Atherosclerosis in rheumatoid arthritis versus diabetes: a comparative study.

OBJECTIVE: The extent to which atherosclerosis is accelerated in chronic inflammatory diseases is not established. We compared preclinical atherosclerosis in rheumatoid arthritis with diabetes mellitus, a known coronary heart disease equivalent. METHODS AND RESULTS: Endothelial function, arterial stiffness, carotid intima-media thickness, and analysis of atheromatous plaques were examined in 84 rheumatoid arthritis patients without cardiovascular disease versus healthy controls matched for age, sex, and traditional cardiovascular disease risk factors, as well as in 48 diabetes patients matched for age, sex, and disease duration with 48 rheumatoid arthritis patients. Rheumatoid arthritis duration associated with arterial stiffening, whereas disease activity associated with carotid plaque vulnerability. All markers of preclinical atherosclerosis were significantly worse in rheumatoid arthritis compared to controls, whereas they did not differ in comparison to diabetes despite a worse cardiovascular risk factor profile in diabetics. Both diseases were associated independently with increased intima-media thickness; rheumatoid arthritis, but not diabetes, was independently associated with endothelial dysfunction. CONCLUSIONS: Preclinical atherosclerosis appears to be of equal frequency and severity in rheumatoid arthritis and diabetes of similar duration with differential impact of traditional risk factors and systemic inflammation. Cardiovascular disease risk factors in rheumatoid arthritis may need to be targeted as aggressively as in diabetes.

Heartscore calculated in individuals younger than 40 years is related to vascular markers of early atherosclerosis.

BACKGROUND: Heartscore is not well validated for individuals less than 40 years of age. In the latest guidelines a relative risk chart is provided with the proposal to be used for young adults aged less than 60 years instead of projecting risk at the age of 60 years. Moreover, coronary artery disease is insidiously manifested in younger patients. DESIGN: Cross-sectional study. METHODS: Two hundred and two young Greeks of age less than 40 years and 232 middle-aged adults aged 40-60 years without clinically overt cardiovascular disease or diabetes were consecutively recruited. Flow-mediated dilatation of the brachial artery, carotid, and femoral intima media thickness (IMT), carotid-radial and carotid-femoral pulse wave velocity (PWV) were measured in all individuals in one session. The European Society of Cardiology online Heartscore calculator was used for mortality risk (MR) 60 and Systematic Coronary Risk Evaluation risk charts for relative risk (RR) computation. RESULTS: MR60 in the younger significantly correlated with all measured vascular markers whereas RR significantly correlated with carotid IMT. By multivariate regression analysis, MR60 was a stronger identifier than RR for PWV, mean carotid and femoral IMT in both groups. Young adults (<40 years) with a high MR60 (>5%) had significantly higher carotid-radial PWV, carotid and femoral IMT whereas those with a high RR (>3rd tertile) had significantly higher carotid IMT. CONCLUSION: MR60 was a stronger identifier of most of the measured markers of early atherosclerosis as compared with RR. These data support Heartscore as a prognostic tool in terms of primary prevention for participants younger than 40 years old.

Percutaneous radiofrequency ablation for malignant liver tumours in challenging locations.

PURPOSE: To evaluate the treatment results of radiofrequency ablation (RFA) for primary and metastatic malignant liver tumours in challenging locations and also to present the treatment strategy that was used in these cases. PATIENTS AND METHODS: From January 2007 to January 2010, we performed CT-guided RFA on 528 lesions in 402 patients (265 men and 137 women; mean age 65.1 years, range 19-82 years) with liver tumours (primary and metastatic) of which 98 lesions in 84 patients (55 men and 29 women; mean age 67.8 years, range 33-82 years) were located in challenging locations, defined as less than 5 mm from a large vessel or an extrahepatic organ (heart, lung, gall bladder, right kidney or gastrointestinal tract). The sizes of the tumours ranged 1.5-6 cm. We used two different RFA systems with an expandable needle electrode (RITA; Rita Medical Systems, Inc, Mountain View, CA, USA and MIRAS; Invatec S.r.l., Roncadelle, Italy).The tumours were considered as ablated completely if no viability was found on dual-phase dynamic contrast-enhanced CT at 1 month after RFA. RESULTS: Complete ablation was obtained in 89.7% (88/98) of the high-risk located lesions, while 10 (10.3%) of the lesions were managed with repeated RFA because of tumour residue. The 1-, 2- and 3-year survival rates were 82.6, 67.3 and 54.1%, respectively. Minor complications occurred in eight of the 84 patients (9.5%), including small sub-capsular haematoma in four, small pleural effusion in three and partial liver infarction in one. Local tumour progression rate was 9.2% (9/98). CONCLUSION: RFA is a safe and effective method of treatment of primary and metastatic liver tumours even located in challenging locations when performed by a well-trained and experienced interventional radiologist.

Recently postmenopausal women have the same prevalence of subclinical carotid atherosclerosis as age and traditional risk factor matched men.

OBJECTIVE: To compare the prevalence of subclinical atherosclerosis between postmenopausal women and men of similar age early after the onset of menopause. METHODS: In the first part of this cross-sectional study 186 non-diabetic young postmenopausal women (n = 101, menopausal age ≤ 10 years) and men (n = 85) aged 40-60 years without overt CVD were consecutively recruited from the outpatients clinics of an academic hospital. Subclinical carotid atherosclerosis was assessed by high-resolution ultrasonography. The presence of carotid atherosclerosis was defined as either increased carotid intima-media thickness (IMT>0.9 mm) and/or the presence of plaques. In the second part, 1:1 matching for age and traditional risk factors (hyperlipidemia, smoking, hypertension and BMI) was performed between men and women of this cohort resulting in a matched sub-sample of 76 subjects. RESULTS: By multivariate analysis, gender was not an independent determinant of any measure of carotid atherosclerosis. In the matched sub-sample, carotid IMT and the number of segments with atherosclerosis did not significantly differ between women and men (0.734 ± 0.119 mm and 1.47 ± 1.6 versus 0.717 ± 0.138 mm and 1.47 ± 1.5, p = 0.575 and p = 0.999, respectively). Also, the prevalence of increased IMT (60.5% in both genders), carotid plaques and subclinical atherosclerosis (31.6% and 63.2% versus 28.9% and 65.8%, p = 0.803 and p = 0.811, respectively) was similar between men and women. CONCLUSIONS: The prevalence and severity of carotid atherosclerosis was similar between men and young postmenopausal women matched for traditional risk factors. Whether these women may be better risk stratified irrespective of gender should be further assessed in prospective studies.

Predictors of new atherosclerotic carotid plaque development in patients with rheumatoid arthritis: a longitudinal study.

INTRODUCTION: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to both classical risk factors and chronic inflammation. We assessed longitudinally the factors associated with new carotid plaques in nondiabetic RA patients and apparently healthy individuals. METHODS: In our present prospective observational study, carotid plaques were identified by ultrasonography at baseline and follow-up end, separated by an average of 3.6 ± 0.2 years, in 64 patients (mean age 59.2 ± 12.0 and disease duration at baseline 7.8 ± 6.2 years, 83% women, clinical and laboratory evaluation every 3 to 6 months). In a substudy, 35 of the patients were matched 1:1 for traditional cardiovascular risk factors with 'healthy' controls and were studied in parallel. RESULTS: New atherosclerotic plaques formed in 30% of patients (first plaque in 9%) who were significantly older than the remaining patients. Tobacco use, blood pressure, body mass index, average cumulative low-density lipoprotein, high-sensitivity C-reactive protein, erythrocyte sedimentation rate level, RA stage, functional class, disease duration and treatment modalities during follow-up did not differ significantly between subgroups after application of the Bonferroni correction. RA was in clinical remission, on average, for approximately 70% of the follow-up time and was not different between subgroups. Multivariate analysis including all the above parameters revealed that age (P = 0.006), smoking (P = 0.009) and duration of low-dose corticosteroid use (P = 0.016) associated independently with new plaque formation. RA patients displayed similar numbers of newly formed carotid plaques to the tightly matched for traditional cardiovascular risk factors 'healthy' controls, although more patients than controls had carotid plaques at baseline. CONCLUSIONS: Formation of new atherosclerotic plaques in this small cohort of patients with well-controlled RA depended mainly on traditional cardiovascular risk factors and corticosteroid use, whereas an adverse effect of residual systemic inflammation was not readily detectable.

Pilot study of circulating prolactin levels and endothelial function in men with hypertension.

BACKGROUND: Hyperprolactinemia has been recently associated with hypertension and endothelial dysfunction in humans, confirming animal studies performed in the 1970s that showed high prolactin levels to exert positive chronotropic and vasoconstrictive effects. Whether prolactin affects endothelial function, in the absence of hyperprolactinemia, remains unknown. Considering that secretion of prolactin presents circadian rhythmicity, we tested the hypothesis that in patients with hypertension, who present diurnal variation in their endothelial function as well, prolactin levels correlate with endothelial function and/or blood pressure. METHODS: Endothelial function, assessed by flow-mediated dilatation (FMD) and serum prolactin were examined successively at 12 PM, 9 PM, and 7 AM in 27 nonhyperprolactinemic men with newly diagnosed, untreated essential hypertension. RESULTS: Both FMD and prolactin presented 24-h variation (P < 0.01). FMD reached its lowest values at 7 AM (2.1 ± 1.8%, mean ± s.d.); concurrently prolactin levels peaked (7.18 ng/ml, median). Across the three time points, prolactin changes inversely interacted with FMD changes (P = 0.002). Systolic and diastolic blood pressure also varied significantly but no interaction with prolactin changes was evident. CONCLUSIONS: Diurnal fluctuations of prolactin levels are associated with decreased endothelial function that occurs early in the morning in men with hypertension, although this study did not assess causality. Additional studies are required to determine whether these responses differ from normotensive individuals.

Time rate of blood pressure variation is superior to central hemodynamics as an associate of carotid intima-media thickness.

OBJECTIVE: The extent of target organ damage has been associated with both central hemodynamics and arterial stiffening, and the time rate of blood pressure (BP) changes in essential hypertension. However, the relative significance of these parameters has not been examined. METHODS: We recruited 232 consecutive uncomplicated newly diagnosed hypertensive patients and 241 normotensive individuals. Twenty-four-hour ambulatory BP monitoring was performed in all individuals. The time rate of SBP variation was computed as the first derivative of the SBP values against time. Aortic central SBP and central DBP, central pulse pressure, central augmentation index and central augmentation pressure were assessed noninvasively by pulse wave analysis. Common carotid artery intima-media thickness was measured by high-resolution ultrasonography. RESULTS: Median 24-h time rate of BP changes was 0.571 +/- 0.114 mmHg/min. Traditional risk factors, office SBP, several ambulatory BP monitoring parameters (24-h SBP, 24-h pulse pressure, 24-h heart rate and BP dipping), 24-h time rate of BP changes, time rate of BP changes at different time intervals, and central SBP, central pulse pressure, central augmentation index and central augmentation pressure significantly correlated with intima-media thickness. Age, sex, BMI, 24-h time rate of BP changes, time rate of BP changes measured at 0100-0600 h and 24-h heart rate remained significant associates of intima-media thickness after adjustment for confounding factors. By multivariate stepwise linear regression, 24-h time rate of BP changes and time rate of BP changes at 0100-0600 h had incremental value over traditional risk factors, other ambulatory BP monitoring parameters and central hemodynamics. CONCLUSION: These findings indicate that time rate of BP variation is superior to central hemodynamics as an associate of carotid intima-media thickness in hypertensive and normotensive individuals.

Subclinical peripheral arterial disease in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis in the carotid arteries, but little is known about the magnitude of this process in peripheral arteries. Assessing preclinical atherosclerosis in both arterial beds in RA might provide additional prognostic value during risk stratification for primary prevention. Therefore in the present structural study we examined femoral versus carotid subclinical atherosclerosis in RA and controls. METHODS: Intima-media thickness (IMT) and atheromatous plaque presence and vulnerability in femoral versus carotid arteries were examined in 80 RA patients without overt cardiovascular disease or diabetes and 80 controls matched 1:1 for age, gender and traditional cardiovascular disease risk factors. RESULTS: Femoral IMT and plaque prevalence were increased in RA than controls (p=0.001 and 0.008, respectively). These increases remained significant after adjustment for potentially confounding factors that differed between groups, such as C-reactive protein and HDL-cholesterol serum levels, and statin use. Femoral plaque vulnerability did not differ between RA and controls. The presence of RA was found to be an independent predictor of increased femoral IMT (p=0.004), after adjustment for traditional cardiovascular risk factors, C-reactive protein and treatment with angiotensin converting enzyme inhibitors and statins. Femoral plaques were less frequent than carotid plaques in RA patients (22.5% vs 45.0% respectively, p=0.003) and in contrast to carotid plaques were independent of age and glucose levels. CONCLUSIONS: Subclinical peripheral atherosclerosis in RA is more advanced than in controls. Prospective studies are required to confirm that RA is an independent risk factor for peripheral arterial disease.

Reversal of increased arterial stiffness in severely depressed women after 6-week antidepressant treatment.

BACKGROUND: Increased arterial stiffness (AS) might be one significant acute mediator of the well-attested association between female depression and cardiovascular disease. METHODS: We tested this hypothesis in an inpatient sample of 20 drug-free women undergoing a new clinically severe major depressive episode of recent onset with an adequately matched mentally healthy control group. Patients' clinical (Hamilton Depression Rating Scale) and vascular (Pulse-Wave-Velocity, PWV) assessments were performed both before the initiation and after the completion of their six-week antidepressant treatment. RESULTS: Although initially patients exhibited significantly higher PWV values than controls, this was decreased and reached comparable levels to controls after treatment completion. Moreover, full-responders exhibited significantly greater vascular improvement than their partial-responders counterparts and the magnitude of their amelioration was strongly associated with the magnitude of their clinical improvement. LIMITATIONS: Our sample-size was small and patients' follow-up short. CONCLUSIONS: Our findings provide support to the hypothesis that current severe major depressive episode in women leads acutely to aggravation of arterial stiffness, reversible however upon timely and effective antidepressant treatment.

Prolactin and preclinical atherosclerosis in menopausal women with cardiovascular risk factors.

Hyperprolactinemia has been associated with endothelial dysfunction and an adverse cardiovascular risk profile, possibly as a result of the vasoconstrictive properties of prolactin. In this cross-sectional study, we examined the hypothesis that prolactin contributes to the increased cardiovascular risk occurring in early menopause by studying apparently healthy women without hyperprolactinemia. Prolactin serum levels were measured by immunoassay in 76 women aged 54.4+/-4.9 years in menopause for 4.9+/-2.8 years, and possible correlations with traditional cardiovascular risk factors and surrogate markers of preclinical atherosclerosis, arterial stiffening, and endothelial and microcirculatory function were examined. Positive correlations between prolactin serum levels and arterial blood pressure, but no other traditional risk factors, were found. Prolactin also correlated with central aortic systolic (r=0.337; P=0.002) and diastolic (r=0.272; P=0.012) blood pressures and pulse wave velocity (r=0.264; P=0.02), a marker of aortic stiffness, but not with endothelial or microcirculatory function or carotid intima-media thickness. By multivariate regression analysis, prolactin levels determined, independent of traditional risk factors, both blood pressures and aortic stiffness. Notably, prolactin correlated with European Society of Cardiology HeartScore (r=0.364; P=0.002), a composite index that predicts 10-year cardiovascular mortality. Prolactin levels >8.0 ng/mL had 100% sensitivity to predict a high peripheral blood pressure. Prolactin may play a role in accelerated arteriosclerosis in early menopause by affecting central/peripheral blood pressure and arterial stiffness. In contrast, no correlation was observed with other risk factors or surrogate markers of atherosclerosis. Prospective studies to assess whether prolactin is an additional hormone increasing cardiovascular risk are warranted.

Arterial stiffness but not intima-media thickness is increased in euthyroid patients with Hashimoto's thyroiditis: The effect of menopausal status.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disorder associated with increased cardiovascular risk, mainly as a result of accelerated atherosclerosis. The aim of this study was to determine the effect of HT on carotid atherosclerosis and arterial stiffness, as possible mediators of this vascular impairment. Menopausal status was also considered in this setting since HT is mainly prevalent in women. METHODS: Fifty-four women with HT and normal thyroid function (thyrotropin [TSH] < 4.5 mU/L) and 72 healthy controls with comparable age and risk factor prevalence were examined in this cross-sectional study. Intima-media thickness (IMT) in the carotid arteries averaged from six sites and carotid-femoral pulse wave velocity (PWV) were measured. RESULTS: Although both groups had TSH levels within normal limits, TSH was higher in HT patients (2.1 +/- 1.16 vs. 1.5 +/- 0.8 mU/L, p = 0.001). PWV (7.95 +/- 2.02 vs. 7.21 +/- 1.24 m/s, p = 0.021), but not IMT (0.644 +/- 0.144 vs. 0.651 +/- 0.169 mm, p = 0.798), was significantly higher in HT patients compared to controls. When the women were divided according to menopausal status, only premenopausal women without HT had significantly lower PWV when compared with the three other subgroups (6.51 +/- 1.09 m/s premenopausal controls vs. 7.64 +/- 2.05 m/s premenopausal HT vs. 7.69 +/- 1.11 m/s postmenopausal controls vs. 8.3 +/- 1.97 m/s postmenopausal HT, p < 0.001). By multivariate analysis PWV independently correlated with age (p = 0.042), the presence of HT (p = 0.002), TSH (p = 0.003), and menopause (p < 0.001) in the whole population while HT was an independent determinant of PWV only in premenopausal women. CONCLUSIONS: HT is associated with increased PWV independent of arterial atheromatosis, indicating a direct impact of this disorder on arterial stiffening. This effect may be masked in postmenopausal women possibly due to their heavier cardiovascular risk profile.