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1.
J Transl Med ; 18(1): 195, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398139

RESUMO

BACKGROUND: Green tea drinking has been proven to lower lipid and exert cardiovascular protection, while the potential mechanism has not been fully determined. This study was to investigate whether the beneficial impact of epigallocatechingallate (EGCG), a type of catechin in green tea on lipids is associated with proprotein convertase subtilisin/kexin type 9 (PCSK9) pathways. METHODS: We studied the effects and underlying molecular mechanism of EGCG or green tea on regulating cholesterol from human, animal and in vitro. RESULTS: In the age- and gender-matched case control observation, we found that individuals with frequent tea consumption (n = 224) had the lower plasma PCSK9 and low density lipoprotein cholesterol (LDL-C) levels compared with ones without tea consumption (n = 224, p < 0.05). In the high fat diet (HFD) fed rats, EGCG administration significantly lowered circulating PCSK9 concentration and liver PCSK9 expression, along with up-regulated LDL receptor (LDLR) expression but decreased level of LDL-C. In hepatic cell study, similar results were obtained regarding the impact of EGCG on LDLR and PCSK9 expression. The assay transposase-accessible chromatic with high-throughput sequencing (ATAC-seq) and subsequent results suggested that two transcription factors, hepatocyte nuclear factor-1α (HNF-1α) and forkhead box class O (FoxO) 3a involved in inhibitory action of EGCG on PCSK9 expression. CONCLUSIONS: The present study demonstrates that EGCG suppresses PCSK9 production by promoting nuclear FoxO3a, and reducing nuclear HNF1α, resulting in up-regulated LDLR expression and LDL uptake in hepatocytes. Thereby inhibiting liver and circulating PCSK9 levels, and ultimately lowering LDL-C levels.

2.
Heart ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381650

RESUMO

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).

3.
Cardiovasc Diabetol ; 19(1): 45, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245386

RESUMO

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.

4.
Cardiovasc Diabetol ; 19(1): 36, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192491

RESUMO

BACKGROUND: The present cohort study aims to examine the relationship between fibrinogen (Fib) levels and glucose metabolism [fasting blood glucose (FBG) and hemoglobin A1c (HbA1c)] and investigate the impact of high Fib on cardiovascular outcomes in patients with stable CAD and pre-diabetes mellitus (pre-DM) or diabetes mellitus (DM). METHODS: This study included 5237 patients from March 2011 to December 2015. Patients were distributed into three groups according to Fib levels (low Fib, median Fib, high Fib) and further categorized by glucose metabolism status [normal glucose regulation (NGR), Pre-DM, DM]. All patients were followed up for the occurrences of major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal MI, stroke, and unplanned coronary revascularization. RESULTS: Linear regression analyses showed that FBG and HbA1c levels were positively associated with Fib in overall CAD participants, either with or without DM (all P < 0.001). During an average of 18,820 patient-years of follow-up, 476 MACEs occurred. High Fib was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.57, 95% confidence interval (CI) 1.26-1.97, P < 0.001]. Furthermore, DM but not pre-DM was a significant predictor of MACEs (P < 0.001 and P > 0.05, respectively). When patients were stratified by both glucose metabolism status and Fib levels, high Fib was associated with a higher risk of MACEs in pre-DM (HR 1.66, 95% CI 1.02-2.71, P < 0.05). Medium and high Fib levels were associated with an even higher risk of MACEs in DM (HR 1.86, 95% CI 1.14-3.05 and HR 2.28, 95% CI 1.42-3.66, all P < 0.05). After adding the combination of Fib and glucose status to the Cox model, the C-statistic was increased by 0.015 (0.001-0.026). CONCLUSIONS: The present study suggested that Fib levels were associated with FBG and HbA1c in stable CAD patients. Moreover, elevated Fib was independently associated with MACEs in CAD patients, especially among those with pre-DM and DM, suggesting that Fib may provide incremental value in the cardiovascular risk stratification of pre-DM and DM patients.

5.
J Am Heart Assoc ; 9(3): e014581, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013705

RESUMO

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.

6.
Cardiovasc Diabetol ; 19(1): 15, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041617

RESUMO

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.

7.
J Womens Health (Larchmt) ; 29(4): 503-510, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31905317

RESUMO

Background: Lipid disorder was one of the major risk factors for coronary artery disease (CAD), especially in postmenopausal women, whose lipid profile significantly changed during the transition period to menopause. The aim of the present study was to examine whether plasma lipoprotein(a) [Lp(a)] was a biomarker for predicting the presence and severity of CAD in postmenopausal women. Methods: A total of 783 postmenopausal women who had their first angina-like chest pain were enrolled and classified into two groups according to the results of coronary angiography: CAD group (n = 309) and age-matched non-CAD group (n = 309). Patients with CAD were further divided into the three groups based on Gensini score (GS). The relationships of plasma Lp(a) levels to the presence and severity of CAD were evaluated, and the predictive value of Lp(a) for CAD was also examined. Results: CAD group had higher Lp(a) levels when compared to non-CAD ones (p < 0.001). The multivariate logistic regression analysis suggested that Lp(a) was an independent predictor for the presence of CAD (p < 0.001). Plasma levels of Lp(a) were significantly related to GS (p < 0.001). In addition, plasma Lp(a) level was significantly elevated according to the tertiles of GS (p = 0.001) and was independently associated with high GS (p < 0.001). In receiver-operating characteristic analysis for predicting the presence of CAD in postmenopausal women, Lp(a) was found to have the area under the curve of 0.703, with an optimal cutoff value of 255.69 mg/L. Conclusions: Lp(a) is an independent risk factor for predicting the presence and the severity of new-onset CAD in postmenopausal women, suggesting that Lp(a) may be a lipid target for prevention and treatment in such patients.

8.
Per Med ; 17(1): 67-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31686591

RESUMO

Aim: The aim of the present study was to examine the predictive value of lipoprotein(a) (Lp[a]) levels for coronary collateral circulation (CCC) in patients with acute myocardial infarction (AMI). Method & methods: A total of 409 consecutive patients with AMI were enrolled for this study. Patients were divided into two groups according to rentrop grades assessed by coronary angiography: bad (n = 277) and good CCC group (n = 132). Result: Patients with bad CCC had a higher level of Lp(a) than that with good CCC (median Lp[a] 219.1 vs 122.0 mg/l). The area under the receiver-operating characteristic curves of Lp(a) in predicting bad CCC was 0.647 (95% CI: 0.592-0.702) with the cut-off value of 199.0 mg/l. Conclusion: Our data firstly suggested that Lp(a) might be a useful marker for CCC after AMI.

9.
J Clin Lab Anal ; 34(5): e23161, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31859412

RESUMO

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) characterized by severe high blood cholesterol levels usually presents an imbalance of systemic oxidative stress (OS). Lipoprotein apheresis (LA), which is the most effective therapy to reduce cholesterol levels, remains unclear in altering OS and scarce in Chinese patient studies. Our study aims to assess the impact of LA on OS status in Chinese patients with FH. METHODS: About 31 patients (22 males, age: 12-69 years) with FH and receiving LA treatment were consecutive enrolled. Free oxygen radicals test (FORT) and free oxygen radicals defense (FORD) values were determined using the free oxygen radical monitor and kit immediately before and after LA, while blood samples were collected to measure plasma lipid levels and hs-CRP by conventional methods. Data were analyzed by paired t test or rank sum test and Spearman-rho correlation analysis. RESULTS: Besides plasma lipid levels, the OS status showed that FORTs were significantly decreased and FORD values significantly enhanced immediately after LA treatment compared with before (both P < .01). In addition, the correlation analysis showed that the removal rates (△%) of TC were positively related to the increased rates (△%) of FORD value (ρ = 0.513, P = .003); LDL-C to FORD (ρ = 0.39, P = .03); Lp(a) to FORD (ρ = 0.473, P = .007); and non-HDL-C to FORD (ρ = 0.46, P = .009). However, no significant difference in hsCRP was found. CONCLUSIONS: The present study indicated, besides effectively lowering plasma lipid levels, LA could significantly improve OS status in Chinese patients with FH.

10.
Atherosclerosis ; 291: 27-33, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31683090

RESUMO

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] has been considered as a causal risk factor for cardiovascular disease (CVD) in the general population and levels vary in different ethnicities. However, no systemic analysis is currently available regarding the relation of plasma Lp(a) levels to cardiovascular events (CVEs) in Chinese patients with heterozygous familial hypercholesterolemia (HeFH). METHODS: Three hundred and ninety-three patients with HeFH undergoing Lp(a) measurement at baseline were consecutively enrolled and followed prospectively for an average of 36.5 months. Lp(a) levels were determined using an immunoturbidimetry assay. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the prognostic value of Lp(a) on CVEs. RESULTS: Thirty-five events occurred during follow-up. Lp(a) was significantly higher in patients with CVEs (53.3 mg/dL versus 31.7 mg/dL, p < 0.001). In Kaplan-Meier analysis, patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.004). After adjusting for confounding risk factors, per log unit increase in baseline Lp(a) was independently associated with CVEs [HR: 2.03(1.28-3.21), p = 0.002]. HRs remained unchanged after accounting for hard endpoints and did not vary too much in several relevant subgroups. Adding Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification and integrated discrimination. Moreover, HR for upper versus lower tertile of change in Lp(a) was 2.68 (1.11-6.48) for CVEs after one year. CONCLUSIONS: Both baseline and on-statin treatment Lp(a) levels were associated with an increased risk of CVEs in patients with HeFH, suggesting that Lp(a) measurement might clinically help further risk stratification of FH patients.

11.
J Transl Med ; 17(1): 367, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711505

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy. METHODS: A total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score ≥ 6) was enrolled and followed up for the occurrence of MACEs. Multidetector CT and coronary angiography were performed to determine coronary artery calcification score (CACS) and Gensini score (GS). Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma PCSK9 concentrations were determined by enzyme immunoassay. RESULTS: PCSK9 was independently and positively associated CACS and GS at baseline. During a mean follow-up of 3 years, 33 (9.8%) events occurred. Patients with MACEs had higher median PCSK9 compared with those without (332.47 vs. 311.89 ng/mL, p = 0.038). Kaplan-Meier analysis revealed that patients with higher PCSK9 presented lower event-free survival (p = 0.0017). PCSK9 was statistically correlated with MACEs after adjusting for confounding factors, with the HR per SD being 1.86 (1.31-2.65) and 3.70 (1.16-11.82) for the highest tertile compared with the lowest tertile. Adding PCSK9 to Cox prediction model led to a statistical improvement in net reclassification and integrated discrimination. CONCLUSION: Elevated levels of PCSK9 were positively associated with the development of CAD and future cardiovascular events, suggesting that measurement of PCSK9 concentration might be useful for cardiovascular risk stratification. Further studies are needed to confirm our results.

12.
Per Med ; 16(6): 467-478, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31691639

RESUMO

Aim: To investigated the potential differences between probable and definite heterozygous familial hypercholesterolemia (HeFH) patients diagnosed by Dutch Lipid Clinic Network criteria. Methods: Clinical characteristics, lipid profile, severity of coronary artery stenosis and gene mutations were compared. Kaplan-Meier curve was performed to evaluate the cardiovascular events. Results: Overall, 325 participants were included and divided into two groups: probable (n = 233) and definite HeFH (n = 92). Definite HeFH patients had higher low-density lipoprotein cholesterol (LDL-C), oxidized-LDL and proprotein convertase subtilisin/kexin 9 levels, and higher prevalence of tendon xanthomas. The incidence of genetic mutations was statistically higher in definite HeFH than probable HeFH patients. The coronary stenosis calculated by Gensini score was statistically severer in definite HeFH patients. The best LDL-C threshold for predicting mutations was 5.14 mmol/l. Definite HeFH had lower event-free survival rates. Conclusion: Definite HeFH patients had higher severity of phenotype and genotype, and higher risk of cardiovascular events.

14.
Cardiovasc Diabetol ; 18(1): 134, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610783

RESUMO

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.

15.
Eur J Prev Cardiol ; : 2047487319880985, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604401

RESUMO

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.

16.
Clin Cardiol ; 42(10): 988-994, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436336

RESUMO

BACKGROUND: Previous studies have observed that high level of lipoprotein (a) [Lp(a)] was common in the phenotypic familial hypercholesterolemia (FH) and may explain part of the clinical diagnosis of FH. HYPOTHESIS: We aim to develop a modified model including Lp(a) and compare its diagnostic performance with Dutch Lipid Clinic Network (DLCN) criteria. METHODS: Data of 10 449 individuals were utilized for the model establishment (7806 for derivation and 2643 for validation) from January 2011 to March 2018. The novel score model was modified on the basis of DLCN. Furthermore, 718 patients were screened for LDLR, APOB, and PCSK9 gene mutations. RESULTS: The novel modified model consisted of untreated low-density lipoprotein cholesterol (LDL-C) level, Lp(a), personal premature coronary heart disease (CHD), tendon xanthomas and family history of CHD and/or hypercholesterolemia. It has shown high discrimination (area under curve [AUC] 0.991, 95% confidence interval [CI[ 0.988-0.994, P < .001) for distinguishing clinical FH from non-FH diagnosed using DLCN. Furthermore, a concordance analysis was performed to compare the modified model with DLCN and it showed a good agreement with DLCN (κ = 0.765). External validation of the novel model also showed good accordance (κ = 0.700). Further genetic analysis showed that the agreements between the new model and mutation improved a little compared to that between DLCN and mutation. CONCLUSIONS: The novel modified model, including Lp(a), could provide new insights into FH diagnosis in Chinese population with more concerns on the patients with high level of Lp(a).


Assuntos
Algoritmos , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteína(a)/sangue , Biomarcadores/sangue , China/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Postgrad Med J ; 95(1128): 534-540, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31315919

RESUMO

BACKGROUND: It has been reported that lipoprotein(a) (Lp(a)) is associated with the risk of cardiovascular disease. The present study aimed to examine the association of Lp(a) levels with the presence and severity of coronary artery disease (CAD) in female patients. METHODS: A total of 3712 female patients who received coronary angiography were consecutively enrolled. The levels of Lp(a) were measured and compared among patients with or without CAD, myocardial infarction and menopause. Spearman correlation analysis and logistic regression analysis were used to examine the association of Lp(a) with the presence of CAD and the severity of coronary atherosclerosis assessed by Gensini score (GS). RESULTS: The average of Lp(a) levels was elevated as age increased in female subjects. Notably, women after menopause had higher Lp(a) levels compared with that before menopause (16.8 mg/dL (IQR 7.54-41.12 mg/dL) vs 14.7 mg/dL (IQR 6.72-30.82 mg/dL), p=0.002). Furthermore, multiple logistic regression analysis identified that Lp(a)>30 mg/dL was an independent risk factor of CAD in the postmenopausal females (OR: 1.33, 95% CI: 1.08 to 1.63, p=0.007). Finally, Lp(a) had a positive correlation with GS (r=0.11, p<0.001), and Lp(a)>30 mg/dL was an independent risk factor for high GS (OR: 1.43, 95% CI: 1.14 to 1.79, p=0.02) in the postmenopausal females. CONCLUSION: Circulating Lp(a) levels were independently associated with the presence and severity of CAD in the postmenopausal females, suggesting that Lp(a) may be useful for prevention and risk-stratification of CAD in female individuals.

19.
Prostaglandins Other Lipid Mediat ; 144: 106345, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31278984

RESUMO

BACKGROUND: Oxidized-low-density lipoprotein (ox-LDL), as well as high-density lipoprotein (HDL) and its subfractions play important role in the development of coronary artery disease (CAD). METHODS: A total of 1417 individuals who received selective coronary angiography (CAG) without lipids-lowering treatments were consecutively enrolled. Patients were divided into CAD (n = 942) and non-CAD group (n = 475). The severity of CAD was assessed by Gensini Scores (GS) system. The correlations of ox-LDL with HDL subfractions were analyzed. RESULTS: Compared with non-CAD subjects, CAD patients had higher ox-LDL but lower concentrations of HDL cholesterol (p = 0.002) and large HDL subfractions (p = 0.004). And ox-LDL was negatively correlated with large HDL subfractions in patients with severe CAD (p < 0.05). Moreover, ox-LDL was elevated and large HDL subfractions decreased with the increase of the number of stenotic coronary arteries and GS (p < 0.05, respectivelly). CONCLUSIONS: The correlations between ox-LDL and cholesterol level of large HDL particles varied among CAD and non-CAD, and CAD with different severities of atherosclerosis.

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