刘慧慧
中国医学科学院北京协和医院 呼吸内科办公室
BACKGROUND:This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea.METHODS AND RESULTS:Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow-up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05-2.04]; P=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10-2.19]; P=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44-1.37]; P=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28-4.38]; P=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32-4.56], P=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men.CONCLUSIONS:In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis.REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.
Journal of the American Heart Association 2024
AIMS:Red blood cell distribution width-to-albumin ratio (RAR), an innovate biomarker of inflammation, can independently predict adverse cardiovascular outcomes. However, the association between RAR and prognosis in patients with non-ischaemic heart failure (NIHF) remains unclear.METHODS AND RESULTS:A total of 2077 NIHF patients admitted to the Heart Failure Care Unit, Fuwai Hospital, were consecutively enrolled from December 2006 to October 2017 in this retrospective study. The primary endpoint was a composite outcome of all-cause mortality and heart transplantation. The correlation between RAR and the composite outcome was assessed by the Kaplan-Meier survival analysis and the Cox regression analysis. Incremental predictive values and the clinical performance of RAR for all-cause mortality or heart transplantation were also assessed based on a 12-variable traditional risk model. The median follow-up time in this study was 1433 (1341, 1525) days. As the gender no longer satisfied the Cox proportional risk assumption after 1150 days, we set 1095 days as the follow-up time for analysis. A total of 500 patients reached the composite outcome. Multivariable Cox regression showed that per log2 increase of RAR was significantly associated with a 132.9% [hazard ratio 2.329, 95% confidence interval (CI) 1.677-3.237, P < 0.001] increased risk of all-cause mortality or heart transplantation. Better model discrimination [concordance index: 0.766 (95% CI 0.754-0.778) vs. 0.758 (95% CI 0.746-0.770), P < 0.001], calibration (Akaike information criterion: 1487.3 vs. 1495.74; Bayesian information criterion: 1566.25 vs. 1569.43; Brier score: 1569.43 vs. 1569.43; likelihood ratio test P < 0.001), and reclassification (integrated discrimination improvement: 1.35%, 95% CI 0.63-2.07%, P < 0.001; net reclassification improvement: 13.73%, 95% CI 2.05-27.18%, P = 0.034) were improved after adding RAR to the traditional model (P < 0.001 for all). A higher overall net benefit was also obtained in the threshold risk probability of 20-55%.CONCLUSIONS:High level of RAR was an independent risk factor of poor outcome in NIHF.
ESC heart failure 2024
N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.
Molecular therapy : the journal of the American Society of Gene Therapy 2024
PURPOSE:It is uncertain whether β-blockers are beneficial for long-term prognosis in older patients following acute myocardial infarction (AMI). Thus, this study sought to examine the effect of β-blockers on long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI.METHODS:In this prospective, consecutive, non-randomized study, a total of 1156 patients with AMI admitted within 24 h after onset of symptoms were enrolled from January 2012 to February 2020. Univariate and multivariate Cox regression analyses were performed to examine the impact of β-blocker use on prognosis. Furthermore, one-to-one propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analyses were used to control for systemic differences between groups. The primary outcome was long-term CVM.RESULTS:Among the enrolled subjects, 972 (85.9%) were prescribed with β-blockers at discharge. Over a mean follow-up of 26.3 months, 224 cardiovascular deaths were recorded. Both univariate [hazard ratio (HR), 1.41, 95% confidence interval (CI) 0.93-2.13] and multivariate (HR, 1.29, 95% CI 0.79-2.10) Cox regression analyses showed that β-blocker use had no significant association with the long-term CVM, which was further demonstrated by PSM (HR, 1.31, 95% CI 0.75-2.28) and IPTW (HR, 1.41, 95% CI 0.73-2.69) analyses. Subgroup analyses according to sex, heart rate, hypertension, diabetes, revascularization, left ventricular ejection fraction, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use showed consistent results as well.CONCLUSION:Our findings first suggested that the use of β-blockers at discharge in oldest old with AMI was not useful for reducing post-discharge CVM, which need to be further verified by randomized controlled trials.
European geriatric medicine 2024
Background:Although experimental studies have demonstrated the protective role of total bilirubin (TBil) in cardiovascular diseases, several previous clinical observations are controversial. More importantly, no data are currently available regarding the relation of TBil to major adverse cardiovascular events (MACE) in patients with previous myocardial infarction (MI).Objectives:This study sought to explore the association between TBil and long-term clinical outcomes in patients with previous MI.Methods:A total of 3,809 patients who are post-MI were consecutively enrolled in this prospective study. Cox regression models using HRs and CIs were applied to investigate associations between the TBil concentration category (group 1: bottom to median tertiles within the reference range; group 2: top tertile; group 3: above reference range) and main outcome (recurrent MACE) as well as secondary outcomes (hard endpoints and all-cause mortality).Results:During the 4-year follow-up period, 440 patients (11.6%) suffered from recurrent MACE. Kaplan-Meier survival analysis showed the lowest MACE incidence in group 2 (P < 0.001). When compared with the reference group (group 1) in multivariable analysis, a J-shaped association was apparent for MACE, with decreased risk in group 2 (HR: 0.76; 95% CI: 0.59-0.96) and elevated risk in group 3 (HR: 1.29; 95% CI: 1.03-1.61). Similar associations were identified regarding hard endpoints and all-cause mortality. Moreover, TBil demonstrated incremental discriminatory strength when added to the predictive model.Conclusions:In this prospective cohort study with long-term follow-up, higher TBil levels within the physiological range reduced the incidence of long-term cardiovascular events in patients who are post-MI.
JACC. Asia 2023
BACKGROUND:Thyroid dysfunction might have a negative impact on the prognosis of patients with heart failure (HF) and affect the lipid metabolism. The aim of our study was to investigate the prognostic role of thyroid dysfunction and its relationship with lipid profile in hospitalized HF patients.HYPOTHESIS:Thyroid dysfunction strongly correlates with prognosis of HF patients and combination with lipid profile improves the prognostic value.METHODS:We performed a single-center retrospective cohort study including hospitalized HF patients between March 2009 and June 2018.RESULTS:Among enrolled 3733 patients, low fT3 (hazard ratio [HR] 1.33; 95% CI: 1.15-1.54; p < .001), elevated TSH (HR 1.37; 95% CI 1.15-1.64; p < .001), LT3S (HR 1.39; 95% CI: 1.15-1.68; p < .001), overt hyperthyroidism (HR 1.73; 95%CI: 1.00-2.98; p = .048), subclinical hypothyroidism (HR 1.43; 95%CI: 1.13-1.82; p = .003) and overt hypothyroidism (HR 1.76; 95%CI: 1.33-2.34; p < .001) independently increased the risk of composite endpoint defined as the combination of all-cause mortality, heart transplantation, or left ventricular assist device requirement. Higher total cholesterol (HR 0.64; 95%CI: 0.49-0.83; p < .001) was still a protective factor in HF patients. When divided into four groups by fT3 and median lipid profiles, comparison of Kaplan-Meier survival curves for various groups showed good risk stratification (p < .001).CONCLUSION:LT3S, overt hyperthyroidism, subclinical and overt hypothyroidism were independently associated with poor outcomes in HF. The combination of fT3 and lipid profile improved the prognostic value.
Clinical cardiology 2023
AIMS:Heart failure (HF) and sleep-disordered breathing (SDB) frequently coexist. We aimed to compare the prognostic value of different nocturnal hypoxic burden metrics in hospitalized HF patients.METHODS AND RESULTS:HF patients underwent polygraphy screening for SDB in this prospective cohort. Hypoxic burden metrics assessed using pulse oximetry included time < 90% oxygen saturation (T90), proportion of total recording time < 90% oxygen saturation (TRT90), oxygen desaturation index (ODI), and mean oxygen saturation (meanSO2 ). The prespecified endpoints were the composite of cardiovascular death or admission for worsening HF. This study included 764 hospitalized HF patients, 16.5% and 36.6% of whom had obstructive and central sleep apnoea, respectively. With a median follow-up time of 2.2 years, endpoint events occurred in 410 (53.7%) patients. In univariate and multivariate analyses, T90, TRT90, and meanSO2 were substantially associated with the composite outcome, whereas ODI was not. After multivariate Cox model adjustment, patients with 5.0 ≤ T90 ≤ 52.0 min [hazard ratio (HR) 1.32, 95% confidence interval (CI): 1.02-1.71, P = 0.034] or T90 > 52.0 min (HR 1.56, 95% CI: 1.21-2.02, P = 0.001) had a greater risk of the composite outcome than those with T90 < 5.0 min. The TRT90 and T90 results were similar. Compared with meanSO2 > 95%, meanSO2 < 93% (HR 1.47, 95% CI: 1.16-1.88, P = 0.002) was correlated with adverse outcomes.CONCLUSIONS:The hypoxic burden metrics T90, TRT90, and meanSO2 , but not ODI, were independent predictors of cardiovascular death or readmission for worsening HF. Indicators of duration and severity, not just the frequency of nocturnal hypoxaemia, should be valued and considered for intervention to improve outcomes in HF patients.
ESC heart failure 2023
BACKGROUND:the relationship between low-density lipoprotein cholesterol (LDL-C) and adverse outcomes among the older people remains controversial.OBJECTIVE:to further clarify the association between admission LDL-C levels and cardiovascular mortality (CVM) among oldest old individuals (≥80 years) with acute myocardial infarction (AMI).DESIGN:a prospective cohort study.SETTING:two-centre.SUBJECTS:a consecutive sample of 1,224 oldest old individuals with AMI admitted to Beijing FuWai and Shenzhen FuWai hospitals.METHODS:all individuals were subdivided according to baseline LDL-C levels (<1.8, 1.8-2.6 and ≥ 2.6 mmol/l) and further stratified by high-sensitivity C-reactive protein (hsCRP) concentrations (<10 and ≥10 mg/l). The primary outcome was CVM. The time from admission to the occurrence of CVM or the last follow-up was analysed in Kaplan-Meier and Cox analyses.RESULTS:the median age of the overall population was 82 years. During an average of 24.5 months' follow-up, 299 cardiovascular deaths occurred. Kaplan-Meier analysis showed that LDL-C < 1.8 mmol/l group had the highest CVM among oldest old individuals with AMI. Multivariate Cox regression analysis further revealed that compared with those with LDL-C levels <1.8 mmol/l, subjects with LDL-C levels ≥2.6 mmol/l (hazard ratio: 0.67, 95% confidence interval: 0.46-0.98) had significantly lower risk of CVM, especially in those with high hsCRP levels. Moreover, when categorising according to LDL-C and hsCRP together, data showed that individuals with low LDL-C and high hsCRP levels had the highest CVM.CONCLUSIONS:LDL-C < 1.8 mmol/l was associated with a high CVM after AMI in oldest old individuals, especially when combined with high hsCRP levels, which may need to be confirmed by randomised controlled trials.
Age and ageing 2022
Background and Aims:Heterogeneity exists among patients with atherosclerotic cardiovascular disease (ASCVD) with regard to the risk of recurrent events. Current guidelines have definitely refined the disease and we aimed to examine the practicability in Chinese population.Methods:A cohort of 9944 patients with ASCVD was recruited. Recurrent events occurred during an average of 38.5 months' follow-up were collected. The respective and combinative roles of major ASCVD (mASCVD) events and high-risk conditions, being defined by 2018 AHA/ACC guideline, in coronary severity and outcome were studied.Results:The number of high-risk conditions was increased with increasing number of mASCVD events (1.95 ± 1.08 vs. 2.16 ± 1.10 vs. 2.42 ± 1.22). Trends toward the higher to the highest frequency of multi-vessel coronary lesions were found in patients with 1- (71.1%) or ≥2 mASCVD events (82.8%) when compared to those without (67.9%) and in patients with 2- (70.5%) or ≥3 high-risk conditions (77.4%) when compared to those with 0-1 high-risk condition (61.9%). The survival rate was decreased by 6.2% between none- and ≥2 mASCVD events or by 3.5% between 0-1 and ≥3 high-risk conditions. Interestingly, diabetes was independently associated with outcome in patients with 1- [1.54(1.06-2.24)] and ≥2 mASCVD events [1.71(1.03-2.84)]. The positive predictive values were increased among groups with number of mASCVD event increasing (1.10 vs. 1.54 vs. 1.71).Conclusion:Propitious refinement of ASCVD might be reasonable to improve the survival. Concomitant diabetes was differently associated with the incremental risk among different ASCVD categories, suggesting the need of an appropriate estimate rather than a 'blanket' approach in risk stratification.
Frontiers in endocrinology 2022
BACKGROUND:Lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular diseases, while its role in vascular calcification has not been well-established. Here, we investigated an association of Lp(a) with vascular calcification using population-based and in vitro study designs.METHODS:A total of 2806 patients who received coronary computed tomography were enrolled to assess the correlation of Lp(a) with the severity of coronary artery calcification (CAC). Human aortic smooth muscle cells (HASMCs) were used to explore mechanisms of Lp(a)-induced vascular calcification.RESULTS:In the population study, Lp(a) was independently correlated with the presence and severity of CAC (all p < 0.05). In vitro study showed that cell calcific depositions and alkaline phosphatase (ALP) activity were increased and the expression of pro-calcific proteins, including bone morphogenetic protein-2 (BMP2) and osteopontin (OPN), were up-regulated by Lp(a) stimulation. Interestingly, Lp(a) activated Notch1 signaling, resulting in cell calcification, which was inhibited by the Notch1 signaling inhibitor, DAPT. Lp(a)-induced Notch1 activation up-regulated BMP2-Smad1/5/9 pathway. In contrast, Noggin, an inhibitor of BMP2-Smad1/5/9 pathway, significantly blocked Lp(a)-induced HASMC calcification. Notch1 activation also induced translocation of nuclear factor-κB (NF-κB) accompanied by OPN overexpression and elevated inflammatory cytokines production, while NF-κB silencing alleviated Lp(a)-induced vascular calcification.CONCLUSIONS:Elevated Lp(a) concentrations are independently associated with the presence and severity of CAC and the impact of Lp(a) on vascular calcification is involved in the activation of Notch1-NF-κB and Notch1-BMP2-Smad1/5/9 pathways, thus implicating Lp(a) as a potential novel therapeutic target for vascular calcification.
Metabolism: clinical and experimental 2022
