A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Systematic Breakfast Consumption of Medium-Quantity and High-Quality Food Choices Is Associated with Better Vascular Health in Individuals with Cardiovascular Disease Risk Factors.

BACKGROUND: Breakfast consumption has been associated with the improvement of many cardiovascular disease (CVD) risk factors, yet data regarding its association with subclinical vascular damage, which precedes the onset of CVD, are scarce. The aim of this study is to investigate this association in a large sample of adults with CVD risk factors. METHODS: Anthropometric measurements, vascular biomarkers and dietary intake with two 24-h dietary recalls, focusing on breakfast frequency and its quantity and content, were assessed in 902 adults (45.2% males). Breakfast quality was assessed by identifying a posteriori breakfast dietary pattern (DP) by using principal component analysis (PCA). RESULTS: Systematic breakfast consumption (SBC) was inversely associated with central systolic blood pressure (b: -3.28, 95% C.I.: -5.7 to -0.86), diastolic blood pressure (b: -1.85, 95% C.I.: -3.34 to -0.36), augmentation index (b: -3.17, 95% C.I.:-4.98 to 1.35) and left carotid intima media thickness (b: -0.03, 95% C.I.:-0.06 to -0.01) compared to breakfast skipping independently of age, sex, hypertension, diabetes, dyslipidemia, smoking, and BMI. SBC of 10-20% of daily total energy intake (dTEI) was inversely associated with Aix (b: -2.31, 95% C.I.:-4.05 to -0.57) compared to <10% dTEI after adjustment for the aforementioned confounders. DP1 (high coffee and sugar consumption, low consumption of low- and full-fat dairy products, fruits, and fresh juices) was positively associated with Aix (b: 1.19, 95% C.I.: 0.48 to 1.90). CONCLUSION: SBC comprised of medium-energy density and high-nutrient content food items may be a simple daily habit associated with better vascular health.

Association of Pressure Wave Reflections With Left Ventricular Mass: a Systematic Review and Meta-Analysis.

BACKGROUND: Pressure wave reflections (PWRs) within the circulation are assessed at various arterial sites by various noninvasive methods. We aimed at reviewing the conflicting data regarding the hypothesis that higher PWRs are associated with higher left ventricular mass and tested whether this association stands for all available indices of PWRs, all (proximal or distal to the heart) sites of assessment, and is modified by sex, age and heart rate. METHODS: Based on a predefined protocol applying the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we identified eligible for meta-analysis data regarding: augmentation index, augmentation pressure, backward pressure (Pb), reflection index, and their association with left ventricular mass index (19 studies, total population n=8686). RESULTS: We found statistically significant associations, independent from blood pressure level, for all indices of PWRs at all arterial sites (carotid augmentation index; odds ratio; standardized beta coefficient [ß]: 0.14 [95% CI, 0.07% to 0.21%], per SD increase), radial augmentation index (ß: 0.21; 0.11 to 0.31), central augmentation pressure (ß: 0.15; 0.03 to 0.27), central Pb (ß: 0.23; 0.05 to 0.42), and central reflection index (ß: 0.14; 0.06 to 0.22), except for aortic augmentation index as estimated by generalized transfer functions. Meta-regression analysis showed that the association between carotid augmentation index and left ventricular mass was higher among populations with higher heart rate (P=0.036, beta: 0.017 [95% CI, 0.001 to 0.033]) and tended to be higher in middle-aged (P=0.07, beta: -0.001; -0.021 to 0.001). CONCLUSIONS: A clinically meaningful association between PWRs and left ventricular mass, assessed at either central or peripheral arterial sites by most available methods was shown, suggesting that PWR reduction strategies might be useful. Based on the present evidence, such trials should target middle-aged populations with high normal heart rate.

Superiority of 24-Hour Aortic Over 24-Hour Brachial Pressure to Associate With Carotid Arterial Damage on the Basis of Pressure Amplification Variability: the SAFAR Study.

BACKGROUND: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association. METHODS: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence). RESULTS: Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P<0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P<0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification. CONCLUSIONS: Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials.

Dietary sodium estimation methods: accuracy and limitations of old and new methods in individuals at high cardiovascular risk.

OBJECTIVE: Accurate and easy to use methods for dietary Na intake estimation in population level are lacking. We aimed at (i) estimating the mean Na intake in the group level using a variety of dietary methods (DM) and urinary methods (UM) and correlating them with 24-h urine collection (24UCol) and (ii) improving the accuracy of the existing DM. DESIGN: The most common DM (three 24-h dietary recalls (24DR) and FFQ) and UM (24UCol and spot urine collection using common equations) were applied. To improve the existing: (i) 24DR, discretionary Na was quantified using salt-related questions or adding extra 15 % in total Na intake and (ii) FFQ, food items rich in Na and salt-related questions were added in the standard questionnaire (NaFFQ). SETTING: National and Kapodistrian University of Athens, Greece. PARTICIPANTS: Totally, 122 high cardiovascular risk subjects (56·0 ± 12·6 years; 55·7 % males). RESULTS: Mean 24 h Na excretion (24UNa) was 2810 ± 1304 mg/d. Spot urine methods overestimated the 24UNa (bias range: -1781 to -492 mg) and were moderately correlated to 24UCol (r = 0·469-0·596, P ≤ 0·01). DM underestimated the 24UNa (bias range: 877 to 1212 mg) and were weakly correlated with 24UCol. The improved DM underestimated the 24UNa (bias range: 877 to 923 mg). The NaFFQ presented the smallest bias (-290 ± 1336 mg) and the strongest correlation with 24UCol (r = 0·497, P ≤ 0·01), but wide limits of agreement in Bland-Altman plots (-2909 mg; 2329 mg), like all the other methods did. CONCLUSIONS: The existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Additional validation studies are needed.

Association of gut microbiota composition and their metabolites with subclinical atheromatosis: A systematic review.

Study objective: The present systematic review investigates the hypothesis that specific components of the intestinal microbiome and/or their metabolites are associated with early stages of subclinical arterial damage (SAD). Design: Based on the MOOSE criteria, we conducted a systematic review of the literature (Scopus, Medline) investigating the potential association between gut microbiota and the most widely applied arterial biomarkers of SAD. Participants: All studies included individuals without established cardiovascular disease, either with or without SAD. Intervention: No interventions were made. Main outcome measures: Association between exposure (components/metabolites of microbiota) and outcome (presence of SAD). Results: Fourteen articles met the predefined criteria. Due to the large heterogeneity, their meta-analysis was not possible. Our review revealed (a) two studies on endothelial dysfunction, out of which one found an inverse relation between plasma trimethylamine N-oxide levels and FMD and the other did not substantiate a statistically significant correlation with RHI. (b) Twelve studies on atheromatosis, assessed as intimal-medial thickness (IMT), coronary artery calcium (CAC) and arterial plaque, of which, seven studies showed statistically significant associations (negative or positive depending on the microorganism or microbiota metabolite) with IMT, one study revealed significant associations with coronary artery calcium, while one showed absence of correlation and four studies reported statistically significant correlations with arterial plaque. (c) Three studies on arterial stiffness (pulse wave velocity - PWV) with two of them concluding in statistically significant association while the third study did not. Some articles investigated multiple of the correlations described and therefore, belonged to more than one section. Conclusion: Evidence of both positive and inverse associations of gut microbiota composition and their metabolites with different types of SVD has been found. However the small number and heterogeneity of available studies cannot allow to confirm or disprove the hypothesis.

Contribution of single office aortic systolic blood pressure measurements to the detection of masked hypertension: data from two separate cohorts.

Masked hypertension (MH) and masked uncontrolled hypertension (MUH) remain largely underdiagnosed with no efficient detection algorithm. We recently proposed a novel classification of office systolic hypertension phenotypes defined on the basis of both brachial and aortic systolic blood pressure (bSBP/aSBP) and showed that type III ("isolated high office aSBP" phenotype: normal office bSBP but high office aSBP) has higher hypertension-mediated organ damage (HMOD). We tested whether MH/MUH (1) can be detected with the "isolated high office aSBP" phenotype and (2) if it is associated with elevated office aSBP with respect to normotension. We classified two separate and quite different cohorts (n = 391 and 956, respectively) on the basis of both bSBP and aSBP into four different phenotypes. Participants were classified as sustained hypertensives, masked hypertensives/masked uncontrolled hypertensives (MHs/MUHs), white coat hypertensives, and normotensives according to their office and out-of-office BP readings. The majority (more than 60% in cohort A and more than 50% in cohort B) of type III individuals were MHs/MUHs. Almost 35% of MHs/MUHs had optimal office bSBP rather than high normal bSBP. In both cohorts, the detection of more than 40% of MH/MUH was feasible with the type III phenotype. MHs/MUHs had higher office aSBP than individuals with sustained normotension (p < 0.05). In conclusion, in the absence of an efficient screening test, the diagnosis of MH/MUH can be assisted by the detection of the "isolated high office aSBP" phenotype, which can be measured in a single office visit. MHs/MUHs have increased aSBP relative to normotensives, further explaining the increased mortality of MH/MUH.

Progression of Subclinical Vascular Damage in People Living With HIV Is Not Predicted by Current Cardiovascular Risk Scores: A Prospective 3-Year Study.

BACKGROUND: People living with HIV (PLWH) are at high cardiovascular disease (CVD) risk. Traditional CVD risk scores do not accurately reflect their CVD risk. Noninvasive subclinical vascular damage (SVD) biomarkers are valid surrogates of CVD and able to stratify CVD risk. SETTING: We tested whether 4 widely applied CVD risk scores [Framingham (FRS), Atherosclerotic CVD, Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D), and Greek-specific European Society of Cardiology (ESC) risk scores] are associated with or detect the presence, incidence, and progression of arteriosclerosis, atheromatosis, and arterial hypertrophy in PLWH and uninfected individuals. METHODS: We prospectively examined (at baseline and 3-year follow-up) 10 different arterial sites applying 5 different noninvasive vascular biomarkers and measured all 4 CVD risk scores at baseline. RESULTS: In both PLWH (n = 138) and uninfected (n = 664) individuals, the CVD risk scores (except the ESC) performed differently but reasonably well in identifying the presence of SVD, but all scores failed to predict the incidence/progression of overall SVD. The most clinically useful biomarkers (carotid plaque/atheromatosis) revealed that in PLWH, only the FRS was able to stratify the progression (11% of the low-risk, 33.3% of the medium-risk, and 0% of the high-risk group). CONCLUSIONS: This extensive vascular phenotyping study demonstrated the clear need to incorporate vascular imaging in CVD risk stratification, in addition to designing more accurate HIV-specific CVD risk models. The use of FRS would further enable treatment optimization and CVD prevention strategies in PLWH at medium CVD risk because one-third of carotid atheromatosis progresses within 3 years.

A clinical score for prediction of elevated aortic stiffness: derivation and validation in 3943 hypertensive patients.

OBJECTIVE: Aortic stiffness assessed by carotid-femoral pulse wave velocity (PWV) is an important predictor to gauge the overall risk of hypertensive patients; nonetheless, it is underutilized in everyday practice. We propose a simple scoring system based on clinical variables that can identify patients with a priority for measurement of PWV, that is, those with elevated PWV (≥10 m/s) and, consequently, at higher risk for events. METHODS: Patient data from three outpatient clinics (n = 3943) were used to form a derivation, internal and external validation cohort. For derivation, independent predictors of high PWV from a binary logistic regression model were split in subcategories and implemented in a simple clinical prediction scoring system with the acronym SAGE (office systolic blood pressure, age, glycemia and eGFR categories). RESULTS: Its performance was validated at the internal and external validation cohorts with c-statistics being 0.83 (95% CI 0.81-0.86) and 0.77 (95% CI 0.73-0.80), respectively. A cut-off of eight points to identify patients with high PWV in the internal/external validation cohorts yielded a positive-predictive value, negative-predictive value, sensitivity and specificity of 52/36%, 88/81%, 56/70% and 88/65%, respectively. CONCLUSION: The SAGE score that takes into account easily measured clinical variables (office SBP, age, fasting glucose and eGFR categories) can be used to accurately predict elevated levels of PWV and prioritize its measurement in specific hypertensive patients. Its use will result in greater acknowledgement of the role of aortic stiffness and aid physicians in implementing it in clinical practice.

The Role of Colchicine in the Treatment of Autoinflammatory Diseases.

Colchicine has been longstanding and widely used for the treatment of acute gout flares and prevention of gout relapses. Its use has been extended to a series of autoinflammatory diseases, such as familial Mediterranean fever and more recently to periodic fever with aphthous stomatitis, pharyngitis and adenitis, Behcet's disease and idiopathic recurrent acute pericarditis. In this review, we summarize current indications of colchicine use, discuss its pharmacokinetics and mechanism of action and examine its use in the treatment of autoinflammatory diseases. Further understanding of the underlying mechanisms of the latter conditions as well as identification of the therapeutic efficacy and treatment target of colchicine may lead to more effective management of these diseases.

Mechanisms of pulse pressure amplification dipping pattern during sleep time: the SAFAR study.

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research.