李宏帆
中国医学科学院阜外医院 询证医学部
PURPOSE:Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups.METHODS:This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models.RESULTS:During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h·d -1 ), those with high genetic risk and high ST (≥10 h·d -1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST ( Ptrend = 0.024).CONCLUSIONS:Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.
Medicine and science in sports and exercise 2024
Previous studies indicated that long-term exposure to high level of fine particulate matter (PM2.5) was associated with elevated blood pressure (BP) and hypertension, but most of them were conducted in high-income countries with low PM2.5 level. Therefore, we aimed to evaluate the adverse impacts of long-term exposure to PM2.5 on BP and hypertension in China with high concentration. A total of 99,084 adults aged ≥18 years old were included from three cohorts among the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. PM2.5 concentrations during 2000-2015 at 1 × 1 km spatial resolution were evaluated using satellite-based spatiotemporal models. Generalized estimating equation was applied to assess the impact of three-year average PM2.5 concentrations on BP level and hypertension. We also examined whether health status and lifestyles modified the effects of PM2.5 on BP and hypertension. Generally, high concentration of PM2.5 was associated with increased BP level and higher risk of hypertension. With each 10 μg/m3 increment in PM2.5 concentration, systolic BP (SBP) and diastolic BP (DBP) increased by 1.67 [95% confidence interval (CI): 1.48, 1.86] mmHg and 0.45 (95% CI: 0.35, 0.56) mmHg, and the prevalence of hypertension increased by 29% [odds ratio (OR): 1.29, 95% CI: 1.26, 1.32]. In comparison with the first quartile of PM2.5 concentration, SBP, DBP and prevalence of hypertension in the fourth quartile were increased by 8.26 (95% CI: 7.73, 8.80) mmHg, 2.85 (95% CI: 2.55, 3.15) mmHg, and 133% (OR: 2.33, 95% CI: 2.21, 2.47), respectively, in the fully adjusted model. However, the relationships of PM2.5 with BP might be non-linear, as BP level started to decline when PM2.5 exceeded 75 μg/m3. In conclusion, long-term PM2.5 exposure could elevate BP level and prevalence of hypertension. People living in high-polluted areas should strengthen their awareness of prevention.
Environmental pollution (Barking, Essex : 1987) 2023
AIMS:LDL cholesterol (LDL-C) is a well-established risk factor for coronary artery disease (CAD). However, the optimal LDL-C level with regard to efficacy and safety remains unclear. We aimed to investigate the causal relationships between LDL-C and efficacy and safety outcomes.METHODS AND RESULTS:We analyzed 353 232 British from the UK Biobank and 41 271 Chinese from the China-PAR project. Linear and non-linear Mendelian randomization (MR) analyses were performed to evaluate the causal relation between genetically proxied LDL-C and CAD, all-cause mortality, and safety outcomes (including haemorrhagic stroke, diabetes mellitus, overall cancer, non-cardiovascular death, and dementia). No significant non-linear associations were observed for CAD, all-cause mortality, and safety outcomes (Cochran Q P > 0.25 in British and Chinese) with LDL-C levels above the minimum values of 50 and 20 mg/dL in British and Chinese, respectively. Linear MR analyses demonstrated a positive association of LDL-C with CAD [British: odds ratio (OR) per unit mmol/L increase, 1.75, P = 7.57 × 10-52; Chinese: OR, 2.06, P = 9.10 × 10-3]. Furthermore, stratified analyses restricted to individuals with LDL-C levels less than the guideline-recommended 70 mg/dL demonstrated lower LDL-C levels were associated with a higher risk of adverse events, including haemorrhagic stroke (British: OR, 0.72, P = 0.03) and dementia (British: OR, 0.75, P = 0.03).CONCLUSION:In British and Chinese populations, we confirmed a linear dose-response relationship of LDL-C with CAD and found potential safety concerns at low LDL-C levels, providing recommendations for monitoring adverse events in people with low LDL-C in the prevention of cardiovascular disease.
European journal of preventive cardiology 2023
BACKGROUND:Several studies reported temperature exposure was associated with altered cardiac automatic function, while this effect of temperature on hourly heart rate variability (HRV) among populations with cardiovascular risks was seldom addressed.METHODS:We conducted this panel study in four Chinese cities with three repeated visits among 296 participants at intermediate to high-risk of cardiovascular disease (CVD). Real-time temperature level and 24-h ambulatory electrocardiogram were monitored during each seasonal visit. Linear mixed-effects models were used to investigate associations between individual temperature and HRV parameters, and the seasonal effects and circadian effect were also evaluated.RESULTS:We found the overall downward trend of hourly HRV associated with acute exposure to higher temperature. For each 1 °C increment in temperature of 1-3 h prior to HRV measurements (lag 1-3 h), hourly standard deviation of normal-to-normal intervals (SDNN) decreased by 0.38% (95% confidence interval [CI]: 0.22, 0.54), 0.28% (95% CI: 0.12, 0.44), and 0.20% (95% CI: 0.04, 0.36), respectively. Similar inverse associations between temperature and HRV were observed in stratified analyses by temperature level. Inverse associations for cold and warm seasons were also observed, despite some effects gradually decreased and reversed in the warm season as lag times extended. Moreover, HRV showed a more significant reduction with increased temperature during daytime than nighttime. Percent change of hourly SDNN was -0.41% (95% CI: -0.62, -0.21) with 1 °C increment of lag 1 h during daytime, while few obvious changes were revealed during nighttime.CONCLUSIONS:Generally, increasing temperature was significantly associated with reduced HRV. Inverse relationships for cold and warm seasons were also observed. Associations during daytime were much more prominent than nighttime. Our findings clarified the relationship of temperature with HRV and provided evidence for prevention approaches to alleviate cardiac automatic dysfunction among populations at intermediate to high-risk of CVD.
The Science of the total environment 2023
Background:Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension.Methods:Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food-frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension.Results:During 640,795 person-years of follow-up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86-0.95), 0.85 (0.81-0.90), 0.82 (0.78-0.86), and 0.83 (0.78-0.88) for the Q2 to Q5 group (p trend < 0.001), respectively. In further analyses categorizing participants according to the recommended intake level (500 g/day), we found that increasing the intake of TFV, even though it was still insufficient for the recommendation, also had a protective effect against the incident hypertension. When considering the intake of fruit or vegetable separately, we found similar trends as the TFV intake.Conclusion:These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.
Chronic diseases and translational medicine 2023
AIM:ATP-binding cassette (ABC) transporters and endonuclease-exonuclease-phosphatase family domain containing 1 (EEPD1) are reported to regulate cellular cholesterol efflux in macrophages. Bioinformatics analysis has revealed that ABCG1 and EEPD1 might be potential targets of microRNA (miR)-320b. This study aimed to elucidate the roles of miR-320b in cholesterol efflux from macrophages and the pathogenesis of atherosclerosis.METHODS:Microarray was conducted to profile microRNA (miRNA) expression, and quantitative real-time PCR (qPCR) was used to validate the differentially expressed miRNAs in peripheral blood mononuclear cells of coronary artery disease (CAD) patients and healthy controls. Luciferase assay was conducted to evaluate the activity of reporter construct containing the 3´-untranslated region (3´-UTR) of target genes. Besides, NBD-cholesterol efflux induced by high-density lipoprotein (HDL) and lipid-free apolipoprotein A1 (apoA1) was detected using fluorescence intensity, respectively. Apoe-/- mice were injected with adeno-associated virus (AAV)2-miR-320b or control via tail vein, thereafter fed with 14 week atherogenic diet to study the roles of miR-320b in vivo.RESULTS:MiR-320b was highly expressed in CAD patients compared with that in the healthy controls in both the microarray analysis and qPCR analysis. In vitro study showed that miR-320b decreased HDL- and apoA1-mediated cholesterol efflux from macrophages partly by directly targeting ABCG1 and EEPD1 genes and partly via suppressing the LXRα-ABCA1/G1 pathway. Consistently, in vivo administration of AAV2-miR-320b into Apoe-/- mice attenuated cholesterol efflux from peritoneal macrophages, which showed reduced expression of ABCA1/G1 and EEPD1, and increased lipid LDL-C level, with a down-regulation of hepatic LDLR and ABCA1. AAV2-miR-320b treatment also increased atherosclerotic plaque size and lesional macrophage content and enhanced pro-inflammatory cytokines levels through the elevated phosphorylation level of nuclear factor-κB p65 in macrophages.CONCLUSION:We identify miR-320b as a novel modulator of macrophage cholesterol efflux and that it might be a promising therapeutic target for atherosclerosis treatment.
Journal of atherosclerosis and thrombosis 2022
BACKGROUND:The causal effects of moderate alcohol consumption on cardiovascular diseases (CVDs) are continuously debated, especially on coronary artery disease (CAD).OBJECTIVES:We aimed to explore the causal associations of alcohol consumption with CVDs and all-cause mortality among Chinese males.METHODS:A prospective cohort study was conducted in 40,386 Chinese males, with 17,676 being genotyped for the rs671 variant in the aldehyde dehydrogenase 2 (ALDH2) gene. A Cox proportional hazards model was conducted to estimate the effects of self-reported alcohol consumption. Mendelian randomization (MR) analysis was performed to explore the causality using rs671 as an instrumental variable.RESULTS:During the follow-up of 303,353 person-years, 2406 incident CVDs and 3195 all-cause mortalities were identified. J-shaped associations of self-reported alcohol consumption with incident CVD and all-cause mortality were observed, showing decreased risks for light (≤25 g/d) and moderate drinkers (25-≤60 g/d). However, MR analyses revealed a linear association of genetically predicted alcohol consumption with the incident CVD (P-trend = 0.02), including both CAD (P-trend = 0.03) and stroke (P-trend = 0.02). The HRs (95% CIs) for incident CVD across increasing tertiles of genetically predicted alcohol consumption were 1 (reference), 1.18 (1.01, 1.38), and 1.22 (1.03, 1.46). After excluding heavy drinkers, the risk of incident CVD and all-cause mortality was increased by 27% and 20% per standard drink increment of genetically predicted alcohol consumption, respectively.CONCLUSIONS:Our analyses extend the evidence of the harmful effect of alcohol consumption to total CVD (including CAD) and all-cause mortality, highlighting the potential health benefits of lowering alcohol consumption, even among light-to-moderate male drinkers.
The American journal of clinical nutrition 2022
BACKGROUND:High sodium intake is an important risk factor for hypertension and cardiovascular disease. However, the association between gut microbiota composition and metabolomic profiles with dietary sodium intake and blood pressure (BP) is not well-understood. The metabolome, microbiome, and dietary salt intervention (MetaSalt) study aimed to investigate microbial and metabolomic profiles related to dietary sodium intake and BP regulation.METHODS:This family-based intervention study was conducted in four communities across three provinces in rural northern China in 2019. Probands with untreated prehypertension or stage-1 hypertension were identified through community-based BP screening, and family members including siblings, offspring, spouses, and parents were subsequently included. All participants participated in a 3-day baseline examination with usual diet consumption, followed by a 10-day low-salt diet (3 g/d of salt or 51.3 mmol/d of sodium) and a 10-day high-salt diet (18 g/d of salt or 307.8 mmol/d of sodium). Differences in mean BP levels were compared according to the intervention phases using a paired Student's t-test.RESULTS:A total of 528 participants were included in this study, with a mean age of 48.1 years, 36.7% of whom were male, 76.8% had a middle school (69.7%) or higher (7.1%) diploma, 23.4% had a history of smoking, and 24.4% were current drinkers. The mean arterial pressure at baseline was 97.2 ± 10.5 mm Hg for all participants, and significantly decreased during the low-salt intervention (93.8 ± 9.3, P < 0.0001) and subsequently increased during the high-salt intervention (96.4 ± 10.0, P < 0.0001).CONCLUSIONS:Our dietary salt intervention study has successfully recruited participants and will facilitate to evaluate the effects of gut microbiota and metabolites on BP regulation in response to sodium burden, which will provide important evidence for investigating the underlying mechanisms in the development of hypertension and subsequent cardiovascular diseases.TRIAL REGISTRATION:The study was registered in the Chinese Clinical Trial Registry database (ChiCTR1900025171).
Chronic diseases and translational medicine 2021
MiR-520b belongs to the miR-373/520 family, is expressed only in human and nonhuman primates. Previous reports indicated that the expression of miR-520b was repressed in human atherosclerotic plaque tissue compared with healthy vessels. However, the role of miR-520b in coronary artery disease still remains to be uncovered. In this study, we demonstrated that endothelial cells (ECs) in human atherosclerotic plaques expressed miR-520b and aimed to elucidate the impact of miR-520b on EC activation and inflammatory response. To determine the potential targets of miR-520b, we performed RNA-seq analysis by transfecting miR-520b mimics in ECs. The quantitative real-time PCR (qPCR) validation suggested that miR-520b over-expression reduced pro-inflammatory gene expression (e.g. ICAM1, VCAM1, SELE) while the inhibition of miR-520b induced their expression. By combining bioinformatics prediction and functional assays, we identified that RELA (Nuclear Factor-κB (NF-κB) Transcription Factor P65) was a direct target of miR-520b. Moreover, miR-520b mimics attenuated monocyte adhesion and monocyte trans-endothelial migration (the initial steps of atherosclerotic formation) in response to lipopolysaccharides (LPS) stimulation. Re-expression of a non-miR-targetable version of p65 could rescue the reduced monocyte cell attachment, suggesting that this process is NF-κB p65 dependent. MiR-520b reduced the abundance of NF-κB p65 in cytoplasmic fractions without corresponding increase in nuclear fractions, indicating that this regulation is independent of p65 translocation process. MiR-520b mimics attenuated the activity of VCAM-1 promoter, whereas miR-520b inhibitor activated its activity. However, miR-520b inhibitor had no effect on promoter activity containing the mutated NF-κB p65 binding sites, strongly demonstrating that the impact of miR-520b on VCAM1 gene is mediated by NF-κB p65. Thus, we concluded that miR-520b suppressed EC inflammation and the cross-talk between monocytes and ECs by down-regulating NF-κB p65-ICAM1/VCAM1 axis and might serve as a potential therapeutic target for EC dysfunction and atherosclerosis.
Biochemical pharmacology 2021
BACKGROUND:Association between tea consumption and incident hypertension remains uncertain. This study conducted to examine the health effects of tea consumption on blood pressure progression and hypertension incidence.METHODS:A population-based cohort of 38,913 Chinese participants without hypertension at baseline were included in the current study. Information on tea consumption was collected through standardized questionnaires. Associations of tea consumption with blood pressure progression and incident hypertension were analyzed using logistic regression models and Cox proportional hazards regression models, respectively.RESULTS:During a median follow-up of 5.9 years, 17,657 individuals had experienced progression to a higher blood pressure stage and 5,935 individuals had developed hypertension. In multivariate analyses, habitual tea drinkers (≥ 3 times/week for at least six months) had a 17% lower risk for blood pressure progression [odds ratio (OR) = 0.83, 95% CI: 0.79-0.88] and a 14% decreased risk for incident hypertension [hazard ratio (HR) = 0.86, 95% CI: 0.80-0.91] compared with non-habitual tea drinkers. Individuals in different baseline blood pressure groups could obtain similar benefit from habitual tea drinking. In terms of tea consumption amount, an inverse, linear dose-response relation between monthly consumption of tea leaves and risk of blood pressure progression was observed, while the risk of incident hypertension did not reduce further after consuming around 100 g of tea leaves per month.CONCLUSIONS:Our study demonstrated that habitual tea consumption could provide preventive effect against blood pressure progression and hypertension incidence.
Journal of geriatric cardiology : JGC 2021
