Di Sun

Association between lipoprotein (a) and proprotein convertase substilisin/kexin type 9 in patients with heterozygous familial hypercholesterolemia: a case control study

BACKGROUND Recent data have suggested an important role of lipoprotein (a) [Lp(a)] and proprotein convertase substilisin/kexin type 9 (PCSK9) in the development of atherosclerotic cardiovascular disease (ASCVD) in both general population and family hypercholesterolemia (FH), while the relation of Lp(a) to PCSK9 has not been examined. OBJECTIVE The aim of the present study was to investigate the association between plasma PCSK9 and Lp(a)in patients with heterozygous FH (HeFH). METHODS Two hundred and fifty-five molecularly confirmed patients with HeFH were compared to 255 age- and gender-matched non-FH controls. Plasma PCSK9 and Lp(a) concentrations were measured using ELISA and immunoturbidimetric method respectively, and finally their association was assessed. RESULTS Both plasma PCSK9 and Lp(a) levels were significantly higher in patients with HeFH compared to control group (p<0.001). Besides, the Lp(a) concentration and percentage of Lp(a)≥300mg/L were increased by PCSK9 tertiles in HeFH group (both p<0.05) while not in control group. In partial correlation analysis, Lp(a) was associated with PCSK9 (r=0.254, p<0.001) in HeFH group but not in control, which were further confirmed by multivariable linear regression analysis. Furthermore, significant associations between Lp(a) and PCSK9 were also found in subgroups of HeFH group irrespective of definite or probable FH, with and without coronary artery disease (CAD), and with statin or not. CONCLUSIONS Plasma Lp(a) level was associated with PCSK9 in patients with HeFH alone, suggesting that much about the interaction of PCSK9 with Lp(a) in FH need further explorations.

Impacts of Prediabetes Mellitus Alone or Plus Hypertension on the Coronary Severity and Cardiovascular Outcomes

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.

Familial hypercholesterolemia in very young myocardial infarction

Familial hypercholesterolemia (FH) is one of the most common causes of premature myocardial infarction (MI). However, The patterns of FH remained unrecognized in clinical care, especially in very young patients (VYPs, ≤35 years) with MI. The present study enrolled a total of 1,093 VYPs (≤35 years) presenting a first MI. Clinical diagnosis of FH was made using Dutch Lipid Clinic Network criteria. Coronary severity was assessed by Gensini score (GS). Patients were followed for a median of 40-months with cardiac death, stroke, MI, post-discharge revascularization or unstable angina as primary endpoints. The detected rates of definite/probable FH were 6.5%. The prevalence reached up to 10.3% in patients ≤25 years. The FH had similar levels of comorbidities but was younger, more likely to be very high risk (VHR) and had higher GS (p < 0.05) than unlikely FH. Notably, the FH on prior lipid-lowering medication presented a lower GS compared to those untreated. Differences in event rates were similar in FH as unlikely FH (11.8% vs. 8.1%, adjusted hazard ratio 1.35 [0.64–2.86], p = 0.434) but patients on treatment improved outcome (6.5% vs. 10.5%, adjusted hazard ratio 0.35[0.13–0.95], p = 0.039). The early identification and treatment might be critical to reduce cardiovascular risk in VYPs with MI.

Lipoprotein(a) level associates with coronary artery disease rather than carotid lesions in patients with familial hypercholesterolemia

Lipoprotein(a) [Lp(a)] level is a novel risk factor for atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH), while its impact on the different sites of arteries remains undetermined. We aim to examine the associations of Lp(a) levels with coronary and carotid atherosclerosis in patients with heterozygous FH (HeFH).

Lipoprotein (a) as a Marker for Predicting the Presence and Severity of Coronary Artery Disease in Untreated Chinese Patients Undergoing Coronary Angiography

OBJECTIVE Low-density lipoprotein cholesterol (LDL-C) has been well known as the risk factor of coronary artery disease (CAD). However, the role of lipoprotein (a) [Lp(a)] in the development of CAD is of great interest but still controversial. Thus, we aim to explore the effect of Lp(a) on predicting the presence and severity of CAD in Chinese untreated patients, especially in combination with LDL-C. METHODS We consecutively recruited 1,980 non-treated patients undergoing coronary angiography, among which 1,162 patients were diagnosed with CAD. Gensini score (GS) was used to assess the severity of CAD. Lp(a) was measured by immunoturbidimetric method. RESULTS Patients with CAD had higher level of LDL-C and Lp(a) compared with non-CAD (P < 0.05). Multivariable logistic regression revealed that Lp(a) > 205 mg/L (highest tertile) predicted 1.437-fold risk for CAD (95% CI: 1.108-1.865, P = 0.006) and 1.480-fold risk for high GS (95% CI: 1.090-2.009, P = 0.012) respectively. Interestingly, concomitant elevated level of Lp(a) and LDL-C conferred the highest risk for both presence [OR = 1.845, 95% CI: 1.339-2.541, P < 0.001] and severity [OR = 1.736, 95% CI: 1.188-2.538, P = 0.004] of CAD. CONCLUSION Lipoprotein (a) is a useful marker for predicting the presence and severity of CAD, especially combined with LDL-C.

The different relations of PCSK9 and Lp(a) to the presence and severity of atherosclerotic lesions in patients with familial hypercholesterolemia

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.

Increased Serum Leptin Levels in New-Onset, Untreated Female Patients with Coronary Artery Disease and Positively Associated with Inflammatory Markers

Background/Aims: Previous studies have suggested that leptin was associated with atherosclerosis and involved in inflammation. Gender differences between leptin and inflammatory markers have been evaluated less in untreated patients with stable coronary artery disease (CAD). Methods: In this study, a total of 394 consecutive Chinese patients who received coronary artery angiography were enrolled, including 243 patients with CAD and 151 non-CAD controls. The baseline clinical characteristics were collected and serum leptin levels were determined using ELISA. Results: The relation of serum leptin levels to inflammatory markers was found only in female patients. Leptin and white blood cell count (WBCC) as well as its subsets were significantly higher in female patients than female controls. In female patients, leptin was positively associated with C-reactive protein (CRP; r = 0.28, p = 0.016), WBCC (r = 0.261, p = 0.02), neutrophil, r = 0.268, p = 0.018, and monocyte, r = 0.228, p = 0.044. Multivariable regression analysis revealed that leptin was significantly and independently associated with CRP (β = 0.317, p = 0.004), WBCC (β = 0.278, p = 0.020), neutrophil (β = 0.262, p = 0.032), and monocyte (β = 0.245, p = 0.032). Conclusions: The serum leptin levels were higher in female patients and independently associated with CRP, WBCC, and its subsets, suggesting a potential interaction between leptin and inflammation in female CAD patients.

Triglyceride glucose and haemoglobin glycation index for predicting outcomes in diabetes patients with new-onset, stable coronary artery disease: a nested case-control study

Abstract 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.