Marta Zanon

Atherosclerosis progression in psoriatic arthritis patients despite the treatment with tumor necrosis factor-alpha blockers: A two-year prospective observational study

OBJECTIVE To evaluate the progression of subclinical atherosclerosis in Psoriatic Arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α agents. METHODS Thirty-two PsA patients classified according to the CASPAR criteria and attending the Rheumatology Unit of the University of Padua Medical Center were enrolled in a two-year prospective, observational study. In accordance with the ASAS/EULAR recommendations on the management of these patients, those studied were prescribed biological agents [etanercept (n=21), adalimumab (n=6), infliximab (n=5)]. Plasma lipids, inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), vessel endothelium growth factor (VEGF), osteoprotegerin (OPG), and TNF-α, as well as Disease Activity Score 28 calculated with CRP (DAS 28-CRP) were evaluated at baseline and after two years of treatment. Bilateral carotid B-mode ultrasound measurements [the mean-intima media thickness (mean-IMT), the mean maximum-IMT (M-Max)] of each carotid artery segment (common, bulb, and internal carotid artery) and the post-occlusion flow-mediated dilation (FMD) of the brachial artery were also assessed at baseline and after two years. RESULTS Despite an improvement in the DAS 28-CRP score (P<0.0005) and lower low-density lipoprotein cholesterol (P<0.013) and triglyceride (P<0.036) values, there was a significant progression in both the mean-IMT (P<0.0005) and M-Max (P<0.0005). Moreover, no recovery in FMD (P=ns) was observed after two years of anti TNF-α treatment. Serum TNF-α levels were increased (P=0.003) and OPG values were decreased (P=0.011) at the end of follow- up with respect to baseline values. CONCLUSIONS Despite improvement in clinical status, arterial remodelling was observed in the PsA patients who were treated with anti TNF-α agents for two years.

Impact of hypertension on vascular remodeling in patients with psoriatic arthritis.

We studied the impact of hypertension along with traditional and new cardiovascular risk factors on the structural and functional properties of arteries in psoriatic arthritis (PsA) patients. We examined 42 PsA subjects (aged 51±9 years) stratified according to hypertensive status (19 normotensive, PsA-NT and 23 hypertensives, PsA-HT). Thirty-eight normotensive subjects (C-NT) and 23 hypertensives (C-HT) comparable by age and sex served as controls. Mean carotid intima-media thickness (mean-IMT) and mean of the maximum IMT (M-Max) were evaluated by ultrasound in carotid artery segment bilaterally. Post-occlusion flow-mediated dilation (FMD) of the brachial artery was evaluated by ultrasonography. These parameters were correlated with risk factors, markers of inflammation and disease activity. Values of mean-IMT were higher in both groups of PsA patients compared with C-NT (0.68 mm in PsA-NT and 0.75 mm in PsA-HT versus 0.61 mm in C-NT). PsA-HT displayed higher M-Max (0.95 mm) versus both C-HT (0.71 mm) and PsA-NT (0.79 mm). FMD was impaired in PsA subjects compared with C-NT (5.7% in PsA-NT and 6.0% PsA-HT versus 9.3% in C-NT), whereas there was no difference among PsA-HT, PsA-NT, and C-HT groups. Values of carotid IMT were directly related to tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), blood pressure and lipid profile levels. FMD showed an inverse relationship with TNF-α and blood pressure, but no correlation with lipids. In conclusion, PsA per se implies a pro-atherogenic remodeling, which is enhanced by the hypertensive status. TNF-α and OPG may have an independent role in the development of such vascular damage.

Intima-media thickness remodelling in hypertensive subjects with long-term well-controlled blood pressure levels

Abstract Aim of this study was to evaluate in a long follow-up the carotid artery remodelling in a cohort of young hypertensive subjects having good blood pressure (BP) control. We studied 20 grade I hypertensives (HT) by assessing the B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each carotid artery segment (common, bulb, internal), bilaterally. We compared their ultrasound measurements with those recorded 5 and 10 years earlier. While the first 5-year follow-up was observational, in the second 5-year follow-up, lifestyle modifications and/or pharmacological therapy were started to obtain well-controlled BP levels. Office BP was measured at the time of the ultrasound studies and every 6 months during the follow-up. BP levels were: 10 years 144/91 mmHg, 5 years 143/90 mmHg and 129 ± 79 mmHg at the time of the study. In the first 5-year observational follow-up, both mean-IMT and M-MAX increased (Δ 0.116 and Δ 0.165 mm, respectively, p < 0.0005). In the 5-year intervention follow-up, characterized by well-controlled BP, mean-IMT slightly but significantly increased (Δ 0.084 mm, p = 0.004), whereas M-MAX remained stable (Δ 0.026 mm). In our HT, well-controlled BP levels were able to prevent pro-atherogenic remodelling (expressed by M-MAX). Conversely, good BP control slightly decreased but did not stop the progression in mean-IMT, which is likely to reflect some hypertrophy of the arterial media layer.

Predictors of vascular remodelling in hypertensive subjects with well-controlled blood pressure levels

We evaluated the structural/functional characteristics of the arterial wall in a cohort of hypertensives with well-controlled blood pressure (BP) levels. We studied 40 hypertensives with well-controlled BP. We assessed by B-mode ultrasound the mean intima-media thickness (mean-IMT) and maximum-IMT (M-MAX) of carotid artery (common, bulb, internal) bilaterally. Endothelial function was evaluated by post-occlusion flow-mediated dilation (FMD) of the brachial artery. Along with traditional risk factors, we studied the impact of serum high-sensitivity C-reactive protein (hs-CRP) and osteoprotegerin (OPG). Forty normotensive subjects served as controls. In the hypertensives, the BP levels were well controlled (office BP: 129/79 mm Hg, ambulatory BP monitoring: 121/75 mm Hg). Compared with controls, higher BP levels and body mass index were present in hypertensives, whereas age and metabolic parameters were similar. In hypertensives, the IMT (mean-IMT 0.68 mm, M-MAX 0.81 mm) was significantly higher than in controls (mean-IMT 0.60 mm, M-MAX 0.71 mm). FMD was impaired in hypertensives (5.9%) compared with controls (9.2%). In multivariate analyses, it turned out that in hypertensives IMT parameters were related to age, hs-CRP and OPG. Low-density lipoprotein (LDL) cholesterol was the only factor related to FMD. IMT and FMD had no relationship with BP levels. In conclusion, in hypertensives with well-controlled BP, the pro-atherogenic remodelling (IMT) is mainly dependent on age and the inflammatory cytokines, OPG in particular. The functional impairment of the arterial wall (FMD) was related to the levels of LDL cholesterol. Under these conditions, when the impact of BP is minimized, the role of inflammatory cytokines and lipids on structural/functional remodelling becomes predominant.

OS 10-06 THE IMPACT OF WELL CONTROLLED BLOOD PRESSURE LEVELS ON ARTERIAL PROPERTIES IN ESSENTIAL HYPERTENSIVES

Objective: The aim of this study was to evaluate the impact of well controlled blood pressure (BP) levels on structural and functional properties of arteries in essential hypertensives. Design and Method: We studied 80 young hypertensives (mean age 49 yo) allocated either to pharmacological treatment (55 of 80) or to lifestyle modifications (25 of 80) for at least 12 months (mean 38 months) to maintain target BP. Follow-up visits were scheduled every 6 months. Office BP was taken three times by the same doctor at the time of the study. We assessed the B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each carotid artery segment (common, bulb, internal), bilaterally. Endothelial function was evaluated by post-occlusion flow mediated dilation (FMD) of the brachial artery using high-sensitivity ultrasonography. Arterial elastic properties were evaluated by assessing carotid distensibility (DC) and compliance (CC). Forty normotensive subjects paired for age and sex served as controls. Results: Throughout the study, BP levels were well controlled in hypertensives (mean BP levels: 131/79 mmHg). The IMT (mean-IMT 0.65 mm, M-MAX 0.79 mm) was significantly higher in hypertensives than in controls (mean-IMT 0.60 mm, M-MAX 0.70 mm). FMD was impaired in hypertensives (5.7%) compared to controls (9.2%). IMT parameters correlated only to age, while LDL-cholesterol was the only factor related to FMD. Compared to controls, arterial elasticity was significantly impaired in hypertensives (DC 25.6 vs 52.4 10–3/kPa, and CC 0.97 vs 1.40 mm2/kPa). Conclusions: In essential hypertensives, despite long-term well controlled BP, the pro-atherogenic remodelling was still present. IMT was mainly dependent upon age, while FMD was mainly related to cholesterol levels. Moreover, carotid elasticity was impaired. The “pseudo-normalization” of BP levels does not result in normalization of structural and functional properties of the arterial wall.

SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH PSORIATIC ARTHRITIS: THE IMPACT OF CLASSICAL AND NEW CARDIOVASCULAR RISK FACTORS: PP.10.391

Objective: Increased cardiovascular morbidity and mortality have been observed in several immune mediated rheumatic diseases, including psoriatic arthritis (PsA). We evaluated subclinical atherosclerosis in PsA patients according with hypertensive status by studying non invasively structural and functional properties of arteries. Design and Method: We studied 41 consecutive patients with PsA (of whom, 23 hypertensives) attending hospital outpatient clinics. 40 normotensives healthy subjects (NC) and 19 hypertensives (HT-C) served as controls. We evaluated by B-mode ultrasound the carotid intima media thickness (IMT). Measurements were expressed as mean-IMT (cumulative mean of mean IMT measured in each carotid segment, common, bulb, and internal carotid artery, bilaterally) and as M-MAX (cumulative mean of maximum IMT). Endothelial function was evaluated by post-occlusion flow mediated dilation (FMD) of the brachial artery using high-sensitivity brachial ultrasonography. NO-independent vasodilation was evaluated by the response to sublingual glyceril trinitrate (GTN). Results: PsA had a higher mean-IMT compared to NC. Hypertensive PsA displayed higher M-MAX versus both HT-C (p = 0.007) and normotensive PsA (p = 0.026). FMD was significantly lower in PsA than in NC (8.9%), whereas there was no difference between hypertensive PsA (6.1%), normotensive PsA (5.7%), and HT-C (6.3%). GTN response was similar in all groups. The TNFα level was much higher in PsA patients than in the other groups. In the entire cohort, the IMT parameters were significantly related to TNFα as well as classical risk factors, including blood pressure and lipid profile, whereas FMD was inversely related to TNFα levels and blood pressure but not lipid parameters. Conclusions: Subclinical atherosclerosis is enhanced in PsA compared to NC. In PsA, the hypertensive status proved to exert an additional effect on M-MAX, a parameter of advanced pro-atherogenic remodelling. FMD was reduced in PsA irrespective of hypertensives status. Thus, PsA per se implies a pro-atherogenic remodelling which is enhanced by the hypertensive status. In addition, TNFα seems to play a role in the hampering the functional properties of vascular wall probably through endothelial dysfunction. Figure 1. No caption available.