Subjects with Low Plasma HDL Cholesterol Levels Are Characterized by an Inflammatory and Oxidative Phenotype

Background

Epidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies.

Objective

To examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels.

Methods and Results

Fifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited. Low HDL cholesterol was defined as ≤10th age/sex specific percentile and high HDL-C was defined as ≥90 age/sex specific percentile. Inflammatory markers in circulation and PBMC gene expression of cholesterol efflux mediators were measured. Our main findings were: (i) subjects with low plasma HDL cholesterol levels were characterized by increased plasma levels of CRP, MMP-9, neopterin, CXCL16 and ICAM-1 as well as low plasma levels of adiponectin, suggesting an inflammatory phenotype; (ii) these individuals also had reduced paraoxonase (PON)1 activity in plasma and PON2 gene expression in peripheral blood mononuclear cells (PBMC) accompanied by increased plasma levels of oxidized LDL suggesting decreased anti-oxidative capacity; and (iii) PBMC from low HDL subjects also had decreased mRNA levels of ABCA1 and ABCG1, suggesting impaired reverse cholesterol transport.

Conclusion

Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype that could contribute to the increased risk of atherosclerotic disorders in these subjects with low HDL levels.     

The Value and Distribution of High-Density Lipoprotein Subclass in Patients with Acute Coronary Syndrome

Background

High-density lipoprotein (HDL) enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS) properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS) and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS.

Methods

Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG) abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD) on coronary angiography.

Results

The small-sized preβ₁-HDL, HDL_3b, and HDL_3a levels were significantly higher, and the large-sized HDL_2a and HDL_2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP) and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP), and the reduction in the high density lipoprotein cholesterol (HDL-C) levels, the HDL_2b contents significantly decreased and the preβ₁-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apo)A-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC) and fasting plasma glucose (FPG) levels were inversely associated with HDL_2a, and HDL_2b. Moreover, the FPG levels were positively related to HDL_3c, HDL_3b, and HDL_3a in ACS patients.

Conclusion

The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL subclass distribution phenotype might be useful as a novel biomarker to assist in the risk stratification of patients with ACS.     

Both Paraoxonase-1 Genotype and Activity Do Not Predict the Risk of Future Coronary Artery Disease; the EPIC-Norfolk Prospective Population Study

Background

Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD), in a large prospective case-control study.

Methodology/Principal Findings

Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237) were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7±45.3 versus 62.6±45.8 U/L, p = 0.3) and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001). The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84–1.15], p = 0.8). Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63–0.95], p = 0.01; p-trend = 0.06). PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001) and more linearly predicted CAD risk (0.79[0.64–0.98], p = 0.03; p-trend = 0.008). However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size) and apolipoproteinA-I (0.94[0.74–1.18], p-trend = 0.3).

Conclusions/Significance

This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis.     

Does Adhesive Capsulitis of the Shoulder Increase the Risk of Stroke? A Population-Based Propensity Score-Matched Follow-Up Study

Objectives

A previous population-based study reported an increased risk of stroke after the occurrence of adhesive capsulitis of the shoulder (ACS), but there were substantial imbalances in the distribution of age and pre-existing vascular risk factors between subjects with ACS and without ACS, which might lead to a confounded association between ACS and stroke. The purpose of the present large-scale propensity score-matched population-based follow-up study was to clarify whether there is an increased stroke risk after ACS.

Methods

We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 22025 subjects with at least two ambulatory visits with the principal diagnosis of ACS in 2001 was enrolled in the ACS group. The non-ACS group consisted of 22025, propensity score-matched subjects without ACS. The stroke-free survival curves for these 2 groups were compared using the Kaplan-Meier method. Stratified Cox proportional hazard regression with patients matched on propensity score was used to estimate the effect of ACS on the occurrence of stroke.

Results

During the two-year follow-up period, 657 subjects in the ACS group (2.98%) and 687 in the non-ACS group (3.12%) developed stroke. The hazard ratio (HR) of stroke for the ACS group was 0.93 compared to the non-ACS group (95% confidence interval [CI], 0.83–1.04, P = 0.1778). There was no statistically significant difference in stroke subtype distribution between the two groups (P = 0.2114).

Conclusions

These findings indicate that ACS itself is not associated with an increased risk of subsequent stroke.     

Reduced Apolipoprotein Glycosylation in Patients with the Metabolic Syndrome

Objective

The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.

Methods

Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.

Results

Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma - apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL - apoB, apoC3, and apoE were increased; (3) LDL - apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001).

Conclusions

Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.     

Role of PON in Anoxia-Reoxygenation Injury: A Drosophila Melanogaster Transgenic Model

Background

Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL), thought to prevent oxidative modification of low-density lipoprotein (LDL). This enzyme has been implicated in lowering the risk of cardiovascular disease. Anoxia-reoxygenation and oxidative stress are important elements in cardiovascular and cerebrovascular disease. However, the role of PON1 in anoxia-reoxygenation or anoxic injury is unclear. We hypothesize that PON1 prevents anoxia-reoxygenation injury. We set out to determine whether PON1 expression in Drosophila melanogaster protects against anoxia-reoxygenation (A-R) induced injury.

Methods

Wild type (WT) and transgenic PON1 flies were exposed to anoxia (100% Nitrogen) for different time intervals (from 1 to 24 hours). After the anoxic period, flies were placed in room air for reoxygenation. Activity and survival of flies was then recorded.

Results

Within 5 minutes of anoxia, all flies fell into a stupor state. After reoxygenation, survivor flies resumed activity with some delay. Interestingly, transgenic flies recovered from stupor later than WT. PON1 transgenic flies had a significant survival advantage after A-R stress compared with WT. The protection conferred by PON1 expression was present regardless of the age or dietary restriction. Furthermore, PON1 expression exclusively in CNS conferred protection.

Conclusion

Our results support the hypothesis that PON1 has a protective role in anoxia-reoxygenation injury, and its expression in the CNS is sufficient and necessary to provide a 100% survival protection.     

Long-Term Risk of Cardiovascular Disease among Type 2 Diabetic Patients with Asymptomatic Intracranial Atherosclerosis: A Prospective Cohort Study

Objective

To investigate whether asymptomatic middle cerebral artery (MCA) stenosis is associated with risk of cardiovascular disease (CVD) in Chinese with type 2 diabetes.

Methods

In this prospective cohort study, 2,144 Hong Kong Chinese with type 2 diabetes and without history of stroke or atrial fibrillation were recruited in 1994–1996 and followed up for a median of 14.51 years. Participants were assessed at baseline for MCA stenosis using transcranial Doppler. We performed survival analysis to assess the association between asymptomatic MCA stenosis and first CVD event, defined as ischemic stroke, acute coronary syndrome (ACS) or cardiovascular death.

Results

Of the 2,144 subjects, MCA stenosis at baseline was detected in 264 (12.3%). Rates of stroke, ACS and cardiovascular death per 100 were, respectively, 2.24, 2.92 and 1.11 among participants with stenosis, higher than among those without stenosis. Ten-year cumulative occurrence of stroke, ACS and cardiovascular death in subjects with MCA stenosis was 20%, 24% and 10%, respectively, higher than the corresponding values for subjects without stenosis(all P<0.001). After adjusting for covariates, MCA stenosis was found to be an independent predictor of stroke [hazard ratio (HR) 1.40, 95%CI 1.05–1.86; P = 0.02], ACS (HR 1.35, 95%CI 1.04–1.75; P = 0.02) and cardiovascular death(HR 1.56, 95%CI 1.04–2.33; P = 0.03).

Conclusions

Asymptomatic MCA stenosis is a risk factor for CVD in Chinese with type 2 diabetes, and detection of asymptomatic MCA stenosis by transcranial Doppler can identify diabetic individuals at high risk of future CVD. This finding is particularly important for diabetic individuals in Asia, where intracranial atherosclerosis is common.     

Elevated Frequencies of Circulating Th22 Cell in Addition to Th17 Cell and Th17/Th1 Cell in Patients with Acute Coronary Syndrome

Background

Atherosclerosis is a chronic inflammatory disease mediated by immune cells. Th22 cells are CD4⁺ T cells that secret IL-22 but not IL-17 or IFN-γ and are implicated in the pathogenesis of inflammatory disease. The roles of Th22 cells in the pathophysiologic procedures of acute coronary syndrome (ACS) remain unclear. The purpose of this study is to investigate the profile of Th22, Th17 and Th17/Th1 cells in ACS patients, including unstable angina (UA) and acute myocardial infarction (AMI) patients.

Design and Methods

In this study, 26 AMI patients, 16 UA patients, 16 stable angina (SA) patients and 16 healthy controls were included. The frequencies of Th22, Th17 and Th17/Th1 cells in AMI, UA, SA patients and healthy controls were examined by flow cytometry. Plasma levels of IL-22, IL-17 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Th22, Th17 and Th17/Th1 cells were significantly increased in AMI and UA patients compared with SA patients and healthy controls. Moreover, plasma IL-22 level was significantly elevated in AMI and UA patients. In addition, Th22 cells correlated positively with IL-22 as well as Th17 cells in AMI and UA patients.

Conclusion

Our findings showed increased frequencies of both Th22 and Th17 cells in ACS patients, which suggest that Th22 and Th17 cells may play a potential role in plaque destabilization and the development of ACS.     

Serum Copeptin and Cortisol Do Not Accurately Predict Sickle Cell Anaemia Vaso-Occlusive Crisis as C-Reactive Protein

Objective

This study assessed the diagnostic performance and prognostic properties of C-reactive protein (CRP), copeptin and cortisol in individuals with sickle cell anaemia (SCA).

Design

Prospective case-control study

Methods

Sixty consecutive SCA subjects (18–40 years) comprising 30 subjects in the steady state and 30 subjects in vaso-occlusive crisis (VOC) were recruited into this study. Thirty (30) apparently healthy individuals with HbAA genotype served as controls. ELISA was used for the determination of serum levels of copeptin, CRP and cortisol. Data obtained were statistically analyzed using the Student’s t-test and Mann Whitney U as appropriate and P<0.05 was considered significant.

Results

SCA subjects in VOC had significantly lower copeptin level and significantly higher CRP level compared with controls. However, serum levels of copeptin, cortisol and CRP were significantly higher in SCA subjects in VOC compared with SCA subjects in steady state. Furthermore, CRP had the widest Area under the ROC curve (AUROC) than copeptin and cortisol. No significant difference was observed in the levels of copeptin, CRP and cortisol when SCA subjects in VOC who were hospitalized for less ≤5 days were compared with subjects who had longer stays.

Conclusion

It could be concluded that C-reactive protein has a superior diagnostic performance for vaso-occlusive crisis in individuals with sickle cell anaemia and that C-reactive protein, cortisol and copeptin are not good prognostic markers in SCA subjects in vaso-occlusive crisis.     

Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus

Introduction

Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity.

Methods

Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol.

Results

HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186).

Conclusions

Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.     

Adrenal Function in Females with Low Plasma HDL-C Due to Mutations in ABCA1 and LCAT

Introduction

Adrenal steroidogenesis is essential for human survival and depends on the availability of the precursor cholesterol. Male subjects with low plasma levels of high density lipoprotein (HDL) cholesterol are characterized by decreased adrenal function. Whether this is also the case in female subjects with low plasma HDL-C levels is unresolved to date.

Findings

15 female ATP binding cassette transporter AI (ABCAI) and 14 female lecithin-cholesterol acyltransferase (LCAT) were included in the study. HDL-C levels were 38% and 41% lower in ABCA1 and LCAT mutation carriers compared to controls, respectively. Urinary steroid excretion of 17-ketogenic steroids or 17-hydroxy corticosteroids did not differ between 15 female ABCA1 mutation carriers (p = 0.27 vs 0.30 respectively) and 30 matched normolipidemic controls or between 14 female LCAT mutation carriers and 28 matched normolipidemic controls (p = 0.10 and 0.14, respectively). Cosyntropin testing in an unselected subgroup of 8 ABCA1 mutation carriers and 3 LCAT mutation carriers did not reveal differences between carriers and controls.

Conclusion

Adrenal function in females with molecularly defined low HDL-C levels is not different from controls. The discrepancy with the finding of impaired steroidogenesis in males with molecularly defined low HDL-C levels underscores the importance of gender specific analyses in cholesterol-related research.     

Prevalence of Alzheimer’s Pathologic Endophenotypes in Asymptomatic and Mildly Impaired First-Degree Relatives

Objective

A positive family history (FH) is a risk factor for late-onset Alzheimer’s disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.

Design

Cross-sectional analyses of data from a national biomarker study.

Setting

The Alzheimer’s Disease Neuroimaging Initiative national study.

Patients

257 subjects (ages 55–89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.

Outcome Measures

Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.

Statistics

Univariate and multivariate analyses.

Results

In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH− subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited “pathologic signature of AD” (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH− controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH− subjects in any group.

Conclusions

A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.     

Hepatic ACAT2 Knock Down Increases ABCA1 and Modifies HDL Metabolism in Mice

Objectives

ACAT2 is the exclusive cholesterol-esterifying enzyme in hepatocytes and enterocytes. Hepatic ABCA1 transfers unesterified cholesterol (UC) to apoAI, thus generating HDL. By changing the hepatic UC pool available for ABCA1, ACAT2 may affect HDL metabolism. The aim of this study was to reveal whether hepatic ACAT2 influences HDL metabolism.

Design

WT and LXRα/β double knockout (DOKO) mice were fed a western-type diet for 8 weeks. Animals were i.p. injected with an antisense oligonucleotide targeted to hepatic ACAT2 (ASO6), or with an ASO control. Injections started 4 weeks after, or concomitantly with, the beginning of the diet.

Results

ASO6 reduced liver cholesteryl esters, while not inducing UC accumulation. ASO6 increased hepatic ABCA1 protein independently of the diet conditions. ASO6 affected HDL lipids (increased UC) only in DOKO, while it increased apoE-containing HDL in both genotypes. In WT mice ASO6 led to the appearance of large HDL enriched in apoAI and apoE.

Conclusions

The use of ASO6 revealed a new pathway by which the liver may contribute to HDL metabolism in mice. ACAT2 seems to be a hepatic player affecting the cholesterol fluxes fated to VLDL or to HDL, the latter via up-regulation of ABCA1.     

Paraoxonase1, its Q192R polymorphism and HDL-cholesterol in relation to intensive cardiac care unit stay in ischemic heart disease

AIMS AND OBJECTIVES:

The present study was evaluated the atheroprotective potential of paraoxonase1 (PON1) and its Q192R polymorphism, to determine whether this polymorphism, which is responsible for differential PON1 activity plays any role in the pathogenesis, severity and extent of coronary artery disease (CAD).

MATERIALS AND METHODS:

This hospital-based cross-sectional study investigated 60 diagnosed cases of CAD and 60 age and gender matched controls. All were assessed for serum PON1 activity, PON1 Q192R polymorphism and for classical cardiovascular risk factors. Individual serum phenotyping for PON1 Q192R polymorphism was determined by double substrate hydrolysis assay. Severity of CAD was assessed by the length of intensive cardiac care unit (ICCU) stay.

RESULTS:

Serum PON1 activity is significantly reduced in cases of CAD (92.6 ± 31.13 IU/L when compared with controls (105.26 ± 32.53 IU/L). Furthermore, serum arylesterase activity is reduced in CAD patients (90.31 ± 23.26 kU) when compared with the control subjects (101.61 ± 28.68 kU). Serum PON1 and arylesterase activities are significantly negatively correlated with the length of ICCU stay (r = −393 and r = −374 respectively). There is no significant difference in the occurrence of CAD and length of ICCU stay among the PON1 phenotypes (P = 0.92). Logistic regression analysis after adjustment of established risk factors revealed no significant association between CAD risk and PON1 Q192R polymorphism (odds ratios: 1.179 [95% confidence intervals: 0.507-2.744], P = 0.702).

SUMMARY AND CONCLUSIONS:

The current study demonstrates that the activity of the PON1 enzyme may be more important factor than the PON1 Q192R polymorphism in the severity and extent of CAD.     

Lack of effects of statins on high-density lipoprotein subfractions in HIV-1-infected patients receiving protease inhibitors

Background

We evaluated the effect of 45 days of rosuvastatin or pravastatin treatment on the distribution of HDL subfractions in HIV-1-infected individuals receiving boosted protease inhibitors (PIs) with cardiovascular risk.

Increased Risk of Acute Coronary Syndrome among Patients with Urinary Stone Disease: A Nationwide Population-Based Cohort Study

Background/Objectives

Urinary stones (US) are associated with systemic metabolic and endocrine disorders that share risk factors typically associated with acute coronary syndrome (ACS).

Methods

For this investigation, 30 142 patients with US were set as the research group, and 121 768 randomly selected patients were set as the comparison group through frequency matching by age, sex, and index year. Each patient was individually tracked to identify those who developed ACS during the follow-up period. Cox proportional hazards regression and the Kaplan-Meier method were adopted to calculate the hazard ratios of ACS risk and plot the survival curve.

Results

Overall, 275 (13.4 per 10 000 person-y) and 736 events (9.1 per 10 000 person-y) were observed among patients in the research and comparison cohorts, respectively. The patients with US had a substantially lower ACS-free survival rate compared with that of the patients in the comparison cohort (P<.001). After adjusting for potential risk factors, the patients with US were observed to have a 1.22-fold higher risk of ACS compared with patients in the comparison cohort (95% confidence interval = 1.05–1.40, P<.001), particularly among younger patients.

Conclusions

The results indicate that US is associated with increased risk of developing ACS, particularly among young (≤49 years) and male adults. Future studies should examine the possible mechanisms of US-related ACS morbidity by conducting multicenter recruitment and measurements of laboratory data.     

Herpes Zoster Is Associated with Prior Statin Use: A Population-Based Case-Control Study

Background

This study investigated the association between statin use and herpes zoster (HZ) occurrence in a population-based case-control study.

Methods

Study subjects were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. This study included 47,359 cases with HZ and 142,077 controls. We performed conditional logistic regression analyses to calculate the odds ratio (OR) to present the association between HZ and having previously been prescribed statin.

Results

We found that 13.0% of the sampled subjects had used statins, at 15.5% and 12.1% for cases and controls, respectively (p<0.001). A conditional logistic regression analysis suggested that the adjusted OR of being a statin user before the index date for cases was 1.28 (95% confidence interval (CI): 1.24∼1.32) compared to controls. Subjects aged 18∼44 years had the highest adjusted OR for prior statin use among cases compared to controls (OR: 1.69; 95% CI: 1.45∼1.92). Furthermore, we found that the ORs of being a regular and irregular statin user before the index date for cases were 1.32 (95% CI: 1.27∼1.38) and 1.23 (95% CI: 1.181.29), respectively, compared to controls.

Conclusions

We concluded that prior statin use was associated with HZ occurrence.     

Fibrinogen Aα Thr312Ala Polymorphism Specifically Contributes to Chronic Thromboembolic Pulmonary Hypertension by Increasing Fibrin Resistance

Background

Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary thromboembolism (PTE), but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated.

Methods

Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP). Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls).

Results

Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037) and 95% confidence interval (95% CI, 1.262–3.289) showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G) genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype.

Conclusions

Fibrinogen Aα Thr312Ala (A/G) polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.     

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors: a meta-analysis

Objectives

To investigate which anthropometric adiposity measure has the strongest association with cardiovascular disease (CVD) risk factors in Caucasian men and women without a history of CVD.

Design

Systematic review and meta-analysis.

Methods

We searched databases for studies reporting correlations between anthropometric adiposity measures and CVD risk factors in Caucasian subjects without a history of CVD. Body mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage were considered the anthropometric adiposity measures. Primary CVD risk factors were: systolic blood pressure, diastolic blood pressure, high density lipoprotein (HDL) cholesterol, triglycerides and fasting glucose. Two independent reviewers performed abstract, full text and data selection.

Results

Twenty articles were included describing 21,618 males and 24,139 females. Waist circumference had the strongest correlation with all CVD risk factors for both men and women, except for HDL and LDL in men. When comparing BMI with waist circumference, the latter showed significantly better correlations to CVD risk factors, except for diastolic blood pressure in women and HDL and total cholesterol in men.

Conclusions

We recommend the use of waist circumference in clinical and research studies above other anthropometric adiposity measures, especially compared with BMI, when evaluating CVD risk factors.     

The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments

Background

Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease.

Methods

The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic.

Principal findings

In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion.

Conclusions

Betaine excretion correlates with homocysteine in subjects with elevated blood lipids.