease risk in most regions. After recalibration in each region, discrimination and calibration were both improved in the overall population. Harrell's C increased from 0.674 to 0.749 in women and from 0.698 to 0.753 in men. The ratios of predicted to observed cases before and after recalibration were 0.189 and 1.027 in women and 0.543 and 1.089 in men. Conclusion: The WHO model for East Asia yielded moderate discrimination for cardiovascular disease in the Chinese population and had limited prediction for cardiovascular disease risk in different regions in China. Recalibration for diverse regions greatly improved discrimination and calibration in the overall population.

Association of air pollution and genetic risks with incidence of elderly-onset atopic dermatitis: A prospective cohort study.

BACKGROUND: Elderly-onset atopic dermatitis (AD) is a remarkable subtype and has been put on the agenda owing to its difficulty to control. Understanding the influence of genetic and environmental exposures is crucial to preventing elderly-onset AD. OBJECTIVES: To explore the association between genes and air pollution on incident elderly-onset AD. MATERIAL AND METHODS: This study was based on UK Biobank that recruited over 500,000 participants. The genetic risks were categorized into low, intermediate, and high groups according to tertiles of polygenic risk scores. Mixed exposure to various air pollutants was assessed using the weighted quantile sum (WQS) and also categorized based on tertiles. Within each genetic risk group, whether air pollutant mixture was associated with incident elderly-onset AD was estimated. RESULTS: 337,910 participants were included in the final analysis, and the mean age was 57.1. The median years for follow-up were 12.0, and the incident cases of AD were 2545. The medium and high air pollution mixture was significantly associated with incident AD compared with the low pollution group, with HRs of 1.182 (P = 0.003) and 1.359 (P < 0.001), respectively. In contrast, HR for medium and high genetic susceptibility was only 1.065 (P = 0.249) and 1.153 (P = 0.008). The population-attributable fraction of air pollution and genetic risk was 15.5 % (P < 0.001) and 6.4 % (P = 0.004). Additionally, compared with low genetic risk and low air pollution, high genetic risk and high air pollution was significantly associated with the incidence of elderly-onset AD with a HR of up to 1.523 (P < 0.001). There were no interactive effects between each group of genetic risks and air pollution. When grouped by sex, females could observe a stronger effect by genetic and air pollutant mixture exposure. CONCLUSION: Air pollution and genetics both independently enhance the risk of newly developed AD, and the effect of air pollutants is stronger than the investigated genes.

Improving Chinese electronic medical record retrieval by field weight assignment, negation detection, and re-ranking.

The technique of information retrieval has been widely used in electronic medical record (EMR) systems. It's a pity that most existing methods have not considered the structures and language features of Chinese EMRs, which affects the performance of retrieval. To improve accuracy and comprehensiveness, we propose an improved algorithm of Chinese EMR retrieval. First, the weights of fields in Chinese EMRs are assigned based on the corresponding importance in clinical applications. Second, negative relations in EMRs are detected, and the retrieval scores of negative terms are adjusted accordingly. Third, the retrieval results are re-ranked by expansion terms and time information to enhance the recall without decreasing precision. Experiment results show that the improved algorithm increases the precision and recall significantly, which shows that the algorithm takes a full account of the characteristics of Chinese EMRs and fits the needs for clinical applications.

Association of accelerated aging with the incidence risk of Cardiometabolic diseases in people with severe mental illnesses: A prospective analysis in UK Biobank.

Cardiometabolic diseases (CMDs) comorbidities among people with severe mental illnesses (SMI) are associated with a high healthcare burden and premature mortality. This study aims to evaluate whether biological aging has an interaction with SMI on incident CMDs, and to examine the association of four biological aging indicators with CMDs incidence in this population. Data were sourced from the UK Biobank, a large prospective cohort study. Four indicators were used to assess biological aging including frailty phenotype, frailty index, KDM-biological age acceleration and phenotypic age acceleration. Cox proportional hazards regression models were used to examine the associations. We observed higher prevalence of frailty and accelerated biological age with SMI than those without SMI. Further analysis found significant interaction effect of pre-frailty and SMI (PPre-frail*SMI=0.005) as well as biological age acceleration and SMI (PQ3 (>P75)*SMI=0.038). 14.7 % of the participants with SMI developed CMDs during the follow-up. Compared with non-frail participants, those with frailty (frailty phenotype: HR=1.68, 95 % CI: 1.50, 1.88, P < 0.001; frailty index: HR=2.44, 95 % CI: 2.11-2.81, P < 0.001) and biological age acceleration (KDM-biological age acceleration (Q3): HR=1.91, 95 % CI: 1.74, 2.11, P < 0.001; phenotypic age acceleration (Q3): HR=2.07, 95 % CI: 1.86, 2.30, P < 0.001) had a significantly higher risk of CMDs in the adjusted model. A series of sensitivity analyses were conducted to illustrate the robustness of the findings. These findings highlight the important implications for concerning about the high incidence of CMDs comorbidities and intervention of aging in people with SMI.

Corrigendum: Untreated depression and anxiety in patients with common skin diseases: a cross-sectional study in China.

[This corrects the article DOI: 10.3389/fpsyg.2023.1150998.].

Untreated depression and anxiety in patients with common skin diseases: a cross-sectional study in China.

Objective: The study aimed to analyze the current status and reasons for the neglect of the psychological need of patients with common skin diseases. Methods: This cross-sectional study was conducted in China using an online self-assessment questionnaire distributed via social media. Demographic, clinical and psychological data were collected, and the main outcomes, i.e., depression (evaluated using the 9-item Patient Health Questionnaire, PHQ-9) and anxiety (evaluated using Generalized Anxiety Disorder-7, GAD-7). Multivariate regression analysis was used for the prediction of variates of mental health service seeking behaviors. Results: A total of 1,010 patients participated in the survey, and 273 (27.0%) patients met the "with need" criteria, i.e., having the need for mental health intervention but not being treated. In the multivariate regression model, income (OR = 0.80, 95%CI: 0.65-0.99), duration of disease (OR = 0.68, 95%CI: 0.49-0.95) and suicide ideation (OR = 2.10, 95%CI: 1.14-3.87) were significant factors. For patients who did not receive mental health care, the lack of knowledge about the availability of mental health services, lack of knowledge of where to seek help, concerns about the side effects of treatment, failure to seek treatment for severe skin diseases, and absence of current psychological distress were associated with their need for psychological intervention. Conclusion: This study examined the current status of the need for psychological intervention and the reasons why the need was unmet in patients with skin diseases. Due to the confusion and a lack of knowledge about their mental health issues, mental health services are often underutilized.

Age at Natural Menopause, Reproductive Lifespan, and the Risk of Late-Onset Psoriasis and Psoriatic Arthritis in Women: A Prospective Cohort Study.

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases. The exposure variables included age at natural menopause (ANM) and duration from menarche to menopause, termed reproductive years. The outcome variables were incident psoriasis and PsA. We employed Cox regression analysis, factoring in polygenic risk scores for psoriatic diseases and recognized risk factors. We found that later ANM and longer reproductive years were significantly associated with decreased risks of late-onset psoriasis and PsA in a dose-dependent manner (P<.05). ANM after age 55 years led to a 34 and 46% risk reduction in late-onset psoriasis and PsA, respectively, compared with ANM before age 45 years (P<.001). The population-attributable risks of ANM were 17.4% for late-onset psoriasis and 21.6% for PsA. In conclusion, reproductive lifespan, with its inherent homeostasis, plays a pivotal yet overlooked role in late-onset psoriatic diseases. Investigations into estrogen-centric causes and sex-specific interventions are imperative.

Corrigendum: Untreated depression and anxiety in patients with common skin diseases: a cross-sectional study in China.

[This corrects the article DOI: 10.3389/fpsyg.2023.1150998.].

Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese.

BACKGROUND AND PURPOSE: Previous studies, mostly focusing on the European population, have reported polygenic risk scores (PRSs) might achieve risk stratification of stroke. We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population. METHODS: Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set (n=22 191) and a population-based testing set (n=72 150). Four previously developed PRSs were included, and new PRSs for stroke and its subtypes were developed. The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set. Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes (ischaemic stroke (IS), intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH)). RESULTS: In the testing set, during 872 919 person-years of follow-up, 8514 incident stroke events were documented. The PRSs of any stroke (AS) and IS were both positively associated with risks of AS, IS and ICH (p<0.05). The HR for per SD increment (HRSD) of PRSAS was 1.10 (95% CI 1.07 to 1.12), 1.10 (95% CI 1.07 to 1.12) and 1.13 (95% CI 1.07 to 1.20) for AS, IS and ICH, respectively. The corresponding HRSD of PRSIS was 1.08 (95% CI 1.06 to 1.11), 1.08 (95% CI 1.06 to 1.11) and 1.09 (95% CI 1.03 to 1.15). PRSICH was positively associated with the risk of ICH (HRSD=1.07, 95% CI 1.01 to 1.14). PRSSAH was not associated with risks of stroke and its subtypes. The addition of current PRSs offered little to no improvement in stroke risk prediction and risk stratification. CONCLUSIONS: In this Chinese population, the association strengths of current PRSs with risks of stroke and its subtypes were moderate, suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asian population.

Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank.

BACKGROUND: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. METHODS: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. RESULTS: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. CONCLUSIONS: In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.

Delay in Seeking Medical Attention and Diagnosis in Chinese Melanoma Patients: A Cross-Sectional Study.

Melanoma is a highly malignant skin tumor, and prolonged delay in seeking medical attention (DSMA) and delay in diagnosis (DD) may result in poor prognoses. Through a web-based questionnaire, we explored the related factors affecting the DSMA and DD of melanoma in a Chinese population. A total of 112 valid answer sheets were received. After obtaining the relevant information, we analyzed the factors associated with DSMA and DD. The median time of DSMA was 8.0 (quartiles: 1.0, 29.3) months, and the median of patients' DD was 1.0 (quartiles: 1.0, 8.3) month. The subsequent analysis showed that DSMA and DD were positively correlated to age and negatively correlated to education background and annual household income. Patients with a history of tumors or previous health-seeking behavior because of other skin lesions had significantly longer DSMA than those without. Patients who sought medical help at general tertiary hospitals for the first time had a significantly shorter DD than those who chose other hospitals. Our study found that DSMA and DD are associated with factors such as age, education, income, and patients' histories. Secondary prevention of Chinese melanoma should be strengthened to reduce DSMA and DD to improve patients' prognoses.

Development of a Model to Predict 10-Year Risk of Ischemic and Hemorrhagic Stroke and Ischemic Heart Disease Using the China Kadoorie Biobank.

BACKGROUND AND OBJECTIVES: Contemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China. METHODS: We derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were age 30-79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure-lowering treatment, current daily smoking, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of 3 submodels. Risk models were recalibrated in each region by 2 methods (practical and ideal) and risk prediction was estimated before and after recalibration. RESULTS: Model derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell C was 0.732 (95% CI 0.706-0.758), 0.759 (0.738-0.779), and 0.803 (0.778-0.827) for IHD, IS, and HS, respectively. The Harrell C for total CVD was 0.734 (0.732-0.736), 0.754 (0.752-0.756), and 0.774 (0.772-0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women. DISCUSSION: Our CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of IHD, IS, and HS in the Chinese population age 30-79 years.

Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study.

Background: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population. Methods: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10 year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module. Results: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR < 0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47 % decrease to a 118 % increase. Mediation analyses revealed 28.5 % of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7 % (P = 0.003) via systolic blood pressure and 6.4 % (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD. Conclusions: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and blood pressure-related pathways to CHD risk. Funding: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).

Bowel movement frequency and risks of major vascular and non-vascular diseases: a population-based cohort study among Chinese adults.

OBJECTIVE: The application of bowel movement frequency (BMF) in primary care is limited by the lack of solid evidence about the associations of BMF with health outcomes apart from Parkinson's disease and colorectal cancer. We examined the prospective associations of BMF with major vascular and non-vascular diseases outside the digestive system. DESIGN: Population-based prospective cohort study. SETTING: The China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008. PARTICIPANTS: 487 198 participants aged 30 to 79 years without cancer, heart disease or stroke at baseline were included and followed up for a median of 10 years. The usual BMF was self-reported once at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident events of predefined major vascular and non-vascular diseases. RESULTS: In multivariable-adjusted analyses, participants having bowel movements 'more than once a day' had higher risks of ischaemic heart disease (IHD), heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus and chronic kidney disease (CKD) when compared with the reference group ('once a day'). The respective HRs (95% CIs) were 1.12 (1.09 to 1.16), 1.33 (1.22 to 1.46), 1.28 (1.22 to 1.36), 1.20 (1.15 to 1.26) and 1.15 (1.07 to 1.24). The lowest BMF ('less than three times a week') was also associated with higher risks of IHD, major coronary events, ischaemic stroke and CKD. The respective HRs were 1.07 (1.02 to 1.12), 1.22 (1.10 to 1.36), 1.11 (1.05 to 1.16) and 1.20 (1.07 to 1.35). CONCLUSION: BMF was associated with future risks of multiple vascular and non-vascular diseases. The integration of BMF assessment and health counselling into primary care should be considered.

Association Between Active Commuting and Incident Cardiovascular Diseases in Chinese: A Prospective Cohort Study.

Background Active commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population. Methods and Results A total of 104 170 urban commuters without major chronic diseases at baseline were included from China Kadoorie Biobank. Self-reported commuting mode was defined as nonactive commuting, work at home or near home, walking, and cycling. Multivariable Cox regression was used to examine associations between commuting mode and cardiovascular disease. Overall, 47.2% of the participants reported nonactive commuting, 13.4% reported work at home or work near home, 20.1% reported walking, and 19.4% reported cycling. During a median follow-up of 10 years, we identified 5374 incidents of ischemic heart disease, 664 events of hemorrhagic stroke, and 4834 events of ischemic stroke. After adjusting for sex, socioeconomic status, lifestyle factors, sedentary time, body mass index, comorbidities, household air pollution, passive smoking, and other domain physical activity, walking (hazard ratio, 0.90; 95% CI, 0.84-0.96) and cycling (hazard ratio, 0.81; 95% CI, 0.74-0.88) were associated with a lower risk of ischemic heart disease than nonactive commuting. Cycling was associated with a lower risk of ischemic stroke (hazard ratio, 0.92; 95% CI, 0.84-1.00). No significant association was found of walking or cycling with hemorrhagic stroke. The associations of commuting mode with major cardiovascular disease were consistent among men and women and across different levels of other domain physical activity. Conclusions In urban China, cycling was associated with a lower risk of ischemic heart disease and ischemic stroke. Walking was associated with a lower risk of ischemic heart disease.

Family History, Tobacco Smoking, and Risk of Ischemic Stroke.

BACKGROUND AND PURPOSE: Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS. METHODS: The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS. RESULTS: About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed (P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS. CONCLUSIONS: Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.