Low prevalence of bone mineral density testing in patients with systemic lupus erythematosus and glucocorticoid exposure.

SummaryPatients with systemic lupus erythematosus (SLE) have an increased risk of developing osteoporosis and fractures due to systemic inflammation and glucocorticoids (GCs). Professional organizations recommend bone mineral density (BMD) testing in SLE patients on GCs, especially within 6 months of initiation. Using a validated algorithm, we identified SLE patients in an electronic health record cohort with long-term GC exposure (≥90 days). Our primary outcome was ever BMD testing. We assessed the impact of patient and provider factors on testing. We identified 693 SLE cases with long-term GC exposure, 41% of whom had BMD testing performed. Only 18% of patients had BMD testing within 6 months of GC initiation. In a logistic regression model for BMD testing, male sex (OR = 0.49, 95% CI 0.27 - 0.87, p = 0.01) was associated with being less likely to have BMD testing after adjusting for race and ethnicity. In contrast, older age (OR = 1.04, p < 0.001) and nephritis (OR = 1.83, p = 0.003) were associated with being more likely to have BMD testing after adjusting for race and ethnicity. Bone health in SLE patients remains an area in need of improvement with attention to patients who are younger and male.

Real-world electronic health record identifies antimalarial underprescribing in patients with lupus nephritis.

Antimalarials (AMs) reduce disease activity and improve survival in patients with systemic lupus erythematosus (SLE), but studies have reported low AM prescribing frequencies. Using a real-world electronic health record cohort, we examined if patient or provider characteristics impacted AM prescribing. We identified 977 SLE cases, 94% of whom were ever prescribed an AM. Older patients and patients with SLE nephritis were less likely to be on AMs. Current age (odds ratio = 0.97, p < 0.01) and nephritis (odds ratio = 0.16, p < 0.01) were both significantly associated with ever AM use after adjustment for sex and race. Of the 244 SLE nephritis cases, only 63% were currently on AMs. SLE nephritis subjects who were currently prescribed AMs were more likely to be followed by a rheumatologist than a nephrologist and less likely to have undergone dialysis or renal transplant (both p < 0.001). Non-current versus current SLE nephritis AM users had higher serum creatinine (p < 0.001), higher urine protein (p = 0.05), and lower hemoglobin levels (p < 0.01). As AMs reduce disease damage and improve survival in patients with SLE, our results demonstrate an opportunity to target future efforts to improve prescribing rates among multi-specialty providers.

Postexercise hypotension reduces cardiovascular responses to stress.

DESIGN: Psychological stress is associated with the development of hypertension. Exercise is purported to have a prophylactic effect on stress. Immediately after a single bout of aerobic exercise there is a transient decrease in blood pressure. OBJECTIVE: We sought to examine the cardiovascular responses to a psychological stressor, the Stroop color word task during the postexercise hypotensive period. METHODS: Eight borderline hypertensive subjects (resting blood pressure 137 +/- 1.9/85 +/- 1.8 mmHg) participated in three randomly assigned experimental trials: Stroop color word task without prior exercise (Stroop); Stroop color word task administered 10 min after 60 min exercise at 60% maximal oxygen uptake (E + Stroop); and 60 min exercise at 60% maximal oxygen uptake followed by 20 min seated recovery (Ex). Blood pressure and heart rate were monitored at the start and end of exercise and at every 2 min of recovery. RESULTS: During the Stroop trial there were significant increases in mean arterial (MAP), systolic (SBP) and diastolic blood pressure (DBP). During the Ex+Stroop trial the increases in MAP, SBP and DBP during the Stroop color word task were significantly less than the increases without prior exercise. During recovery in the Ex trial there were significant decreases in MAP and SBP. However, there were no significant changes in DBP during the Ex trial. CONCLUSIONS: These results suggest that following an acute bout of exercise there is a reduction in blood pressure, and during this postexercise hypotensive period the blood pressure response to a psychological stressor is attenuated.

Differential effects of exercise training intensity on blood pressure and cardiovascular responses to stress in borderline hypertensive humans.

BACKGROUND: Psychologic stress has been associated with the development of hypertension. Aerobic exercise training appears to decrease cardiovascular responses to psychologic stress. OBJECTIVE: To determine the efficacy of low-intensity and moderate-intensity exercise training in reducing blood pressure and cardiovascular responses to stress. DESIGN: We sought to compare the cardiovascular responses to a psychologic stressor, the Stroop Color Word Task (Stroop), before and after 12 weeks of low-intensity (about 45% maximal oxygen uptake) and moderate-intensity (about 75% maximal oxygen uptake) aerobic exercise training. METHODS: Eighteen borderline hypertensive subjects (resting blood pressure 139 +/- 9/92 +/- 9 mmHg) were divided randomly into three groups: control (no exercise), low-intensity exercise (40-50% maximal oxygen uptake), and moderate-intensity exercise (70-80% maximal oxygen uptake). Training groups exercised three times per week at the prescribed exercise intensity. Heart rate and blood pressure were recorded during the Stroop before, and after 4 and 8 weeks of exercise training. RESULTS: In the low-intensity exercise group, exercise training attenuated mean blood pressure, systolic blood pressure, and diastolic blood pressure responses to the Stroop and decreased resting blood pressure. The moderate-intensity exercise group demonstrated a reduced diastolic blood pressure response to the Stroop. CONCLUSIONS: These results suggest that, in borderline hypertensive humans, 12 weeks of aerobic exercise training attenuates the cardiovascular responses to the Stroop. Furthermore, low-intensity exercise training appears to be a more effective stimulus than moderate-intensity exercise training in reducing resting blood pressure and blood pressure responses to stress.

Proenkephalin gene expression in the brainstem regulates post-exercise hypotension.

The opioid receptor antagonist naloxone reverses the reduction in blood pressure following exercise. We have previously demonstrated that compared to genetically matched controls, spontaneously hypertensive rats (SHR) have decreased proenkephalin mRNA levels in the nucleus tractus solitarius (NTS), the caudal (CVLM) and rostral ventrolateral medulla (RVLM) of the brainstem. We hypothesized that in SHR an acute bout of exercise would increase proenkephalin mRNA in the NTS and RVLM. Female 12-week-old SHR (n = 4/group) were randomly assigned to exercise and control groups. Mean arterial pressure (MAP) and heart rate were recorded at rest and every 5 min for 30 min following: (1) 40 min of treadmill running at 30 m/min, 10% grade; or (2) 40 min of rest on the treadmill. Rats were sacrificed 30 min post-exercise or post-rest. Exercise induced increases in MAP and heart rate, approximately 18 mmHg and approximately 140 beats/min, respectively, P < 0.001. There were no differences in pre-exercise/rest MAP between groups, or in control rats following rest on the treadmill, 162.5 +/- 3 vs. 163.1 +/- 4 mmHg, control and control after treadmill rest, respectively; NS P > 0.05. The pre- to post-exercise reduction in MAP after 40 min of treadmill running was from 164 +/- 5.1 to 146 +/- 2.0 mmHg (P < 0.001) as recorded 30 min post-exercise. At 30 min post-exercise proenkephalin mRNA levels in the NTS, CVLM and RVLM were increased: 97, 198 and 227%, respectively, P < 0.01. These data reconfirm the existence of post-exercise hypotension in SHR and suggest that increases in enkephalin synthesis and release in the NTS, CVLM, and RVLM may be involved in regulating post-exercise hypotension.

Proenkephalin gene expression is altered in the brain of spontaneously hypertensive rats during the development of hypertension.

Enkephalins have been discovered in various regions of the brain involved in cardiovascular regulation. Sympathoadrenal hyperactivity and altered baroreflex activity have been implicated in the development of hypertension. The purpose of this investigation was to determine whether proenkephalin gene expression is altered in the arterial baroreceptor reflex region of the brain and in neurons involved in regulating sympathetic outflow, during the development of hypertension. Proenkephalin mRNA levels were compared, using in situ hybridization, in 4- and 14 week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Systolic blood pressure was measured by tail-cuff impedance plethysmography. There were no differences in blood pressure at 4 weeks, however by 14 weeks resting systolic blood pressure was approximately 40% higher in SHR (162.5 +/- 1.6 vs. 117.3 +/- 1.5 mmHg). Proenkephalin gene expression in the nucleus tractus solitarius (NTS), caudal (CVLM) and rostral ventrolateral medulla (RVLM) was lower (approximately 67, 50, and 55%, respectively) in the SHR at 14 weeks. However, in the locus coeruleus (LC), anterior (AH) and lateral hypothalamus (LH), proenkephalin mRNA was significantly increased (approximately 50, 100 and 100%, respectively) in the SHR. The decrease in proenkephalin mRNA in the NTS, CVLM, and RVLM may attenuate arterial baroreceptor reflex activity, while the increase in proenkephalin mRNA in the LC, AH and LH may increase sympathetic tone by inhibiting the activity of sympathodepressor preganglionic neurons in the intermediolateral cell column of the spinal cord.

Differential effects of prolonged restraint stress on proenkephalin gene expression in the brainstem.

Enkephalins have been discovered in various regions of the brain involved in cardiovascular regulation. The primary source of plasma Met-enkephalin released in response to stress, appears to be from sympathetic nerves. However, levels of Met-enkephalin are 2-3-fold higher at 2 min versus 30 min of restraint stress. Therefore, the purpose of this investigation was 2-fold; to determine whether proenkephalin gene expression is altered in the brainstem during restraint stress, and whether the magnitude of the change is attenuated with prolonged stress. Proenkephalin mRNA levels were compared in the area postrema (AP), nucleus tractus solitarius (NTS), rostral (RVLM) and caudal ventrolateral medulla (CVLM) following 2 and 30 min of restraint stress. During 2 min restraint stress, there was an approximately 1 fold increase in proenkephalin gene expression in the NTS, CVLM and RVLM with a approximately 50% decrease in the AP. With 30 min restraint stress, the increase in proenkephalin gene expression was maintained in the CVLM and RVLM, however mRNA levels had returned to control levels in the NTS and were approximately 1-fold higher than control in the AP. If the increases of proenkephalin gene expression in the NTS, CVLM and RVLM reflect changes in enkephalinergic neuronal activity in those regions, the alterations in enkephalinergic neuronal activity may be an important regulator of blood pressure homeostasis.

Plasma Met-enkephalin and catecholamine responses to intense exercise in humans.

Native and cryptic Met-enkephalin and catecholamines are coreleased in response to stress. However, it is not known whether Met-enkephalin and catecholamines exhibit concurrent temporal relationships in response to exercise. The purpose of this investigation was to examine the corelease of catecholamines and Met-enkephalin in endurance-trained (n = 6) and untrained (n = 6) male subjects during a 6-min bout of exercise: 4 min at 70% of maximal O2 uptake (VO2max) followed by 2 min at 120% VO2max. Peak catecholamine levels were found at 1 min of recovery. In trained subjects, native Met-enkephalin peaked during exercise at 70% VO2max, declined during exercise at 120% VO2max, and returned to basal levels by 1 min of recovery. In the untrained subjects, native Met-enkephalin peaked at 120% VO2max (6 min) and returned to baseline by 5 min of recovery. In both groups, cryptic Met-enkephalin peaked at 70% VO2max and returned to basal levels during exercise at 120% VO2max. These data demonstrate that during exercise there is a temporal dissociation in plasma levels of Met-enkephalin and catecholamines.

Effects of 4- and 8-h preexercise feedings on substrate use and performance.

Seven well-trained male cyclists were studied during 105 min of cycling (65% of maximal oxygen uptake) and a 15-min "performance ride" to compare the effects of 4- and 8-h preexercise carbohydrate (CHO) feedings on substrate use and performance. A high CHO meal was given 1) 4-h preexercise (M-4), 2) 8-h preexercise (M-8), 3) 4-h preexercise with CHO feedings during exercise (M-4CHO), and 4) 8-h preexercise with CHO feedings during exercise (M-8CHO). Blood samples were obtained at 0, 15, 60, 105, and 120 min and analyzed for lactate, glucose, insulin, and glycerol. Total work output during the performance ride was similar for the M-4 (217,893 +/- 13,348 N/m) and M-8 trials (216,542 +/- 13,905) and was somewhat higher for the M-4CHO (223,994 +/- 14,387) and M-8CHO (224,702 +/- 15,709) trials (P = 0.059, NS). Glucose was significantly elevated throughout exercise, and insulin levels were significantly elevated at 15 and 60 min during M-4CHO and M-8CHO compared with M-4 and M-8 trials. Glycerol levels were significantly lower during the CHO feeding trials compared with placebo and were not significantly different during exercise when the subject had fasted an additional 4 h. The results of this study suggest that when preexercise meals are ingested 4 or 8 h before submaximal cycling exercise, substrate use and performance are similar.

Opioid receptor modulation of postexercise hypotension.

Previous studies of both hypertensive and normotensive individuals have indicated a prolonged reduction in blood pressure for several hours after aerobic exercise. In related studies of spontaneously hypertensive rats, this postexercise hypotension has been prevented with naloxone. The purpose of the present investigation was to examined whether the postexercise hypotension may be reversed by antagonism of opioid sensitive receptors with naloxone in normotensive humans. Eight males 22-34 yr of age, participated in two 60-min cycling trials at 60% of VO2 peak, followed by 29 min of recovery. Beginning at 7-min recovery, naloxone or saline (control) was administered intravenously through an indwelling catheter. Blood pressure and heart rate were monitored every 15 min during exercise and every 2 min during recovery. Heart rate was significantly elevated (P < 0.05) over basal levels for the first 11 min of recovery, but from 13 to 29 min was not different from that measured at rest. In both trials, after 11 min of recovery, systolic and mean arterial blood pressures were significantly (P < 0.05) lower than pre-exercise levels (9 +/- 1 mm Hg and 4 +/- 1 mm Hg, respectively). Injection of naloxone (0.1 mg.kg-1) reversed the hypotensive response. However, the reversal was transient, lasting from minutes 15 to 27. Since naloxone reverses postexercise hypotension, opioid sensitive receptors appear to be involved in the reduction in systolic blood pressure following a single bout of submaximal exercise in normotensive humans.

Serum haptoglobin and ferritin during a competitive running and swimming season.

The purpose of the study was to examine ferritin, haptoglobin, and red cell indices during a competitive running and swimming season. Male runners (N = 8) and swimmers (N = 5) were tested four times during their respective seasons. The runners were tested before the start of organized practice (RT1), after 3 wk of increased training (RT2), 3 wk prior to the conference championship (pre-taper, RT3), and 3 d after the conference championship (post-taper, RT4). The swimmers were tested after the first 9 wk of training (ST1), after completing 2 wk of hard training (ST2), after an additional 6wk of training (pre-taper, ST3), and 1 wk following the conference championship (post-taper, ST4). For the runners, hemoglobin, hematocrit, and red blood cell number were lower (p < 0.05) at RT2 and were not accompanied by significant changes in other red cell indices or haptoglobin. Serum ferritin in the runners was lower at RT3 and RT4 compared to RT1 despite an adequate dietary iron intake. Hemoglobin and mean cell hemoglobin concentration were lower and mean cell volume was higher in the swimmers at ST3 and ST4. No significant changes were observed in other red cell indices for swimmers; however, serum haptoglobin tended (p = 0.07) to be reduced at ST2. In conclusion, collegiate male runners and swimmers do not demonstrate clinical hypoferritinemia, hypohaptoglobinemia, or alterations in red cell indices suggestive of the early stage of anemia with or without iron deficiency during their respective season.

Resistance exercise effects on plasma cortisol, testosterone and creatine kinase activity in anabolic-androgenic steroid users.

Anabolic-androgenic steroids (AS) users have been reported to have an improved ability to withstand exhaustive resistance workouts and to recover more rapidly. The purpose of this investigation was to study the effects of AS usage on the cortisol (C), testosterone (T) and creatine kinase (CK) response to a resistance training session. Eleven trained body builders and power lifters (5.0 +/- 1.6 training years, mean +/- SD), 5 AS users (SU) and 6 nonusers (NU), completed a standardized resistance training session consisting of 10 sets of back squats at preset percentages of the subject's 1 RM max. Blood samples were obtained at rest, immediately post exercise and 24 hours after the exercise session. SU had significantly lower T at rest. Neither group exhibited a significant change in T at 1 min or at 24 h post exercise. Both the NU and SU exhibited a significant increase in CK at 1 min post exercise (129 +/- 23.3 U.l-1, 81 +/- 15.3 U.l-1, respectively), with the NU response significantly greater than the SU. After 24 h, CK for NU was significantly elevated (171.9 +/- 54.5 U.l-1) above resting level. In contrast, CK for SU had returned to resting level. NU had a significant increase in cortisol (C) (p less than 0.05) at 1 min post exercise (156.8 +/- 10.9 nmol.l-1), while the SU cortisol was not significantly changed. By 24 h C for the NU returned to resting level. The results of this investigation support the concept that AS users have a diminished CK response and an altered stress response to a single bout of resistance exercise.

Indices of training stress during competitive running and swimming seasons.

Eight male cross-country runners and five male swimmers were tested four times during their collegiate seasons. Each trial corresponded to a different training load. The runners' trials were conducted before the start of organized practice (RT1), after 3 wk of increased training (RT2), 3 wk prior to the conference championship (pre-taper, RT3), and 4 d after the conference championship (post-taper, RT4). The swimmers' trials were conducted after the first 9 wk of training (ST1), after completing 2 wk of hard training (ST2), after an additional 6 wk of training (pre-taper, ST3) and during a week following the conference championship (post-taper, ST4). Venous blood samples, heart rate (HR) and blood pressure (BP) were obtained after 15 min supine rest (0700 h). Serum was analyzed for cortisol (C), total testosterone (TT), free testosterone (FT), and creatine kinase (CK). Blood samples (lactate), HR and RPE were obtained during a fixed velocity run (75% preseason VO2max) and blood samples and RPE following a 365.8 m swim (90% preseason VO2max). The runners then completed a "performance run" to exhaustion (110% preseason VO2max) and the swimmers completed maximal 22.9 and 365.8 m swims. Serum CK, C, TT, FT, and the TT:C and FT:C ratios were not significantly different among trials for the runners. Serum TT and FT were significantly (P < 0.05) lower for the swimmers at ST2 (TT 16.7 +/- 2.5; FT 85.3 +/- 8.5) compared to ST1 (TT 30.3 +/- 2.8; FT 130.2 +/- 20.9) whereas, C, TT:C or FT:C were not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)