Associations of Plasma Metabolites With Risks of Incident Stroke and Its Subtypes in Chinese Adults.

BACKGROUND: Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. METHODS AND RESULTS: We performed a nested case-control study within the Dongfeng-Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow-up period of 6.1±2.3 years. Fifty-five metabolites in fasting plasma were measured by ultra-high-performance liquid chromatography-mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 [1.08-1.34] and 1.22 [1.09-1.36], respectively; both Benjamini-Hochberg-adjusted P <0.05). When examining stroke subtypes, asymmetrical/symmetrical dimethylarginine was nominally associated with both IS and HS (odds ratios [95% CIs]: 1.16 [1.03-1.31] and 1.39 [1.07-1.81], respectively), while glutamate was associated with only IS (odds ratios [95% CI]: 1.26 [1.11-1.43]). The associations of glutamate with IS risk were significantly stronger among participants with hypertension and diabetes than among those without these diseases (both P for interaction <0.05). CONCLUSIONS: This study validated the positive associations of asymmetrical/symmetrical dimethylarginine and glutamate with stroke risk, mainly that of IS, in a Chinese population, and revealed a novel unanimous association of with both IS and HS. Our findings provided potential intervention targets for stroke prevention.

Associations of physical activity intensity with incident cardiovascular diseases and mortality among 366,566 UK adults.

BACKGROUND: The associations of the proportion of vigorous physical activity (VPA) to moderate to vigorous physical activity (MVPA) with incident cardiovascular disease (CVD) and all-cause mortality are unclear. METHODS: The present study included 366,566 participants (aged 40-69 years) without baseline CVD from the UK biobank during 2006 to 2010. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of outcomes. RESULTS: During a median 11.8 years of follow-up, among 366,566 participants (mean age [SD]: 56.0 [8.1]), 31,894 incident CVD and 19,823 total deaths were documented. Compared with no VPA, 0%-30% of VPA to MVPA was associated with 12% and 19% lower risks of incident CVD (HR, 0.88 [95% CI, 0.86-0.91]) and all-cause mortality (HR, 0.81 [95% CI, 0.78-0.84]), respectively. Furthermore, we found that the maximum reduction of risks of incident CVD and all-cause mortality occurred at performing approximately 30% of VPA to MVPA (P < 0.001). Compared with participants reporting the lowest levels of MVPA (moderate physical activity [MPA], 0-150 min/week; VPA, 0-75 min/week), those performing 150-300 min/week of MPA and ≥ 150 min/week of VPA experienced the lowest risk of incident CVD (HR, 0.87 [95% CI, 0.79-0.95]) and all-cause mortality (HR, 0.71 [95% CI, 0.63-0.80]). Interestingly, we found that smokers yielded more cardiovascular benefits than non-smokers by performing a higher volume of VPA. CONCLUSIONS: Comparing with UK adults reporting no VPA, engaging in 30% of VPA was associated with the lowest risk of incident CVD and all-cause mortality.

Reliability and Validity of Common Subjective Instruments in Assessing Physical Activity and Sedentary Behaviour in Chinese College Students.

The reliability and validity of common physical activity (PA) questionnaires are not well investigated in college students. This study aims to evaluate the reliability and validity of common subjective instruments in measuring PA and sedentary behaviour (SB) among college students. A total of 142 college students were included through convenience sampling. Each participant was asked to wear Actigraph wGT3X-BT accelerometers and fill physical activity logs (PAL) for 7 consecutive days. The Global Physical Activity Questionnaire (GPAQ), the International Physical Activity Questionnaire long-form (IPAQ-LF), and short-form (IPAQ-SF) were interviewed by face-to-face at both day 0 and day 8. Reliability was evaluated by intraclass correlation coefficient (ICC), while the validity was evaluated by Spearman correlation coefficient and Bland-Altman statistics. The instruments showed moderate reliability in reporting total PA (ICC = 0.50-0.62) and SB (ICC = 0.47-0.52), while moderate validity in reporting moderate and vigorous PA (MVPA) (r = 0.37-0.42), but fair to poor validity in reporting SB (r = 0.09-0.28). Bland-Altman plots showed that all the instruments would underestimate MVPA and overestimate SB. Thus, in Chinese younger adults, the GPAQ, IPAQ-LF, IPAQ-SF, and PAL provide limited but acceptable reliability and validity in measuring MVPA and SB, among which GPAQ might be the most valid instrument.

Association Between Change in Leisure-Time Physical Activity During the Postretirement Period and Incident Stroke.

OBJECTIVE: To investigate the association of change in leisure-time physical activity (LTPA) occurring during the post-retirement period with incident stroke. METHODS: The present study enrolled 12 644 retired workers from the Dongfeng-Tongji cohort (DFTJ) during April to October 2013. The change in LTPA was categorized as follows according to whether their LTPA time meeting the World Health Organization (WHO) recommended minimum (at least 150 minutes per week): (i) stayed inactive at both surveys; (ii) stayed inactive at 2008 survey but became active at 2013 survey; (iii) stayed active at 2008 survey but became inactive at 2013 survey; (iv) stayed active at both surveys. We used multivariable-adjusted Cox proportional hazards regression models to examine the association between change in LTPA and the risk of incident stroke. RESULTS: During 68 476 person-years of follow-up, we documented 549 incident stroke cases, including 434 incident ischemic stroke (IS) cases and 115 incident hemorrhagic stroke (HS) cases. Compared with participants who stayed active at both 2008 and 2013 surveys, those stayed active at 2008 survey but became inactive at 2013 survey had significant higher risks of incident total stroke (hazard ratio [HR] = 1.30; 95% confidence interval [95% CI]: 1.03, 1.65) and HS (HR = 2.34; 95% CI: 1.51, 3.63). When stratified by body mass index (BMI) categories, a significant elevated risk of total stroke was seen among over-weight participants who stayed active at 2008 survey but became inactive at 2013 survey (HR = 1.65; 95% CI: 1.20, 2.27). The risk of incident stroke decreased with increasing LTPA levels between two surveys (HR of per 150 minutes/week increase of LTPA: HR=0.97; 95% CI: 0.94, 1.00). In addition, we found that compared with participants who maintained their BMI and stayed active at both 2008 and 2013 surveys, those both inactive or became inactive had higher risks of stroke (HR = 2.13, 95% CI: 1.09, 4.15; HR = 1.50, 95% CI: 1.07, 2.08; respectively). CONCLUSION: Among Chinese older adults, increasing LTPA levels during the post-retirement period was associated with a lower risk of incident stroke. Retired individuals should be encouraged to participate in LTPA more frequently to lessen future risk of incident stroke.

Leisure-time physical activity and risk of incident cardiovascular disease in Chinese retired adults.

The optimum amounts and types of leisure-time physical activity (LTPA) for cardiovascular disease (CVD) prevention among Chinese retired adults are unclear. The prospective study enrolled 26,584 participants (mean age [SD]: 63.3 [8.4]) without baseline disease from the Dongfeng-Tongji cohort in 2013. Cox-proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean 5.0 (1.5) years of follow-up, 5704 incident CVD cases were documented. Compared with less than 7.5 metabolic equivalent of task-hours per week (MET-hours/week) of LTPA, participating LTPA for 22.5-37.5 MET-hours/week, which was equivalent to 3 to 5 times the world health organization (WHO) recommended minimum, was associated with a 18% (95% CI 9 to 25%) lower CVD risk; however, no significant additional benefit was gained when exceeding 37.5 MET-hours/week. Each log10 increment of MET-hours/week in square dancing and cycling was associated with 11% (95% CI 2 to 20%) and 32% (95% CI 21 to 41%), respectively, lower risk of incident CVD. In Chinese retired adults, higher LTPA levels were associated with lower CVD risk, with a benefit threshold at 3 to 5 times the recommended physical activity minimum. Encouraging participation in square dancing and cycling might gain favourable cardiovascular benefits.

Trans-ethnic genome-wide association study of severe COVID-19.

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.

Associations of coagulation factor X and XI with incident acute coronary syndrome and stroke: A nested case-control study.

BACKGROUND: Coagulation cascade contributes to thrombotic and hemorrhagic diseases, but it remains unclear whether coagulation factors X (FX) and XI (FXI) levels are associated with cardiovascular diseases. OBJECTIVE: To evaluate prospective associations of FX and FXI levels with incident acute coronary syndrome (ACS), stroke, and their subtypes (acute myocardial infarction, unstable angina, ischemic stroke, and hemorrhagic stroke). METHODS: We performed a nested case-control study (n = 1846) within the Dongfeng-Tongji cohort from 2013 to 2016 matched on age (within 1 year), sex, and sampling date (within 1 month) by incidence density sampling, and measured plasma FX and FXI levels by enzyme-linked immunosorbent assay. FX and FXI levels were categorized into three groups (low, <25th; middle, 25th to <75th; and high ≥75th percentiles) according to distributions, and conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After adjustment for traditional cardiovascular risk factors, compared with middle groups, the OR (95% CI) in high levels of FX and FXI were 1.11 (0.79-1.56) and 0.96 (0.68-1.36) for incident ACS, and 1.01 (0.63-1.62) and 1.72 (1.14-2.60) for incident stroke, respectively. As for subtypes of ACS and stroke, only high FXI levels were significantly associated with incident ischemic stroke (OR 1.66, 95% CI 1.05-2.65). Moreover, all associations remained steady after additional adjustment for platelet and leukocyte. CONCLUSION: FXI levels were associated with a greater risk of incident ischemic stroke but not hemorrhagic stroke or ACS. FX levels were not associated with incident ACS or stroke.