刘钟应
中国医学科学院阜外医院 流行病
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
OBJECTIVE:To examine whether adherence to ideal cardiovascular health (CVH) can mitigate the genetic risk of coronary artery disease (CAD) in non-European populations.METHODS:Fine and Grey's models were used to calculate HRs and their corresponding 95% CIs, as well as the lifetime risk of CVH metrics across Polygenic Risk Score (PRS) categories.RESULTS:We included 39 755 individuals aged 30-75 years in Chinese prospective cohorts. 1275 CAD cases were recorded over a mean follow-up of 12.9 years. Compared with unfavourable CVH profile (zero to three ideal CVH metrics), favourable CVH profile (six to seven ideal CVH metrics) demonstrated similar relative effects across PRS categories, with the HRs of 0.40 (95% CI 0.24 to 0.67), 0.41 (95% CI 0.32 to 0.52) and 0.36 (95% CI 0.26 to 0.52) in low (bottom quintile of PRS), intermediate (two to four quintiles of PRS) and high (top quintile of PRS) PRS categories, respectively. For the absolute risk reduction (ARR), individuals with high PRS achieved the greatest benefit from favourable CVH, mitigating the risk to the average level of population (from 21.1% to 8.7%), and the gradient was strengthened in individuals at the top 5% of PRS. Moreover, compared with individuals at low PRS, those at high PRS obtained longer CAD-free years (2.6 vs 1.1) from favourable CVH at the index age of 35 years.CONCLUSION:Favourable CVH profile reduced the CAD relative risk by similar magnitude across PRS categories, while the ARR from favourable CVH was most pronounced in high PRS category. Attaining favourable CVH should be encouraged for all individuals, especially in individuals with high genetic susceptibility.
Heart (British Cardiac Society) 2023
AIMS:To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations.METHODS AND RESULTS:Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS.CONCLUSION:The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.
European heart journal 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
Although emerging researches have linked ambient fine particulate matter (PM2.5) to obesity, evidence from high-polluted regions is still lacking. We thus assessed the long-term impacts of PM2.5 on body mass index (BMI) and the risk of the prevalence of overweight/obesity (BMI≥25 kg/m2), by incorporating the well-established Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project comprising 77,609 participants with satellite-based PM2.5 estimates at 1-km spatial resolution. The average of long-term PM2.5 level was 70.4 μg/m3, with the range of 32.1-94.2 μg/m3. Each 10 μg/m3 increment of PM2.5 was associated with 0.421 kg/m2 (95% confidence interval [CI]: 0.402, 0.439) and 13.5% (95% CI: 12.8%, 14.3%) increased BMI and overweight/obesity risk, respectively. Moreover, compared with the lowest quartile of PM2.5 (≤57.5 μg/m3), the relative risk of the prevalence of overweight/obesity from the highest quartile (>85.9 μg/m3) was 1.611 (95% CI: 1.566, 1.657). The exposure-response curve suggested a non-linear relationship between PM2.5 exposure and overweight/obesity. Besides, the association was modified by age, diabetes mellitus, hypertension and dyslipidemia status. Our study provides the evidence for the adverse impacts of long-term PM2.5 on BMI and overweight/obesity in China, and the findings are important for policy development on air quality, especially in severely polluted areas.
Environmental research 2021
OBJECTIVE:To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.METHODS:Using a meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals.RESULTS:During a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.66-2.38), with the lifetime risk of stroke being 25.2% (95% CI 22.5%-27.7%) and 13.6% (95% CI 11.6%-15.5%), respectively. Individuals with both high polygenic risk and family history displayed lifetime risk as high as 41.1% (95% CI 31.4%-49.5%). Individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of low polygenic risk (from 34.6% to 13.2%).CONCLUSIONS:Our metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH.CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that metaPRS is predictive of stroke risk.
Neurology 2021
