Association between small dense LDL levels and hepatic fibrosis in patients with nonalcoholic fatty liver disease

While patients with nonalcoholic fatty liver disease (NAFLD) continue to increase worldwide, few hematological biomarkers are helpful. This study examined the potential of small dense low density lipoprotein (sdLDL) as a noninvasive biomarker for NAFLD and investigated the relevance of liver fibrosis. One hundred seventy two patients were enrolled: 121 NAFLD patients and 51 healthy controls. The lipoprotein profiles of NAFLD patients and controls were analyzed, and transient elastography (Fibroscan®) was performed to evaluate the degree of NAFLD. The liver biopsy results in some NAFLD patients were also analyzed. Age-gender matching was performed among the 172 patients, and a comparison with 46 NAFLD patients with the control group confirmed that the sdLDL (P < .001) is significantly higher in the NAFLD group. A liver fibrosis test performed on 121 NAFLD patients confirmed a positive correlation between the degree of hepatic fibrosis and the sdLDL/LDL ratio (R = 0.215, P = .017). The area under the curve of the sdLDL for the diagnosis of NAFLD was 0.734 (95% CI, 0.631–0.838), and the area under the curve of the sdLDL/LDL ratio was 0.730 (95% CI, 0.621–0.829). The sdLDL and NAFLD activity scores of the 11 NAFLD patients who underwent liver biopsy showed a positive correlation, but it was not statistically significant. The sdLDL was higher in NAFLD patients than in controls and showed a tendency to increase gradually with increasing degree of hepatic steatosis and fibrosis. In particular, the sdLDL/LDL ratio showed a significant correlation with the degree of hepatic fibrosis, and the sdLDL measurement could be useful in NAFLD patients.     

Subclinical carotid atherosclerosis in patients with psoriatic arthritis

OBJECTIVE: To examine the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) compared with healthy controls, and to identify clinical and biologic markers for atherosclerotic disease in this patient population. METHODS: Subclinical atherosclerosis was defined as the average of intima-media thickness (IMT) measures in the common carotid artery, bifurcation, and internal carotid artery on both sides above the 95th percentile of healthy controls. IMT was measured using carotid ultrasonography in 82 consecutive PsA patients and 82 healthy controls matched on age, sex, and ethnicity. We also ascertained traditional and novel cardiovascular (CV) risk factors, Framingham risk score (FRS), disease severity, treatment, and inflammatory markers in all PsA patients. RESULTS: No PsA patients had clinically overt CV diseases. After adjusting for traditional CV risk factors, PsA patients had a higher prevalence of subclinical atherosclerosis. PsA patients with subclinical atherosclerosis had significantly increased sugar, total triglyceride levels, total cholesterol/high-density cholesterol, white cell count, and patients' global assessment score compared with those without subclinical atherosclerosis. Using logistic regression analysis, independent explanatory variables associated with subclinical atherosclerosis in PsA included increased sugar and total triglyceride levels. The FRS was similar in PsA patients with or without subclinical atherosclerosis. Twenty-six (35%) of 74 patients had subclinical atherosclerosis despite having a low CV risk. CONCLUSION: PsA is associated with subclinical atherosclerosis after adjusting for traditional CV risk factors. Independent explanatory variables associated with subclinical atherosclerosis in PsA included increased sugar and total triglyceride levels. Carotid IMT can identify PsA patients with subclinical atherosclerosis who may benefit from early intervention.     

Association between environmental factors and onset of psoriatic arthritis in patients with psoriasis

Objective

To investigate the association between potential environmental exposures and the development of psoriatic arthritis (PsA) in patients with psoriasis.

Methods

In this case–control study, the cases were patients with recent‐onset PsA. The controls were psoriasis patients without arthritis. The occurrence of the following environmental exposures was recorded through a standardized questionnaire: smoking, alcohol consumption, infections, injuries, physically demanding occupational tasks, stressful life events, vaccinations, and female hormonal exposures. The association between each exposure to environmental events and disease status was assessed through logistic regression after adjustment for age, sex, education level, and duration and severity of psoriasis.

Results

There were 159 subjects in each group. The following exposures remained significantly associated with PsA following multivariate logistic regression: lifting cumulative loads of at least 100 pounds/hour (odds ratio [OR] 2.8, 95% confidence interval [95% CI] 1.51–5.05), infections that required antibiotics (OR 1.7, 95% CI 1.00–2.77), smoking (OR 0.6, 95% CI 0.36–0.89), and injuries (OR 2.1, 95% CI 1.11–4.01). The results were not appreciably changed with the inclusion of each of these factors in a single regression model; however, the level of significance for injuries had become borderline. No association was found between PsA and alcohol consumption, vaccination, stressful life events, and female hormonal exposures.

Conclusion

Lifting heavy loads and infections that required antibiotics were associated with the occurrence of arthritis among patients with psoriasis. There was an inverse association between smoking and PsA. Further studies are necessary to determine whether these and other environmental factors are moderated by predisposing genetic factors.     

Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis

OBJECTIVES: To evaluate the extent of subclinical atherosclerosis by measuring the intima-media wall thickness (IMT) of the common carotid artery in patients with psoriatic arthritis (PsA) and to identify vascular risk factors associated with PsA. METHODS: Forty-seven patients with PsA were compared with 100 allegedly healthy subjects. Carotid duplex scanning was used to measure common carotid artery IMT. Traditional risk factors, such as gender, age, body mass index (BMI), hypertension, smoking, and lipids were checked. Assessment of PsA activity included clinical patterns of involvement, degree of severity, duration of morning stiffness, number of tender and swollen joints, degree of pain and fatigue, the Bath Ankylosing Spondylitis Disease Activity Index, the Psoriasis Area and Severity Index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen. RESULTS: The average IMT (mean +/- standard deviation) for PsA patients was significantly higher compared with controls (0.76 +/- 0.11 versus 0.64 +/- 0.27, respectively, P < 0.00001) for the whole group and after adjustment for age, gender, BMI, hypertension, and hyperlipidemia. The PsA subjects had significantly higher levels of hypertension, hyperlipidemia, ESR, CRP, and fibrinogen, and their average IMT significantly correlated with age, BMI, duration of skin and joint disease, spine involvement, ESR, and fibrinogen. IMT did not correlate with the presence of oligo- or polyarthritis but was increased in patients with clinical spinal involvement. IMT was not associated with the degree of severity or the use of different therapies for PsA, including methotrexate or tumor necrosis factor-alpha-blocking agents. CONCLUSIONS: PsA patients exhibited greater IMT than healthy controls. Increased IMT independently correlated with parameters of disease activity and conventional risk factors of atherosclerosis.     

银屑病性关节炎患者动脉粥样硬化的机制和危险因素

流行病学研究显示,银屑病以及银屑病关节炎(PsA)患者动脉粥样硬化(AS)的危险因素(如肥胖、糖尿病、高脂血症)增加,并且主要心血管不良事件(MACE)的发病率升高。PsA与心血管疾病、代谢综合征等疾病存在着一些共同的涉及慢性炎症的通路以及细胞因子,可能是此类患者合并心血管疾病、代谢综合征的基础。本文综述了PsA患者合并AS的危险因素,为PsA患者罹患AS的监测及预防提供指导。     

Association between HLA-BW38 and peripheral psoriatic arthritis

The frequency distribution of HLA antigens was studied in a group of psoriatic patients with and without arthritis. HLA-BW38 was found significantly increased in the group with peripheral psoriatic arthritis. There were no differences in the clinical features of the arthritis in the BW38 positive (+) and BW38 negative (-) individuals. It is suggested that BW38 is a genetic marker and/or an indicator of peripheral joint involvement in psoriatic patients.     

Treatment of small dense LDL

The increased frequency of small, dense LDL is associated with the risk of coronary heart disease (CHD). Possible mechanisms include the increased susceptibility of small, dense LDL to oxidation and its high affinity for LDL-receptor-independent cell surface binding sites. Although more than 30% of adult men in the USA have been reported to have small,dense LDL, only 5.4% of young Japanese men are affected. However, more than 76% of Japanese diabetics with coronary heart disease have small, dense LDL. Furthermore, almost half of all obese women (BMI > 35 kg/m(2)) have small, dense LDL. Our previous observation revealed that type 2 diabetics had smaller LDL even if they were apparently normolipidemic. In the normotriglycelidemic group there was also a close relationship between LDL size and plasma triglyceride. Diabetics with microalbuminuria had smaller LDL than those with normoalbuminuria, indicating the early nephrotoxicity of small, dense LDL. We also found that young men with high-normal blood pressure have smaller LDL than those with optimal blood pressure. Furthermore, LDL size was decreased not only in preeclamptic women but also in normal pregnant women. Finally, weight reduction by obese women through strict diet control, the treatment of diabetics by acarbose or troglitazone, and the treatment of hyperlipidemia by new statins as well as fibrates were all successful in increasing LDL size associated with decreased plasma triglyceride.     

Association between the interleukin-1 family gene cluster and psoriatic arthritis

OBJECTIVE: The interleukin-1 (IL-1) cytokine elicits a wide variety of biologic activities that initiate and promote an inflammatory response. The loci in the IL1 gene cluster have recently been associated with ankylosing spondylitis (AS). Since there is clinical and immunologic overlap between psoriatic arthritis (PsA) and AS, we wanted to examine the association between a panel of single-nucleotide polymorphisms (SNPs) in the IL1 gene family cluster and chromosome 2q12-13 in a PsA cohort. METHODS: Two hundred twelve PsA patients and 150 ethnically matched controls were genotyped with 11 SNPs in IL1A, 9 SNPs in IL1B, and 9 SNPs in IL1F5-10. Univariate analyses of the 29 single markers and short intragenic haplotypes identified several associated regions. Seventeen markers of interest were noted and further investigated to determine which markers or short haplotypes independently predict case-control status, using a stepwise logistic model. RESULTS; Two regions contributing independently to risk of disease in PsA were noted: a region spanned by markers rs3783547, rs3783543, and rs17561 in IL1A, and a region near the end of IL1B, through IL1F7, IL1F8, and into IL1F10. The best model contained markers rs3811047, rs1562304, and rs3811058, and 1 haplotype constructed from the 3 markers in region 1, with a likelihood ratio of 25.34 (4 degrees of freedom). CONCLUSION: The IL1 locus appears to be a high-priority susceptibility locus in PsA, with at least 2 independent regions that confer increased risk.     

Effects of treatment with Sandostatin LAR on small dense LDL and remnant-like lipoproteins in patients with acromegaly

OBJECTIVE: Acromegalic patients have been shown to have an increase in the concentrations of small dense low-density lipoprotein (LDL) and remnant-like lipoprotein particles (RLP). These lipoproteins are atherogenic and may contribute to the cardiovascular risk of these patients. The aim of this study was to determine whether treatment of acromegaly using Sandostatin LAR could lower these atherogenic lipoproteins. METHODS: Fourteen patients with active acromegaly were recruited and Sandostatin LAR, a long-acting somatostatin analogue, was given every 4 weeks by intramuscular injection for 6 months. Fasting lipids, lipoproteins, lipolytic enzymes were determined at baseline, 12 and 24 weeks after treatment. Small dense LDL was measured using density gradient ultracentrifugation and RLP-cholesterol (RLP-C) by an immunoseparation assay. RESULTS: There was already a marked reduction in GH and IGF-1 by week 8 and, in all subjects, IGF-1 levels within their respective age-specific normal range were achieved. At week 12, plasma triglyceride significantly decreased (P < 0.01) and both HDL2 (P < 0.01) and HDL3 (P < 0.01) subfractions increased. A reduction was seen in small dense LDL concentration (P < 0.05) and RLP-C (P < 0.05). Lipoprotein lipase (LPL) activity increased (P < 0.01) and the magnitude of the increase in LPL activity correlated with the increase in HDL at 3 months (r = 0.55, P < 0.05) but not with the changes in plasma triglyceride, small dense LDL or RLP-C. The improvement in plasma lipids and lipoproteins persisted until the end of the study. CONCLUSION: Sandostatin LAR is effective in the treatment of acromegaly and is associated with favourable changes in plasma lipids and a reduction in small dense LDL and RLP-C.     

Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects

OBJECTIVE: To examine the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: Carotid artery intima-media thickness (IMT) and carotid plaque were measured using high-resolution B-mode ultrasound in 204 patients with RA, ages 40-85, and 102 age- and sex-matched healthy persons. No subject in either group had ever smoked cigarettes. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to measure systemic inflammation. The relationship of the carotid artery IMT and carotid plaque to inflammation markers was examined, adjusting for age, sex, RA versus control status, and the cardiovascular (CV) risk factors hypercholesterolemia, systolic blood pressure, diabetes mellitus, and body mass index (BMI). RESULTS: A significant linear trend for increased carotid artery IMT was associated with increasing ESR and CRP categories (r = 0.16, P = 0.004 for ESR, and r = 0.13, P = 0.02 for CRP). These trends did not differ among RA cases and controls, and were independent of age, sex, and CV risk factors. The difference in carotid artery IMT between the lowest and highest categories of ESR was 0.221 mm (95% confidence interval [95% CI] 0.767-1.020, P = 0.02). The difference between extreme CRP categories was 0.275 mm (95% CI 0.039-0.509, P = 0.02). Both remained significant after CV risk factor adjustment. Carotid plaque displayed a similar relationship to markers of inflammation. CONCLUSION: Increased carotid artery IMT and the presence of carotid plaque are associated with markers of systemic inflammation in patients with RA and in healthy subjects. This observation is consistent with hypotheses that assign a role to systemic inflammation in atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.     

Autoantibodies against oxidized low-density lipoprotein (LDL) and carotid atherosclerosis in patients with rheumatoid arthritis

OBJECTIVES: To examine the relationship between autoantibodies against oxidized low-density lipoprotein (oxLDL-Abs) and the progression of carotid atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients without evidence of risk factors for atherosclerosis (RA group) and 30 healthy volunteers (normal group) were investigated. The mean intima-media thickness of the common carotid artery (mean CCA-IMT) was measured by high-resolution B-mode ultrasonography. The titer of IgG oxLDL-Abs was measured by enzyme-linked immunosorbent assay. The relationships among mean CCA-IMT, IgG oxLDL-Ab titer and patient factors such as body mass index, systolic blood pressure, diastolic blood pressure, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum lipid levels were examined. RESULTS: Mean CCA-IMT, CRP, ESR and titer of IgG oxLDL-Abs were significantly higher in the RA group than in the normal group. Although mean CCA-IMT showed a positive correlation only with age in multivariate analysis, IgG oxLDL-Ab titers in the RA group were positively associated with mean CCA-IMT and independently with age and sex by multiple regression analysis. CONCLUSIONS: IgG oxLDL-Abs appear to be associated with the degree of carotid atherosclerosis in patients with RA, and are independent of traditional risk factors for atherosclerotic diseases. These results suggest a possible link between autoimmune mechanisms and accelerated atherosclerosis in RA.     

Association of nuclear factor-kappaB in psoriatic arthritis

OBJECTIVE: To examine the association of single nucleotide polymorphisms (SNP) in the NFKB1 gene, as well as 2 genes in the nuclear factor (NF)-kappaB functional complex (RelA and NFKBIA), in patients with psoriatic arthritis (PsA) from Newfoundland. METHODS: Patients with PsA and controls were genotyped for one 4-base insertion/deletion and 5 SNP in NFKB1, 4 SNP in RelA, and 7 SNP in NFKBIA by time-of-flight mass spectrometry, using the Sequenom platform. Chi-square analysis was used to test the single locus associations between SNP in the NF-kappaB complex and PsA. Associations between multi-locus haplotypes and case or control status were tested using the software PHASE. RESULTS: Two hundred and twenty-four patients with PsA (52% male) and 88 ethnically matched controls (64% male) were genotyped. No association was noted with any of the SNP tested for the single locus associations in NFKB1, RelA, and NFKBIA or with multi-locus haplotypes. In particular, the allele frequency for the NFKB1 -94delATTG was 41.7% in cases and 41.6% in the controls (p = 0.97). CONCLUSION: No association between the NFKB1 -94 ins/delATTG promoter polymorphism or with other NF-kappaB complex SNP in patients with PsA from Newfoundland was observed.     

Rhythm profile in patients with psoriatic arthritis

OBJECTIVE: To analyze the rhythmic profile in patients with psoriatic arthritis (PA). DESIGN: In order to evaluate the rhythmic profile of patients with PA, we have carried out ambulatory 24 hour ECG recordings in 22 patients presented consecutively to the Holter ECG laboratory. SETTING: Patients followed in a specialised rheumatology consultation, in Santa Maria Hospital. PATIENTS: We have studied 22 patients (pts), 10 male and 12 female, aged 49.8 +/- 8.4 years, presenting PA diagnosed in average 12.9 years before. A group of 36 individuals, 25 male and 11 female, aged 37 +/- 8 years and without disease, were used as control. RESULTS: All patients were in sinus rhythm with a mean heart rate of 71 +/- 6 (min - 51.5 +/- 7.0 and max - 130.3 +/- 15.0). In 8 (36.6%) there were sinus bradycardia less than 50/min and sinus tachycardia (greater than 120/min) in 15 patients (68.1%). Two patients (9%) presented supraventricular tachycardia and one had AV block. There were premature atrial systoles in 14 pts (63.6%), and ventricular arrhythmias in 9 (40.9%). In control group, there were sinus bradycardia in 16.6%, sinus tachycardia in 33.3%, premature atrial systoles in 33.3% and ventricular arrhythmias in 25% of them; in 11% there were conduction disturbances. CONCLUSIONS: a) Premature atrial systoles were the rhythm disturbance more prevalent. b) Patients with PA presented a significant higher incidence of sinus bradycardia and sinus tachycardia. c) Cardiac conduction disturbances were not frequent. d) Our results may suggest the presence of a subtle autonomic dysfunction in patients with psoriatic arthritis.     

Gastrointestinal comorbidities in patients with psoriatic arthritis

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel’s largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients’ records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn’s disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn’s disease (OR 2.4, 95 %CI: 1.75–3.32, p < 0.0001), ulcerative colitis (OR 2.1, 95 %CI: 1.33–3.26, p = 0.001), reflux esophagitis (OR 1.6, 95 %CI: 1.44–1.78, p < 0.0001), PUD (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001) and IBS (OR 1.4, 95 %CI: 1.01–1.86, p = 0.045). After controlling for known risk factors, the association remained significant between PsA and Crohn’s disease (OR 2.2, 95 %CI: 1.59–3.03, p < 0.0001), ulcerative colitis (OR 1.9, 95 %CI: 1.21–3.00, p = 0.005), reflux esophagitis (OR 1.5, 95 %CI: 1.31–1.63, p < 0.0001), and PUD (OR 1.3, 95 %CI: 1.12–1.47, p < 0.0001). No significant association was found between PsA and celiac disease. In the current study PsA was associated with gastrointestinal morbidities including Crohn’s disease, ulcerative colitis, PUD and IBS. Physicians treating patients with PsA should be aware of these associations.