暂无摘要。

OBJECTIVE: Currently little is known about the joint association of lipoprotein (a) [Lp(a)] and Lipoprotein-associated phospholipase A2 (Lp-PLA2) with stroke recurrence.
METHODS: In this prospective multicenter cohort study, 10,675 consecutive acute ischemic stroke (IS) and transient ischemic attack patients (TIA) with Lp(a) and Lp-PLA2 were enrolled. The association of stroke recurrence within 1 year with Lp(a) and Lp-PLA2 was assessed using Cox proportional hazards models and Kaplan-Meier curves. The interaction between Lp(a) and Lp-PLA2 with stroke recurrence was evaluated by multiplicative and additive scales.
RESULTS: A significant joint association of Lp(a) and Lp-PLA2 with the risk of stroke recurrence was observed. Multivariate cox regression analysis demonstrated that the combination of elevated Lp(a) (≥ 50 mg/dL) and Lp-PLA2 (≥175.1 ng/ml) was independently associated with the risk of stroke recurrence (adjusted hazard ratio: 1.42; 95 % CI: 1.15-1.76). Both significant multiplicative [(exp(β3):1.63, 95 % CI: 1.17-2.29, P = 0.004] and additive interaction (RERI:0.55, 95 % CI: 0.20-0.90, P = 0.002; AP: 0.39, 95 %CI, 0.24-0.53) were observed between Lp(a) and Lp-PLA2.
CONCLUSIONS: Our results indicated that Lp(a) and Lp-PLA2 have a joint association with the risk of stroke recurrence in IS/TIA patients. Patients with concomitant presence of elevated Lp(a) and Lp-PLA2 have greater risk of stroke recurrence.

BACKGROUND: Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated.
METHODS: Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death.
RESULTS: Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01-2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02-3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24-3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21-2.73, P = 0.0043), 2.76 (1.57-4.86, P = 0.0004), and 1.72 (1.09-2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75-4.49, P < 0.0001), cardiac death (aHR: 4.10, 95% CI: 2.18-7.70, P < 0.0001), and all-cause death (aHR: 3.00, 95% CI, 1.73-5.19, P < 0.0001) were significantly greater in patients with both RIR and RCR (highest hsCRP and RC tertile) than in patients with neither RIR nor RCR (lowest hsCRP and RC tertile). Notably, the RIR and RCR was associated with an increased risk of ischemic events especially in patients with adequate low-density lipoprotein cholesterol (LDL-C) control (LDL-C < 70 mg/dl) (Pinteraction=0.04). Furthermore, the RIR and RCR provide more accurate evaluations of risk in addition to the GRACE score in these patients [areas under the curve (AUC) for ischemic events: 0.64 vs. 0.66, P = 0.003].
CONCLUSIONS: Among ACS patients receiving contemporary statin treatment who underwent PCI, high risks of both residual inflammation and cholesterol, as assessed by hsCRP and RC, were strongly associated with increased risks of ischemic events, cardiac death, and all-cause death.

BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.
METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.
RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.
CONCLUSIONS: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

BACKGROUND: It remains controversial whether prenatal screening or diagnostic testing should be offered to fetuses with nasal bone (NB) absence or hypoplasia, and there are no studies comparing the yield of chromosomal microarray analysis (CMA) to non-invasive prenatal screening (NIPS). The aim of this study was to evaluate the residual risk of clinically significant copy number variations (CNVs) in fetuses with NB absence or hypoplasia after excluding theoretically NIPS-detectable abnormalities, and to assess their clinical outcomes.
METHODS: This prospective study encompassed 400 fetuses with NB absence or hypoplasia undergoing CMA testing between 2015 and 2022. Clinically significant CMA findings were categorized into three subgroups, including three-NIPS-detectable (trisomies 21, 18 and 13), five-NIPS-detectable (trisomies 21, 18 and 13 and sex chromosome aneuploidies) and genome-wide NIPS-detectable (variants over 7 Mb). We calculated the theoretical residual risk and compared it with the results of a control cohort of low-risk pregnancies. We further evaluated their clinical outcomes.
RESULTS: The overall diagnostic yield in our cohort was 7.8% (31/400). The detection rate of clinically significant CMA findings in fetuses with non-isolated NB absence or hypoplasia was significantly higher than that in fetuses with isolated NB absence or hypoplasia (20.0% vs. 6.6%, P =.005). The theoretical residual risks in all NIPS models were significantly higher when compared with the control cohort. The normal infant rate in fetuses with normal CMA results was 97.9% (323/330), and a significant higher incidence was observed in fetuses with isolated NB absence or hypoplasia compared with non-isolated NB absence or hypoplasia (98.4% vs. 91.7%, P =.028).
CONCLUSIONS: The residual risk of clinically significant CNVs in fetuses with NB absence or hypoplasia following the exclusion of theoretically NIPS-detectable findings was higher than that in low-risk pregnancies. This risk should be considered in genetic counseling to make a more comprehensive and precise choice regarding prenatal genetic testing.

OBJECTIVE: To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT).
METHODS: The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected.
RESULTS: Study group was composed of 1470 single pregnancies, including 864 with NT 2.5-2.9 mm, 350 with NT 3.0-3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1-10.1%) in fetuses with NT 3.0-3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders.
CONCLUSIONS: Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm.

Background The multitrajectory model can identify joint longitudinal patterns of different lipids simultaneously, which might help better understand the heterogeneous risk of premature cardiovascular disease (CVD) and facilitate targeted prevention programs. This study aimed to investigate the associations between multitrajectories of lipids with premature CVD. Methods and Results The study enrolled 78 526 participants from the Kailuan study, a prospective cohort study in Tangshan, China. Five distinct multitrajectories of triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol over 6-year exposure were identified on the basis of Nagin\'s criteria, using group-based multitrajectory modeling. During a median follow-up of 6.75 years (507 645.94 person-years), 665 (0.85%) premature CVDs occurred. After adjustment for confounders, the highest risk of premature CVD was observed in group 4 (the highest and increasing triglyceride, optimal and decreasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (hazard ratio [HR], 2.13 [95% CI, 1.36-3.32]), followed by group 5 (high and decreasing triglyceride, optimal and increasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (HR, 2.07 [95% CI, 1.45-2.98]), and group 3 (optimal and increasing triglyceride, borderline high and increasing LDL-C, optimal and decreasing high-density lipoprotein cholesterol) (HR, 1.90 [95% CI, 1.32-2.73]). Conclusions Our results showed that the residual risk of premature CVD caused by increasing triglyceride levels remained high despite the fact that LDL-C levels were optimal or declining over time. These findings emphasized the importance of assessing the joint longitudinal patterns of lipids and undertaking potential interventions on triglyceride lowering to reduce the residual risk of premature CVD, even among individuals with optimal LDL-C levels.

Randomized controlled trials confirm that risks of residual cholesterol and residual inflammation remains in patients with cardiovascular disease (CVD) even after lipid-lowering therapy. This study aims to investigate the association between dual residual risk of cholesterol and inflammation and all-cause mortality in a real-world population with CVD.
Patients with a CVD history who first took statins between 1 January 2010 and 31 December 2017 in the Kailuan Study were selected as study participants. According to low-density lipoprotein cholesterol (LDL-C) and hypersensitive C-reactive protein levels, patients were divided into those with no residual risk, residual inflammatory risk (RIR), residual cholesterol risk (RCR), and residual cholesterol and inflammatory risk (RCIR). Cox proportional hazard model was conducted to determine hazard ratio (HR) of all-cause mortality for RIR, RCR, and RCIR. Stratified analysis was conducted according to good medication adherence and 75% of the percentage LDL-C decline, high SMART 2 risk score, and blood pressure and blood glucose at standard levels.
After 6.10 years of follow-up, 377 all-cause deaths occurred in 3509 participants (mean age 63.69 ± 8.41 years, 86.78% men). After adjusting for related risk factors, the HR and (95% confidence interval [CI]) of all-cause mortality in the RIR, RCR, and RCIR was 1.63 (1.05, 2.52), 1.37 (0.98, 1.90), and 1.75 (1.25, 2.46), compared with no residual risk. Similar associations were observed in participants with moderate or low statin compliance, a lower percentage of LDL-C decline, high SMART 2 risk score, uncontrolled blood pressure, and uncontrolled blood glucose, in the RCIR had a 1.66-fold, 2.08-fold, 1.69-fold, 2.04-fold, and 2.05-fold higher risk of all-cause mortality, respectively, than the reference.
Risks of residual cholesterol and residual inflammation remain in patients with CVD after receiving statins, and their combined effect significantly increases the risk of all-cause mortality. Here, this increased risk was dependent on statin compliance, LDL-C reduction, SMART 2 risk score, and blood pressure and blood glucose control.

High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility.
HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value.
Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model.
Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D.

OBJECTIVE: To discuss the residual risk (RR) of noninvasive prenatal screening (NIPS) for the mothers with fetal ultrasound abnormalities.
METHODS: 880 pregnant women with fetal ultrasound abnormalities accepted prenatal diagnosis by chromosomal microarray analysis (CMA) after amniocentesis. Furthermore, the detection efficiency of NIPS was evaluated and calculated based on our previous studies and other literatures. The RR of the chromosome abnormality results was then analyzed.
RESULTS: A total of 103 cases were confirmed as fetal chromosome abnormalities, including 65 (63.1%) of aneuploidies and 38 (36.9%) of clinical significant copy number variations (CNVs). Of which, based on the estimated NIPS efficacy, 87 cases could also be detected by NIPS. The detection rate (DR) was 84.5%, while 16 cases would be missed. The total of RR of NIPS in the fetuses with ultrasound anomalies was 2.0% (16/793), approximately one in 51. The top three RR of fetal ultrasound abnormalities were echogenic bowel (5.9%), multiple systems of structural anomalies (4.5%), and nervous system anomalies (4.2%).
CONCLUSIONS: The overall residual risk of NIPS in the fetuses with ultrasound anomalies was approximately 2.0%, especially in echogenic bowel, multiple systems of structural anomalies and nervous system anomalies.