曹杰
中国医学科学院阜外医院 流行病研究部
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
Importance:The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown.Objective:To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition.Design, Setting, and Participants:This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021.Exposures:CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition.Main Outcomes and Measures:The main outcome was first incident CHD.Results:Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS.Conclusions:This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.
JAMA cardiology 2024
BACKGROUND:Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors.METHODS:This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications.RESULTS:Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride.CONCLUSIONS:Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.
Stroke 2024
The utility of the polygenic risk score (PRS) to identify individuals at higher risk of stroke beyond clinical risk remains unclear, and we clarified this using Chinese population-based prospective cohorts. Cox proportional hazards models were used to estimate the 10-year risk, and Fine and Gray's models were used for hazard ratios (HRs), their 95% confidence intervals (CIs), and the lifetime risk according to PRS and clinical risk categories. A total of 41,006 individuals aged 30-75 years with a mean follow-up of 9.0 years were included. Comparing the top versus bottom 5% of the PRS, the HR was 3.01 (95%CI 2.03-4.45) in the total population, and similar findings were observed within clinical risk strata. Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories. Notably, among individuals with intermediate clinical risk, the 10-year risk for those in the top 5% of the PRS (7.3%, 95%CI 7.1%-7.5%) reached the threshold of high clinical risk (⩾7.0%) for initiating preventive treatment, and this effect of the PRS on refining risk stratification was evident for ischemic stroke. Even among those in the top 10% and 20% of the PRS, the 10-year risk would also exceed this level when aged ⩾50 and ⩾60 years, respectively. Overall, the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.
Science China. Life sciences 2023
BACKGROUND:The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).METHODS:A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.RESULTS:A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).CONCLUSIONS:Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
Journal of geriatric cardiology : JGC 2023
Objective:This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness.Methods:We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges.Results:Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83).Conclusion:Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.
Biomedical and environmental sciences : BES 2023
Previous studies have established a significant link between ambient fine particulate matter (PM2.5) exposure and atherosclerotic cardiovascular disease (ASCVD) incidence, but whether this association varies across populations with different predicted ASCVD risks was uncertain previously. We included 109,374 Chinese adults without ASCVD at baseline from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. We obtained PM2.5 data of participants' residential address from 2000 to 2015 using a satellite-based spatiotemporal model. Participants were classified into low-to-medium and high-risk groups according to the ASCVD 10-year and lifetime risk prediction scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PM2.5 exposure-related incident ASCVD, as well as the multiplication and additive interaction, were calculated using stratified Cox proportional hazard models. The additive interaction between risk stratification and PM2.5 exposure was estimated by the synergy index (SI), the attributable proportion due to the interaction (API), and the relative excess risk due to interaction (RERI). Over the follow-up of 833,067 person-years, a total of 4230 incident ASCVD cases were identified. Each 10 μg/m3 increment of PM2.5 concentration was associated with 18% (HR: 1.18; 95% CI: 1.14-1.23) increased risk of ASCVD in the total population, and the association was more pronounced among individuals having a high predicted ASCVD risk than those having a low-to-medium risk, with the HR (95% CI) of 1.24 (1.19-1.30) and 1.11 (1.02-1.20) per 10 μg/m3 increment in PM2.5 concentration, respectively. The RERI, API, and SI were 1.22 (95% CI: 0.62-1.81), 0.22 (95% CI: 0.12-0.32), and 1.37 (95% CI: 1.16-1.63), respectively. Our findings demonstrate a significant synergistic effect on ASCVD between ASCVD risk stratification and PM2.5 exposure and highlight the potential health benefits of reducing PM2.5 exposure in Chinese, especially among those with high ASCVD risk.
Environmental science & technology 2023
BACKGROUND:Remarkable heterogeneity has been observed among population-based studies on egg consumption and risk of coronary artery disease (CAD). Whether genetic susceptibility serves as a potential explanation for this inconsistency remains unknown.OBJECTIVES:We performed a prospective cohort study to investigate the association of egg consumption with incident CAD at different genetic susceptibilities.METHODS:We included 34,111 participants without CAD at baseline from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Egg consumption was assessed with food frequency questionnaires. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants. The hazard ratio (HR) and 95% confidence interval (95% CI) of incident CAD associated with egg consumption and PRS were estimated using the Cox proportional hazards models.RESULTS:Over a median 11.7 y of follow-up, 1,128 incident cases of CAD were recorded. Both higher egg consumption and increased PRS were related to higher risk of CAD. When stratified by genetic risk, each increment of 3 eggs/wk was associated with a 5% higher risk of CAD for participants at low to intermediate genetic risk (HR: 1.05; 95% CI: 1.01, 1.09), whereas risk increased to HR 1.10 (95% CI: 1.05, 1.16) for those at high genetic risk; a significant synergistic interaction was also indicated at both multiplicative (Pinteraction = 0.007) and additive (relative excess risk: 0.73; 95% CI: 0.24, 1.22) scales. When the joint effect was examined, in comparison with those at low to intermediate genetic risk and consuming <1 egg/wk, the HR (95% CI) was 2.95 (2.41, 3.62) for participants with high genetic risk and consumption of ≥10 eggs/wk, and the corresponding standardized 10-y CAD rates increased from 1.37% to 4.24%.CONCLUSIONS:Genetic predisposition may synergistically interact with egg consumption in relation to increased CAD risk. PRS-stratified recommendations on egg consumption may help formulate personalized nutrition policies.
The American journal of clinical nutrition 2023
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
BACKGROUND:The effect of long-standing prediabetes or its transition on incident cardiovascular disease (CVD) is unclear. This study aimed to evaluate the association of changes in fasting blood glucose (FBG) status with the risk of developing CVD.METHODS:This research included 12 145 Chinese adults aged 35-74 years and free from diabetes mellitus (DM) at baseline. Study participants were cross-classified into six categories according to glucose at the first (1998-2001) and the second visit after 8 years: normal fasting glucose (NFG; 50-99 mg/dl), impaired FBG (IFG; 100-125 mg/dl), and DM. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for CVD associated with transition of glucose status.RESULTS:During a median follow-up of 5.5 years, 373 incident CVD cases occurred. Compared with participants remaining persistent NFG, a higher risk of developing CVD was identified among those remaining persistent IFG, progressing to DM from NFG or from IFG, with the multivariate-adjusted HR (95% CI) of 1.792 (1.141, 2.816), 1.723 (1.122, 2.645) and 1.946 (1.120, 3.381), respectively. Furthermore, when stratified by glucose status at baseline, persistent IFG and progression from IFG to DM still increased CVD risk in comparison with reversion from IFG to NFG, with the multivariate-adjusted HR (95% CI) of 1.594 (1.003, 2.532) and 1.913 (1.080, 3.389).CONCLUSIONS:Participants with long-standing IFG and progressing to DM had a higher risk of developing CVD. Further well-designed studies are warranted to assess the association of other phenotypes or prediabetes duration with CVD.
Journal of diabetes 2023
