Martin Li

Cardiovascular risk profile of patients with psoriatic arthritis compared to controls—the role of inflammation

OBJECTIVE To examine the distribution of traditional and novel risk factors of cardiovascular disease (CVD) in patients with PsA compared with healthy controls. METHODS We compared risk factors for CVD between 102 consecutive PsA patients and 82 controls, adjusting for BMI. We also assessed the role of inflammation on the CVD risk factor by using a BMI and high-sensitivity CRP (hsCRP)-adjusted model. RESULTS The BMI of PsA patients were significantly higher than healthy controls. After adjusting for the BMI, PsA patients still have a higher prevalence of diabetes mellitus (DM) [odds ratio (OR) 9.27, 95% CI 2.09, 41.09) and hypertension (OR 3.37, 95% CI 1.68, 6.72), but a lower prevalence of low high density lipoprotein (HDL) cholesterol (OR 0.16, 95% CI 0.07, 0.41). PsA patients have significantly increased systolic and diastolic blood pressures, insulin resistance and inflammatory markers (hsCRP and white cell count) compared to controls. PsA patients have higher HDL cholesterol and apolipoprotein (Apo) A1 levels; and lower total cholesterol (TC) and low density lipoprotein cholesterol levels; and a lower TC/HDL ratio. However, the Apo B level (P < 0.05), and the Apo B/Apo A1 ratio (P = 0.07) were higher in PsA patients. Further adjustment for hsCRP level rendered the differences in the prevalence of hypertension and DM; the TC, and sugar levels; and white cell count non-significant between the two groups; while the differences in other parameters remained significant. CONCLUSION These data support the hypothesis that PsA may be associated with obesity, hypertension, dyslipidaemia and insulin resistance because of the shared inflammatory pathway.

Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause.

ObjectivePueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen. DesignTo examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone. ResultsOnly participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group. ConclusionsThis study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study.

Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis

OBJECTIVE To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis. METHODS A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment. RESULTS At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2. CONCLUSIONS Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.

High prevalence of asymptomatic vertebral fractures in Chinese women with systemic lupus erythematosus.

Objective. To investigate the prevalence of vertebral fractures and to identify risk factors associated with vertebral fractures in Chinese women with systemic lupus erythematosus (SLE). Methods. One hundred fifty-two consecutive patients with SLE were recruited in this cross-sectional study. Bone mineral density (BMD) measurements of the hip and spine were performed using the same dual energy X-ray absorptiometry (DEXA). Lateral radiographs of the spine (T5–L4) were assessed for vertebral fractures using a method described by Genant. Inflammatory and biochemical markers included C-reactive protein, receptor activator of nuclear factor-κB ligand, serum ß-CrossLaps assay for C-terminal telopeptides of type 1 collagen, and osteoprotegerin (OPG). Results. Asymptomatic vertebral fractures occurred in 20.4% of patients with SLE. Univariate analyses of variables associated with fractures were older age, higher body mass index (BMI), lower BMD spine, lower BMD hips, higher serum C3 and C4, longer estrogen exposure, higher levels of OPG, and the use of sunscreen. Multivariate analysis showed older age (p = 0.017), higher BMI (p < 0.036), and lower BMD of the spine were significantly associated with vertebral fractures in the thoracic and/or lumbar spine (odds ratio 1.068, 1.166, 0.005; p = 0.018, p = 0.025, p = 0.003, respectively). Conclusion. Asymptomatic vertebral fractures occur in 20.4% of patients with SLE and 30% of these patients have normal BMD. The current method using DEXA to predict the presence of vertebral fracture has limited value and there is a need for assessment of bone quality. Vertebral morphometry in patients with SLE is recommended and early therapeutic intervention is necessary to prevent vertebral fractures in patients with SLE.

Population Bone Mineral Density Measurements for Chinese Women and Men in Hong Kong

Abstract: The aim of the study was to establish population ranges of bone mineral density (BMD) for Hong Kong Chinese men and women for the Hologic QDR 2000 bone densitometer, to compare these values with the manufacturer’s reference ranges, to compare these values with population ranges for women obtained for the Norland X26 bone densitometer, and to examine variations between the two densitometers. The subjects were 164 men aged 40–79 years and 436 women aged 20–89 years, who were all ethnic Chinese, recruited from volunteers, social centers for the elderly and general practice clinics. BMD in women began to decline rapidly between ages 50 and 79 years, averaging about 10% loss per decade from the young adult (20–29 years) mean. The percentage losses from young adult mean values in the spine, femroal neck, trochanter and total femur were 23%, 30%, 31% and 33%, respectively, from 20 to 79 years. In the ninth decade no further decrease in BMD occurred with the exception of a further 4% at the hip sites. In men, no decrease in spine BMD occurred between 40 and 70 years. Compared with BMD in the fourth decade, 10%, 13%, and 11% of BMD was lost at the femoral neck, trochanter and total femur, respectively, by the seventh decade. These values show differences compared with the manufacturer’s reference ranges for Caucasians and Japanese. BMD values for the spine were comparable between Hologic and Norland densitometers, but Hologic values for femoral neck and trochanteric regions were lower than the Norland values. Data provided by this study may thus be used as normative values for the Hologic QDR2000 bone densitometer, instead of values provided by the manufacturer. BMD values at the hip sites are not interchangeable between Norland and Hologic bone densitometers, and estimation of numbers of the population with osteoporosis will depend on the model of densitometer used.

Tumour necrosis factor alpha blockade is associated with sustained regression of carotid intima-media thickness for patients with active psoriatic arthritis: a 2-year pilot study

We have reported that psoriatic arthritis (PsA) patients without overt cardiovascular diseases have evidence of premature atherosclerosis as indicated by an increased carotid intima-media thickness (IMT).1 Whether an increase in IMT reflects current (but reversible) inflammation of the vessel wall rather than more permanent structural vessel changes in PsA has never been assessed. We undertook a prospective, observational study to determine whether a 12-week treatment of tumour necrosis factor alpha (TNFα) blockers may reduce IMT in patients with active PsA, and whether the changes in IMT can be sustained in patients who were continued on long-term TNFα blockers. Twenty consecutive PsA patients with active disease were recruited to receive TNFα blockers. After 12 weeks, nine patients continued (group 1) while 11 patients discontinued TNFα blockers due to financial constraints (group 2). Twenty PsA patients who were naive to TNFα blockers were recruited as controls (group 3). Patients …

Infliximab is associated with improvement in arterial stiffness in patients with early rheumatoid arthritis -- a randomized trial.

Objective. To determine the efficacy of methotrexate (MTX) with infliximab (IFX) compared with MTX alone in the prevention of atherosclerosis and arterial stiffness in patients with early rheumatoid arthritis (RA). Methods. A randomized, open-label study in which early RA patients with active disease were treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients were assessed every 3 months. Patients from the MTX-alone group who failed to achieve 28-joint Disease Activity Score remission (DAS28 ≤ 2.6) at 6 months were permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months, and 12 months. Results. At 6 months, there was a significantly greater reduction in PWV in the MTX-alone group (0.18 ± 1.59 m/s) compared with the MTX plus IFX group (−0.78 ± 1.13 m/s; p = 0.044), accompanied by significantly greater reduction in patient’s global assessment, number of swollen joints, C-reactive protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The changes in IMT and AIx were similar between the 2 groups. At 12 months, there was a trend favoring early combination treatment with regard to the reduction in PWV (p = 0.06). Conclusion. MTX plus IFX causes a more significant reduction in PWV than MTX alone in patients with early RA after 6-month treatment, and further improvement may be achieved in patients who continued on longterm tumor necrosis factor-α blockers, suggesting that early, effective suppression of inflammation may prevent progression of atherosclerosis by improving vascular function.

Estrogen receptor gene polymorphism and bone mineral density in postmenopausal Chinese women

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) for the estrogen receptor gene (ERG) and its relation to bone mineral density (BMD) were examined in 454 postmenopausal Chinese women, aged 55-79 years. The RFLPs were represented as P or p (PvuII) and X or x (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. There was no significant difference in BMD between the PP, Pp, and pp genotypes. However, women of the XX genotype had significantly higher BMD at the spine than women of the Xx or xx genotype. The magnitude of the difference in BMD was 80% of a standard deviation (SD) for BMD in elderly women and 40% of a SD in postmenopausal women. There was no statistically significant interaction between the PvuII genotype and the XbaI genotype in determining BMD. We conclude that postmenopausal Chinese women who were homozygous for the XX genotype had slightly higher BMD than the others. However, the difference in BMD was small and was unlikely to have any clinical significance. The ERG is not a major determinant of BMD in Chinese women in Hong Kong.

Alendronate for the prevention of bone loss in patients on inhaled steroid therapy

One hundred women on inhaled steroid therapy (dose range from 800 to <1600 microg per day) were randomized to receive 10 mg of oral alendronate or placebo (with 500 mg of calcium in the form of daily calcium carbonate). Bone mineral density (BMD) was measured at baseline, 6 months, and 12 months. The percentage changes in BMD were -0.80% in the placebo group and 2.99% in the alendronate group at the spine (p < 0.001 by analysis of covariance [ANCOVA]), and were -0.51% in the placebo group and 0.97% in the alendronate group at the femoral neck (p < 0.05 by ANCOVA). Five patients in the alendronate-treated group, and a similar number of patients in the placebo group, complained of mild gastric discomfort. We conclude that women on inhaled steroid therapy were at risk of accelerated bone loss, which could be prevented by a daily dose of 10 mg of alendronate.

Bone Microarchitecture Assessment by High-Resolution Peripheral Quantitative Computed Tomography in Patients with Systemic Lupus Erythematosus Taking Corticosteroids

Objective. We assessed the relationship between vertebral fracture and bone microarchitecture in patients with systemic lupus erythematosus (SLE) on chronic corticosteroid therapy using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods. Fifty-nine Chinese women with SLE taking corticosteroid were selected to participate in a cross-sectional study. Vertebral fracture was confirmed semiquantitatively by lateral radiographs of the thoracic and lumbar spine. Density and microarchitecture at the distal radius were measured with HR-pQCT. Areal bone mineral density (aBMD) at hip and lumbar spine was measured by dual-energy x-ray absorptiometry (DEXA). Results. Twelve patients had vertebral fractures. The aBMD of spine or hip did not differ between those with and without vertebral fractures. Measures by HR-pQCT revealed that patients with vertebral fractures had significantly lower level of average bone density (p = 0.007), cortical bone density (p = 0.029), trabecular bone density (p = 0.024), trabecular bone volume to tissue volume (p = 0.023), and trabecular thickness (p = 0.011) than those without vertebral fractures. Independent explanatory variables associated with higher risk of vertebral fractures were older age (p = 0.013) and lower average cortical bone density (p = 0.029). Conclusion. Vertebral fracture in patients with SLE on chronic corticosteroid treatment was associated with alterations of bone density and microarchitectures measured by HR-pQCT and DEXA. However, alterations were more pronounced in measurements by HR-pQCT. Low cortical bone density and old age were significant predictors of vertebral fracture risk.