Christos Papamichael

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.

Time Rate of Blood Pressure Variation Is Associated With Increased Common Carotid Artery Intima-Media Thickness

The extent of target-organ damage has been positively associated with the magnitude of blood pressure (BP) variability in essential hypertension. However, the clinical implications of the rate of BP changes have never been investigated. We evaluated the association between the rate of systolic BP (SBP) variation derived from ambulatory BP monitoring (ABPM) data analysis and the extent of common carotid artery (CCA) intima-media thickness (IMT) in normotensive (n=280) and in uncomplicated hypertensive subjects (n=234). The 24-hour rate of SBP variation was significantly (P<0.001) higher in hypertensive (0.608 mm Hg/min; 95% confidence interval [CI], 0.595 to 0.622) than in normotensive individuals (0.567 mm Hg/min; 95% CI, 0.555 to 0.578), even after adjusting for baseline characteristics, day–night BP changes, 24-hour heart rate (HR), SBP, and HR variability. In the entire group of patients, multiple linear regression models revealed independent determinants of CCA-IMT in the following rank order: age (P<0.001), 24-hour rate of SBP variation (P<0.001), male gender (P=0.004), cholesterol (P=0.009), and smoking (P=0.014). A 0.1 mm Hg/min increase in the 24-hour rate of SBP variation was associated to an increment of 0.029 mm (95% CI, 0.018 to 0.040) in CCA-IMT independent of BP and HR levels, BP and HR variability, and dipping status. The rate of SBP variation during the morning BP surge correlated independently (P<0.001) to larger CCA-IMT values after adjustment for baseline characteristics and other ABPM parameters. Thus, the rate of BP fluctuations is greater in hypertensive patients and correlates to increased CCA-IMT. This finding indicates that steeper BP variations may produce a greater stress on the vessel wall and consequently result in medial hypertrophy of the large arteries.

The Athens Stroke Registry: Results of a Five-Year Hospital-Based Study

The advent and wide application of new technology, especially noninvasive techniques, has enabled physicians to more completely investigate and clarify the etiopathogenic mechanisms of stroke. Such data have not been available until recently for Southeastern Europe. In addition, during the last decades, strategies for the modification of risk factors and primary prevention may have changed the prevalence of each subgroup of stroke as well. We investigated 1,042 consecutive patients who had first strokes, during a period of 5 years (from June 1992 to May 1997) and classified them prospectively based on etiopathogenic mechanisms. Patients with transient ischemic attacks and subarachnoid hemorrhage were excluded. There were 613 male and 429 female patients, with a mean age of 70.2 ± 11.9 years. Forty-six percent of the patients arrived within 3 h from stroke onset. The probable mechanisms were: large-artery atherosclerosis, 156 (15%); lacunes, 177 (17%); cardioembolic, 335 (32.1%); infarct of unknown cause, 182 (17.5%); miscellaneous causes, 35 (3.3%), and intracerebral hemorrhage (ICH), 157 (15.1%). In the cardioembolic group, nonvalvular atrial fibrillation (NVAF) was the probable cause in 225 patients, especially in patients older than 75 years (65%). The overall hospital mortality was 15.2% (from 0.6% for lacunar stroke to 34% for ICH). In our population, cardioembolism is the most frequent subtype of stroke. NVAF is the most likely source, especially in older patients.

Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes.

OBJECTIVE To assess whether otherwise healthy women with a history of gestational diabetes mellitus (GDM) may have abnormalities in endothelial function at a very early stage, before glucose intolerance occurs. RESEARCH DESIGN AND METHODS A total of 33 women with previous GDM (17 nonobese [BMI <27] and 16 obese [BMI ≥27]) and 19 healthy nonobese women were examined. A 75-g oral glucose tolerance test was performed, and insulin levels and biochemical parameters were also measured. Using high-resolution ultrasound, we measured vasodilatory responses of the brachial artery during reactive hyperemia (endothelium-dependent vasodilatation), and after nitroglycerin administration, an endothelium-independent vasodilator. RESULTS Flow-mediated dilatation (FMD) was significantly and equally decreased in both groups of women with previous GDM, compared with control subjects (1.6 ± 3.7% in the nonobese GDM group and 1.6 ± 2.5% in the obese GDM group vs. 10.3 ± 4.4% in control subjects, P <0.001). FMD correlated inversely with serum uric acid levels, BMI, serum total cholesterol, and basal insulin resistance (homeostasis model assessment). Nitrate-induced dilatation was significantly decreased only in the obeseGDM group compared with control subjects (21.4 ± 5.1 vs. 27.9 ± 9.5, P < 0.05). CONCLUSIONS Endothelial dysfunction, which is considered as a very early index of atherogenesis, is alreadypresent in both obese and nonobese women with a history of GDM, even when they have normal glucose tolerance.

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.

Target Organ Damage in “White Coat Hypertension” and “Masked Hypertension”

BACKGROUND In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. METHODS A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. RESULTS WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 +/- 30.6, 107.1 +/- 29.1 vs. 101.4 +/- 29.9 g/m(2) and 0.68 +/- 0.16, 0.68 +/- 0.21 vs. 0.63 +/- 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 +/- 25.9 vs. 101.4 +/- 29.9 g/m(2)); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 +/- 0.15 vs. 0.63 +/- 0.15 mm). CONCLUSIONS WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

Effect of Acute Cigarette Smoking on Endothelium-Dependent Brachial Artery Dilatation in Healthy Individuals

The effect of short-term smoking on endothelium-dependent and endothelium-independent dilatation of the brachial artery was tested in 27 healthy volunteers using high-resolution ultrasound imaging. Short-term smoking led to a significant decrease in endothelium-dependent dilatation.

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.