Search

Background: According to epidemiological studies, particulate matter 2.5 (PM2.5) is a significant contributor to cardiovascular disease (CVD). However, making causal inferences is difficult due to the methodological constraints of observational studies. In this study, we used two-sample Mendelian randomization (MR) to examine the causal relationship between PM 2.5 and the risk of CVD., Methods: Genome-wide association study (GWAS) statistics for PM2.5 and CVD were collected from the FinnGen and UK Biobanks. Mendelian randomization analyses were applied to explore the causal effects of PM2.5 on CVD by selecting single-nucleotide polymorphisms(SNP) as instrumental variables., Results: The results revealed that a causal effect was observed between PM2.5 and coronary artery disease(IVW: OR 2.06, 95% CI 1.35, 3.14), and hypertension(IVW: OR 1.07, 95% CI 1.03, 1.12). On the contrary, no causal effect was observed between PM2.5 and myocardial infarction(IVW: OR 0.73, 95% CI 0.44, 1.22), heart failure(IVW: OR 1.54, 95% CI 0.96, 2.47), atrial fibrillation(IVW: OR 1.03, 95% CI 0.71, 1.48), and ischemic stroke (IS)(IVW: OR 0.98, 95% CI 0.54, 1.77)., Conclusion: We discovered that there is a causal link between PM2.5 and coronary artery disease and hypertension in the European population, using MR methods. Our discovery may have the significance of public hygiene to improve the understanding of air quality and CVD risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background and Aims: The association of triglyceride-rich lipoprotein-cholesterol (TRL-C) with recurrent cardiovascular events (RCVEs) has not been studied. Moreover, whether inflammation can affect TRL-C-associated cardiovascular risk is unknown. This study sought to examine the association between TRL-C and RCVEs, and whether this relationship is modulated by systemic inflammation in statin-treated patients with coronary artery disease (CAD) and nearly normal triglyceride., Methods: In this study, 6723 CAD patients were consecutively enrolled, following a first CVE with triglyceride <2.3 mmol/L. Baseline lipid profile and high-sensitivity C-reactive protein (hsCRP) levels were determined. All patients were searched for RCVEs. The risk of RCVEs was assessed across quartiles (Q) of baseline TRL-C and further stratified by the median of hsCRP., Results: Over a mean follow-up of 58.91 ± 17.79 months, 538 RCVEs were recorded. After adjustment for potential confounders, Q4 of TRL-C was significantly associated with the risk of RCVEs, which remained unchanged after hsCRP stratification. When subjects were grouped according to both TRL-C and hsCRP levels, patients with Q4 of TRL-C and hsCRP had the highest increase of the risk of RCVEs compared with the reference group (TRL-C Q1-3 and hsCRP Q1-3; HR, 1.90; 95%CI: 1.27-2.87). Furthermore, adding TRL-C to the original predicting model led to a slight but significant improvement., Conclusions: The present analysis firstly showed that elevated TRL-C was associated with an increased RCVEs risk in statin-treated patients with CAD independent of systemic inflammation, suggesting that it might be a useful marker for risk stratification and a treatment target in this patient population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

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.

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.

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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: Previous studies have suggested that patients with diabetes mellitus (DM) have higher prevalence of atherosclerotic cardiovascular disease (ASCVD), and plasma levels of free fatty acids (FFAs) are a useful marker for predicting ASCVD. We hypothesized that FFAs could predict both coronary and carotid lesions in an individual with type 2 DM (T2DM). The present study, hence, was to investigate the relation of plasma FFA level to the presence and severity of coronary and carotid atherosclerosis in patients with T2DM., Methods: Three hundred and two consecutive individuals with T2DM who have received carotid ultrasonography and coronary angiography due to chest pain were enrolled in this study. Plasma FFAs were measured using an automatic biochemistry analyzer. Coronary and carotid severity was evaluated by Gensini score and Crouse score respectively. Subsequently, the relation of FFA levels to the presence and severity of coronary artery disease (CAD) and carotid atherosclerotic plaque (CAP) in whole individuals were also assessed., Results: Increased plasma FFA levels were found in the groups either CAD or CAP compared to those without. Patients with higher level of FFAs had a higher CAD (89.9%) and elevated prevalence of CAP (69.7%). And also, patients with higher level of FFAs had a higher Gensini and Crouse scores. Multivariate regression analysis showed that FFA levels were independently associated with the presence of CAD and CAP (OR = 1.83, 95%CI: 1.27-2.65, P = 0.001; OR = 1.62, 95%CI: 1.22-2.14, P = 0.001, respectively). The area under the curve (AUC) was 0.68 and 0.65 for predicting the presence of CAD and CAP in patients with DM respectively., Conclusions: The present study firstly indicated that elevated FFA levels appeared associated with both the presence and severity of CAD and CAP in patients with T2DM, suggesting that plasma FFA levels may be a useful biomarker for improving management of patients with T2DM.

Background: Whether plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels is a predictor for cardiovascular outcomes has currently been controversial. No data is currently available regarding the relation of PCSK9 to cardiovascular metabolic markers (CVMMs) and major adverse cardiovascular events (MACEs) in stable coronary artery disease (CAD) patients with diabetes or without diabetes., Methods: A total 1225 untreated patients with stable CAD were consecutively enrolled and their baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients followed up for the occurrence of MACEs and received standard therapy after admission. The associations of PCSK9 with CVMMs and MACEs were evaluated., Results: PCSK9 levels were positively correlated with multiple CVMMs including total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A 1c at baseline (all p < 0.05). During a median follow-up of 3.3 years, 103 (8.4%) events occurred. PCSK9 levels were higher in patients with events compared to those without (p < 0.05). The Kaplan-Meier analysis displayed that patients in high PCSK9 group had lower event-free survival than that in low group (p < 0.05). Multivariable Cox regression analysis revealed that PCSK9 levels were independently associated with MACEs in diabetic patients (adjusted hazard ratio [HR]: 1.361, 95% confidence interval [CI]: 1.037-1.785, p < 0.05). When added the combination of PCSK9 levels and diabetic status to stratifying factors, patients in high PCSK9 group appeared to have extremely high risk of subsequent MACEs with diabetes (adjusted HR: 5.233, 95% CI: 2.546-10.757, p < 0.01)., Conclusions: The present study firstly showed that elevated PCSK9 levels were related to multiple CVMMs and MACEs in stable CAD with diabetes, suggesting that plasma PCSK9 measurement could help to identify diabetic patients with CAD at higher cardiovascular risk. More studies may be needed to confirm our findings.

Background: Elevated lipoprotein(a) [Lp(a)] and fibrinogen (Fib) are both associated with coronary artery disease (CAD). The atherogenicity of Lp(a) can be partly due to the potentially antifibrinolytic categories. We hypothesize that patients with higher Lp(a) and Fib may have worse outcomes., Methods: In this prospective study, we consecutively enrolled 8,417 Chinese patients with stable CAD from March 2011 to March 2017. All subjects were divided into 9 groups according to Lp(a) (Lp(a)-Low, Lp(a)-Medium, Lp(a)-High) and Fib levels (Fib-Low, Fib-Medium, Fib-High) and followed up for CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed., Results: During a median of 37.1 months' follow-up, 395 (4.7%) CVEs occurred. The occurrence of CVEs increased by Lp(a) (3.5 vs. 5.3 vs. 5.6%, p = 0.001) and Fib (4.0 vs. 4.4 vs. 6.1%, p < 0.001) categories. When further classified into 9 groups by Lp(a) and Fib levels, the CVEs were highest in the 9th (Lp(a)-High and Fib-High) compared with the 1st (Lp(a)-Low and Fib-Low) group (7.2 vs. 3.3%, p < 0.001). The highest risk of subsequent CVEs was found in the 9 th group (HR adjusted 2.656, 95% CI 1.628-4.333, p < 0.001), which was more significant than Lp(a)-High (HR adjusted 1.786, 95% CI 1.315-2.426, p < 0.001) or Fib-High (HR adjusted 1.558, 95% CI 1.162-2.089, p = 0.003) group. Moreover, adding the combined Lp(a) and Fib increased the C-statistic by 0.013., Conclusion: Combining Fib and Lp(a) enhance the prognostic value for incident CVEs beyond Lp(a) or Fib alone.

Background: Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status., Methods: A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs., Results: During a median of 5.1 (interquartile range 3.9 to 5.9) years' follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149-2.955), 1.828 (1.165-2.867), 2.212 (1.396-3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively., Conclusions: In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.

Objective: Whether lipoprotein(a) (Lp(a)) is a predictor for recurrent cardiovascular events (RCVEs) in patients with coronary artery disease (CAD) has not been established. This study, hence, aimed to examine the potential impact of Lp(a) on RCVEs in a real-world, large cohort of patients with the first cardiovascular event (CVE)., Methods: In this multicentre, prospective study, 7562 patients with angiography-diagnosed CAD who had experienced a first CVE were consecutively enrolled. Lp(a) concentrations of all subjects were measured at admission and the participants were categorised according to Lp(a) tertiles. All patients were followed-up for the occurrence of RCVEs including cardiovascular death, non-fatal myocardial infarction and stroke., Results: During a mean follow-up of 61.45±19.57 months, 680 (9.0%) RCVEs occurred. The results showed that events group had significantly higher Lp(a) levels than non-events group (20.58 vs 14.95 mg/dL, p<0.001). Kaplan-Meier analysis indicated that Lp(a) tertile 2 (p=0.001) and tertile 3 (p<0.001) groups had significantly lower cumulative event-free survival rates compared with tertile 1 group. Moreover, multivariate Cox regression analysis further revealed that Lp(a) was independently associated with RCVEs risk (HR: 2.01, 95% CI: 1.44 to 2.80, p<0.001). Moreover, adding Lp(a) to the SMART risk score model led to a slight but significant improvement in C-statistic (∆C-statistic: 0.018 (95% CI: 0.011 to 0.034), p=0.002), net reclassification (6.8%, 95% CI: 0.5% to 10.9%, p=0.040) and integrated discrimination (0.3%, 95% CI: 0.1% to 0.7%, p<0.001)., Conclusions: Circulating Lp(a) concentration was indeed a useful predictor for the risk of RCVEs in real-world treated patients with CAD, providing additional information concerning the future clinical application of Lp(a)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status., Methods: Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals., Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. ., Conclusions: In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.

Background: Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM., Methods: A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated., Results: A total of 464 MACEs were documented. Both Kaplan-Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24-2.70, p < 0.05). However, no significant association was observed for high sdLDL plus Pre-DM or NGR., Conclusions: The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD, suggesting that sdLDL may be useful for CAD risk stratification in DM.

Background: Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM., Methods: A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs., Results: During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p = 0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05)., Conclusions: Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.

Background Although several studies have indicated that lipoprotein(a) is a useful prognostic predictor for patients following percutaneous coronary intervention (PCI), previous observations have somewhat been limited by either small sample size or short-term follow-up. Hence, this study aimed to evaluate the impact of lipoprotein(a) on long-term outcomes in a large cohort of stable coronary artery disease patients after PCI. Methods and Results In this multicenter and prospective study, we consecutively enrolled 4078 stable coronary artery disease patients undergoing PCI from March 2011 to March 2016. They were categorized according to both the median of lipoprotein(a) levels and lipoprotein(a) values of <15 (low), 15 to 30 (medium), and ≥30 mg/dL (high). All patients were followed up for occurrence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average of 4.9 years of follow-up, 315 (7.7%) cardiovascular events occurred. The events group had significantly higher lipoprotein(a) levels than the nonevents group. Compared with the low lipoprotein(a) group, Kaplan-Meier analysis showed that the high lipoprotein(a) group had a significantly lower cumulative event-free survival rate, and multivariate Cox regression analysis further revealed that the high lipoprotein(a) group had significantly increased cardiovascular events risk. Moreover, adding continuous or categorical lipoprotein(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. Conclusions With a large sample size and long-term follow-up, our data confirmed that high lipoprotein(a) levels could be associated with a poor prognosis after PCI in stable coronary artery disease patients, suggesting that lipoprotein(a) measurements may be useful for patient risk stratification before selective PCI.

High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, can promote atherosclerosis and predict cardiovascular events. However, no data are currently available about the combined effects of hsCRP and hypertension on cardiovascular risk. This study sought to elucidate this matter. A total of 7325 consecutive patients with angina-like chest pain undergoing coronary angiography were evaluated, and 4291 patients with stable, newly diagnosed coronary artery disease (CAD) were enrolled. They were subdivided into three groups according to baseline hsCRP levels (<1, 1-3, and >3 mg/L) and further stratified by hypertension status. The severity of CAD was assessed by the Gensini score and number of diseased vessels. All participants were followed for the occurrence of cardiovascular events. The coronary severity and cardiovascular outcomes were compared among these groups. We observed 530 (12.35%) incident cardiovascular events over 14,210 person-years. Elevated hsCRP was associated with more severe coronary lesions (p < 0.05) and an elevated but nonsignificant increased risk of cardiovascular events (p > 0.05). When hypertension was included as a stratifying factor, both patients with high hsCRP and normal blood pressure and hypertensive patients with any level of hsCRP had more severe coronary lesions compared with the reference group with low hsCRP and normotension. However, compared with the reference group, the cardiovascular event risk was only significantly elevated in patients with high hsCRP and hypertension (p < 0.05). The combination of elevated hsCRP and hypertension greatly increased the cardiovascular risk in patients with stable, newly diagnosed CAD, supporting that hsCRP could be treated as a marker for stratification in high-risk patients.

Background: The aim of the present study is to examine the effects of free fatty acids (FFAs) on major cardiovascular events (MACEs) in patients with stable coronary artery disease (CAD) and different glucose metabolism status., Methods: In this study, we consecutively enrolled 5443 patients from March 2011 to May 2015. Patients were categorized according to both status of glucose metabolism status [diabetes mellitus (DM), pre-diabetes (Pre-DM), normal glycaemia regulation (NGR)] and FFAs levels. All subjects were followed up for the occurrence of the MACEs., Results: During a median of 6.7 years' follow-up, 608 MACEs occurred. A twofold higher FFAs level was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.242, 95% confidence interval (CI) 1.084-1.424, p value = 0.002]. Adding FFAs to the Cox model increased the C-statistic by 0.015 (0.005-0.027). No significant difference in MACEs was observed between NGR and Pre-DM groups (p > 0.05). When patients were categorized by both status of glucose metabolism and FFAs levels, medium and high FFAs were associated with significantly higher risk of MACEs in Pre-DM [1.736 (1.018-2.959) and 1.779 (1.012-3.126), all p-value < 0.05] and DM [2.017 (1.164-3.494) and 2.795 (1.619-4.824), all p-value < 0.05]., Conclusions: The present data indicated that baseline FFAs levels were associated with the prognosis in DM and Pre-DM patients with CAD, suggesting that FFAs may be a valuable predictor in patients with impaired glucose metabolism.

Objective: The aim of the current study is to determine the impact of elevated lipoprotein(a) [Lp(a)] on cardiovascular events (CVEs) in stable coronary artery disease (CAD) patients with different glucose metabolism status., Research Design and Methods: In this multicenter study, we consecutively enrolled 5,143 patients from March 2011 to February 2015. Patients were categorized according to status of glucose metabolism (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]) levels and further classified into 12 groups by Lp(a) levels. CVE end points included nonfatal acute myocardial infarction (MI), stroke, and cardiovascular mortality. All subjects were followed up for the occurrence of the CVEs., Results: During a median of 6.1 years' follow-up, 435 (8.5%) CVEs occurred. No significant difference in occurrence of CVEs was observed between NGR and pre-DM groups (hazard ratio 1.131 [95% CI 0.822-1.556], P > 0.05). When status of glucose metabolism was incorporated in stratifying factors, 30 ≤ Lp(a) < 50 mg/dL and Lp(a) ≥50 mg/dL were associated with significantly higher risk of subsequent CVEs in pre-DM (2.181 [1.099-4.327] and 2.668 [1.383-5.415], respectively; all P < 0.05) and DM (3.088 [1.535-5.895] and 3.470 [1.801-6.686], all P < 0.05). Moreover, adding Lp(a) to the Cox model increased the C-statistic by 0.022 and 0.029 in pre-DM and DM, respectively, while the C-statistic was not statistically improved when Lp(a) was included for CVEs prediction in NGR., Conclusions: Our findings, for the first time, indicated that elevated Lp(a) levels might affect the prognosis in patients with pre-DM with stable CAD, suggesting that Lp(a) may help further stratify stable CAD patients with mild impaired glucose metabolism., (© 2019 by the American Diabetes Association.)

Introduction: Whether non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular risk has still been controversial. The reasons for this disparity may be associated with subject selection, events definition, diagnostic criteria of NAFLD, or research methods. The aim of this study was to determine the relationship of NAFLD to cardiovascular disease (CVD) outcomes in patients with stable, new-onset coronary artery disease (CAD)., Methods: A matched case-control study based on the cohort with stable, new-onset CAD was implemented in 162 cases (patients who developed all-cause death, non-fatal myocardial infarction and stroke during an average of 11,484 patient-years of follow-up) and 162 controls without cardiovascular events matched with the same sex, the age difference ≤3 years old, and the admission date within 3 months. Abdominal ultrasonography and coronary angiography were performed at admission. COX proportional hazard models and conditional logistic regression analysis were used to assess the effect of NAFLD on CVD outcomes., Results: NAFLD was more common in the event group than in the control group (P = 0.012). Kaplan-Meier analysis showed a significant association between NAFLD and CVD outcomes (P = 0.007). Moreover, Cox regression (hazard ratios 1.56; 95% confidence interval, 1.04-2.34, P = 0.031) and conditional logistic regression (odds ratio 2.72, 95% confidence interval, 1.16-6.39, P = 0.022) analyses further demonstrated that NAFLD was an independent risk factor for CVD outcomes., Conclusions: NAFLD is indeed an independent predictor of CVD outcomes in patients with stable, new-onset CAD. Further randomized controlled trials may be needed to confirm our findings.

Background: Patients with monogenic familial hypercholesterolemia (FH) have high risk for coronary artery disease (CAD). A recent FH Expert Panel suggested that FH was underdiagnosed and undertreated which needs early diagnosis. Moreover, the proportion of DNA-confirmed FH patients hospitalized with very early-onset (≤ 35 years) CAD remains uncertain., Methods: One hundred and five patients with age ≤ 35 years and LDL-C ≥ 3.4 mmol/L were tested for 9 genes (LDLR, APOB, PCSK9, APOE, STAP1, LIPA, LDLRAP1, ABCG5/8). Dutch Lipid Clinic Network (DLCN) and Simon Broome (SB) criteria for FH were also performed., Results: The prevalence of genetically confirmed FH was 38.1% (n = 40) in 105 patients. DLCN categorized 26.7% patients to probable and definite FH while SB identified 17.1% of patients with possible to definite FH. Twenty-five (62.5%) and seventeen (42.5%) patients with pathogenic mutations were undiagnosed according to SB and DLCN criteria. FH variant carriers, especially homozygotes, had significantly higher plasma LDL-C levels. The best LDL-C threshold for genetically confirmed FH was 4.56 mmol/L in the present study., Conclusions: FH is really a common cause for very young CAD patients (≤ 35 years) with a 38.1% of causative mutations in China and best LDL-C threshold for predicting mutations was 4.56 mmol/L. The underdiagnostic rate of clinical criteria was around 42.5-62.5%, suggesting that the expanded genetic testing could indeed promote the diagnosis of FH.

Aim: Previous studies have shown that both triglyceride glucose (TyG) and haemoglobin glycation indexes (HGI) are predictors of cardiovascular risk. However, the prognostic value of TyG index and HGI in patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD) is not determined., Methods: We conducted a nested case-control study among 1282 T2DM patients with stable CAD. Patients were followed up for 3846 person-years. A total of 160 patients with events (12.5%) were identified and matched individually on age, gender, previous use of lipid lowering agents and duration of follow-up with 640 controls., Results: In Kaplan-Meier analysis, the upper tertiles of TyG index and HGI had a significant lower event-free survival (p = .002; p = .036, respectively). Of the note, both TyG index and HGI were associated with increased risk of MACCEs after adjusting for confounding risk factors [adjusted HR (95% CI): 1.693 (1.238-2.316); 1.215 (1.046-1.411), respectively]. Moreover, adding TyG index to the Cox model increased the C-statistic to 0.638 (95%CI: 0.595-0.683, p = .002) while the C-statistic was not statistically improved when HGI was included (p = .240)., Conclusions: Both TyG index and HGI could predict cardiovascular outcomes in T2DM patients with new-onset, stable CAD while TyG index might be better. Key messages Both TyG and HGI are predictors of cardiovascular risk. The prognostic value of TyG index and HGI in T2DM patients with stable coronary artery disease is not determined. Our study firstly indicates that TyG index might have better prognostic value than HGI in T2DM patients with new-onset, stable CAD.

Background and Aims: The relation of lipoprotein (a) [Lp(a)] and proprotein convertase substilisin/kexin type 9 (PCSK9) levels to coronary artery disease (CAD) has been well established in the general population, while little is known about the association between Lp(a) or PCSK9 and atherosclerotic lesions of different artery sites in patients with familial hypercholesterolemia (FH)., Methods: One hundred and fifty-one patients with verified genotyped heterozygous FH (HeFH) were enrolled. There were available data regarding coronary angiography and carotid ultrasonography in 151 patients and femoral ultrasonography in 55 patients. Coronary and carotid severity was evaluated by Gensini score and Crouse score. PCSK9 and Lp(a) concentrations were determined by ELISA and immunoturbidimetry, respectively. Finally, the correlation of PCSK9 and Lp(a) with the presence and severity of CAD and peripheral artery disease (PAD) was assessed., Results: The distributions of PCSK9 and Lp(a) were skewed and a close correlation between them in HeFH patients was found. PCSK9 levels were significantly higher in patients with coronary and carotid atherosclerotic lesions compared to their non-atherosclerotic groups, while no difference was found in femoral atherosclerotic lesions groups. Lp(a) levels only differed between patients with or without coronary atherosclerotic lesions. Patients with highest PCSK9 and Lp(a) concentrations had the highest prevalence and severity of atherosclerotic lesions. Multivariate regression analysis showed that PCSK9 was independently associated with CAD and PAD, while Lp(a) was only associated with CAD., Conclusions: Circulating PCSK9 concentrations were associated with an increased risk of CAD and PAD, while Lp(a) was only a marker for CAD in HeFH patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Whether prediabetes mellitus (Pre-DM) alone or combined with hypertension is an independent risk factor for cardiovascular disease has not been fully clarified. This study aimed to further confirm whether the relation of Pre-DM to cardiovascular disease differs between individuals with or without hypertension. A total of 7121 consecutive patients with angina-like chest pain who received coronary angiography were evaluated and 4193 patients with angiography-proven stable, new-onset coronary artery disease were enrolled into the study. They were divided into 3 groups according to diabetes mellitus status and further stratified by hypertension. The severity of coronary artery disease was assessed by number of diseased vessels and Gensini score. All subjects were regularly followed up for the occurrence of the composite end points. Comparisons of coronary artery disease severity and outcomes were performed among these groups. During an average of 11 338 patient-years of follow-up, 434 (10.35%) cardiovascular events occurred. No significant difference was observed in coronary severity and composite end point events between Pre-DM and normal glucose regulation groups (both P >0.05). However, when hypertension was also incorporated as a stratifying factor, cardiovascular disease risk, assessed by coronary severity and clinical prognosis, was significantly elevated in Pre-DM plus hypertension and diabetes mellitus plus hypertension groups, compared with the reference group with normal glucose regulation and normal blood pressure (all P <0.05). The present study indicated that among patients with stable, new-onset coronary artery disease, the increased cardiovascular risk with Pre-DM is largely driven by the coexistence of hypertension rather than Pre-DM per se., (© 2018 American Heart Association, Inc.)

Objective: Whether lipoprotein(a) (Lp(a)) is a predictor for recurrent cardiovascular events (RCVEs) in patients with coronary artery disease (CAD) has not been established. This study, hence, aimed to examine the potential impact of Lp(a) on RCVEs in a real-world, large cohort of patients with the first cardiovascular event (CVE).Methods: In this multicentre, prospective study, 7562 patients with angiography-diagnosed CAD who had experienced a first CVE were consecutively enrolled. Lp(a) concentrations of all subjects were measured at admission and the participants were categorised according to Lp(a) tertiles. All patients were followed-up for the occurrence of RCVEs including cardiovascular death, non-fatal myocardial infarction and stroke.Results: During a mean follow-up of 61.45±19.57 months, 680 (9.0%) RCVEs occurred. The results showed that events group had significantly higher Lp(a) levels than non-events group (20.58 vs 14.95 mg/dL, p<0.001). Kaplan-Meier analysis indicated that Lp(a) tertile 2 (p=0.001) and tertile 3 (p<0.001) groups had significantly lower cumulative event-free survival rates compared with tertile 1 group. Moreover, multivariate Cox regression analysis further revealed that Lp(a) was independently associated with RCVEs risk (HR: 2.01, 95% CI: 1.44 to 2.80, p<0.001). Moreover, adding Lp(a) to the SMART risk score model led to a slight but significant improvement in C-statistic (∆C-statistic: 0.018 (95% CI: 0.011 to 0.034), p=0.002), net reclassification (6.8%, 95% CI: 0.5% to 10.9%, p=0.040) and integrated discrimination (0.3%, 95% CI: 0.1% to 0.7%, p<0.001).Conclusions: Circulating Lp(a) concentration was indeed a useful predictor for the risk of RCVEs in real-world treated patients with CAD, providing additional information concerning the future clinical application of Lp(a). [ABSTRACT FROM AUTHOR]