These data support the hypothesis that PsA may be associated with obesity, hypertension, dyslipidaemia and insulin resistance because of the shared inflammatory pathway.
Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. TNF-alpha is a critical mediator of inflammation and metabolic response in patients with RA. Increased insulin resistance and dyslipidemia were known risk factors in patients with active RA, however, the regulation of these metabolic parameters by TNF-alpha is poorly understood. Neutralization of TNF-alpha with infliximab offers a unique opportunity to study TNF-alpha-mediated regulation of these metabolic parameters in RA. The aim of the study was to assess the in vivo TNF-alpha-mediated regulation of insulin resistance and lipids levels in RA. Nineteen patients with active RA treated with infliximab were prospectively followed for 14 weeks. Plasma lipids levels and insulin resistance were measured at baseline, 6 and 14 weeks after infliximab treatment. At week 14, the disease activity (DAS-28 score) improved significantly (p < 0.000), with a significant reduction in both C-reactive protein (p = 0.007) and erythrocyte sedimentation rate (p = 0.006) levels. The body weight did not change during the study period. After infliximab treatment, insulin resistance improved as reflected by the significant reduction in the Homeostasis Model Assessment Index. Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoprotein B (apoB) levels all increased significantly from baseline. Nonetheless, the atherogenic index, LDL-cholesterol/HDL-cholesterol ratio, and the LDL/apoB ratio remained unchanged. Infliximab improves insulin sensitivity and alters lipid profile in patients with active RA.
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.
The ATP-binding cassette G2 (ABCG2) c.421C>A (rs2231142) polymorphism influences the pharmacokinetics of rosuvastatin. We examined whether this polymorphism influences the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of the drug. In 305 Chinese patients with hypercholesterolemia who were treated with rosuvastatin at a dosage of 10 mg daily, the c.421A variant was found to be significantly associated with greater reduction in LDL-C level, in a gene-dose-dependent manner. As compared with subjects with the c.421CC genotype, those with the c.421AA genotype showed a 6.9% greater reduction in LDL-C level, which would be equivalent to the effect obtained by doubling the dose of rosuvastatin.
Previous studies have suggested that Lingzhi (Ganoderma lucidum) has antioxidant effects and possibly beneficial effects on blood pressure, plasma lipids and glucose, but these have not been confirmed in subjects with mild hypertension or hyperlipidaemia. The objective of the present study was to assess the cardiovascular, metabolic, antioxidant and immunomodulatory responses to therapy with Lingzhi in patients with borderline elevations of blood pressure and/or cholesterol in a controlled cross-over trial. A total of twenty-six patients received 1·44 g Lingzhi daily or matching placebo for 12 weeks in a randomised, double-blind, cross-over study with placebo-controlled run-in and cross-over periods. Body weight, blood pressure, metabolic parameters, urine catecholamines and cortisol, antioxidant status and lymphocyte subsets were measured after each period. Lingzhi was well tolerated and data from twenty-three evaluable subjects showed no changes in BMI or blood pressure when treated with Lingzhi or placebo. Plasma insulin and homeostasis model assessmentinsulin resistance were lower after treatment with Lingzhi than after placebo. TAG decreased and HDL-cholesterol increased with Lingzhi but not with placebo in the first treatment period, but significant carry-over effects prevented complete analysis of these parameters. Urine catecholamines and cortisol, plasma antioxidant status and blood lymphocyte subsets showed no significant differences across treatments. Results indicate that Lingzhi might have mild antidiabetic effects and potentially improve the dyslipidaemia of diabetes, as shown previously in some animal studies. Further studies are desirable in patients with hyperglycaemia.
Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.
Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9×10−8) for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5×10−4 and 2.9×10−5 in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7×10−5) for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening.
Introduction: In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. Materials and methods: A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. Results: No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. Conclusions: No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype.
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