Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

Study on the Cooling Performance of a Focused Ultrasonic Radiator for Electrical Heating Elements.

In this work, a focused ultrasonic radiator is proposed for cooling the electrical heating elements in the focal region, and its working characteristics are investigated. The analyses of the FEM computational and flow field visualization test results indicate that focused ultrasound can generate forced convective heat transfer by the acoustic streaming in the focal region, which can cool the heating elements effectively. Experiments show that when the input voltage is 30Vp-p and the ambient temperature is 25 °C, the focused ultrasonic radiator can cause the surface temperature of the heating element (high-temperature alumina ceramic heating plate with a diameter of 5 mm) in the focal region to drop from 100 °C to about 55 °C. When the diameter of the electrical heating element is changed from 5 mm to 30 mm, the cooling effect is similar in the focal region. Compared with a fan, the focused ultrasound radiator has a shorter cooling time and a more concentrated cooling area. The focused ultrasonic radiator proposed in this work is suitable for some special environments.

Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.

PURPOSE: The main objectives were to test whether (1) a decrease in myelin is associated with enhanced rate of fibrillar tau accumulation and cognitive decline in Alzheimer's disease, and (2) whether apolipoprotein E (APOE) ε4 genotype is associated with worse myelin decrease and thus tau accumulation. METHODS: To address our objectives, we repurposed florbetapir-PET as a marker of myelin in the white matter (WM) based on previous validation studies showing that beta-amyloid (Aß) PET tracers bind to WM myelin. We assessed 43 Aß-biomarker negative (Aß-) cognitively normal participants and 108 Aß+ participants within the AD spectrum with florbetapir-PET at baseline and longitudinal flortaucipir-PET as a measure of fibrillar tau (tau-PET) over ~ 2 years. In linear regression analyses, we tested florbetapir-PET in the whole WM and major fiber tracts as predictors of tau-PET accumulation in a priori defined regions of interest (ROIs) and fiber-tract projection areas. In mediation analyses we tested whether tau-PET accumulation mediates the effect of florbetapir-PET in the whole WM on cognition. Finally, we assessed the role of myelin alteration on the association between APOE and tau-PET accumulation. RESULTS: Lower florbetapir-PET in the whole WM or at a given fiber tract was predictive of faster tau-PET accumulation in Braak stages or the connected grey matter areas in Aß+ participants. Faster tau-PET accumulation in higher cortical brain areas mediated the association between a decrease in florbetapir-PET in the WM and a faster rate of decline in global cognition and episodic memory. APOE ε4 genotype was associated with a worse decrease in the whole WM florbetapir-PET and thus enhanced tau-PET accumulation. CONCLUSION: Myelin alterations are associated in an APOE ε4 dependent manner with faster tau progression and cognitive decline, and may therefore play a role in the etiology of AD.

Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease.

OBJECTIVE: We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum. METHODS: We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, 18 F-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas. Based on a brain-parcellation atlas superimposed onto all modalities, we obtained region of interest (ROI)-to-ROI functional connectivity, ROI-level PET values, and MAPT gene expression. In stepwise regression analyses, we tested connectivity, MAPT gene expression, and amyloid-PET as predictors of group-averaged and individual tau-PET ROI values in amyloid-positive participants. RESULTS: Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau-PET ROI values averaged across amyloid-positive participants. Stepwise addition of MAPT gene expression and amyloid-PET increased the proportion of explained variance to 30.2 to 46.0% and 45.0 to 49.9%, respectively. Similarly, for the prediction of patient-level tau-PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R2 range across studies = 0.118-0.148, 0.156-0.196, and 0.251-0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively). INTERPRETATION: Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD. ANN NEUROL 2024;95:274-287.

Design and Experiment of a Clamping-Drive Alternating Operation Piezoelectric Actuator.

In recent years, piezoelectric actuators, represented by inertial and inchworm actuators, have been widely applied because of their high accuracy and excellent responsiveness. Despite the development of various piezoelectric actuators, there remain some flaws in this technology. The sticking point is that the piezoelectric actuators based on the friction driving principle are prone to unwanted backward motion when outputting stepping motion. It is thus urgent to explore solutions from the perspectives of principle and structure. In this paper, a clamping-drive alternating operation piezoelectric actuator is proposed, the two feet of which are driven by two piezoelectric stacks, respectively. Due to double-foot alternate drive guide movement, backward movement is prevented in theory. By adopting the double-layer stator structure, integrated processing and assembly are facilitated. Meanwhile, a double flexible hinge mechanism is installed in the stator to prevent the drive foot from being overturned due to ineffectiveness and premature wear. In addition, the stator is equipped with the corresponding preload mechanism and clamping device. After the cycle action mechanism of one cycle and four steps is expounded, a model is established in this study to further demonstrate the principle. With the prototype produced, a series of experiments are performed. In addition, the amplitude of actuation of the stator is tested through amplitude experiment. The performance of the stator is evaluated by conducting experiments in the alternating step and single step actuation modes. Finally, the test results are analyzed to conclude that the actuator operating in either of these two modes can meet the practical needs of macro and micro actuation.

Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease.

BACKGROUND: Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline. Further, we aimed to determine whether tau-PET-informed personalized cognitive composites capture patient-specific cognitive trajectories more sensitively than conventional cognitive measures. METHODS: We included Alzheimer's Disease Neuroimaging Initiative (ADNI) participants classified as controls (i.e., amyloid-negative, cognitively normal, n = 121) or Alzheimer's disease-spectrum (i.e., amyloid-positive, cognitively normal to dementia, n = 140), plus 111 AVID-1451-A05 participants for independent validation (controls/Alzheimer's disease-spectrum=46/65). All participants underwent baseline 18F-flortaucipir tau-PET, amyloid-PET, and longitudinal cognitive testing to assess annual cognitive changes (i.e., episodic memory, language, executive functioning, visuospatial). Cognitive changes were calculated using linear mixed models. Independent meta-analytical task-fMRI activation maps for each included cognitive domain were obtained from the Neurosynth database and applied to tau-PET to determine tau-PET signal in cognitive-domain-specific brain regions. In bootstrapped linear regression, we assessed the strength of the relationship (i.e., partial R2) between cognitive-domain-specific tau-PET vs. global or temporal-lobe tau-PET and cognitive changes. Further, we used tau-PET-based prediction of domain-specific decline to compose personalized cognitive composites that were tailored to capture patient-specific cognitive decline. RESULTS: In both amyloid-positive cohorts (ADNI [age = 75.99±7.69] and A05 [age = 74.03±9.03]), cognitive-domain-specific tau-PET outperformed global and temporal-lobe tau-PET for predicting future cognitive decline in episodic memory, language, executive functioning, and visuospatial abilities. Further, a tau-PET-informed personalized cognitive composite across cognitive domains enhanced the sensitivity to assess cognitive decline in amyloid-positive subjects, yielding lower sample sizes required for detecting simulated intervention effects compared to conventional cognitive endpoints (i.e., memory composite, global cognitive composite). However, the latter effect was less strong in A05 compared to the ADNI cohort. CONCLUSION: Combining tau-PET with task-fMRI-derived maps of major cognitive domains facilitates the prediction of domain-specific cognitive decline. This approach may help to increase the sensitivity to detect Alzheimer's disease-related cognitive decline and to determine personalized cognitive endpoints in clinical trials.

A closed-loop recycling process for carbon fiber-reinforced polymer waste using thermally activated oxide semiconductors: Carbon fiber recycling, characterization and life cycle assessment.

The objective of this study is to investigate the properties of recycled carbon fiber (rCF) and its environmental impact, with a specific focus on the energy consumption of the recycling process based on the use of thermally activated oxide semiconductors (TASC). The mechanical and surface properties of rCF obtained under the optimal process parameters were characterized. The life cycle assessment method was used to evaluate the environmental impact of a closed-loop recycling process for carbon fiber-reinforced polymer (CFRP) waste using TASC. The results indicated that the decomposition rate of resin was 95.5 %, and no carbonaceous solid was generated. The gaseous produced of the recycling process were mainly CO2 and H2O, and no liquid products were produced. The surface oxidation degree of rCF was relatively slight. COOH was generated on the surface of rCF, which was conducive to improving the interfacial adhesion viscosity with resin. The monofilament tensile strength of rCF was maintained above 97 %. Compared with landfill and incineration, CFRP waste recycling using TASC can make global warming potential, acidification potential and eutrophication potential reduced by 28 %, 32 %, and 25 %, respectively. Ozone layer depletion potential, human toxicity potential and terrestrial ecotoxicity potential in disposing CFRP waste using TASC were 30 %, 21 % and 41 % of that using pyrolysis, respectively. The energy consumption in carbon fiber recycling by TASC was only 23 % of that in virgin carbon fiber manufacturing. TASC is found to be a promising potential strategy for managing CFRP waste.

Serum microRNA miR-491-5p/miR-206 Is Correlated with Poor Outcomes/Spontaneous Hemorrhagic Transformation after Ischemic Stroke: A Case Control Study.

BACKGROUND: It is unclear whether miR-491-5p, miR-206, miR-21-5p or miR-3123 are associated with functional outcomes and hemorrhagic transformation (HT) after acute ischemic stroke (AIS). In this study, we aimed to investigate the correlation between these four microRNAs and functional outcomes, as well as spontaneous HT after AIS; Methods: We included 215 AIS patients and retrospectively assayed for miR-21-5p, miR-206, miR-3123 and miR-491-5p levels in serum. Poor functional outcome was defined as a modified Rankin Scale score ≥ 3. Spontaneous HT referred to hemorrhage detected in follow-up brain imaging but not on admission, without reperfusion therapies. Logistic regression, generalized additive model and 2-piecewise regression model were used to explore the independent, non-linear correlation between miRNA expression levels and outcomes; Results: We included 215 AIS patients. Higher miR-491-5p level independently reduced the risk of poor functional outcomes at 1 year (OR 0.90, 95% CI 0.82-0.98, corrected p value = 0.044). Higher miR-206 level significantly increased the risk of spontaneous HT (OR 1.64, 95% CI 1.17-2.30, corrected p value = 0.016). There was a nonlinear correlation found between miR-491-5p level and 1 year outcome with an inflection point of 2.180, while an approximately linear correlation was observed with an inflection point of 2.037 between miR-206 level and spontaneous HT; Conclusions: Higher serum miR-491-5p level independently reduced risk of 1-year poor functional outcome of AIS patients. Higher serum miR-206 level independently increased the risk of spontaneous HT in AIS patients. These two miRNAs may be as the potential biomarkers for improving prognosis after AIS.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed-location intracerebral hemorrhage.

OBJECTIVE: To study the relationship between cerebral small vessel disease (CSVD) and hematoma volume in mixed-location intracerebral hemorrhage (ICH), and non-mixed ICH (hypertensive arteriopathy/cerebral amyloid angiopathy-related ICH). METHODS: We consecutively collected patients with primary ICH with MRI. Mixed-location ICH was defined as having ICH or cerebral microbleeds (CMBs) in both lobar and deep regions. CSVD markers including lacunes, white matter hyperintensities (WMH), CMBs, and enlarged perivascular spaces (EPVS) were assessed on brain MRI during hospitalization. Multivariable binary logistic regression (≥30 ml vs. <30 ml) and linear regression analyses (log-transformed hematoma volume as dependent variable) were implemented to explore the association between CSVD and hematoma volume. RESULTS: Of the 167 included patients, 69 (41.3%) had mixed-location ICH, with higher prevalence of lacune, more CMB count, higher WMH score and total CSVD score than those with non-mixed ICH (all p < .001). Higher WMH score was associated with lower risk of hematoma volume ≥30 ml (adjusted OR 0.521, 95% CI 0.299-0.908, p = .021) in patients with mixed-location ICH. Also, multivariable linear regression showed the association of smaller hematoma volume with higher CSVD burden, especially in mixed-location ICH (ß = -0.349, p = .019 for CMB ≥ 5; ß = -0.183, p < .001 for WMH score; ß = -0.456, p = .002 for EPVS>20 in basal ganglia and/or centrum semiovale; ß = -0.256, p = .002 for CSVD score), while these relationships were not observed in non-mixed ICH. CONCLUSIONS: Higher CSVD burden is associated with smaller hematoma volume in mixed-location ICH, but not in non-mixed ICH, which is novel and needs further studies with larger sample size to confirm our results and explore the underlying mechanisms.

Association between admission blood fibrinogen-to-albumin ratio and clinical outcomes after acute lacunar stroke.

Aim: We aimed to investigate the influence of admission fibrinogen-to-albumin ratio (FAR) on 3-month outcomes after acute lacunar stroke. Materials & methods: Consecutive patients with acute lacunar stroke were included and classified into two groups according to an optimized FAR cut-off value determined by receiver operating characteristic curve analysis. Results: Compared with those with low FAR (<0.077), patients from the high FAR group (≥0.077) had significantly higher risk for 3-month disability and the composite outcome of death/disability. After logistic regression adjustment, high FAR was still significantly associated with 3-month disability and death/disability. Conclusion: FAR ≥0.077 on admission might be an independent predictor of disability and death/disability at 3 months after lacunar stroke, which needs to be verified in future studies.

Serum Albumin as a Potential Predictor of Pneumonia after an Acute Ischemic Stroke.

BACKGROUND: Serum albumin level is associated with infection after stroke, but whether albumin predicts post-stroke pneumonia is unclear. The potential relationship between albumin level and pneumonia in patients with acute ischemic stroke (AIS) was evaluated in this study. METHODS: A consecutive sample of 798 AIS patients who were admitted to West China Hospital within 24 h after onset, from the year 2017 to 2018, were retrospectively analyzed. Blood was collected on admission and assayed for serum albumin. Univariate analyses, multivariate logistic regression, and stratified logistic regression were performed to identify the risk factors of post-stroke pneumonia. RESULTS: Out of the 798 patients, 240 (30.2%) developed pneumonia at a median of 48 h after onset (interquartile range, 27-74 h). Patients with pneumonia had significantly lower serum albumin levels than those without pneumonia (40.6 vs. 42.9 g/l, p<0.001). After adjustment, the albumin level was still significantly associated with pneumonia in multivariate logistic regression (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.81-0.94). The association between serum albumin and pneumonia tended to depend on National Institutes of Health Stroke Scale score (p = 0.045), but this was significant only in patients with mild stroke (OR 0.84, 95% CI 0.77-0.93). A dosedependent inverse relationship was found between albumin levels and the risk of pneumonia after AIS. Albumin values predicted pneumonia with an area under the curve of 0.661 (95% CI 0.620- 0.701), and the optimal cutoff was 42.6 g/L. CONCLUSION: Low serum albumin levels may be independent predictors of pneumonia in patients with AIS, especially in mild stroke. In fact, the risk of pneumonia may vary inversely with albumin level.

Trends in Outcomes of Patients With Ischemic Stroke Treated Between 2002 and 2016: Insights From a Chinese Cohort.

BACKGROUND: Little is known about long-term trends in outcomes of patients with ischemic stroke in China. We aimed to assess longitudinal trends in these outcomes over the past 15 years in China and explore possible factors behind the trends. METHODS AND RESULTS: Patients with ischemic stroke admitted to the Department of Neurology at West China Hospital were prospectively and consecutively enrolled in a central registry since 2002, and the present study analyzed data from those admitted to hospital within 7 days of stroke during the period 2002 to 2016. Patients were binned into three 5-year intervals for temporal analysis. Death, disability, and death/disability at 3 and 12 months after stroke were compared among the time intervals across the entire sample and in subsets stratified by age (<65 or ≥65 years). To explore the possible factors related to the trends in outcomes, interaction between the factors and time on outcomes was entered separately into the multivariable logistic regression model. Of 6462 patients with ischemic stroke in the final analysis, 3837 (59.4%) were men, and mean age was 64.2 years (SD, 13.7). Mean age at stroke onset and National Institutes of Health Stroke Scale score at admission decreased significantly during the 15-year period (P<0.001). Between 2002 to 2006 and 2012 to 2016, cumulative incidences declined significantly for death at 3 months (from 9.6% to 6.4%), disability at 3 months (from 36.8% to 28.7%), and death/disability at 3 months (from 42.9% to 33.3%), as well as for death at 12 months (from 15.9% to 10.7%), disability at 12 months (from 23.2% to 17.6%), and death/disability at 12 months (from 35.4% to 26.4%; all P<0.001). The decreases in disability and death/disability at 3 and 12 months between 2002 to 2006 and 2012 to 2016 remained significant after adjusting for confounders, and the results were similar for the entire cohort and for subgroups of patients <65 or ≥65 years. Only interactions of National Institutes of Health Stroke Scale score on admission and time period (2012-2016) were found to significantly correlate with disability and death/disability at 3 and 12 months (all P≤0.03). CONCLUSIONS: Our study from a large medical center in southwest China suggests that since 2002, risks of disability and death/disability at 3 and 12 months after ischemic stroke have declined. This appears to be due, at least in part, to a significant decline in National Institutes of Health Stroke Scale score on admission, which may reflect greater public awareness of stroke detection, willingness to seek medical attention, and ease of access to healthcare infrastructure. The factors behind this apparent improvement require further study.

Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: A cohort study and systematic review.

BACKGROUND AND PURPOSE: The relationship between neutrophil to lymphocyte ratio (NLR) and prognosis after acute ischemic stroke (AIS) remains controversial. The aim of this cohort study and systematic review was to ascertain the association of admission NLR with major clinical poor outcomes after AIS. METHODS: We analyzed data from Chengdu stroke registry and performed a systematic review for previous literature. The outcomes were hemorrhagic transformation (HT), parenchymal hematoma (PH), symptomatic intracranial hemorrhage (sICH), 3-month death or disability (modified Rankin Scale≥3), and 3-month death. Odds ratios (ORs) and 95% confidence intervals (CIs) of NLR as a continuous and categorical variable and poor outcomes were pooled separately. We also calculated the predictive accuracy of admission NLR in different outcomes. RESULTS: We included 808 patients from registry database and 9563 patients from previous studies. Our registry data showed that NLR ≥5 was associated with HT (OR 2.03, 95%CI 1.19-3.46), PH (OR 2.54, 95%CI 1.20-5.35) and 3-month death (OR 5.55, 95%CI 1.41-21.89); meta-analysis with our data and other observational studies indicated that higher NLR was associated with HT (OR 1.99, 95% CI 1.45-2.73), sICH (OR 2.22, 95% CI 1.60-3.09), 3-month death or disability (OR 1.68, 95% CI 1.18-2.38), and 3-month death (OR 2.79, 95% CI 1.57, 4.94). NLR had the highest predictive accuracy for 3-month death. CONCLUSIONS: Higher NLR is positively associated with the risk of HT and 3-month death after stroke. Considering the limited predictive ability of a single biomarker, more studies should validate the role of NLR in prognostic models.

MMP-9-Related microRNAs as Prognostic Markers for Hemorrhagic Transformation in Cardioembolic Stroke Patients.

Studies suggest that microRNAs that regulate expression of matrix metalloproteinase (MMP)-9 may be involved in hemorrhagic transformation (HT) after cardioembolic stroke, so we examined whether such microRNAs could predict HT in acute cardioembolic stroke patients. Blood samples were prospectively collected from patients who later experienced HT (n = 29) or did not (n = 29), and the samples were assayed for eight microRNAs identified as related to MMP-9 based on three microRNA databases. Expression levels of these microRNAs were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in 28 of the 58 patients, 14 of whom suffered HT and 14 of whom did not. Four differentially expressed miRNAs were identified: hsa-miR-21-5p, hsa-miR-206, hsa-miR-491-5p, and hsa-miR-3123. Subsequent qRT-PCR analysis of these four miRNAs across all 58 patients showed that levels of miR-21-5p, miR-206, and miR-3123 were significantly higher in patients with HT than in those without HT, while expression of miR-491-5p was similar between the two groups. The area under the receiver operating characteristic curve for predicting HT was 0.677 (95% CI 0.535-0.818) for miR-21-5p, 0.687 (95% CI 0.543-0.830) for miR-206, and 0.661 (95% CI 0.512-0.810) for miR-3123. Our results suggest that these three microRNAs may be prognostic markers for HT after cardioembolic stroke, which should be verified by future studies with large samples.

Genotype-guided antiplatelet therapy compared with conventional therapy for patients with acute coronary syndromes: a systematic review and meta-analysis.

To evaluate whether genotype-guided antiplatelet therapy reduces the rates of cardiovascular events and bleeding events in patients with acute coronary syndrome (ACS). We systematically searched Pubmed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) (searched in September 2018) for controlled studies evaluating genotype-guided antiplatelet therapy in ACS with percutaneous coronary intervention (PCI) or without PCI. The primary endpoint was a composite of death, myocardial infarction (MI), stroke, targeted vessel revascularization and/or major bleeding. A total of five studies involving 2900 patients were included. Compared with the conventional group, the genotype-guided group had a decreased risk of primary composite outcomes (RR= 0.54; 95% CI: 0.41-0.72; I2 = 30%), death (RR = 0.54; 95% CI: 0.32-0.94; I2 = 21%), MI (RR = 0.52; 95% CI: 0.31-0.88; I2 = 49%), targeted vessel revascularization (RR = 0.59; 95% CI: 0.35-0.98; I2 = 0%), but not for stroke (RR = 0.53; 95% CI: 0.22-1.24; I2 = 0%) and bleeding events (RR = 0.80; 95% CI: 0.51-1.25; I2 = 33%). Genotype-guided strategies could reduce the rates of cardiovascular events without increasing bleeding events compared with conventional treatment in ACS. Future multi-centre genotype-based randomized control trials are required to confirm these findings.