Kimon Stamatelopoulos

Ankle-brachial index as a predictor of the extent of coronary atherosclerosis and cardiovascular events in patients with coronary artery disease

Resting ankle-brachial pressure index (ABI) is a noninvasive method to assess the patency of the lower extremity arterial system. This study aimed to examine the relation between ABI and the extent of coronary atherosclerosis, the extracoronary atherosclerosis lesions, and the prognosis of patients referred for elective coronary angiography. One hundred sixty-five consecutive patients underwent coronary angiography, ultrasound imaging for intima-media thickness measurement of carotid and femoral arteries and ABI evaluation; subjects were followed up for 14.5 +/- 2.4 months. With regard to vascular risk factors, only smoking (p = 0.025) and diabetes (p = 0.01) were related to ABI in the multiple regression analysis. ABI was independently and inversely related to carotid bifurcation (p = 0.0002) and common femoral artery intima-media thickness (p = 0.018). ABI was related to the extent of coronary artery disease as measured by number of coronary arteries diseased (analysis of variance, p = 0.04) and Gensini angiographic score (p = 0.01). In the follow-up study ABI < 0.90 was a univariate predictor of cardiovascular events (cardiac death, nonfatal myocardial infarction, unstable angina) and revascularization procedures. The estimated cumulative rate free of cardiovascular events was 90% for ABI > 0.90 and 73% for ABI < 0.90 (p = 0.02). In logistic regression analysis, ABI < 0.90 was an independent predictor for cardiovascular events after adjustment for age, low-density lipoprotein cholesterol, carotid and femoral intima-media thickness, and Gensini score. Further adjustment for the confounding effect of insulin weakened the relation between ABI and cardiovascular events (p = 0.1). In conclusion, ABI is a simple index related to the extent of atherosclerosis in coronary and noncoronary arterial beds, reflecting generalized atherosclerosis. ABI could be useful in assessing the risk for cardiovascular events in patients with coronary artery disease.

Atherosclerotic changes of extracoronary arteries are associated with the extent of coronary atherosclerosis.

The aim of the present study was to examine the association between carotid and femoral artery intima media thickness (IMT) and the extent and severity of coronary artery disease (CAD) as well as the effects of traditional vascular risk factors on the atherosclerotic changes in the carotid and femoral arteries. Two hundred twenty-four patients who underwent coronary angiography for suspected CAD were evaluated by B-mode ultrasound imaging of the common carotid, internal carotid, carotid bifurcation, and femoral artery for measurement of IMT; traditional vascular risk factors were also evaluated in these patients. CAD extent was evaluated by the number of diseased vessels and by Gensini score. Age, male gender, and diabetes were common risk factors for higher CAD extent and higher carotid and femoral IMT. Insulin levels were correlated with femoral IMT and CAD extent, whereas blood lipids were correlated predominantly with carotid IMT. IMT from carotid and femoral arteries increased significantly with an increase in CAD extent. Using multiple stepwise regression analysis, the following parameters were found to be independent predictors of CAD extent: male gender (p<0.0001), common femoral artery IMT (p = 0.0028), common carotid artery IMT (p = 0.015), age (p = 0.02), diabetes mellitus (p = 0.035), and carotid artery bulb IMT (p = 0.04). Common femoral IMT was the only independent parameter for predicting Gensini score (p<0.0001). In conclusion, there are territorial differences in the various arterial beds regarding their response to risk factors. Femoral artery and carotid bulb are independent predictors of CAD extent and the inclusion of these measurements would add information to that provided by the common carotid artery.

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.

Effects of acute cigarette smoking on endothelium-dependent arterial dilatation in normal subjects

The effects of acute cigarette smoking on endothelial function were evaluated in the brachial artery of 10 nonsmoking healthy subjects. Endothelial dysfunction observed after cigarette smoking is a phenomenon lasting at least 60 minutes and does not appear to be attenuated with repeat exposure.

Effect of coffee on endothelial function in healthy subjects: the role of caffeine

Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.

Oral L-arginine improves endothelial dysfunction in patients with essential hypertension.

BACKGROUND L-Arginine is a nitric oxide precursor, which augments endothelium-dependent vasodilatation in hypercholesterolemic humans and animals. Endothelium-dependent vasodilation is attenuated in patients with hypertension; however the effects of oral L-arginine on endothelial function of the conduit arteries in patients with essential hypertension have not previously been investigated. METHODS In a prospective randomized double blind trial, 35 patients with essential hypertension received either 6 g L-arginine (18 subjects) or placebo (17 subjects). Patients were examined for flow-mediated endothelium-dependent dilatation of the brachial artery before and 1.5 h after administration of L-arginine or placebo. At the end of the protocol the nitrate-induced, endothelium-independent vasodilatation was evaluated. RESULTS Two groups of L-arginine and placebo were similar regarding age, sex, blood lipids, smoking, diabetes, coronary artery disease, body mass index, intima-media thickness of the common carotid artery, clinics blood pressure and baseline brachial artery parameters. Administration of L-arginine or placebo did not change significantly heart rate, blood pressure, baseline diameter, blood flow or reactive hyperemia. L-Arginine resulted in a significant improvement of flow-mediated dilatation (1.7+/-3.4 vs. 5.9+/-5.4%, P=0.008) while placebo did not significantly change this parameter (3.0+/-2.7 vs. 3.1+/-2.2%, P=ns). The effect of L-arginine on flow-mediated dilatation was significantly different from the effect of placebo (P=0.05). L-Arginine did not significantly influence nitrate-induced dilatation (16+/-6.9 vs. 17.7+/-6.7%, P=ns). CONCLUSIONS Oral administration of L-arginine acutely improves endothelium-dependent, flow-mediated dilatation of the brachial artery in patients with essential hypertension. The long-term effects of L-arginine in these patients require further investigation.

Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheumatoid arthritis.

TL1A is a novel TNF-like cytokine, which provides co-stimulatory and Th1-polarizing signals to activated lymphocytes, via binding to death-domain receptor 3 (DR3). These functions are inhibited when TL1A associates to decoy receptor 3 (DcR3). We investigated the serum expression of TL1A and DcR3 in 81 patients with RA and 51 healthy controls. TL1A concentrations were elevated in patients by 5-fold (P<0.00001). This increase was more prominent in RFactor-positive patients and correlated with clinical activity in this subgroup. DcR3 was detected more frequently and in significantly higher values in RA-derived sera, correlated strongly with TL1A, and was present in inflammatory synovial fluid. Severe RA stage was associated with highly elevated TL1A and DcR3 serum levels. Treatment with an anti-TNF agent significantly decreased TL1A serum levels. We conclude that TL1A may serve as an inflammatory marker in RA. Interactions between TL1A and its receptors may be important in the pathogenesis of RA.

Common Carotid Artery Intima-Media Thickness and the Risk of Stroke Recurrence

Background and Purpose— Increased common carotid artery intima-media thickness (CCA-IMT) has been associated with an increased risk of myocardial infarction and stroke. We investigated the relationship between CCA-IMT and recurrent stroke in a cohort of ischemic stroke patients. Methods— High-resolution B-mode ultrasonographic measurements of the CCA-IMT were performed in a consecutive series of 238 patients hospitalized in our institution with first-ever ischemic stroke. Stroke risk factors and secondary prevention therapies were documented. Patients were followed-up prospectively and the outcome event of interest was recurrent stroke. Results— During a mean follow-up period of 28.9 months (range: 6 to 60 months), 27 recurrent strokes were documented. Patients who experienced recurrent cerebrovascular events had significantly (P=0.005) higher CCA-IMT values (1.01 mm, 95% CI:0.92 to 1.11 mm) than subjects who were free of stroke recurrence (0.88 mm, 95% CI:0.85 to 0.91 mm). After adjustment for baseline characteristics, risk factors and stroke subtypes and secondary prevention therapies increasing CCA-IMT was found to be an independent predictor of stroke recurrence. For each increment of 0.1 mm in CCA-IMT the probability of experiencing recurrent stroke increased by 18.0% (95% CI:2.0% to 36.0%, P=0.027). Conclusions— Increased CCA-IMT values are associated with a higher risk of long-term stroke recurrence.

Short-term estrogen administration improves abnormal endothelial function in women with systemic sclerosis and Raynaud’s phenomenon

BACKGROUND Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynauds phenomenon. The aim of this study was to evaluate the endothelium-dependent vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients. METHODS AND RESULTS The study included 12 female patients with systemic sclerosis and Raynauds phenomenon (aged 49+/-14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83+/-0.3 vs 0.46+/-0.2 mm, P= .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6%+/-7% vs 11.9%+/- 4.6%, P = .003); endothelium-independent dilatation also was reduced in patients with Raynauds phenomenon (14%+/-7% vs 23%+/-6%, P= .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7%+/-4% to 6.3%+/-4%, P= .01), whereas endothelium-independent dilatation did not change (13.4%+/-8% to 15.5%+/-7%, not significant). CONCLUSIONS Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynauds phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Short-term estrogen administration can improve endothelial dysfunction in this group of patients.

A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis

Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL-6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in rheumatoid arthritis has not been examined. In a non-randomized prospective pilot study we asked whether endothelial dysfunction, defined as impaired flow mediated dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV) improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased from 3.3 ± 0.8 to 4.4 ± 1.2 to 5.2 ± 1.9% (p = 0.003), whereas PWV decreased from 8.2 ± 1.2 to 7.7 ± 1.3 to 7.0 ± 1.0m/s (p < 0.001). Whether these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor pathway inhibition, maintained over time and translate into better clinical outcome warrants further studies.