Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in Acute Coronary Syndrome: Relationship With Low-Density Lipoprotein Cholesterol

Background

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) might play a role in the formation of vulnerable atherosclerotic plaques. Its plasma distribution and mass in subjects with acute coronary syndrome (ACS) has yet to be characterized.

Methods

We compared plasma levels of Lp-PLA₂ in 24 patients within 48 hours of an ACS (acute) and 12 weeks after (recovery), in 26 patients with stable coronary artery disease and in 10 normal healthy control subjects. Lp-PLA₂ mass was determined using enzyme-linked immunosorbent assay.

Results

The ACS patients (mean age 57 ± 8.7 years) had high-sensitivity C-reactive protein (hsCRP) levels of 30.46 ± 57.57 mg/L (ACS acute) vs 1.69 ± 1.32 mg/L (ACS recovery). Plasma Lp-PLA₂ levels were significantly higher in ACS acute subjects than in ACS recovery subjects (143.13 ± 60.88 ng/mL vs 88.74 ± 39.12 ng/mL; P < 0.0001). Interestingly, stable coronary artery disease patients had higher Lp-PLA₂ levels than ACS recovery patients (121.72 ± 31.11 ng/mL vs 88.74 ± 39.12 ng/mL; P = 0.0018). There was a strong correlation between Lp-PLA₂ and low-density lipoprotein (LDL) cholesterol (LDL-C) (r = 0.709; P < 0.0001) or changes in LDL (r = 0.449; P = 0.027), suggesting that the major determinant of plasma Lp-PLA₂ is LDL-C. No significant correlations were observed between Lp-PLA₂ and hsCRP or high-density lipoprotein (HDL) cholesterol. When separated using high-performance liquid chromatography, > 65%-70% of Lp-PLA₂ mass was within the apolipoprotein B-containing lipoprotein fraction, with approximately 30%-35% on HDL fraction, with no significant change in distribution between ACS acute and recovery.

Conclusions

Subjects with an ACS have markedly increased Lp-PLA₂ levels acutely related to LDL-C levels.     

Caregiving in heart failure: Relationship quality is associated with caregiver benefit finding and caregiver burden

Objective

To determine whether relationship quality is associated with caregiver benefit or burden and how depression influences these associations.

Background

Caregivers influence outcomes of patients with heart failure (HF). Relationship quality, caregiver benefit and burden are key factors in the caregiving experience.

Methods

Nineteen caregivers of HF outpatients completed measures of relationship quality, caregiver benefit, burden and depression. Associations were assessed using Pearson's correlations.

Results

Relationship quality was positively associated with caregiver benefit (r = 0.45, P = 0.05) and negatively associated with burden (r = −0.80, P < 0.0001) and depression (r = −0.77, P = 0.0001). Relationship quality and burden remained associated after controlling for depression.

Conclusions

In this exploratory study, relationship quality was positively associated with caregiver benefit and negatively associated with burden. Future studies are needed to further understand these key caregiving factors, which may lead to opportunities to help caregivers see benefits and reduce burden.     

Endothelial microparticles exert differential effects on functions of Th1 in patients with acute coronary syndrome

Background

Endothelial microparticles (EMPs) can be involved in inflammatory process, blood coagulation, and regulation of vascular function. However, it remains unclear whether EMPs participate in the pathogenesis of ACS. The purpose of this study is to investigate the impact of EMPs on Th1/Th2 development and functions in vitro.

Methods

Eight-five patients were allocated into SAP group (n = 27), UAP group (n = 28), and AMI group (n = 30). Twenty hospitalized patients with normal coronary angiography were recruited as controls. The frequency of EMPs, IFN-γ, and IL-4 levels were measured, and the correlation between EMPs and Th1/Th2 cytokine was analyzed. PBMCs isolated from patients with ACS were treated in vitro with EMPs. This was followed by flow cytometry for Th1/Th2 counts, real-time PCR and western blotting for T-bet and GATA mRNA and protein expression, and ELISA for IFN-γ, TNF-α, IL-4, and IL-10.

Results

This study proved that the frequency of EMPs was significantly increased in ACS patients. There was a significant positive correlation between EMPs and IFN-γ. EMPs could significantly upregulate the differentiation and function of Th1 through increasing the expression of T-bet mRNA and protein. Furthermore, this study also indicated that EMP treatment in vitro could promote the expression of TNF-α, which exerts adverse effects on the pathogenesis and progression of atherosclerosis.

Conclusions

EMPs may be involved in the immune and inflammatory processes that take part in artery atherosclerosis and that they do so by regulating Th1/Th2 differentiation and function. They may play an important role in the pathogenesis of coronary atherosclerosis and plaque instability.     

Arrhythmias in patients with acute coronary syndrome in the first 24 hours of hospitalization

Objectives

In patients with acute coronary syndrome (ACS), we sought to: 1) describe arrhythmias during hospitalization, 2) explore the association between arrhythmias and patient outcomes, and 3) explore predictors of the occurrence of arrhythmias.

Methods

In a prospective sub-study of the IMMEDIATE AIM study, we analyzed electrocardiographic (ECG) data from 278 patients with ACS. On emergency department admission, a Holter recorder was attached for continuous 12-lead ECG monitoring.

Results

Approximately 22% of patients had more than 50 premature ventricular contractions (PVCs) per hour. Non-sustained ventricular tachycardia (VT) occurred in 15% of patients. Very few patients (≤1%) had a malignant arrhythmia (sustained VT, asystole, torsade de pointes, or ventricular fibrillation). Only more than 50 PVCs/hour independently predicted an increased length of stay (p < .0001). No arrhythmias predicted mortality. Age greater than 65 years and a final diagnosis of acute myocardial infarction independently predicted more than 50 PVCs per hour (p = .0004).

Conclusions

Patients with ACS seem to have fewer serious arrhythmias today, which may have implications for the appropriate use of continuous ECG monitoring.     

A peripheral blood gene expression score is associated with atherosclerotic Plaque Burden and Stenosis by cardiovascular CT-angiography: Results from the PREDICT and COMPASS studies

Objective

We previously validated a gene expression score (GES) based on age, sex and peripheral blood cell expression levels of 23 genes measured by quantitative real-time PCR (qRT-PCR) for diagnosis of obstructive coronary artery disease (CAD) (≥50% luminal diameter stenosis). In this study we sought to determine the association between the GES and coronary arterial Plaque Burden and Stenosis by CT-angiography.

Methods

A total of 610 patients (mean age: 57 ± 11; 50% male) from the PREDICT and COMPASS studies from 59 centers were analyzed. Coronary artery calcium (CAC) scoring, CT angiography (CTA)-based plaque and stenosis and GES measurements were performed. CAC was expressed as Agatston score and CTA evaluated for stenosis severity: 0. None; 1. Minimal, 2. Mild, 3. Moderate, 4. Severe and 5. Occluded. Correlation analysis, one-way analysis of variance (ANOVA) and receiver operating characteristics (ROC) analyses were performed.

Results

GES was significantly associated with plaque burden by CAC (r = 0.50; p < 0.001) and CTA (segment involvement score index: r = 0.37, p < 0.001); a low score (≤15) had sensitivity of 0.71 and a high score (≥28) a specificity of 0.97 for the prediction of zero vs. non-zero CAC. Increasing GES was associated with a greater degree of categorical stenosis by ANOVA (p < 0.001); GES significantly correlated with maximum luminal stenosis (r = 0.41; p < 0.01) and segment stenosis score index (r = 0.38; p < 0.01). A low score had sensitivity of 0.90 and a high score a specificity of 0.87 for ≥70% stenosis.

Conclusions

A previously validated GES is significantly associated with Plaque Burden and Stenosis by CT.

Clinical trial registration.

(PREDICT [NCT00500617] and COMPASS [NCT01117506]), www.clinicaltrials.gov     

Polymorphisms on Chromosome 9p21 Confer a Risk for Acute Coronary Syndrome in a Chinese Han Population

Background

Genome-wide association studies have identified 2 single-nucleotide polymorphisms (SNPs) on chromosome arm 9p21, rs10757278, and rs2383207 that confer susceptibility to myocardial infarction. However, these data are mostly from Italian, American Caucasian, South Korean, and Japanese cohorts. This study is the first to investigate whether 6 SNPs (rs10757277, rs10757278, rs10757279, rs1333049, rs1333047, and rs10811656) are associated with acute coronary syndrome (ACS) in a Chinese Han population.

Methods

We performed a case-control analysis in 359 patients with ACS diagnosed by coronary angiography and 398 non-ACS controls of Han background between April 2007 and January 2008 to determine whether these 6 SNPs were associated with ACS. Exon fragments were genotyped by polymerase chain reaction–restriction fragment length polymorphism.

Results

After we adjusted for clinical parameters, we found the rs10757278 GG genotype to be associated with a significantly elevated risk of ACS (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.35-2.68; P = 0.00035), the rs10811656 T allele to be associated with a higher risk of ACS (OR, 1.67; 95% CI, 1.26-2.23; P = 0.0016) than the CC genotype, and the rs1333047 TT genotype also to be associated with a higher risk of ACS (OR, 1.57; 95% CI, 1.15-2.06; P = 0.0052) than the CC and CT genotypes. After 14.2 ± 4.5 months of follow-up, the end-point data were obtained: death (cardiac and noncardiac), nonfatal myocardial infarction, and recurrent angina leading to repeated coronary angiography. We found that the rs10757278 GG genotype was significantly associated with recurrent angina compared with the AA and AG genotypes (P = 0.013).

Conclusions

Polymorphisms on 9p21 were associated with ACS in a Chinese Han population. The rs10757278 GG genotype was further associated with adverse cardiac outcomes after ACS.     

Association between HMW adiponectin,HMW-total adiponectin ratio and early-onset coronary artery disease in Chinese population

Objective

Adiponectin is an adipose-secreting protein that shows atheroprotective property and has inverse relation with coronary artery disease (CAD). High-molecular weight (HMW) adiponectin is reported as the active form of adiponectin. In the present study, we aimed to investigate the association between total adiponectin, HMW adiponectin, HMW-total adiponectin ratio and the severity of coronary atherosclerosis, and to compare their evaluative power for the risk of CAD.

Methods

Serum levels of total and HMW adiponectin were measured in 382 early-onset CAD (EOCAD) patients and 305 matched controls undergoing coronary angiography by enzyme-linked immunosorbent assay (ELISA). Gensini score was used to evaluate the severity of coronary atherosclerosis.

Results

CAD onset age was positively correlated with HMW adiponectin (r = 0.383, P < 0.001) and HMW-total adiponectin ratio (r = 0.429, P < 0.001) in EOCAD patients. Total and HMW adiponectin and HMW-total adiponectin ratio were all inversely correlated with Gensini score (r = −0.417, r = −0.637, r = −0.578, respectively; all P < 0.001). Multivariate binary logistic regression analysis demonstrated that HMW adiponectin and HMW-total adiponectin ratio were both inversely correlated with the risk of CAD (P < 0.05). ROC analysis indicated that areas under the ROC curves of HMW adiponectin and HMW-total adiponectin ratio were larger than that of total adiponectin (P < 0.05).

Conclusions

Adiponectin is cardioprotective against coronary atherosclerosis onset in EOCAD patients. HMW adiponectin and HMW-total adiponectin ratio show stronger negative associations with the severity of coronary atherosclerosis than total adiponectin does. HMW adiponectin and HMW-total adiponectin ratio are effective biomarkers for the risk of CAD in Chinese population.     

S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population

Objective

Although homocysteine has been proposed as a cardiovascular risk factor, interventional trials lowering homocysteine have not consistently demonstrated clinical benefit. Recent evidence proposed the homocysteine metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by the kidneys, and cannot be lowered by vitamin supplementation. Due to its cumbersome measurement, data from large studies on the association between SAH, kidney function and cardiovascular disease are not available.

Methods

We recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among all study participants, we assessed parameters of C1 metabolism (homocysteine, SAH and S-adenosylmethionine), renal function (estimated glomerular filtration rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media-thickness [IMT]). eGFR was estimated by the CKD-EPI_creat-cys equation.

Results

Traditional cardiovascular risk factors and subclinical atherosclerosis were associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010; IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more closely correlated with SAH than with homocysteine (eGFR vs SAH: r = −0.335; p < 0.001; eGFR vs homocysteine: r = −0.250; p < 0.001). The association between eGFR and SAH remained significant after adjustment for traditional cardiovascular risk factors.

Conclusion

In summary, cardiovascular risk factors, subclinical atherosclerosis and eGFR are more strongly associated with SAH than with homocysteine in apparently healthy subjects. Thus, SAH might represent a more promising target to prevent cardiovascular disease than homocysteine.     

Frailty and Outcome in Elderly Patients With Acute Coronary Syndrome

Background

Frailty is superior to chronological age as a predictor of outcome. The Edmonton Frail Scale (EFS) is a simple valid measure of frailty, covering multiple important domains, with scores ranging from 0 (not frail) to 17 (very frail). The purpose of this pilot study was to assess the EFS in a group of elderly patients with acute coronary syndrome (ACS).

Methods

The EFS was administered to 183 consecutive patients with ACS aged ≥ 65 years admitted to a single centre in Edmonton, Alberta, Canada.

Results

Scores ranged from 0-13. Patients with higher EFS scores were older, with more comorbidities, longer lengths of stay (EFS 0-3: mean, 7.0 days; EFS 4-6: mean, 9.7 days; and EFS ≥ 7: mean, 12.7 days; P = 0.03), and decreased procedure use. Crude mortality rates at 1 year were 1.6% for EFS 0-3, 7.7% for EFS 4-6, and 12.7% for EFS ≥ 7 (P = 0.05). After adjusting for baseline risk differences using a “burden of illness” score, the hazard ratio for mortality for EFS ≥ 7 compared with EFS 0-3 was 3.49 (95% confidence interval [CI], 1.08-7.61; P = 0.002).

Conclusions

The EFS is associated with increased comorbidity, longer lengths of stay, and decreased procedure use. After adjustment for burden of illness, the highest frailty category is independently associated with mortality in elderly patients with ACS. Further work is needed to determine whether the use of a validated frailty instrument would better delineate medical decision making in this important, often disadvantaged population.     

Local carotid atherosclerotic plaque proteins for the identification of circulating biomarkers in coronary patients

Objective

To identify circulating biomarkers that originate from atherosclerotic vulnerable plaques and that could predict future cardiovascular events.

Methods

After a protein enrichment step (combinatorial peptide ligand library approach), we performed a two-dimensional electrophoresis comparative analysis on human carotid plaque protein extracts (fibrotic and hemorrhagic atherosclerotic plaques). In silico analysis of the biological processes was applied on proteomic data. Luminex xMAP assays were used to quantify inflammatory components in carotid plaques. The systemic quantification of proteins originating from vulnerable plaques in blood samples from patients with stable and unstable coronary disease was evaluated.

Results

A total of 118 proteins are differentially expressed in fibrotic and hemorrhagic plaques, and allowed the identification of three biological processes related to atherosclerosis (platelet degranulation, vascular autophagy and negative regulation of fibrinolysis). The multiplex assays revealed an increasing expression of VEGF, IL-6, IL-8, IP-10 and RANTES in hemorrhagic as compared to fibrotic plaques (p < 0.05). Measurement of protein expressions in plasmas from patients with stable and unstable coronary disease identified a combination of biomarkers, including proteins of the smooth muscle cell integrity (Calponin-1), oxidative stress (DJ-1) and inflammation (IL-8), that allows the accurate classification of patients at risk (p = 0.0006).

Conclusion

Using tissue protein enrichment technology, we validated proteins that are differentially expressed in hemorrhagic plaques as potential circulating biomarkers of coronary patients. Combinations of such circulating biomarkers could be used to stratify coronary patients.     

Predictors of Radial Artery Size in Patients Undergoing Cardiac Catheterization: Insights From the Good Radial Artery Size Prediction (GRASP) Study

Background

Radial artery occlusion occurs after transradial cardiac catheterization or percutaneous coronary intervention. Although use of a sheath larger than the artery is a risk factor for radial artery occlusion, radial artery size is not routinely measured. We aimed to identify bedside predictors of radial artery diameter.

Methods

Using ultrasound, we prospectively measured radial, ulnar, and brachial artery diameters of 130 patients who presented for elective percutaneous coronary intervention or diagnostic angiography. Using prespecified candidate variables we used multivariable linear regression to identify predictors of radial artery diameter.

Results

Mean internal diameters of the right radial, ulnar, and brachial arteries were 2.44 ± 0.60, 2.14 ± 0.53, and 4.50 ± 0.88 mm, respectively. Results for the left arm were similar. The right radial artery was larger in men than in women (2.59 vs 1.91 mm; P < 0.001) and smaller in patients of South Asian descent (2.00 vs 2.52 mm; P < 0.001). Radial artery diameter correlated with wrist circumference (r² = 0.26; P < 0.001) and shoe size (r² = 0.25; P < 0.001) and weakly correlated with height (r² = 0.14; P < 0.001), weight (r² = 0.18; P < 0.001), body mass index (r² = 0.07; P = 0.002), and body surface area (r² = 0.22; P < 0.001). The independent predictors of a larger radial artery were wrist circumference (r² = 0.26; P < 0.001), male sex (r² = 0.06; P < 0.001), and non-South Asian ancestry (r² = 0.05; P = 0.006; final model r² = 0.37; P < 0.001). A risk score using these variables predicted radial artery diameter (c-statistic, 0.71).

Conclusions

Wrist circumference, male sex, and non-South Asian ancestry are independent predictors of increased radial artery diameter. A risk score using these variables can identify patients with small radial arteries.     

Thoughts and behaviors of women with symptoms of acute coronary syndrome

Objective

Women delay seeking care for symptoms of acute coronary syndrome (ACS) because of atypical symptoms, perceptions of invulnerability, or keeping symptoms to themselves. The purpose of this study was to explore how women recognized and interpreted their symptoms and subsequently decided whether to seek treatment within the context of their lives.

Method

Grounded theory was used to provide the methodological basis for data generation and analysis. Data were collected using in-depth interviews with 9 women with ACS.

Results

All participants went through a basic social process of searching for the meaning of their symptoms which informed their decisions about seeking care. Stages in the process included noticing symptoms, forming a symptom pattern, using a frame of reference, finding relief, and assigning causality. The evolving MI group (n = 5) experienced uncertainty about bodily cues, continued life as usual, until others moved them toward care. The immediately recognizable MI group (n = 4) labeled their condition quickly, yet delayed, as they prepared themselves and others for their departure.

Conclusions

All women delayed, regardless of their ability to correctly label their symptoms. Education aimed at symptom recognition/interpretation addresses only part of the problem. Women should also be educated about the potential danger of overestimating the time they have to seek medical attention.     

Correlation between soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) expression and endoscopic activity in inflammatory bowel diseases

Background

Recently, a triggering receptor expressed on myeloid cells-1 was shown to be upregulated in the intestines of patients with inflammatory bowel diseases.

Aims

To investigate the relationship between serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) level and endoscopic activity in patients with inflammatory bowel diseases.

Methods

A total of 85 patients with ulcerative colitis and 34 patients with Crohn's disease were prospectively enrolled. Endoscopic disease activity was determined using the Mayo score and the Simplified Endoscopic Activity Score for Crohn's disease.

Results

In ulcerative colitis, sTREM-1 level was correlated more strongly with the endoscopic activity (r = 0.498) than the C-reactive protein level (r = 0.386) or erythrocyte sedimentation rate (r = 0.272), although not superior to the partial Mayo score (r = 0.611). Moreover, only sTREM-1 was correlated significantly with the endoscopic activity irrespective of the disease extent. In Crohn's disease, the Simplified Endoscopic Activity Score for Crohn's disease was correlated with both the C-reactive protein level (r = 0.585) and erythrocyte sedimentation rate (r = 0.474), but not with sTREM-1 level (r = 0.097).

Conclusions

In ulcerative colitis, sTREM-1 level was correlated most closely with the endoscopic disease activity among serum biomarkers, but was not superior to the clinical activity index. Our results suggest that sTREM-1 level may represent a complementary marker for the assessment of endoscopic activity in ulcerative colitis, but not in Crohn's disease.     

Prevalence and severity of ventricular dysfunction in patients with HIV-related pulmonary arterial hypertension

Objectives

To evaluate the occurrence of ventricular systolic dysfunction in human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH).

Background

Patients with HIV-related PAH may develop ventricular systolic dysfunction both as a consequence of PAH progression or of the myocardial involvement from the HIV infection itself.

Methods

Cardiac magnetic resonance imaging was applied to measure ejection fraction for the left ventricle and the right ventricle in patients with HIV-related PAH (n = 27) and in patients with PAH from other aetiologies (n = 115).

Results

In HIV-related PAH, ejection fraction values were lower and a higher proportion of patients presented with an advanced stage of ventricular dysfunction (55% vs. 25%; p = 0.009). In a multivariate model, PAH related to HIV infection remained independently associated with advanced ventricular dysfunction (p = 0.011).

Conclusions

Patients with HIV-related PAH have more prevalent and severe ventricular systolic dysfunction compared to patients with PAH from other aetiologies.     

The inverse association of incident cardiovascular disease with plasma bilirubin is unaffected by adiponectin

Objective

Bilirubin may protect against atherosclerotic cardiovascular disease (CVD). The heme oxygenase pathway is crucial for bilirubin generation, and is stimulated by adiponectin. We tested the relationship of plasma bilirubin with adiponectin, and determined whether the association of incident CVD with bilirubin is modified by adiponectin.

Methods

A community-based prospective nested case–control study (PREVEND cohort) was carried out in 87 non-diabetic men who developed a first cardiovascular event (cases) and 94 controls during a median follow-up of 6.1 (2.8–10.6) years.

Results

In all subjects combined, bilirubin was positively related to adiponectin (r = 0.205, P = 0.006). Age-adjusted incident CVD was inversely associated with bilirubin (hazard ratio (HR): 0.80 (95% CI 0.65–0.99), P = 0.048), independently of adiponectin (HR: 0.78 (95% CI 0.63–0.97), P = 0.027). Adiponectin did not modify the association of CVD with bilirubin (interaction term: P = 0.65). After additional adjustment for CVD risk factors, neither the association of incident CVD with bilirubin nor with adiponectin remained significant (P > 0.20 for both), and there was again no interaction between bilirubin and adiponectin on CVD risk (P = 0.67).

Conclusion

Bilirubin is related to adiponectin, but the association of bilirubin with CVD risk is largely unaffected by adiponectin.     

Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels

Objectives

Serum low density lipoprotein-cholesterol (LDL-C) correlates positively with serum PCSK9 in the general population, consistent with PCSK9 being a determinant of LDL-C levels. Patients with chronic kidney disease (CKD) on hemodialysis (HD) have lower total cholesterol (TC) and LDL-C compared to the general population. Serum PCSK9 and its relationship with serum lipids have not been reported in CKD patients on HD (CKD-HD).

Methods

We measured serum PCSK9 by ELISA and lipid levels in 66 CKD-HD patients and compared them to 178 non-CKD subjects. Since statins increase serum PCSK9 levels, CKD-HD patients were separated into those not on statin therapy (HD-NS, n = 32) and those taking statins (HD-S, n = 34). No control subjects were on statin therapy.

Results

Serum PCSK9, TC, LDL-C and HDL-C levels were significantly lower in the CKD-HD group (n = 66) compared to the control group. HD-NS patients showed lower PCSK9, TC and LDL-C levels than control subjects and PCSK9 levels correlated with TC and LDL-C levels (r = 0.35, p = 0.050; r = 0.423, p = 0.0158 respectively) as well as TG levels (r = 0.413, p = 0.0188). In HD-S patients, PCSK9 levels were not significantly different from the non-CKD group. There was no correlation between PCSK9 levels and TC and LDL-C levels in the HD-S group.

Conclusion

Our data are the first quantitative analysis of serum PCSK9 levels in CKD-HD patients. We show that serum PCSK9 in HD-NS patients is decreased and it retains a positive correlation with LDL-C, suggesting that PCSK9 may remain a significant determinant of LDL-C in CKD-HD subjects. We also show that statin therapy disrupts the correlation between LDL-C and PCSK9 in CKD-HD patients. These data suggest that the regulation of LDL-C by PCSK9 remains intact in CKD-HD patients. PCSK9 may also play a role in the metabolism of triglyceride-rich lipoproteins in CKD-HD patients.     

High hexacosanoic acid levels are associated with coronary artery disease

Aims

Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear.

Method

We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas–liquid chromatography mass spectrometry.

Results

C26:0 levels were significantly higher in the CAD group than in the control group (2.42 ± 0.32 vs. 2.27 ± 0.24 μg/ml, P = 0.01) and positively correlated with BMI (r = 0.23, P = 0.008), triglyceride levels (r = 0.22, P = 0.01), and hypertension (P = 0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls (P = 0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure.

Conclusion

High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.     

Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis

Aims

The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets.

Methods and results

Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKβ) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls.

Conclusions

There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.     

Potential pathological roles for oxidized low-density lipoprotein and scavenger receptors SR-AI,CD36, and LOX-1 in aortic valve stenosis

Objective

To clarify the potential mechanisms by which oxidized low-density lipoprotein (oxLDL) could contribute to the progression of aortic valve stenosis (AVS).

Methods

We investigated a total of 46 stenotic and 20 control human aortic valves. The mRNA expression levels of scavenger receptor class A type 1 (SR-A1), CD36, Lectin-like oxidized LDL receptor-1 (LOX-1), and scavenger receptor class B type 1 (SR-B1) were studied using qPCR. Their cellular distribution in the valves was assessed by immunohistochemistry, and the potential effects of oxLDL were studied in cultured myofibroblasts isolated from the aortic valves.

Results

In AVS, the proinflammatory SR-A1 and the angiogenic LOX-1 were upregulated (p = 0.003 and p = 0.002), whereas the antiangiogenic CD36 was downregulated (p = 0.02). The expression of the atheroprotective SR-B1 remained unchanged. Immunohistochemistry revealed that SR-A1 was expressed by macrophages, whereas the expression of CD36 and LOX-1 was confined to myofibroblasts and endothelial cells in the diseased valves. In cultured valvular myofibroblasts, mast cell-derived components and TNF-α induced LOX-1 expression (p = 0.05 and p < 0.001), whereas oxLDL promoted the expression of proinflammatory cytokines. Furthermore, the expression of osteoprotegerin, an inhibitor of valvular calcification, decreased in response to oxLDL. Finally, myofibroblasts derived from stenotic valves accumulated more DiI-labeled oxLDL than myofibroblasts derived from macroscopically healthy valves (p = 0.035), so revealing enhanced foam cell-forming potential of myofibroblasts in the diseased valves.

Conclusion

This study unveils the presence of SR-A1, CD36, and LOX-1 in aortic valves and suggests potential mechanisms by which they may contribute to the pathological angiogenesis, inflammation, calcification, and lipid accumulation in AVS.