Jonny Hisdal

Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study

Objectives To compare markers of cardiovascular disease (CVD) risk between patients with rheumatoid arthritis (RA) in an active disease state and those with RA in remission, and to compare both groups with community controls. Methods 113 patients with RA and 86 community controls were assessed across a panel of biomarkers for CVD. RA in remission was defined as Clinical Disease Activity Index ≤2.8. Community controls were selected at random by Statistics Norway, and controls were matched with patients in the cohorts in strata using details of age, sex and residential area. A panel of biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), total cholesterol, reactive hyperaemia index (RHI), pressure measurements, measures of arterial stiffness and intima-media thickness) were compared between patients with active RA and those with RA in remission. Both groups were compared with controls. In addition, biomarker levels were compared across subgroups based on anticyclic citrullinated peptide status, level of joint destruction and presence of extra-articular manifestations. Results Patients with active RA had significantly higher levels of NT-proBNP, brachial systolic pressure, augmentation index and central systolic pressure but lower cholesterol than patients in remission and controls. In addition, patients with active RA had significantly higher levels of pulse wave velocity and worse RHI than patients in remission. Comparison across other subgroups gave less consistent differentiations in levels of CVD risk markers. Conclusion Patients with active RA, but not those in remission, had significantly increased levels of CVD risk markers. These results link inflammatory activity to markers of CVD risk in patients with RA and may indirectly support the notion that remission in RA confers diminished cardiovascular morbidity.

Poor agreement between respiratory variations in pulse oximetry photoplethysmographic waveform amplitude and pulse pressure in intensive care unit patients.

Background: To identify fluid responsiveness, a correlation between respiratory variations in pulse pressure (&Dgr;PP) and respiratory variations in pulse oximetry photoplethysmographic waveform amplitude (&Dgr;POP) in mechanically ventilated patients has been demonstrated. To evaluate the agreement between the two methods, knowledge about the repeatability of the methods is imperative. However, no such data exist. Based on knowledge of slow oscillation in skin blood flow, the authors hypothesized that the variability of &Dgr;POP would be larger than that of &Dgr;PP when calculations were performed continuously over a long recording period. Methods: Respiration, continuous invasive blood pressure, pulse oximetry, and skin microcirculation were recorded in 14 mechanically ventilated intensive care unit patients. No intravenous fluid challenges were given, and no other interventions were performed during the measurements. Seventy consecutive comparisons between &Dgr;PP and &Dgr;POP were calculated for each of the 14 patients. Results: For all patients, &Dgr;POP was 13.7 ± 5.8% and &Dgr;PP was 5.8 ± 2.6% (P < 0.001). There was a larger intraindividual (8.94 vs. 1.29; P < 0.001) and interindividual (26.01 vs. 5.57; P < 0.001) variance of &Dgr;POP than of &Dgr;PP. In six patients, there was no significant correlation between &Dgr;PP and &Dgr;POP. A Bland–Altman plot showed poor agreement between the two methods. Conclusion: A large variability of &Dgr;POP and a poor agreement between &Dgr;PP and &Dgr;POP limits &Dgr;POP as a tool for evaluation of fluid responsiveness in intensive care unit patients. This is in contrast to &Dgr;PP, which shows a small variability.

Carotid plaque characteristics and disease activity in rheumatoid arthritis.

Objective. Carotid plaques (CP) are predictive of acute coronary syndrome in patients with rheumatoid arthritis (RA), suggesting that atherosclerotic plaques in these patients are vulnerable. The objective of our study was to characterize vulnerability of CP in patients with RA compared to a control population, and between RA patients with different levels of disease activity. Methods. Ultrasound examination of carotid arteries was performed in 152 patients with RA and 89 controls. CP echolucency was evaluated by the Gray-Scale Median (GSM) technique. Lower GSM values indicate higher vulnerability of plaques. CP characteristics were compared between RA patients with active disease and in remission, and between patients and controls. All analyses were performed with adjustment for confounding factors (sex, age, smoking, and blood pressure). Poisson regression analysis was used for count data, mixed modeling for GSM and area per plaque, and analysis of covariance for minimum GSM value per patient. Results. Patients with RA more frequently had CP (median 2, range 0, 4) compared with controls (median 1, range 0, 3; p < 0.001), after adjustment for age and sex. Patients with active RA disease according to the Clinical Disease Activity Index (CDAI) had lower median GSM (p = 0.03), minimum GSM (p = 0.03), and a larger CP area (although the latter finding was not significant; p = 0.27), compared with patients with RA in remission. These findings were not confirmed for other disease measures (Simplified Disease Activity Index, Disease Activity Score-28, C-reactive protein, erythrocyte sedimentation rate). Conclusion. Patients with RA had more CP compared with controls and patients in CDAI remission, and controls had more stable CP than patients with active disease; these findings point to the importance of achieving remission in RA.

Haemodynamic responses to exercise in patients with COPD

The present study aimed to explore the prevalence of pre-capillary pulmonary hypertension (PH) and characterise haemodynamic vascular responses to physical exercise in chronic obstructive pulmonary disease (COPD) outpatients, where left ventricular dysfunction and comorbidities were excluded. 98 patients with COPD underwent right heart catheterisation at rest and during supine exercise. Mean pulmonary artery pressure (Ppa), pulmonary capillary wedge pressure (Ppcw) and cardiac output (CO) were measured at rest and during exercise. Exercise-induced increase in mean Ppa was interpreted relative to increase in blood flow, mean Ppa/CO, workload (W) and mean Ppa/W. Pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC) were calculated. PH at rest was defined as mean Ppa at rest ≥25 mmHg and Ppcw at rest <15 mmHg. Prevalence of PH was 5%, 27% and 53% in Global Initiative for Chronic Obstructive Lung Disease stages II, III and IV, respectively. The absolute exercise-induced rise in mean Ppa did not differ between subjects with and without PH. Patients without PH showed similar abnormal haemodynamic responses to exercise as the PH group, with increased PVR, reduced PAC and steeper slopes for mean Ppa/CO and mean Ppa/W. Exercise revealed abnormal physiological haemodynamic responses in the majority of the COPD patients. The future definition of PH on exercise in COPD should rely on the slope of mean Ppa related to cardiac output and workload rather than the absolute values of mean Ppa.

Impaired endothelial function in persons with obstructive sleep apnoea: impact of obesity

Objective Obstructive sleep apnoea (OSA) and obesity are both associated with endothelial dysfunction, which precedes the development of atherosclerosis. As obesity is highly prevalent in OSA, we wanted to test the hypothesis that OSA is associated with endothelial dysfunction independently of obesity. Design Cross-sectional, population-based study. Setting Norwegian university hospital. Patients Seventy-one subjects (median age 44 years, 35% female) were recruited from a population-based study in Norway. Participants were categorised as obese (body mass index (BMI) ≥30 kg/m2), non-obese (BMI<30 kg/m2) with OSA (apnoea–hypopnoea index (AHI)≥10), or non-obese without OSA (AHI<5). Interventions None. Main outcome measures Endothelial function measured by brachial artery ultrasound and expressed as percentage of flow-mediated dilation (FMD%). Results When non-obese subjects without OSA were used as the reference (FMD% (mean±SD) 10.1±6.3), endothelial function was found to be impaired in subjects with OSA (FMD% 6.4±3.2) (p=0.003). FMD% did not differ between obese (6.0±3.4) and non-obese (6.7±3.1) OSA subjects (p=0.3). By univariate linear regression analysis, AHI, BMI, gender and baseline brachial artery diameter were significantly associated with FMD%. When these variables were entered into a multivariate model, only AHI was significantly associated with FMD%. Conclusions OSA is associated with endothelial dysfunction independently of obesity and conventional risk factors.

Intraocular pressure increases in parallel with systemic blood pressure during isometric exercise.

PURPOSE Normal-tension glaucoma has been found to be related to transient increases in intraocular pressure (IOP). Isometric exercise induces a pressor response with a characteristic increase in blood pressure. The purpose of the present study was to investigate how transient changes in systemic blood pressure, induced by isometric exercise, affect IOP. METHODS Nine healthy volunteers participated in the study. Systemic blood pressure, heart rate (ECG) and IOP (electronic continuous-indentation tonometer) were recorded continuously before, during, and after a 2-minute period of isometric exercise (40% maximum voluntary contraction of the forearm). RESULTS During the 2-minute isometric exercise, heart rate increased from 74+/-6 beats/min (mean +/- SEM) to 93+/-6 beats/min (P<0.005) and systolic and diastolic arterial blood pressure increased from 125+/-6 to 169+/-8 mm Hg (P<0.005) and from 65+/-3 to 96+/-5 mm Hg (P<0.005), respectively. IOP increased from 15+/-1 mm Hg at rest to 19+/-2 mm Hg at the end of the isometric exercise (P<0.005). CONCLUSIONS During isometric exercise, IOP increased continuously, as long as the isometric exercise persisted, in parallel to the increase in systemic blood pressure.

Rosuvastatin‐Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study

Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low‐density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA‐AS) study was to evaluate the effect of 18 months of intensive lipid‐lowering treatment with rosuvastatin with regard to change in carotid plaque height.

Supervised Exercise Training Reduces Plasma Levels of the Endothelial Inflammatory Markers E-Selectin and ICAM-1 in Patients With Peripheral Arterial Disease

Elevated plasma levels of vascular inflammatory markers have been reported in patients with peripheral arterial disease (PAD). We assessed the effect of supervised exercise training (ET) on vascular inflammation, hypothesizing that ET reduces plasma levels of the endothelial adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Twenty-nine patients with PAD underwent a supervised ET program for 8 weeks. Before and after ET, walking distances (pain-free, PWD; maximal, MWD) were determined by a standard treadmill test. Plasma levels of E-selectin and ICAM-1 were significantly reduced (E-selectin: 45.5-40.4 ng/mL, P = .013); ICAM-1: 342.0-298.0 ng/mL, P = .016). VCAM-1 levels were unchanged. Walking distances increased significantly (PWD: median 77-150 m, P < .001; MWD: median 306-535 m, P < .001). In conclusion, 8 weeks of ET in patients with PAD reduces plasma levels of the specific endothelium-derived inflammatory markers E-selectin and ICAM-1.

Blood pressure response to isometric exercise in patients with peripheral atherosclerotic disease

Background  The purpose of this study was to compare the circulatory responses to isometric exercise in patients with peripheral atherosclerotic disease (PAD) with healthy controls.

Predictive Value of Arterial Stiffness and Subclinical Carotid Atherosclerosis for Cardiovascular Disease in Patients with Rheumatoid Arthritis

Objective. We evaluated the predictive value of these vascular biomarkers for cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA): aortic pulse wave velocity (aPWV), augmentation index (AIx), carotid intima-media thickness (cIMT), and carotid plaques (CP). They are often used as risk markers for CVD. Methods. In 2007, 138 patients with RA underwent clinical examination, laboratory tests, blood pressure testing, and vascular biomarker measurements. Occurrence of CVD events was recorded in 2013. Predictive values were assessed in Kaplan-Meier plots, log-rank, and crude and adjusted Cox proportional hazard (PH) regression analyses. Results. Baseline median age and disease duration was 59.0 years and 17.0 years, respectively, and 76.1% were women. CVD events occurred in 10 patients (7.2%) during a mean followup of 5.4 years. Compared with patients with low aPWV, AIx, cIMT, and without CP, patients with high aPWV (p < 0.001), high AIx (p = 0.04), high cIMT (p = 0.01), and CP (p < 0.005) at baseline experienced more CVD events. In crude Cox PH regression analyses, aPWV (p < 0.001), cIMT (p < 0.001), age (p = 0.01), statin (p = 0.01), and corticosteroid use (p = 0.01) were predictive of CVD events, while AIx was nonsignificant (p = 0.19). The Cox PH regression estimates for vascular biomarkers were not significantly altered when adjusting individually for demographic variables, traditional CVD risk factors, RA disease-related variables, or medication. All patients who developed CVD had CP at baseline. Conclusion. CP, aPWV, and cIMT were predictive of CVD events in this cohort of patients with RA. Future studies are warranted to examine the additive value of arterial stiffness and carotid atherosclerosis markers in CVD risk algorithms. Regional Ethical Committee approval numbers 2009/1582 and 2009/1583.