Athanassios D. Protogerou

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.

Red wine's antioxidants counteract acute endothelial dysfunction caused by cigarette smoking in healthy nonsmokers

BACKGROUND Long-term smoking is believed to cause endothelial dysfunction via increased oxidative stress, whereas short-term smoking impairs vasodilatation through an as yet undefined mechanism. However, red wine and its constituents have a powerful antioxidant effect both in long-term and acute consumption. The aim of the current study was to investigate whether red wine, with or without alcohol, influences endothelial dysfunction induced by acute cigarette smoking. METHODS Sixteen healthy volunteers (8 males and 8 females) were recruited for a double-blind, crossover study, comprising 3 study days. Each subject smoked 1 cigarette, or smoked and drank 250 mL of red wine, or smoked and drank 250 mL of dealcoholized red wine. Flow-mediated dilatation (FMD) was measured after fasting and 15, 30, 60, and 90 minutes after each trial (smoke or smoke and drink either beverage). RESULTS Acute smoking of 1 cigarette caused a reduction in FMD (P <.001), which was statistically significant 15, 30, and 60 minutes after the inhalation of smoke compared to baseline levels (P <.001, P <.001, P =.043, respectively). However, simultaneous ingestion of either red wine or dealcoholized red wine with smoking did not lead to a change in FMD. CONCLUSIONS Acute smoking caused a significant impairment in endothelial function. Simultaneous consumption of red wine or dealcoholized red wine with smoking decreased smokes harmful effect on endothelium.

Non-Invasive Methods and Techniques for Central Blood Pressure Estimation: Procedures, Validation, Reproducibility and Limitations

Hypertension is a major risk factor for a wide range of cardiovascular diseases and is typically identified by measuring blood pressure (BP) at the brachial artery. Although such a measurement may accurately determine diastolic BP, it does not accurately reflect systolic BP. This is mainly attributed to the fact that blood pressure waveform is distorted as it travels outward from the heart due to the presence of wave reflections from the peripheral arteries. Due to this distortion, blood pressure measured at the brachial artery provides an inaccurate measure of central aortic systolic pressure. However, central systolic BP is an important factor determining cardiac function and work, while central diastolic BP may determine coronary flow. Consequently central (aortic and carotid) pressures are pathophysiologically more relevant than peripheral pressures and thus their non-invasive accurate estimation is challenging and clinically necessary. The purpose of this review is to present methods and techniques that are used for the estimation of central blood pressures and to describe and discuss issues regarding methodological procedures, reproducibility, validity and limitations.

Diagnostic accuracy of a home blood pressure monitor to detect atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with an increased long-term risk of stroke. A screening test for early diagnosis has the potential to prevent AF-related strokes. This study assessed the diagnostic accuracy of an automated device for self-home blood pressure (BP) monitoring, which implements an algorithm for AF detection. A modified, automated oscillometric device for self-home BP monitoring (Microlife BPA100 Plus, Microlife, Heerbrugg, Switzerland) with an AF detector was used to carry out triplicate BP measurements in subjects with sinus rhythm, AF and non-AF arrhythmias. During each BP measurement, the electrocardiogram (ECG) was recorded simultaneously. A total of 217 simultaneous BP measurements and ECG recordings were obtained from 73 subjects. Twenty-seven subjects (37%) had AF, 23 (31%) non-AF arrhythmias and 23 (31%) had sinus rhythm. A single measurement had 93% sensitivity and 89% specificity for detecting AF. For two measurements, in which one of them was required to detect AF, the sensitivity was 100% and specificity 76%, whereas for three measurements, in which two of them were required to detect AF, the sensitivity was 100% and specificity 89% (κ=0.86 for an agreement with ECG). Using the latter approach, there were five false positive cases all having irregularities in ∼50% of the heartbeats. In patients with tachyarrhythmia, the device underestimated heart rate. These data suggest that an electronic device for self-home BP monitoring, which implements an algorithm for AF diagnosis has an excellent diagnostic accuracy and might, therefore, be used as a reliable screening test for the early diagnosis.

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities.

The increased severity of obstructive sleep apnoea syndrome (OSAS) is associated with a parallel increase in the incidence of cardiovascular events. Whether the increased severity of OSAS is in fact associated with impaired arterial properties has never been thoroughly studied. In patients with OSAS who carry a high burden of cardiovascular risk factors, we investigated whether the severity of OSAS is associated with deterioration in the arterial properties, independent of classical cardiovascular risk factors. In 74 consecutive patients with OSAS, we non-invasively assessed, by means of tonometry and high-resolution ultrasound: carotid intima-media thickness (IMT), carotid diameter and plaques, carotid-femoral pulse wave velocity (PWV), central augmentation index (AI) and central blood pressures. The respiratory disturbance index was an independent predictor of IMT and PWV but not of carotid plaques, carotid diameter, AI or central blood pressures. Several parameters of nocturnal hypoxaemia were independently correlated with carotid IMT and PWV. In conclusion, arterial stiffening and thickening are modulated by the severity of OSAS, independently from age and cardiovascular risk factors.

Hour-to-hour and week-to-week variability and reproducibility of wave reflection indices derived by aortic pulse wave analysis: implications for studies with repeated measurements.

Background Wave reflections are implicated increasingly in clinical research. Aims The purpose of the present study was to investigate whether wave reflection indices are reproducible when measured repeatedly (more than twice) at longer time intervals, namely hour-to-hour and week-to-week, in healthy subjects; something that has not yet been examined. Methods Bland–Altman plots, the interclass correlation coefficients (ICC) and coefficient of variation were used for this purpose. Two series, with measurements repeated in triplicate, were performed in 22 healthy subjects: the first at intervals of 1 h and the second at 1-week time intervals. Augmentation index (AIx), heart rate-corrected AIx (AI@75) and arrival time of reflected waves at the central aorta (tr) were calculated by aortic pulse wave analysis. Results AIx and AI@75 presented very good to excellent reproducibility (ICC = 0.86) for hour-to-hour repeated measurements, while tr was also highly reproducible (ICC = 0.79). AIx, AI@75 and tr were substantially reproducible when measured repeatedly with 1-week intervals, providing ICCs greater than 0.70. Bland–Altman plots confirmed these results, indicating that more than 90% of AIx, AI@75 and tr measurements fell within two standard deviations of the mean difference. Conclusions Wave reflections are substantially reproducible even when measurements repeated in triplicate are performed at longer time intervals (hours and weeks). A quantifiable amount of variation was reported, which should be taken carefully into consideration in interventional studies with repeated measurements and in observational studies investigating differences or correlations of these indices.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: Current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension

Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67±2.94 vs 6.06±4.91% and 145.8±22.7 vs 135.7±20.3%, P<0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52±4.29 vs 10.73±5.77% and 139.5±21.7 vs 124.5±17.0%, P<0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837–0.99, P=0.04 and OR:1.023, 95%CI:1.023–1.040 P=0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (−2 log likelihood=139.368, change of χ2=4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.

The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part I: (Patho)-physiology, rationale and perspective on pulse pressure amplification.

The blood pressure (BP) waveform varies substantially between the peripheral conduit (brachial) and the central elastic (aorta) arteries mainly do a gradual increase of systolic BP, as the wave propagates distally. This phenomenon is called BP amplification and is principally generated by the presence of arterial stiffness gradient and wave reflections along the arterial bed. More and more clinical studies suggest that central BP may provide additional information regarding cardiovascular risk beyond peripheral BP. Arterial properties and thus pressure amplification, are modulated by age, cardiovascular risk factors, vasoactive substances and drugs. Recent evidence suggests, beyond any doubt, that antihypertensive drugs affect peripheral and central BP differentially and alter pressure amplification. In the present review (Part I) we deal with the mechanisms underlying: (i) the genesis and recording of BP difference between central and peripheral arteries (pressure amplification), (ii) the rational of differential effect of antihypertensive drugs on pressure amplification, (iii) the pathophysiological role of pressure amplification on cardiovascular disease as well as its clinical and research implications.

Association of left ventricular diastolic dysfunction with 24-h aortic ambulatory blood pressure: the SAFAR study

Aortic blood pressure (BP) and 24-h ambulatory BP are both better associated with target organ damage than office brachial BP. However, it remains unclear whether a combination of these two techniques would be the optimal methodology to evaluate patients’ BP in terms of left ventricular diastolic dysfunction (LVDD) prevention. In 230 participants, office brachial and aortic BPs were measured by a validated BP monitor and a tonometry-based device, respectively. 24-h ambulatory brachial and aortic BPs were measured by a validated ambulatory BP monitor (Mobil-O-Graph, Germany). Systematic assessment of patients’ LVDD was performed. After adjustment for age, gender, hypertension and antihypertensive treatment, septum and lateral E/Ea were significantly associated with office aortic systolic BP (SBP) and pulse pressure (PP) and 24-h brachial and aortic SBP and PP (P⩽0.04), but not with office brachial BP (P⩾0.09). Similarly, 1 standard deviation in SBP was significantly associated with 97.8±20.9, 86.4±22.9, 74.1±23.3 and 51.3±22.6 in septum E/Ea and 68.6±20.1, 54.2±21.9, 37.9±22.4 and 23.1±21.4 in lateral E/Ea, for office and 24-h aortic and brachial SBP, respectively. In qualitative analysis, except for office brachial BP, office aortic and 24-h brachial and aortic BPs were all significantly associated with LVDD (P⩽0.03), with the highest odds ratio in 24-h aortic SBP. Furthermore, aortic BP, no matter in the office or 24-h ambulatory setting, showed the largest area under receiver operating characteristic curves (P⩽0.02). In conclusion, 24-h aortic BP is superior to other BPs in the association with LVDD.