Coronary artery disease (CAD) due to obstructive atherosclerosis is a leading cause of death and has been recognized as a worldwide health threat. Measures to decrease low-density lipoprotein cholesterol (LDL-C) levels are the cornerstone in the management of patients with atherosclerotic cardiovascular disease, particularly those with CAD, for over two decades. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly recognized protein, plays a key role in cholesterol homeostasis by enhancing degradation of hepatic LDL receptor (LDLR). Interestingly, PCSK9 is also involved in the inflammatory process. Plasma PCSK9 and lipid or nonlipid cardiovascular risk factors are correlated, and the associations between PCSK9 with cardiovascular health and disease make this protein worthy of attention for the treatment of hyperlipidemia and atherosclerosis. Here, we provide an overview of the physiological role of PCSK9, which contributes to atherosclerosis, and provide data on PCSK9 as a novel pharmacological target. Clinical evidence shows that PCSK9 inhibition is as promising as statins as a target to treat CAD. The efficacy of these drugs may potentially enable effective CAD prophylaxis for more patients.

View full abstract

Aim: The role of gastrectomy in glycemic control has been established in the current era of bariatric surgery for obesity. Gastrectomy in obese patients is associated with increased levels of high-density lipoprotein cholesterol (HDL-C). However, limited data on the effects of gastrectomy in nonobese patients are available. We herein investigated the long-term plasma lipid changes in nonobese patients who had undergone gastrectomy.
Methods: Patients were enrolled as part of routine healthcare examinations from 1984 to 2003. Preoperative and postoperative data from patients who had undergone curative gastrectomy were analyzed for up to 10 years postoperatively. Three age- and sex-matched controls were assigned to each case.
Results: Sixty-four nonobese patients without diabetes mellitus or a history of having taken lipidlowering drugs who underwent curative gastrectomy during the study period were enrolled (60 subtotal gastrectomies, four total gastrectomies). The median follow-up period was 7.6 years. The mean body mass index was 9.6% lower one year after gastrectomy (p＜0.01), then plateaued with a slight recovery. Intriguingly, the preoperative HDL-C level was 21% higher one year after gastrectomy (p＜0.01), increased by another 30% six years after gastrectomy and remained at this level for the rest of the follow-up period. No significant changes in the HDL-C level were observed in the controls. The degree of HDL-C elevation was consistently significant, irrespective of the baseline triglyceride level, HDL-C level or body weight.
Conclusions: Gastrectomy in nonobese patients was associated with consistent and distinct long-term HDL-C elevations and body mass index reductions.

View full abstract

Aim: Cardiac and renal diseases are common disorders that frequently coexist. We tested the hypothesis that the levels of circulating endothelial-derived apoptotic microparticles (EDA-MPs; CD31^＋CD42b⁻AN⁻V^＋) and platelet-derived apoptotic microparticles (PDA-MPs; CD31^＋CD42b^＋AN⁻V^＋) are useful biomarkers for predicting the presence of cardiorenal disease (CRD).
Methods: A total of 68 patients with chronic kidney disease (CKD) and angina pectoris (CKD-AP) undergoing cardiac catheterization were prospectively enrolled into group 1, 10 patients with coronary artery disease (CAD) without CKD were enrolled into group 2 (CAD^＋CKD⁻) and 10 patients without CAD and CKD were enrolled into group 3 (CAD⁻CKD⁻).
Results: The serum creatinine levels were significantly higher, whereas the estimated glomerular filtration rates (eGFRs) were significantly lower, in group 1 than in the other two groups (all p＜0.02). The circulating levels of EDA-MPs and PDA-MPs did not differ between the patients with and without CKD (all p＞0.2). However, the circulating levels of EDA-MPs and PDA-MPs were significantly higher in group 2 than in groups 1 and 3 (all p＜0.03). In addition, differences were noted in the circulating EDA-MP and PDA-MP levels between groups 1 and 3, although without statistical significance (all p＞0.09). Meanwhile, among the CKD patients, the subgroup analysis showed that the levels of MPs were significantly higher in those with CAD than in those without (all p=0.001), while a multivariate analysis demonstrated that CAD was the only factor independently predictive of high levels of circulating EDA-MPs and PDA-MPs (p=0.033).
Conclusions: The link with increased circulating levels of MPs is more consistent in patients with CAD than in those with CKD.

View full abstract

Aim: Nephrotic syndrome (NS) is associated with an increased rate of cardiovascular events. The YKL-40 level is associated with atherosclerosis, endothelial dysfunction and proteinuria in renal and non-renal populations. The aim of this study was to investigate the relationships between the YKL-40 level and both vascular injury and proteinuria in NS patients.
Methods: Sixty-nine NS patients and 20 healthy subjects were enrolled in the present study. The endothelial function was assessed according to the flow mediated dilatation (FMD) and the degree of arterial stiffness was determined based on the pulse wave velocity (PWV). The serum YKL-40 levels were measured using ELISA.
Results: The YKL-40 levels and PWV values were higher and the FMD values were lower in the NS patients than in the healthy controls. However, the CA-IMT and LVEF levels were not statistically different between the two groups. The patients were divided into three groups with respect to the extent of proteinuria: the normoproteinuria group (n:18), non-nephrotic proteinuria group (n:33) and nephrotic proteinuria group (n:18). Consequently, the YKL-40 levels and PWV values were significantly increased and the FMD values were decreased in the nephrotic proteinuria group compared to that observed in both the non-nephrotic proteinuria and normoproteinuria groups. Furthermore, the YKL-40 level correlated with the FMD and PWV values in the NS patients. In addition, proteinuria correlated with the YKL-40, FMD, PWV, eGFR and fasting LDL cholesterol values in this patient group. Multivariate linear regression analyses showed that the YKL-40 and eGFR values were effective in predicting proteinuria in the NS patients.
Conclusions: The serum YKL-40 level is associated with endothelial dysfunction and increased arterial stiffness in NS patients and may be an indicator of the level of proteinuria in this patient population.

View full abstract

Aims: Acquired Von Willebrand syndrome (AVWS) is an acquired bleeding disorder that has been reported to aggravate bleeding complications in patients with ventricular assist devices or aortic stenosis. AVWS is characterized by the loss of the high-molecular-weight (HMW) multimers of Von Willebrand factor (VWF) with consequent impaired VWF binding to platelets and collagen. The aim of this study was to investigate the development of AVWS in patients treated with veno-venous ECMO (extracorporeal membrane oxygenation) support.
Methods: We examined the presence of AVWS in adult patients receiving ECMO support (n=18) and control subjects treated without ECMO support (n=18). The diagnosis of AVWS was made based on the ratio of collagen-binding capacity to VWF-antigen (VWF:CB/VWF:Ag) and a VWF multimeric analysis. In addition, bleeding episodes were monitored.
Results: All patients supported with ECMO developed AVWS. AVWS was identified in the early period after ECMO implantation, i.e. within 24 hours after ECMO implantation. In 17 patients, the VWF:CB/VWF:Ag ratio was significantly reduced and HMW multimers were severely missing, and 17 of the 18 patients developed bleeding complications and required transfusions of blood, FFP and/or platelet concentrates.In addition, nine patients without an ECMO device were investigated (prior to ECMO implantation: n=2, after ECMO explantation: n=7).
Conclusions: In this study, all patients treated with ECMO support developed AVWS, and AVWS was detectable within 24 hours after ECMO implantation. However, the AVWS was reversible after ECMO explantation. Making an early diagnosis of AVWS and providing appropriate treatment may reduce the incidence of life-threatening bleeding.

View full abstract

Aim: The cardio-ankle vascular index (CAVI) is a sensitive non-invasive marker of arterial stiffness and atherosclerosis. The aim of this work was to compare the CAVI values in patients with dyslipidemia (without diabetes mellitus and hypertension) and healthy controls.
Methods: A Total 248 subjects with dyslipidemia (104 men, 144 women), 55.0 (95% CI 30-70) years of age with combined hyperlipidemia or primary hypercholesterolemia and 537 healthy controls (244 men, 293 women) 40.0 (95% CI 26-62) years of age were included in this study. Fasting blood samples were collected to measure the serum total cholesterol, triglyceride, HDL-cholesterol and apolipoprotein A1 and B levels. The LDL cholesterol level was also calculated, and the CAVI was measured using the VaSera^® 1500 system.
Results: The CAVI values were significantly higher in the dyslipidemic patients (8.08, 95% CI 6.00-10.05) than in the controls (7.11, 95% CI 5.77-9.05; p＜0.01). In addition, the CAVI values were elevated in both subgroups of patients with hypercholesterolemia (7.95, 95% CI 5.85-6.90; p＜0.01) and combined hyperlipidemia (8.30, 95% CI 6.60-10.15; p＜0.01) in comparison with those observed in the controls. After adopting the propensity score method in order to balance the confounding factors (age, gender, body mass index) and adjust the analysis for diastolic blood pressure, the CAVI values in the dyslipidemic patients remained significantly high (7.78, 95% CI 5.80-9.69) compared to that observed in the controls (7.31, 95% CI 5.44-9.35; p＜0.001). However, the CAVI values did not differ significantly between the controls and both subgroups of dyslipidemic patients(primary hypercholesterolemia, combined hyperlipidemia).
Conclusions: The present findings demonstrated that dyslipidemia increases the CAVI values in comparison to that seen in healthy subjects.

View full abstract

Aim: The aim of this study was to examine whether the termination of long-term clopidogrel therapy results in a proinflammatory state and whether lipid parameters influence the inflammatory response after stopping the drug.
Methods: A prospective, multicenter study was conducted among 200 patients with implanted coronary stents who received dual antiplatelet therapy for one year, without ischemic or bleeding events. According to the guidelines, clopidogrel was discontinued after one year. In all patients, the high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand (sCD40L) and lipid [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] levels were measured twice: on the day of cessation of clopidogrel and 45 days after the termination of clopidogrel treatment.
Results: In men (n=151), the sCD40L serum levels were significantly higher 45 days after the discontinuation of clopidogrel (p=0.007), while the hsCRP levels were not significantly different (p=0.407). Furthermore, when analyzed across the HDL-C quartiles, the hsCRP and sCD40L values were found to be associated with the levels of HDL-C after the discontinuation of clopidogrel in men. In addition, the men in the first HDL-C quartile exhibited the most pronounced increase in the sCD40L levels (p=0.001) and had significantly higher hsCRP levels (p=0.001) compared to the subjects in the other quartiles. Other lipid parameters did not show any associations with the sCD40L or hsCRP levels.
Conclusions: The discontinuation of clopidogrel is associated with higher increments in the sCD40L level, and a pronounced proinflammatory response is associated with a lower HDL-C concentration.

View full abstract

Aim: We investigated the proportion of people who would qualify for statin treatment with an atherosclerotic cardiovascular disease (ASCVD) 10-year risk of ≥7.5% and who exhibit an LDL cholesterol (LDL-C) of 70 to 189 mg/dL according to the new ACC/AHA guidelines for the treatment of increased cardiovascular risk.
Methods: The study population (8,742 subjects) included individuals who underwent health examinations at Kangbuk Samsung Hospital in South Korea in 2010. We also evaluated the data obtained from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES) of 16,892 adults.
Results: Approximately 90% of men ≥60 years of age and women ≥70 years of age had an ASCVD 10-year risk of ≥7.5% and LDL-C level of ≥70 mg/dL. The proportions of subjects with a Framingham 10-year risk of ≥10%, coronary artery calcium score of ＞20 and ＞100 and fatty liver each increased in association with an increasing ASCVD 10-year risk quartile in both sexes. Furthermore, age was significantly associated with the ASCVD 10-year risk in both sexes (all p-value ＜0.001). The KNHANES data also showed that over 85.0% of men ≥60 years of age and 95.0% of women ≥70 years of age had an ASCVD 10-year risk of ≥7.5% and an LDL-C level of ≥70 mg/dL.
Conclusions: Adopting the new ASCVD prevention guidelines would result in the treatment of almost all Korean men and women (≥60 years and ≥70 years of age, respectively) without evidence of cardiovascular disease. Therefore, Asian-specific guidelines are needed to avoid unnecessary over treatment in an aging global population.

View full abstract

Aim: Arterial stiffness is recognized to be an independent risk factor for cardiovascular morbidity and mortality. Recent studies have found that osteoprotegerin (OPG) is associated with increased pulse wave velocity and may reflect endothelial dysfunction. The aim of this study was to evaluate the relationship between the serum OPG level and arterial stiffness in hypertensive patients using the cardio-ankle vascular index (CAVI).
Methods: Fasting blood samples were obtained from 115 hypertensive patients and 52 healthy participants. The CAVI value was derived using the waveform device (CAVI-VaSera VS-1000). The serum OPG levels were measured using a commercially available enzyme-linked immunosorbent assay. A CAVI value of ≥9 defined the high arterial stiffness group.
Results: Sixty-five hypertensive patients (56.5%) were included in the high arterial stiffness group. Diabetes (p=0.032), smoking (p=0.044), age (p＜0.001), systolic blood pressure (p=0.001), diastolic blood pressure (p=0.024), pulse pressure (p=0.046) and the creatinine (p=0.013) and serum OPG (p＜0.001) levels were higher in the high arterial stiffness group than in the low arterial stiffness group, while the glomerular filtration rate (p=0.003) was lower in the high arterial stiffness group than in the low arterial stiffness group among the hypertensive patients. The results of the Spearman’s rank correlation coefficient test also indicated a strong positive correlation between the OPG and CAVI values (r=0.484, p＜0.001) in the hypertensive patients. In addition, a multivariate logistic regression analysis showed that age (odds ratio: 1.162, 95% confidence interval (CI): 1.070-1.263, p＜0.001), diastolic blood pressure (odds ratio: 1.109, 95% CI: 1.033-1.190, p=0.004), and serum OPG level (odds ratio: 1.275, 95% CI: 1.030-1.580, p=0.026) were independent predictors of arterial stiffness in hypertensive patients.
Conclusions: The serum OPG level is positively associated with arterial stiffness in hypertensive patients.

View full abstract

Aim: Paraoxonase-1 (PON1) is an antiatherosclerotic enzyme located on high-density lipoprotein (HDL). The effects of anaerobic exercise on PON1 activity are unknown. Here we investigated the effects of anaerobic judo training on three different activities of same PON1 enzyme (TDPON1), including basal PON1, salt-stimulated PON1 (SPON1), and arylesterase (AE) activities, of serum, HDL, and HDL subgroups (HDLs; HDL and its subgroups) and its relationship with PON1-Q192R phenotype (PON1P).
Methods: Our study included 18 Turkish national female judoists (mean age: 17.9±0.8 years). Before and after 5 months of anaerobic training, critical speed (CS), TDPON1 activities, cholesterol levels in the serum and supernatants of HDLs obtained by polyethylene glycol, and other major blood lipids and lipoproteins (BLLPs) including triglycerides were determined using blood samples taken after overnight fasting. PON1P groups (PGs) were categorized as QQ (QG; persons with low activity) and R carriers (QR＋RR) (RG; persons with high activity) according to SPON1/AE activity ratios. The results were considered statistically significant at P≤0.05.
Results: Anaerobic training resulted in significantly increased the cholesterol levels of HDLs (except HDL₂-C) in all subjects, but not HDLs-C in PGs. Anaerobic training resulted in significant increases in most TDPON1 activities of serum and HDLs in all subjects and (except AE) in PGs, whereas SPON1 and HDL₂ AE activities increased only in the RG, which was related to PON1P. However, PON1P was not related to other measured markers, including basal BLLP profiles.
Conclusions: Anaerobic training improved most TDPON1 activities of serum and HDLs and HDLs -C levels (except HDL₂-C) in all subjects, but not HDLs-C in PGs. The beneficial effects of anaerobic training on SPON1 and HDL₂ AE activities were depend on PON1P. The lack of response of HDL₂-C to anaerobic exercise will require further research.

View full abstract