Athanasios D. Protogerou

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Inflammatory and endothelial markers in women with polycystic ovary syndrome

Background  Women with polycystic ovary syndrome (PCOS) carry a pattern of cardiovascular risk factors. Endothelial dysfunction and chronic inflammation are early findings in the atherosclerotic process. The purpose of the study was to investigate the coexistence of active inflammation markers and endothelial dysfunction in young women with PCOS, and their relationship with metabolic and hormonal abnormalities of the syndrome.

Validation of the Microlife Watch BP Office professional device for office blood pressure measurement according to the International protocol.

ObjectiveTo assess the accuracy of oscillometric and auscultatory blood pressure (BP) measurement taken using the professional electronic device Microlife Watch BP Office according to the European Society of Hypertension International Protocol. MethodsThirty-three participants were included for the assessment of each measurement mode (oscillometric and auscultatory). Simultaneous BP measurements were taken by two observers (mercury sphygmomanometers) four times, sequentially with three measurements taken using the tested device. Absolute observer device BP differences were calculated. For each participant the number of measurements with a difference within 5 mmHg was calculated. ResultsIn phase 1 the device produced 32, 40 and 40 oscillometric systolic BP (SBP) measurements within 5, 10 and 15 mmHg, respectively and diastolic BP (DBP) 30, 40 and 43 (for auscultatory SBP 29, 42, 45 and DBP 33, 43, 45). In phase 2.1 the device produced 71, 90 and 96 SBP measurements within 5, 10 and 15 mmHg, respectively and DBP 71, 88 and 97 (for auscultatory SBP 72, 96, 99 and DBP 83, 96, 99). Twenty-four participants had at least two of their SBP differences within 5 mmHg and one participant had no difference within 5 mmHg, and DBP 23 and three participants, respectively (for auscultatory SBP 29 and 0 and DBP 29 and 1). Mean SBP difference was −1.4±6.3 mmHg and DBP −0.8±6.0 mmHg (auscultatory SBP −1.8±4.5 and DBP −0.4±4.0). ConclusionThe Microlife Watch BP Office device used in the oscillometric or the auscultatory mode fulfills the validation criteria of the International protocol and therefore can be recommended for clinical use.

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.

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.

Miliary Tuberculous Peritonitis Mimicking Advanced Ovarian Cancer

Primary peritoneal tuberculosis is a rare presentation of this disease. It is usually associated with ascites and raised CA-125 levels. Occasionally a pelvic mass may be present making the preoperative differential diagnosis from advanced ovarian cancer extremely difficult. Acid-fast stains and special cultures of the ascitic fluid for Mycobacterium tuberculosis are frequently negative, and confirmation of the diagnosis commonly requires histologic examination of biopsy specimens, in which epithelioid granulomas with central caseous necrosis can be identified. We present a case of unexplained pyrexial ascites in a postmenopausal woman in whom the diagnosis of miliary peritoneal tuberculosis was confirmed laparoscopically. The role of noninvasive tools such as measurement of ascitic fluid adenosine deaminase levels is also discussed.

Effect of CPAP treatment on endothelial function and plasma CRP levels in patients with sleep apnea

Summary Background Continuous positive airway pressure (CPAP) is the most effective method for treating obstructive sleep apnea syndrome (OSAS) and alleviating symptoms. Improved sleep quality with effective CPAP therapy might also contribute to attenuated systemic inflammation and improved endothelial function, with subsequent reduction of cardiovascular risk. The aim of this study was to assess the effect of 3-month CPAP therapy on brachial artery flow-mediated dilation (FMD) and plasma C-reactive protein (CRP) levels in patients with OSAS. Material/Methods Our study group consisted of 38 male patients with no prior history of cardiovascular disease. Twenty patients with an Apnea-Hypopnea Index (AHI) ≥15 were assigned to receive CPAP treatment and 18 subjects with an AHI<5 were included in the control group. Six patients failed to comply with the CPAP treatment. Measurement of FMD and blood analysis was performed at baseline and 3 months after CPAP therapy. Results Baseline FMD values were negatively correlated with age, BMI, AHI, DSI,% of time <90% Sa02, and CRP (p<0.05). Plasma CRP values were positively correlated with BMI, AHI, DSI and% of time <90% Sa02 (p<0.05). In the group of patients who complied with the CPAP treatment, there was a significant increase in the FMD values (9.18±0.55 vs. 6.27±0.50) and a decrease in the levels of CRP (0.67±0.15 vs. 0.84±0.18) (p<0.05). Conclusions Appropriate CPAP therapy improved both CRP and FMD values, suggesting its potentially beneficial role in reducing cardiovascular risk in OSAS patients.

Subclinical atherosclerosis in Systemic Lupus Erythematosus: Comparable risk with Diabetes Mellitus and Rheumatoid Arthritis☆

OBJECTIVE Although a high risk of subclinical atherosclerosis has been reported in Systemic Lupus Erythematosus (SLE), it is not adequately compared with that observed in other rheumatic and non-rheumatic high-cardiovascular (CVD) risk diseases, such as Rheumatoid Arthritis (RA) and Diabetes Mellitus (DM). Our objective was to evaluate the relative risk (RR) of subclinical atherosclerosis in SLE, RA and DM patients compared to healthy controls, and examine potential associations with traditional and disease-related CVD risk factors in SLE. METHODS We examined for atherosclerotic plaques 460 individuals (92% female) without CVD history, using carotid and femoral artery ultrasound: 115 SLE patients and matched 1:1 for age and gender RA, DM, and control subjects. Multivariate models were used to determine relative risk estimates for the number of atherosclerotic plaques in patient groups versus controls, and associations of plaques with traditional CVD and disease-related factors in SLE. RESULTS A nearly two-fold higher number of atherosclerotic plaques in the carotid and femoral arteries was detected in each of SLE, RA and DM groups compared to controls, after adjusting for the effect of traditional CVD risk factors (RR=1.80, 95% CI 1.05-3.08, p=0.033, RR=1.90 (1.11-3.26), p=0.019, RR=1.93 (1.14-3.28), p=0.015, respectively). In SLE patients, the number of atherosclerotic plaques was associated with age (p<0.001), smoking (p=0.016), hypertension (p=0.029), and cumulative corticosteroid dose (p=0.007). CONCLUSION The relative risk of subclinical atherosclerosis in SLE was comparable to that found in RA and DM, indicating that SLE patients merit a similar diligence in CVD risk assessment and management measures.

Comorbidity of Cognitive Impairment and Late-Life Depression Increase Mortality: Results From a Cohort of Community-Dwelling Elderly Individuals in Rural Greece.

Objective: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece. Methods: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders. Results: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI. Conclusion: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.

Automated device that complies with current guidelines for office blood pressure measurement: design and pilot application study of the Microlife WatchBP Office device.

ObjectiveCurrent guidelines for office blood pressure (BP) measurement recommend mercury devices, both arms measurement in the initial assessment and at least duplicate measurements at follow-up visits. This study presents the design and a pilot application study of an automated device that fulfils American, European, and International guidelines for office BP measurement. Design and functionsThe Microlife WatchBP Office is a professional electronic mercury-free device with three function modes designed for: (a) initial assessment: triplicate automated simultaneous oscillometric both arms measurement at 60-s intervals and when there is a consistent interarm difference more than 20 mmHg systolic and/or more than 10 mmHg diastolic, the arm with the higher BP is indicated. (b) Follow-up assessment: triplicate automated oscillometric single arm measurements at 60-s intervals and their average is displayed. (c) Auscultatory measurement: by an observer using a stethoscope and a digital countdown BP display for patients with arrhythmias and other individuals in whom the oscillometric measurement is not accurate. Pilot application studyThe ‘initial assessment’ mode was applied by three physicians in 63 patients (189 readings). Average interarm systolic BP difference was 0.04±5.1 mmHg and diastolic 0.4±3.2 mmHg. A value more than 10 mmHg interarm difference in nine systolic BP readings (5%) and three (2%) diastolic. No patient had a consistent interarm difference more than 10 mmHg in all three or two of the three readings. ConclusionThe Microlife WatchBP Office professional device fulfils current international requirements for office BP measurement and seems to overcome several limitations of this method when applied in clinical practice.