Myron Mavrikakis

U‐shaped relationship between mortality and admission blood pressure in patients with acute stroke

Objective.  To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke.

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.

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.

Common carotid arterial stiffness and the risk of ischaemic stroke

In the present case–control study we aimed to investigate the association of common carotid arterial (CCA) stiffness with ischaemic stroke (IS) and to determine whether this relationship was independent of conventional risk factors including CCA intima‐media thickness (CCA‐IMT). CCA distensibility, defined as the change of CCA‐diameter during the cardiac cycle, and CCA‐IMT were evaluated by means of high‐resolution B‐mode carotid ultrasound examination in consecutive, first‐ever IS patients (n = 193) and in age‐ and sex‐matched control subjects (n = 106). The CCA distensibility (inverse of CCA stiffness) was significantly (P = 0.007) lower in IS (0.353 mm, 95% CI: 0.326–0.379) than in control subjects (0.415 mm, 95% CI: 0.378–0.451) even after adjusting for blood pressure values, diastolic CCA‐diameter and height. The multivariate logistic regression procedure selected CCA‐IMT and CCA distensibility as the only independent predictor variables of IS. Each 1 SD increase in the CCA‐IMT and each 1 SD decrease in the CCA distensibility independently increased the likelihood of IS by 167.0% (OR: 2.67, 95% CI: 1.80–3.96, P < 0.001) and 59.0% (OR: 1.59, 95% CI: 1.22–2.07, P = 0.001) respectively. Increased CCA stiffness is associated with IS independent of conventional risk factors and CCA‐IMT. The causal interrelationship between the elastic properties of the CCA and the risk of stroke deserves further investigation by longitudinal studies.

Common Carotid Artery Intima-Media Thickness in Patients with Brain Infarction and Intracerebral Haemorrhage

An increase in the intima-media thickness of the common carotid artery (CCA-IMT) is generally considered as an early marker of atherosclerosis and has been associated with a higher risk of stroke and myocardial infarction. There is no evidence of an association between the IMT and cerebral bleeding. We investigated cross-sectionally the diagnostic ability of vascular risk factors, including CCA-IMT, to distinguish between brain infarction (BI) and intracerebral haemorrhage (ICH). Patients suffering from BI (n = 126) had significantly (p < 0.05) higher CCA-IMT when compared to the ICH population (n = 30). The multinomial logistic regression procedure selected CCA-IMT as an independent factor able to discriminate between BI and ICH. The risk of BI versus ICH increased continuously with increasing CCA-IMT. After adjustment for cardiovascular risk factors the odds ratio for BI per 0.1 mm CCA-IMT increase was 1.29 (95% CI: 1.03–1.61). The present results demonstrate the possible predictive power of non-invasive measurement of the CCA-IMT with respect to BI versus ICH and deserve further investigation.

Diurnal and seasonal variation of stroke incidence in patients with cardioembolic stroke due to atrial fibrillation.

A seasonal variation with an incidence peak during the colder period of the year, as well as a circadian distribution with a single peak of stroke onset in the morning hours are described in various countries. Cardioembolic stroke seems to be the most frequent stroke subtype among Greek patients. Atrial fibrillation is identified as the most frequent cause of stroke. Analysis of the temporal pattern of symptom onset in a series of over 300 Greek patients with first-ever cardioembolic acute stroke due to atrial fibrillation revealed a circannual distribution with a peak during winter and a decline of stroke occurrence during summer. Analysis of the diurnal variation of symptom onset in this stroke subgroup showed a distribution with 2 incidence peaks between 08:00–10:00 and 16:00–18:00. A relation between the second, however lower, frequency peak and the traditional Greek habit of afternoon sleep (siesta) could be assumed. Possible clustering of cardiologic events in patients with atrial fibrillation, especially during the time interval after awakening from night and afternoon sleep, could be a plausible explanation, which certainly deserves to be further investigated.

Markers of bone remodeling and skeletal morbidity in patients with solid tumors metastatic to the skeleton receiving the biphosphonate zoledronic acid

The molecular triad, which includes the receptor activator of nuclear factor kappa-B ligand (RANKL), its receptor RANK, and the endogenous soluble RANKL decoy receptor osteoprotegerin (OPG), has emerged as an important determinant of bone metabolism. We aimed to evaluate the effect of treatment with the biphosphonate zoledronic acid (ZA) on biochemical markers of bone remodeling and to detect possible correlations of markerlevel changes with skeletal morbidity and clinical outcomes in patients with solid tumors and osseous metastases. The following serum markers were measured at the onset of skeletal metastases and after 6 months of treatment with ZA (4 mg intravenously monthly) in 70 patients with breast (n = 30), lung (n = 18), or prostate (n = 22) cancer: RANKL, OPG, C-terminal cross-linking telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), bone-specific alkaline phosphatase (bALP), and osteopontin (OPN). Logistic regression models were applied to assess the correlation between marker-level changes and skeletal related events (SRE, primary endpoint), recurrence or progression, and death. Within a median follow-up of 32 months, 34 patients (48.6%) presented with at least 1 SRE and 48 patients (68.6%) relapsed. The RANKL/OPG ratio was upregulated in patients with breast and lung cancer, and it tended to decline after treatment with ZA, whereas prostate cancer patients presented with profound elevation of OPG only that persisted after treatment. CTX levels were significantly reduced after treatment in the whole study population (P = 0.003). None of the markers was able to predict skeletal morbidity or clinical outcomes independently of well-established prognostic clinical parameters.

Arterial wave reflection is associated with severity of extracoronary atherosclerosis in patients with coronary artery disease

Background Arterial wave reflection is a major determinant of left ventricular function, coronary perfusion and cardiovascular risk. We investigated whether arterial wave reflection may detect atherosclerosis of peripheral arteries in patients with documented coronary artery disease (CAD). Methods Radial artery applanation tonometry and pulse wave analysis was performed in 184 patients with documented CAD at coronary angiography; central blood pressures and augmentation index (AI) were measured. Ankle-brachial (ABI) index and intima-media thickness (IMT) were used as indices of atherosclerosis of the lower limbs and the carotid arteries respectively. Results Patients with abnormal IMT (>0.7 mm, first tertile) or ABI (<0.94, first tertile) had higher Al than patients with lower IMT or higher ABI (24 ± 17 versus 17 ± 16% and 23 ± 18 versus 18 ± 13%, respectively, P<0.05). In multivariate analysis, increasing Al was associated with age, female gender, heart rate, mean blood pressure, hyperlipidaemia, and use of statins (regression coefficient (β) = 0.50, β = 0.15, β=-0.60, β = 0.23, β = 0.16 and β=-0.14, respectively, P<0.05). Increasing Al was associated with an adjusted-odds ratio of 1.035 [95% confidence interval (CI), 1.005–1.066], P=0.02 for an abnormal IMT and of 1.08 (95% CI, 1.024–1.146), P= 0.005 for ABI after adjustment for age, gender, heart rate, height, blood pressure, atherosclerotic risk factors, obesity and medication. No relation was found between Al and Gensini score or for the number of diseased coronary vessels. Conclusion Augmentation index is a marker of extensive extracoronary atherosclerosis in patients with CAD.

Electrophysiologic abnormalities of cardiac function in progressive systemic sclerosis

The heart has been generally recognized as a target organ in progressive systemic sclerosis. Noninvasive studies have assessed the incidence and prognostic importance of cardiac arrhythmias in these patients. However, detailed exploration of the function of impulse formation and the conduction system of the heart in these patients has never been reported. Therefore, invasive electrophysiologic studies were performed in 30 patients with systemic sclerosis, all of whom had neither obvious cardiac involvement nor cardiac arrhythmias, and in 32 subjects with no evidence of heart disease, who served as a control group. Corrected sinus node recovery time in patients with systemic sclerosis was significantly longer (P < .001) than in the control group, as was the HV interval (P < .05). Of the 30 patients with systemic sclerosis, 10 had an HV interval of 60 ms or longer. In four patients with systemic sclerosis, the recorded AH interval exceeded 125 ms. The intra-atrial conduction time tended to increase to a significant degree (P < .05) in patients with systemic sclerosis. The interatrial conduction time was much longer (P < .001), and the maximal conduction delay to the atrioventricular junction and to the distal coronary sinus was much greater in the patients with systemic sclerosis than in the control group (P < .001 for both). Supraventricular tachyarrhythmias were induced in 15 patients with systemic sclerosis versus 3 control group subjects (P < .001). With respect to corrected sinus node recovery time, AH and HV intervals, atrial vulnerability, and ventricular tachycardia, 3 of the 30 patients with systemic sclerosis had abnormal findings in one of these parameters and 14 had abnormalities in more than one. These results suggest that a broad spectrum of electrophysiologic abnormalities is present in patients with systemic sclerosis, which can be revealed only by invasive studies. Furthermore, this study provides additional support for the hypothesis that diffuse myocardial involvement is characteristic of scleroderma patients, since a number of these patients showed more than one electrophysiologic defect.

Endothelial dysfunction and type of cigarette smoked: the impact of 'light' versus regular cigarette smoking

Acute cigarette smoking leads to temporary endothelial dysfunction, which is an early event in atherogenesis. Sufficient data concerning the effect of cigarettes with low tar and nicotine yield are lacking. Seventeen healthy individuals (nine women, eight men, aged 27.8 3.6 years) were subjected to evaluation of endothelial function by means of endothelium-dependent, flow-mediated dilatation (FMD) of the brachial artery, before, immediately after and 30, 60 and 90 min after smoking a regular cigarette (nicotine 0.9 mg, tar 12 mg) or the corresponding ‘light’ cigarette (nicotine 0.6 mg, tar 8 mg). The following day, measurements were repeated after smoking the opposite kind of cigarette. Baseline FMD was 6.1 1.6% and 7.2 2.0% in the light and regular cigarette groups, respectively (p 1/4 NS). The overall effect of the regular cigarette over time on FMD compared with the light cigarette was significantly different (F 1/4 3.039, p 1/4 0.023). FMD was significantly depressed after smoking both types (light: F 1/4 8.192, p < 0.001; regular: F 1/4 16.698, p < 0.001). Immediately after smoking, FMD declined in both groups (light: 3.0 2.4% and regular: 1.6 3.2%, p < 0.001 and p < 0.001, respectively), and it remained significantly depressed in the regular cigarette group at 30 min (0.75 1.5%, p < 0.001) and 60 min (3.5 3.1%, p 1/4 0.024), while in the light cigarette group FMD differences were abolished at 30, 60 and 90 min after smoking. In conclusion, acute smoking of both regular and light cigarettes leads to temporary vasomotor dysfunction; its duration is shorter after smoking a ‘light’ cigarette.