Corrigendum: The value of HDL subfractions in predicting cardiovascular outcomes in untreated, diabetic patients with stable coronary artery disease: an age- and gender-matched case-control study.

[This corrects the article DOI: 10.3389/fendo.2022.1041555.].

Clinical impact of blood pressure on cardiovascular death in patients 80 years and older following acute myocardial infarction: a prospective cohort study.

Numerous trials have shown that lowering blood pressure (BP) reduces cardiovascular risk and mortality, yet data about the impact of BP on cardiovascular death risk in patients aged ≥80 years with acute myocardial infarction (AMI) are sparse. This study explored the prognostic value of BP for cardiovascular death during the first 48 h after admission following AMI among patients aged ≥80 years. A total of 1005 patients ≥80 years with AMI were enrolled. Average BP parameters, including systolic, diastolic, and pulse BP, over the first 48 h after admission were calculated. The end point was cardiovascular death. Receiver operating curve (ROC) analysis was used to identify whether BP was relevant to cardiovascular death. The relationship between BP levels and cardiovascular death was evaluated by Cox regression models. ROC analysis showed that average diastolic blood pressure (aDBP), but not systolic and pulse BP, was relevant to cardiovascular death, and the optimal cutoff was 65 mmHg. During the 2.9-year follow-up, patients who died from a cardiovascular cause had lower aDBP levels than those who did not (p = 0.002). Patients with aDBP <65 mmHg had a 1.5-fold higher incidence of cardiovascular death than those with aDBP ≥65 mmHg (35.9% vs. 24.0%; p < 0.001). In multivariable regression analysis, low aDBP remained a strong and independent predictor of cardiovascular death (adjusted hazard ratio 1.907; 95% CI 1.303-2.792). aDBP was independently associated with cardiovascular death in patients aged ≥80 years with AMI, suggesting that aDBP may be a useful index to predict worse outcome in these patients.

Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Different Metabolic Phenotypes.

Background: The positive relationship between metabolic healthy obesity (MHO) and cardiovascular risk has been under debate in recent years. Previously, strong evidence supported the causal role of increased plasma lipoprotein(a) [Lp(a)] levels in cardiovascular disease (CVD). The current study aimed to investigate the different associations of Lp(a) and cardiovascular events (CVEs) in patients with coronary artery disease (CAD) and different metabolic phenotypes. Methods: A total of 5,089 patients who were angiography-proven CAD were consecutively included and followed up for CVEs. Obesity was defined as a body mass index (BMI) ≥25 kg/m2 according to Asia-specific BMI criteria. Patients were divided into four groups according to metabolic phenotypes, namely metabolically healthy/unhealthy non-obese and metabolically healthy/unhealthy obese [metabolically healthy non-obese (MHN), MHO, metabolically unhealthy non-obese (MUN), and metabolically unhealthy obesity (MUO)]. Comparisons of CAD severity and outcomes were performed among four groups. Cox regression analyses and cubic spline models were used to examine the relationship between Lp(a) and CVEs in patients with different metabolic phenotypes. Results: During a median of 7.5 years' follow-up, 540 (10.6%) CVEs occurred. MUN and MUO populations had more severe coronary stenosis than MHN ones, while no significant difference in the Gensini score (GS) was observed between MHN and MHO. Patients with MUN and MUO presented a higher risk of CVEs than patients with MHN (hazard ratio [HR]: 1.414, 95% CI: 1.024-1.953-1.556 and HR: 1.747, 95% CI: 1.295-1.363, p < 0.05). In subgroup analysis, restricted cubic spline models showed that there was no association between Lp(a) and CVEs in patients in MHN and MHO, while the MUN and MUO groups presented increasing associations between Lp(a) and CVEs and such association was stronger in the MUO group. In Cox regression analysis, Lp(a) >50 mg/dl was associated with a 2.032- and 2.206-fold higher risk of subsequent CVEs in the MUO and MUN subgroups, respectively. Conclusion: Among patients with angiography-proven stable CAD, Lp(a) had a more significant prognostic value in both MUO and MUN individuals regardless of obesity, suggesting the importance of screening for cardiovascular risk with Lp(a) in metabolically unhealthy patients.

Three-Dimensional Morphology and Configuration Analyses of the Craniovertebral Junction in Children with Hemifacial Microsomia.

STUDY DESIGN: Observational and morphological study with three-dimensional (3D) computed tomography (CT) analysis. OBJECTIVE: To discover the morphology and configuration deformities of craniovertebral junction (CVJ) and upper cervical spine in children with unilateral hemifacial microsomia (HFM). To determine whether there are specific HFM patients who are at higher risk of certain cervical vertebral anomaly. SUMMARY OF BACKGROUND DATA: The evaluation for cervical vertebrae anomaly in HFM children, especially in CVJ region, is underreported. METHODS: Eighty-eight unilateral HFM children (64 males, 24 females) with four Pruzansky-Kaban types (I, Ila, Ilb, and III) underwent cranial and cervical CT scanning from skull to C5 in neutral position. The 3D morphology and configuration of the occipital condyle, atlas, and axis, etc. were evaluated on the presence of deformed detailed structures of CVJ region. RESULTS: No C1 deformation was found in type I group. Six (14.3%) type Ila cases, seven (33.3%) type IIb cases, and six (37.5%) type Ill cases had lateral masses asymmetry of C1 (P  < 0.05). Five (55.6%) type I cases, 17 (40.5%) type Ila cases, 12 (57.1%) type Ilb cases, and 10 (62.5%) type Ill cases had C2 anomaly (P > 0.05). The incidence rate of C1-C2 instability for four groups were 33.3% (type I), 33.3% (type IIa), 33.3% (type IIb), and 31.3% (type Ill), respectively (P > 0.05). CONCLUSION: For HFM children, the incidence of C1 deformation increased from type I to type Ill. The probability of C2 anomaly and C1-C2 instability in children with different types of HFM is nearly the same. The craniovertebral junction of every HFM child must be monitored carefully for C1-C2 instability before any surgical procedure to avoid atlantoaxial dislocation and spinal cord injury.Level of Evidence: N/A.

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.

Association of diabetes mellitus with clinical outcomes in patients with different coronary artery stenosis.

BACKGROUND: It has been demonstrated that patients with type 2 diabetes mellitus (DM) is associated with increased cardiovascular risk. However, little is known regarding the long-term prognosis in diabetic patients who experience mild-to-intermediate coronary artery stenosis (CAS). This study was to assess the clinical outcomes of diabetic patients with different severity of CAS. METHODS: We consecutively enrolled 10,940 patients hospitalized due to angina-like chest pain and followed up for major adverse cardiovascular events (MACEs) covering cardiac death, myocardial infarction, ischemic stroke, unplanned coronary revascularization and angina-related hospitalization. According to coronary angiography, patients were divided into non-obstructive CAS (NOCAS, < 50% stenosis), intermediate CAS (ICAS, 50-69% stenosis), and severe CAS (SCAS, 70-100% stenosis) subgroups, and were further categorized into six groups as NOCAS with DM and non-DM, ICAS with DM and non-DM, and SCAS with DM and non-DM. RESULTS: During a median follow-up of 40 months, 1,017 (11.1%) MACEs occurred. In patients with ICAS or SCAS, the incidence of events was higher when patients coexisted with DM (p < 0.05, respectively). In subgroup analyses, patients with ICAS and DM, SCAS and non-DM, SCAS and DM had increased risk of events [adjusted hazard ratio (HR): 1.709, 95% confidence interval (CI) 1.106-2.641, p = 0.016; HR: 1.911, 95% CI 1.460-2.501, p < 0.001; HR: 2.053, 95% CI 1.514-2.782, p < 0.001] compared to ones with NOCAS and non-DM. Besides, the Kaplan-Meier curves indicated the highest risk of MACEs in patients with SCAS and DM than others (p < 0.001). CONCLUSIONS: Diabetic patients with ICAS had the worse outcome, which was comparable to patients with SCAS alone.

Metabolic-associated fatty liver disease and major adverse cardiac events in patients with chronic coronary syndrome: a matched case-control study.

BACKGROUND AND AIMS: A consensus of experts suggests that nonalcoholic fatty liver disease (NAFLD) does not appropriately reflect current knowledge and metabolic-associated fatty liver disease (MAFLD) is supposed to be a more suitable overarching concept. However, the association of MAFLD with cardiovascular outcomes in patients with coronary artery disease has not been examined yet. Thus, this study aimed to assess the impact of MAFLD on major adverse cardiac events (MACEs) in patients with chronic coronary syndrome (CCS). METHODS: This study included 3306 patients with CCS who were diagnosed with MAFLD. Controls without MAFLD were matched (1:1) to cases by age and gender. All participants were followed up for the occurrence of MACEs. Finally, the association between MAFLD and the risk of MACEs was assessed. RESULTS: During an average of 55.09 ± 19.92 months follow-up, 376 and 248 MACEs were observed in MAFLD and control groups, respectively. When compared with controls, Kaplan-Meier analysis showed that patients with MAFLD had significantly lower event-free survival rate and multivariate Cox regression analysis further revealed that MAFLD group had significantly increased MACEs risk (both p < 0.05). Stratification analysis suggested that patients with MAFLD overlapped with NAFLD or MAFLD-only had 1.33-fold and 2.32-fold higher risk of MACEs respectively compared with controls (both p < 0.05). CONCLUSION: This study firstly showed that MAFLD was significantly associated with the risk of MACEs in patients with CCS. Moreover, this relationship remained unchanged irrespective of whether satisfying the NAFLD criteria, providing novel evidence for the good utility of MAFLD criteria in clinical practice.

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.

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.

Prognostic value of NT-proBNP in patients with chronic coronary syndrome and normal left ventricular systolic function according to glucose status: a prospective cohort study.

BACKGROUND: The prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with coronary artery disease (CAD) with different glucose status has not been established. This study sought to evaluate the significance of NT-proBNP in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) and normal left-ventricular systolic function (LVSF) according to different glucose status, especially in those with abnormal glucose metabolism. METHODS: A total of 8062 patients with CCS and normal LVSF were consecutively enrolled in this prospective study. Baseline plasma NT-proBNP levels were measured. The follow-up data of all patients were collected. Kaplan-Meier and Cox regression analyses were used to assess the risk of MACEs according to NT-proBNP tertiles stratified by glucose status. RESULTS: Over an average follow-up of 59.13 ± 18.23 months, 569 patients (7.1 %) suffered from MACEs, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Kaplan-Meier analysis showed that high NT-proBNP levels had a significant association with MACEs in subjects with prediabetes mellitus (pre-DM) or DM, but not in patients with normoglycemia. Multivariate Cox regression analysis revealed that NT-proBNP remained an independent predictor of MACEs in patients with pre-DM [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.34-4.91] or DM (HR: 2.34, 95% CI: 1.32-4.16). Moreover, adding NT-proBNP to the original Cox model including traditional risk factors significantly increased the C-statistic by 0.035 in pre-DM and DM, respectively. CONCLUSIONS: The present study indicated that NT-proBNP could well predict worse outcomes in dysglycemic patients with CCS and normal LVSF, suggesting that NT-proBNP may help with risk stratification in this population.

Plasma proprotein convertase subtilisin/kexin type 9 concentration and recurrent cardiovascular events in patients with familial hypercholesterolemia.

AIMS: Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined. METHODS: A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval. RESULTS: Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan-Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11-1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events. CONCLUSIONS: Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.

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.

Impact of liver fibrosis score on prognosis in patients with previous myocardial infarction: A prospective cohort study.

BACKGROUND & AIMS: Liver fibrosis score (LFS) has been used for predicting the cardiovascular outcomes (CVOs) in diverse populations. However, the association of LFS with CVOs in patients with previous myocardial infarction (MI) remains undetermined. We aimed to examine the prognostic value of LFS in patients with prior MI in a prospective cohort. METHODS: A total of 3718 patients with previous MI were consecutively enrolled from March 2009 to January 2019. Five LFSs including the fibrosis-4 (FIB-4) score, non-alcohol fatty liver disease fibrosis score (NFS), Forns score, HUI score and BARD score were used. The CVOs covered major adverse cardiac event (MACEs), cardiovascular mortality and all-cause mortality. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a mean follow-up of 47.4 ± 24.8 months, 431 (11.6%) MACEs occurred. Kaplan-Meier analysis demonstrated that higher LFSs resulted in a significantly higher probability of CVOs. Compared to the lowest score group, multivariable-adjusted HRs (95% CIs) of the highest group of FIB-4, NFS, Forns score, HUI score and BARD score were 1.75 (1.32-2.33), 2.37 (1.70-3.33), 2.44 (1.61-3.73), 1.58 (1.16-2.14) and 1.27 (1.03-1.57) respectively. These LFSs were also independent predictors of cardiovascular mortality and all-cause mortality. Similar results were observed across subgroups analysis. The addition of LFSs to a prediction model significantly increased the C-statistic for CVOs. CONCLUSIONS: The present study firstly demonstrated that LFS could be used as a risk stratification tool for predicting CVOs in patients with previous MI, which should be evaluated further.

Atherogenic dyslipidaemia and cardiovascular events in patients with diabetes or pre-diabetes and stable coronary artery disease: a prospective, cohort study.

OBJECTIVE: The aim of the study was to investigate the impacts of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) dyslipidaemia on prognosis in coronary artery disease (CAD) patients with different glucose metabolism status. DESIGN: An observational cohort study. SETTING/PARTICIPANTS: A total of 3057 patients with stable CAD were consecutively enrolled and divided into three groups according to different glucose metabolism status. Atherogenic dyslipidaemia (AD) was defined as TG ≥1.7 mmol/L and HDL-C <1.0 mmol/L for men or <1.3 mmol/L for women. The patients were further classified into six subgroups by status of AD. All subjects were followed up for the cardiovascular events (CVEs). PRIMARY OUTCOME MEASURES: The primary endpoints were cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke. RESULTS: During a median follow-up of 6.1 years, 308 (10.1%) CVEs occurred. No significant difference in the occurrence of CVEs was observed between normal glucose regulation (NGR) and pre-diabetes (pre-DM) groups (HR: 1.25, 95% CI 0.89 to 1.76) while DM group presented 1.45-fold higher risk of CVEs (HR: 1.45, 95% CI 1.02 to 2.05). When the participants were categorised according to combined status of two parameters, the cardiovascular risk was significantly elevated in pre-DM or DM plus AD group compared with the NGR plus non-AD group (HR: 1.76, 95% CI 1.10 to 2.80 and HR: 1.87, 95% CI 1.17 to 2.98). CONCLUSIONS: The present study suggested that the presence of AD might affect the prognosis in patients with DM or pre-DM and stable CAD.

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.

Improvement of Definite Diagnosis of Familial Hypercholesterolemia Using an Expanding Genetic Analysis.

Background: The deeper understanding of the complex hereditary basis of familial hypercholesterolemia (FH) has raised the rationale of genetic testing, which has been underutilized in clinical practice. Objectives: The present study aimed to explore the variant spectrum of FH in an expanding manner and compare its diagnostic performance. Methods: A total of 169 Chinese individuals (124 index cases and 45 relatives) with clinical definite/probable FH were consecutively enrolled. Next-generation sequencing was performed for genetic analysis of 9 genes associated with hypercholesterolemia (major genes: LDLR, APOB, and PCSK9; minor genes: LDLRAP1, LIPA, STAP1, APOE, ABCG5, and ABCG8) including the evaluations of small-scale variants and large-scale copy number variants (CNVs). Results: Among the 169 clinical FH patients included, 98 (58.0%) were men. A total of 85 (68.5%) index cases carried FH-associated variants. The proportion of FH caused by small-scale variants in LDLR, APOB, and PCSK9 genes was 62.1% and then increased by 6.5% when other genes and CNVs were further included. Furthermore, the variants in LDLR, APOB, and PCSK9 genes occupied 75% of all FH-associated variants. Of note, there were 8 non-LDLR CNVs detected in the present study. Conclusions: LDLR, APOB, and PCSK9 genes should be tested in the initial genetic screening, although variants in minor genes also could explain phenotypic FH, suggesting that an expanding genetic testing may be considered to further explain phenotypic FH.

Lipoprotein(a) as a predictor for the presence and severity of premature coronary artery disease: a cross-sectional analysis of 2433 patients.

BACKGROUND: Lipoprotein(a) [Lp(a)] has been emerged as a risk factor for coronary artery disease (CAD), but there is currently insufficient data on the relationship between Lp(a) and premature CAD (PCAD). Thus, this study aimed to examine the association between Lp(a) and PCAD in a Chinese cohort. METHODS: Data on 2433 individuals (male <55 years old and female <65 years old) who underwent coronary angiography from March 2016 to February 2019 were included in this study and were divided into the PCAD group (n = 1751) and non-CAD group (n = 682) according to the angiography results. Their clinical and laboratory parameters were collected, and plasma Lp(a) level was measured by immunoturbidimetry. The severity of CAD was evaluated using Gensini score (GS) and divided into three subgroups. The relationship between plasma Lp(a) levels and the presence and severity of PCAD was analyzed. RESULTS: The level of plasma Lp(a) in the PCAD group was significantly higher than that in the non-CAD group (P < 0.001). The plasma Lp(a) concentration in the highest GS group was significantly higher than that in the lowest GS group (P < 0.001). Multivariate linear regression analysis showed that elevated plasma Lp(a) levels were correlated with higher GS (b = 0.41, P < 0.001). Multivariate logistic regression showed that elevated plasma Lp(a) levels were independently associated with PCAD (odds ratio = 2.91, P < 0.001). Moreover, elevated plasma Lp(a) levels correlated with higher GS (b = 0.41, P < 0.001). CONCLUSION: In this study, Lp(a) concentration was associated with the presence and severity of PCAD, suggesting that Lp(a) may be a marker or target for patients with PCAD.

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.

Lipoprotein(a) and Cardiovascular Outcomes in Patients with Previous Myocardial Infarction: A Prospective Cohort Study.

Lipoprotein(a) [Lp(a)] has been documented to be associated with atherothrombotic diseases. However, the prognostic impact of Lp(a) on long-term clinical outcomes among patients with previous myocardial infarction (MI) remains unclear. In this prospective cohort study, we consecutively enrolled 3,864 post-MI patients to assess the cardiovascular events (CVEs), including MI, ischemic stroke, and cardiac mortality. Lp(a) levels were determined using an immunoturbidimetry assay and the participants were categorized according to Lp(a) quartiles. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). During a median follow-up of 4.1 years, 331 (8.6%) CVEs were identified. Lp(a) was significantly higher in patients with CVEs (25.17 [11.13-47.83] vs. 18.18 [7.90-40.30] mg/dL, p = 0.001). The cumulative rates of CVEs and cardiac mortality were significantly higher in patients with high Lp(a) levels (both log-rank p < 0.001). Multivariate Cox regression analysis showed a significant correlation between Lp (a) levels treated as a natural logarithm-transformed continuous variable and increased CVEs (adjusted HR:1.22, 95% CI:1.09-1.35, p = 0.001) or cardiac mortality (HR:1.30, 95% CI:1.14-1.48, p < 0.001). The addition of Lp(a) to a prognostic model revealed a significant improvement in C-statistic, net reclassification, and integrated discrimination. In conclusion, elevated levels of Lp(a) were indeed associated with long-term worse outcomes in patients with prior MI, suggesting a novel hint that the measurement of Lp(a) might help in risk stratification and future management in those high-risk individuals.

Heart-type fatty acid binding protein predicts cardiovascular events in patients with stable coronary artery disease: a prospective cohort study.

BACKGROUND: Heart-type fatty acid binding protein (H-FABP) has been reported to be a prognostic predictor for cardiovascular outcome in acute coronary syndrome (ACS). However, its prognostic utility in patients with stable coronary artery disease (CAD) has not been well established. The aim of this study was to assess the association between H-FABP with the severity of coronary disease and cardiovascular events (CVEs) in patients with stable CAD. METHODS: A total of 4,370 angiography-proven CAD patients were consecutively enrolled. The severity of CAD was assessed by Gensini Score (GS) and the numbers of diseased vessels. The CVEs included cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the relation of H-FABP to CVEs in this cohort. RESULTS: During a median follow-up of 51 months, 353 CVEs occurred. Overall, patients in the highest levels of H-FABP group had increased rate of multi-vessel stenosis and higher GS compared with those in the lowest group (P<0.05, respectively). Moreover, H-FABP levels were significantly higher in patients with events compared to those without (P<0.001). In Cox regression analysis, elevated H-FABP levels were found to be independently associated with a high risk of CVEs [adjusted HRs: 1.453; 95% confidence intervals (CIs): 1.040-2.029, P=0.028], especially with cardiovascular death (adjusted HRs: 2.865; 95% CI: 1.315-6.243, P=0.008). CONCLUSIONS: Our results demonstrated that H-FABP was also a useful predictor for CVEs in patients with stable CAD, which needed to be verified by further studies.