曹晔萱

中国医学科学院阜外医院 心血管内科

Circulating Total Bilirubin and Long-Term Prognosis in Patients With Previous Myocardial Infarction.

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.

第一作者

JACC. Asia 2023

Remnant cholesterol as a lipid-lowering target may have a long way to go.

39.3
1区
第一作者

European heart journal 2023

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study.

BACKGROUND:The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown.METHODS:A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs.RESULTS:158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels.CONCLUSIONS:This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

4.5
2区

Lipids in health and disease 2022

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein in Patients With Previous Myocardial Infarction.

Background:Patients with previous myocardial infarction (MI) have a poor prognosis and stratification for recurrent major adverse cardiovascular events (MACE) among these patients is of considerable interest. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) are considered to be potential cardiovascular risk factors, but less is known about their prognostic importance in post-MI patients. This study aimed to evaluate the prognostic value of NT-proBNP and hs-CRP alone or together in patients who reported a prior MI.Methods:In this prospective study, we consecutively enrolled 3,306 post-MI patients to assess the recurrent MACE. The predictive values of NT-proBNP and hs-CRP alone and together were assessed by multivariable Cox regression using hazard ratios (HR) and 95% confidence intervals (CI).Results:During the 4-year follow-up period, 335 patients developed recurrent MACE. Multivariate Cox regression analysis showed a significant correlation between NT-proBNP levels and MACE (HR: 2.99, 95%CI: 2.06-4.36, p < 0.001), hard endpoints (HR: 5.44, 95%CI: 2.99-9.90, p < 0.001), cardiac mortality (HR: 5.92, 95%CI: 2.34-14.96, p < 0.001) and all-cause mortality (HR: 5.03, 95%CI: 2.51-10.09, p < 0.001). However, hs-CRP was not an independent predictor after adjusting for NT-proBNP. When patients were divided into six groups by using tertiles values of NT-proBNP and median values of hsCRP, patients with high NT-proBNP/hs-CRP values were 3.27 times more likely to experience MACE than patients with low NT-proBNP/hs-CRP values. The addition of NT-proBNP and hs-CRP to a prognostic model revealed a significant improvement in C-statistic, net reclassification, and integrated discrimination.Conclusions:Increased NT-proBNP levels were associated with long-term worse outcomes and the combination of NT-proBNP and hs-CRP has an incremental value in the further risk stratification of post-MI patients.

3.6
3区
第一作者

Frontiers in cardiovascular medicine 2022

Liver fibrosis scores and coronary atherosclerosis: novel findings in patients with stable coronary artery disease.

BACKGROUND:Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up.METHODS:A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively.RESULTS:During a median follow-up of 7 years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan-Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs [hazard ratio (95% confidence interval): 1.150 (1.063-1.244), p < 0.001 and 1.128 (1.026-1.240), p = 0.012].CONCLUSION:The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs.CLINICAL TRIALS REGISTRATION:None.

6.6
2区

Hepatology international 2021

Liver Fibrosis Scoring Systems as Novel Tools for Predicting Cardiovascular Outcomes in Patients Following Elective Percutaneous Coronary Intervention.

Background Previous studies have suggested a strong association of liver fibrosis scores (LFSs) with cardiovascular outcomes in patients with different cardiovascular diseases. Nonetheless, it is basically blank regarding the prognostic significance of LFSs in patients following percutaneous coronary intervention (PCI). This study sought to examine the potential role of LFSs in predicting long-term outcomes in a large cohort of patients with stable coronary artery disease after elective PCI. Methods and Results In this multicenter, prospective study, we consecutively enrolled 4003 patients with stable coronary artery disease undergoing PCI. Eight currently available noninvasive LFSs were assessed for each subject. All patients were followed up for the occurrence of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average follow-up of 5.0±1.6 years, 315 (7.87%) major cardiovascular events were recorded. Subjects who developed cardiovascular events were more likely to have intermediate or high LFSs, including nonalcoholic fatty liver disease fibrosis score; fibrosis-4 score; body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score (BARD); and aspartate aminotransferase/alanine aminotransferase ratio. Furthermore, compared with subjects with low scores, those with intermediate plus high score levels had significantly increased risk of cardiovascular events (adjusted hazard ratios ranging 1.57-1.92). Moreover, the addition of non-alcoholic fatty liver disease fibrosis score; fibrosis-4 score; or body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score into a model with established cardiovascular risk factors significantly improved the prediction ability. Conclusions High LFSs levels might be useful for predicting adverse prognosis in patients with stable coronary artery disease following PCI, suggesting the possibility of the application of LFSs in the risk stratification before elective PCI.

5.4
1区

Journal of the American Heart Association 2021

Association of small dense LDL-cholesterol with disease severity, hypertension status and clinical outcome in patients with coronary artery disease.

OBJECTIVE:Previous studies have demonstrated that small dense LDL-cholesterol (sdLDL-C) is related to the pathogenesis of coronary artery disease (CAD). However, its prognostic role in hypertensive patients with CAD has been undetermined. The aim of the study was to investigate the association between sdLDL-C with disease severity, hypertensive status and clinical outcome in patients with CAD.METHODS:A total of 4594 patients with angiography-proven CAD were consecutively enrolled and categorized into subgroups according to blood pressure status. Serum sdLDL-C levels were measured by direct quantitative measurement using automated chemistry analyzers. The severity of coronary artery lesions were determined by Gensini score, Syntax score and the number of lesion vessels. The associations of sdLDL-C with disease severity, hypertensive status and cardiovascular events (CVEs) were evaluated.RESULTS:Patients with hypertension had higher sdLDL-C levels than ones without (P = 0.010). In hypertensive patients, sdLDL-C was positively associated with the severity of CAD (P < 0.05). In addition, hypertensive patients with poorly controlled hypertension had higher sdLDL-C levels than those with well controlled (P < 0.05). Moreover, 149 CVEs occurred in patients with poorly controlled hypertension and Cox regression analysis indicated that elevated sdLDL-C levels were independently associated with CVEs in hypertensive patients with poorly controlled hypertension (adjusted hazard ratio: 1.673, 95% confidence interval: 1.105-2.535, P = 0.015).CONCLUSION:The current data, for the first time, showed that serum sdLDL-C levels were correlated with hypertension control, disease severity and worse outcomes in hypertensive patients with CAD, suggesting that paying more attention on sdLDL-C in these patients were warranted.

4.9
2区

Journal of hypertension 2021

Visit-to-visit variability of lipid and cardiovascular events in patients with familial hypercholesterolemia.

BACKGROUND:Visit-to-visit variability in lipid has been suggested as a predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy.METHODS:A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in the triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM).RESULTS:During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In the multivariate Cox analysis, only Lp(a)-related parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV, and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival. The results were consistent in various subgroups.CONCLUSIONS:Our study firstly suggested that Lp(a) variability was associated with MACEs in real-world patients with FH, which emphasized the importance of regular lipid monitoring in the patients with high risk.

4区
第一作者

Annals of translational medicine 2021

The difference between fasting and non-fasting lipid measurements is not related to statin treatment.

BACKGROUND:Non-fasting blood samples are routinely used to assess plasma lipid profiles except in patients with severe hypertriglyceridemia according to the previous consensus. However, the impact of statin use on non-fasting plasma lipid measurements has not been thoroughly evaluated.METHODS:In this cross-sectional study, 686 patients with normal triglyceride (TG) levels, who were hospitalized due to chest pain, were enrolled. Fasting (8-12 h) and non-fasting (2-4 h after breakfast) lipid profiles were measured on the second day of admission. Patients were divided into the non-statin (n=499) group and statin treatment (n=187) group. Differences in fasting and non-fasting lipid profiles between the statin and non-statin groups were compared.RESULTS:The mean age of participants was 57±13 years, and 54.4% were male. A linear correlation was observed between fasting and non-fasting lipid profiles. Although a postprandial impact on lipid parameters was observed, the general pattern of differences between fasting and non-fasting lipids was similar in both groups. Additionally, the diff(%) [(non-fasting-fasting)/fasting ×100%] of lipid panels did not vary by statin treatment. Moreover, no effects of statin types or duration of use on non-fasting lipid profiles were identified.CONCLUSIONS:The current study found fasting and non-fasting lipid panels were similar in individuals with or without statin treatment. Non-fasting lipid panels were not significantly affected by statin types or duration of use, suggesting that non-fasting lipid measurement is an acceptable test for patients receiving statin treatment.

4区

Annals of translational medicine 2021

Lipoprotein (a), hypertension, and cardiovascular outcomes: a prospective study of patients with stable coronary artery disease.

Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10-30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11-2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.

5.4
2区

Hypertension research : official journal of the Japanese Society of Hypertension 2021