Association of Nocturnal Hypertension With Disease Activity in Rheumatoid Arthritis.

OBJECTIVES: Both nocturnal hypertension (HT) and systemic inflammation underlying rheumatoid arthritis (RA) have been shown to be independent predictors of cardiovascular disease (CVD), although little is known on the relationship between nocturnal blood pressure (BP) and disease activity in RA patients. METHODS: We performed 24-hour ambulatory BP monitoring (ABPM) in 71 RA patients to examine the relationship of nocturnal fall in BP and RA disease activity based on a disease activity score of 28 joint counts with C-reactive protein (CRP, 28-joint disease activity score (DAS28)-CRP). Among them, 25 RA patients whose consent obtained were reexamined by ABPM to assess the improvement of nocturnal fall in BP after RA therapeutic intervention. RESULTS: The mean DAS28-CRP level was 4.8±1.6 in 71 RA patients. The mean nocturnal fall in BP was 5.6±8.9%. DAS28-CRP was associated significantly and independently in a negative manner with the nocturnal fall in BP (ß = -0.388, P = 0.004). In 25 RA patients, DAS28-CRP improved from 5.4±1.1 to 3.5±0.8 (P < 0.0001) and the nocturnal fall in BP increased significantly from 4.5±9.2% to 10.6±5.8% (P = 0.002) with the significant decrease of nighttime systolic BP (SBP) from 121.2±22.5mm Hg to 112.5±18.8mm Hg (P = 0.02) in spite of no change in daytime BP after 4 weeks of RA treatment. CONCLUSIONS: The present study observed that higher RA activity was associated with lower nocturnal fall in BP, but not daytime BP, in RA patients.

Teriparatide Therapy Reduces Serum Phosphate and Intima-Media Thickness at the Carotid Wall Artery in Patients with Osteoporosis.

Although cross-sectional and longitudinal studies report a relationship between osteoporosis and cardiovascular disorders (known as the bone-cardiovascular axis), the benefits of osteoporosis treatment on atherosclerosis are largely unclear. Teriparatide is a bone-forming agent that increases urinary phosphate excretion. Because elevated serum phosphate is associated with the development of atherosclerosis, the purpose of our study was to examine the relationship among lumbar spine bone mineral density (LS-BMD), intima-media thickness at the carotid artery (CA-IMT), and phosphate metabolism in response to daily teriparatide therapy. Osteoporotic patients (n = 28) with low LS-BMD (T-score < -2.5) and/or at least one vertebral fracture were treated with teriparatide (20 µg/day) for 12 months. Metabolic bone markers, LS-BMD, and CA-IMT were measured over the course of treatment. The LS-BMD significantly increased by 0.046 ± 0.038 g/cm(2) over the 12-month period (P < 0.001). CA-IMT decreased from 0.701 mm (interquartile range: 0.655-0.774 mm) at baseline to 0.525 mm (0.477-0.670 mm) at 12 months (P < 0.05); however, CA-IMT change was not significantly associated with LS-BMD change. Serum phosphate decreased after 1 month of teriparatide administration, and the change in serum phosphate at 1 months was associated with the change in CA-IMT at 12 months (ρ = 0.431, P = 0.025). Teriparatide improved LS-BMD and CA-IMT, suggesting the existence of the bone-cardiovascular axis. The association between serum phosphate and CA-IMT suggests that the teriparatide decreased CA-IMT in part by reducing serum phosphate, a well-known vascular toxin, in addition to the improvement of bone-cardiovascular axis.

Association between poor glycemic control, impaired sleep quality, and increased arterial thickening in type 2 diabetic patients.

OBJECTIVE: Poor sleep quality is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and objective sleep architecture and its influence on arteriosclerosis in patients with type-2 diabetes mellitus (DM). The present study examined the association of objective sleep architecture with both glycemic control and arteriosclerosis in type-2 DM patients. DESIGN: Cross-sectional study in vascular laboratory. METHODS: The subjects were 63 type-2 DM inpatients (M/F, 32/31; age, 57.5±13.1) without taking any sleeping promoting drug and chronic kidney disease. We examined objective sleep architecture by single-channel electroencephalography and arteriosclerosis by carotid-artery intima-media thickness (CA-IMT). RESULTS: HbA1c was associated significantly in a negative manner with REM sleep latency (interval between sleep-onset and the first REM period) (ß=-0.280, p=0.033), but not with other measurements of sleep quality. REM sleep latency associated significantly in a positive manner with log delta power (the marker of deep sleep) during that period (ß=0.544, p=0.001). In the model including variables univariately correlated with CA-IMT (REM sleep latency, age, DM duration, systolic blood pressure, and HbA1c) as independent variables, REM sleep latency (ß=-0.232, p=0.038), but not HbA1c were significantly associated with CA-IMT. When log delta power was included in place of REM sleep latency, log delta power (ß=-0.257, p=0.023) emerged as a significant factor associated with CA-IMT. CONCLUSIONS: In type-2 DM patients, poor glycemic control was independently associated with poor quality of sleep as represented by decrease of REM sleep latency which might be responsible for increased CA-IMT, a relevant marker for arterial wall thickening.

Association between glycemic control and morning blood pressure surge with vascular endothelial dysfunction in type 2 diabetic patients.

OBJECTIVE: Morning blood pressure surge (MBPS) is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and MBPS, and its effect on vascular injury in patients with type 2 diabetes mellitus (T2DM). The current study examined the association between glycemic control and MBPS, and the involvement of MBPS in the development of vascular dysfunction in T2DM patients. RESEARCH DESIGN AND METHODS: We examined MBPS in T2DM patients (25 male patients/25 female patients; mean age, 60.1 ± 13.2 years; n = 50) using 24-h ambulatory blood pressure monitoring, and assessed vascular function by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). RESULTS: HbA1c (ρ = 0.373, P = 0.009) and triglyceride (TG) (ρ = 0.375, P = 0.009) levels correlated significantly and positively with MBPS. In multiple regression analysis, including TG and HbA1c levels in addition to age and 24-h systolic blood pressure (SBP) as independent variables, HbA1c (ß = 0.328, P = 0.016) and TG (ß = 0.358, P = 0.014) were associated significantly in a positive manner with MBPS. In a noninsulin user, when homeostasis model assessment ratio (HOMA-R) was included in place of TG, HOMA-R emerged as a significant factor. MBPS (ρ = -0.289, P = 0.043) and HbA1c (ρ = -0.301, P = 0.035) correlated significantly and negatively with FMD, whereas 24-h SBP correlated with both FMD (ρ = -0.359, P = 0.012) and NMD (ρ = -0.478, P = 0.004). In multiple regression analysis, including age, gender, 24-h SBP, MBPS, LDL cholesterol, and HbA1c, MBPS (ß = -0.284, P = 0.044) alone associated significantly in a negative manner with FMD, but not with NMD. CONCLUSIONS: The current study demonstrated that poor glycemic control and insulin resistance are independently associated with the occurrence of MBPS in T2DM patients, which might be significantly associated with endothelial dysfunction.

Increased soluble IL-2 receptor levels in serum from a patient with painless thyroiditis.

CONTEXT: Serum concentration of soluble interleukin-2 receptor (sIL-2R) has been established as a reliable marker of T-lymphocyte activation. However, there have been no reports describing the relationship between serum sIL-2R and painless thyroiditis. OBJECTIVE: We report a case of a 76-yr-old female with a significant and temporary increase of sIL-2R concomitant with painless thyroiditis. CASE ILLUSTRATION: The patient was diagnosed with malignant lymphoma at the age of 73. After 6 cycles of CHOP-R complete remission was induced and no recurrence was observed up to 3.5 years. At 76 years of age, she exhibited hyperthyroidism and was diagnosed with painless thyroiditis based upon US examination and 99mTc-Thyroid scintigraphy. Her AST and ALT were mildly elevated, and her serum level of sIL-2R increased up to 2230 U/mL from the approximately 540 U/mL, which had been stable for 3 years before.These abnormal data normalized without requiring any treatment. The time-course of the reduction in sIL-2R did not correlate with FT4 or FT3, but was very similar to that of AST and ALT. CONCLUSION: There was no evidence of relapse of the malignant lymphoma. We conclude that the increase of sIL-2R was associated with painless thyroiditis. Considering the similar time-course between the reduction of serum sIL-2R and those of AST and ALT, which are often accompanied by autoimmune processes in painless thyroiditis during the development of hyperthyroidism, it was suggested that the increase of serum sIL-2R in this case resulted from activation of an autoimmune process.

Impaired response of FGF-23 to oral phosphate in patients with type 2 diabetes: a possible mechanism of atherosclerosis.

BACKGROUND: Fibroblast growth factor (FGF)-23, secreted from osteocytes/osteoblasts, plays major roles in phosphate (Pi)-mediated stimulation of PTH secretion and consequently in regulation of serum Pi. Osteocyte/osteoblast dysfunction develops in patients with type 2 diabetes mellitus (DM). OBJECTIVE: Our objective was to examine whether increases in serum FGF-23 and PTH after oral Pi stimulation are impaired in type 2 DM. DESIGN AND METHODS: The subjects were 10 DM and 10 non-DM patients without chronic kidney disease stage 3-5. Serum FGF-23, intact PTH (iPTH), and Pi were measured serially after oral Pi administration at a daily dose of 2.0 g. RESULTS: Pi administration caused significant increases of FGF-23 by 2 h and iPTH by 4 h in non-DM patients. These increases were attenuated in DM patients. After 2 d of Pi stimulation, serum FGF-23 and iPTH remained elevated in non-DM patients but not in DM. In all subjects, initial changes of serum FGF-23 (0-2 h) and iPTH (0-4 h) were positively correlated (r = 0.528) and showed significant negative correlations with later changes in serum Pi (2-4 h) (r = -0.457 and r = -0.673, respectively). Serum Pi (2-4 h) significantly increased in DM patients, consistent with the lack of change in serum FGF-23 and iPTH, whereas serum Pi did not change significantly in non-DM patients. CONCLUSION: These results show that increases of serum FGF-23 and PTH in response to Pi stimulation are impaired in type 2 DM and that serum Pi is significantly increased thereafter. This may be a mechanism underlying advanced atherosclerosis in type 2 DM.

Poor muscle quality as a predictor of high mortality independent of diabetes in hemodialysis patients.

BACKGROUND: Poor muscle quality provides a clinically relevant measure for mortality in general population, particularly in the elderly people. Our previous reports indicating poorer muscle quality in diabetes mellitus (DM) hemodialysis patients than in non-DM counterparts prompted us to examine the association between two parameters in hemodialysis patients, independent of DM prevalence. METHODS: The study was performed from 1997 to 2005. Grip dynamometry and dual-energy X-ray absorptiometry (DXA) were used to measure handgrip strength (HGS) and arm lean mass (ALM), respectively, with the muscle quality defined as the ratio of HGS to ALM. RESULTS: During the mean follow-up period of 77 months, 90 out of 272 patients died. The patients were divided into higher and lower groups based on the values of muscle quality. In Kaplan-Meier analysis, the higher group revealed lower mortality than the lower group. Cox regression hazards analysis identified higher muscle quality as a significant independent predictor for better survival in hemodialysis patients (HR; 0.889, 95% CI 0.814-0.971; P<0.05), after adjustment for age, sex and the prevalence of DM. Since DM prevalence is a major factor for poorer muscle quality, another analysis was performed after restriction of the subjects to non-DM patients. The result also indicated that muscle quality provides a relevant measure independent of the presence of DM to predict the mortality in hemodialysis patients (HR; 0.849, 95% CI 0.759-0.950; P<0.05). CONCLUSION: The study suggested that muscle quality provides a good marker for survival in hemodialysis patients, independently of the presence DM, age and serum albumin.